Potential causes of BA such as drugs, toxins, viruses, and genetic defects can induce changes in DNA methylation, and there may be differential effects of environmental factors on different epigenetic backgrounds. Moreover, epigenetic alterations of DNA methylation may demonstrate non-Mendelian inheritance,49 thus accounting
for occasional familial cases and nonconcordance in monozygotic twins. Our results suggest the possibility of a unifying etiology to BA, in which multiple GS-1101 purchase possible primary insults lead to a common epigenetic effect in biliary cells, resulting in a chronic destructive inflammatory process targeting the biliary system. We thank Weilong Gong, Liyuan Ma, Mani Methamani, Louis Capecci, and Erin Smith for expert technical assistance. We also thank Dr. Eric Rappaport and other members of the Nucleic Acid/Protein Core at CHOP. We thank Dr. Barbara Haber, Dr. Joshua Friedman, and Dr. David Piccoli for critical reviews of
the article. Additional supporting information may be found in the online version of this article. “
“Autoimmune hepatitis (AIH) can lead to cirrhosis, hepatic failure, and death. We aimed to identify predictors of advanced liver fibrosis at presentation, predictors of incomplete response to initial immunosuppression, and predictors R788 of poor liver-related outcomes in the population-based AIH cohort from Canterbury, New Zealand. Cases diagnosed after 1980 that fulfilled standard diagnostic criteria were included. Cases were censored at death or liver transplantation and had a median follow-up of 9 years. Analyses were performed with Cox proportional hazards regression and logistic binary regression. The times to event outcomes were summarized using Kaplan-Meier curves. A total of 133 AIH patients were included. Predictors for advanced liver fibrosis at diagnosis were age at presentation of ≤20 years or >60 years (P = 0.02), serum albumin <36 g/L
(P < 0.01), platelet <150 U/L (P < 0.01), and International Normalized Ratio (INR) >1.2 (P < 0.01). The only independent 上海皓元医药股份有限公司 predictor for incomplete normalization of alanine aminotransferase (ALT) at 6 months was age at presentation ≤20 years. Independent predictors of poor liver-related outcomes were incomplete normalization of ALT at 6 months (P < 0.01), serum albumin <36 g/L (P < 0.01), and age at presentation of ≤20 years or >60 years (P = 0.01). Kaplan-Meier estimates showed that 10-year adverse liver event-free survival was 80% for age at presentation ≤20 years and >60 years, and 93% and 100% for age at presentation between 21-40 years and 41-60 years, respectively.