Chronic Hepatitis B and C Virus Infection and Risk for Non-Hodgkin Lymphoma in HIV-Infected Patients: A Cohort Study

Ann Intern Med. 2017 Jan 3;166(1):9-17. doi: 10.7326/M16-0240. Epub 2016 Oct 18.

Abstract

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear.

Objective: To investigate whether chronic HBV and HCV infection are associated with increased incidence of NHL in HIV-infected patients.

Design: Cohort study.

Setting: 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE).

Patients: HIV-infected patients with information on HBV surface antigen measurements and detectable HCV RNA, or a positive HCV antibody test result if HCV RNA measurements were not available.

Measurements: Time-dependent Cox models to assess risk for NHL in treatment-naive patients and those initiating ART, with inverse probability weighting to control for informative censoring.

Results: A total of 52 479 treatment-naive patients (1339 [2.6%] with chronic HBV infection and 7506 [14.3%] with HCV infection) were included, of whom 40 219 (77%) later started ART. The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving ART. A total of 252 treatment-naive patients and 310 treated patients developed NHL, with incidence rates of 219 and 168 cases per 100 000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 (95% CI, 0.69 to 2.56) and 0.67 (CI, 0.40 to 1.12), respectively, in treatment-naive patients and 1.74 (CI, 1.08 to 2.82) and 1.73 (CI, 1.21 to 2.46), respectively, in treated patients.

Limitation: Many treatment-naive patients later initiated ART, which limited the study of the associations of chronic HBV and HCV infection with NHL in this patient group.

Conclusion: In HIV-infected patients receiving ART, chronic co-infection with HBV and HCV is associated with an increased risk for NHL.

Primary funding source: European Union Seventh Framework Programme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Biomarkers / blood
  • Cohort Studies
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • Hepatitis Antibodies / blood
  • Hepatitis B Core Antigens / immunology
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis C / immunology
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / diagnosis
  • Humans
  • Immunoglobulin G / blood
  • Lymphoma, Non-Hodgkin / complications*
  • Lymphoma, Non-Hodgkin / mortality
  • Male
  • RNA, Viral / blood
  • Risk Factors

Substances

  • Anti-HIV Agents
  • Biomarkers
  • Hepatitis Antibodies
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Immunoglobulin G
  • RNA, Viral