Curing hepatitis C reduces liver-related complications and death

People with hepatitis C who achieve sustained virological response to treatment had lower liver-related morbidity and mortality rates compared to people who were not successfully treated, according to research presented at the 2016 AASLD Liver Meeting in November.

Over years or decades chronic hepatitis C virus (HCV) infection can lead to severe liver damage including cirrhosis, hepatocellular carcinoma (HCC) and hepatic decompensation or liver failure. Successful hepatitis C treatment can slow or halt liver disease progression, but people who start treatment after they have already developed cirrhosis remain at risk for HCC and end-stage liver disease.

Sofie Hallager of Copenhagen University Hospital and colleagues assessed liver-related morbidity and mortality among people with hepatitis C who have cirrhosis in Denmark, and looked at how these were affected by sustained virological response, defined as continued undetectable HCV RNA at 24 weeks after the end of treatment (SVR24).

This analysis included 1032 adults with chronic hepatitis C in the Danish Database for Hepatitis B and C (DANHEP) and national health registries from January 2002 to the end of December 2013. A majority (69%) were men and the median age was 52 years. Most had HCV genotypes 1 (43%) or 3 (37%).

A total of 550 people underwent treatment, of whom 232 (42%) achieved SVR24 and 275 were non-responders. People with HCV genotype 1 were less likely to be cured. The study period ended before all-oral direct-acting antiviral therapy was available, so most were presumably treated with interferon-based therapy; first-generation HCV protease inhibitors used with interferon/ribavirin were available in the final years.

Cirrhosis was determined based on liver biopsy (fibrosis stage F4), FibroScan transient elastography (> 17 kPa) or clinical signs including ascites (abdominal fluid accumulation), spontaneous bacterial peritonitis (abdominal infection), bleeding varices (enlarged veins) in the oesophagus and hepatic encephalopathy (brain impairment). At baseline 21% had decompensated cirrhosis and 4% had liver cancer.

Looking at all people together, cumulative HCC incidence at five years was 9.2%. The overall HCC incidence rate was 2.51 per 100 person-years. HCC was more common among heavy alcohol users and people with HCV genotype 3.

The cumulative incidence of decompensation at five years was 14.3% and the incidence rate was 3.44 per 100 person-years. Alcohol use was the only significant risk factor for decompensation. In their abstract the study authors reported that just over 10% developed ascites, about 8% had bleeding varices, about 3% had hepatic encephalopathy and just over 1% developed bacterial peritonitis.

Nearly a third of people died during follow-up, for an all-cause mortality rate of 7.33 per 100 person-years for the whole cohort.

Looking at the effect of sustained response, HCC, decompensation and death rates were lower for people who achieved SVR24 compared to those who were not cured.

After adjusting for confounding factors, the five-year cumulative incidence of HCC was 5.4% in the SVR24 group versus 13.3% in the non-SVR group. Incidence rates were 0.9 versus 3.6 per 100 person-years, respectively, for an incidence rate ratio of 0.37.

For decompensation, five-year cumulative incidence was 4.8% in the SVR24 group versus 17.1% in the non-SVR group. Incidence rates were 0.8 versus 4.0 per 100 person-years, for an incidence rate ratio of 0.24.

All-cause mortality rates were 2.2 per 100 person-years in the SVR24 group versus 6.7 per 100 person-years in the non-SVR group, for an incidence rate ratio of 0.66.

"Liver-related morbidity and mortality [were] high among patients with chronic hepatitis C and cirrhosis in Denmark," the researchers concluded. "SVR24 was associated with reduced morbidity and mortality." These findings, they added, underscore the "urgent need to cure patients with chronic hepatitis C."

A related study also presented at The Liver Meeting showed that the risk of HCC fell by 80% among people in British Columbia, Canada, who were cured of hepatitis C compared to those without sustained response. Another analysis from Spain found that successful hepatitis C treatment moderately reduced the likelihood of portal hypertension, or high blood pressure in the portal vein due to scar tissue in the liver, which can lead to symptoms of decompensation. However, people who already had advanced cirrhosis before treatment saw less benefit, emphasising the importance of treating early.