ABSTRACT
AIM/BACKGROUND: Hepatitis B virus (HBV) is an important factor in the development of hepatocellular carcinoma (HCC). We studied the influence of HBV viral load on HCC occurrence in HBV related liver cirrhosis (LC). PATIENTS AND METHODS: Ninety-one LC patients were followed up over a period of 7 years. Twenty three patients received Interferon (IFN) therapy. RESULTS: In 7 years, 23 patients developed HCC. Of them twenty-two (95.6%) were of genotype C. HBV DNA was found to be the only significant variable associated with HCC occurrence on both univariate (P = 0.029) and multivariate analysis (odds ratio 2.33; P < 0.033). The cumulative survival at 5 years was 83% and the annual rate of hepatitis B surface antigen clearance was 0.9 %. All of 17 HCC patients observed over a period of 5 years or more belonged to the continuously high HBV DNA group (annual average >3.7 log copies/ml) and all but one belonged to the continuously high alanine aminotransferase group (annual average >40 IU/l). CONCLUSION: Patients with genotype C and a continuously high HBV DNA for 5 years or more are at a high-risk group for HCC development. Maintaining continuously low HBV DNA for 3 years or more with anti-viral therapy, may be useful in preventing or delaying HCC occurrence.
Subject(s)
Carcinoma, Hepatocellular/virology , Hepatitis B, Chronic/pathology , Hepatitis C, Chronic/pathology , Liver Cirrhosis/virology , Liver Neoplasms/virology , Adult , Age Distribution , Aged , Aged, 80 and over , Analysis of Variance , Biopsy, Needle , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/pathology , Case-Control Studies , Cohort Studies , DNA, Viral/analysis , Disease Progression , Female , Genotype , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/genetics , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/genetics , Humans , Liver Cirrhosis/epidemiology , Liver Cirrhosis/pathology , Liver Neoplasms/epidemiology , Liver Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Prevalence , Probability , Prognosis , Risk Assessment , Severity of Illness Index , Sex Distribution , Survival Rate , Viral LoadABSTRACT
Oxidative stress (OS) plays a major role in chronic hepatitis C. Various OS markers have been found to be elevated in hepatitis C virus (HCV)-related liver disease. This study detected the presence of OS in serum and liver biopsy specimens of HCV patients. Reactive oxygen molecules (ROM) in sera of 54 HCV patients were compared with 23 controls. OS markers 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal, malondialdehyde, and thioredoxin were measured in liver biopsy specimens of 18 HCV patients with fibrosis staging F1 (six); F2 (two), F3 (four), and F4 (six). The interferon (IFN) response and hepatocellular carcinoma (HCC) occurrence in the presence of OS markers were also evaluated. The level of ROM in HCV patients was 318 +/- 56.7 Carr compared with 248 +/- 40.8 Carr in controls (p=0.032). Multivariate analysis found age (p=0.0236) to be the only independent variable associated with increase in ROM in sera. In liver biopsy specimens, OS markers were found mainly around the area of piecemeal necrosis or the periportal area. The presence of OS markers seemed to increase with fibrosis staging, although not significantly. The OS DNA damage marker 8-OHdG was detected in the nucleus of hepatocytes. Thirteen patients received IFN therapy. During the 4-year follow-up period, HCC developed in four nonresponders to IFN and in one untreated patient. OS markers were stained in both HCC cells and non-HCC cells in HCC patients. OS markers were found in serum and liver specimens of HCV-associated liver disease and in HCC tissue. Detection of OS markers may be important for monitoring disease progression in HCV patients. Antioxidant therapy in combination with antiviral therapy may minimize liver damage and aid in the prevention and subsequent development of HCC.
