People with HIV/HCV-co-infection and advanced liver fibrosis can rapidly develop decompensated liver disease

Implications for use of new anti-HCV drugs

Michael Carter
Published: 02 September 2013

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 telaprevir.

“Immediate therapy 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 advanced fibrosis.”

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.

Traditional 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 compensated cirrhosis.

Direct-acting 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.

Investigators 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.

Fibrosis was staged by liver biopsy in 317 people. Individuals with fibrosis stage F3 or F4  were classified as having advanced fibrosis.

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 January 2013.

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.

Progression to 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 person-years.

For people 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.

Significantly, 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 authors.

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.”

Reference

Macias J et al. Risk of liver decompensations among human immunodeficiency virus/hepatitis C virus-coinfected individuals with advanced fibrosis: implications for the timing of therapy. Clin Infect Dis, online edition, 2013.

Hepatitis information

For more information on hepatitis visit infohep.org.

Infohep is a project we're working on in partnership with the European Liver Patients Association (ELPA).

Visit infohep.org >

Related news selected from other sources

More editors' picks on hepatitis C treatment >