title: Ongoing liver inflammation in patients with chronic hepatitis C and sustained virological response.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine 1, JW Goethe-University Hospital, Frankfurt/Main, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Welsch
authors.affiliation: Department of Internal Medicine 1, JW Goethe-University Hospital, Frankfurt/Main, Germany.
authors.forename: Mira
authors.initials: M
authors.lastname: Efinger
authors.affiliation: Department of Internal Medicine 1, JW Goethe-University Hospital, Frankfurt/Main, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: von Wagner
authors.affiliation: Institute of Biostatistics and Mathematical Modelling, Faculty of Medicine, Goethe-University, Frankfurt/Main, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.affiliation: Department of Internal Medicine 1, JW Goethe-University Hospital, Frankfurt/Main, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Department of Internal Medicine 1, JW Goethe-University Hospital, Frankfurt/Main, Germany.
authors.forename: Tania M
authors.initials: TM
authors.lastname: Welzel
authors.affiliation: Department of Internal Medicine 1, JW Goethe-University Hospital, Frankfurt/Main, Germany.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Lange
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005234:Fatty Liver / Q000150:complications / Q000175:diagnosis; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006505:Hepatitis / Q000150:complications / Q000175:diagnosis*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000737:chemistry / Q000627:therapeutic use; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D017063:Outcome Assessment, Health Care; D011092:Polyethylene Glycols / Q000737:chemistry; D011446:Prospective Studies; D012189:Retrospective Studies; D012254:Ribavirin / Q000737:chemistry / Q000627:therapeutic use; D012307:Risk Factors; D000072230:Sustained Virologic Response; D013997:Time Factors; D000637:Transaminases / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D012254:Ribavirin; D000637:Transaminases