IL-4Ra1 KO mice showed a significantly decreased expression of M2 markers such as YM1 throughout all stages of fibrosis progression and reversal. Using Sirius

red staining and biochemical quantification, CCL4treated mice with systemic and cell specific IL4Ra1 knockout showed significantly less collagen accumulation compared to wildtype controls during fibrosis progression. This was rversed during fibrosis regression. Compared to wildtype littermate controls, IL-4Ra1 ΔLysM but not systemic IL-4Ra1 KO mice showed an attenuated ALT elevation. Interestingly, macrophage markers like CD68, IL-1b, Arg1 and fibrosis related genes such as procollagen α1(I) and αSMA were significantly downregulated in IL-4Ra1 ΔLysM and systemic IL-4Ra1 KO mice during fibrogenesis, but upregulated during fibrosis regression. We show a

central role of IL-4Ra1 signaling in M2 macrophage polarization, with a profibrotic role during liver Alectinib BAY 73-4506 fibrosis progression and a fibrolytic role during its regression. Modulation of IL-4Ra1 by specific pharmacological intervention could be a novel approach to modulate fibrosis progression or induce its reversal. Disclosures: Detlef Schuppan – Advisory Committees or Review Panels: Aegerion, Eli Lilly, Gilead; Consulting: Boehringer-Ingelheim, Isis, Takeda; Grant/Research Support: Boehringer-Ingelheim The following people have nothing to disclose: Shih-Yen Weng, Kornelius Padberg, Yong Ook Kim, Xiao-Yu Wang, Brombacher Frank Background and Objectives: In Phase 2 trials of combination therapy for hepatitis C virus infection, 3 patients developed aplastic anemia. Two had been treated with peginterferon (PEG)+ribavirin (RBV)+tegobuvir+GS-9451 and 1 with PEG+RBV+ledipasvir+GS-9451. While bone marrow suppression is common with interferon therapy, aplastic anemia has been rare. Whole genome sequencing may identify rare genetic variants and

reveal disease-causing variants in small samples. Methods: DNA extracted from 3 blood samples from studies GS-US-248-0121, GS-US-196-0123, Carnitine palmitoyltransferase II and GS-US-1960140 were sequenced using the Illumina Whole Genome Sequencing (WGS) protocol and HiSeq 2000 sequencer. Average sequence coverage was 35X. Sequences were aligned to the most recent human reference genome (NCBI37/hg19). Entire genome sequences were compared with 425 whole genomes and 1054 whole exome sequenced population controls matched by ethnicity. The analysis focused on listing and prioritizing putatively functional rare (control MAF<0.001) variations predicted to alter amino acid sequence of protein coding genes carried by the aplastic anemia cases. A gene-wise collapsing test was performed to prioritize the genes enriched with such functional variants, and the Ingenuity Pathway Analysis (IPA) was used to analyze the prioritized list. PolyPhen-2 was used to predict the functional effects of genetic variants.