Five-Year Follow-Up of Cured HCV Patients under Real-World Interferon-Free Therapy.

Robert Flisiak,Tomasz Mikuła,Monika Pazgan-Simon,Ewa Janczewska,Krzysztof Tomasiewicz,Katarzyna Flejscher-Stępniewska,Dorota Zarębska-Michaluk,Jerzy Jaroszewicz,Tadeusz Łapiński,Magdalena Rogalska,Hanna Berak,Kornelia Karwowska,Beata Bolewska,Aleksander Garlicki,Anna Piekarska,Ewa Karpińska,Jolanta Białkowska,Olga Tronina

doi:10.3390/cancers13153694

Abstract

Simple SummaryHepatitis C virus (HCV) is the major factor responsible for hepatocellular carcinoma (HCC). Currently available treatments for HCV infection are short, simple, effective and safe. Long-term monitoring of patients is essential to demonstrate the efficacy of antiviral therapy, including the risk of HCC development. Since highly effective treatment options only became available in the middle of the past decade, we evaluated patients treated during this period five years after treatment. We have shown that the risk of death due to HCC as well as death due to HCV persists through 5 years of follow-up after successful treatment. Therefore, longer follow-up is necessary to assess the long-term risk of developing HCC, especially in patients with cirrhosis.(1) Background: Treatment of hepatitis C virus (HCV) infections with direct-acting antivirals (DAA) has demonstrated high efficacy and an excellent safety profile. The cured patients showed a sustained virological response and improved liver function, but also a continued risk of hepatocellular carcinoma (HCC) during the 2–3 years of follow-up after treatment; (2) Methods: A total of 192 patients out of 209 of the primary AMBER study were analyzed five years after treatment with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin. Results: We confirmed that HCV clearance after DAA treatment is stable regardless of baseline liver fibrosis. We found that sustained virologic response is associated with a gradual but significant reduction in liver stiffness over 5 years. Liver function improved during the first 2 years of follow-up and remained stable thereafter. The risk of death due to HCC as well as death due to HCV persists through 5 years of follow-up after successful DAA treatment. However, in non-cirrhotic patients, it appears to clear up 3 years after treatment; (3) Conclusions: Monitoring for more than 5 years after curing HCV infection is necessary to assess the long-term risk of possible development of HCC, especially in patients with cirrhosis of the liver.

Highlights

Effective and safe direct acting antivirals (DAAs) have changed the global epidemiological situation of hepatitis C virus (HCV) infection
Reports of HCV RNA tests at 5yFU were available in 148 patients and all were undetectable for HCV RNA
Deaths related to HCV or hepatocellular carcinoma (HCC) in the last 2 years were recorded only in patients with baseline cirrhosis (Table 3)

Summary

Introduction

Effective and safe direct acting antivirals (DAAs) have changed the global epidemiological situation of hepatitis C virus (HCV) infection. DAAs significantly improved the efficacy and safety of HCV treatment compared to previous interferon-based regimens [4]. One of the first available treatment options not requiring interferon included the NS5A inhibitor ombitasvir (OBV), the NS3/4A protease inhibitor paritaprevir (PTV) ritonavir-boosted (r), and the NS5B polymerase inhibitor dasabuvir (DSV), was used with or without ribavirin (RBV), and was approved for the treatment of HCV-infected patients at the end of 2014 [5,6,7]. AMBER was the first RWE study in the world with this therapeutic regimen to demonstrate a high SVR rate and an excellent safety profile, even in patients with cirrhosis, a history of interferon-based therapy failure, and after liver transplantation [8]. Effective therapy did not prevent liver decompensation, HCC, or cirrhosis-related deaths, which supported the need for longer monitoring [15]

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