Chronic Hepatitis B, C Linked With Non-Hodgkin Lymphoma in HIV Patients


Chronic infection with hepatitis B or C virus was associated with an increased risk for non-Hodgkin lymphoma among patients with HIV who are on antiretroviral therapy.

Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) was associated with an increased risk for non-Hodgkin lymphoma among patients with HIV who are on antiretroviral therapy, according to the results of a study published in Annals of Internal Medicine.

“Early diagnosis and treatment of HIV infection in conjunction with routine screening for chronic HBV and HCV infection is essential to further decrease non-Hodgkin lymphoma morbidity and mortality in HIV-infected persons,” wrote Qing Wang, PhD, from Basel Institute for Clinical Epidemiology & Biostatistics at University Hospital Basel in Switzerland, and colleagues. “Our findings provide strong evidence that HCV co-infected patients with poor immune status or restoration are at high risk for non-Hodgkin lymphoma and death and deserve high priority for access to well-tolerated, interferon-free, direct-acting antiviral treatment programs similar to those for patients with advanced liver fibrosis or cirrhosis.”

Wang and colleagues investigated whether chronic HBV or HCV was associated with increased incidence of non-Hodgkin lymphoma in patients with HIV. They looked at data from 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) for patients with HIV and information on HBV surface antigen measurement and detectable HCV RNA, or a positive HCV antibody test.

Of 52,479 treatment-naive patients, they identified 1,339 with HBV (2.6%) and 7,506 with HCV (14.3%); 0.4% of patients had dual infection. Seventy-seven percent of these patients later started antiretroviral therapy.

The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving antiretroviral therapy. During that time, 252 treatment-naive patients and 310 treated patients developed non-Hodgkin lymphoma.

Infection with HBV and HCV was associated with an increased risk for non-Hodgkin lymphoma. Among treatment-naive patients, the hazard ratio (HR) for non-Hodgkin lymphoma with HBV was 1.33 (95% CI, 0.69–2.56) and with HCV was 0.67 (95% CI, 0.40–1.12). Among treated patients, the HR with HBV was 1.74 (95% CI, 1.08–2.82) and with HCV was 1.73 (95% CI, 1.21–2.46).

The researchers acknowledged that risk estimated in treatment-naive patients was less certain, “possibly due to the lower number of events, limited follow-up due to some patients initiating antiretroviral therapy, or other unmeasured competing factors masking the effect of chronic HBV and HCV infection in this population.”

They also noted that a large number of non-Hodgkin lymphoma types were not classified and therefore “had to be coalesced, which precluded an analysis according to non-Hodgkin lymphoma subtype. In addition, ascertainment of non-Hodgkin lymphoma was not uniformly reported by all cohorts. Therefore, our findings might not accurately reflect the prognosis of chronic HCV and HBV co-infection relevant for different types of non-Hodgkin lymphoma.”

In an editorial that accompanied the article, Charles S. Rabkin, MD, and James J. Goedert, MD, of the National Cancer Institute, listed several reasons for caution when interpreting the results. Among them were the fact that the researchers extrapolated non-Hodgkin lymphoma risk estimates up to 10 years based on data from 13 months of follow-up, and the fact that several previous studies looking at this association failed to find a link between AIDS-related non-Hodgkin lymphoma and co-infection with hepatitis virus.

However, Rabkin and Goedert noted that “the finding that non-Hodgkin lymphoma risk during antiretroviral therapy is elevated 1.7-fold with HCV or HBV co-infection may partially explain the persistent excess of non-Hodgkin lymphoma in patients with well-controlled HIV infection. More important, this study highlights the urgent need to prevent HCV and HBV infection in people living with HIV and to treat those who are co-infected.”

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