Editing Hepatitis (section)

== Causes ==
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.<ref>[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</ref>

=== Infectious ===

==== Viral hepatitis ====
{{Main|Viral hepatitis}}
[[Viral hepatitis]] is the most common type of hepatitis worldwide, especially in Asia and Africa.<ref>{{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}}</ref> Viral hepatitis is caused by five different viruses (hepatitis A, B, C, D, and E).<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /> [[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.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /><ref>{{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}}</ref><ref>{{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}}</ref>

[[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.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /> 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.<ref>{{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}}</ref> 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.<ref>{{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}}</ref>

Hepatitis B and C can present either acutely or chronically.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /> Hepatitis D is a defective virus that requires hepatitis B to replicate and is only found with hepatitis B co-infection.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /> 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.<ref name="WHO Hepatitis B" /> Infection in infants and children frequently leads to chronic infection.<ref name="WHO Hepatitis B" />

Unlike hepatitis B, most cases of hepatitis C lead to chronic infection.<ref name="CDC FAQ on Hepatitis C">{{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}}</ref> Hepatitis C is the second most common cause of cirrhosis in the US (second to alcoholic hepatitis).<ref name="Friedman 55e">{{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}}</ref> In the 1970s and 1980s, blood transfusions were a major factor in spreading hepatitis C virus.<ref name="CDC FAQ on Hepatitis C" /> 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.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" />

==== Parasitic hepatitis ====
[[File:Echinococcus granulosus.JPG|thumb|Echinococcus granulosus]]
[[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).<ref name="Harder & Mehlhorn">{{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}}</ref> Of the [[protozoa]]ns, [[Trypanosoma cruzi]], [[Leishmaniasis|Leishmania]] species, and the [[malaria]]-causing [[Plasmodium]] species all can cause liver inflammation.<ref name="Harder & Mehlhorn" /> Another protozoan, [[Entamoeba histolytica]], causes hepatitis with distinct liver abscesses.<ref name="Harder & Mehlhorn" />

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]].<ref name="Harder & Mehlhorn" /> The liver [[Fluke (parasite)|flukes]] [[Fasciola hepatica]] and [[Clonorchis sinensis]] live in the bile ducts and cause progressive hepatitis and liver fibrosis.<ref name="Harder & Mehlhorn" />

==== Bacterial hepatitis ====
Bacterial infection of the liver commonly results in [[pyogenic liver abscess]]es, acute hepatitis, or [[granuloma]]tous (or chronic) liver disease.<ref name="Wisplinghoff & Appleton">{{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}}</ref> 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.<ref name="Wisplinghoff & Appleton" /> Acute hepatitis is caused by ''[[Neisseria meningitidis]]'', ''[[Neisseria gonorrhoeae]]'', ''[[Bartonella henselae]]'', ''[[Borrelia burgdorferi]]'', [[salmonella]] species, [[brucella]] species and [[campylobacter]] species.<ref name="Wisplinghoff & Appleton" /> Chronic or granulomatous hepatitis is seen with infection from [[Mycobacterium|mycobacteria]] species, ''[[Tropheryma whipplei]]'', ''[[Treponema pallidum]]'', ''[[Coxiella burnetii]]'', and [[rickettsia]] species.<ref name="Wisplinghoff & Appleton" />

=== Metabolic ===

==== Alcoholic hepatitis ====
{{Main|Alcoholic hepatitis}}
Excessive alcohol consumption is a significant cause of hepatitis and is the most common cause of cirrhosis in the U.S.<ref name="Friedman 55e" /> 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).<ref name="Friedman 55e" /> Hepatitis usually develops over years-long exposure to alcohol, occurring in 10 to 20% of alcoholics.<ref name="Harrison's Principles chapter 363 (Alcohol)">{{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}}</ref> The most important risk factors for the development of alcoholic hepatitis are quantity and duration of alcohol intake.<ref name="Harrison's Principles chapter 363 (Alcohol)" /> 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).<ref name="Friedman 55e" /> Alcoholic hepatitis can vary from asymptomatic [[hepatomegaly]] (enlarged liver) to symptoms of acute or chronic hepatitis to liver failure.<ref name="Friedman 55e" />

==== Toxic and drug-induced hepatitis ====
Many chemical agents, including medications, industrial toxins, and herbal and dietary supplements, can cause hepatitis.<ref name="Harrison's Principles chapter 361 (Toxic and Drug-Induced)">{{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}}</ref><ref name="Occupational exposure to solvents" /> The spectrum of drug-induced liver injury varies from acute hepatitis to chronic hepatitis to acute liver failure.<ref name="Harrison's Principles chapter 361 (Toxic and Drug-Induced)" /> Toxins and medications can cause liver injury through a variety of mechanisms, including direct [[cell damage]], disruption of cell metabolism, and causing structural changes.<ref>{{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}}</ref> 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.<ref name="Harrison's Principles chapter 361 (Toxic and Drug-Induced)" /> There are wide variations in the mechanisms of liver injury and [[latency period]] from exposure to development of clinical illness.<ref name="Friedman 55e" />

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]].<ref name="Friedman 55e" /> 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.<ref name="Harrison's Principles chapter 361 (Toxic and Drug-Induced)" />

[[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.<ref>{{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}}</ref> The United States–based Drug Induced Liver Injury Network linked more than 16% of cases of hepatotoxicity to herbal and dietary supplements.<ref name="NIH - herbal 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}}</ref> In the United States, herbal and dietary supplements – unlike [[pharmaceutical drug]]s – are unregulated by the [[Food and Drug Administration]].<ref name="NIH - herbal supplements" /> The [[National Institutes of Health]] maintains the LiverTox database for consumers to track all known prescription and non-prescription compounds associated with liver injury.<ref>{{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}}</ref>

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.<ref name="Harrison's Principles chapter 361 (Toxic and Drug-Induced)" /><ref name="Occupational exposure to solvents">{{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 }}</ref><ref>{{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}}</ref>

==== Non-alcoholic fatty liver disease ====
{{Main|Non-alcoholic fatty liver disease}}

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.<ref name="Harrison's Principles chapter 364 (Nonalcoholic)">{{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}}</ref>

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.<ref name="Friedman 55e" /> Over time, non-alcoholic fatty liver disease can progress to non-alcoholic [[steatohepatitis]], which additionally involves liver cell death, liver inflammation and possible fibrosis.<ref name="Friedman 55e" /> 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 ultrasound steatosis score.<ref name="Friedman 55e" />

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]].<ref name="Friedman 55e" /> As the disease progresses, symptoms typical of chronic hepatitis may develop.<ref name="National Digestive Diseases Information Clearinghouse NDDIC">{{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}}</ref> While imaging can show fatty liver, only [[liver biopsy]] can demonstrate inflammation and fibrosis characteristic of NASH.<ref name="Masuoka 2013 106–122">{{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}}</ref> 9 to 25% of patients with NASH develop cirrhosis.<ref name="Friedman 55e" /> NASH is recognized as the third most common cause of liver disease in the United States.<ref name="National Digestive Diseases Information Clearinghouse NDDIC" />

=== Autoimmune ===
{{Main|Autoimmune hepatitis}}

Autoimmune hepatitis is a chronic disease caused by an abnormal immune response against liver cells.<ref>{{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}}</ref> The disease is thought to have a genetic predisposition as it is associated with certain [[human leukocyte antigen]]s involved in the immune response.<ref>{{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 }}</ref> As in other autoimmune diseases, circulating [[Autoantibody|auto-antibodies]] may be present and are helpful in diagnosis.<ref name="Czaja Autoimmune">{{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}}</ref> 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)]].<ref name="Czaja Autoimmune" /> 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).<ref name="Czaja Autoimmune" /> 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]]).<ref name="Friedman 55e" />

Autoimmune hepatitis can present anywhere within the spectrum from asymptomatic to acute or chronic hepatitis to fulminant liver failure.<ref name="Friedman 55e" /> Patients are asymptomatic 25–34% of the time, and the diagnosis is suspected on the basis of abnormal liver function tests.<ref name="Czaja Autoimmune" /> Some studies show between 25% and 75% of cases present with signs and symptoms of acute hepatitis.<ref name="Friedman 55e" /><ref name=":0">{{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}}</ref> 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]].<ref name="Friedman 55e" /> Autoimmune hepatitis increases the risk for cirrhosis, and the risk for liver cancer is increased by about 1% for each year of the disease.<ref name="Friedman 55e" />

Many people with autoimmune hepatitis have other [[autoimmune disease]]s.<ref>{{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 }}</ref> 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.<ref name="Friedman 55e" /><ref name="Czaja Autoimmune" />

=== Genetic ===
Genetic causes of hepatitis include [[Alpha 1-antitrypsin deficiency|alpha-1-antitrypsin deficiency]], [[HFE hereditary haemochromatosis|hemochromatosis]], and [[Wilson's disease]].<ref name="Friedman 55e" /> 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.<ref>{{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}}</ref> Hemochromatosis and Wilson's disease are both [[autosomal recessive]] diseases involving abnormal storage of minerals.<ref name="Friedman 55e" /> In hemochromatosis, excess amounts of iron accumulate in multiple body sites, including the liver, which can lead to cirrhosis.<ref name="Friedman 55e" /> In Wilson's disease, excess amounts of copper accumulate in the liver and brain, causing cirrhosis and dementia.<ref name="Friedman 55e" />

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.<ref name="Friedman 55e" /> Hemochromatosis typically presents in adulthood, with the onset of clinical disease usually after age 50.<ref name="Friedman 55e" />

=== Ischemic hepatitis ===
{{Main|Ischemic hepatitis}}
[[Ischemic hepatitis]] (also known as shock liver) results from reduced blood flow to the liver as in shock, heart failure, or vascular insufficiency.<ref name="Hepatic ischemia">{{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}}</ref> 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.<ref>{{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}}</ref>

=== Other ===
{{Main|Neonatal hepatitis}}
Hepatitis can also occur in neonates and is attributable to a variety of causes, some of which are not typically seen in adults.<ref name="Biliary disease in infancy">{{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}}</ref> Congenital or perinatal infection with the hepatitis viruses, [[Toxoplasma gondii|toxoplasma]], [[rubella]], [[cytomegalovirus]], and [[syphilis]] can cause neonatal hepatitis.<ref name="Biliary disease in infancy" /> Structural abnormalities such as [[biliary atresia]] and [[choledochal cysts]] can lead to [[Cholestasis|cholestatic liver injury]] leading to neonatal hepatitis.<ref name="Biliary disease in infancy" /> [[Inborn error of metabolism|Metabolic diseases]] such as [[Glycogen storage disease|glycogen storage disorders]] and [[Lysosomal storage disease|lysosomal storage disorders]] are also implicated.<ref name="Biliary disease in infancy" /> Neonatal hepatitis can be [[Idiopathy|idiopathic]], and in such cases, biopsy often shows large multinucleated cells in the liver tissue.<ref>{{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}}</ref> This disease is termed giant cell hepatitis and may be associated with viral infection, autoimmune disorders, and drug toxicity.<ref>{{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 }}</ref><ref>{{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}}</ref>