The Relationship between Viral Replication and the Severity of Hepatic Necroinflammatory Damage Changed before HBeAg Loss in Patients with Chronic Hepatitis B Virus Infection

Leijie Wang; Jian Wang; Kunyu Zhao; Lina Jiang; Xinxin Zhang; Jingming Zhao; Jie Li; Fengmin Lu

doi:10.14218/JCTH.2023.00378

The Relationship between Viral Replication and the Severity of Hepatic Necroinflammatory Damage Changed before HBeAg Loss in Patients with Chronic Hepatitis B Virus Infection

J Clin Transl Hepatol. 2024 Apr 28;12(4):381-388. doi: 10.14218/JCTH.2023.00378. Epub 2024 Feb 27.

Authors

Leijie Wang^{1

2}, Jian Wang³, Kunyu Zhao¹, Lina Jiang⁴, Xinxin Zhang⁵, Jingming Zhao⁴, Jie Li³, Fengmin Lu²

Affiliations

¹ Department of Microbiology and Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
² Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University, Beijing, China.
³ Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
⁴ Department of Pathology and Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China.
⁵ Department of Infectious Diseases, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Background and aims: Disease progression of chronic hepatitis B virus (HBV) infection is driven by the interactions between viral replication and the host immune response against the infection. This study aimed to clarify the relationship between HBV replication and hepatic inflammation during disease progression.

Methods: Two cross-sectional, one validation cohort, and meta-analyses were used to explore the relationship between HBV replication and liver inflammation. Spearman analysis, multiple linear regression, and logistic regression were used to explore the relationship between variables.

Results: In the cross-sectional cohorts A and B including 1,350 chronic hepatitis B patients, Spearman analysis revealed a negative relationship between HBV replication (such as HBV DNA) and liver inflammation (such as ALT) in HBeAg-positive patients with higher HBV DNA >2×10⁶ IU/mL (rho=-0.160 and -0.042) which turned to be positive in HBeAg-positive patients with HBV DNA ≤2×10⁶ IU/mL (rho=0.278 and 0.260) and HBeAg-negative patients (rho=0.450 and 0.363). After adjustment for sex, age, and anti-HBe, results from logistic regression and multiple linear regression showed the opposite relationship still existed in HBeAg-positive patients with different DNA levels; the opposite relationship in HBeAg-positive patients with different DNA levels was validated in a third cohort; the opposite relationship in patients with different HBeAg status was partially confirmed by meta-analysis (overall R: -0.004 vs 0.481).

Conclusions: These results suggested a negative relationship between viral replication and liver inflammation in HBeAg-positive patients with high HBV DNA, which changed to a positive relationship for those HBeAg-positive patients with DNA less than 2×10⁶ IU/mL and HBeAg-negative patients.

Keywords: ALT; Chronic hepatitis B; HBV DNA; HBeAg.