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Array ( [0] => {{short description|Inflammation of the liver}} [1] => {{Redirect|Hepatite|the mineral of that name|Baryte}} [2] => {{Infobox medical condition (new) [3] => | name = Hepatitis [4] => | image = Alcoholic_hepatitis.jpg [5] => | caption = [[Alcoholic hepatitis]] as seen with a microscope, showing fatty changes (white circles), remnants of dead liver cells, and [[Mallory bodies]] (twisted-rope shaped inclusions within some liver cells). ([[H&E stain]]) [6] => | field = [[Infectious disease (medical specialty)|Infectious disease]], [[gastroenterology]], [[hepatology]] [7] => | pronounce = [8] => | symptoms = [[jaundice|Yellowish skin]], poor appetite, abdominal pain [9] => | complications = [[cirrhosis|Scarring of the liver]], [[liver failure]], [[liver cancer]] [10] => | onset = [11] => | duration = Short term or long term [12] => | causes = [[Viruses]], [[ethanol|alcohol]], toxins, autoimmune [13] => | risks = [14] => | diagnosis = [15] => | differential = [16] => | prevention = Vaccination (for viral hepatitis), avoiding excessive alcohol [17] => | treatment = Medication, [[liver transplant]] [18] => | medication = [19] => | frequency = > 500 million cases [20] => | deaths = > One million a year [21] => }} [22] => [23] => '''Hepatitis''' is [[inflammation]] of the [[liver parenchyma|liver tissue]].{{cite web|title=Hepatitis|url=https://www.niaid.nih.gov/diseases-conditions/hepatitis|website=NIAID|access-date=2 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161104002228/https://www.niaid.nih.gov/diseases-conditions/hepatitis|archive-date=4 November 2016}}{{cite web | title=Hepatitis | website=MedlinePlus | date=2020-05-20 | url=https://medlineplus.gov/hepatitis.html | access-date=2020-07-19 | quote=Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. Hepatitis is an inflammation of the liver.}} Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes ([[jaundice]]), [[Anorexia (symptom)|poor appetite]], [[vomiting]], [[fatigue (medicine)|tiredness]], [[abdominal pain]], and [[diarrhea]]. Hepatitis is ''[[acute (medicine)|acute]]'' if it resolves within six months, and ''[[chronic condition|chronic]]'' if it lasts longer than six months.{{cite web|title=Hepatitis|url=https://medlineplus.gov/hepatitis.html|website=MedlinePlus|access-date=10 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161111061624/https://medlineplus.gov/hepatitis.html|archive-date=11 November 2016}}{{cite web|title=Hepatitis (Hepatitis A, B, and C) {{!}} ACG Patients|url=http://patients.gi.org/topics/viral-hepatitis/|website=patients.gi.org|url-status=live|archive-url=https://web.archive.org/web/20170223163352/http://patients.gi.org/topics/viral-hepatitis/|archive-date=2017-02-23}} Acute hepatitis can [[self-limiting (biology)|resolve on its own]], progress to chronic hepatitis, or (rarely) result in [[acute liver failure]].{{cite journal |author1=Bernal W. |author2=Wendon J. | year = 2013 | title = Acute Liver Failure | journal = New England Journal of Medicine | volume = 369 | issue = 26| pages = 2525–2534 | doi=10.1056/nejmra1208937| pmid=24369077|s2cid=205116503 | doi-access = free }} Chronic hepatitis may progress to scarring of the liver ([[cirrhosis]]), [[liver failure]], and [[liver cancer]].{{Cite web |title=Esto es la hepatitis: Conócela, enfréntate a ella |url=https://www.infoterio.com/2022/08/Esto-es-la-hepatitis-Conocela-enfrentate-a-ella.html |access-date=2023-02-12 |website=Infoterio Noticias {{!}} Ciencia y Tecnología |date=8 August 2022 |language=es}} [24] => [25] => Hepatitis is most commonly caused by the virus ''[[hepatovirus A]]'', ''[[hepatitis B virus|B]]'', ''[[hepatitis C virus|C]]'', ''[[hepatitis D virus|D]]'', and ''[[hepatitis E virus|E]]''.{{cite web|title=What is hepatitis?|url=https://www.who.int/features/qa/76/en/|website=WHO|access-date=10 November 2016|date=July 2016|url-status=live|archive-url=https://web.archive.org/web/20161107003115/http://www.who.int/features/qa/76/en/|archive-date=7 November 2016}} Other [[Viral hepatitis|viruses can also cause liver inflammation]], including [[cytomegalovirus]], [[Epstein–Barr virus]], and [[Yellow fever|yellow fever virus]]. Other common causes of hepatitis include [[alcoholism|heavy alcohol use]], certain medications, toxins, other infections, [[autoimmune diseases]], and [[non-alcoholic steatohepatitis]] (NASH).{{cite web|title=Fatty Liver Disease (Nonalcoholic Steatohepatitis) |url=https://www.niddk.nih.gov/health-information/health-topics/liver-disease/nonalcoholic-steatohepatitis/pages/facts.aspx |website=NIDDK |access-date=10 November 2016 |date=May 2014 |archive-url=https://web.archive.org/web/20161111061658/https://www.niddk.nih.gov/health-information/health-topics/liver-disease/nonalcoholic-steatohepatitis/pages/facts.aspx |archive-date=11 November 2016 |url-status=dead }} Hepatitis A and E are mainly spread by contaminated food and water. Hepatitis B is mainly [[sexually transmitted infection|sexually transmitted]], but may also be [[vertically transmitted infection|passed from mother to baby]] during [[pregnancy]] or [[childbirth]] and spread through infected [[blood]]. Hepatitis C is commonly spread through infected blood such as may occur during [[needle sharing]] by [[drug injection|intravenous drug users]]. Hepatitis D can only infect people already infected with hepatitis B. [26] => [27] => Hepatitis A, B, and D are [[vaccine-preventable diseases|preventable]] with [[immunization]]. Medications may be used to treat chronic viral hepatitis. Antiviral medications are recommended in all with chronic hepatitis C, except those with conditions that limit their life expectancy.{{Cite journal|last=AASLD/IDSA HCV Guidance Panel|date=2015-09-01|title=Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus|journal=Hepatology|volume=62|issue=3|pages=932–954|doi=10.1002/hep.27950|issn=1527-3350|pmid=26111063|doi-access=free}} There is no specific treatment for NASH; physical activity, a [[healthy diet]], and [[weight loss]] are recommended. [[Autoimmune hepatitis]] may be treated with [[immunosuppressants|medications to suppress the immune system]].{{cite web|title=Autoimmune Hepatitis|url=https://www.niddk.nih.gov/health-information/health-topics/liver-disease/autoimmune-hepatitis/Pages/facts.aspx|website=NIDDK|access-date=10 November 2016|date=March 2014|url-status=dead|archive-url=https://web.archive.org/web/20161111061856/https://www.niddk.nih.gov/health-information/health-topics/liver-disease/autoimmune-hepatitis/Pages/facts.aspx|archive-date=11 November 2016}} A [[liver transplant]] may be an option in both acute and chronic liver failure.{{cite web|title=Liver Transplant|url=https://www.niddk.nih.gov/health-information/health-topics/liver-disease/liver-transplant/Pages/facts.aspx|website=NIDDK|access-date=10 November 2016|date=April 2012|url-status=dead|archive-url=https://web.archive.org/web/20161111061924/https://www.niddk.nih.gov/health-information/health-topics/liver-disease/liver-transplant/Pages/facts.aspx|archive-date=11 November 2016}} [28] => [29] => Worldwide in 2015, hepatitis A occurred in about 114 million people, chronic hepatitis B affected about 343 million people and chronic hepatitis C about 142 million people.{{cite journal|title=Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015|journal=The Lancet|date=October 2016|volume=388|issue=10053|pages=1545–1602|doi=10.1016/S0140-6736(16)31678-6|pmid=27733282|pmc=5055577|last1=Vos|first1=Theo|last2=Allen|first2=Christine|last3=Arora|first3=Megha|last4=Barber|first4=Ryan M.|last5=Bhutta|first5=Zulfiqar A.|last6=Brown|first6=Alexandria|last7=Carter|first7=Austin|last8=Casey|first8=Daniel C.|last9=Charlson|first9=Fiona J.|last10=Chen|first10=Alan Z.|last11=Coggeshall|first11=Megan|last12=Cornaby|first12=Leslie|last13=Dandona|first13=Lalit|last14=Dicker|first14=Daniel J.|last15=Dilegge|first15=Tina|last16=Erskine|first16=Holly E.|last17=Ferrari|first17=Alize J.|last18=Fitzmaurice|first18=Christina|last19=Fleming|first19=Tom|last20=Forouzanfar|first20=Mohammad H.|last21=Fullman|first21=Nancy|last22=Gething|first22=Peter W.|last23=Goldberg|first23=Ellen M.|last24=Graetz|first24=Nicholas|last25=Haagsma|first25=Juanita A.|last26=Hay|first26=Simon I.|last27=Johnson|first27=Catherine O.|last28=Kassebaum|first28=Nicholas J.|last29=Kawashima|first29=Toana|last30=Kemmer|first30=Laura|display-authors=29}} In the United States, NASH affects about 11 million people and [[alcoholic hepatitis]] affects about 5 million people.{{cite journal|last1=Basra|first1=Sarpreet|title=Definition, epidemiology and magnitude of alcoholic hepatitis|journal=World Journal of Hepatology|date=2011|volume=3|issue=5|pages=108–13|doi=10.4254/wjh.v3.i5.108|pmid=21731902|pmc=3124876 |doi-access=free }} Hepatitis results in more than a million deaths a year, most of which occur indirectly from liver scarring or liver cancer.{{cite journal|title=Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015|journal=The Lancet|date=October 2016|volume=388|issue=10053|pages=1459–1544|doi=10.1016/S0140-6736(16)31012-1|pmid=27733281|pmc=5388903|last1=Wang|first1=Haidong|last2=Naghavi|first2=Mohsen|last3=Allen|first3=Christine|last4=Barber|first4=Ryan M.|last5=Bhutta|first5=Zulfiqar A.|last6=Carter|first6=Austin|last7=Casey|first7=Daniel C.|last8=Charlson|first8=Fiona J.|last9=Chen|first9=Alan Zian|last10=Coates|first10=Matthew M.|last11=Coggeshall|first11=Megan|last12=Dandona|first12=Lalit|last13=Dicker|first13=Daniel J.|last14=Erskine|first14=Holly E.|last15=Ferrari|first15=Alize J.|last16=Fitzmaurice|first16=Christina|last17=Foreman|first17=Kyle|last18=Forouzanfar|first18=Mohammad H.|last19=Fraser|first19=Maya S.|last20=Fullman|first20=Nancy|last21=Gething|first21=Peter W.|last22=Goldberg|first22=Ellen M.|last23=Graetz|first23=Nicholas|last24=Haagsma|first24=Juanita A.|last25=Hay|first25=Simon I.|last26=Huynh|first26=Chantal|last27=Johnson|first27=Catherine O.|last28=Kassebaum|first28=Nicholas J.|last29=Kinfu|first29=Yohannes|last30=Kulikoff|first30=Xie Rachel|display-authors=29}} In the United States, hepatitis A is estimated to occur in about 2,500 people a year and results in about 75 deaths.{{cite web|title=Statistics & Surveillance Division of Viral Hepatitis CDC|url=https://www.cdc.gov/hepatitis/statistics/index.htm|website=CDC|access-date=10 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161111012229/http://www.cdc.gov/hepatitis/Statistics/index.htm|archive-date=11 November 2016}} The word is derived from the [[Ancient Greek|Greek]] ''hêpar'' ({{lang|grc|[[wikt:ἧπαρ|ἧπαρ]]}}), meaning "liver", and ''[[wikt:-itis|-itis]]'' ({{lang|grc|-ῖτις}}), meaning "inflammation".{{cite web |url=http://www.etymonline.com/index.php?search=hepatitis&searchmode=none |title=Online Etymology Dictionary |publisher=Etymonline.com |access-date=2012-08-26 |url-status=live |archive-url=https://web.archive.org/web/20121020195733/http://www.etymonline.com/index.php?search=hepatitis&searchmode=none |archive-date=2012-10-20 }} [30] => {{TOC limit|3}} [31] => [32] => == Signs and symptoms == [33] => [[File:Jaundice eye.jpg|thumb|upright=1.3|Jaundiced eyes]] [34] => Hepatitis has a broad spectrum of presentations that range from a complete lack of symptoms to severe [[liver failure]].{{Cite book|title=Harrison's Principles of Internal Medicine, 19e|last=Dienstag|first=JL|publisher=McGraw-Hill|year=2015|isbn=978-0-07-180215-4|editor-last=Kasper|editor-first=D|location=New York, NY|chapter=Chapter 360: Acute Viral Hepatitis|editor-last2=Fauci|editor-first2=A|editor-last3=Hauser|editor-first3=S|editor-last4=Longo|editor-first4=D|editor-last5=Jameson|editor-first5=J|editor-last6=Loscalzo|editor-first6=J}}{{Cite book|title=CURRENT Diagnosis & Treatment: Gastroenterology, Hepatology, & Endoscopy, 3e|last1=Rutherford|first1=A|last2=Dienstag|first2=JL|publisher=McGraw-Hill|year=2016|isbn=978-0-07-183772-9|editor-last=Greenberger|editor-first=NJ|location=New York, NY|chapter=Chapter 40: Viral Hepatitis|editor-last2=Blumberg|editor-first2=RS|editor-last3=Burakoff|editor-first3=R}}{{Cite book|title=Pathophysiology of Disease: An Introduction to Clinical Medicine, 7e|last1=Khalili|first1=M|last2=Burman|first2=B|publisher=McGraw-Hill|year=2013|isbn=978-1-25-925144-3|editor-last=Hammer|editor-first=GD|chapter=Chapter 14: Liver Disease|editor-last2=McPhee|editor-first2=SJ}} The acute form of hepatitis, generally caused by viral infection, is characterized by [[constitutional symptoms]] that are typically self-limiting. Chronic hepatitis presents similarly, but can manifest [[medical sign|signs]] and symptoms specific to liver dysfunction with long-standing inflammation and damage to the organ.{{Cite book|title=Harrison's Principles of Internal Medicine, 19e|last=Dienstag|first=JL|publisher=McGraw-Hill|year=2015|isbn=978-0-07-180215-4|editor-last=Kasper|editor-first=D|location=New York, NY|chapter=Chapter 362: Chronic Hepatitis|editor-last2=Fauci|editor-first2=A|editor-last3=Hauser|editor-first3=S|editor-last4=Longo|editor-first4=D|editor-last5=Jameson|editor-first5=J|editor-last6=Loscalzo|editor-first6=J}} [35] => [36] => === Acute hepatitis === [37] => Acute viral hepatitis follows three distinct phases: [38] => # The initial [[Prodrome|prodromal phase]] (preceding symptoms) involves [[non-specific]] and [[flu-like]] symptoms common to many acute viral infections. These include [[Fatigue (medical)|fatigue]], [[nausea]], [[vomiting]], poor appetite, joint pain, and headaches. Fever, when present, is most common in cases of hepatitis A and E. Late in this phase, people can experience liver-specific symptoms, including [[choluria]] (dark urine) and clay-colored stools. [39] => # [[Jaundice|Yellowing of the skin and whites of the eyes]] follow the prodrome after about 1–2 weeks and can last for up to 4 weeks. The non-specific symptoms seen in the prodromal typically resolve by this time, but people will develop an [[hepatomegaly|enlarged liver]] and right upper abdominal pain or discomfort. 10–20% of people will also experience an [[Splenomegaly|enlarged spleen]], while some people will also experience a mild unintentional weight loss. [40] => # The recovery phase is characterized by resolution of the clinical symptoms of hepatitis with persistent elevations in [[Liver function tests|liver lab values]] and potentially a persistently enlarged liver. All cases of hepatitis A and E are expected to fully resolve after 1–2 months. Most hepatitis B cases are also self-limiting and will resolve in 3–4 months. Few cases of hepatitis C will resolve completely. [41] => Both [[drug-induced hepatitis]] and [[autoimmune hepatitis]] can present very similarly to acute viral hepatitis, with slight variations in symptoms depending on the cause.{{Cite journal|last1=Fontana|first1=Robert|last2=Hayashi|first2=Paul|date=2014-05-01|title=Clinical Features, Diagnosis, and Natural History of Drug-Induced Liver Injury|journal=Seminars in Liver Disease|language=en|volume=34|issue=2|pages=134–144|doi=10.1055/s-0034-1375955|pmid=24879979|doi-access=free}}{{Cite journal|last1=Manns|first1=Michael P.|last2=Lohse|first2=Ansgar W.|last3=Vergani|first3=Diego|title=Autoimmune hepatitis – Update 2015|journal=Journal of Hepatology|volume=62|issue=1|pages=S100–S111|doi=10.1016/j.jhep.2015.03.005|pmid=25920079|year=2015|doi-access=free}} Cases of drug-induced hepatitis can manifest with systemic signs of an allergic reaction including rash, fever, [[serositis]] (inflammation of membranes lining certain organs), elevated [[Eosinophil granulocyte|eosinophils]] (a type of white blood cell), and [[Bone marrow suppression|suppression of bone marrow activity]]. [42] => [43] => === Fulminant hepatitis === [44] => Fulminant hepatitis, or massive hepatic [[necrosis|cell death]], is a rare and life-threatening complication of acute hepatitis that can occur in cases of hepatitis B, D, and E, in addition to drug-induced and autoimmune hepatitis. The complication more frequently occurs in instances of hepatitis B and D co-infection at a rate of 2–20% and in pregnant women with hepatitis E at rate of 15–20% of cases. In addition to the signs of acute hepatitis, people can also demonstrate signs of [[coagulopathy]] (abnormal coagulation studies with easy bruising and bleeding) and [[encephalopathy]] (confusion, disorientation, and [[somnolence|sleepiness]]). Mortality due to fulminant hepatitis is typically the result of various complications including [[cerebral edema]], [[gastrointestinal bleeding]], [[sepsis]], [[respiratory failure]], or [[kidney failure]]. [45] => [46] => === Chronic hepatitis === [47] => Acute cases of hepatitis are seen to be resolved well within a six-month period. When hepatitis is continued for more than six months it is termed chronic hepatitis.{{cite book|last1=Munjal|first1=Y. P.|last2=Sharm|first2=Surendra K.|title=API Textbook of Medicine, Ninth Edition, Two Volume Set|date=2012|publisher=JP Medical Ltd|isbn=9789350250747|page=870|url=https://books.google.com/books?id=L7pW3yGjj7kC&pg=PA870|language=en|url-status=live|archive-url=https://web.archive.org/web/20170910162730/https://books.google.com/books?id=L7pW3yGjj7kC&pg=PA870|archive-date=2017-09-10}} Chronic hepatitis is often asymptomatic early in its course and is detected only by liver laboratory studies for [[Screening (medicine)|screening]] purposes or to evaluate non-specific symptoms. As the inflammation progresses, patients can develop constitutional symptoms similar to acute hepatitis, including fatigue, nausea, vomiting, poor appetite, and joint pain. Jaundice can occur as well, but much later in the disease process and is typically a sign of advanced disease. Chronic hepatitis interferes with hormonal functions of the liver which can result in acne, [[hirsutism]] (abnormal hair growth), and [[Amenorrhoea|amenorrhea]] (lack of menstrual period) in women. Extensive damage and scarring of the liver over time defines [[cirrhosis]], a condition in which the liver's ability to function is permanently impeded. This results in jaundice, weight loss, coagulopathy, [[ascites]] (abdominal fluid collection), and [[peripheral edema]] (leg swelling). Cirrhosis can lead to other life-threatening complications such as [[hepatic encephalopathy]], [[esophageal varices]], [[hepatorenal syndrome]], and [[Hepatocellular carcinoma|liver cancer]]. [48] => [49] => == Causes == [50] => Causes of hepatitis can be divided into the following major categories: infectious, metabolic, ischemic, autoimmune, genetic, and other. Infectious agents include viruses, bacteria, and parasites. Metabolic causes include prescription medications, toxins (most notably [[Alcoholic liver disease|alcohol]]), and [[non-alcoholic fatty liver disease]]. [[Autoimmune hepatitis|Autoimmune]] and genetic causes of hepatitis involve genetic predispositions and tend to affect characteristic populations.[https://www.vinmec.com/vi/tieu-hoa-gan-mat/thong-tin-suc-khoe/viem-gan-tu-mien-la-gi/ Viêm gan tự miễn.] Phần nội dung "Yếu tố nguy cơ mắc bệnh viêm gan tự miễn". Bệnh viện đa khoa quốc tế Vinmec. Truy cập 28/12/2023 [51] => [52] => === Infectious === [53] => [54] => ==== Viral hepatitis ==== [55] => {{Main|Viral hepatitis}} [56] => [[Viral hepatitis]] is the most common type of hepatitis worldwide, especially in Asia and Africa.{{cite web|url=https://www.who.int/topics/hepatitis/en/|title=Hepatitis|publisher=World Health Organization|access-date=25 November 2013|author=World Health Organization|url-status=live|archive-url=https://web.archive.org/web/20131202223841/http://www.who.int/topics/hepatitis/en/|archive-date=2 December 2013}} Viral hepatitis is caused by five different viruses (hepatitis A, B, C, D, and E). [[Hepatitis A]] and [[hepatitis E]] behave similarly: they are both transmitted by the [[fecal–oral route]], are more common in developing countries, and are self-limiting illnesses that do not lead to chronic hepatitis.{{Cite web|url=https://www.cdc.gov/hepatitis/hav/afaq.htm|title=Hepatitis A Questions and Answers for the Public {{!}} Division of Viral Hepatitis {{!}} CDC|website=www.cdc.gov|access-date=2016-03-14|url-status=live|archive-url=https://web.archive.org/web/20160312094721/http://www.cdc.gov/hepatitis/hav/afaq.htm|archive-date=2016-03-12}}{{Cite web|url=https://www.who.int/mediacentre/factsheets/fs280/en/|title=Hepatitis E|website=World Health Organization|language=en-GB|access-date=2016-03-14|url-status=live|archive-url=https://web.archive.org/web/20160312074914/http://www.who.int/mediacentre/factsheets/fs280/en/|archive-date=2016-03-12}} [57] => [58] => [[Hepatitis B]], [[hepatitis C]], and [[hepatitis D]] are transmitted when blood or [[mucous membrane]]s are exposed to infected blood and body fluids, such as semen and vaginal secretions. Viral particles have also been found in saliva and breastmilk. Kissing, sharing utensils, and breastfeeding do not lead to transmission unless these fluids are introduced into open sores or cuts.{{Cite web|url=https://www.cdc.gov/hepatitis/HBV/PDFs/HepBWhenSomeoneClose.pdf|title=When Someone Close to You Has Hepatitis|last=Centers for Disease Control & Prevention|date=June 2010|access-date=March 14, 2016|url-status=live|archive-url=https://web.archive.org/web/20160306084204/http://www.cdc.gov/hepatitis/HBV/PDFs/HepBWhenSomeoneClose.pdf|archive-date=March 6, 2016}} Many families who do not have safe drinking water or live in unhygienic homes have contracted hepatitis because saliva and blood droplets are often carried through the water and blood-borne illnesses spread quickly in unsanitary settings.{{Cite web |title=Hepatitis A |url=https://www.who.int/news-room/fact-sheets/detail/hepatitis-a |access-date=2023-05-07 |website=www.who.int |language=en}} [59] => [60] => Hepatitis B and C can present either acutely or chronically. Hepatitis D is a defective virus that requires hepatitis B to replicate and is only found with hepatitis B co-infection. In adults, hepatitis B infection is most commonly self-limiting, with less than 5% progressing to chronic state, and 20 to 30% of those chronically infected developing cirrhosis or liver cancer. Infection in infants and children frequently leads to chronic infection. [61] => [62] => Unlike hepatitis B, most cases of hepatitis C lead to chronic infection.{{Cite web|url=https://www.cdc.gov/hepatitis/hcv/cfaq.htm|title=Hepatitis C FAQs for the Public {{!}} Division of Viral Hepatitis {{!}} CDC|website=www.cdc.gov|access-date=2016-03-14|url-status=live|archive-url=https://web.archive.org/web/20160315151117/http://www.cdc.gov/hepatitis/hcv/cfaq.htm|archive-date=2016-03-15}} Hepatitis C is the second most common cause of cirrhosis in the US (second to alcoholic hepatitis).{{Cite book|title=Current Medical Diagnosis & Treatment 2016 55e|last=Friedman|first=Lawrence S.|publisher=McGraw Hill|year=2015|isbn=978-0071845090|editor-last=Papadakis, M |editor2=McPhee, SJ |editor3=Rabow, MW|chapter=Chapter 16: Liver, Biliary Tract, & Pancreas Disorders}} In the 1970s and 1980s, blood transfusions were a major factor in spreading hepatitis C virus. Since widespread screening of blood products for hepatitis C began in 1992, the risk of acquiring hepatitis C from a blood transfusion has decreased from approximately 10% in the 1970s to 1 in 2 million currently. [63] => [64] => ==== Parasitic hepatitis ==== [65] => [[File:Echinococcus granulosus.JPG|thumb|Echinococcus granulosus]] [66] => [[Parasites of humans|Parasites]] can also infect the liver and activate the immune response, resulting in symptoms of acute hepatitis with increased serum [[Immunoglobulin E|IgE]] (though chronic hepatitis is possible with chronic infections).{{Cite book|title=Comparative Hepatitis|url=https://archive.org/details/comparativehepat00webe|url-access=limited|author1=Harder, A |author2=Mehlhorn, H |publisher=Birkhauser|year=2008|isbn=978-3764385576|editor1=Weber, O |editor2=Protzer, U |pages=[https://archive.org/details/comparativehepat00webe/page/n171 161]–216|chapter=Diseases Caused by Adult Parasites or Their Distinct Life Cycle Stages}} Of the [[protozoa]]ns, [[Trypanosoma cruzi]], [[Leishmaniasis|Leishmania]] species, and the [[malaria]]-causing [[Plasmodium]] species all can cause liver inflammation. Another protozoan, [[Entamoeba histolytica]], causes hepatitis with distinct liver abscesses. [67] => [68] => Of the worms, the [[Cestode infection|cestode]] [[Echinococcus granulosus]], also known as the dog tapeworm, infects the liver and forms characteristic hepatic [[Echinococcosis|hydatid cysts]]. The liver [[Fluke (parasite)|flukes]] [[Fasciola hepatica]] and [[Clonorchis sinensis]] live in the bile ducts and cause progressive hepatitis and liver fibrosis. [69] => [70] => ==== Bacterial hepatitis ==== [71] => Bacterial infection of the liver commonly results in [[pyogenic liver abscess]]es, acute hepatitis, or [[granuloma]]tous (or chronic) liver disease.{{Cite book|title=Comparative Hepatitis|url=https://archive.org/details/comparativehepat00webe|url-access=limited|author1=Wisplinghoff, H |author2=Appleton, DL |publisher=Birkhauser|year=2008|isbn=978-3764385576|editor1=Weber, O |editor2=Protzer, U |pages=[https://archive.org/details/comparativehepat00webe/page/n153 143]–160|chapter=Bacterial Infections of the Liver}} Pyogenic abscesses commonly involve [[enteric]] bacteria such as ''[[Escherichia coli]]'' and ''[[Klebsiella pneumoniae]]'' and are composed of multiple bacteria up to 50% of the time. Acute hepatitis is caused by ''[[Neisseria meningitidis]]'', ''[[Neisseria gonorrhoeae]]'', ''[[Bartonella henselae]]'', ''[[Borrelia burgdorferi]]'', [[salmonella]] species, [[brucella]] species and [[campylobacter]] species. Chronic or granulomatous hepatitis is seen with infection from [[Mycobacterium|mycobacteria]] species, ''[[Tropheryma whipplei]]'', ''[[Treponema pallidum]]'', ''[[Coxiella burnetii]]'', and [[rickettsia]] species. [72] => [73] => === Metabolic === [74] => [75] => ==== Alcoholic hepatitis ==== [76] => {{Main|Alcoholic hepatitis}} [77] => Excessive alcohol consumption is a significant cause of hepatitis and is the most common cause of cirrhosis in the U.S. Alcoholic hepatitis is within the spectrum of [[alcoholic liver disease]]. This ranges in order of severity and reversibility from [[Alcoholic fatty liver|alcoholic steatosis]] (least severe, most reversible), [[alcoholic hepatitis]], cirrhosis, and liver cancer (most severe, least reversible). Hepatitis usually develops over years-long exposure to alcohol, occurring in 10 to 20% of alcoholics.{{Cite book|title=Harrison's Principles of Internal Medicine 19e|author1=Mailliard, ME |author2=Sorrell, MF |publisher=McGraw-Hill|year=2015|isbn=978-0-07-180215-4|editor1=Kasper, D |editor2=Fauci, A |editor3=Hauser, S |editor4=Longo, D |editor5=Jameson, J |editor6=Loscalzo, J |chapter=Chapter 363: Alcoholic Liver Disease}} The most important risk factors for the development of alcoholic hepatitis are quantity and duration of alcohol intake. Long-term alcohol intake in excess of 80 grams of alcohol a day in men and 40 grams a day in women is associated with development of alcoholic hepatitis (1 beer or 4 ounces of wine is equivalent to 12g of alcohol). Alcoholic hepatitis can vary from asymptomatic [[hepatomegaly]] (enlarged liver) to symptoms of acute or chronic hepatitis to liver failure. [78] => [79] => ==== Toxic and drug-induced hepatitis ==== [80] => Many chemical agents, including medications, industrial toxins, and herbal and dietary supplements, can cause hepatitis.{{Cite book|title=Harrison's Principles of Internal Medicine 19e|author1=Lee, WM |author2=Dienstag, JL |publisher=McGraw-Hill|year=2015|isbn=978-0-07-180215-4|editor1=Kasper, D |editor2=Fauci, A |editor3=Hauser, S |editor4=Longo, D |editor5=Jameson, J |editor6=Loscalzo, J |chapter=Chapter 361: Toxic and Drug-Induced Hepatitis}} The spectrum of drug-induced liver injury varies from acute hepatitis to chronic hepatitis to acute liver failure. Toxins and medications can cause liver injury through a variety of mechanisms, including direct [[cell damage]], disruption of cell metabolism, and causing structural changes.{{cite journal|last=Lee|first=William M.|title=Drug-Induced Hepatotoxicity|journal=New England Journal of Medicine|date=31 July 2003|volume=349|issue=5|pages=474–485|doi=10.1056/NEJMra021844|pmid=12890847}} Some drugs such as [[paracetamol]] exhibit predictable dose-dependent liver damage while others such as [[isoniazid]] cause idiosyncratic and unpredictable reactions that vary by person. There are wide variations in the mechanisms of liver injury and [[latency period]] from exposure to development of clinical illness. [81] => [82] => Many types of drugs can cause liver injury, including the [[analgesic]] paracetamol; [[antibiotic]]s such as isoniazid, [[nitrofurantoin]], [[Amoxicillin/clavulanic acid|amoxicillin-clavulanate]], [[erythromycin]], and [[Trimethoprim/sulfamethoxazole|trimethoprim-sulfamethoxazole]]; [[anticonvulsant]]s such as [[valproate]] and [[phenytoin]]; cholesterol-lowering [[statin]]s; [[steroid]]s such as [[Oral contraceptive pill|oral contraceptives]] and [[anabolic steroid]]s; and [[Highly Active Anti-Retroviral Therapy|highly active anti-retroviral therapy]] used in the treatment of [[HIV/AIDS]]. Of these, amoxicillin-clavulanate is the most common cause of drug-induced liver injury, and [[paracetamol toxicity]] the most common cause of acute liver failure in the United States and Europe. [83] => [84] => [[Herb|Herbal remedies]] and [[dietary supplement]]s are another important cause of hepatitis; these are the most common causes of drug-induced hepatitis in Korea.{{cite journal|last=Suk|first=Ki Tae|year=2012|title=Drug-induced liver injury: present and future|journal=Clinical and Molecular Hepatology|volume=18|issue=3|pages=249–57|doi=10.3350/cmh.2012.18.3.249|pmc=3467427|pmid=23091804|author2=Kim, Dong Joon}} The United-States-based [http://www.dilin.org/ Drug Induced Liver Injury Network] linked more than 16% of cases of hepatotoxicity to herbal and dietary supplements.{{Cite journal|url=http://livertox.nih.gov/Herbals_and_Dietary_Supplements.htm|title=Herbals_and_Dietary_Supplements|website=livertox.nih.gov|date=2012 |pmid=31643176 |access-date=2016-03-14|url-status=live|archive-url=https://web.archive.org/web/20160508234736/http://livertox.nih.gov/Herbals_and_Dietary_Supplements.htm|archive-date=2016-05-08}} In the United States, herbal and dietary supplements – unlike [[pharmaceutical drug]]s – are unregulated by the [[Food and Drug Administration]]. The [[National Institutes of Health]] maintains the [https://livertox.nlm.nih.gov LiverTox] {{Webarchive|url=https://web.archive.org/web/20190724165846/https://livertox.nlm.nih.gov/ |date=2019-07-24 }} database for consumers to track all known prescription and non-prescription compounds associated with liver injury.{{Cite news|url=https://www.nih.gov/news-events/news-releases/nih-launches-free-database-drugs-associated-liver-injury|title=NIH launches free database of drugs associated with liver injury|date=2015-09-30|work=National Institutes of Health (NIH)|access-date=2018-09-18|language=en}} [85] => [86] => Exposure to other [[hepatotoxin]]s can occur accidentally or intentionally through ingestion, inhalation, and skin absorption. The industrial toxin [[carbon tetrachloride]] and the wild mushroom [[Amanita phalloides]] are other known hepatotoxins.{{cite journal|last1=Malaguarnera|first1=Giulia|last2=Cataudella|first2=E|last3=Giordano|first3=M|last4=Nunnari|first4=G|last5=Chisari|first5=G|last6=Malaguarnera|first6=M|year=2012|title=Toxic hepatitis in occupational exposure to solvents|journal=World Journal of Gastroenterology|volume=18|issue=22|pages=2756–66|doi=10.3748/wjg.v18.i22.2756|pmc=3374978|pmid=22719183 |doi-access=free }}{{cite book|chapter-url=http://www.accessmedicine.com/content.aspx?aID=6361074|title=Tintinalli's Emergency Medicine: A Comprehensive Study Guide.|publisher=McGraw-Hill|year=2011|edition=7th|location=New York|chapter=Chapter 83. Hepatic Disorders, Jaundice, and Hepatic Failure|chapter-format=Online|vauthors=O'Mara SR, Gebreyes K|veditors=Cydulka RK, Meckler GD|access-date=26 November 2013|url-status=live|archive-url=https://web.archive.org/web/20131202233459/http://www.accessmedicine.com/content.aspx?aID=6361074|archive-date=2 December 2013}} [87] => [88] => ==== Non-alcoholic fatty liver disease ==== [89] => {{Main|Non-alcoholic fatty liver disease}} [90] => [91] => Non-alcoholic hepatitis is within the spectrum of non-alcoholic liver disease (NALD), which ranges in severity and reversibility from [[non-alcoholic fatty liver disease]] (NAFLD) to non-alcoholic steatohepatitis (NASH) to cirrhosis to liver cancer, similar to the spectrum of alcoholic liver disease.{{Cite book|title=Harrison's Principles of Internal Medicine 19e|author1=Abdelmalek, MF |author2=Diehl AM |publisher=McGraw-Hill|year=2015|isbn=978-0-07-180215-4|editor1=Kasper, D |editor2=Fauci, A |editor3=Hauser, S |editor4=Longo, D |editor5=Jameson, J |editor6=Loscalzo, J |chapter=Chapter 364: Nonalcoholic Liver Diseases and Nonalcoholic Steatohepatitis}} [92] => [93] => Non-alcoholic liver disease occurs in people with little or no history of alcohol use, and is instead strongly associated with [[metabolic syndrome]], obesity, [[insulin resistance]] and [[Diabetes mellitus type 2|diabetes]], and hypertriglyceridemia. Over time, non-alcoholic fatty liver disease can progress to non-alcoholic [[steatohepatitis]], which additionally involves liver cell death, liver inflammation and possible fibrosis. Factors accelerating progression from NAFLD to NASH are obesity, older age, non-African American ethnicity, female gender, diabetes mellitus, hypertension, higher [[Alanine transaminase|ALT]] or [[Aspartate transaminase|AST]] level, higher AST/ALT ratio, low platelet count, and an [http://www.nature.com/ijo/journal/v28/n10/fig_tab/0802734t1.html ultrasound steatosis score]. [94] => [95] => In the early stages (as with NAFLD and early NASH), most patients are asymptomatic or have mild [[Quadrant (abdomen)|right upper quadrant]] pain, and diagnosis is suspected on the basis of abnormal [[liver function tests]]. As the disease progresses, symptoms typical of chronic hepatitis may develop.{{cite web|url=http://digestive.niddk.nih.gov/ddiseases/pubs/nash/index.aspx|title=Nonalcoholic Steatohepatitis|publisher=National Digestive Diseases Information Clearinghouse (NDDIC)|access-date=27 November 2013|author=National Digestive Diseases Information Clearinghouse (NDDIC)|url-status=live|archive-url=https://web.archive.org/web/20131202231555/http://digestive.niddk.nih.gov/ddiseases/pubs/nash/index.aspx|archive-date=2 December 2013}} While imaging can show fatty liver, only [[liver biopsy]] can demonstrate inflammation and fibrosis characteristic of NASH.{{cite journal|last=Masuoka|first=Howard C.|author2=Chalasani, Naga|title=Nonalcoholic fatty liver disease: an emerging threat to obese and diabetic individuals|journal=Annals of the New York Academy of Sciences|date=April 2013|volume=1281|issue=1|pages=106–122|doi=10.1111/nyas.12016|bibcode=2013NYASA1281..106M|pmid=23363012|pmc=3646408}} 9 to 25% of patients with NASH develop cirrhosis. NASH is recognized as the third most common cause of liver disease in the United States. [96] => [97] => === Autoimmune === [98] => {{Main|Autoimmune hepatitis}} [99] => [100] => Autoimmune hepatitis is a chronic disease caused by an abnormal immune response against liver cells.{{cite web|url=http://digestive.niddk.nih.gov/ddiseases/pubs/autoimmunehep/|title=Autoimmune Hepatitis|publisher=National Digestive Diseases Information Clearinghouse (NDDIC)|access-date=27 November 2013|author=National Digestive Diseases Information Clearinghouse (NDDIC)|url-status=dead|archive-url=https://web.archive.org/web/20100915033205/http://digestive.niddk.nih.gov/ddiseases/pubs/autoimmunehep/|archive-date=15 September 2010}} The disease is thought to have a genetic predisposition as it is associated with certain [[human leukocyte antigen]]s involved in the immune response.{{cite journal|last1=Teufel|first1=Andreas|last2=Galle|first2=PR|last3=Kanzler|first3=S|year=2009|title=Update on autoimmune hepatitis|journal=World Journal of Gastroenterology|volume=15|issue=9|pages=1035–41|doi=10.3748/wjg.15.1035|pmc=2655176|pmid=19266594 |doi-access=free }} As in other autoimmune diseases, circulating [[Autoantibody|auto-antibodies]] may be present and are helpful in diagnosis.{{Cite journal|last=Czaja|first=Albert J|title=Diagnosis and Management of Autoimmune Hepatitis: Current Status and Future Directions|journal=Gut and Liver|volume=10|issue=2|doi=10.5009/gnl15352|pmc=4780448|pmid=26934884|pages=177–203|year=2016}} Auto-antibodies found in patients with autoimmune hepatitis include the [[Sensitivity and specificity|sensitive but less specific]] [[Anti-nuclear antibody|anti-nuclear antibody (ANA)]], smooth muscle antibody (SMA), and [[Anti-neutrophil cytoplasmic antibody|atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA)]]. Other autoantibodies that are less common but more specific to autoimmune hepatitis are the antibodies against liver kidney microsome 1 (LKM1) and soluble liver antigen (SLA). Autoimmune hepatitis can also be triggered by drugs (such as [[nitrofurantoin]], [[hydralazine]], and [[methyldopa]]), after liver transplant, or by viruses (such as hepatitis A, [[Epstein–Barr virus|Epstein-Barr virus]], or [[measles]]). [101] => [102] => Autoimmune hepatitis can present anywhere within the spectrum from asymptomatic to acute or chronic hepatitis to fulminant liver failure. Patients are asymptomatic 25–34% of the time, and the diagnosis is suspected on the basis of abnormal liver function tests. Some studies show between 25% and 75% of cases present with signs and symptoms of acute hepatitis.{{Cite journal|last=Czaja|first=Albert J.|date=2016-03-15|title=Diagnosis and Management of Autoimmune Hepatitis: Current Status and Future Directions|journal=Gut and Liver|volume=10|issue=2|pages=177–203|doi=10.5009/gnl15352|issn=1976-2283|pmc=4780448|pmid=26934884}} As with other autoimmune diseases, autoimmune hepatitis usually affects young females (though it can affect patients of either sex of any age), and patients can exhibit classic signs and symptoms of autoimmunity such as fatigue, anemia, anorexia, [[Amenorrhoea|amenorrhea]], acne, arthritis, [[pleurisy]], [[thyroiditis]], [[ulcerative colitis]], [[nephritis]], and [[maculopapular rash]]. Autoimmune hepatitis increases the risk for cirrhosis, and the risk for liver cancer is increased by about 1% for each year of the disease. [103] => [104] => Many people with autoimmune hepatitis have other [[autoimmune disease]]s.{{cite journal|last=Krawitt|first=Edward-L|title=Clinical features and management of autoimmune hepatitis|journal=World Journal of Gastroenterology|year=2008|volume=14|issue=21|pages=3301–5|doi=10.3748/wjg.14.3301|pmid=18528927|pmc=2716584 |doi-access=free }} Autoimmune hepatitis is distinct from the other autoimmune diseases of the liver, [[primary biliary cirrhosis]] and [[primary sclerosing cholangitis]], both of which can also lead to scarring, fibrosis, and cirrhosis of the liver. [105] => [106] => === Genetic === [107] => Genetic causes of hepatitis include [[Alpha 1-antitrypsin deficiency|alpha-1-antitrypsin deficiency]], [[HFE hereditary haemochromatosis|hemochromatosis]], and [[Wilson's disease]]. In alpha-1-antitrypsin deficiency, a [[Co-dominant expression|co-dominant]] mutation in the gene for alpha-1-antitrypsin results in the abnormal accumulation of the mutant AAT protein within liver cells, leading to liver disease.{{Cite journal|last=Teckman|first=Jeffrey H.|date=2013-03-07|title=Liver Disease in Alpha-1 Antitrypsin Deficiency: Current Understanding and Future Therapy|journal=COPD: Journal of Chronic Obstructive Pulmonary Disease|volume=10|issue=sup1|pages=35–43|doi=10.3109/15412555.2013.765839|pmid=23527737|s2cid=35451941|issn=1541-2555}} Hemochromatosis and Wilson's disease are both [[autosomal recessive]] diseases involving abnormal storage of minerals. In hemochromatosis, excess amounts of iron accumulate in multiple body sites, including the liver, which can lead to cirrhosis. In Wilson's disease, excess amounts of copper accumulate in the liver and brain, causing cirrhosis and dementia. [108] => [109] => When the liver is involved, alpha-1-antitrypsin deficiency and Wilson's disease tend to present as hepatitis in the neonatal period or in childhood. Hemochromatosis typically presents in adulthood, with the onset of clinical disease usually after age 50. [110] => [111] => === Ischemic hepatitis === [112] => {{Main|Ischemic hepatitis}} [113] => [[Ischemic hepatitis]] (also known as shock liver) results from reduced blood flow to the liver as in shock, heart failure, or vascular insufficiency.{{cite web|title=Hepatic ischemia|url=https://www.nlm.nih.gov/medlineplus/ency/article/000214.htm|publisher=National Library of Medicine|access-date=4 December 2013|author=Medline Plus|date=2012-08-10|url-status=live|archive-url=https://web.archive.org/web/20131208021441/http://www.nlm.nih.gov/medlineplus/ency/article/000214.htm|archive-date=8 December 2013}} The condition is most often associated with [[heart failure]] but can also be caused by [[Shock (circulatory)|shock]] or [[sepsis]]. [[Blood testing]] of a person with ischemic hepatitis will show very high levels of [[Elevated transaminases|transaminase enzymes]] ([[Aspartate transaminase|AST]] and [[Alanine transaminase|ALT]]). The condition usually resolves if the underlying cause is treated successfully. Ischemic hepatitis rarely causes permanent liver damage.{{cite book|title=Sleisenger and Fordtran's Gastrointestinal and Liver Disease|year=2010|publisher=Saunders|isbn=978-1416061892|chapter-url=http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4160-6189-2..00083-4--s0085&isbn=978-1-4160-6189-2&type=bookPage&from=content&uniqId=431734887-1227|editor1=Feldman, Friedman |editor2=Feldman, Brandt|access-date=4 December 2013|chapter-format=Online|chapter=Chapter 83 Vascular Diseases of the Liver|url-status=live|archive-url=https://web.archive.org/web/20160304110546/http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4160-6189-2..00083-4--s0085&isbn=978-1-4160-6189-2&type=bookPage&from=content&uniqId=431734887-1227|archive-date=4 March 2016}} [114] => [115] => === Other === [116] => {{Main|Neonatal hepatitis}} [117] => Hepatitis can also occur in neonates and is attributable to a variety of causes, some of which are not typically seen in adults.{{cite journal |author1=Samyn, M |author2=Mieli-Vergani, G |date=November 2015 |title=Liver and Biliary Disease in Infancy |journal=Medicine |volume=43 |issue=11 |pages=625–630 |doi= 10.1016/j.mpmed.2015.08.008}} Congenital or perinatal infection with the hepatitis viruses, [[Toxoplasma gondii|toxoplasma]], [[rubella]], [[cytomegalovirus]], and [[syphilis]] can cause neonatal hepatitis. Structural abnormalities such as [[biliary atresia]] and [[choledochal cysts]] can lead to [[Cholestasis|cholestatic liver injury]] leading to neonatal hepatitis. [[Inborn error of metabolism|Metabolic diseases]] such as [[Glycogen storage disease|glycogen storage disorders]] and [[Lysosomal storage disease|lysosomal storage disorders]] are also implicated. Neonatal hepatitis can be [[Idiopathy|idiopathic]], and in such cases, biopsy often shows large multinucleated cells in the liver tissue.{{cite journal |last=Roberts |first=Eve A. |date=2003-10-01 |title=Neonatal hepatitis syndrome |journal=Seminars in Neonatology |volume=8 |issue=5 |pages=357–374 |doi=10.1016/S1084-2756(03)00093-9 |issn=1084-2756 |pmid=15001124}} This disease is termed giant cell hepatitis and may be associated with viral infection, autoimmune disorders, and drug toxicity.{{cite book |last1=Sokol |first1=Ronald J. |last2=Narkewicz |first2=Michael R. |chapter=Chapter 22: Liver & Pancreas |editor1-last=Hay |editor1-first=William W. |display-editors=etal |title=Current diagnosis & treatment: pediatrics |edition=21st |location=New York |publisher=McGraw-Hill Medical |isbn=978-0-07-177970-8 |chapter-url=http://www.accessmedicine.com/content.aspx?aID=56821699 |access-date=2 December 2013 |url-status=live |archive-url=https://web.archive.org/web/20131210093945/http://www.accessmedicine.com/content.aspx?aID=56821699 |archive-date=10 December 2013 |date=2012-06-21 }}{{cite journal |last=Alexopoulou |first=Alexandra |author2=Deutsch, Melanie |author3=Ageletopoulou, Johanna |author4=Delladetsima, Johanna K. |author5=Marinos, Evangelos |author6=Kapranos, Nikiforos |author7=Dourakis, Spyros P. |date=May 2003 |title=A fatal case of postinfantile giant cell hepatitis in a patient with chronic lymphocytic leukaemia |journal=European Journal of Gastroenterology & Hepatology |volume=15 |issue=5 |pages=551–555 |doi=10.1097/01.meg.0000050026.34359.7c |pmid=12702915}} [118] => [119] => == Mechanism == [120] => [121] => The specific mechanism varies and depends on the underlying cause of the hepatitis. Generally, there is an initial insult that causes liver injury and activation of an inflammatory response, which can become chronic, leading to progressive [[fibrosis]] and [[cirrhosis]]. [122] => [123] => === Viral hepatitis === [124] => [125] => [[File:Stages of Liver disease NIDDK NIH.gif|thumb|upright=1.3|Stages of liver disease]] [126] => The pathway by which hepatic viruses cause [[viral hepatitis]] is best understood in the case of hepatitis B and C. The viruses do not directly activate [[apoptosis]] (cell death).{{Cite journal|last1=Nakamoto|first1=Yasunari|last2=Kaneko|first2=Shuichi|date=2003-09-01|title=Mechanisms of viral hepatitis induced liver injury|journal=Current Molecular Medicine|volume=3|issue=6|pages=537–544|issn=1566-5240|pmid=14527085|doi=10.2174/1566524033479591}} Rather, infection of liver cells activates the [[Innate immune system|innate]] and [[Adaptive immune system|adaptive]] arms of the [[immune system]] leading to an inflammatory response which causes cellular damage and death, including viral-induced apoptosis via the induction of the death receptor-mediated signaling pathway.{{Cite journal|last1=Lin|first1=Shaoli|last2=Zhang|first2=Yan-Jin|date=August 2017|title=Interference of Apoptosis by Hepatitis B Virus|journal=Viruses|language=en|volume=9|issue=8|page=230|doi=10.3390/v9080230|pmid=28820498|pmc=5580487|doi-access=free}}{{Cite journal|last1=Cao|first1=Lei|last2=Quan|first2=Xi-Bing|last3=Zeng|first3=Wen-Jiao|last4=Yang|first4=Xiao-Ou|last5=Wang|first5=Ming-Jie|date=2016|title=Mechanism of Hepatocyte Apoptosis|journal=Journal of Cell Death|language=en|volume=9|pages=19–29|doi=10.4137/JCD.S39824|pmid=28058033|pmc=5201115}} Depending on the strength of the immune response, the types of immune cells involved and the ability of the virus to evade the body's defense, infection can either lead to clearance (acute disease) or persistence (chronic disease) of the virus. The chronic presence of the virus within liver cells results in multiple waves of [[inflammation]], injury and [[wound healing]] that over time lead to scarring or [[fibrosis]] and culminate in [[hepatocellular carcinoma]].{{Cite journal|last=Wong|first=Grace Lai-Hung|date=2014-09-01|title=Prediction of fibrosis progression in chronic viral hepatitis|journal=Clinical and Molecular Hepatology|volume=20|issue=3|pages=228–236|doi=10.3350/cmh.2014.20.3.228|issn=2287-285X|pmc=4197170|pmid=25320725}} People with impaired immune response are at greater risk of developing chronic infection. [[Natural killer cell]]s are the primary drivers of the initial innate response and create a [[cytokine]] environment that results in the recruitment of [[T helper cell|CD4 T-helper]] and [[Cytotoxic T cell|CD8 cytotoxic T-cells]].{{Cite journal|last=Rehermann|first=Barbara|date=2015-11-01|title=Natural Killer Cells in Viral Hepatitis|journal=Cellular and Molecular Gastroenterology and Hepatology|volume=1|issue=6|pages=578–588|doi=10.1016/j.jcmgh.2015.09.004|issn=2352-345X|pmc=4678927|pmid=26682281}}{{Cite journal|last1=Heim|first1=Markus H.|last2=Thimme|first2=Robert|date=2014-11-01|title=Innate and adaptive immune responses in HCV infections|journal=Journal of Hepatology|volume=61|issue=1 Suppl|pages=S14–25|doi=10.1016/j.jhep.2014.06.035|issn=1600-0641|pmid=25443342|doi-access=free}} [[Interferon type I|Type I interferons]] are the cytokines that drive the antiviral response. In chronic Hepatitis B and C, natural killer cell function is impaired. [127] => [128] => === Steatohepatitis === [129] => [130] => [[Steatohepatitis]] is seen in both alcoholic and non-alcoholic liver disease and is the culmination of a cascade of events that began with injury. In the case of [[Non-alcoholic fatty liver disease|non-alcoholic steatohepatitis]], this cascade is initiated by changes in metabolism associated with obesity, insulin resistance, and lipid dysregulation.{{Cite journal|last1=Hardy|first1=Timothy|last2=Oakley|first2=Fiona|last3=Anstee|first3=Quentin M.|last4=Day|first4=Christopher P.|date=2016-03-03|title=Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum|journal=Annual Review of Pathology|doi=10.1146/annurev-pathol-012615-044224|issn=1553-4014|pmid=26980160|volume=11|pages=451–96|url=https://zenodo.org/record/3452754}}{{Dead link|date=February 2022 |bot=InternetArchiveBot |fix-attempted=yes }}{{Cite journal|last1=Yoon|first1=Hye-Jin|last2=Cha|first2=Bong Soo|date=2014-11-27|title=Pathogenesis and therapeutic approaches for non-alcoholic fatty liver disease|journal=World Journal of Hepatology|volume=6|issue=11|pages=800–811|doi=10.4254/wjh.v6.i11.800|issn=1948-5182|pmc=4243154|pmid=25429318 |doi-access=free }} In [[alcoholic hepatitis]], chronic excess alcohol use is the culprit. Though the inciting event may differ, the progression of events is similar and begins with accumulation of free [[fatty acid]]s (FFA) and their breakdown products in the liver cells in a process called [[steatosis]]. This initially reversible process overwhelms the [[hepatocyte]]'s ability to maintain lipid homeostasis leading to a toxic effect as fat molecules accumulate and are broken down in the setting of an [[Cellular stress response|oxidative stress response]]. Over time, this abnormal lipid deposition triggers the [[immune system]] via [[Toll-like receptor|toll-like receptor 4]] (TLR4) resulting in the production of inflammatory [[cytokine]]s such as TNF that cause liver cell injury and death. These events mark the transition to [[steatohepatitis]] and in the setting of chronic injury, [[fibrosis]] eventually develops setting up events that lead to cirrhosis and hepatocellular carcinoma. Microscopically, changes that can be seen include steatosis with large and swollen hepatocytes ([[Ballooning degeneration|ballooning]]), evidence of cellular injury and cell death (apoptosis, necrosis), evidence of inflammation in particular in [[Liver|zone 3 of the liver]], variable degrees of fibrosis and [[Mallory body|Mallory bodies]].{{Cite journal|last1=Basra|first1=Sarpreet|last2=Anand|first2=Bhupinderjit S.|date=2011-05-27|title=Definition, epidemiology and magnitude of alcoholic hepatitis|journal=World Journal of Hepatology|volume=3|issue=5|pages=108–113|doi=10.4254/wjh.v3.i5.108|issn=1948-5182|pmc=3124876|pmid=21731902 |doi-access=free }}{{Cite journal|last1=Haga|first1=Yuki|last2=Kanda|first2=Tatsuo|last3=Sasaki|first3=Reina|last4=Nakamura|first4=Masato|last5=Nakamoto|first5=Shingo|last6=Yokosuka|first6=Osamu|date=2015-12-14|title=Nonalcoholic fatty liver disease and hepatic cirrhosis: Comparison with viral hepatitis-associated steatosis|journal=World Journal of Gastroenterology|volume=21|issue=46|pages=12989–12995|doi=10.3748/wjg.v21.i46.12989|issn=2219-2840|pmc=4674717|pmid=26675364 |doi-access=free }} [131] => [132] => == Diagnosis == [133] => {| class="wikitable" style = "float: right; margin-left:15px; text-align:center" [134] => ! scope="col" |Most elevated aminotransferase [135] => ! scope="col" |Cause [136] => |- [137] => | rowspan="9" | ALT [138] => |Chronic hepatitis B, C, and D [139] => |- [140] => |Nonalcoholic liver disease [141] => |- [142] => |Acute viral hepatitis [143] => |- [144] => |Medications/toxins [145] => |- [146] => |Autoimmune hepatitis [147] => |- [148] => |Wilson's disease [149] => |- [150] => |Alpha-1-antitrypsin deficiency [151] => |- [152] => |Hemochromatosis [153] => |- [154] => |''Ischemic hepatitis (severe elevation up to thousands)'' [155] => |- [156] => | rowspan="2" | AST [157] => |Alcoholic liver disease [158] => |- [159] => |Cirrhosis [160] => |} [161] => [[File:Histopathology of acute hepatitis.jpg|thumb|Histopathology of acute hepatitis with lobular disarray and associated lymphocytic inflammation, acidophil body formation (arrow) and bilirubinostasis.]] [162] => Diagnosis of hepatitis is made on the basis of some or all of the following: a person's signs and symptoms, medical history including sexual and substance use history, blood tests, [[Medical imaging|imaging]], and [[liver biopsy]]. In general, for viral hepatitis and other acute causes of hepatitis, the person's blood tests and clinical picture are sufficient for diagnosis. For other causes of hepatitis, especially chronic causes, blood tests may not be useful. In this case, liver biopsy is the [[Gold standard (test)|gold standard]] for establishing the diagnosis: [[Histopathology|histopathologic]] analysis is able to reveal the precise extent and pattern of inflammation and [[fibrosis]]. Biopsy is typically not the initial diagnostic test because it is invasive and is associated with a small but significant risk of bleeding that is increased in people with liver injury and cirrhosis.{{cite journal|last=Grant|first=A|year=1999|title=Guidelines on the use of liver biopsy in clinical practice|journal=Gut|volume=45|issue=Suppl 4|pages=1–11|doi=10.1136/gut.45.2008.iv1|pmc=1766696|pmid=10485854|quote=The main cause of mortality after percutaneous liver biopsy is intraperitoneal haemorrhage as shown in a retrospective Italian study of 68 000 percutaneous liver biopsies in which all six patients who died did so from intraperitoneal haemorrhage. Three of these patients had had a laparotomy, and all had either cirrhosis or malignant disease, both of which are risk factors for bleeding.|author2=Neuberger J}} [163] => [164] => Blood testing includes [[Liver function tests|liver enzymes]], [[serology]] (i.e. for autoantibodies), [[nucleic acid test]]ing (i.e. for hepatitis virus DNA/RNA), [[Blood chemistry study|blood chemistry]], and [[complete blood count]]. Characteristic patterns of liver enzyme abnormalities can point to certain causes or stages of hepatitis.{{cite journal|last=Green|first=RM|date=October 2002|title=AGA technical review on the evaluation of liver chemistry tests|journal=Gastroenterology|volume=123|issue=4|pages=1367–84|doi=10.1053/gast.2002.36061|pmid=12360498|author2=Flamm, S|doi-access=free}}{{cite journal|last=Pratt|first=DS|date=Apr 27, 2000|title=Evaluation of abnormal liver-enzyme results in asymptomatic patients|journal=The New England Journal of Medicine|volume=342|issue=17|pages=1266–71|doi=10.1056/NEJM200004273421707|pmid=10781624|author2=Kaplan, MM}} Generally, [[Aspartate transaminase|AST]] and [[Alanine transaminase|ALT]] are elevated in most cases of hepatitis regardless of whether the person shows any symptoms. The degree of elevation (i.e. levels in the hundreds vs. in the thousands), the predominance for AST vs. ALT elevation, and the ratio between AST and ALT are informative of the diagnosis. [165] => [166] => [[Medical ultrasound|Ultrasound]], [[CT scan|CT]], and [[Magnetic resonance imaging|MRI]] can all identify steatosis (fatty changes) of the liver tissue and nodularity of the liver surface suggestive of cirrhosis.{{Cite journal|last1=Ito|first1=Katsuyoshi|last2=Mitchell|first2=Donald G.|title=Imaging Diagnosis of Cirrhosis and Chronic Hepatitis|journal=Intervirology|volume=47|issue=3–5|pages=134–143|doi=10.1159/000078465|pmid=15383722|year=2004|s2cid=36112368}}{{Cite journal|last1=Allan|first1=Richard|last2=Thoirs|first2=Kerry|last3=Phillips|first3=Maureen|date=2010-07-28|title=Accuracy of ultrasound to identify chronic liver disease|journal=World Journal of Gastroenterology|volume=16|issue=28|pages=3510–3520|doi=10.3748/wjg.v16.i28.3510|issn=1007-9327|pmc=2909550|pmid=20653059 |doi-access=free }} CT and especially MRI are able to provide a higher level of detail, allowing visualization and characterize such structures as vessels and tumors within the liver.{{Cite journal|last1=Sahani|first1=Dushyant V.|last2=Kalva|first2=Sanjeeva P.|date=2004-07-01|title=Imaging the Liver|journal=The Oncologist|language=en|volume=9|issue=4|pages=385–397|doi=10.1634/theoncologist.9-4-385|issn=1083-7159|pmid=15266092|doi-access=free}} Unlike steatosis and cirrhosis, no imaging test is able to detect liver inflammation (i.e. hepatitis) or fibrosis. Liver biopsy is the only definitive diagnostic test that is able to assess inflammation and fibrosis of the liver. [167] => [168] => === Viral hepatitis === [169] => {{Main|Viral hepatitis}} [170] => [171] => Viral hepatitis is primarily diagnosed through blood tests for levels of viral [[antigen]]s (such as the [[HBsAg|hepatitis B surface]] or [[HBcAg|core]] antigen), anti-viral antibodies (such as the anti-hepatitis B surface antibody or anti-hepatitis A antibody), or viral DNA/RNA. In early infection (i.e. within 1 week), [[Immunoglobulin M|IgM]] antibodies are found in the blood. In late infection and after recovery, [[Immunoglobulin G|IgG]] antibodies are present and remain in the body for up to years. Therefore, when a patient is positive for IgG antibody but negative for IgM antibody, he is considered [[Immunity (medical)|immune]] from the virus via either prior infection and recovery or prior vaccination. [172] => [173] => In the case of hepatitis B, blood tests exist for multiple virus antigens (which are different components of the [[:File:HBV.png|virion particle]]) and antibodies.{{cite journal |year=2015 |title=Update on hepatitis B and C virus diagnosis |journal=World Journal of Virology |volume=4 |issue=4 |pages=323–42 |doi=10.5501/wjv.v4.i4.323 |pmc=4641225 |pmid=26568915 |vauthors=Villar LM, Cruz HM, Barbosa JR, Bezerra CS, Portilho MM, Scalioni Lde P |doi-access=free }} The combination of antigen and antibody positivity can provide information about the stage of infection (acute or chronic), the degree of viral replication, and the infectivity of the virus. [174] => [175] => === Alcoholic versus non-alcoholic === [176] => The most apparent distinguishing factor between [[Alcoholic hepatitis|alcoholic steatohepatitis]] (ASH) and [[Nonalcoholic Steatohepatitis|nonalcoholic steatohepatitis]] (NASH) is a history of excessive alcohol use.{{Cite journal|last1=Neuman|first1=Manuela G.|last2=French|first2=Samuel W.|last3=French|first3=Barbara A.|last4=Seitz|first4=Helmut K.|last5=Cohen|first5=Lawrence B.|last6=Mueller|first6=Sebastian|last7=Osna|first7=Natalia A.|last8=Kharbanda|first8=Kusum K.|last9=Seth|first9=Devanshi|date=2014-12-01|title=Alcoholic and non-alcoholic steatohepatitis|journal=Experimental and Molecular Pathology|volume=97|issue=3|pages=492–510|doi=10.1016/j.yexmp.2014.09.005|pmc=4696068|pmid=25217800}} Thus, in patients who have no or negligible alcohol use, the diagnosis is unlikely to be alcoholic hepatitis. In those who drink alcohol, the diagnosis may just as likely be alcoholic or nonalcoholic hepatitis especially if there is concurrent obesity, diabetes, and metabolic syndrome. In this case, alcoholic and nonalcoholic hepatitis can be distinguished by the pattern of liver enzyme abnormalities; specifically, in alcoholic steatohepatitis AST>ALT with ratio of AST:ALT>2:1 while in nonalcoholic steatohepatitis ALT>AST with ratio of ALT:AST>1.5:1. [177] => [178] => Liver biopsies show identical findings in patients with ASH and NASH, specifically, the presence of [[Granulocyte|polymorphonuclear]] infiltration, hepatocyte [[necrosis]] and [[apoptosis]] in the form of [[ballooning degeneration]], [[Mallory body|Mallory bodies]], and fibrosis around veins and sinuses. [179] => [180] => == Virus screening == [181] => The purpose of screening for viral hepatitis is to identify people infected with the disease as early as possible, even before symptoms and transaminase elevations may be present. This allows for early treatment, which can both prevent disease progression and decrease the likelihood of transmission to others.{{Cite web |date=2021-08-13 |title=Hepatitis Testing |url=https://www.testing.com/hepatitis-testing/ |access-date=2023-05-12 |website=Testing.com |language=en-US}} [182] => [183] => === Hepatitis A === [184] => Hepatitis A causes an acute illness that does not progress to chronic liver disease. Therefore, the role of screening is to assess immune status in people who are at high risk of contracting the virus, as well as in people with known liver disease for whom hepatitis A infection could lead to liver failure.{{Cite web|url=https://www.cdc.gov/hepatitis/statistics/surveillanceguidelines.htm|title=Guidelines For Viral Hepatitis Surveillance And Case Management|website=www.cdc.gov|access-date=2016-03-12|url-status=live|archive-url=https://web.archive.org/web/20160310094046/http://www.cdc.gov/hepatitis/statistics/surveillanceguidelines.htm|archive-date=2016-03-10}}{{Cite book|title=Harrison's Manual of Medicine|edition=18|chapter=Chapter 164: Chronic Hepatitis|last1=Harrison|first1=Tindsley Randolph|editor-last1=Longo|editor-first1=Dan L.|editor-last2=Fauci|editor-first2=Anthony S.|editor-link2=Anthony Fauci|editor-last3=Kasper|editor-first3=Dennis L.|editor-last4=Hauser|editor-first4=Stephen L.|editor-last5=Jameson|editor-first5=L. Jerry|editor-last6=Loscalzo|editor-first6=Jerry|publisher=McGraw-Hill|date=2013|location=New York, NY}} People in these groups who are not already immune can receive the [[hepatitis A vaccine]].{{cn|date=March 2023}} [185] => [186] => Those at high risk and in need of screening include:{{cite web|title=Adult Immunization Schedule by Vaccine and Age Group|url=https://www.cdc.gov/vaccines/schedules/hcp/child-adolescent.html|website=www.CDC.gov|access-date=March 7, 2016|url-status=live|archive-url=https://web.archive.org/web/20160305212647/http://www.cdc.gov/vaccines/schedules/hcp/child-adolescent.html|archive-date=March 5, 2016}} [187] => * People in close contact (either living with or having sexual contact) with someone who has hepatitis A [188] => * People traveling to an area with endemic hepatitis A [189] => * People who do not have access to clean water [190] => * People who use illicit drugs [191] => * People with liver disease [192] => * People with poor sanitary habits such as not washing hands after using the restroom or changing diapers [193] => [194] => The presence of anti-hepatitis A [[Immunoglobulin G|IgG]] in the blood indicates past infection with the virus or prior vaccination.{{Cite book|title=Chapter 163: "Acute Hepatitis." Harrison's Manual of Medicine, 18e.|last=Longo, Dan L.|publisher=McGraw-Hill|year=2013|location=New York, NY|display-authors=etal}} [195] => [196] => === Hepatitis B === [197] => [[File:Hepatitis B virus v2.png|thumb|Hepatitis B virus v2]] [198] => The [[Centers for Disease Control and Prevention|CDC]], [[World Health Organization|WHO]], [[United States Preventive Services Task Force|USPSTF]], and [[American Congress of Obstetricians and Gynecologists|ACOG]] recommend routine hepatitis B screening for certain high-risk populations.{{Cite web|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5708a1.htm#fig3|title=Recommendations for Identification and Public Health Management of Persons with Chronic Hepatitis B Virus Infection|website=www.cdc.gov|access-date=2016-03-11|url-status=live|archive-url=https://web.archive.org/web/20160306035320/http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5708a1.htm#fig3|archive-date=2016-03-06}}{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK208504/|title=Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults: Systematic Review to Update the 2004 U.S. Preventive Services Task Force Recommendation|last1=Chou|first1=Roger|last2=Dana|first2=Tracy|last3=Bougatsos|first3=Christina|last4=Blazina|first4=Ian|last5=Zakher|first5=Bernadette|last6=Khangura|first6=Jessi|date=2014-01-01|publisher=Agency for Healthcare Research and Quality (US)|series=U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews|location=Rockville (MD)|pmid=24921112}}{{Cite web|url=https://www.who.int/hiv/pub/hepatitis/hepatitis-b-guidelines/en/|title=Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection|website=World Health Organization|language=en-GB|access-date=2016-03-11|url-status=dead|archive-url=https://web.archive.org/web/20160220104219/http://www.who.int/hiv/pub/hepatitis/hepatitis-b-guidelines/en/|archive-date=2016-02-20}}{{Cite web|url=http://www.acog.org/Resources-And-Publications/Practice-Bulletins/Committee-on-Practice-Bulletins-Obstetrics/Viral-Hepatitis-in-Pregnancy|title=ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists: Viral Hepatitis in Pregnancy|website=www.acog.org|access-date=2016-03-12|archive-date=2020-08-07|archive-url=https://web.archive.org/web/20200807231110/https://www.acog.org/Resources-And-Publications/Practice-Bulletins/Committee-on-Practice-Bulletins-Obstetrics/Viral-Hepatitis-in-Pregnancy|url-status=dead}} Specifically, these populations include people who are: [199] => * Beginning [[Immunosuppressive drug|immunosuppressive]] or [[Chemotherapy|cytotoxic therapy]] [200] => * Blood, organ, or tissue donors [201] => * Born in countries where the prevalence of hepatitis B is high (defined as ≥2% of the population), whether or not they have been vaccinated [202] => * Born in the United States whose parents are from countries where the prevalence of hepatitis B is very high (defined as ≥8% of the population), and who were not vaccinated [203] => * Found to have elevated [[Liver function tests|liver enzymes]] without a known cause [204] => * [[HIV/AIDS|HIV]] positive [205] => * In close contact with (i.e. live or have sex with) people known to have hepatitis B [206] => * Incarcerated [207] => * [[Intravenous drug users]] [208] => * [[Men who have sex with men]] [209] => * On [[hemodialysis]] [210] => * Pregnant [211] => Screening consists of a blood test that detects hepatitis B surface antigen ([[HBsAg]]). If HBsAg is present, a second test – usually done on the same blood sample – that detects the antibody for the hepatitis B core antigen (anti-[[HBcAg]]) can differentiate between acute and chronic infection.{{Cite book|title=CURRENT Practice Guidelines in Primary Care 2015|author1=Esherick JS |author2=Clark DS |author3=Slater ED |publisher=McGraw-Hill|year=2015|location=New York, NY|display-authors=etal}} People who are high-risk whose blood tests negative for HBsAg can receive the [[hepatitis B vaccine]] to prevent future infection. [212] => [213] => === Hepatitis C === [214] => [[File:HCV structure.png|thumb|HCV structure]] [215] => [[File:ABHD5CGI-58-the-Chanarin-Dorfman-Syndrome-Protein-Mobilises-Lipid-Stores-for-Hepatitis-C-Virus-ppat.1005568.s014.ogv|thumb|ABHD5CGI-58-the-Chanarin-Dorfman-Syndrome-Protein-Mobilises-Lipid-Stores-for-Hepatitis-C-Virus-ppat.1005568.s014]] [216] => The [[Centers for Disease Control and Prevention|CDC]], [[World Health Organization|WHO]], [[United States Preventive Services Task Force|USPSTF]], [[AASLD]], and [[American Congress of Obstetricians and Gynecologists|ACOG]] recommend screening people at high risk for hepatitis C infection.{{Cite web|url=https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/hepatitis-c-screening|title=Final Recommendation Statement: Hepatitis C: Screening – US Preventive Services Task Force|website=www.uspreventiveservicestaskforce.org|access-date=2016-03-21|url-status=live|archive-url=https://web.archive.org/web/20160321180306/http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/hepatitis-c-screening|archive-date=2016-03-21}} These populations include people who are: [217] => * Adults in the United States born between 1945 and 1965 [218] => * Blood or organ donors. [219] => * Born to HCV-positive mothers [220] => * HIV-positive [221] => * Incarcerated, or who have been in the past [222] => * Intranasal illicit drug users [223] => * Intravenous drug users (past or current) [224] => * Men who have sex with men [225] => * On long-term hemodialysis, or who have been in the past [226] => * Pregnant, and engaging in high-risk behaviors [227] => * Recipients of blood products or organs prior to 1992 in the United States [228] => * Recipients of tattoos in an "unregulated setting" [229] => * Sex workers [230] => * Workers in a healthcare setting who have had a needlestick injury [231] => For people in the groups above whose exposure is ongoing, screening should be periodic, though there is no set optimal screening interval. The AASLD recommends screening men who have sex with men who are HIV-positive annually. People born in the US between 1945 and 1965 should be screened once (unless they have other exposure risks). [232] => [233] => Screening consists of a blood test that detects anti-hepatitis C virus antibody. If anti-hepatitis C virus antibody is present, a confirmatory test to detect HCV RNA indicates chronic disease. [234] => [235] => === Hepatitis D === [236] => The [[Centers for Disease Control and Prevention|CDC]], [[World Health Organization|WHO]], [[United States Preventive Services Task Force|USPSTF]], [[AASLD]], and [[American Congress of Obstetricians and Gynecologists|ACOG]] recommend screening people at high risk for hepatitis D infection. These populations include people who are: [237] => * Blood or organ donors. [238] => * Incarcerated, or who have been in the past [239] => * Intranasal illicit drug users [240] => * Intravenous drug users (past or current) [241] => * Sex workers [242] => * Workers in a healthcare setting who have had a needlestick injury [243] => [244] =>

Hepatitis D is extremely rare. Symptoms include chronic diarrhea, anal and intestinal blisters, purple urine, and burnt popcorn scented breath. [245] => [246] => Screening consists of a blood test that detects the anti-hepitits D virus antibbody. If anti-hepitits D virus antibody is present, a confirmatory test to detect HDV RNA DNA indicates chronic disease.

[247] => [248] => == Prevention == [249] => [250] => === Vaccines === [251] => ==== Hepatitis A ==== [252] => [253] => {{Main|Hepatitis A vaccine}} [254] => [[File:Havrix-rokote.jpg|thumb|Havrix vaccine]] [255] => The CDC recommends the [[hepatitis A vaccine]] for all children beginning at age one, as well as for those who have not been previously immunized and are at high risk for contracting the disease.{{cite web|title=Hepatitis A Fact sheet N°328|url=https://www.who.int/mediacentre/factsheets/fs328/en/|website=WHO Media Centre|access-date=March 7, 2016|url-status=live|archive-url=https://web.archive.org/web/20140221042107/http://www.who.int/mediacentre/factsheets/fs328/en/|archive-date=February 21, 2014}}{{cite journal|last1=Voise|first1=Nathan|title=Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention. A shot at hepatitis prevention.|journal=J Am Osteopath Assoc|date=Oct 2011|volume=111|issue=10 Suppl 6|pages=S13–6|pmid=22086888}} [256] => [257] => For children 12 months of age or older, the vaccination is given as a shot into the muscle in two doses 6–18 months apart and should be started before the age 24 months.{{cite web|title=Birth-18 Years and Catchup Immunization Schedules for Providers.|url=https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html|website=www.CDC.gov|access-date=March 7, 2016|url-status=live|archive-url=https://web.archive.org/web/20160306220930/http://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html|archive-date=March 6, 2016}} The dosing is slightly different for adults depending on the type of the vaccine. If the vaccine is for hepatitis A only, two doses are given 6–18 months apart depending on the manufacturer. If the vaccine is [[Hepatitis A vaccine|combined hepatitis A and hepatitis B]], up to 4 doses may be required. [258] => [259] => ==== Hepatitis B ==== [260] => {{Main|Hepatitis B vaccine|l1=Hepatitis B vaccine}} [261] => [[File:WHO-UNICEF estimates of hepatitis B vaccine (HepB-BD) coverage in countries from the European WHO region in the years 2000-2015.png|thumb|WHO-UNICEF estimates of hepatitis B vaccine (HepB-BD) coverage in countries from the European WHO region in the years 2000–2015]] [262] => The CDC recommends the routine vaccination of all children under the age of 19 with the [[hepatitis B vaccine]].{{cite web|last1=Centers for Disease Control|title=Update: recommendations to prevent hepatitis B virus transmission—United States. MMWR 1999|date=1999|volume=48|pages=33–4|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/00056293.htm|access-date=March 7, 2016|url-status=live|archive-url=https://web.archive.org/web/20160514225848/http://www.cdc.gov/mmwr/preview/mmwrhtml/00056293.htm|archive-date=May 14, 2016}} They also recommend it for those who desire it or are at high risk. [263] => [264] => Routine vaccination for hepatitis B starts with the first dose administered as a shot into the muscle before the newborn is discharged from the hospital. An additional two doses should be administered before the child is 18 months. [265] => [266] => For babies born to a mother with hepatitis B surface antigen positivity, the first dose is unique – in addition to the vaccine, the hepatitis immune globulin should also be administered, both within 12 hours of birth. These newborns should also be regularly tested for infection for at least the first year of life. [267] => [268] => There is also a combination formulation that includes [[Hepatitis A vaccine|both hepatitis A and B vaccines]].{{Cite web|url=https://www.mayoclinic.org/drugs-supplements/hepatitis-a-and-hepatitis-b-vaccine-intramuscular-route/description/drg-20061965|title=Hepatitis A And Hepatitis B Vaccine (Intramuscular Route)|website=Mayo Clinic|access-date=25 January 2018}} [269] => [270] => ==== Other ==== [271] => [272] => There are currently no vaccines available in the United States for hepatitis C or E. In 2015, a group in China published an article regarding the development of a [[vaccine for hepatitis E]].{{Cite journal|last=Zhang|date=March 5, 2015|title=Long-Term Efficacy of a Hepatitis E Vaccine|journal=NEJM|doi=10.1056/NEJMoa1406011|pmid=25738667|display-authors=etal|volume=372|issue=10|pages=914–22|doi-access=free}} As of March 2016, the United States government was in the process of recruiting participants for the [[Phases of clinical research|phase IV trial]] of the hepatitis E vaccine.{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT02189603|title=Phase IV Clinical Trial of Recombinant Hepatitis E Vaccine（Hecolin） - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov|access-date=2016-03-09|url-status=live|archive-url=https://web.archive.org/web/20160309154410/https://clinicaltrials.gov/ct2/show/NCT02189603|archive-date=2016-03-09}} [273] => [274] => === Behavioral changes === [275] => [276] => ==== Hepatitis A ==== [277] => Because hepatitis A is transmitted primarily through the [[Fecal-oral route|oral-fecal route]], the mainstay of prevention aside from vaccination is good hygiene, access to clean water and proper handling of sewage. [278] => [279] => ==== Hepatitis B and C ==== [280] => As hepatitis B and C are transmitted through blood and multiple [[bodily fluids]], prevention is aimed at screening blood prior to [[Blood transfusion|transfusion]], abstaining from the use of injection drugs, safe needle and sharps practices in healthcare settings, and safe sex practices. [281] => [282] => ====Hepatitis D==== [283] => [[File:Hep D Epidemiology Figure 1.svg|thumb|350x350px|Worldwide prevalence of HDV among HBV carriers in 2015. Eight genotypes have been identified worldwide by comparative phylogenetic analysis. Genotype 1 is the most frequent and has variable pathogenicity, Genotypes 2 and 4 are found in East Asia causing relatively mild disease. Genotype 3 is found in South America in association with severe hepatitis. Genotypes 5, 6, 7, 8 have been found only in Africa.{{Cite journal|last=Rizzetto|first=Mario | name-list-style = vanc |date=2020|title=Epidemiology of the Hepatitis D virus|url=https://en.wikiversity.org/wiki/WikiJournal_of_Medicine/Epidemiology_of_the_Hepatitis_D_virus|journal=WikiJournal of Medicine|language=en|volume=7|pages=7|doi=10.15347/wjm/2020.001 |doi-access=free}}]] [284] => The hepatitis D virus requires that a person first be infected with hepatitis B virus, so prevention efforts should focus on limiting the spread of hepatitis B. In people who have chronic hepatitis B infection and are at risk for [[superinfection]] with the hepatitis D virus, the preventive strategies are the same as for hepatitis B.{{Cite web|url=https://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html|title=WHO {{!}} Hepatitis D|website=www.who.int|access-date=2016-03-09|url-status=live|archive-url=https://web.archive.org/web/20160308152650/http://www.who.int/csr/disease/hepatitis/whocdscsrncs20011/en/index5.html|archive-date=2016-03-08}} [285] => [286] => ====Hepatitis E==== [287] => [288] => Hepatitis E is spread primarily through the oral-fecal route but may also be spread by blood and from mother to fetus. The mainstay of hepatitis E prevention is similar to that for hepatitis A (namely, good hygiene and clean water practices).{{Cite web|url=https://www.who.int/mediacentre/factsheets/fs280/en/|title=Hepatitis E|website=World Health Organization|language=en-GB|access-date=2016-03-09|url-status=live|archive-url=https://web.archive.org/web/20160306175719/http://www.who.int/mediacentre/factsheets/fs280/en/|archive-date=2016-03-06}} [289] => [290] => ====Alcoholic and metabolic hepatitis==== [291] => [292] => As excessive alcohol consumption can lead to hepatitis and cirrhosis, the following are maximal recommendations for alcohol consumption:{{Cite web|url=http://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking|title=Drinking Levels Defined {{!}} National Institute on Alcohol Abuse and Alcoholism (NIAAA)|website=www.niaaa.nih.gov|date=14 September 2011|access-date=2016-03-09|url-status=live|archive-url=https://web.archive.org/web/20160323085131/http://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking|archive-date=2016-03-23}} [293] => * Men – ≤ 4 drinks on any given day and ≤ 14 drinks per week [294] => * Women – ≤ 3 drinks on any given day and ≤ 7 drinks per week [295] => To prevent MAFLD it is recommended to maintain a normal weight, eat a healthy diet, avoid [[added sugar]], and exercise regularly.{{cite web |title=Preventing fatty liver disease before it's too late |url=https://wexnermedical.osu.edu/blog/fatty-liver-disease |website=wexnermedical.osu.edu |access-date=4 September 2023 |language=en |date=17 June 2020}}{{cite web |title=Nonalcoholic Fatty Liver Disease (NAFLD) |url=https://liverfoundation.org/liver-diseases/fatty-liver-disease/nonalcoholic-fatty-liver-disease-nafld/ |website=liverfoundation.org |access-date=4 September 2023 |date=23 May 2022}} [296] => [297] => === Successes === [298] => [299] => ====Hepatitis A==== [300] => [301] => In the United States, universal immunization has led to a two-thirds decrease in hospital admissions and medical expenses due to hepatitis A.{{Cite journal|last1=Franco|first1=Elisabetta|last2=Meleleo|first2=Cristina|last3=Serino|first3=Laura|last4=Sorbara|first4=Debora|last5=Zaratti|first5=Laura|date=2012-03-27|title=Hepatitis A: Epidemiology and prevention in developing countries|journal=World Journal of Hepatology|volume=4|issue=3|pages=68–73|doi=10.4254/wjh.v4.i3.68|issn=1948-5182|pmc=3321492|pmid=22489258 |doi-access=free }} [302] => [303] => ====Hepatitis B==== [304] => [305] => In the United States new cases of hepatitis B decreased 75% from 1990 to 2004.{{Cite web|url=https://www.cdc.gov/vaccines/pubs/pinkbook/hepb.html|title=Pinkbook {{!}} Hepatitis B {{!}} Epidemiology of Vaccine Preventable Diseases {{!}} CDC|website=www.cdc.gov|access-date=2016-03-09|url-status=live|archive-url=https://web.archive.org/web/20160307091653/http://www.cdc.gov/vaccines/pubs/pinkbook/hepb.html|archive-date=2016-03-07}} The group that saw the greatest decrease was children and adolescents, likely reflecting the implementation of the 1999 guidelines. [306] => [307] => ====Hepatitis C==== [308] => [309] => Hepatitis C infections each year had been declining since the 1980s, but began to increase again in 2006.{{Cite web|url=https://www.cdc.gov/hepatitis/statistics/2013surveillance/commentary.htm|title=Commentary {{!}} U.S. 2013 Surveillance Data for Viral Hepatitis {{!}} Statistics & Surveillance {{!}} Division of Viral Hepatitis {{!}} CDC|website=www.cdc.gov|access-date=2016-03-09|url-status=live|archive-url=https://web.archive.org/web/20160305151134/http://www.cdc.gov/hepatitis/statistics/2013surveillance/commentary.htm|archive-date=2016-03-05}} The data are unclear as to whether the decline can be attributed to [[needle exchange programme]]s.Wright NMJ, Millson CE, Tompkins CNE (2005). What is the evidence for the effectiveness of interventions to reduce hepatitis C infection and the associated morbidity? Copenhagen, WHO Regional Office for Europe (Health Evidence Network report; {{cite web |url=http://www.euro.who.int/document/E86159.pdf |title=WHO/Europe | Home |access-date=2016-03-09 |url-status=live |archive-url=https://web.archive.org/web/20100501124733/http://www.euro.who.int/document/e86159.pdf |archive-date=2010-05-01 }}, accessed 9 Mar 2016). [310] => [311] => ====Alcoholic hepatitis==== [312] => [313] => [[File:Depiction of a liver failure patient.png|thumb|Depiction of a liver failure patient]] [314] => Because people with alcoholic hepatitis may have no symptoms, it can be difficult to diagnose and the number of people with the disease is probably higher than many estimates.{{Cite journal|last1=Basra|first1=Sarpreet|last2=Anand|first2=Bhupinderjit S|date=2011-05-27|title=Definition, epidemiology and magnitude of alcoholic hepatitis|journal=World Journal of Hepatology|volume=3|issue=5|pages=108–113|doi=10.4254/wjh.v3.i5.108|issn=1948-5182|pmc=3124876|pmid=21731902 |doi-access=free }} Programs such as [[Alcoholics Anonymous]] have been successful in decreasing death due to [[cirrhosis]], but it is difficult to evaluate their success in decreasing the incidence of alcoholic hepatitis.{{Cite web|url=http://pubs.niaaa.nih.gov/publications/arh27-3/209-219.htm|title=The Epidemiology of Alcoholic Liver Disease|website=pubs.niaaa.nih.gov|access-date=2016-03-09|url-status=live|archive-url=https://web.archive.org/web/20160303180417/http://pubs.niaaa.nih.gov/publications/arh27-3/209-219.htm|archive-date=2016-03-03}} [315] => [316] => == Treatment == [317] => The treatment of hepatitis varies according to the type, whether it is acute or chronic, and the severity of the disease. [318] => * Activity: Many people with hepatitis prefer bed rest, though it is not necessary to avoid all physical activity while recovering. [319] => * Diet: A high-calorie diet is recommended. Many people develop nausea and cannot tolerate food later in the day, so the bulk of intake may be concentrated in the earlier part of the day. In the acute phase of the disease, intravenous feeding may be needed if patients cannot tolerate food and have poor oral intake subsequent to nausea and vomiting. [320] => * Drugs: People with hepatitis should avoid taking drugs metabolized by the liver. [[Glucocorticoid]]s are not recommended as a treatment option for acute viral hepatitis and may even cause harm, such as development of chronic hepatitis. [321] => * Precautions: [[Universal precautions]] should be observed. Isolation is usually not needed, except in cases of hepatitis A and E who have fecal incontinence, and in cases of hepatitis B and C who have uncontrolled bleeding. [322] => [323] => === Hepatitis A === [324] => {{main|Hepatitis A}} [325] => [326] => Hepatitis A usually does not progress to a chronic state, and rarely requires hospitalization. Treatment is supportive and includes such measures as providing intravenous (IV) hydration and maintaining adequate nutrition. [327] => [328] => Rarely, people with the hepatitis A virus can rapidly develop liver failure, termed ''fulminant hepatic failure'', especially the elderly and those who had a pre-existing liver disease, especially hepatitis C. Mortality risk factors include greater age and chronic hepatitis C. In these cases, more aggressive supportive therapy and liver transplant may be necessary. [329] => [330] => === Hepatitis B === [331] => {{main|Hepatitis B}} [332] => [333] => ==== Acute ==== [334] => In healthy patients, 95–99% recover with no long-lasting effects, and antiviral treatment is not warranted. Age and comorbid conditions can result in a more prolonged and severe illness. Certain patients warrant hospitalization, especially those who present with clinical signs of ascites, peripheral edema, and hepatic encephalopathy, and laboratory signs of [[hypoglycemia]], prolonged [[prothrombin time]], low serum [[Albumin human|albumin]], and very high serum [[bilirubin]]. [335] => [336] => In these rare, more severe acute cases, patients have been successfully treated with antiviral therapy similar to that used in cases of chronic hepatitis B, with nucleoside analogues such as [[entecavir]] or [[Tenofovir disoproxil|tenofovir]]. As there is a dearth of clinical trial data and the drugs used to treat are prone to developing [[Drug resistance|resistance]], experts recommend reserving treatment for severe acute cases, not mild to moderate. [337] => [338] => ==== Chronic ==== [339] => Chronic hepatitis B management aims to control viral replication, which is correlated with progression of disease. Seven drugs are approved in the United States: [340] => * [[Adefovir dipivoxil]], a nucleotide analogue, has been used to supplement lamivudine in patients who develop resistance, but is no longer recommended as first-line therapy. [341] => * [[Entecavir]] is safe, well tolerated, less prone to developing resistance, and the most potent of the existing hepatitis B antivirals; it is thus a first-line treatment choice. It is not recommended for lamivudine-resistant patients or as monotherapy in patients who are HIV positive. [342] => * Injectable [[interferon alpha]] was the first therapy approved for chronic hepatitis B. It has several side effects, most of which are reversible with removal of therapy, but it has been supplanted by newer treatments for this indication. These include long-acting interferon bound to [[polyethylene glycol]] (pegylated interferon) and the oral nucleoside analogues. [343] => * [[Lamivudine]] was the first approved oral nucleoside analogue. While effective and potent, lamivudine has been replaced by newer, more potent treatments in the Western world and is no longer recommended as first-line treatment. It is still used in areas where newer agents either have not been approved or are too costly. Generally, the course of treatment is a minimum of one year with a minimum of six additional months of "consolidation therapy." Based on viral response, longer therapy may be required, and certain patients require indefinite long-term therapy. Due to a less robust response in Asian patients, [[consolidation therapy]] is recommended to be extended to at least a year. All patients should be monitored for viral reactivation, which if identified, requires restarting treatment. Lamivudine is generally safe and well tolerated. Many patients develop resistance, which is correlated with longer treatment duration. If this occurs, an additional antiviral is added. Lamivudine as a single treatment is contraindicated in patients coinfected with HIV, as resistance develops rapidly, but it can be used as part of a multidrug regimen. [344] => * [[Pegylated interferon]] (PEG IFN) is dosed just once a week as a subcutaneous injection and is both more convenient and effective than standard interferon. Although it does not develop resistance as do many of the oral antivirals, it is poorly tolerated and requires close monitoring. PEG IFN is estimated to cost about $18,000 per year in the United States, compared to $2,500–8,700 for the oral medications. Its treatment duration is 48 weeks, unlike oral antivirals which require indefinite treatment for most patients (minimum one year). PEG IFN is not effective in patients with high levels of viral activity and cannot be used in immunosuppressed patients or those with cirrhosis. [345] => * [[Telbivudine]] is effective but not recommended as first-line treatment; as compared to entecavir, it is both less potent and more resistance prone. [346] => * [[Tenofovir disoproxil|Tenofovir]] is a nucleotide analogue and an antiretroviral drug that is also used to treat HIV infection. It is preferred to adefovir both in lamivudine-resistant patients and as initial treatment since it is both more potent and less likely to develop resistance. [347] => First-line treatments currently used include PEG IFN, entecavir, and tenofovir, subject to patient and physician preference. Treatment initiation is guided by recommendations issued by The American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) and is based on detectable viral levels, [[HBeAg]] positive or negative status, [[Alanine transaminase|ALT]] levels, and in certain cases, family history of HCC and liver biopsy. In patients with compensated cirrhosis, treatment is recommended regardless of HBeAg status or ALT level, but recommendations differ regarding HBV DNA levels; AASLD recommends treating at DNA levels detectable above 2x10³ IU/mL; EASL and WHO recommend treating when HBV DNA levels are detectable at any level. In patients with decompensated cirrhosis, treatment and evaluation for liver transplantation are recommended in all cases if HBV DNA is detectable. Currently, multidrug treatment is not recommended in treatment of chronic HBV as it is no more effective in the long term than individual treatment with entecavir or tenofovir. [348] => [349] => === Hepatitis C === [350] => {{main|Hepatitis C}} [351] => The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) recommend antiviral treatment for all patients with chronic hepatitis C infection except for those with additional chronic medical conditions that limit their life expectancy. [352] => [353] => Once it is acquired, persistence of the hepatitis C virus is the rule, resulting in chronic hepatitis C. The goal of treatment is prevention of hepatocellular carcinoma (HCC).{{Cite journal|last1=Messori|first1=Andrea|last2=Badiani|first2=Brigitta|last3=Trippoli|first3=Sabrina|date=2015-12-01|title=Achieving Sustained Virological Response in Hepatitis C Reduces the Long-Term Risk of Hepatocellular Carcinoma: An Updated Meta-Analysis Employing Relative and Absolute Outcome Measures|journal=Clinical Drug Investigation|volume=35|issue=12|pages=843–850|doi=10.1007/s40261-015-0338-y|issn=1179-1918|pmid=26446006|s2cid=41365729}} The best way to reduce the long-term risk of HCC is to achieve sustained virological response (SVR). SVR is defined as an undetectable viral load at 12 weeks after treatment completion and indicates a cure.{{Cite journal|last1=Thiagarajan|first1=Prarthana|last2=Ryder|first2=Stephen D.|date=2015-12-01|title=The hepatitis C revolution part 1: antiviral treatment options|journal=Current Opinion in Infectious Diseases|volume=28|issue=6|pages=563–571|doi=10.1097/QCO.0000000000000205|issn=1473-6527|pmid=26524328|s2cid=11926260}}{{Cite journal|last1=Gogela|first1=Neliswa A.|last2=Lin|first2=Ming V.|last3=Wisocky|first3=Jessica L.|last4=Chung|first4=Raymond T.|date=2015-03-01|title=Enhancing our understanding of current therapies for Hepatitis C virus (HCV)|journal=Current HIV/AIDS Reports|volume=12|issue=1|pages=68–78|doi=10.1007/s11904-014-0243-7|issn=1548-3568|pmc=4373591|pmid=25761432}} Currently available treatments include indirect and direct acting antiviral drugs. The indirect acting antivirals include [[pegylated interferon]] (PEG IFN) and [[ribavirin]] (RBV), which in combination have historically been the basis of therapy for HCV. Duration of and response to these treatments varies based on genotype. These agents are poorly tolerated but are still used in some resource-poor areas. In high-resource countries, they have been supplanted by direct acting antiviral agents, which first appeared in 2011; these agents target proteins responsible for viral replication and include the following three classes: [354] => * [[NS3 (HCV)|NS3]] and [[NS4A (Hepacivirus)|NS4A]] [[Protease inhibitor (pharmacology)|protease inhibitor]]s, including [[telaprevir]], [[boceprevir]], [[simeprevir]], and others [355] => * [[NS5A (hepacivirus)|NS5A]] inhibitors, including [[ledipasvir]], [[daclatasvir]], and others [356] => * [[NS5B inhibitors]], including [[sofosbuvir]], [[dasabuvir]], and others [357] => These drugs are used in various combinations, sometimes combined with ribavirin, based on the patient's [[genotype]], delineated as genotypes 1–6. Genotype 1 (GT1), which is the most prevalent genotype in the United States and around the world, can now be cured with a direct acting antiviral regimen. First-line therapy for GT1 is a combination of sofosbuvir and ledipasvir (SOF/LDV) for 12 weeks for most patients, including those with advanced fibrosis or cirrhosis. Certain patients with early disease need only 8 weeks of treatment while those with advanced fibrosis or cirrhosis who have not responded to prior treatment require 24 weeks. Cost remains a major factor limiting access to these drugs, particularly in low-resource nations; the cost of the 12-week GT1 regimen (SOF/LDV) has been estimated at US$94,500. [358] => [359] => === Hepatitis D === [360] => {{main|Hepatitis D}} [361] => Hepatitis D is difficult to treat, and effective treatments are lacking. Interferon alpha has proven effective at inhibiting viral activity but only on a temporary basis.{{cite journal|title=Interferon alpha for chronic hepatitis D|journal = Cochrane Database of Systematic Reviews|issue = 12|pages = CD006002|last2=Khan|first2=Muhammad Arsalan|last3=Salih|first3=Mohammad|last4=Jafri|first4=Wasim|date=2011-12-07|language=en|doi=10.1002/14651858.cd006002.pub2|pmid = 22161394|pmc = 6823236|last1=Abbas|first1=Zaigham| volume=2011 }} [362] => [363] => === Hepatitis E === [364] => {{main|Hepatitis E}} [365] => [[File:Hepatitis E virus.jpg|thumb|Hepatitis E virus]] [366] => Similar to hepatitis A, treatment of hepatitis E is supportive and includes rest and ensuring adequate nutrition and hydration.{{Cite web|url=https://www.cdc.gov/hepatitis/hev/hevfaq.htm|title=HEV FAQs for Health Professionals {{!}} Division of Viral Hepatitis {{!}} CDC|website=www.cdc.gov|access-date=2016-03-17|url-status=live|archive-url=https://web.archive.org/web/20160308031004/http://www.cdc.gov/hepatitis/hev/hevfaq.htm|archive-date=2016-03-08}} Hospitalization may be required for particularly severe cases or for pregnant women. [367] => [368] => === Alcoholic hepatitis === [369] => First-line treatment of alcoholic hepatitis is treatment of alcoholism. For those who abstain completely from alcohol, reversal of liver disease and a longer life are possible; patients at every disease stage have been shown to benefit by prevention of additional liver injury. In addition to referral to psychotherapy and other treatment programs, treatment should include nutritional and psychosocial evaluation and treatment.{{Cite journal|last1=Singh|first1=Siddharth|last2=Murad|first2=Mohammad Hassan|last3=Chandar|first3=Apoorva K.|last4=Bongiorno|first4=Connie M.|last5=Singal|first5=Ashwani K.|last6=Atkinson|first6=Stephen R.|last7=Thursz|first7=Mark R.|last8=Loomba|first8=Rohit|last9=Shah|first9=Vijay H.|date=2015-10-01|title=Comparative Effectiveness of Pharmacological Interventions for Severe Alcoholic Hepatitis: A Systematic Review and Network Meta-analysis|journal=Gastroenterology|volume=149|issue=4|pages=958–970.e12|doi=10.1053/j.gastro.2015.06.006|issn=1528-0012|pmid=26091937}} Patients should also be treated appropriately for related signs and symptoms, such as ascites, hepatic encephalopathy, and infection. [370] => [371] => Severe alcoholic hepatitis has a poor prognosis and is notoriously difficult to treat. Without any treatment, 20–50% of patients may die within a month, but evidence shows treatment may extend life beyond one month (i.e., reduce short-term mortality).{{Cite journal|last1=Thursz|first1=Mark|last2=Forrest|first2=Ewan|last3=Roderick|first3=Paul|last4=Day|first4=Christopher|last5=Austin|first5=Andrew|last6=O'Grady|first6=John|last7=Ryder|first7=Stephen|last8=Allison|first8=Michael|last9=Gleeson|first9=Dermot|date=2015-12-01|title=The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2 × 2 factorial randomised controlled trial|journal=Health Technology Assessment|volume=19|issue=102|pages=1–104|doi=10.3310/hta191020|issn=2046-4924|pmid=26691209|pmc=4781103}} Available treatment options include [[pentoxifylline]] (PTX), which is a nonspecific [[TNF inhibitor]], [[corticosteroid]]s, such as [[prednisone]] or [[prednisolone]] (CS), corticosteroids with ''[[N-Acetylcysteine|N]]''[[N-Acetylcysteine|-acetylcysteine]] (CS with NAC), and corticosteroids with pentoxifylline (CS with PTX). Data suggest that CS alone or CS with NAC are most effective at reducing short-term mortality. Unfortunately, corticosteroids are contraindicated in some patients, such as those who have active gastrointestinal bleeding, infection, kidney failure, or pancreatitis. In these cases PTX may be considered on a case-by-case basis in lieu of CS; some evidence shows PTX is better than no treatment at all and may be comparable to CS while other data show no evidence of benefit over placebo. Unfortunately, there are currently no drug treatments that decrease these patients' risk of dying in the longer term, at 3–12 months and beyond. [372] => [373] => Weak evidence suggests [[Milk Thistle|milk thistle]] extracts may improve survival in alcoholic liver disease and improve certain liver tests (serum bilirubin and [[Gamma-glutamyl transpeptidase|GGT]]) without causing side effects, but a firm recommendation cannot be made for or against milk thistle without further study.{{Cite journal|title=Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases|last1=Rambaldi|first1=Andrea|last2=Jacobs|first2=Bradly P|last3=Gluud|first3=Christian|date=2007-10-17|issn=1465-1858|language=en|doi=10.1002/14651858.cd003620.pub3|journal=Protocols|volume=2009 |pmid=17943794|pages=CD003620|issue=4|pmc=8724782 }} [374] => [375] => The [[modified Maddrey's discriminant function]] may be used to evaluate the severity and prognosis in alcoholic hepatitis and evaluates the efficacy of using alcoholic hepatitis corticosteroid treatment. [376] => === Metabolic hepatitis=== [377] => {{main|Non-alcoholic_fatty_liver_disease#Management}} [378] => The main treatment of NASH is gradual weight loss and increased physical activity. In the United States, no medications have been approved to treat this disease.{{cite web |title=Treatment for NAFLD & NASH - NIDDK |url=https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/treatment |website=National Institute of Diabetes and Digestive and Kidney Diseases |access-date=4 September 2023}} [379] => === Autoimmune hepatitis === [380] => [381] => Autoimmune hepatitis is commonly treated by immunosuppressants such as the corticosteroids prednisone or prednisolone, the active version of prednisolone that does not require liver synthesis, either alone or in combination with azathioprine, and some have suggested the combination therapy is preferred to allow for lower doses of corticosteroids to reduce associated side effects, although the result of treatment efficacy is comparative.{{Cite journal|last1=Summerskill|first1=W. H.|last2=Korman|first2=M. G.|last3=Ammon|first3=H. V.|last4=Baggenstoss|first4=A. H.|date=1975-11-01|title=Prednisone for chronic active liver disease: dose titration, standard dose, and combination with azathioprine compared|journal=Gut|volume=16|issue=11|pages=876–883|doi=10.1136/gut.16.11.876|issn=0017-5749|pmc=1413126|pmid=1104411}} [382] => [383] => Treatment of autoimmune hepatitis consists of two phases; an initial and maintenance phase. The initial phase consists of higher doses of corticosteroids which are tapered down over a number of weeks to a lower dose. If used in combination, azathioprine is given during the initial phase as well. Once the initial phase has been completed, a maintenance phase that consists of lower dose corticosteroids, and in combination therapy, azathioprine until liver blood markers are normalized. Treatment results in 66–91% of patients achieving normal liver test values in two years, with the average being 22 months. [384] => [385] => == Prognosis == [386] => [387] => === Acute hepatitis === [388] => Nearly all patients with hepatitis A infections recover completely without complications if they were healthy prior to the infection. Similarly, acute hepatitis B infections have a favorable course towards complete recovery in 95–99% of patients. Certain factors may portend a poorer outcome, such as co-morbid medical conditions or initial presenting symptoms of ascites, edema, or encephalopathy. Overall, the mortality rate for acute hepatitis is low: ~0.1% in total for cases of hepatitis A and B, but rates can be higher in certain populations (super infection with both hepatitis B and D, pregnant women, etc.). [389] => [390] => In contrast to hepatitis A & B, hepatitis C carries a much higher risk of progressing to chronic hepatitis, approaching 85–90%.{{Cite book|title=Hepatitis C Virus: From Molecular Virology to Antiviral Therapy|publisher=Springer|year=2013|editor-last=Bartenschlager}} Cirrhosis has been reported to develop in 20–50% of patients with chronic hepatitis C.{{citation needed|date=March 2022}} [391] => [392] => Other rare complications of acute hepatitis include [[pancreatitis]], [[aplastic anemia]], [[peripheral neuropathy]], and [[myocarditis]]. [393] => [394] => ==== Fulminant hepatitis ==== [395] => Despite the relatively benign course of most viral cases of hepatitis, fulminant hepatitis represents a rare but feared complication. Fulminant hepatitis most commonly occurs in hepatitis B, D, and E. About 1–2% of cases of hepatitis E can lead to fulminant hepatitis, but pregnant women are particularly susceptible, occurring in up to 20% of cases.{{Cite journal|last=Khuroo|first=MS|date=1981|title=Incidence and severity of viral hepatitis in pregnancy|journal=Am J Med|doi=10.1016/0002-9343(81)90796-8 |pmid=6781338|volume=70|issue=2|pages=252–5}} Mortality rates in cases of fulminant hepatitis rise over 80%, but those patients that do survive often make a complete recovery. Liver transplantation can be life-saving in patients with fulminant liver failure.{{Cite journal|last=Gill|first=RQ|date=2001|title=Acute Liver Failure|journal=J Clin Gastroenterol|doi=10.1097/00004836-200109000-00005|pmid=11500606|volume=33|issue=3|pages=191–8}} [396] => [397] => Hepatitis D infections can transform benign cases of hepatitis B into severe, progressive hepatitis, a phenomenon known as [[superinfection]].{{Cite journal|last1=Smedile|first1=A|display-authors=etal|date=1981|title=Infection with the delta agent in chronic HBsAg carriers|journal=Gastroenterology|doi= 10.1016/S0016-5085(81)80003-0|pmid=7286594|volume=81|issue=6|pages=992–7|url=https://www.gastrojournal.org/article/S0016-5085(81)80003-0/fulltext|doi-access=free}} [398] => [399] => === Chronic hepatitis === [400] => Acute hepatitis B infections become less likely to progress to chronic forms as the age of the patient increases, with rates of progression approaching 90% in vertically transmitted cases of infants compared to 1% risk in young adults. Overall, the five-year survival rate for chronic hepatitis B ranges from 97% in mild cases to 55% in severe cases with cirrhosis. [401] => [402] => Most patients who acquire hepatitis D at the same time as hepatitis B (co-infection) recover without developing a chronic infection. In people with hepatitis B who later acquire hepatitis D (superinfection), chronic infection is much more common at 80–90%, and liver disease progression is accelerated.{{cite journal |title=Interferon alpha versus any other drug for chronic hepatitis D |journal = Cochrane Database of Systematic Reviews|last1=Abbas |first1=Zaigham |last2=Ali |first2=Syed Salman |last3=Shazi |first3=Lubna |date=2015-06-02 |language=en |doi=10.1002/14651858.cd011727 | s2cid=70629280 }} [403] => [404] => Chronic hepatitis C progresses towards cirrhosis, with estimates of cirrhosis prevalence of 16% at 20 years after infection.{{Cite journal|last1=Thein|first1=Hla-Hla|last2=Yi|first2=Qilong|last3=Dore|first3=Gregory J.|last4=Krahn|first4=Murray D.|date=2008-08-01|title=Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: a meta-analysis and meta-regression|journal=Hepatology|volume=48|issue=2|pages=418–431|doi=10.1002/hep.22375|issn=1527-3350|pmid=18563841|s2cid=20771903|doi-access=free}} While the major causes of mortality in hepatitis C is end stage liver disease, hepatocellular carcinoma is an important additional long term complication and cause of death in chronic hepatitis. [405] => [406] => Rates of mortality increase with progression of the underlying liver disease. Series of patients with compensated cirrhosis due to HCV have shown 3,5, and 10-year survival rates of 96, 91, and 79% respectively.{{Cite journal|last=Fattovich|first=G|date=1997|title=Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients|journal=Gastroenterology|doi=10.1053/gast.1997.v112.pm9024300|pmid=9024300|volume=112|issue=2|pages=463–72}} The 5-year survival rate drops to 50% upon if the cirrhosis becomes decompensated. [407] => [408] => == Epidemiology == [409] => [410] => === Viral hepatitis === [411] => [412] => ==== Hepatitis A ==== [413] => Hepatitis A is found throughout the world and manifests as large [[outbreak]]s and [[epidemic]]s associated with fecal contamination of water and food sources.{{Cite book|title=Medical Microbiology|last=Carroll|first=Karen|publisher=McGraw-Hill|year=2015|isbn=978-0071824989|location=New York|chapter=Chapter 35: Hepatitis Viruses}} Hepatitis A viral infection is predominant in children ages 5–14 with rare infection of infants. Infected children have little to no apparent clinical illness, in contrast to adults in whom greater than 80% are symptomatic if infected.{{Cite web|url=https://www.cdc.gov/hepatitis/hav/|title=Hepatitis A Information {{!}} Division of Viral Hepatitis {{!}} CDC|website=www.cdc.gov|access-date=2016-03-08|url-status=live|archive-url=https://web.archive.org/web/20160304081005/http://www.cdc.gov/hepatitis/hav/|archive-date=2016-03-04}} Infection rates are highest in low resource countries with inadequate public sanitation and large concentrated populations.{{Cite journal|last1=Aggarwal|first1=Rakesh|last2=Goel|first2=Amit|title=Hepatitis A|journal=Current Opinion in Infectious Diseases|volume=28|issue=5|pages=488–496|doi=10.1097/qco.0000000000000188|pmid=26203853|year=2015|s2cid=22340290}} In such regions, as much as 90% of children younger than 10 years old have been infected and are immune, corresponding both to lower rates of clinically symptomatic disease and outbreaks.{{Cite web|url=https://www.who.int/mediacentre/factsheets/fs328/en/|title=WHO {{!}} Hepatitis A|website=www.who.int|access-date=2016-03-08|url-status=live|archive-url=https://web.archive.org/web/20140221042107/http://www.who.int/mediacentre/factsheets/fs328/en/|archive-date=2014-02-21}} The availability of a childhood [[vaccine]] has significantly reduced infections in the United States, with incidence declining by more than 95% as of 2013.{{Cite web|url=https://www.cdc.gov/hepatitis/hav/havfaq.htm#general|title=Hepatitis A Questions and Answers for Health Professionals {{!}} Division of Viral Hepatitis {{!}} CDC|website=www.cdc.gov|access-date=2016-03-08|url-status=live|archive-url=https://web.archive.org/web/20160306221037/http://www.cdc.gov/hepatitis/hav/havfaq.htm#general|archive-date=2016-03-06}} Paradoxically, the highest rates of new infection now occur in young adults and adults who present with worse clinical illness. Specific populations at greatest risk include: travelers to endemic regions, men who have sex with men, those with occupational exposure to non-human primates, people with [[clotting disorder]]s who have received [[clotting factors]], people with history of [[chronic liver disease]] in whom co-infection with hepatitis A can lead to fulminant hepatitis, and intravenous drug users (rare). [414] => [415] => ==== Hepatitis B ==== [416] => {{main|Hepatitis B}} [417] => [[File:HBV replication.png|thumb|HBV replication]] [418] => [[Hepatitis B]] is the most common cause of viral hepatitis in the world with more than 240 million chronic carriers of the virus, 1 million of whom are in the United States.{{Cite web|url=https://www.who.int/mediacentre/factsheets/fs204/en/|title=Hepatitis B|website=World Health Organization|language=en-GB|access-date=2016-03-09|url-status=live|archive-url=https://web.archive.org/web/20141109161444/http://www.who.int/mediacentre/factsheets/fs204/en/|archive-date=2014-11-09}} In approximately two-thirds of patients who develop acute hepatitis B infection, no identifiable exposure is evident. Of those acutely infected, 25% become lifetime carriers of the virus. Risk of infection is highest among intravenous drug users, people with high-risk sexual behaviors, healthcare workers, people who had multiple transfusions, organ transplant patients, dialysis patients and newborns infected during the birthing process. Close to 780,000 deaths in the world are attributed to hepatitis B. The most endemic regions are in sub-Saharan Africa and East Asia, where as many as 10% of adults are chronic carriers. Carrier rates in developed nations are significantly lower, encompassing less than 1% of the population. In endemic regions, transmission is thought to be associated with exposure during birth and close contact between young infants. [419] => [420] => ==== Hepatitis C ==== [421] => {{main|Hepatitis C}} [422] => [[File:HepC replication.png|thumb|HepC replication]] [423] => Chronic [[hepatitis C]] is a major cause of liver cirrhosis and hepatocellular carcinoma.{{Cite journal|last=Rosen|first=Hugo R.|date=2011-06-23|title=Clinical practice. Chronic hepatitis C infection| journal=The New England Journal of Medicine| volume=364| issue=25| pages=2429–2438| doi=10.1056/NEJMcp1006613|issn=1533-4406|pmid=21696309}} It is a common medical reason for liver transplantation due to its severe complications. It is estimated that 130–180 million people in the world are affected by this disease representing a little more than 3% of the world population.{{Cite web|url=https://www.who.int/mediacentre/factsheets/fs164/en/|title=Hepatitis C|website=World Health Organization|language=en-GB|access-date=2016-03-08|url-status=live|archive-url=https://web.archive.org/web/20160131041006/http://www.who.int/mediacentre/factsheets/fs164/en/|archive-date=2016-01-31}} In the developing regions of Africa, Asia and South America, prevalence can be as high as 10% of the population. In Egypt, rates of hepatitis C infection as high as 20% have been documented and are associated with [[Iatrogenesis|iatrogenic]] contamination related to [[schistosomiasis]] treatment in the 1950s–1980s. Currently in the United States, approximately 3.5 million adults are estimated to be infected.{{Cite journal|last1=Edlin|first1=Brian R.|last2=Eckhardt|first2=Benjamin J.|last3=Shu|first3=Marla A.|last4=Holmberg|first4=Scott D.|last5=Swan|first5=Tracy|date=2015-11-01|title=Toward a more accurate estimate of the prevalence of hepatitis C in the United States|journal=Hepatology|language=en|volume=62|issue=5|pages=1353–1363|doi=10.1002/hep.27978|issn=1527-3350|pmc=4751870|pmid=26171595}} Hepatitis C is particularly prevalent among people born between 1945 and 1965, a group of about 800,000 people, with prevalence as high as 3.2% versus 1.6% in the general U.S. population. Most chronic carriers of hepatitis C are unaware of their infection status. The most common mode of transmission of hepatitis C virus is exposure to blood products via blood transfusions (prior to 1992) and intravenous drug injection. A history of intravenous drug injection is the most important risk factor for chronic hepatitis C. Other susceptible populations include those engaged in high-risk sexual behavior, infants of infected mothers, and healthcare workers. [424] => [425] => ==== Hepatitis D ==== [426] => {{main|Hepatitis D}} [427] => The [[hepatitis D]] virus causes chronic and fulminant hepatitis in the context of co-infection with the hepatitis B virus. It is primarily transmitted via non-sexual contact and via needles. Susceptibility to hepatitis D differs by geographic region. In the United States and Northern Europe, populations at risk are intravenous drug users and people who receive multiple transfusions. In the Mediterranean, hepatitis D is predominant among hepatitis B virus co-infected people. [428] => [429] => ==== Hepatitis E ==== [430] => {{main|Hepatitis E}} [431] => Similar to Hepatitis A, [[hepatitis E]] manifests as large outbreaks and epidemics associated with fecal contamination of water sources. It accounts for more than 55,000 deaths annually with approximately 20 million people worldwide thought to be infected with the virus. It affects predominantly young adults, causing acute hepatitis.{{Cite web|url=https://www.cdc.gov/hepatitis/hev/hevfaq.htm#section1|title=HEV FAQs for Health Professionals {{!}} Division of Viral Hepatitis {{!}} CDC|website=www.cdc.gov|access-date=2016-03-09|url-status=live|archive-url=https://web.archive.org/web/20160308031004/http://www.cdc.gov/hepatitis/hev/hevfaq.htm#section1|archive-date=2016-03-08}} In infected pregnant women, Hepatitis E infection can lead to fulminant hepatitis with third trimester mortality rates as high as 30%. Those with weakened immune systems, such as organ transplant recipients, are also susceptible. Infection is rare in the United States but rates are high in the developing world (Africa, Asia, Central America, Middle East). Many genotypes exist and are differentially distributed around the world.

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