Hepatitis C cure associated with significant improvement in liver stiffness in people with HIV and HCV co-infection

A successful response to hepatitis C virus (HCV) therapy is associated with a significant improvement in liver stiffness among people with HIV and HCV co-infection, French investigators report in the online edition of AIDS. Patients were followed for an average of 45 months, and significant regression of liver stiffness from pre-treatment levels was observed in successful responders with fibrosis and cirrhosis. Liver stiffness is considered to be a good non-invasive marker of liver fibrosis stage.

“A SVR [sustained virological response] to HCV therapy was independently associated with a decrease in liver stiffness,” comment the authors. “It is noteworthy that this decrease in liver stiffness occurred not only in patients with fibrosis but also in patients with cirrhosis.”

Large numbers of people living with HIV also have hepatitis C (HCV co-infection). Liver disease is now a leading cause of illness and death for people with this co-infection. Treatment is available for HCV, and its aim is sustained virological response – an undetectable HCV viral load six months after the completion of treatment. A successful response to HCV therapy has been associated with a reduction in the risk of liver disease.

Glossary

sustained virological response (SVR)

The continued, long-term suppression of a virus as a result of treatment. In hepatitis C, refers to undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 12 or 24 weeks after ending treatment and is considered to be a cure (SVR12 or SVR24).

fibrosis

Thickening and scarring of connective tissue. Often refers to fibrosis of the liver, which can be caused by an inflammatory reaction to long-term hepatitis infection. See also ‘cirrhosis’, which is more severe scarring.

cirrhosis

Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 

regression

Improvement in a tumour. Also, a mathematical model that allows us to measure the degree to which one of more factors influence an outcome.

invasive

In medical terms, going inside the body.

But the impact of SVR on fibrosis regression is unclear. Liver stiffness can give a good indication of fibrosis stage and has the advantage of being measured by a non-invasive scan. Investigators from the French ANRS CO13 HEPAVIH cohort designed a prospective observational study to assess the impact of SVR on liver stiffness up to two years after the completion of HCV therapy.

Their study population comprised 98 individuals who had at least one pre-HCV therapy liver stiffness measurement of 7.1kPa or above – correlated with fibrosis stage F2. A significant regression of liver stiffness was defined as a 30% or more reduction from pre-treatment levels. The investigators compared the proportion people with and without SVR who achieved this outcome. A sub-analysis monitored liver stiffness changes in people with pre-treatment liver stiffness of 12.5kPa or above – liver cirrhosis.

Approximately three-quarters (77%) of participants in the study were male and the average age was 46 years. All the study participants were taking antiretroviral therapy, and at the time HCV treatment was started, median CD4 count was 328 cell/mm3 and 86% had an undetectable HIV viral load. Median baseline liver stiffness was 10.6kPa and 36% had a value indicative of liver fibrosis.

HCV therapy for 89 people consisted of pegylated interferon and ribavirin; the remaining individuals received a first-generation HCV protease inhibitor. Overall, 54% of participants had a sustained response to treatment. People with an SVR were significantly more likely to experience a 30% or more reduction in liver stiffness than people who did not have an SVR. After one year of follow-up, this outcome was observed in 51% of people with SVR compared to 28% of people without SVR, the difference increasing by the two-year follow-up point (74% vs 28%).

Analysis of the participants who had cirrhosis at baseline showed that 14 of the 18 people with SVR experienced a 30% or greater reduction in liver stiffness, compared to three of the people who did not respond to treatment.

After taking into account potential confounders, SVR was shown to be independently associated with a 30% or more reduction in liver stiffness, in both the overall study group (HR = 5.77; 95% CI, 2.00-16.22, p = 0.001) and in the people with pre-treatment cirrhosis (HR = 8.21; 95% CI, 2.15-31.43, p = 0.002).

People with SVR also had a 2.6-fold higher chance of experiencing a decrease in at least one fibrosis stage (95% CI, 1.4-4.7, p = 0.001). Analysis of people with baseline cirrhosis showed that at the two-year follow-up interval, 68% of those with SVR had experienced regression to at least fibrosis stage F3, compared to 20% of people who did not have SVR.

“The therapeutic eradication of HCV induces rapid and durable regression of liver stiffness even in patients with cirrhosis,” conclude the investigators. They want longer-term studies to see if this decrease in liver stiffness is correlated with a reduced risk of serious liver disease, “even in patients with advanced disease and decompensated cirrhosis.”

References

The ANRS CO13 HEPAVIH Cohort Regression of liver stiffness after sustained HCV virological responses among HIV/HCV-coinfected patients. AIDS, online edition. DOI: 10.1097/QAD.0000000000000787, 2015.