The RESIST-HCV study followed the clinical outcomes of all people treated with direct-acting antivirals in Sicily between March 2015 and December 2016. The study excluded people with a prior history of hepatocellular carcinoma or liver transplant. A total of 4668 people were included in the analysis, 69.2% with Child-Pugh A cirrhosis (compensated), 8.8% with Child-Pugh B cirrhosis and 22% with chronic infection. Genotype 1b infection predominated (68%). The mean age of people with cirrhosis and people without cirrhosis was 66 years and 62 years respectively. Fifty-eight per cent were male. Liver stiffness measurements by Fibroscan showed a mean liver stiffness of 10 kPA in people with chronic infection, 21.8 kPA in people with Child-Pugh A and 27.3 kPA in people with Child-Pugh B.
Intent-to-treat analysis showed that the overall rate of sustained virologic response (cure) was 90.7% (93.1% in the chronic hepatitis group, 90.9% in the Child-Pugh A group and 83.1% in the Child-Pugh B group). People with Child-Pugh B cirrhosis were more likely to die during treatment (p < 0.001).
People with Child-Pugh B cirrhosis were also more likely to die during a median follow-up period of 72 weeks. 6.3% of the Child-Pugh B group died compared to 1% of the Child-Pugh A group and 0.3% of the chronic infection group. An increased risk of death for people who failed to achieve a sustained virologic response began to become apparent after 48 weeks of follow-up (p < 0.0001). Liver-related events (decompensation and new hepatocellular carcinoma) occurred more frequently in people with Child-Pugh A cirrhosis who did not achieve a sustained virologic response but there was no significant difference in the incidence of these events in people with chronic hepatitis or Child-Pugh B cirrhosis.
Multivariate analysis showed that people with Child-Pugh A cirrhosis were 15 times more likely to die of a liver-related cause if they did not achieve a sustained virologic response (HR 15.5, 95% CI 4.42-54.49, p < 0.001). An albumin level below 3.5 g/dl increased the risk of death sixfold (HR 6.01, 95% CI 2.3-15.73, p < 0.001).
People with chronic hepatitis C or Child-Pugh A cirrhosis who did not achieve a sustained virologic response were also at higher risk of death due to cardiovascular disease (HR 10.56, 95% CI 3.43-32.46, p < 0.001). Diabetes was also a risk factor for death due to cardiovascular disease (HR 4.111, 95% CI 1.3-12.98, p = 0.011).