Study shows value of hepatitis C therapy for HIV co-infected patients with compensated cirrhosis

Spanish research published in the online edition of Clinical Infectious Diseases shows the benefits of successful hepatitis C therapy for people co-infected with HIV who have compensated liver cirrhosis. Achievement of a sustained virological response (SVR) was associated with lower rates of progression to decompensated cirrhosis and a lower risk of death.

“The results found in this study demonstrate that SVR following HCV therapy reduces the risk of emerging hepatic decompensation and occurrence of death due to any cause in HIV-infected individuals with cirrhosis,” comment the authors.

Patients received dual therapy with pegylated interferon and ribavirin. The authors suggest that all co-infected people with compensated cirrhosis should be evaluated for therapy with regimens that also include newly available direct-acting antiviral agents.

Infection with hepatitis C can lead to hardening (fibrosis) or scarring (cirrhosis) of the liver. People are said to have 'compensated cirrhosis' when their liver can still cope – or compensate – for this scarring. People are diagnosed with decompensated cirrhosis when they develop serious liver-related disease. Decompensated cirrhosis is associated with a poor prognosis.

Little is known about the benefits of hepatitis C therapy for co-infected people with compensated cirrhosis.

A team of Spanish investigators therefore designed a prospective study involving 166 co-infected people with baseline compensated cirrhosis who received hepatitis C therapy between 2001 and 2011. Treatment consisted of pegylated interferon and weight-based ribavirin and lasted 48 weeks.

The authors gathered data on the proportion of people who achieved an SVR (undetectable hepatitis C viral load 24 weeks after the completion of treatment, regarded as a cure). Over a median of 55 months of follow-up, rates of progression to decompensated cirrhosis and death were compared between people who achieved an SVR and those who did not.

Overall, 25% of patients achieved an SVR. A total of 25 people (21%) progressed to decompensated cirrhosis. The rate of disease progression was 5 cases per 100 person-years.

Analysis of outcomes according to treatment response showed that 5% of people with an SVR progressed to decompensated disease compared to 27% of individuals without an SVR (p = 0.002). The rate of disease progression was 0.89 per 100 person-years among those with an SVR, compared to 6.4 per 100 person-years for people who did not respond to therapy.

The probabilities of developing decompensated cirrhosis for people with an SVR one year and three years after completing therapy were 0 and 4% respectively. The corresponding probabilities for patients without an SVR were 15 and 32%.

After controlling for other factors associated with liver disease progression, achievement of an SVR was confirmed as reducing the risk of decompensated cirrhosis (p = 0.042).

However, an SVR did not significantly reduce the risk of liver cancer. One patient with a treatment response developed hepatocellular carcinoma (HCC), compared to four patients without an SVR. “We cannot exclude that the association between SVR and a lesser incidence of HCC did not reach statistical significance due to lack of statistical power and insufficient follow-up,” write the authors. They recommend that co-infected people with compensated cirrhosis “should be followed-up in the long-term, and screening programmes for HCC should be continued, even after achieving SVR”.

A total of 24 people (15%) died during follow-up, including two (5%) who had an SVR and 22 (18%) without an SVR. The mortality rate was 0.87 per 100 person-years for people with a treatment response, versus 4.1 per 100 person-years for people without an SVR.

The probabilities of death for people with an SVR one and three years after treatment were 0 and 3% respectively. The corresponding probabilities for people without a treatment response were 12 and 20%. The association between an SVR and a reduced mortality risk was confirmed in multivariate analysis (p = 0.043).

Overall, 10% of patients died because of liver failure. SVR reduced the risk of liver-related deaths. The rate of liver-related mortality for people with an SVR was 0.87 per 100 person-years compared to a rate of 2.8 deaths per 100 person-years for people who did not eradicate their hepatitis C infection.

“This study shows that the achievement of SVR following peg-IFN plus RBV treatment is associated with a marked reduction in the risk of hepatic decompensations and overall mortality in HIV-infected patients with compensated HCV-related cirrhosis,” comment the investigators. “Data from this study strongly support that therapy-driven HCV eradication is a priority in HIV-infected individuals with compensated HCV-related cirrhosis in order to prevent liver-related decompensation and mortality secondary to any cause.”

They conclude, “treating these patients with the best treatment available for chronic HCV infection is a priority”.

Mira JA et al. Benefits from sustained virological response to pegylated interferon plus ribavirin in HIV/HCV-coinfected patients with compensated cirrhosis. Clin Infect Dis, online edition, 2013.