ADAM10 gene polymorphism and its relationship to hepatocellular carcinoma in Egyptian HCV patients receiving direct-acting antiviral therapies (DAAs)

Abstract Background: Hepatocellular carcinoma (HCC) is a multifactorial disease needs widened genetic studies. Taking in consideration the probable role of new direct-acting antiviral therapies (DAAs) of Hepatitis C infection (HCV) as predisposing factor of HCC as it provides longer lifetime for many late cirrhotic patients to develop hepatocellular carcinoma. Considering the reported potential biological roles of ADAM 10 in inflammation and carcinogenesis. These intrigued the idea of the study to investigate the ADAM 10 rs.653765 SNP genetic polymorphism in the HCC occurrence (de novo and post DAAs).Methods: This prospective study was conducted on 360 participants divided to 4 groups. Group 1: 90 chronic adult patients infected with HCV received couple of DAAs regimens and evolved HCC during the period of follow up(36 months) . Group 2: Another 90 HCV patients received the same DAAs regimens and did not show HCC spread or manifestations during the same follow up period. Group 3 included 90 de novo HCC patients (did not receive any DAAs). Finally, a 90 apparently healthy participants as group4. ADAM 10 genotyping. clinical and laboratory data were evaluated in Laboratories of Clinical Biochemistry and Molecular Diagnostics Department National Liver Institute, Menoufia University.Results: the study showed a statistically significant difference between HCC denovo and HCC deterioration on top of DAAs treatment study group regarding child Pugh scoring system, BCLC and HKLC staging scorings, p- value(<0.05) and that (90%) of HCC denovo group were in child score( A 5,6) and (40%) of them were in HKLC (IIIa )stage in addition (56.7%) were in (B) BCLC stage. Also, a statistically highly significant difference between HCC on top of treatment group and HCV study group regarding DAAs drug regimen received (p value=0.000) was found where (85.6%) of HCC on top of treatment received (SOF/DAC/RBV) drug regimen for treatment of HCV and regarding SVR in the 2 groups where (33.3%) of HCC on top of treatment group undergone relapse (p value=0.000).The study showed a statistically highly significant difference between CC versus CT+TT genotypes of HCC study groups regarding their child ,BLC and HKLC staging system. No difference in survival distribution between HCC de novo and on top of DAAs.Conclusion: No differences in the registered death rate recorded between the followed studied groups denovoHCC and HCC post DAAs treatment with more aggressiveness and advanced staging of HCC post DAAs. Also, showed increased risk of HCC incidence among HCV patients receiving(SOF/DAC/RBV) drug regimen and appreciates ADAM 10 genotyping