Abstract
Oxidative stress contributes to hepatitis C virus (HCV)–induced liver damage. Host genetic factors may be involved in progression of HCV infection. The present study was conducted to determine the influence of glutathione S-transferase (GST)-M1 and T1 gene polymorphisms during different stages of HCV infection, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The study population comprised 190 patients (47 with chronic hepatitis, 83 with cirrhosis (without HCC), and 60 with HCC). GSTM1 and GSTT1 gene polymorphisms were analyzed via multiplex polymerase chain reaction. The GSTT1-null genotype was more commonly detected in patients with cirrhosis (n = 17; 20.5%) and HCC (n = 13; 21.7%) than those with chronic hepatitis (n = 3; 6.4%). The differences in GSTT1-null genotype frequencies were significant for cirrhosis vs. chronic hepatitis (odds ratio, OR, 3.778 (95% confidence interval, CI, 1.045–13.659); p = 0.043) and HCC vs. chronic hepatitis (OR, 4.057 (95% CI, 1.083–15.201); p = 0.038) groups. However, the incidence of individual GSTM1-null or combined GSTM1/GSTT1 double-null genotypes did not vary significantly between the groups. Our collective findings support the utility of the GSTT1-null genotype as a useful biomarker for liver disease progression in Brazilian patients with chronic hepatitis C.
Highlights
With a reported 905,677 new cases and 830,180 deaths in 2020, liver cancer is predicted to be the sixth leading cause of cancer and third highest cause of cancer-associated mortality worldwide, presenting a major global health problem [1]
The Brazilian population has a highly admixed genetic background [28], and candidate gene-based association studies exploring the relationship between genetic polymorphisms and Hepatocellular carcinoma (HCC) are rare in Brazil
The present study is the first to investigate the association of GSTM1 and GSTT1 polymorphisms with advanced liver disease induced by hepatitis C virus (HCV) infection in Brazilian patients
Summary
With a reported 905,677 new cases and 830,180 deaths in 2020, liver cancer is predicted to be the sixth leading cause of cancer and third highest cause of cancer-associated mortality worldwide, presenting a major global health problem [1]. Cirrhosis of any etiology is a main risk factor for development of HCC Among cirrhotic patients, those with hepatitis C virus (HCV) infection have the highest risk of developing. 2019 [5], the major risk factor being chronic HCV infection, which accounted for ~65% of the cases [6]. Limited published data are available on the influence of GST polymorphisms in the late stages of HCV infection, development of cirrhosis and HCC [23,24,25], and no studies have been conducted on the Brazilian population to date. HCV grouped according to stage of liver disease (chronic hepatitis, cirrhosis, and HCC), with a view to investigating their potential involvement in risk of disease progression in Brazilian patients with chronic hepatitis C infection
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