To develop new tools integrating host immune response and viral activity to predict Peg-IFNα therapy efficiency in nucleos(t)ide analogs (NUCs)-treated chronic hepatitis B (CHB) patients. This post-hoc study analyzed data from 758 NUCs-experienced, HBeAg-negative CHB patients with baseline HBsAg < 1500 IU/mL and undetectable serum HBV DNA who completed 48 weeks of Peg-IFNα add-on therapy in a prospective study. Clinical and biochemical data were collected every 12 weeks and evaluated for their predictive value of HBsAg seroclearance and seroconversion. Age, qHBsAg, and ALT levels at Week 12 were associated with both HBsAg seroclearance and seroconversion. The ASAP-12 score (ALT/[qHBsAg × Age] at Week 12), demonstrated strong discrimination for both endpoints (AUROCs: 0.802 [cut-off 0.07] and 0.787 [cut-off 0.12], respectively; p < 0.05). Patients with scores above the respective cut-offs had significantly higher cumulative probabilities of HBsAg seroclearance (63.4% vs. 17.8%, Log-rank test p < 0.001) and seroconversion (47.3% vs. 11.0%, Log-rank test p < 0.001). Higher ASAP-12 scores (β = 0.206, p = 0.006) independently correlated with elevated Week 48 HBsAb levels. The ASAP-12 score may serve as a useful tool to predict both HBsAg seroclearance and seroconversion at Week 48 of Peg-IFNα add-on therapy in NUCs-experienced CHB patients, supporting individualized therapeutic decisions.
China has the largest number of hepatitis B patients globally, making early detection, intervention, and treatment crucial. This study assessed the knowledge, attitude, and practice (KAP) toward antiviral treatment among chronic hepatitis B (CHB) patients. A web-based cross-sectional study was conducted among hepatitis B patients at the author's Hospital, Tianjin, China, between October 2022 and January 2023. Primary outcomes were KAP scores (knowledge: 0-18, attitude: 0-35, practice: 0-50). Secondary outcomes included factors associated with KAP. A total of 457 hepatitis B patients participated. The Mean KAP scores were 9.70 ± 4.64 (knowledge), 24.00 ± 3.28 (attitude), and 38.85 ± 6.56 (practice). Factors independently associated with adequate knowledge included household income 5,000-10,000 CNY (OR = 1.81, 95%CI: 1.05-3.12; positive factor), > 10,000 CNY (OR = 2.05, 95%CI: 1.01-4.17; positive factor), rural cooperative medical insurance (OR = 0.5, 95%CI: 0.27-0.94; negative factor), carrier-stage hepatitis B (OR = 0.34, 95%CI: 0.13-0.91; negative factor), and treatment > 10 years (OR = 2.74, 95%CI: 1.09-6.88; positive factor). Positive attitude was associated with income > 10,000 CNY (OR = 2.77, 95%CI: 1.41-5.44; positive factor) but negatively with cirrhosis (OR = 0.43, 95%CI: 0.24-0.76; negative factor) and liver cancer (OR = 0.19, 95%CI: 0.05-0.71; negative factor). Knowledge (OR = 1.20, 95%CI: 1.13-1.27) was independently associated with a proactive practice, while female sex (OR = 0.58, 95%CI: 0.35-0.95) and use to drink (OR = 0.43, 95% CI: 0.22-0.82) were independently associated with worse practice. CHB patients demonstrated suboptimal KAP levels regarding antiviral therapy. Policy support should prioritize low-income populations to improve treatment adherence and outcomes.
The global burden of hepatitis B virus (HBV) infection remains high, with chronic hepatitis B (CHB) patients facing a significantly increased risk of developing cirrhosis and hepatocellular carcinoma (HCC). The ultimate objective of antiviral therapy is to achieve a sterilizing cure for HBV. This necessitates the elimination of intrahepatic covalently closed circular DNA (cccDNA) and the complete eradication of integrated HBV DNA. This review aims to summarize the oncogenetic role of HBV integration and the significance of clearing HBV integration in sterilizing cure. It specifically focuses on the molecular mechanisms through which HBV integration leads to HCC, including modulation of the expression of proto-oncogenes and tumor suppressor genes, induction of chromosomal instability, and expression of truncated mutant HBV proteins. The review also highlights the impact of antiviral therapy in reducing HBV integration and preventing HBV-related HCC. Additionally, the review offers insights into future objectives for the treatment of CHB. Current strategies for HBV DNA integration inhibition and elimination include mainly antiviral therapies, RNA interference and gene editing technologies. Overall, HBV integration deserves further investigation and can potentially serve as a biomarker for CHB and HBV-related HCC.
Tenofovir alafenamide fumarate (TAF) is a first-line drug for the antiviral treatment of patients with chronic hepatitis B (CHB) in China. In the present study, the efficacy and renal safety of TAF were evaluated in treatment-naive patients with CHB. Patients with CHB who had not been previously treated with nucleoside analogues (NAs) were recruited before TAF treatment was initiated. Changes in the levels of hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) were analyzed at 24 and 48 weeks using immunoassays. In addition, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were analyzed using transient elastography, while alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels, calcium (Ca) and inorganic phosphorus (IP) levels were measured using biochemistry assay. In addition, the estimated glomerular filtration rate (eGFR) was calculated. After 48 weeks, the ALT normalization rate was 95.24% (40/42), the complete virological response (HBV DNA <20 IU/ml) rate was 69.05% (29/42) and the HBeAg seroconversion rate was 8.57% (3/35). The levels of HBV DNA and HBsAg were significantly decreased from the baseline at 5.49±1.95 to 1.26±0.66 log10 IU/ml and from 3.59±0.81 to 3.32±0.55 log10 IU/ml after 48 weeks of treatment, respectively. Compared with that in the baseline measurements, LSM at 48 weeks was significantly decreased from 13.00±8.15 to 8.66±4.45 kPa. No significant differences were observed in the TG, TC, LDL-C, CAP, eGFR, Ca and IP measurements. According to the baseline ALT levels, patients were divided into group A [ALT ≤1 x upper limit of normal (ULN); ULN=50 U/l; n=21], group B (1 x ULN < ALT <2 x ULN; n=22) and group C (ALT ≥2 x ULN; n=18). A significant decrease in HBsAg levels was observed in group B (3.63±0.68 vs. 3.53±0.63 log10 IU/ml) and group C (4.15±0.57 vs. 3.66±0.48 log10 IU/ml) at 24 weeks compared with the baseline. In conclusion, TAF was found to be effective and safe in NA treatment-naive patients with CHB. Moreover, the higher the ALT levels, the more prominent the curative effect from TAF treatment. Therefore, NA treatment-naive CHB patients could benefit from TAF treatment in real world.