Incidence of HCC in Chronic Hepatitis C Patients With Advanced Hepatic Fibrosis who Achieved SVR Following DAAs

A Prospective Study

Gamal Shiha; Nasser Mousa; Reham Soliman; Nabiel NNH Mikhail; Mohamed Adel Elbasiony; Mahmoud Khattab

Disclosures

J Viral Hepat. 2020;27(7):671-679. 

In This Article

Abstract and Introduction

Abstract

Liver cirrhosis is an important risk factor for hepatocellular carcinoma. The reported annual incidence of HCC is about 3%-8% in CHC cirrhotic patients. Based on the Cochrane systematic review, there was no clear evidence, on the long-term clinical effects of DAAs in patients achieving SVR, as regard liver cirrhosis-related HCC incidence. The aim of the study was to determine the incidence of HCC in chronic hepatitis C patients genotype IV with liver cirrhosis and advanced liver fibrosis after achieving SVR following DAA treatment in a prospective large cohort of HCV patients with long follow-up. This was a prospective observational cohort study including 2372 CHC patients with advanced liver fibrosis or cirrhosis receiving DAA therapy in outpatient clinics at the Egyptian Liver Research Institute and Hospital since January 2015. Liver fibrosis was assessed using transient elastography. Abdominal ultrasonography and AFP measurement were done at baseline and follow-up visits every 6 months, in addition to triphasic abdominal MSCT when needed. Patients were followed up after achieving SVR12 for at least 12 months. HCC developed in 109 cases during the follow-up period (mean 23.60 ± 8.25 months). Overall HCC incidence was 2.338/100 PY, 95% CI = 1.942–2.814. In patients with cirrhosis, the incidence of HCC was 2.917/100 PY, 95% CI = 2.407–3.535, while in patients with advanced liver fibrosis the incidence of HCC was 0.664/100 PY, 95% CI = 0.333–1.326. In conclusion, the incidence of HCC was reduced in chronic hepatitis C genotype 4 patients with liver cirrhosis (F4) and advanced hepatic fibrosis (F3) who achieved SVR following DAA therapy.

Introduction

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the fourth most frequent cause of cancer-related deaths worldwide, accounting for 7% of all cancers.[1] Liver cirrhosis is an important risk factor for HCC and the risk is high in patients with chronic viral hepatitis, with the highest incidence rates in East Asia and sub-Saharan Africa.[2]

The reported annual incidence of HCC is about 3%-8% in chronic HCV cirrhotic patients.[3] The 5-year cumulative risk for the development of HCC in patients with cirrhosis is 30%, depending on the cause (with the highest risk among those infected with HCV), region or ethnic group and stage of cirrhosis.[4]

During the era of interferon (IFN) therapy, meta-analysis studies reported that achieving SVR leads to decreased risk of liver related complications, mortality, as well as decrease in the incidence of HCC compared with non-SVR patients.[5–7] This was confirmed in a large prospective multicenter Japanese study where the 5-year cumulative incidence rates of HCC for SVR was 18.9%, which is significantly lower than in the nonresponder group (39.4%) (P = .03) with median follow-up of 3.5 years.[8] Similar results were reported by El-Serag et al[9] and Nahon et al[10] These findings confirm that viral clearance after IFN therapy decreased the incidence of HCC but did not eliminate it.

The availability of DAAs with excellent safety profiles and higher efficacy enables treatment of CHC patients with advanced fibrosis and cirrhosis; however, the impact of achieving SVR in patients treated with DAAs therapy on the incidence of HCC is still a matter of debate.[11] Several studies reported unexpected high HCC occurrence or recurrence in cirrhotic patients following DAA therapy where others have not supported this observation.[12–14] These studies were retrospective, performed in heterogenous populations and had inconsistent methodologies so definitive conclusion cannot be withdrawn. This is supported by the findings of the Cochrane systematic review in 2017 which concluded that there was no clear or sufficient evidence in the long-term clinical effect of DAAs in patients achieving SVR as regard liver cirrhosis-related HCC incidence.[15]

In 2018, Romano et al[16] based on a prospectively recording database of all patients with hepatitis C receiving DAAs (n = 3197) in Italy with mean follow-up of 536.2 ± 197.6 days, revealed that the risk of HCC during the first year is lower than that of untreated patients. HCC incidence in the whole cohort of 2710 cirrhotic patients was 1.18 per 100 person-years (95% CI 0.92–1.49). Also, Li et al[17] reported results of a retrospective cohort study among 2859 HCV-infected cirrhotic patients in the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) with mean follow-up time of 396.4 days. HCC incidence rates were 2.28/100 person-years for 1160 DAA treated patients compared with 2.12 for 463 IFN treated patients and 4.53 per 100 person-years in untreated patients with cirrhosis (n = 1236) and concluded that DAAs decrease the incidence of HCC in CHC patients who achieved SVR.[17] The same conclusion was recently reached by Carrat et al[18] and Ide et al[19]

In the previous four studies, genotype IV represents a minority of patients. Furthermore, they did not clearly report the incidence of HCC in patients with advanced fibrosis (F3).

Our aim thus was to determine the incidence of HCC in chronic hepatitis C patients, genotype IV with liver cirrhosis and advanced hepatic fibrosis after achieving SVR with DAAs in a prospective large cohort of HCV patients with long follow-up period.

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