DAA in the Risk of Recurrence After Curative Treatment of HCC

The Role of DAA in Reducing the Risk of Recurrence After Curative Treatment of HCC in Patients With Chronic Hepatitis C and Early Stage HCC

Kaohsiung Medical University Chung-Ho Memorial Hospital, China Medical University Hospital, Chi Mei Medical Hospital, Chiayi Christian Hospital, National Taiwan University Hospital, Chang Gung Memorial Hospital, Tri-Service General Hospital, National Cheng-Kung University Hospital

For early stage of HCC, surgical resection or radiofrequency ablation (RFA) is the mainstay curative treatments. However, recurrence is still a major issue after the surgery or RFA. Only selected patients are eligible and tolerable to IFN-based treatment after surgical resection and the sustained virological response varied. Harvoni for genotype 1 HCV and sovaldi plus ribavirin for genotype 2 HCV can achieve high SVR and being recommended by AASLD and EASL. Mixed HCV genotype infection accounts for 10% of CHC patients in Taiwan. Sovaldi-based treatment plus ribavirin should be as effective as Sovaldi plus rivavirin in the treatment of genotype 2 HCV, as well as mixed genotype 1 and 2 HCV infection. As genotype 1 and 2 are the leading HCV genotypes in Taiwan, It can simplify the regimen of anti-HCV treatment in Taiwan by using Harvoni plus ribavirin, not only for genotype 1 and 2 HCV but also for mixed genotype 1 and 2 HCV infection. Although an unexpected high recurrence rate in HCC patients under DAA treatment was reported once. However, one recent study showed a low risk of HCC recurrence after DAA treatment. In this study, the investigators plan to enroll 130 HCV-HCC patients after confirming curative treatment for their HCC, either by surgery or RFA. For the cases fulfilling the inclusion/exclusion criteria, a 12 weeks Harvoni plus ribavirin treatment will be provided for all cases (single armed design). The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years. A hospital-based cohorts of HCV-related HCC undergoing surgical resection or RFA from Taipei Veterans General Hospital and Investigated Sites will be recruited as historical controls.

Chronic hepatitis C virus (HCV) infection is a major etiology of hepatocellular carcinoma (HCC). For early stage of HCC, surgical resection or radiofrequency ablation (RFA) is the mainstay curative treatments. However, recurrence is still a major issue after the surgery or RFA. According to our previous report, the cumulated recurrence rate for small HCV-HCC was 72.4% at 5 year. PEG-interferon plus RBV treatment is the standard of care for chronic hepatitis C (CHC) in Taiwan. NHIRD data showed that PEG-IFN plus RBV treatment can reduce 12% of recurrence rate in 5 years (64% vs 52%) after curative resection of HCC. However, only selected patients are eligible and tolerable to IFN-based treatment after surgical resection and the sustained virological response varied. Harvoni for genotype 1 HCV and sovaldi plus ribavirin for genotype 2 HCV can achieve high SVR and being recommended by AASLD and EASL. All-oral regimen, being more tolerable and effective for HCC patients after curative treatment than IFN-based treatment. Mixed HCV genotype infection accounts for 10% of CHC patients in Taiwan. Sovaldi-based treatment plus ribavirin should be as effective as Sovaldi plus rivavirin in the treatment of genotype 2 HCV, as well as mixed genotype 1 and 2 HCV infection. As genotype 1 and 2 are the leading HCV genotypes in Taiwan, It can simplify the regimen of anti-HCV treatment in Taiwan by using Harvoni plus ribavirin, not only for genotype 1 and 2 HCV but also for mixed genotype 1 and 2 HCV infection. Although an unexpected high recurrence rate in HCC patients under DAA treatment was reported once. However, one recent study showed a low risk of HCC recurrence after DAA treatment. Harvoni is an all-oral regimen, being more tolerable and effective for HCC patients after surgery than IFN-based treatment. The all oral regimen would be beneficial in eradicating HCV viral load and subsequently reduce the risk of recurrence after curative resection of HCV-HCC. In this study, the investigators plan to enroll 130 HCV-HCC patients after confirming curative treatment for their HCC, either by surgery or RFA. For the cases fulfilling the inclusion/exclusion criteria, a 12 weeks Harvoni plus ribavirin treatment will be provided for all cases (single armed design). The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years. The secondary objectives of the study are SVR 4/12/24 by DAA, regression of fibrosis, incidence of liver-related complications (EV bleeding, ascites) after DAA treatment, and overall survival for 5 years. A hospital-based cohorts of HCV-related HCC undergoing surgical resection or RFA from Taipei Veterans General Hospital and Investigated Sites will be recruited as historical controls. The historical controls include HCV-HCC undergoing curative treatment without Peg-interferon plus ribavirin treatment (cohort 1) or with Peg-interferon plus ribavirin treatment (cohort 2) after curative treatment (surgical resection or RFA) for HCC.

Active DAA treatment ('Ledipasvir 90mg/Sofosbuvir 400 mg plus Ribavirin' ) for HCV-HCC patients after curative resection or ablation.

A 12 week Harvoni (Ledipasvir 90mg/Sofosbuvir 400 mg ) plus ribavirin will be provided after confirmation of curative treatment.

A 12 week Harvoni (Ledipasvir 90mg/Sofosbuvir 400 mg ) plus ribavirin will be provided after confirmation of curative treatment.

The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years.

The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years.

SVR: sustained virological response. DAA: direct antiviral agent. SVR 4/12/24 means undetectable HCV viral load 4/12/24 weeks after completing DAA treatment.

Inclusion Criteria: Anti-HCV positive and HBsAg-negative HCV genotype 1 or 2 infection, mixed infection GT 1 & 2 is allowed HCV RNA ≥ 10,000 IU/ml at the time of screening Age > 20 y/o BCLC stage 0 or A HCC confirmed by pathology and receiving the first time of curative treatment No recurrence of HCC confirmed by contrast-enhanced image studies (CT or MRI) within 3 months post the curative treatment. Performance status Eastern Cooperative Oncology Group (ECOG) 0-1 Child-Pugh score ≤7 Exclusion Criteria: HBV, or HIV coinfection Co-existing other malignancy Intolerance to ribavirin Marked decompensated liver cirrhosis (CTP score>7) Uremia or renal impaired patients (eGFR<30)