Programmed Death-Ligand 1 (PD-L1) Gene Polymorphisms as Predictive Markers for Development of Hepatocellular Carcinoma in Chronic Hepatitis C Virus Patients

Abstract

Abstract Background Hepatocellular carcinoma is the sixth most common cause of cancer, and ranks fourth among the causes of cancer-related death. Major risk factors for HCC include chronic alcohol consumption, hepatitis B, hepatitis C and non-alcoholic fatty liver disease. Other, less common causes are Wilson’s disease, hereditary hemochromatosis, alpha1-antitrypsin deficiency, primary biliary cirrhosis and autoimmune hepatitis. Objective To investigate the associations of the genetic variants of PD-L1 (rs4143815 and rs2297136) with the risk of HCC in the Egyptian population. Patients and Methods This study was conducted in co-operation between Gastroenterology and Hepatology Department, Ain-Shams University and the Gastroenterology and Hepatology Department, Theodor Bilharz Research Institute “between” March 2020 to July 2020. It included total participants of 138 Divided to Group (A): 35 normal people as control. Group (B): 51 patients with HCV infection and cirrhosis Group (c): 52 patients with HCV infection and cirrhosis with HCC. The patients were recruited from the outpatient clinic of Theodor Bilharz Research Institute Hospital (after consents were obtained). Results Also, the present study demonstrated that the functional polymorphisms (rs4143815) (CG) of the PD-L1 gene were associated with HCC risk as it is expressed in (53.3%) in HCC, (25.6%) in cirrhosis and (23.1%) in control group. And, rs4143815 (CG) show significant increase in Child C patients as (75%) Child C vs. (10%) Child A and (45%) was MELD/NA (20-29) vs. (10%) <9 with (61%) of patients were stage D in BCLC. There is significant increase in rs4143815 (CG) with age as 95% of gene positive patients more than 50years.With no significant in gender as 70% males and 30% females and there is no significant in smoking and DM. So, PDL-1 gene polymorphism rs4143815 (CG) could be used as a predictive marker for HCC after validation by larger studies or met analysis. Conclusion The present study demonstrated that the functional polymorphisms (rs4143815) (CG) of the PD-L1 gene were associated with HCC risk as it is expressed in (53.3%) of HCC, (25.6%) of cirrhosis and (23.1) % of control group. There is significant increase in rs4143815 (CG) with age as 95% of gene positive patients more than 50 years with no significance in gender smoking and DM. rs4143815 (CG) show significant increase in Child C patients as (75%) Child C vs. (10%) Child A and (45%) of patients was MELD/NA (20-29) vs. (10%) <9 and (70%) of patients were stage D in BCLC.