The effect of sustained virological response on the risk of extrahepatic manifestations of hepatitis C virus infection

Gut. 2018 Mar;67(3):553-561. doi: 10.1136/gutjnl-2017-313983. Epub 2017 Jun 20.

Abstract

Background and aim: Chronic HCV infection is associated with several extrahepatic manifestations (EHMs). Data on the effect of sustained virological response (SVR) on the risk of EHMs are limited.

Methods: We conducted a retrospective cohort study using data of patients from the US Veterans Affairs HCV Clinical Case Registry who had a positive HCV RNA test (10/1999-08/2009). Patients receiving interferon-based antiviral therapy (AVT) were identified. SVR was defined as negative HCV RNA at least 12 weeks after end of AVT. Risks of eight incident EHMs were evaluated in Cox regression models.

Results: Of the 160 875 HCV-infected veterans, 31 143 (19.4%) received AVT, of whom 10 575 (33.9%) experienced SVR. EHM risk was reduced in the SVR group compared with untreated patients for mixed cryoglobulinaemia (adjusted HR (aHR)=0.61; 95% CI 0.39 to 0.94), glomerulonephritis (aHR=0.62; 95% CI 0.48 to 0.79), porphyria cutanea tarda (PCT) (aHR=0.41; 95% CI 0.20 to 0.83), non-Hodgkin's lymphoma (NHL) (aHR=0.64; 95% CI 0.43 to 0.95), diabetes (aHR=0.82; 95% CI 0.76 to 0.88) and stroke (aHR=0.84; 95% CI 0.74 to 0.94), but not for lichen planus (aHR=1.11; 95% CI 0.78 to 1.56) or coronary heart disease (aHR=1.12; 95% CI 0.81 to 1.56). Risk reductions were also observed when patients with SVR were compared with treated patients without SVR for mixed cryoglobulinaemia, glomerulonephritis, PCT and diabetes. Significant reductions in the magnitude of aHRs towards the null with increasing time to initiation of AVT after HCV diagnosis were observed for glomerulonephritis, NHL and stroke.

Conclusions: Risks of several EHMs of HCV infection are reduced after AVT with SVR. However, early initiation of AVT may be required to reduce the risk of glomerulonephritis, NHL and stroke.

Keywords: Hepatitis C virus; antiviral therapy; extrahepatic manifestations; sustained virological response.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Coronary Disease / epidemiology
  • Cryoglobulinemia / epidemiology
  • Diabetes Mellitus / epidemiology
  • Female
  • Follow-Up Studies
  • Glomerulonephritis / epidemiology
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Incidence
  • Lichen Planus / epidemiology
  • Lymphoma, Non-Hodgkin / epidemiology
  • Male
  • Middle Aged
  • Porphyria Cutanea Tarda / epidemiology
  • RNA, Viral / blood*
  • Registries
  • Retrospective Studies
  • Risk Factors
  • Stroke / epidemiology
  • Sustained Virologic Response*
  • United States / epidemiology
  • United States Department of Veterans Affairs
  • Young Adult

Substances

  • Antiviral Agents
  • RNA, Viral