Author information
1Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, SC, USA.
2Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC, USA.
3Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.
4Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
5Division of Infectious Diseases, Medical University of South Carolina, Charleston, SC, USA.
6Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
Abstract
Treatment of chronic hepatitis C virus with direct-acting antivirals usually eradicates infection, but liver fibrosis does not resolve concurrently. In patients who develop cirrhosis prior to hepatitis C virus treatment, hepatic decompensation and hepatocellular carcinoma can still occur after viral elimination due to residual fibrosis. We hypothesized the liver proteome would exhibit meaningful changes in inflammatory and fibrinogenic pathways change upon hepatitis C virus eradication, which could impact subsequent fibrosis regression. We analysed the liver proteome and phosphoproteome of paired liver biopsies obtained from 8 hepatitis C virus-infected patients before or immediately after treatment with direct-acting antivirals. Proteins in interferon signalling and antiviral pathways decreased concurrent with hepatitis C virus treatment, consistent with prior transcriptomic analyses. Expression of extracellular matrix proteins associated with liver fibrosis did not change with treatment, but the phosphorylation pattern of proteins present within signalling pathways implicated in hepatic fibrinogenesis, including the ERK1/2 pathway, was altered concurrent with hepatitis C virus treatment. Hepatitis C virus treatment leads to reduced expression of hepatic proteins involved in interferon and antiviral signalling. Additionally, changes in fibrosis signalling pathways are detectable before alteration in extracellular matrix proteins, identifying a putative chronology for the dynamic processes involved in fibrosis reversal.