The progression of
liver disease is slowed in patients co-infected with HIV and hepatitis B when
their antiretroviral therapy includes drugs that are active against both
infections, Spanish investigators report in the online edition of AIDS.
A minority of patients
cleared hepatitis B infection and 17% of individuals experienced an improvement
in their fibrosis stage.
However, one patient developed
liver cancer despite having only mild fibrosis.
Nevertheless, the
investigators believe that the results of their study “strongly suggest that
long-term control of HBV [hepatitis B virus] replication with potent anti-HBV
active antiretroviral regimens may slow down liver fibrosis progression in
HIV-HBV-co-infected patients.”
Co-infection with HIV
accelerates the pace of liver disease caused by hepatitis B. However, some anti-HIV
drugs from the nucleoside/nucleotide reverse transcriptase inhibitor class – 3TC
(lamivudine, Epivir), FTC
(emtricitabine, Emtriva), and
tenofovir (Viread) – are also active
against hepatitis B. It is therefore recommended that HIV/hepatitis B
co-infected patients should be treated with an antiretroviral regimen that
includes a combination of these drugs.
Encouraging short-term
results have been seen in co-infected individuals, but longer-term data
concerning the impact of therapy with these drugs on liver disease are
currently lacking.
Investigators in
Madrid therefore designed a retrospective study involving 92 co-infected
patients. Liver fibrosis was assessed using FibroScan, a non-invasive scan for liver damage, and both virologic and clinical outcomes were monitored.
Most of the patients
(88%) were men and the median on entry to the study was 41 years. At baseline,
the patients had been living with diagnosed HIV/hepatitis B co-infection for a
median of four years.
A total of 42 patients
were HBeAg-positive, and 75% were taking anti-HIV drugs with activity against
both viruses. A quarter of patients had a FibroScan
before starting HIV therapy, 21% were co-infected with hepatitis delta, and a further 31% with hepatitis
C.
Fibrosis stage at
baseline was null or mild in 48%, moderate to severe in 28%, and 24% had
cirrhosis.
The patients were
followed for a median of 35 months. Overall, 13 individuals were lost to
follow-up, and of the 79 remaining patients, all but two took antiretroviral
therapy that included drugs with activity against hepatitis B.
At the end of
follow-up, 71 patients had an undetectable hepatitis B viral load. HBsAg was
cleared by seven patients, all of whom had achieved an undetectable hepatitis B
viral load. Two of the patients were co-infected with hepatitis delta.
In addition, eleven
patients cleared HBe-Ag.
Six patients died, and
the overall mortality rate was 2.2 per 100 person-years. Four of the deaths
were directly attributable to liver disease. Eight patients experienced at
least one episode of decompensated liver disease, the incidence rate being 2.9 per
100 person-years. One of the patients, a 62-year old man, had only mild fibrosis at
baseline and did not have any other hepatitis co-infections. He nevertheless
developed liver cancer.
The investigators
emphasise that half of the patients who experienced decompensated liver disease
were co-infected with hepatitis delta.
A repeat FibroScan was performed on 71 patients.
Compared to baseline, there was a significant increase in the proportion of
patients with either no or mild fibrosis (65% vs. 48%, p = 0.03).
Overall, fibrosis
stage remained unchanged in 75% of individuals, worsened in 8% and improved in
17%.
Factors associated
with the development of cirrhosis were co-infection with hepatitis C (p <
0.01) and a low CD4 cell count (p <0.01).
“The use of potent nucleos(t)ide
analogues as part of antiretroviral therapy in HIV-HBV-coinfected patient seems
to be associated with increased rates of serum HBeAg and HBsAg clearance and
amelioration of liver fibrosis progression, which ultimately leads to an
improvement in survival,” comment the researchers.
However, they
emphasise, “oral nucleos(t)ide analogue therapy does not entirely annul the risk
of hepatic decompensation events or death in this population, including the
development of hepatocellular carcinoma.”