Clinical And Pathological Features Of140Patients With Drug-induced Liver Injury(DILI) And The Risk Factors Of Chronicity

Objective：The aim of this study was to determine the association between theprognosis with the clinical, serological and histological features of drug-induced liverinjury(DILI), and to find the relative risk factors of chronic DILI.Methods：We included inpatients in our hospital between January2009andDecember2012, according to the causality relationship between the administration ofthe suspected drugs and the apparent onset of symptoms/the liver functionabnormality and excluded patients who were diagnosed of other causes or combinedwith other causes of liver injury. We established a DILI database in where the wholeclinical, serological, and histological characteristics and the follow-up informationwere retrospectively recorded.Results： We all retrieved197DILI patients, of which22patients didn’t meet thediagnosis criteria of DILI,33patients combined with other liver-injured diseases,2patients failed to attend follow up. Finally140patients had fulfilled our researchcriteria.97.1%patients had the RUCAM score≥6. Generally, the average age of140DILI patients was53.0years old, female consisted of80.7%. The most frequentcomplains of DILI patients were dark urine(55.7%), jaundice(50.7%), weakness(50.0%) and anorexia(50.0%). The patterns of liver injury were hepatocellular patternin82.9%, mixed pattern in9.3%, and cholestasis pattern in7.9%. The average age ofdifferent patterns of liver injury were different,53.1±14.8,43.9±15.0,61.4±17.1inhepatocellular, mixed and cholestasis pattern respectively, whose results hadstatistically significance(P<0.05). However, the percentage of lymphocyte in serumwas the highest in mixed pattern(45.1±1.0) than hepatocellular(34.2±10.8) and cholestasis(29.6±6.8) pattern, which had statistically significance(P<0.05).Herb(61.4%), antimicrobial agents (15.0%) and lipid-lowering drugs(4.3%) weremost commonly implicated. The mean follow-up time was19.5m.74.3%patientscould recover before6months in hepatocellular type and1year in mixed/cholestasistype after withdraw the suspected drugs.22.1%patients couldn’t recover within theprescribed time, which was termed as chronicity. According to the clinical symptomsand the changes of laboratory data, we classified the types of chronicity into6phenotypes, which were included slow-down, recurrent, protracted, drug-inducedAIH, chronic cholestasic, and cirrhosis. Compared chronic and recover group of DILI,we found the declining intervals of ALT and TBIL from peak to0.5peak existedsignificant differences,6.0(4.0-8.0) vs.8.0(6.8-17.3) and8.0(6.0-12.0) vs.27.0(10.0-35.0), respectively. In a multiple Logistic regression analysis, we found thedeclining interval of TBIL from peak to0.5peak was the risk factor independentlyassociated with the chronic development of DILI(OR:1.253;95%CI:1.079-1.456;P=0.003). In the histological respect, there had statistically significance in canalicularcholestasis and interface hepatitis between recover group and chronic one.Conclusions: The incidence of chronic DILI is about20%. According to the dynamictrend of laboratory data, we conclude six phenotypes of chronicity. Although thetypes of liver injury and the baseline laboratory data can’t predict the development ofchronicity, the pathological features, such as canalicular cholestasis and interfacehepatitis, can help to predict chronicity. The declining interval of TBIL from peak to0.5peak is the independent risk factor of chronicity.