Antiviral Therapy with Entecavir following Antituberculosis Therapy Alleviates Liver Injury and Restores Innate Immunity in Tuberculosis Patients Coinfected with Hepatitis B Virus

Abstract

Objective. Coinfection of tuberculosis (TB) and viral hepatitis may increase the risk of antituberculosis treatment-induced hepatotoxicity, which is regarded as a common cause of termination of the first-line antituberculosis drugs. The study aimed at investigating the protective effects of antiviral therapy on the liver and innate immunity in patients with TB-HBV coinfection. Methods. A total of 100 patients with TB-HBV coinfection were recruited and split into antituberculosis and antiviral groups, 50 per group, according to odd or even date of hospital admission from December 2019 to October 2020. The patients in the anti-TB group received antituberculosis therapy, and those in the antiviral group received antiviral therapy. The clinical effectiveness; HBV-DNA negative conversion rate; liver function assessment involving alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL); immune function evaluation including CD4+, CD8+, CD4+/CD8+, and CD3+ T cells; inflammatory cytokines containing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interferon-γ (IFN-γ); and intestinal microflora including bifidobacterium, lactobacillus, enterobacterium, enterococcus, and clostridium were main outcome measures after treatment. Results. It was found that the total response rate in the antiviral group was significantly higher than the anti-TB group after treatment (χ2 = 3.157, $P=0.017$ ). There was a significant difference in HBV-DNA negative conversion rates between the antiviral group and anti-TB group (82% vs. 58%, χ2 = 6.384, $P=0.001$ ). The ALT, AST, and TBIL in the two groups were all increased after treatment ( $P<0.05$ ), but the antiviral group indicated a rise of the above indices compared to the anti-TB group ( $P<0.05$ ). The two groups showed a rise on the concentration of CD3+, CD4+, and CD4+/CD8+ T cells and a decline on the CD8+ T cells after treatment ( $P<0.05$ ), but these changes in the antiviral group were more evident to those in the anti-TB group ( $P<0.05$ ). There was an increase on the IFN-γ level and decrease on the TNF-α and IL-6 levels in both groups after treatment ( $P<0.05$ ), but the antiviral group revealed a higher level of IFN-γ with lower levels of TNF-α and IL-6 compared to the anti-TB group ( $P<0.05$ ). After treatment, the number of bifidobacteria and lactobacilli was increased, and the number of enterobacteria, enterococci, and clostridium were decreased in the two groups ( $P<0.05$ ), while these changes in the antiviral group were more remarkable compared to the anti-TB group ( $P<0.05$ ). There was no significant difference in the incidence of adverse reactions between the two groups (χ2 = 0.267, $P=0.731$ ). Conclusion. Antiviral therapy for tuberculosis-HBV coinfected patients could inhibit HBV replication, providing protection against liver damage, improving innate immunity, and balancing intestinal microflora.