MORPHOLOGYAlthoughautoimmunehepatitissharespatternsofinjurywithacuteorchronicviralhepatitis,thetimecourseofhistologicprogressiondiffers.Inviralhepatitis,fibrosistypicallyfollowsmanyyearsofslowlyaccumulatingparenchymalinjury,whereasinautoimmunehepatitis,thereisanearlyphaseofsevereparenchymaldestructionfollowedrapidlybyscarring.Forunclearreasons,thisearlywaveofhepatocytedamageisoftensubclinical.Thefollowingfeaturesaretypicalofautoimmunehepatitis: •Necrosis and inflammation,indicatedbyextensiveinterfacehepatitisorfociofconfluent(perivenularorbridging)necrosisorparenchymalcollapse
An acute clinical illness is a common presentation (40%); sometimes the disease is fulminant, progressing to hepatic encephalopathy within 8 weeks of onset. Mortality for patients with severe untreated autoimmune hepatitis is approximately 40% within 6 months of diagnosis, and cirrhosis develops in at least 40% of survivors. Hence, diagnosis and intervention are imperative. Immunosuppressive therapy is usually effective, leading to remission in 80% of patients and enabling long-term survival. End-stage disease is an indication for liver transplantation. The 10-year survival rate after liver transplant is 75%, but recurrence in the transplanted organ occurs in 20% of cases.
SUMMARY•Therearetwoprimarytypesofautoimmunehepatitis:
Type1autoimmunehepatitisismostoftenseeninmiddle-agewomenandischaracteristicallyassociatedwithantinuclearandanti–smoothmuscleantibodies.
Type2autoimmunehepatitisismostoftenseeninchildrenorteenagersandisassociatedwithanti–liverkidneymicrosomalautoantibodies.
Autoimmunehepatitismayeitherdevelopwitharapidlyprogressiveacutediseaseorfollowamoreindolentpath;ifuntreated,botharelikelytoleadtoliverfailure.
Plasmacellsareaprominentandcharacteristiccomponentoftheinflammatoryinfiltrateinbiopsyspecimensshowingautoimmunehepatitis.
As the major drug metabolizing and detoxifying organ in the body, the liver is subject to injury from an enormous array of therapeutic and environmental chemicals. Injury may result from direct toxicity, may occur through hepatic conversion of a xenobiotic compound to an active toxin, or may be produced by immune mechanisms, such as by the drug or a metabolite acting as a hapten to convert a cellular protein into an immunogen. A diagnosis of drugor toxin-induced liver injury may be made on the basis of a temporal association of liver damage with drug or toxin exposure, recovery (usually) upon removal of the inciting agent, and exclusion of other potential causes. Exposure to a toxin or therapeutic agent should always be included in the differential diagnosis of any form of liver disease.
Principles of drug and toxic injury are discussed in Chapter 8. Here it suffices to note that drug reactions may be predictable (intrinsic) or unpredictable (idiosyncratic).
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Table 16.3 Patterns of Injury in Drugand Toxin-Induced Hepatic Injury
Pattern of Injury Morphologic Findings Examples of Associated Agents
CholestaticBlandhepatocellularcholestasis,withoutContraceptiveandanabolicsteroids,antibiotics,HAARTinflammation
CholestatichepatitisCholestasiswithlobularnecrosisandinflammation;Antibiotics,phenothiazines,statinsmayshowbileductdestruction
HepatocellularnecrosisSpottyhepatocytenecrosisMethyldopa,phenytoin
MassivenecrosisAcetaminophen,halothane