At the same abstract session, Santiago Moreno of Ramon
y Cajal Hospital in Madrid presented findings from a study of liver fibrosis
regression after hepatitis C treatment in people with HIV and HCV co-infection,
and how this influences liver-related complications, hospital admissions and
Several studies of people with HCV monoinfection have shown that
successful treatment with interferon-based therapy can halt or even partially
reverse liver fibrosis, and this improvement is associated with a reduction in
liver disease complications and death over time. However, even people who have
been cured of HCV are not completely protected against developing liver-related
complications or liver cancer. Direct-acting antiviral agents in
interferon-free regimens have not yet been around long enough to have long-term
data on outcomes.
Less is known about disease progression after hepatitis C treatment in people
with HIV and HCV co-infection. But a study
presented at this year's Conference on Retroviruses and Opportunistic Infections
(CROI) showed that people with co-infection remain at risk for liver failure, liver cancer and
liver-related death even after being cured, with outcomes worsening the longer
treatment is delayed.
Moreno's team compared the incidence rate and time to develop
complications and death in co-infected people with cirrhosis, according to
whether they achieved sustained virological response and liver fibrosis regression
using interferon-based therapy.
This study included 133 people with co-infection
treated with pegylated interferon and ribavirin at Ramon y Cajal Hospital since
2004. More than three-quarters were men and the average age was 42 years. Most
(59%) had HCV genotype 1, followed by 3 (34%), 4 (17%) and 2 (3%). They had
been living with HCV for more than 20 years and were followed-up for nearly
seven years after hepatitis C treatment.
Participants had a liver biopsy or transient
elastography done at baseline, and follow-up elastography scans were done
starting in 2006. Fibrosis regression was defined as a 1-point decrease in
Metavir score, as estimated by transient elastography liver stiffness
Overall, 42 participants, or 32%, achieved SVR, with
the rest being non-responders or relapsers. While cure rates using the new
interferon-free direct-acting antivirals are typically above 90%, SVR rates
below 50% are not unusual for people with co-infection using interferon and
A total of 37 participants experienced fibrosis
regression, which was much more likely to occur in people who were cured (55%) compared
to those without sustained response (15%).
Fibrosis regression rates among people with SVR were
22%, 9%, 52% and 17% for HCV genotypes 1, 2, 3 and 4, respectively. Among the
14 people who showed fibrosis regression without SVR, 79% had genotype 1, with
a single study participant with each of the other three genotypes. Regression
without SVR was relatively more likely among relapsers – those who had
undetectable HCV at the end of therapy but saw the virus rebound after stopping
Overall, people who achieved SVR were less likely than
people who were not cured to experience liver-related complications,
hospitalisation, liver-related death or death due to any cause. But fibrosis
regression also played a major role.
Among people with SVR, rates of liver-related
complications and hospitalisation were much lower than rates for people without
SVR. Within the SVR group, fibrosis regression conferred an added advantage,
but it did not make much difference among those without SVR. Looking at
liver-related or all-cause death, however, the risk was much lower for people
with fibrosis regression in both the SVR and non-SVR groups. In fact, death
rates were higher for people who were cured but did not experience fibrosis
regression (FR) than for those who had regression without SVR.
SVR+FR SVR/no FR No SVR/FR No SVR or FR
All-cause death 17% 32% 14% 48%
Liver-related death 4% 16% 7% 38%
Liver complications 4% 11% 36% 43%
Hospitalisation 9% 16% 29% 30%
Fibrosis regression was the only factor significantly
associated with lower risk of death in a multivariate analysis, with a 64% reduction
in the risk of all-cause death (adjusted hazard ratio [HR] 0.36) and a 85%
reduction in liver-related death (HR 0.15). Both fibrosis regression and SVR were
associated with lower likelihood of liver-related complications, cutting the
risk by 91% (HR 0.09) and 76% (HR 0.24), respectively.
"Our study clarifies
the risk of complications after therapy in HIV-infected patients with
cirrhosis, showing a lower rate if fibrosis regression is attained in addition
to SVR," the researchers concluded.
application, [transient elastography liver stiffness measurement] is useful in
demarcating cirrhotic patients at a high risk for complications after therapy
and who would require a more frequent check-up," they added. "Sequential
[transient elastography] after therapy could be useful in the management of the
patients, irrespective of achieving SVR."