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Abstract: Hepatitis B surface antigen (HBsAg) loss under antiviral therapy is rare in chronic hepatitis B patients and the dynamics of serum HBsAg in these patients are not available. The changes in serum HBsAg following treatment with adefovir (n =31) or peg-interferon-α-2a (n =23) were studied in hepatitis B e-antigen (HBeAg) positive chronic hepatitis B patients. Abbott Architect HBsAg assay was used to quantify serum HBsAg. HBsAg levels were significantly decreased during the first 12 weeks of treatment with median change of −397.0IU/ml and −555.4IU/ml, respectively for adefovir and peg-interferon-α-2a (p =0.005 and 0.001, respectively). Beyond 12 weeks, no further significant HBsAg reductions were found even in patients with sustained viral replication inhibition in either group. Three distinct patterns of HBsAg changes were observed in most patients in both treatment groups: biphasic pattern (rapid HBsAg reduction from baseline to week 12); assurgent pattern (higher HBsAg level at week 12 than at baseline); and wavy pattern (HBsAg reduction from baseline to week 12, followed by relapse at week 24 or week 28). These results might offer insights into the possible mechanism(s) underlying the unusual occurrences of HBsAg loss under antiviral therapy. [Copyright &y& Elsevier]

Background: Whether serum hepatitis B virus (HBV) RNA associates with hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients has not been fully elucidated.Methods: We enrolled 2974 patients receiving nucleos(t)ide analogues (NAs) from a prospective, observational CHB cohort to investigate the effect of serum HBV RNA, measured at study entry (baseline), on HCC development, using Cox regression analyses.Results: During median follow-up of 4.4 years, 90 patients developed HCC. Patients with detectable baseline HBV RNA (n = 2072) exhibited significantly higher HCC risk than those with undetectable level (5-year HCC incidence estimated by Kaplan-Meier method: 4.1% versus 1.8%, P = .009; adjusted hazard ratio [aHR] = 2.21, P = .005). HBV RNA levels of 609-99 999 and ≥100 000 copies/mL were associated with incrementally increasing HCC risk (aHR = 2.15 and 3.05, respectively; P for trend = .003), compared to undetectable level (<609 copies/mL). Moreover, patients with single-detectable either HBV DNA or RNA and double-detectable DNA and RNA had 1.57- and 4.02-fold higher HCC risk, respectively, than those with double-undetectable DNA and RNA (P for trend = .001).Conclusions: High-level HBV RNA is associated with increased HCC risk in NAs-treated patients. Achieving undetectable HBV RNA may contribute to better clinical outcomes, indicating it could be a valuable endpoint of anti-HBV treatment. [ABSTRACT FROM AUTHOR]

Summary: Background: Obesity is typically associated with metabolic dysfunction, but its impact on hepatocellular carcinoma (HCC) remains unclear in patients with chronic hepatitis B (CHB). Aim: To study the effect of obesity on HCC development in patients with CHB receiving antiviral therapy. Methods: We included patients from a Chinese multicentre, prospective, observational, treated CHB cohort in this study. General obesity was evaluated by body‐mass index (BMI). Central obesity was evaluated by waist circumference, waist‐to‐hip ratio and waist‐to‐height ratio. Results: A total of 5754 nucleos(t)ide analogue treated patients were enrolled in the analysis. The 5‐year cumulative incidence of HCC was 2.9%. Waist‐to‐height ratio performed better in predicting HCC development than BMI, waist circumference or waist‐to‐hip ratio. Patients with central obesity (defined as waist‐to‐height ratio >0.5) had significantly higher 5‐year incidence of HCC than those without central obesity in the overall population (3.9% vs 2.1%, hazard ratio [HR]: 2.06, P = 0.0001) and 745 propensity score matched pairs (4.7% vs 2.3%, HR: 2.04, P = 0.026), respectively. Besides cirrhosis status and aMAP HCC risk score, central obesity was also independently associated with HCC risk (HR: 1.63, P = 0.013). Waist‐to‐height ratio gain within 1 year was associated with a significantly higher HCC risk with an adjusted HR value of 1.88 (95% confidence interval: 1.12‐3.13, P = 0.017). Conclusions: Central obesity, evaluated by the waist‐to‐height ratio, was associated with a twofold increase in HCC risk among CHB patients receiving antiviral treatment, highlighting the important role of abnormal metabolic function in the progression of liver disease. [ABSTRACT FROM AUTHOR]

Background and Aim: Tri‐typing of acute‐on‐chronic liver failure (ACLF), as proposed by the World Gastroenterology Organization (WGO), has not been validated in patients infected with hepatitis B virus (HBV). We aim to compare the three types of ACLF patients in clinic characteristics. Methods: Hospitalized ACLF patients with chronic hepatitis B from five hepatology centers were retrospectively selected and grouped according to the WGO classification. For each group, we investigated laboratory tests, precipitating events, organ failure, and clinical outcome. Results: Compared with type‐B (n = 262, compensated cirrhosis) and type‐C (n = 129, decompensated cirrhosis) ACLF, type‐A patients (n = 195, non‐cirrhosis) were associated with a younger age, the highest platelet counts, the highest aminotransferase levels, and the most active HBV replications. HBV reactivation were more predominant in type‐A, while bacterial infections in type‐B and type‐C ACLF cases. Liver failure (97.4%) and coagulation failure (86.7%) were most common in type‐A compared with type‐B or type‐C ACLF patients. Kidney failure was predominantly identified in type‐C subjects (41.9%) and was highest (23/38, 60.5%) in grade 1 ACLF patients. Furthermore, type‐C ACLF showed the highest 28‐day (65.2%) and 90‐day (75.3%) mortalities, compared with type‐A (48.7% and 54.4%, respectively) and type‐B (48.4% and 62.8%, respectively) ACLF cases. Compared with type‐A (11.7%) ACLF patients, the increased mortality from 28 to 90 days was higher in type‐B (31.6%) and type‐C (37.5%). Conclusion: Tri‐typing of HBV‐related ACLF in accordance with the WGO definition was able to distinguish clinical characteristics, including precipitating events, organ failure, and short‐term prognosis in ACLF patients. [ABSTRACT FROM AUTHOR]

Background Little is known about cause and intervention for alanine aminotransferase (ALT) elevation after complete viral suppression in patients with chronic hepatitis B (CHB). Methods In this prospective cohort study, patients with CHB who were treated with nucleos(t)ide analogs and maintained undetectable levels of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) for at least 6 months were enrolled. Patients were followed up at 6-month intervals, and anthropometric, biochemical, and virological assessments were performed. Results Of 1965 patients with median follow-up of 18.36 months, one third of patients experienced ALT elevation. Baseline high body mass index ([BMI] defined as ≥25 kg/m2), younger age, and liver cirrhosis independently increased the risk of longitudinal ALT elevation. At the end of follow-up, 89 (4.8%) patients reverted to low BMI, and 92 (5.0%) developed to high BMI. Compared with persistent high BMI, reversion to low BMI reduced the risk of ALT elevation (adjusted odds ratio [aOR], 0.38; 95% confidence interval [CI], 0.19–0.77); compared with persistent low BMI, onset of high BMI increased the risk of ALT elevation (aOR, 1.78; 95% CI, 1.02–3.11). Conclusions High BMI is an independent predictor for ALT elevation after complete HBV DNA suppression. Improvement of BMI may have a beneficial effect on ALT normalization and even long-term outcomes. [ABSTRACT FROM AUTHOR]

Background & Aims: The role of cigarette smoking in the development of chronic hepatitis B (CHB) remains poorly understood. We assessed the potential contributions of cigarette smoking to liver fibrosis and its regression after starting antiviral therapy in CHB patients. Methods: In this cohort study, 2144 consecutive male CHB patients under no antiviral therapy were evaluated and 206 patients with significant liver fibrosis (≥F2) initiating antiviral therapy had longitudinal follow‐up. Liver fibrosis was measured by liver stiffness measurement using transient elastography. To adjust for imbalances between smoking history and never smoking groups, propensity score (PS) matching model with 1:1 ratios were performed. Cigarette smoking history and intensity (pack‐years) were collected and documented using a standardized questionnaire. Results: Before PS matching, 432/2144 patients had advanced fibrosis in prevalence cohort. Patients with smoking history (n = 1002) had a greater prevalence of advanced fibrosis than those without (n = 1142) (24.4% vs 16.5%, P = 0.001). Multivariate logistic regression analysis demonstrated that smoking contributed to advanced fibrosis (OR, 1.458; 95% CI, 1.114‐1.908). In longitudinal cohort, multivariate logistic regression analysis demonstrated retarded fibrosis regression in patients with history of smoking ≥10 pack‐years (OR, 0.288; 95% CI, 0.1‐0.825). After PS matching, patients with smoking history had higher prevalence of advanced fibrosis (22.8% vs 18%, P = 0.024) than those non‐smokers. In post‐PS‐matching logistic regression, the effect of smoking on advanced fibrosis persisted (OR, 1.415; 95% CI, 1.047‐1.912; P = 0.024). Conclusions: Cigarette smoking in male CHB patients aggravated liver fibrosis prior to and delayed fibrosis regression under antiviral therapy. [ABSTRACT FROM AUTHOR]

Toll-like receptor 2 (TLR2) plays an important role in the immunopathogenesis of hepatitis B virus (HBV) infection. The relationship between TLR2 expression and clinical outcome of chronic HBV infection is not yet elucidated in details so far. Here, we employed clinical cohorts to investigate TLR2 expression and function in different phases of HBV infection and dynamic changes of TLR2 expression in HBeAg-positive chronic hepatitis B (CHB) patients during antiviral therapy. TLR2 was mainly expressed in monocytes and its ligand stimulation resulted in TNF-α, IL-6 and IL-10 production. Serum soluble TLR2 (sTLR2) levels were negatively correlated with TLR2 mRNA in PBMCs. As compared with immunotolerant carriers and inactive carriers, CHB patients showed an elevated TLR2 expression and TNF-α, IL-6 induction in PBMC, but had a decreased level of sTLR2 in serum. However, TLR2 expression and TNF-α induction in monocytes of CHB patients remained lower than healthy controls. Furthermore, higher TLR2 expression in PBMCs and lower level of sTLR2 in serum at baseline were predictive of a complete response to 52 weeks of telbivudine (LdT) therapy. Temporal dynamic analysis showed that TLR2 expression was restored with viral suppression and ALT normalization from week 12 to 24. However, peg-IFN-α-2a therapy induced a slightly decline in TLR2 expression. In conclusion, TLR2 expression and function in monocytes were impaired by chronic HBV infection. Higher TLR2 expression in PBMC and lower level of sTLR2 in serum at baseline were associated with a complete response to LdT therapy, and dynamic TLR2 expression was differently regulated by LdT and peg-IFN-α-2a therapy. [ABSTRACT FROM AUTHOR]

Keywords: Hepatitis B virus; Acute-on-chronic liver failure; Prognosis EN Hepatitis B virus Acute-on-chronic liver failure Prognosis 479 480 2 12/30/20 20210201 NES 210201 To the Editor: We read the paper "The PREDICT study uncovers three clinical courses in acutely decompensated cirrhosis with distinct pathophysiology" published in Journal of Hepatology with great interest.[1] This multicenter study reported on 3 different clinical courses with distinct pathophysiology and prognosis in patients with acute decompensation (AD) of cirrhosis. Clinical and laboratory characteristics of the pre-ACLF patients (n = 90), ACLF patients at the time of admission (n = 189) and patients with AD without ACLF development (n = 587) were compared in Table 1. The prevalence of HBV reactivation was different (p <0.001) among these patients and higher in pre-ACLF patients (56.7%) and ACLF patients (57.7%). [Extracted from the article]

Background: Little is known about cause and intervention for alanine aminotransferase (ALT) elevation after complete viral suppression in patients with chronic hepatitis B (CHB).Methods: In this prospective cohort study, patients with CHB who were treated with nucleos(t)ide analogs and maintained undetectable levels of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) for at least 6 months were enrolled. Patients were followed up at 6-month intervals, and anthropometric, biochemical, and virological assessments were performed.Results: Of 1965 patients with median follow-up of 18.36 months, one third of patients experienced ALT elevation. Baseline high body mass index ([BMI] defined as ≥25 kg/m2), younger age, and liver cirrhosis independently increased the risk of longitudinal ALT elevation. At the end of follow-up, 89 (4.8%) patients reverted to low BMI, and 92 (5.0%) developed to high BMI. Compared with persistent high BMI, reversion to low BMI reduced the risk of ALT elevation (adjusted odds ratio [aOR], 0.38; 95% confidence interval [CI], 0.19-0.77); compared with persistent low BMI, onset of high BMI increased the risk of ALT elevation (aOR, 1.78; 95% CI, 1.02-3.11).Conclusions: High BMI is an independent predictor for ALT elevation after complete HBV DNA suppression. Improvement of BMI may have a beneficial effect on ALT normalization and even long-term outcomes. [ABSTRACT FROM AUTHOR]