People cured of hepatitis C remain at higher risk of death due to liver- and drug-related causes

People who have been cured of hepatitis C remain at higher risk of dying from liver-related causes than the general population, but their risk of cardiovascular events goes down after being cured, large studies in the United Kingdom, Canada and France have concluded.

The study carried out in the United Kingdom and Canada also found that compared to the rest of the population, people cured of hepatitis C remain at higher risk of dying from drug-related causes such as overdose.

The findings were presented at the 2022 International Liver Congress in London.

A study carried out in England, Scotland and the Canadian province of British Columbia looked at death rates in 20,031 people cured of hepatitis C compared to mortality in the general population in each territory. The study also looked at the proportion of deaths in people cured of hepatitis C that were attributable to liver cancer, liver-related causes other than cancer, or drug-related causes.

Mortality rates were assessed according to liver disease stage (no cirrhosis, compensated cirrhosis or end-stage liver disease) and standardised to reflect the age-sex distribution in each cohort.

On average, participants were followed for between two and four years after being cured, depending on which national cohort they belonged to.

Mortality rates ranged from 11.7 per 1000 person-years in people without cirrhosis in the Scottish cohort to 118.2 deaths per 1000 person-years in people with end-stage liver disease in British Columbia.

Presenting the findings, Dr Victoria Hamill of Glasgow Caledonian University said that these rates showed that approximately 1.2% of the Scottish cohort without cirrhosis died each year, whereas 12% of the British Columbia cohort with end-stage liver disease died each year.

When the researchers looked at excess deaths – how much the death rate in people cured of hepatitis C exceeded the death rate in the regional population with similar characteristics – they found that mortality rates were approximately three-and-a-half times higher in people without cirrhosis cured of hepatitis C. Death rates were four to five times higher in people with compensated cirrhosis and between eight and 15 times higher in people with end-stage liver disease, depending on the cohort.

In Scotland, the cause of death was more often drug-related than liver-related in people without cirrhosis or compensated cirrhosis. Seventy-seven per cent of deaths in people without cirrhosis in Scotland were drug-related.

In England and British Columbia, the cause of death was more often liver-related in people with compensated cirrhosis and in all cohorts, the cause of death was predominantly liver-related in people with end-stage liver disease.

Dr Hamill said the findings demonstrated the need for a range of post-cure interventions including harm reduction services for people who use drugs, overdose prevention and ongoing monitoring of liver health.

Numerous studies in Asia, Europe and North America have reported that people with hepatitis C are more likely to experience cardiovascular events and non-liver cancers. It is unclear to what extent the risk of these conditions is reduced by being cured of hepatitis C. French researchers looked at the incidence of cardiovascular events and non-liver cancers in people who had received direct-acting antivirals in France.

The study looked at people enrolled into the HEPATHER cohort, a national cohort of people awaiting hepatitis C treatment who were enrolled from August 2012 to December 2015 in 32 French liver centres. Post-treatment outcomes of interest to the end of 2018 were tracked through the French National Health Insurance Database.

The study looked for cardiovascular events (stroke, acute coronary syndrome, pulmonary embolism, heart failure, arrhythmias and conduction disorders [ACD], peripheral arterial disease [PAD]) and non-liver cancers (colorectal, bladder, prostate, kidney, lung, pancreas, thyroid, head/neck, breast).

The study analysed 12,905 person-years of no-DAA follow-up (not exposed to DAAs) and 22,326 person-years of post-treatment follow-up from 8148 people. Cohort members had a median age of 56 years, 54% were male and 51% who received treatment had F3 or F4 fibrosis (compared to 27% of those who remained untreated). There was no significant difference in the history of cardiovascular events or cardiovascular risk factors between treated and untreated groups at baseline.

Direct-acting antiviral treatment was associated with a substantial reduction in the risk of being diagnosed with peripheral artery disease in the post-treatment period compared to the pre-treatment period (hazard ratio 0.54) and a reduced risk of experiencing a cardiovascular event in people with advanced fibrosis (HR 0.58). However, DAA treatment was associated with an increased risk of being diagnosed with an arrhythmia or conduction disorder, especially in the first year after treatment (HR 1.46). The risk of arrhythmia or conduction disorder was associated with exposure to sofosbuvir; people who received a sofosbuvir-containing regimen had a 54% higher risk of ACD compared to people who remained untreated.

DAA treatment did not affect the risk of developing a non-liver cancer.

Presenting the results, Dr Laurent Lam of Paris’s Sorbonne University said that long-term cardiac monitoring of people cured of hepatitis C may be warranted, especially those exposed to sofosbuvir.