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High Mortality despite SVR Cure Due to Lack of Surveillance & Continued Drug/Alcohol Use
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Our findings bring into focus the importance of establishing robust care and harm reduction pathways after successful HCV treatment. As we move towards HCV elimination, treatment programmes must strike the right balance between treating HCV and treating the patient surveillance programmes are poorly implemented .....patients need more support to reduce drug and alcohol misuse after HCV cure. Combining HCV treatment with wider intervention and wraparound services .........there is evidence that successful HCV treatment could be used as an opportunity to encourage changes in behaviour...... (eg, referral pathways to addiction services, prescription of opioid agonist treatment,36 and drugs for alcohol dependence37) to more innovative approaches such as housing support interventions.
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 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.
Policy implications
Our findings bring into focus the importance of establishing robust care and harm reduction pathways after successful HCV treatment. As we move towards HCV elimination, treatment programmes must strike the right balance between treating HCV and treating the patient. For example, patients with cirrhosis who have received successful HCV treatment benefit from liver cancer surveillance, yet these surveillance programmes are poorly implemented in the UK and other countries.33 Additionally, our data suggest patients need more support to reduce drug and alcohol misuse after HCV cure. Combining HCV treatment with wider intervention and wraparound services should be considered, especially because there is evidence that successful HCV treatment could be used as an opportunity to encourage changes in behaviour.143435 Potential initiatives range from optimising delivery of established interventions (eg, referral pathways to addiction services, prescription of opioid agonist treatment,36 and drugs for alcohol dependence37) to more innovative approaches such as housing support interventions.38Population level action—for example, prescribed safer supply of drugs and drug decriminalisation policies recently implemented in British Columbia—will also be crucial to improve mortality in people successfully treated for HCV.3940 Our results also have implications for public health surveillance of HCV. At present, the current emphasis (eg, in the UK 41) is on monitoring progress towards WHO mortality targets,11 which focus narrowly on deaths from viral hepatitis alone. In contrast, our study suggests a much wider lens is needed to understand the population impact of interferon-free treatments, and respond or adapt to the evolving landscape. New indicators should be introduced to convey the broader epidemiological context.
Excess mortality risk among hepatitis C patients after being "cured" in the interferon-free era: results from three population-based cohorts
EASL International Liver Congress 2022, London, June 22-26, 2022. Abstract FRI383. Abstract OS005.
https://www.natap.org/2022/EASL/EASL_73.htm
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