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Improvements in HIV treatment and care have had no impact on rates of endstage liver disease among HIV-positive people with viral hepatitis
Michael Carter, 2016-09-05 07:30:00
endstage liver disease (ESLD) among HIV-positive people with viral hepatitis changed
little between 1996 and 2010, despite major improvements in HIV treatment and
care, investigators from Canada and the United States report in the online
edition of Clinical Infectious Diseases.
Over 36,000 people were included in the
analysis. There was little evidence that the major advances in HIV therapy that
occurred during the study period had a meaningful impact on incidence of ESLD,
which remained high among people with hepatitis B virus (HBV)
and/or hepatitis C virus (HCV) co-infection. Even in the modern antiretroviral era
(2006-2010), over a third of people with HBV infection were not taking tenofovir –
a drug potent against both HIV and HBV – and just 1% of
individuals with HCV infection received therapy against this infection.
“This study is the
largest and longest prospective evaluation of validated ESLD outcomes conducted
in an HIV-infected population,” write the investigators. “ESLD events were
common in all time periods studied and occurred more frequently among those
with viral hepatitis co-infection.”
Endstage liver disease in this study refers to liver failure leading to liver transplant or laboratory and clinical evidence of severe fibrosis or a clinical event indicating decompensated cirrhosis, such as ascites, bacterial peritonitis, variceal haemorrhage, hepatic encephalopathy or hepatocellular carcinoma.
Around one in five people living with HIV have HCV co-infection and between 5 and 15% have HBV co-infection. Liver disease is a leading cause of serious illness and
death in these people.
HIV therapy has
improved dramatically since it was first introduced in 1996, resulting in greatly improved life expectancy and a steep reduction in illness and death, but it is unclear
if these gains in antiretroviral treatment have been accompanied by a fall in
rates of ESLD, especially among people with viral hepatitis co-infection.
the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD)
therefore designed a prospective observational study to see if incidence of
ESLD as validated by physicians changed according to antiretroviral era – early
(1996-2000), middle (2001-2005) and modern (2006-2010) and by viral hepatitis
co-infection status. Results were adjusted to take account of hepatitis status,
age, sex, race, cohort, CD4 count and HIV viral load.
Adults in 12 cohorts were included in the analysis, the study population comprising
34,119 individuals. Overall, 19% had HCV co-infection, 5% had HBV and 2% had triple infection (HIV/HBV/HCV). Individuals were followed for a
median of 2.9 years and contributed 129,818 person-years of follow-up. During
this time there were 380 incident ESLD events, an incidence ratio of 2.9 per
developing ESLD were older, more likely to be male, white, had a history of
injecting drug use, had co-infection with HCV and/or HBV, had evidence of liver
dysfunction or fibrosis at baseline, a low CD4 count and a detectable viral load.
proportion of people developing ESLD did not vary by calendar period or
incidence of ESLD was observed among people with triple infection (11.57 per 1000
person-years), followed by HBV (9.72 per 1000 person-years), HCV (6.10 per 1000
person-years) and HIV mono-infection (1.27 per 1000 person-years). The authors
suggest that ESLD in people with mono-infection was probably due to alcohol abuse
and/or the side-effects of older anti-HIV drugs.
the early and modern antiretroviral eras showed there was little if any evidence
in a change of adjusted incidence rate ratios (aIRR) of ESLD among people
with viral hepatitis: HCV = 0.95, 95% CI, 0.61-1.47; HBV = 0.95, 95% CI,
0.40-2.26; triple infection = 1.52, 95% CI, 0.46-5.02.
of HIV suppression were observed over the study period, reaching 85% in the
modern treatment era with no difference in suppression rates according to viral
continuing high rates be explained by sub-optimal hepatitis care? There was
some evidence to suggest this could be the case. Only 1% of people with HCV infection received treatment against this infection, and in the modern
antiretroviral era, 35% of people with HBV infection were not receiving tenofovir.
patients co-infected with HBV or HCV are at markedly increased risk of ESLD
compared with those infected with HIV alone,” conclude the investigators. “The
continued high incidence of ESLD despite modern ART underscores the urgent need
to specifically address HCV and HBV infections in HIV-infected adults. Improved
identification, staging, monitoring and treatment of co-infected persons should
The author of an
accompanying editorial calls for further studies to investigate the impact of
new HCV therapies on ESLD events in people with HIV/HCV co-infection, adding “a
close follow-up on the effect of cART including drugs active against both HIV
and HBV in HBV/HIV co-infected patients is needed to confirm a reduced risk of
hepatic decompensation in these patients.”