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People cured of hepatitis C still face substantial risk of death

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People who have been cured of hepatitis C infection still face a substantially greater risk of death compared with the general population, according to a new study, funded by the Medical Research Foundation and led by researchers from Glasgow Caledonian University.

We should be doing much more to support patients after cure. Otherwise, when we look back in years to come, we may see hepatitis C elimination not only as a great achievement, but as a great missed opportunity too.
Dr Hamish Innes

The largest study of its kind, published today in the British Medical Journal (BMJ), found that deaths were three to 14 times higher in patients cured of hepatitis C, depending on liver disease stage.

Based on data from more than 20,000 patients in England, Scotland and British Columbia with a hepatitis C cure, the results show that drug and liver-related causes of death were the main drivers of excess deaths. They also highlight the importance of continued support to fully realise the benefits of a hepatitis C cure.

The data from England was drawn from HCV Research UK, a clinical research database and biobank, also funded by the Foundation.

Hepatitis C is a virus that can infect the liver which, if left untreated, can cause serious and potentially life-threatening liver damage over many years. The UK is committed to eliminating hepatitis C by 2025, ahead of many other countries.

Historically, hepatitis C was treated with interferon-based therapy, which was often ineffective. But in 2011, new medications called direct acting antivirals (DAA) were developed. Now more than 95 per cent of patients treated with DAAs achieve a ‘virological cure’ and have a significantly lower risk of death than untreated patients.

The theme of World Hepatitis Day last week was ‘We’re not waiting’, which emphasised the urgent need for action to accelerate elimination efforts of viral hepatitis, and increase testing and treatment around the world.

However, authors of the BMJ study have raised concerns that antiviral treatment for hepatitis C is not enough to save lives and more must be done to support patients post-cure.

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Dr Hamish Innes

Dr Hamish Innes, a Medical Research Foundation Fellow from Glasgow Caledonian University, said: “Our research shows that cured patients continue to face very high mortality rates after achieving a hepatitis C cure, driven by liver and drug-related causes.

“While antiviral therapies are crucial, it is clear they are not a panacea. The UK and other countries are on course to eliminate hepatitis C, but after it is eliminated, we will still be left with high mortality rates.

“The question is what can we do to pre-empt this? Hepatitis C treatment is an opportune time to address competing health problems, including alcohol and drug use, and to establish life-saving screening for liver cancer.

“We should be doing much more to support patients after cure. Otherwise, when we look back in years to come, we may see hepatitis C elimination not only as a great achievement, but as a great missed opportunity too.”

The researchers measured mortality rates in individuals with a hepatitis C cure and assessed how these rates compare with the general population.

They analysed data from three population studies carried out in British Columbia, Scotland and England involving 21,790 individuals who achieved a hepatitis C cure between 2014 and 2019.

Individuals were grouped by the severity of liver disease at the time of cure: pre-cirrhosis (British Columbia and Scotland studies only), compensated cirrhosis, and end stage liver disease.

Data were then linked to national medical registries and several causes of death were examined, including liver cancer, liver failure, drug-related death, external causes which were mainly accidents, homicides and suicides, and diseases of the circulatory system, over an average follow-up period of two to four years.

Most participants did not have cirrhosis at cure. The average age of pre-cirrhosis patients in Scotland was 44 years and 56 years in British Columbia, and males outnumbered females across all studies and disease severity groups (65-75 per cent).

A total of 1,572 (7 per cent) of participants died during follow-up. The leading causes of death were drug-related (24 per cent), liver failure (18 per cent) and liver cancer (16 per cent).

In Scotland, the death rate for all patients was 4.5 times greater than the general population, with 442 deaths versus 98 expected. In British Columbia, rates were 3.9 times greater, with 821 deaths versus 209 expected.

In England, the total number of observed deaths was five times higher than the number expected. However, as this study did not include pre-cirrhosis patients, this estimate cannot be directly compared with British Columbia and Scotland.

Death rates increased appreciably with liver disease severity. For example, from three times higher in pre-cirrhosis patients from British Columbia up to 14 times higher for end stage liver disease patients in British Columbia.

For patients without cirrhosis, the leading cause of excess death was drug-related death, accounting for 74 per cent and 44 per cent of all excess deaths in Scotland and British Columbia, respectively. Conversely, in patients with cirrhosis, the two leading drivers were liver cancer and liver failure, where together, these causes accounted for up to 80 per cent of excess deaths.

Across all disease stages and settings, older age, recent substance use, alcohol use and pre-existing conditions were associated with higher death rates.

These are observational findings and the researchers acknowledge that they may not apply to all settings, particularly where injecting drug use is not the dominant mode of hepatitis C transmission.

Read the full research paper: Hamill et al (2023) “Mortality rates among patients successfully treated for hepatitis C in the era of interferon-free antivirals”, British Medical Journal.