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