Direct-Acting Antivirals Are Associated With Increased Risk of De novo Hepatocellular Carcinoma in HCV Cirrhotic Patients - Real World Data

Abstract

Introduction: Chronic Hepatitis C virus (HCV) infection is common in Pakistan with estimated prevalence of 6.7% and a total of 10 million individuals infected with HCV and because of persistence of risk factors such as unsafe medical injections the prevalence continues to increase.. HCV treatment with Direct acting antivirals (DAAs) has been variably associated with an increased risk of HCC in cirrhotic patients. Two manuscripts showed increased risk but 3 larger studies have concluded that there is no increased risk. Methods: 662 HCV patients presenting in OPD of Doctors hospital & Medical center and Lahore General Hospital, Lahore were enrolled in this prospective observational study after confirming the eligibility criteria based on hematological, biochemical and virological studies. They were offered Pegylated IFN, sofosbuvir and ribavirin (12 weeks), sofosbuvir and ribavirin (24 weeks) or sofosbuvir, daclatasvir with or without ribavirin treatment (12-24 weeks) according to the national guidelines and preferences of the patient after an informed consent from October 2014 to March 2017. Patients were declared cirrhotic based on shear wave Elastography (Aixplorer) results.Occurrence of HCC was confirmed by a triphasic CT scan abdomen on MDCT 64 slice scanner. The primary outcome is the development of new HCC following SVR achieved with DAA. Results: Among 662,327 patients ( 49.4%) had evidence of cirrhosis. HCC was detected in 42(12.8%) patients suffering from cirrhosis with a mean age of 57.42 years (29-70), F/M ratio was 1.2:1. 22/42 were IFN naïve, 20/42 IFN exposed. Median time from exposure of DAAs to the development of HCC was 28 ± 10.2 weeks. None of the patients without cirrhosis developed HCC. HCC was detected in 29/256(11%) compensated cirrhotic and 13/71(18%) decompensated cirrhotic.20/42 had diabetes mellitus, 5/42 had BMI more than 35. 35/281(12.45%) developed HCC in patients who achieved SVR VS 5/40 (12.5%) in those who did not achieve SVR. SVR of two patients who developed HCC was not available. None of the baseline characteristics of the cohort including age, sex, obesity, Diabetes mellitus, genotype, previous interferon exposure, and advanced disease in form of decompensated cirrhosis was independent predictor for development of HCC Conclusion: It is concluded that despite effective eradication of HCV, HCC is more common in cirrhotic patients receiving direct acting antiviral therapy as compared to untreated cirrhotic patients as per historic control