P1705ARE DIRECT-ACTING ANTI-VIRAL DRUGS ACCUSED OF INCREASED INCIDENCE OF HEPATOCELLULAR CARCINOMA IN ENDEMIC AREA: A PILOT STUDY
Authors: Elmowafy Ahmed , Abbas Mohamed , Abouelkheir Rasha T , Refaie Ayman , Rostaing Lionel , Bakr Mohammed 
Published: June 2020

Abstract

Background and Aims
Great progression in treating hepatitis C infection has been made with the new Interferon-free regimens. Reports about developing hepatocellular carcinoma after DAAs have been spotlighted. Kidney transplantation and hemodialysis are considered risk factors for developing malignancies. Here we are evaluating the prevalence of HCC after DAAs treatment in high risk population.

Method
This cross-sectional study was held in Urology and Nephrology Center, Mansoura University, Egypt including. Total number of 165 patients received DAAs included in this study in 2 phases. The first phase included 50 patients (12 hemodialysis and 38 kidney transplant recipients). All patients completed DAAs course as treatment for hepatitis C infection (HCV) 24 months ago. Alfa feto protein and liver ultrasound (Use of both modalities combined yielded sensitivity (99.2%) and specificity (68.3%)) was used to screening of HCC for all patients. Triphasic CT liver with 86% to 94% sensitivity was done for all hemodialysis patients and KTRs with suspicious lesions or high alfa-feto protein.

Results
Our patients mean age was 52.32±3.2 years with male predominance. Mean Hemodialysis duration was 48.21±12.3 months and mean kidney transplantation duration was 36.21±6.7 months. Baseline laboratory investigations: ALT: 39.17±16.3 iu/l, Albumin: 3.6±1.32 g/dl, Bilirubin: 0.54±0.21, Hemoglobin: 10.57±1.9 g/dl, AFP: 5.3±2.4 ng/ml. Baseline liver US: normal (49%), enlarged (42%) and cirrhotic (9%) (No focal lesions). Fibro scan: F0 (26%), F1 (31%), F2 (32%) and F3 (11%). None of them experienced hepatic encephalopathy attacks or bleeding varices. All hemodialysis patients received Ombitasvir/Paritaprevir/Ritonavir (OMV/PTV/RTV) regimen (3 months). Only 2 KTRs received OMV/PTV/RTV regimen (3 months), the remaining 36 KTRs received Sofosbuvir/Daclatasvir regimen (6 months). Only 1 case reported relapse within 3 month after completing treatment. The rest achieved 12-week and 24-week SVR successfully. After 2 years from completing treatment, there was significant improvement in ALT levels. Four KTRs passed to graft failure due to accelerated immunologic response (rejection episodes) and 7 KTRs showed rise of serum creatinine (biopsy-proven rejection). Mean AFP rose up to 7.6±2.4 ng/ml with no statistical difference. Three hemodialysis patients and 4 KTRs showed rise in alfa-feto protein above normal values (10ng/dl). Four out of them exceeded 500ng/ml (1 HD and 3 KTRs). Abdominal US revealed: no change (39 patients), enlargement (6 patients) and cirrhosis (5 patients). Suspicious mass was found in 11 patients. Triphasic CT then was done for all hemodialysis patients and 9 KTRs. Regarding hemodialysis, 1 patient was diagnosed as HCC based on increased enhancement by Triphasic CT and alfa-fetoprotein was &gt;500 ng/ml. Regarding KTRs, HCC was diagnosed in 2 patients and liver metastasis secondary to lymphoma was diagnosed in 1 case. The other patients with suspicious lesions (5 patients) showed uniform enhancement by Triphasic CT suggesting benign lesions. So, we have 3 (6%) out of 50 patients has been diagnosed as HCC after DAAs. By retrieval of their data, HCV duration was over 10 years and the liver was cirrhotic or enlarged with cirrhotic changes by ultrasound. Baseline ALT was slightly high without significant improvement after treatment. Also, baseline alfa-feto protein was high. The 3 patients were F2 or F3.

Conclusion
Hepatocellular carcinoma incidence after Direct-acting anti-virals is related mostly to the poor condition of the patients at baseline not to the drug itself and HCC in such cases could be considered as a part of disease progression not a drug complication.