Chronic hepatitis B infection associated with twice the risk of liver-related death compared to hepatitis C

The risk of death due to liver disease is twice as high for patients with chronic hepatitis B infection compared to individuals with chronic hepatitis C, US researchers report in the online edition of Clinical Infectious Diseases.

The study involved gay and other men who have sex with men, most of whom were HIV positive. Hepatitis B remained associated with a two-fold increase in the risk of liver-related death when analysis was restricted to HIV-positive individuals. The risk of liver-related mortality was especially high for people with a low CD4 cell count.

“This is the first study to clearly demonstrate that the risk of liver-related death is twice as high for CH-B [chronic hepatitis B] compared to CH-C [chronic hepatitis C] in HIV-infected and -uninfected subjects,” write the investigators. “This study emphasizes the need for a more aggressive approach to the prevention, diagnosis, and treatment of CH-B including increasing vaccination rates among all HBV [hepatitis B virus] susceptible individuals.”

Chronic infection with either hepatitis B or hepatitis C can cause liver damage, increasing the risk of liver-related disease and death. However, it is uncertain which of these infections is associated with the greater risk of liver-related mortality.

Investigators from the Multicenter AIDS Cohort Study (MACS) noted that their study population includes equal numbers of patients with chronic hepatitis B and hepatitis C. As these men have similar characteristics, the cohort provides an opportunity to compare the mortality risk associated with these two infections.

Individuals with chronic hepatitis B or hepatitis C were followed from their entry into the study until their death, last follow-up visit, or the end of March 2010, whichever came first.

Causes of death were obtained from death registries and death certificates. Mortality was considered to be liver-related if these sources listed any of the following causes: hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, chronic liver disease, portal hypertension, liver cirrhosis, liver failure, hepatic coma, hepatorenal syndrome, or liver cancer.

Information was extracted on the patients’ age, race, drug and alcohol use, HIV status, CD4 cell count, and use of antiretroviral therapy, and treatment with an antiretroviral drug which is also active against hepatitis B (3TC, FTC, tenofovir). 

Of the 6972 men enrolled in MAC, 680 (10%) had chronic hepatitis B (337 people) or chronic hepatitis C (343 people) on recruitment to the study. Approximately 70% of patients in both groups were co-infected with HIV.

The patients were well matched at baseline and contributed a total of 6728 person-years of follow-up. During this time 293 individuals died. All-cause mortality incidence was 44 per 1000 person years. As expected, incidence of all-cause mortality was significantly higher in the HIV-positive patients compared to HIV-negative individuals (63 per 1000 person years vs 9 per 1000 person years; p < 0.001).

There was no difference in incidence of all-cause mortality between the hepatitis B-infected patients and those with hepatitis C (41 per 1000 person years vs 46 per 1000 person years).

A total of 51 deaths (17%) were attributed to liver-related causes. This yielded a mortality incidence of 8 per 1000 person years. The vast majority (90%) of liver-related deaths involved HIV-positive patients (incidence 11 per 1000 person years vs HIV-negative 2 per 1000 person years; p < 0.001).

The incidence of liver-related death was twice as high in patients with chronic hepatitis B compared to individuals with chronic hepatitis C (10 per 1000 person years vs 5 per 1000 person years; p = 0.027).

Since nearly all the liver-related deaths occurred in HIV-positive patients subsequent analysis was restricted to this group.

After adjusting for other factors related to liver disease, chronic hepatitis B infection remained associated with a significantly increased risk of liver-related death (p = 0.03).

The risk was especially high for patients with a CD4 cell count below 200 cells/mm³, which was associated with a 16-fold increase in the risk of liver-related death compared to a CD4 cell count above 350 cells/mm³ (IRR = 16.2; 95% CI, 6.1-42.8).

“These data…support recent trends towards earlier treatment of HIV and HBV infected subjects,” comment the authors

Older age was also a significant risk factor for liver-related death (p = 0.01).

Hepatitis B infection remained associated with a risk of death twice as high as that associated with hepatitis C when the investigators excluded the small number of patients whose hepatitis C infection was cleared (p = 0.02).

Rates of liver-related death among hepatitis C-infected patients were comparable in the eras before and after the introduction of effective antiretroviral therapy.

In contrast, the incidence of hepatitis B liver-related deaths dropped from 13 per 1000 person years in the pre-therapy era to 8 per 1000 person years in the period following the availability of combination HIV therapy. This reduction was not significant, but the investigators also observed a reduction in the risk of liver-related death following the introduction of tenofovir.

“These temporal trends suggest a potential beneficial effect of the use of HBV-active agents, as part of HAART in HBV-infected individuals,” suggest the authors.

Falade-Nwulia O et al. Comparative risk of liver-related mortality from chronic hepatitis B versus chronic hepatitis C virus infection. Clin Infect Dis, online edition. DOI: 10.1093/cid/cis404 (click here for the open-access article).