Long-term follow-up of patients with hepatitis B e antigen negative chronic hepatitis B


Makoto Arai, Department of Medicine and Clinical Oncology (K1), Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba 260-8670, Japan. Email: araim-cib@umin.ac.jp


Background and Aim:  After hepatitis B virus (HBV) e antigen (HBeAg) seroconversion, HBV-DNA continues to replicate, and HBeAg-negative patients still face the risk of liver disease progression. We investigated the predictive factors for alanine aminotransferase (ALT) elevation, antiviral drug use, and hepatocellular carcinoma (HCC) occurrence in HBeAg-negative patients.

Methods:  Age, sex, ALT, platelet counts, HBV-DNA levels, genotype, antidiabetic drug use, body mass index, smoking, and alcohol consumption were analyzed for a total of 244 HBV carriers who were HBeAg-negative.

Results:  Of 244 HBeAg-negative patients, 158 (64.8%) showed normal ALT levels at baseline. Multivariate Cox hazard regression analysis identified high HBV-DNA levels and high ALT at baseline as independent risk factors for ALT elevation in the patients with normal ALT at baseline. The threshold ALT and HBV-DNA levels were determined to be 31 IU/L and 5.3 logcopies/mL, respectively. Seventeen (7.0%) patients used antiviral drugs. Multivariate Cox hazard regression analysis identified high HBV-DNA levels (threshold, 5.7 log copies/mL), the use of antidiabetic drugs, and daily alcohol consumption at baseline as an independent risk factor for the use of antiviral drugs in HBeAg-negative patients. In 10 patients (4.1%), HCC was detected, and a low platelet count (threshold, 10.0 × 104/mm3) was associated with the occurrence of HCC.

Conclusion:  This study identified predictors of future active liver disease in HBeAg-negative patients, i.e. ALT elevation, unavoidable use of antiviral drugs, and occurrence of HCC.