People Cured of Hepatitis C Still Face Significant Mortality Risk

Victoria Hamill, PhD

Credit: ResearchGate

Patients with hepatitis C virus (HCV) achieving cure from successful treatment via interferon-free direct acting antivirals (DAAs) remain at a significantly greater risk of death than the general population, according to new research from the UK.

In new data published Wednesday evening, a team of investigators from the UK and Canada reported that, while the era of interferon-free DAAs has resulted in a significant improvement in mortality for treated versus untreated patients with HCV, the demographic is nonetheless associated with an approximate 4-fold increased mortality rate relative to the general population in regions including Scotland and British Columbia.

A team of investigators led by Victoria Hamill, PhD, of the School of Health and Life Sciences at Glasgow Caledonian University, and Stanley Wong, MBBS, DrPH, of the British Columbia Center for Disease Control, sought a quantified mortality rate for patients who had been successfully treated for HCV during the past decade’s era of available DAA treatment; they would then compare those mortality rates with those of the general population.

Since the first DAA’s marketing approval in 2014, the drug class has been consistently associated with a ≥95% virological cure rate among patients who receive a full regimen; particularly, patients with cirrhosis have benefited from the highly efficacious drugs.

“However, it is important to understand the overall prognosis for people who have been successfully treated for HCV,” investigators wrote. “Most observational studies have focused on quantifying the relative benefits of an HCV cure. These benefits include a lower mortality risk compared with untreated patients with chronic HCV infection and those in whom treatment has failed.”

In seeking to establish more larger and representative cohort data for a spectrum of patients with liver disease, investigators hoped to provide a more “reliable picture of prognosis for people who have been successfully treated for HCV.”

The team analyzed data from a trio of population-based cohorts including patients successfully treated for HCV since the advent of interferon-free DAAs in 2014. The cohorts consisted of patients from British Columbia, Scotland, and England—with available England data only consisting of patients with cirrhosis.

The population included 21,790 persons successfully treated for HCV from 2014 – 2019. Study participants were stratified into 3 groups based on liver disease severity: those without cirrhosis (pre-cirrhosis), those with compensated cirrhosis, and those with end-stage liver disease (ESLD). Across each regional- and disease severity-stratified cohort, mean patient age was 44.4 – 60.3 years old; approximately two-thirds of participants were male.

Hamill, Wong and colleagues conducted their follow-up analysis from 12 weeks post-antiviral therapy regimen completion until death or end of 2019. They sought a primary outcome of crude and age-sex standardized mortality rates, as well as standardized mortality ratio comparing deaths with the general population—adjusted for age, sex and year.

Investigators reported 1572 (7%) participants died during analysis follow-up. Leading causes of death included drug-related mortality (24%), liver failure (18%), and liver cancer (16%). Crude all-cause mortality rates among the 3 region-based cohorts were as follow:

• British Columbia, 31.4 per 1000 person-years (95% CI, 29.3 – 33.7)
• Scotland, 22.7 per 1000 person-years (95% CI, 20.7 – 25.0)
• England, 39.6 per 1000 person-years (95% CI, 35.4 – 44.3)

Based on age-sex standardized analysis, the following cohorts had the worst mortality rates per 1000 person-years:

• Patients with ESLD in British Columbia, 118.18 (95% CI, 103.33 – 134.55)
• Patients with ESLD in England, 68.36 (95% CI, 58.03 – 78.70)
• Patients with ESLD in Scotland, 64.84 (95% CI, 43.22 – 86.46)
• Patients with cirrhosis in British Columbia, 37.75 (95% CI, 30.72 – 45.92)
• Patients with cirrhosis in England, 37.33 (95% CI, 30.72 – 45.92)

All patient cohorts reported a mortality rate of >20 per 1000 person-years after successful virological cure from HCV. As such, each cohort reported a standardized mortality ratio ranging from 2.96 (95% CI, 2.71 – 3.23) to 13.61 (95% CI, 11.95 – 15.49) greater than the general population (P <.001).

“Standardized mortality ratios remained high even when adjusting for area-based deprivation; therefore, the high mortality rates observed cannot be explained by generic health inequalities,” investigators wrote. “Predictors of a higher mortality rate included recent hospital admission for alcohol and substance misuse and a greater comorbidity burden.”

The team stressed the need for improved avenues of care and harm reduction pathways for recently cured HCV patients. “As we move towards HCV elimination, treatment programs must strike the right balance between treating HCV and treating the patient,” they wrote. “For example, patients with cirrhosis who have received successful HCV treatment benefit from liver cancer surveillance, yet these surveillance programs are poorly implemented in the UK and other countries.”

They concluded their findings show that people cured of HCV face continued substantial mortality risk, driven largely by liver disease and drug-related issues.

“These findings highlight the importance of establishing robust follow-up pathways after successful HCV treatment as we move towards HCV elimination,” investigators wrote.

References

^{Hamill V, Wong S, Benselin J, Krajden M, et al. Mortality rates among patients successfully treated for hepatitis C in the era of interferon-free antivirals: population based cohort study. BMJ 2023; 382 doi: https://doi.org/10.1136/bmj-2022-074001}