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Curing hepatitis C infection significantly reduces deaths from liver disease and reduces the incidence of decompensation, two large prospective studies from Italy and Scotland show. The findings were presented on Saturday at the 2018 International Liver Congress in Paris.

In particular, Italian researchers showed that people with compensated cirrhosis who were not cured of hepatitis C after direct-acting antiviral treatment were 15 times more likely to die of a liver-related cause during the 18-month period after starting treatment than people with compensated cirrhosis who were cured.

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).

The Scottish government has committed to a national Hepatitis C Action Plan which aims to eliminate hepatitis C and reduce liver-related mortality and morbidity. A key target is to reduce hepatitis C virus-related liver decompensation by 75% between 2015 and 2020 through direct-acting antiviral treatment.

Decompensation represents a major reduction in liver function and places people who suffer it at high risk of death from liver failure. Reducing the incidence of decompensation in people with cirrhosis is a critical step towards reducing liver-related mortality.

Professor Sharon Hutchinson of Glasgow Caledonian University reported on national surveillance data that links all persons diagnosed and treated with hospital admission records for decompensation, enabling accurate monitoring of liver-related events among all people diagnosed with hepatitis C in Scotland.

Approximately 4800 people have received treatment for hepatitis C over the past three years, 83% with direct-acting antivirals. Ninety-four per cent of all people treated achieved a sustained virologic response. Between 2013 and 2016 cases of decompensation declined by 29%. A time-series analysis of six-month periods since the introduction of direct-acting antivirals showed that decompensation events declined by an average of 11% in each six-month period. The investigators estimate that 97 decompensation events were averted in the first two years after the introduction of direct-acting antivirals.

Calvaruso V et al. Disease outcomes after DAA-induced SVR: data from the Resist-HCV cohort. The International Liver Congress, Paris, abstract PS-149, 2018. Journal of Hepatology 68: S83, 2018.

Hutchinson S et al. Reduction in the incidence of hepatitis C-related decompensated cirrhosis associated with national scale-up of direct-acting antiviral therapies targeting patients with advanced liver fibrosis. The International Liver Congress, Paris, abstract GS-017, 2018. Journal of Hepatology 68: S67, 2018.