HepatitisAlcoholic hepatitis evident by fatty change, cellnecrosis, Mallory bodiesClassification and external resourcesSpecialty Infectious disease, gastroenterologyICD-10 K75.9ICD-9-CM 573.3DiseasesDB 2!"MedlinePlus ""5#MeSH $!55Hepatitis %plural& hepatitides' is a (edical condition defined by the infla((ation of the liver and characteri)ed by the presence of infla((atory cells in the tissue of the organ. *epatitis (ay occur +ith li(ited or no sy(pto(s, but often leads to ,aundice %a yello+ discoloration of the s-in, (ucous (e(brane, and con,unctiva', poor appetite, and (alaise. *epatitis is acute +hen it lasts less than si. (onths and chronic +hen it persists longer.Acute hepatitis can be self/li(iting %healing on its o+n', can progress to chronic hepatitis, or, rarely, can cause acute liver failure.0"1 2hronic hepatitis (ay have no sy(pto(s, or (ay progress over ti(e to fibrosis %scarring of the liver' and cirrhosis %chronic liver failure'.021 2irrhosis of the liver increases the ris- of developing hepatocellular carcino(a %a for( of liver cancer'.0313orld+ide, viral hepatitis is the (ost co((on cause of liver infla((ation.0#1 4ther causes include autoi((une diseases and ingestion of to.ic substances %notably alcohol', certain (edications %such as paraceta(ol', so(e industrial organic solvents, and plants.5he ter( is derived fro( the 6ree- hpar % 789', (eaning :liver:, and the suffi. -itis %/ ;y(pto(s and physical e.a( findings are si(ilar to other causes of hepatitis. Haboratory findings are significant for elevated transa(inases, usually +ith elevation of aspartate transa(inase %A>5' in a 2&" ratio to alanine transa(inase %AH5'.02"10221Alcoholic hepatitis (ay lead to cirrhosis and is (ore co((on in patients +ith long/ter( alcohol consu(ption and those infected +ith hepatitis 2.0231 Aatients +ho drin- alcohol to e.cess are also (ore often than others found to have hepatitis 2.02#1 5he co(bination of hepatitis 2 and alcohol consu(ption accelerates the develop(ent of cirrhosis.0251#oxic and drug-induced hepatitisMain article& *epatoto.icityA large nu(ber of (edications and other che(ical agents can cause hepatitis. In the Jnited >tates aceta(inophen, antibiotics, and central nervous syste( (edications are a(ong the (ost co((on causes of drug/induced hepatitis. Aceta(inophen, also -no+n as paraceta(ol, is the leading cause of acute liver failure in the Jnited >tates.02!1 *erbal re(edies and dietary supple(ents (ay also cause hepatitisM these are the (ost co((on causes of drug/induced hepatitis in Korea.0271 Cis- factors for drug/induced hepatitis include increasing age, fe(ale se., and previous drug/induced hepatitis. 6enetic variability is increasingly understood as a -ey predisposing ris- factor to drug/induced hepatitis.02B102915o.ins and (edications can cause liver in,ury through a variety of (echanis(s, including direct cell da(age, disrupting cell (etabolis(, and inducing structural changes.031 >o(e (edications, li-e aceta(inophen, cause predictable dose/related liver da(age, +hereas otherscause idiosyncratic reactions that vary a(ong individuals.0291D.posure to other hepatoto.ins can occur accidentally or intentionally through ingestion, inhalation, and s-in absorption. 4ccupational e.posure (ay occur in (any +or- fields and can present acutely or insidiously.03"1 Mushroo( poisoning is a co((on to.ic e.posure that (ay result in hepatitis.0321!utoiuneMain article& Autoi((une hepatitisAutoi((une hepatitis is a chronic disease caused by an abnor(al i((une response against liver cells.0331 5he disease is thought to have a genetic predisposition as it is associated +ith certain hu(an leu-ocyte antigens.03#1 5he sy(pto(s of autoi((une hepatitis are si(ilar to other hepatitides and (ay have a fluctuating course fro( (ild to very severe. 3o(en +ith the disease (ay have abnor(al (enstruation or beco(e a(enorrheic. 5he disease occurs in people of all ages but (ost co((only in young +o(en. Many people +ith autoi((une hepatitis have other autoi((une diseases.0351$on-alcoholic fatty li%er diseaseMain article& @on/alcoholic fatty liver disease@on/alcoholic fatty liver disease %@ANH$' is the occurrence of fatty liver in people +ho havelittle or no history of alcohol use. In the early stage there are usually no sy(pto(s, as the disease progresses sy(pto(s typical of chronic hepatitis (ay develop.03!1 @ANH$ is associated +ith (etabolic syndro(e, obesity, diabetes, and hyperlipide(ia.0371 >evere @ANH$ leads to infla((ation, fibrosis, and cirrhosis, a state referred to as non/alcoholic steatohepatitis %@A>*'. $iagnosis reIuires e.cluding other causes of hepatitis, including e.cessive alcohol inta-e.03B1 3hile i(aging can sho+ fatty liver, only liver biopsy can de(onstrate infla((ation and fibrosis characteristic of @A>*.0391 @A>* is recogni)ed as thethird (ost co((on cause of liver disease in the Jnited >tates.03!1Ischeic hepatitisMain article& Ische(ic hepatitisIn,ury to liver cells due to insufficient blood or o.ygen results in ische(ic hepatitis %or shoc- liver'.0#1 5he condition is (ost often associated +ith heart failure but can also be caused by shoc- or sepsis. Elood testing of a person +ith ische(ic hepatitis +ill sho+ very high levels of transa(inase en)y(es %A>5 and AH5'. 5he condition usually resolves if the underlying cause is treated successfully. Ische(ic hepatitis rarely causes per(anent liver da(age.0#"1&iant cell hepatitis6iant cell hepatitis is a rare for( of hepatitis that predo(inantly occurs in ne+borns and children. $iagnosis is (ade on the basis of the presence of (ultinucleated hepatocyte giant cells on liver biopsy.0#21 5he cause of giant cell hepatitis is un-no+n but the condition is associated +ith viral infection, autoi((une disorders, and drug to.icity.0#310##1Mechanis5he specific (echanis( varies and depends on the underlying cause for the condition. In viral hepatitis, the presence of the virus in the liver cells causes the i((une syste( to attac- the liver, resulting in infla((ation and i(paired function.0#51 In autoi((une hepatitis, the i((une syste( attac-s the liver due to the autoi((une disease.0#!1 In so(e hepatitis, often including hepatitis caused by alcoholis(, fat deposits accu(ulate in the liver, resulting in fatty liver disease, also called steatohepatitis.0#71Diagnosis$iagnosis is (ade by assessing an individualKs sy(pto(s, physical e.a(, and (edical history, in con,unction +ith blood tests, liver biopsy, and i(aging. Elood testing includes blood che(istry, liver en)y(es, serology and nucleic acid testing. Abnor(alities in blood che(istry and en)y(e results (ay be indicative of certain causes or stages of hepatitis.0#B10#91 I(aging can identify steatosis of the liver but liver biopsy is reIuired to de(onstrate fibrosis and cirrhosis.0391 A biopsy is unnecessary if the clinical, laboratory, and radiologic data suggests cirrhosis. Nurther(ore, there is a s(all but significant ris- to liver biopsy, and cirrhosis itself predisposes for co(plications caused by liver biopsy.051'i%er cheistry test Clinical iplication of a(noralityAlanine transa(inase %AH5' *epatocellular da(ageAspartate transa(inase %A>5' *epatocellular da(ageEilirubin 2holestasisAl-aline phosphatase 2holestasisArothro(bin ti(e I(paired synthetic functionAlbu(in %AHE' I(paired synthetic function6a((a/gluta(yl transpeptidase %665' 2holestasisEile acids 2holestasisHactate dehydrogenase *epatocellular da(age"iral hepatitisMain article& viral hepatitis?iral hepatitis is (ostly diagnosed through clinical laboratory testing. >o(e of these tests react +ith the virus or parts of the virus, such as the *epatitis E surface antigen test or nucleic acid tests.05"10521 Many of the tests are serological tests that react to the antibodies for(ed by the i((une syste(. Nor so(e (a,or causes of viral hepatitis, such as *epatitis E, there are (ultiple serological tests used that provide additional infor(ation for diagnosis.0531Differential diagnosis>everal diseases can present +ith signs, sy(pto(s, andLor liver function test abnor(alities si(ilar to hepatitis. In severe cases of alpha "/antitrypsin deficiency %A"A$', e.cess protein in liver cells causes infla((ation and cirrhosis.05#1 >o(e (etabolic disorders cause da(age tothe liver through a variety of (echanis(s. In he(ochro(atosis and 3ilsonKs disease to.ic accu(ulation of dietary (inerals results in infla((ation and cirrhosis.0551Pathology5he liver, li-e all organs, responds to in,ury in a li(ited nu(ber of +ays and a nu(ber of patterns have been identified. Hiver biopsies are rarely perfor(ed for acute hepatitis and because of this the histology of chronic hepatitis is better -no+n than that of acute hepatitis.!cuteIn acute hepatitis the lesions %areas of abnor(al tissue' predo(inantly contain diffuse sinusoidal and portal (ononuclear infiltrates %ly(phocytes, plas(a cells, Kupffer cells' and s+ollen hepatocytes. Dosinophilic cells %2ouncil(an bodies' are co((on. *epatocyte regeneration and cholestasis %canalicular bile plugs' typically are present. Eridging hepatic necrosis %areas of necrosis connecting t+o or (ore portal tracts' (ay also occur. 5here (ay be so(e lobular disarray. Although aggregates of ly(phocytes in portal )ones (ay occur these are usually neither co((on nor pro(inent. 5he nor(al architecture is preserved. 5here is no evidence of fibrosis or cirrhosis %fibrosis plus regenerative nodules'. In severe cases pro(inent hepatocellular necrosis around the central vein %)one 3' (ay be seen.In sub(assive necrosis G a rare presentation of acute hepatitis G there is +idespread hepatocellular necrosis beginning in the centri)onal distribution and progressing to+ards portal tracts. 5he degree of parenchy(al infla((ation is variable and is proportional to duration of disease.05!10571 5+o distinct patterns of necrosis have been recognised& %"' )onal coagulative necrosis or %2' panlobular %non)onal' necrosis.05B1 @u(erous (acrophages and ly(phocytes are present. @ecrosis and infla((ation of the biliary tree occurs.0591 *yperplasiaof the surviving biliary tract cells (ay be present. >tro(al hae(orrhage is co((on.5he histology (ay sho+ so(e correlation +ith the cause& Oone " %periportal' occurs in phosphorus poisoning or ecla(psia. Oone 2 %(id)onal' G rare G is seen in yello+ fever. Oone 3 %centrilobular' occurs +ith ische(ic in,ury, to.ic effects, carbon tetrachloride e.posure or chlorofor( ingestion. $rugs such as aceta(inophen (ay be (etaboli)ed in )one " to to.ic co(pounds that cause necrosis in )one 3.3here patients have recovered fro( this condition, biopsies co((only sho+ (ultiacinar regenerative nodules %previously -no+n as adeno(atous hyperplasia'.0!1Massive hepatic necrosis is also -no+n and is usually rapidly fatal. 5he pathology rese(bles that of sub(assive necrosis but is (ore (ar-ed in both degree and e.tent.Chronic2hronic hepatitis has been better studied and several conditions have been described.2hronic hepatitis +ith piece(eal %periportal' necrosis %or interface hepatitis' +ith or +ithout fibrosis0!"1 %for(erly chronic active hepatitis' is any case of hepatitis occurring for (ore than ! (onths +ith portal based infla((ation, fibrosis, disruption of the ter(inal plate, and piece(eal necrosis. 5his ter( has no+ been replaced by the diagnosis of Kchronic hepatitisK.2hronic hepatitis +ithout piece(eal necrosis %for(erly called chronic persistent hepatitis' hasno significant periportal necrosis or regeneration +ith a fairly dense (ononuclear portal infiltrate. 2ouncil(an bodies are freIuently seen +ithin the lobule. Instead it includes persistent parenchy(al focal hepatocyte necrosis %apoptosis' +ith (ononuclear sinusoidal infiltrates.5he older ter(s have been deprecated because the conditions are no+ understood as being able to alter over ti(e so that +hat (ight have been regarded as a relatively benign lesion could still progress to cirrhosis. 5he si(pler ter( chronic hepatitis is no+ preferred in association +ith the causative agent %+hen -no+n' and a grade based on the degree of infla((ation, piece(eal or bridging necrosis %interface hepatitis' and the stage of fibrosis. >everal grading syste(s have been proposed but none have been adopted universally.2irrhosis is a diffuse process characteri)ed by regenerative nodules that are separated fro( one another by bands of fibrosis. It is the end stage for (any chronic liver diseases. 5he pathophysiological process that results in cirrhosis is as follo+s& hepatocytes are lost through a gradual process of hepatocellular in,ury and infla((ation. 5his in,ury sti(ulates a regenerative response in the re(aining hepatocytes. 5he fibrotic scars li(it the e.tent to +hich the nor(al architecture can be reestablished as the scars isolate groups of hepatocytes. 5his results in nodule for(ation. Angiogenisis %ne+ vessel for(ation' acco(panies scar production +hich results in the for(ation of abnor(al channels bet+een the central hepatic veins and the portal vessels. 5his in turn causes shunting of blood around the regenerating parenchy(a. @or(al vascular structures including the sinusoidal channels (ay be obliteratedby fibrotic tissue leading to portal hypertension. 5he overall reduction in hepatocyte (ass, in con,unction +ith the portal blood shunting, prevents the liver fro( acco(plishing its usual functions G the filtering of blood fro( the gastrointestinal tract and seru( protein production.5hese changes give rise to the clinical (anifestations of cirrhosis.Specific causesMost of the causes of hepatitis cannot be distinguished on the basis of the pathology but so(edo have particular features that are suggestive of a particular diagnosis. 5he presence of (icronodular cirrhosis, Mallory bodies and fatty change +ithin a single biopsy are highly suggestive of alcoholic in,ury.0!21 Aerivenular, pericellular fibrosis %-no+n as Kchic-en +ire fibrosisK because of its appearance on trichro(e or ?an 6iesonKs stains' +ith partial or co(plete obliteration of the central vein is also very suggestive of alcohol abuse.2ardiac, ische(ic and venous outflo+ obstruction all cause si(ilar patterns.0!31 5he sinusoids are often dilated and filled +ith erythrocytes. 5he liver cell plates (ay be co(pressed. 2oagulative necrosis of the hepatocytes can occur around the central vein. *e(osiderin and lipochro(e laden (acrophages and infla((atory cells (ay be found. At the edge of the fibrotic )one cholestasis (ay be present. 5he portal tracts are rarely significantly involved until late in the course.Eiliary tract disease including pri(ary biliary cirrhosis, sclerosing cholangitis, infla((atory changes associated +ith idiopathic infla((atory bo+el disease and duct obstruction have si(ilar histology in their early stages. Although these diseases tend to pri(arily involve the biliary tract they (ay also be associated +ith chronic infla((ation +ithin the liver and difficult to distinguish on histological grounds alone. 5he fibrotic changes associated +ith these diseases principally involve the portal tracts +ith cholangiole proliferation, portal tract infla((ation +ith neutrophils surrounding the cholangioles, disruption of the ter(inal plate by (ononuclear infla((atory cells and occasional hepatocyte necrosis. 5he central veins are either not involved in the fibrotic process or beco(e involved only late in the course of the disease. 2onseIuently the centralGportal relationships are (ini(ally distorted. 3here cirrhosis is present it tends to be in the for( of a portalGportal bridging fibrosis.*epatitis D causes different histological patterns that depend on the hostKs bac-ground.0!#1 In i((unoco(petent patients the typical pattern is of severe intralobular necrosis and acute cholangitis in the portal tract +ith nu(erous neutrophils. 5his nor(ally resolves +ithout seIuelae. $isease is (ore severe in those +ith pree.isting liver disease such as cirrhosis. In the i((unoco(pro(ised patients chronic infection (ay result +ith rapid progression to cirrhosis. 5he histology is si(ilar to that found in hepatitis 2 virus +ith dense ly(phocytic portal infiltrate, constant piece(eal necrosis and fibrosis.Prognosis5he outco(e of hepatitis depends heavily on the disease or condition that is causing the sy(pto(s. Nor so(e causes, such as subclinical *epatitis A infection, the person (ay not e.perience any sy(pto(s and +ill recover +ithout any long/ter( effects. Nor other causes hepatitis can result in irreparable da(age to the liver and reIuire a liver transplant.0!1 A subset referred to in a "993 classification as :hyperacute: liver failure can happen in less than a +ee-.0!515he liver can regenerate da(aged cells.0!!1 2hronic da(age to the liver can result in the for(ation of scar tissue called fibrosis and can result in nodules that bloc- the liver fro( functioning properlyM this condition is called cirrhosis and is not reversible.0!71 2irrhosis (ay indicate a liver transplant is necessary. Another co(plication of chronic hepatitis is liver cancer, specifically hepatocellular carcino(a.0!B1In March 2"5 the 3orld *ealth 4rganisation issued its first guidelines for the treat(ent of chronic hepatitis E. 5his condition is affecting so(e 2# (illion people +orld+ide. 5hese guidelines are for the prevention, care and treat(ent of persons living +ith chronic hepatitis E.0!91Pre%ention"accines6lobal distribution of hepatitis E?accines are available to prevent hepatitis A and E. *epatitis A i((unity is achieved in 99/"F of persons receiving the t+o/dose inactivated virus vaccine. 5he hepatitis A vaccine is not approved for children under one year of age.071 ?accines to prevent hepatitis E have been available since "9B! and have been incorporated into at least "77 national i((uni)ation progra(s for children. I((unity is achieved in greater than 95F of children and young adults receiving the three/dose reco(binant virus vaccine. ?accination +ithin 2# hours of birth can prevent trans(ission fro( an infected (other. Adults over # years of age have decreased i((une response to the vaccine. 5he 3orld *ealth 4rgani)ation reco((ends vaccination of all children, particularly ne+borns in countries +here hepatitis E is co((on toprevent trans(ission fro( the (other to child.07"1