In the largest study of its kind, researchers have found that people cured of hepatitis C were between three and 14 times more likely to die than those who had never had hep C, depending on the severity of liver disease caused by the illness.
The study by Glasgow Caledonian University researchers, which was published in The BMJ, also found that deaths among Scottish patients were 4.5 times greater than the general population, with 442 deaths versus 98 expected.
Deaths in England were slightly higher, with patients facing a mortality rate five times higher than the expected number, reports The Independent.
More than 21 790 patients were examined, and results showed that drug and liver-related causes of death were the main drivers of excess deaths. All individuals studied had achieved a hepatitis C cure between 2014 and 2019.
Researchers have called for more to be done to highlight the importance of continued support to fully realise the benefits of a hep C cure.
The virus can lead to severe and life-threatening liver damage if left untreated over many years.
Direct acting antivirals (DAA) were developed in 2011 and more than 95% of patients treated with the drugs achieve a “virological care” and have a much lower risk of death than untreated patients, said the authors.
The study’s principal investigator Dr Hamish Innes, senior research fellow in the university’s school of health and life sciences’ research centre for health (ReaCH), 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.”
The findings were co-authored by biostatisticians Dr Victoria Hamill of Glasgow Caledonian University and Dr Stanley Wong of the British Columbia Centre for Disease Control in Canada, with his colleague Dr Naveed Janjua, also playing a key role.
They spent more than two years as part of a team of 31 global experts.
The study also examined patients in British Columbia where death rates among successfully treated individuals were 3.9 times higher than those who have never had hep C, with 821 deaths versus 209 expected.
Death rates increased from three times higher in pre-cirrhosis patients from British Columbia up to 14 times higher for end stage liver disease patients.
In total, 1 572 (7%) of participants died during follow-up.
The leading causes of death were drug-related (24%), liver failure (18%) and liver cancer (16%).
Study details
Mortality rates among patients successfully treated for hepatitis C in the era of interferon-free antivirals: population based cohort study
Victoria Hamill, Stanley Wong, Jennifer Benselin, Hamish Innes, et al.
Published in The BMJ on 2 August 2023
Abstract
Objectives
To quantify mortality rates for patients successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals and compare these rates with those of the general population.
Design
Population based cohort study.
Setting
British Columbia, Scotland, and England (England cohort consists of patients with cirrhosis only).
Participants
A total of 21 790 people who were successfully treated for hepatitis C in the era of interferon-free antivirals (2014-19). Participants were divided into three liver disease severity groups: people without cirrhosis (pre-cirrhosis), those with compensated cirrhosis, and those with end stage liver disease. Follow-up started 12 weeks after antiviral treatment completion and ended on date of death or 31 December 2019.
Main outcome measures
Crude and age-sex standardised mortality rates, and standardised mortality ratio comparing the number of deaths with that of the general population, adjusting for age, sex, and year. Poisson regression was used to identify factors associated with all cause mortality rates.
Results
1572 (7%) participants died during follow-up. The leading causes of death were drug related mortality (n=383, 24%), liver failure (n=286, 18%), and liver cancer (n=250, 16%). Crude all cause mortality rates (deaths per 1000 person years) were 31.4 (95% confidence interval 29.3 to 33.7), 22.7 (20.7 to 25.0), and 39.6 (35.4 to 44.3) for cohorts from British Columbia, Scotland, and England, respectively. All cause mortality was considerably higher than the rate for the general population across all disease severity groups and settings; for example, all cause mortality was three times higher among people without cirrhosis in British Columbia (standardised mortality ratio 2.96, 95% confidence interval 2.71 to 3.23; P<0.001) and more than 10 times higher for patients with end stage liver disease in British Columbia (13.61, 11.94 to 15.49; P<0.001). In regression analyses, older age, recent substance misuse, alcohol misuse, and comorbidities were associated with higher mortality rates.
Conclusion
Mortality rates among people successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals are high compared with the general population. Drug and liver related causes of death were the main drivers of excess mortality. These findings highlight the need for continued support and follow-up after successful treatment for hepatitis C to maximise the impact of direct acting antivirals.
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