The risk for new liver-related complications is reduced in patients with chronic hepatitis C virus (HCV) treated with direct-acting antivirals (DAAs), according to data from clinical trials (www.clinicaltrials.gov no: NCT03775798) published in Clinical Gastroenterology and Hepatology.

To understand how sustained virologic response to treatment of HCV infection with DAAs may affect mortality and the development of new liver-related complications, investigators performed a prospective multicenter cohort study of 1760 patients. These patients received DAA treatment at 23 hospitals in Latin America, from May 1, 2016 through November 21, 2019. Patients with history of liver decompensation, hepatocellular carcinoma (HCC), or solid organ transplantation were excluded and disease progression after starting DAA therapy included any of the following new events: liver decompensation, HCC, liver transplantation, or death.

The overall cumulative incidence of disease progression was 4.1% (95% CI, 3.2%-5.1%) during a median follow-up of 26.2 months (interquartile range, 15.3-37.5). Following assessment of sustained virologic response, the cumulative incidence of disease progression was 3.6% (95% CI, 2.7%-4.7%). Several baseline variables were associated with disease progression. These included advanced liver fibrosis (hazard ratio [HR], 3.4; 95% CI, 1.2-9.6), clinically significant portal hypertension (HR, 2.1; 95% CI, 1.2-3.8), and level of albumin below 3.5 mg/dL (HR, 4.1; 95% CI, 2.3-7.6), adjusted for attainment of sustained virologic response as a time-covariable. In the overall cohort the risk for liver decompensation (HR, 0.3; 95% CI, 0.1-0.8; P=.016) and de novo HCC (HR, 0.2; 95% CI, 0.1%-0.8%; P=.02) was reduced after attaining sustained virologic response.


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Study limitations included the possibility that after excluding patients with a history of decompensated cirrhosis and solid organ transplantation the potential benefits of DAAs were underestimated. Further, the follow-up period was relatively short—a consequence of the later introduction of DAAs in Latin America. Finally, despite controls for as numerous factors, it is possible that results were influenced by nonmeasurable or unmeasured factors.

Investigators concluded that this study, “demonstrates that achieving [sustained virologic response] with DAA regimens was associated with a significant reduction in the risk of all-cause mortality, hepatic decompensation and HCC in patients with no previous liver decompensation.” They noted, however, that the risk of developing liver-related events still exists after attaining viral eradication, especially in those with advanced liver fibrosis. Investigators also suggested that, “a policy shift towards treating all individuals with HCV, irrespective of disease stage, has the potential to decrease not only morbidity and mortality but transmission, as well.”

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To achieve this goal, researchers suggested the development of public health programs adapted to national settings. Furthermore, future work to assess the predictive accuracy of post-treatment markers and their kinetics during follow-up are needed to refine the concepts of appropriate management of patient’s after sustained virologic response.

Reference

Mendizabal M, Piñero F, Ridruejo E, et al. Disease progression in patients with hepatitis C virus infection treated with direct-acting antiviral agents. [published online February 27 2020]. Clin Gastroenterol Hepatol. doi:10.1016/j.cgh.2020.02.044.