Moreover, we also did not found a correlation between the triggering factors with severity of HE (data nor shown). ALF (30.8%), and preceding surgery in general anesthesia (11.5%), respectively. Unfortunately, 6 out of 52 patients (11.5%) did not survive ALF and 3 patients (5.7%) underwent liver transplantation (LT). Comparing data of survivors and patients with non-recovery following treatment, MELD-score ( 0.001), age ( 0.05), creatinine ( 0.01), and finally, ALT-values ( 0.05) reached statistical Daun02 significance. CONCLUSION Drugs, viral infections, and previous surgery may trigger ALF as the initial presentation of AIH. Advanced age and high MELD-score were associated with lethal outcome. DILI-AIH involves the collection of historical and laboratory data, including the latency in onset, the rate of resolution after discontinuing treatment, hSNFS and exclusion of other reasonable causes of liver injury. The advantage of the RUCAM instrument is that it is systematic, thorough, and objective. We therefore used this instrument in our study population as – at present – it is considered the best method for assessing causality in DILI. Liver histology Liver biopsy was performed in all patients with evidence of typical histopathological features of AIH, namely presence of interface hepatitis, lymphoplasmacytic cell infiltration exceeding the borders of the portal tract, emperipolesis, and rosette formations, respectively. Differentiating between drug-induced ALF and AIH-induced ALF is difficult on the basis of histology alone. In both cases plasma cell rich inflammation with interface hepatitis can be present. In order to differentiate DILI from AIH clinical, historical, and laboratory data have to be considered. If EBV, CMV or HEV infection was suspected, viral detection by means of immunohistochemistry, in situ hybridization, and PCR was also performed. Immunosuppressive therapy and definition of non-recovery After diagnosis of AIH-induced ALF, each patient received standard steroid therapy (1 mg per kg body weight/d) intravenously with consecutive down-tapering to a maintenance dose of 7.5 mg daily. Non-recovery was defined as death or liver transplantation (LT) within 28 d despite steroid treatment and initiation of immunosuppressive therapy with azathioprine. Statistical analysis Statistical analysis was performed with GraphPad Prism, version 6.00 for MacOsX (GraphPad Software, San Diego, CA, United States). For descriptive statistics medians and IQR were determined. All variables were tested for normal distribution with the Kolmogorov-Smirnov test, the Shapiro-Wilk test, and calculation of skew and kurtosis. The Mann-Whitney test was used to compare differences between independent groups. Categorical data were tested with the chi-square test and the Kruskal-Wallis test was used for multiple comparisons. 0.05 was considered statistically significant. The whiskers used in the graphs extend down to the 5th percentile and up to the 95th percentile. RESULTS Patients demographics, laboratory data, and immunosuppressive regime Fifty-two out of 565 patients with AIH suffered from ALF as their initial presentation (9.2%) (Figure ?(Figure1A1A and B) and were included in the study. Mean age of the study population was 43.6 14.9 (19-76) years while the majority was of female gender (44/52, 84.6%). Laboratory parameters with median values on admission were as follows: ALT: 1391.0 (843.5-2154.5) U/L, Daun02 total bilirubin: 14.3 (11.7-18.7) mg/dL, serum creatinine: 0.76 (0.55-0.95) mg/dL, INR: 1.78 (1.64-2.00), immunoglobulin G: 17.2 (13.1-22.8) g/L, and finally, -globulin-fraction: 24.5% (19.5%-29.3%). Calculated median labMELD-score was 24 (22-26) points. All patients with AIH-induced ALF received a pulse therapy with steroids starting with 1 mg/kg body weight intravenously. A total of 30 patients (57.7%) continued steroids in a daily dose Daun02 of 7.5 mg to maintain remission. Azathioprine (in 27 patients, 51.9%) and also cyclosporine A (in 7 patients, 13.5%) were also used to maintain remission. Hepatic encephalopathy (HE) was classified using the West Haven criteria. We found HE grade?I in 46 of our 52 patients (88.4%), HE.