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The effect of sustained virological response on the risk of extrahepatic manifestations of hepatitis C virus infection
  1. Parag Mahale1,2,3,
  2. Eric A Engels1,
  3. Ruosha Li4,
  4. Harrys A Torres5,
  5. Lu-Yu Hwang2,
  6. Eric L Brown2,
  7. Jennifer R Kramer2,3,6
  1. 1 Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
  2. 2 Department of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas School of Public Health, Houston, Texas, USA
  3. 3 Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
  4. 4 Department of Biostatistics, The University of Texas School of Public Health, Houston, Texas, USA
  5. 5 Department of Infectious Diseases, Infection Control & Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  6. 6 Department of Medicine, Section of Health Services Research, Baylor College of Medicine, Houston, Texas, USA
  1. Correspondence to Dr Parag Mahale, Infections and Immunoepidemiology Branch Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr, Room 6E214, Rockville, MD 20850, USA; parag.mahale{at}


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.

  • Hepatitis C virus
  • extrahepatic manifestations
  • antiviral therapy
  • sustained virological response

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  • Contributors PM, EAE and JRK designed the study; PM and JRK acquired the data; PM, EAE, RL and JRK conducted the statistical analyses; PM, EAE, RL, HAT, LYH, ELB and JRK interpreted the data, drafted the manuscript, and provided critical revisions for important intellectual content.

  • Funding Eric Engels was supported by the Intramural Research Program of the National Cancer Institute.

  • Competing interests HAT is a consultant for Gilead Sciences, Janssen Pharmaceuticals, Merck and Co., Dynavax Technologies, Vertex Pharmaceuticals, and Genentech, and has received research grants from Gilead Sciences, Merck and Co., and Vertex Pharmaceuticals. Other authors have no conflicts of interest to declare.

  • Patient consent Patients are not identified in this study, and grouped findings are reported. A waiver of informed consent was obtained from the IRB.

  • Ethics approval Baylor College of Medicine’s Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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