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Improvements in HIV treatment and care have had no impact on rates of endstage liver disease among HIV-positive patients with viral hepatitis
Michael Carter, 2016-09-05 07:30:00
endstage liver disease (ESLD) among HIV-positive patients 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 patients 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 patients co-infected with hepatitis B virus (HBV)
and/or hepatitis C virus (HCV). Even in the modern antiretroviral era
(2006-2010), over a third of HBV-infected patients were not taking tenofovir –
a drug potent against both HIV and HBV – and just 1% of HCV-infected
individuals 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.”
End-stage 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 are co-infected with HCV and between 5%-15% are
co-infected with HBV. Liver disease is a leading cause of serious illness and
death in these patients.
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 patients 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.
Adult patients in
twelve cohorts were included in the analysis, the study population comprising
34,119 individuals. Overall, 19% were co-infected with HCV, 5%
with HBV and 2% were triply infected (HIV/HBV/HCV). Patients 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
1000 person years.
developing ESLD were older, more likely to be male, white, had a history of
injecting drug use, were co-infected 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 patients developing ESLD did not vary by calendar period or
incidence of ESLD was observed among triply infected patients (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 mono-infected patients was probably due to alcohol abuse
and/or the side-effects of older anti-HIV drugs.
the early and modern antiretroviral eras showed here was little if any evidence
in a change of adjusted incidence rate ratios (aIRR) of ESLD among patients
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 HCV-infected
patients received treatment against this infection, and in the modern
antiretroviral era, 35% of HBV-infected patients 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 ESLS 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 HIV/HCV-co-infected patients, 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.”