Background and Aims:The impact of nonalcoholic fatty liver disease (NAFLD) on the treatment outcome of chronic hepatitis B (CHB) is undefined and deserves an in-depth investigation. Methods: Histologically-proven CHB receiving first-line antiviral regimens as initial therapy was enrolled and grouped by the concurrence of NAFLD, and followed up at six monthly intervals. Therapeutic response related data were recorded and compared at multiple time points. Kaplan-Meier and Cox regression analyses were utilized to estimate the impact of NAFLD on complete virological response (CVR). Results: We enrolled 267 patients (CHB: 164; CHB with NAFLD: 103) with comparable follow-up durations. They were also comparable in baseline HBV DNA levels and HBeAg positivity. Patients with concomitant NAFLD showed less significant decline in HBV DNA, qHBsAg, pgRNA, and liver enzyme levels over time; moreover, their cumulative incidences of CVR were significantly lower and that of low-level viremia (LLV) were significantly higher at 6, 12, 18, 24 months. First CVR of CHB was delayed with the presence NAFLD (11.0 vs. 7.0 months, p<0.001) and further prolonged with higher grade of liver steatosis (Grade 2-3 vs. 1: 13.0 vs. 9.0 months). On multivariate analysis, HBeAg positivity (HR: 0.650, p=0.036), grade of steatosis (G2 [HR: 0.447, p=0.004]; G3 [HR: 0.085, p=0.002]) and HBV DNA (log10 IU/mL) (HR: 0.687, p<0.001) were significantly associated with delayed CVR, whereas grade of necroinflammation (HR: 1. 758, p<0.001) accelerated the CVR. Conclusions: In CHB patients receiving initial antivi-ral therapy, NAFLD was associated with higher levels of HBV DNA, pgRNA, and liver enzymes, and higher incidence of LLV and delayed CVR.

The aim of this study was to identify potential plasma biomarkers for hepatitis B virus (HBV)‐related liver diseases. High‐throughput transcriptome sequencing analysis was performed on five patients with chronic hepatitis B (CHB), five patients with HBV‐associated liver fibrosis/liver cirrhosis (LF/LC), and four healthy participants. By short time‐series expression miner and functional analysis, aquaporin 1 (AQP1), dystroglycan 1 (DAG1), and hemoglobin subunit beta (HBB) were identified as potential biomarkers. Immunohistochemical analysis revealed that the expression levels of AQP1, DAG1, and HBB were upregulated in the three groups. Subsequent enzyme‐linked immunosorbent assay tests on the training cohort (n = 150) indicated that the plasma levels of AQP1 and DAG1 were highest in LF/LC patients, followed by those in CHB patients, and the lowest in healthy controls. APAD model, a diagnostic panel incorporating age, platelet, AQP1, and DAG1 levels, exhibited the strongest stratification ability to distinguish LF/LC patients from CHB patients, and to differentiate CHB patients from healthy controls. Furthermore, the diagnostic accuracies of the biomarkers and APAD model were verified in an independent cohort consisting of 230 participants. In conclusion, both AQP1 and DAG1 have good diagnostic values and APAD model greatly enhances the diagnostic accuracy for HBV‐related hepatic diseases.

Aim: To explore the predictive value of plasma YAP1 for esophageal varices (EV) and high-risk EV (HRV) in patients with liver cirrhosis. Materials & methods: A total of 208 patients with liver cirrhosis were enrolled and categorized into four groups. Correlation analysis, logistic regression analysis and receiver operating characteristic curve analysis were performed to evaluate the diagnostic performance of plasma YAP1 for EV and HRV. Results: Plasma YAP1 levels were significantly elevated with the occurrence and progression of EV in cirrhotic patients. The multivariate logistic regression analysis revealed that plasma YAP1 is an independent predictor for EV and HRV. For predicting EV and HRV, the YAP1 cut-off values of 5.43 and 6.98 ng/ml yielded the area under the receiver operating characteristic curves of 0.944 and 0.955, respectively. Conclusion: Plasma YAP1 is a potential novel noninvasive biomarker for predicting EV and HRV in patients with liver cirrhosis.