Relationship between oxidative stress in patients with HBV-induced liver disease and HBV genotype/drug-resistant mutation

Objective

To explore the correlation of oxidative stress in patients with chronic hepatitis B and degree of severity of the disease with HBV genotype and drug-resistant mutation.

Methods

A total of 296 patients with diagnosed chronic hepatitis B were selected from Febuary 2014 to April 2016 in Mianyang Central Hospital, including 145 cases of chronic hepatitis B (CHB), 101 cases of hepatitis B cirrhosis (HBC), and 50 cases of hepatocellular carcinoma (HCC). Three HBV genotypes (B, C and D) and eight drug-resistant mutation genes (rt180L, rt204M, rt207V, rt236N, rt250M, rt181A, rt184T and rt202S) were detected by PCR-reverse dot blot method. In addition, total oxidative stress (TOS), and total antioxidant status (TAS) were measured, on the basis of which oxidative stress index (OSI) was calculated. Furthermore, the differences of TOS, TAS and OSI levels were compared between different liver diseases, different genotypes or drug-resistant mutation, and also the correlations were analyzed between HBV genotype, drug-resistant mutation, patient’s oxidative stress status and disease severity.

Results

Serum TOS and OSI levels, HBV-B/C ratios and drug-resistant mutation rates increased gradually with the severity of liver disease (CHB < HBC<HCC, P < 0.05). Serum TAS levels decreased with degree of severity of the disease, but there was no statistical difference between CHB group and HCC group. Except TAS levels in patients at PHC group, compared with patients without mutation in HBV, the patients with drug-resistant mutation had higher TOS and OSI levels, but lower serum TAS levels (P < 0.05). Drug-resistant mutation rate was positively correlated with TOS (r = 0.476, P < 0.001) and OSI (r = 0.441, P < 0.001) levels, but negatively correlated with TAS level (r = −0.249, P < 0.001), except TAS level in patients at PHC group. In addition, the number of mutation sites was positively correlated with disease severity (γ = 0.614, P < 0.001).

Conclusions

There are different degrees of oxidative damage in patients with HBV-induced liver disease, and the degree of the damage depends on HBV genotypes and drug-resistant mutations. Therefore, oxidative stress parameters might be useful indicators of progression of HBV-induced liver disease in patients.