Ongoing liver inflammation in patients with chronic hepatitis C and sustained virological response

PLoS One. 2017 Feb 14;12(2):e0171755. doi: 10.1371/journal.pone.0171755. eCollection 2017.


Background: Novel direct-acting antiviral DAA combination therapies tremendously improved sustained virologic response (SVR) rates in patients with chronic HCV infection. SVR is typically accompanied by normalization of liver enzymes, however, hepatic inflammation, i.e. persistently elevated aminotransferase levels may persist despite HCV eradication. Aim: To investigate prevalence and risk factors for ongoing hepatic inflammation after SVR in two large patient cohorts.

Methods: This post-hoc analysis was based on prospectively collected demographic and clinical data from 834 patients with SVR after HCV treatment with either PegIFN- or DAA-based treatment regimens from the PRAMA trial (n = 341) or patients treated at our outpatient clinic (n = 493).

Results: We observed an unexpected high prevalence of post-SVR inflammation, including patients who received novel IFN-free DAA-based therapies. Up to 10% of patients had ongoing elevation of aminotransferase levels and another 25% showed aminotransferase activity above the so-called healthy range. Several baseline factors were independently associated with post-SVR aminotransferase elevation. Among those, particularly male gender, advanced liver disease and markers for liver steatosis were strongly predictive for persistent ALT elevation. The use of IFN-based antiviral treatment was independently correlated with post-SVR inflammation, further supporting the overall benefit of IFN-free combination regimens.

Conclusion: This is the first comprehensive study on a large patient cohort investigating the prevalence and risk factors for ongoing liver inflammation after eradication of HCV. Our data show a high proportion of patients with ongoing hepatic inflammation despite HCV eradication with potential implications for the management of approximately one third of all patients upon SVR.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Fatty Liver / complications
  • Fatty Liver / diagnosis
  • Hepacivirus / drug effects*
  • Hepacivirus / physiology
  • Hepatitis / complications
  • Hepatitis / diagnosis*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-alpha / chemistry
  • Interferon-alpha / therapeutic use
  • Logistic Models
  • Middle Aged
  • Multivariate Analysis
  • Outcome Assessment, Health Care
  • Polyethylene Glycols / chemistry
  • Prospective Studies
  • Retrospective Studies
  • Ribavirin / chemistry
  • Ribavirin / therapeutic use
  • Risk Factors
  • Sustained Virologic Response*
  • Time Factors
  • Transaminases / metabolism


  • Antiviral Agents
  • Interferon-alpha
  • Polyethylene Glycols
  • Ribavirin
  • Transaminases

Grant support

This research was supported by the research funding programm Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz (LOEWE) of the State of Hessen, Research Center for Translational Medicine and Pharmacology TMP, and the Else Kröner-Fresenius Foundation (EKFS), Research Training Group Translational Research Innovation - Pharma (TRIP). Grant support from the Deutsche Forschungsgemeinschaft is acknowledged for C.W. (WE 4388/6-1) and C.M.L. (LA 2806/2-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.