Hepatitis: Difference between revisions

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.<ref>{{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}}</ref> In the United States, NASH affects about 11 million people and [[alcoholic hepatitis]] affects about 5 million people.<ref name=NASH2014/><ref>{{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 }}</ref> Hepatitis results in more than a million deaths a year, most of which occur indirectly from liver scarring or liver cancer.<ref name=NIH2016/><ref>{{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}}</ref> In the United States, hepatitis A is estimated to occur in about 2,500 people a year and results in about 75 deaths.<ref>{{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}}</ref> 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".<ref>{{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 }}</ref>

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.{{citation<ref>[https://www.vinmec.com/vi/tieu-hoa-gan-mat/thong-tin-suc-khoe/viem-gan-tu-mien-la-gi/ needed|date=MarchViêm 2022}}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>

[[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 [http://www.dilin.org/ Drug Induced Liver Injury Network] linked more than 16% of cases of hepatotoxicity to herbal and dietary supplements.<ref name="NIH - herbal supplements">{{Cite webjournal|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 [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.<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>

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" />

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" />

[[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.<ref name="Hardy Oakley Anstee Day">{{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 }}</ref><ref name="Yoon & Cha Pathogenesis">{{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 }}</ref> In [[alcoholic hepatitis]], chronic excess alcohol use is the culprit.<ref name="Chayanupatkul & Liangpunsakul" /> 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]].<ref name="Hardy Oakley Anstee Day" /><ref name="Yoon & Cha Pathogenesis" /><ref name="Chayanupatkul & Liangpunsakul" /> 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]].<ref name="Hardy Oakley Anstee Day" /><ref name="Yoon & Cha Pathogenesis" /><ref name="Chayanupatkul & Liangpunsakul" /> 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.<ref name="Hardy Oakley Anstee Day" /><ref name="Yoon & Cha Pathogenesis" /><ref name="Chayanupatkul & Liangpunsakul" /> 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.<ref name="Hardy Oakley Anstee Day" /> 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]].<ref name="Hardy Oakley Anstee Day" /><ref name="Definition, epidemiology, and magnitude">{{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 }}</ref><ref>{{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 }}</ref>

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]].<ref name="Friedman 55e" /> Characteristic patterns of liver enzyme abnormalities can point to certain causes or stages of hepatitis.<ref>{{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}}</ref><ref>{{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}}</ref> Generally, [[Aspartate transaminase|AST]] and [[Alanine transaminase|ALT]] are elevated in most cases of hepatitis regardless of whether the person shows any symptoms.<ref name="Friedman 55e" /> 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.<ref name="Friedman 55e" />

[[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.<ref>{{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}}</ref><ref>{{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 }}</ref> 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.<ref>{{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}}</ref> Unlike steatosis and cirrhosis, no imaging test is able to detect liver inflammation (i.e. hepatitis) or fibrosis.<ref name="Friedman 55e" /> Liver biopsy is the only definitive diagnostic test that is able to assess inflammation and fibrosis of the liver.<ref name="Friedman 55e" />

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.<ref name="pmid26568915">{{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 }}</ref> 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.<ref name="pmid26568915" />

[[File:Hepatitis B virus v2.svgpng|thumb|Hepatitis B virus v2]]

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 inidicatesindicates chronic disease.<ref name="Final Recommendation Statement: Hepatitis C: Screening" /><ref name="AASLD-IDSA" /></blockquote>

There are currently no vaccines available in the United States for hepatitis C or E.<ref name="Final Recommendation Statement: Hepatitis C: Screening" /><ref name="WHO - Hepatitis E" /><ref name="WHO Hepatitis D" /> In 2015, a group in China published an article regarding the development of a [[vaccine for hepatitis E]].<ref>{{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}}</ref> 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.<ref>{{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}}</ref>

====Alcoholic and metabolic hepatitis====

In the United States, universal immunization has led to a two-thirds decrease in hospital admissions and medical expenses due to hepatitis A.<ref>{{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 }}</ref>

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.<ref>{{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 }}</ref> 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.<ref>{{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}}</ref>

First-line treatments currently used include PEG IFN, entecavir, and tenofovir, subject to patient and physician preference.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> 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.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> 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 2x10<sup href="jaundice">3</sup> IU/mL; EASL and WHO recommend treating when HBV DNA levels are detectable at any level.<ref name="Harrison's Principles, chapter 362 (Chronic)" /><ref name="WHO guidelines for chronic Hepatitis B" /> In patients with decompensated cirrhosis, treatment and evaluation for liver transplantation are recommended in all cases if HBV DNA is detectable.<ref name="Harrison's Principles, chapter 362 (Chronic)" /><ref name="WHO guidelines for chronic Hepatitis B" /> 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.<ref name="Harrison's Principles, chapter 362 (Chronic)" />

[[Alcoholic hepatitis]] (AH) in its severe form has a one-month mortality as high as 50%.<ref name="Chayanupatkul & Liangpunsakul">{{Cite journal|last1=Chayanupatkul|first1=Maneerat|last2=Liangpunsakul|first2=Suthat|date=2014-05-28|title=Alcoholic hepatitis: a comprehensive review of pathogenesis and treatment|journal=World Journal of Gastroenterology|volume=20|issue=20|pages=6279–6286|doi=10.3748/wjg.v20.i20.6279|issn=2219-2840|pmc=4033465|pmid=24876748 |doi-access=free }}</ref><ref name="Definition, epidemiology, and magnitude" /><ref name="Singal Kamath Gores Shah">{{Cite journal|last1=Singal|first1=Ashwani K.|last2=Kamath|first2=Patrick S.|last3=Gores|first3=Gregory J.|last4=Shah|first4=Vijay H.|date=2014-04-01|title=Alcoholic hepatitis: current challenges and future directions|journal=Clinical Gastroenterology and Hepatology|volume=12|issue=4|pages=555–564; quiz e31–32|doi=10.1016/j.cgh.2013.06.013|issn=1542-7714|pmc=3883924|pmid=23811249}}</ref> Most people who develop AH are men but women are at higher risk of developing AH and its complications likely secondary to high body fat and differences in alcohol metabolism.<ref name="Definition, epidemiology, and magnitude" /> Other contributing factors include younger age <60, binge pattern drinking, poor nutritional status, obesity and hepatitis C co-infection.<ref name="Definition, epidemiology, and magnitude" /> It is estimated that as much as 20% of people with AH are also infected with hepatitis C.<ref name="Shoreibah, Bhupinderjit, Singal">{{Cite journal|last1=Shoreibah|first1=Mohamed|last2=Anand|first2=Bhupinderjit S.|last3=Singal|first3=Ashwani K.|date=2014-09-14|title=Alcoholic hepatitis and concomitant hepatitis C virus infection|journal=World Journal of Gastroenterology|volume=20|issue=34|pages=11929–11934|doi=10.3748/wjg.v20.i34.11929|issn=2219-2840|pmc=4161778|pmid=25232227 |doi-access=free }}</ref> In this population, the presence of hepatitis C virus leads to more severe disease with faster progression to cirrhosis, hepatocellular carcinoma and increased mortality.<ref name="Definition, epidemiology, and magnitude" /><ref name="Shoreibah, Bhupinderjit, Singal" /><ref>{{Cite journal|last1=Singal|first1=Ashwani K.|last2=Anand|first2=Bhupinder S.|date=2007-09-01|title=Mechanisms of synergy between alcohol and hepatitis C virus|journal=Journal of Clinical Gastroenterology|volume=41|issue=8|pages=761–772|doi=10.1097/MCG.0b013e3180381584|issn=0192-0790|pmid=17700425|s2cid=19482895}}</ref> Obesity increases the likelihood of progression to cirrhosis in cases of alcoholic hepatitis.<ref name="Definition, epidemiology, and magnitude" /> It is estimated that 70% of people who have AH will progress to cirrhosis.<ref name="Definition, epidemiology, and magnitude" />

Around 400 B.C., [[Hippocrates]] recorded the first documentation of an epidemic jaundice, in particular noting the uniquely fulminant course of a cohort of patients who all died within two weeks. He wrote, "The bile contained in the liver is full of phlegm and blood, and erupts...After such an eruption, the patient soon raves, becomes angry, talks nonsense and barks like a dog."<ref>{{cite journal |date=July 2012 |title=Viral hepatitis—the silent killer. |journal=Annals of the Academy of Medicine, Singapore |volume=41 |issue=7 |pages=279–80 |pmid=22892603 |last1=Oon |first1=GC|doi=10.47102/annals-acadmedsg.V41N7p279 |s2cid=2757948 |doi-access=free }}</ref>

Hepatitis B accounts for a much larger percentage of health care spending in endemic regions like Asia.<ref>{{Cite journal|last1=Chan|first1=Henry Lik-Yuen|last2=Jia|first2=Jidong|date=2011-01-01|title=Chronic hepatitis B in Asia—new insights from the past decade|journal=Journal of Gastroenterology and Hepatology|language=en|volume=26|pages=131–137|doi=10.1111/j.1440-1746.2010.06544.x|pmid=21199524|s2cid=23548529|issn=1440-1746|doi-access=free}}</ref><ref name="Economics of treating in Asia">{{Cite journal|last1=Dan|first1=Yock Young|last2=Aung|first2=Myat Oo|last3=Lim|first3=Seng Gee|date=2008-09-01|title=The economics of treating chronic hepatitis B in Asia|journal=Hepatology International|volume=2|issue=3|pages=284–295|doi=10.1007/s12072-008-9049-2|issn=1936-0533|pmc=2716880|pmid=19669256}}</ref> In 1997 it accounted for 3.2% of South Korea's total health care expenditures and resulted in $696 million in direct costs.<ref name="Economics of treating in Asia" /> A large majority of that sum was spent on treating disease symptoms and complications.<ref>{{Cite journal|last=Lavanchy|first=D.|date=2004-03-01|title=Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures|journal=Journal of Viral Hepatitis|volume=11|issue=2|pages=97–107|issn=1352-0504|pmid=14996343|doi=10.1046/j.1365-2893.2003.00487.x|s2cid=163757}}</ref> Chronic hepatitis B infections are not as endemic in the United States, but accounted for $357 million in hospitalization costs in the year 1990.<ref name="Udompap, Kim & Kim" /> That number grew to $1.5 billion in 2003, but remained stable as of 2006, which may be attributable to the introduction of effective drug therapies and vaccination campaigns.<ref name="Udompap, Kim & Kim" /><ref name="Reducing the neglected burden" />