Lower CD4 Count Linked to Increased Risk of Liver Cancer in HIV Positive People, Especially Those with Hepatitis B Coinfection

By Liz Highleyman

Colored scanning electron micrograph of a T4 cell (green) infected with HIV (red).

Evidence continues to accumulate suggesting that immunosuppression is linked to conditions other than classic AIDS-defining opportunistic infections and cancers. The SMART trial, showed that patients who interrupted treatment when their CD4 count fell below 350 cells/mm3 had a higher risk heart, liver, and kidney disease, while a recent analysis of the D:A:D cohort showed that low CD4 counts predicted both AIDS-defining and non-AIDS-defining malignancies.

In an article published in the October 18, 2008 issue of AIDS, researchers studying the Swiss HIV Cohort reported data from a case-control study to assess HIV-related immunodeficiency as a risk factor for hepatocellular carcinoma (HCC) among HIV positive people, controlling for coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV).

The investigators identified 26 patients with HCC in the Swiss HIV Cohort Study or through linkage with Swiss cancer registries. These individuals were matched to 251 control subjects without HCC according to study site, HIV transmission category, age, and year at enrollment. Odds ratios (OR) were estimated using conditional logistic regression.

Results

• All individuals with HCC were positive for hepatitis B surface antigen (HBsAg) and/or antibodies against HCV:

• HBV only: 11 patients;
• HCV only: 12 patients;
• Both HBV and HCV: 5 patients.

• There was a strong relationship between HIV transmission route and type of hepatitis virus coinfection.

• The patients with HCC included 14 injection drug users (3 with HBV; 13 with HCV) and 12 men who have sex with men (11 with HBV; 3 with HCV).

• The latest CD4 cell count was significantly associated with developing HCC (OR 1.33, or 33% increased risk, per 100 cells/mm3 decrease).

• This was also the case for CD4 cell percentage (OR 1.65, or 65% increased risk, per 10% decrease).

• The effects of CD4 cell count were most pronounced among transmission groups other than injection drug users (e.g., men who have sex with men, heterosexuals, or other risk factors).

• Use of combination antiretroviral therapy was not significantly associated with HCC risk (OR 0.59 for ever versus never used).

In conclusion, the study authors wrote, "Lower CD4 cell counts increased the risk for HCC among persons infected with HIV, an effect that was particularly evident for hepatitis B virus-related HCC arising in non-injecting drug users."

10/10/08

Reference
GM Clifford, M Rickenbach, J Polesel, and others (Swiss HIV Cohort Study). Influence of HIV-related immunodeficiency on the risk of hepatocellular carcinoma. AIDS 22(16): 2135-2141. October 18, 2008. (Abstract).