People living with HIV who have hepatitis C virus (HCV) co-infection and advanced liver fibrosis
can rapidly develop decompensated liver disease even though they do not have cirrhosis of the liver, according to Spanish research
published in the online edition of Clinical
Infectious Diseases. The authors believe their findings have implications
for HCV treatment strategies and that people with advanced fibrosis should be
considered for early therapy with combinations based on boceprevir or
for chronic hepatitis C should be considered for HIV-infected patients with
advanced fibrosis without cirrhosis. These patients are at risk of liver
decompensations during the initial one to three years after diagnosis,” say the
authors. “The current usual practice of giving maximal priority to HIV/HCV
genotype 1-coinfected patients with cirrhosis for combination therapy with
telaprevir or boceprevir needs to be expanded to also include individuals with
Up to a third of people living with HIV also have hepatitis C co-infection. Liver disease can progress
rapidly in people with HIV/HCV co-infection and there is a high mortality risk after the
development of decompensated liver disease.
treatment for HCV consists of pegylated interferon and ribavirin. Only a
minority of people living with HIV who have chronic HCV infection achieve a
sustained virological response (SVR, a cure) with this treatment, and response
rates are especially poor in people with more advanced fibrosis or
antivirals (DAAs) can improve treatment outcomes. Boceprevir and telaprevir
have already been approved, but they need to be taken in combination with
existing HCV therapies, have significant drug-drug interactions, can cause
unpleasant side-effects and have complex dosing schedules. These limitations
mean that treatment based on these drugs is currently targeted at people with HIV/HCV co-infection who have cirrhosis and a high risk of liver decompensation. Other groups
of patients, including those with advanced fibrosis, are often recommended to await
the introduction of more tolerable and effective combinations of DAAs.
wished to see if this strategy was safe by looking at the risk of liver
decompensation among people with co-infection and advanced liver fibrosis.
The study was
retrospective and its population comprised 892 people with co-infection who
received care between 1990 and 2012. All were naive to HCV therapy (had not taken HCV treatment) or had taken treatment but did not
achieve an SVR.
staged by liver biopsy in 317 people. Individuals with fibrosis stage F3 or
F4 were classified as having advanced
The remaining study participants were monitored using FibroScan.
Liver stiffness between 9.5-14.5 KPa was classified as pre-cirrhosis and liver stiffness above 14.6 as cirrhosis.
Participants in the study were
followed up until the development of decompensated liver disease, death or 1
A total of 15% of participants with a baseline liver biopsy died during follow-up. Liver disease was
the cause of death in 52% of cases. There was a 10% mortality rate among people assessed with FibroScan.
Once again, 52% of deaths were attributed to liver disease.
decompensated liver disease was observed in 13% of biopsy patients at a rate of
2.3 events per 100 person-years.
Some 9% of FibroScan
patients also developed decompensated disease, a rate of 3.98 per 100
assessed by biopsy, the probabilities of remaining free of liver decompensation
at years one, three and five were 99, 95 and 90%, respectively. Three
people with baseline F3 fibrosis and 28 people with baseline cirrhosis progressed
to decompensated disease. The incidence of decompensations was 1.4 per 100
person-years for individuals with fibrosis stage F3 and 3.1 per 100 person-years
for those with baseline cirrhosis.
cases of end-stage liver disease and liver decompensations were observed within
a year of diagnosis with F3 fibrosis.
For people with
a baseline assessment of liver stiffness, the probabilities of remaining free
of decompensated disease at years one, three and five were 95, 83 and 77%,
respectively. The incidence of decompensations was 0.9 per 100 person-years for people with liver stiffness between 9.6 KPa and 14.5 KPa and 4 per 100 person-years
for people with a KPa of 14.6 or above. However, decompensations were
observed among people with less severe liver stiffness after one year of
follow-up. Platelet count was associated with an increased risk of developing
decompensated liver disease.
“We found that the
likelihood of decompensation among coinfected patients with fibrosis stage 3 in
the liver biopsy or [liver stiffness] >9.5 KPa and < 14.6 KPa is
clinically meaningful, with patients showing decompensations as soon as one
year after the fibrosis evaluation and with an increasing risk of presenting
end-stage liver disease manifestations over the following years,” write the
They believe their
findings have implications for HCV treatment strategies and that therapy should
be considered for people with advanced fibrosis, especially if they have a
low platelet count. People who do not receive treatment should be closely
monitored with liver stiffness tests “with the aim of identifying early
increasing [liver stiffness] and progression to cirrhosis.”