Clinical Implications of Serum Hepatitis B Virus Pregenomic RNA Kinetics in Chronic Hepatitis B Patients Receiving Antiviral Treatment and Those Achieving HBsAg Loss

Serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) is correlated with covalently closed circular DNA. We aimed to investigate the utility of serum HBV pgRNA in chronic hepatitis B patients receiving nucleos(t)ide analogue treatment and those achieving HBsAg loss. One hundred and eighty-five patients were enrolled for studying long-term HBV pgRNA kinetics during treatment. Twenty patients achieving HBsAg loss after treatment were enrolled for examining HBV pgRNA kinetics around HBsAg loss. HBV pgRNA significantly decreased in the high baseline HBV pgRNA (≥6 log copies/mL) group but significantly increased in the low baseline HBV pgRNA (<4 log copies/mL) group after 3-month entecavir treatment. Among the 20 patients achieving HBsAg loss, 13 (65%) patients had serum HBV pgRNA higher than the limit of detection (LOD, 1466 copies/mL) when they achieved HBsAg loss. Finally, all 20 patients had HBV pgRNA going below the LOD within 3 years after achieving HBsAg loss. In conclusion, baseline serum HBV pgRNA alone is insufficient for predicting the trajectory of HBV pgRNA. Most patients still had HBV pgRNA higher than the LOD when they achieved HBsAg loss. Further studies on HBV pgRNA kinetics around HBsAg loss would provide an enhanced basis for further applications of HBV pgRNA.

Relationship Between Serum Hepatitis B Core-Related Antigen and Hepatitis B Surface Antigen in Hepatitis B Cirrhosis Patients With HBV-DNA Negative Status: A Cross-Sectional Study

Background: The relationship between serum hepatitis B surface antigen (HBsAg) and HBV core-related antigen (HBcrAg) titers, which is especially clinically important in monitoring virus replication activity and progression of liver disease, is not thoroughly studied in patients with hepatitis B cirrhosis, particularly in HBV-DNA negative patients. This retrospective study explored the relationship between serum HBcrAg and HBsAg titers in hepatitis B cirrhosis patients with HBV-DNA negative status. Methods: We analyzed data and samples from 180 patients diagnosed with HBV liver cirrhosis. Statistical analyses included baseline characteristics, univariate analysis, stratification analysis, three different analytical models, Spearman’s correlation analysis, generalized additive model, and two-piecewise linear regression model. Results: After adjusting for confounders (age, sex, primary hepatic carcinoma, HBeAg, Child–Pugh class, alcoholic liver disease, Diabetes mellitus , and type and duration of use of anti-HBV agents), a non-linear relationship was found between HBsAg and HBcrAg. The inflection point was 0.58. The effect sizes, confidence intervals, and P value on the left and right sides of the inflection point were 0.10, (–0.23–0.42), 0.555 and 0.62, (0.46–0.78), ＜0.0001, respectively. There was statistical significance (all p<0.01) between HBcrAg and HBsAg among all the stratification variables except for the "others" group in type of anti-HBV agents. Spearman’s correlation coefficient between HBsAg and HBcrAg was 0.613 (P<0.0001). Conclusions: There was a clear non-linear relationship between HBcrAg and HBsAg in patients with hepatitis B cirrhosis who were HBV-DNA negative, and the correlation between serum HBcrAg and HBsAg was moderate.