Low Recurrence Rate of Hepatocellular Carcinoma Following Ledipasvir and Sofosbuvir Treatment in a Real-world Chronic Hepatitis C Patients Cohort

Ramazan Idilman; Mehmet Demir; Murat Aladag; Cihan Erol; Bilger Cavus; Raim Iliaz; Hayrettin Koklu; Yilmaz Cakaloglu; Memduh Sahin; Galip Ersoz; İftihar Koksal; Zeki Karasu; Meric Ozgenel; İlker Turan; Feyza Gunduz; Huseyin Ataseven; Meral Akdogan; Murat Kiyici; Aydın Seref Koksal; Sila Akhan; Fulya Gunsar; Fehmi Tabak; Sabahattin Kaymakoglu; Ulus S Akarca; Early Access Program (EAP) Study Group

Disclosures

J Viral Hepat. 2019;26(6):666-674. 

In This Article

Abstract and Introduction

Abstract

The aims of the present study were to evaluate the efficacy and tolerability of ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin in the treatment of chronic hepatitis C (CHC) in patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence of hepatocellular carcinoma (HCC) during and after LDV/SOF treatment. The Turkish Early Access Program provided LDV/SOF treatment to a total of 200 eligible CHC patients with advanced liver disease. The median follow-up period was 22 months. All patients were Caucasian, 84% were infected with genotype 1b, and 24% had a liver transplantation before treatment. The sustained virological response (SVR12) was 86.0% with ITT analysis. SVR12 was similar among patients with Child-Pugh classes A, B and C disease and transplant recipients. From baseline to SVR12, serum ALT level and MELD score were significantly improved (P < 0.001). LDV/SOF treatment was generally well tolerated. Only one patient developed a new diagnosed HCC. Seventeen of the 35 patients, who had a history of previous HCC, developed HCC recurrence during the LDV/SOF treatment or by a median follow-up of 6 months after treatment. HCC recurrence was less commonly observed in patients who received curative treatment for HCC compared with those patients who received noncurative treatment (P = 0.007). In conclusion, LDV/SOF with or without ribavirin is an effective and tolerable treatment in CHC patients with advanced liver disease. Eradication is associated with improvements in liver function and a reduced risk of developing a new occurrence of HCC.

Ledipasvir and sofosbuvir with or without ribavirin is an effective and tolerable treatment in hepatitis C virus–infected patients with advanced liver disease. Eradication is associated with improvements in liver function and reduces the risk of developing a new occurrence of hepatocellular carcinoma.

Introduction

The main objectives of hepatitis C virus (HCV) treatment are to prevent disease progression to cirrhosis, the development of decompensation and hepatocellular carcinoma (HCC), and to improve survival and quality of life as a result of suppression of HCV replication.[1–5] To date, in contrast to interferon (IFN)-based antiviral therapy, HCV cure rates with direct-acting antivirals (DAA) exceed 90% within a short time.[1,4–10] DAAs are also effectively working in patients with compensated and decompensated cirrhosis, including those awaiting liver transplantation (LT).[4–10] Sustained virological response (SVR) rates of the combination of ledipasvir (LDV) and sofosbuvir (SOF) with or without ribavirin (RBV) were approximately 94%-99% in noncirrhotic and compensated cirrhotic patients and 85%-90% in decompensated cirrhotic patients.[6,7,10] This regimen is generally safe and tolerable.[6,7,10]

In Turkey, the prevalence of anti-HCV antibody positivity is around 1%, based on the result of an epidemiological study.[11] Chronic hepatitis C (CHC) causes liver cirrhosis in approximately 15%-17% of patients, leading to increased liver-related morbidity and mortality. LDV/SOF treatment was approved in February 2015 and reimbursed in June 2016 in Turkey. During that time, an early access program (EAP) provided life-saving LDV/SOF treatment for CHC patients with advanced liver disease with or without LT and for cirrhotic patients with extrahepatic manifestation.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide.[12] Hepatitis B virus (HBV)- and HCV-related cirrhosis are the most common risk factors for the development of HCC.[13–16] In addition, older age, male gender and active hepatic inflammation are as independent risk factors for HCC development.[13–16] Antiviral therapy-induced SVR in CHC patients has been shown to decrease the risk of HCC development.[17–21] Several previous studies reported unexpectedly high rates of HCC incidence under and following DAA regimens in cirrhotic patients,[22–27] and some did not confirm.[20,21] Therefore, data regarding the risk of HCC in HCV-infected cirrhotic patients treated with DAA therapy are still controversy.[17–27] The aims of the present study were to evaluate the efficacy and tolerability of LDV/SOF with or without RBV combination treatment in CHC patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence and/or recurrence of HCC during and after antiviral treatment.

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