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Summary: Background: Optimal glycaemic control has well‐established health benefits in patients with diabetes mellitus (DM). It is uncertain whether optimal glycaemic control can benefit liver‐related outcomes. Aims: To examine the association of optimal glycaemic control with hepatocellular carcinoma (HCC) and liver‐related mortality. Methods: In a population‐based cohort, we identified patients with newly diagnosed DM between 2001 and 2016 in Hong Kong. Optimal glycaemic control was defined as mean haemoglobin A1c (HbA1c) <7% during the 3‐year lead‐in period after DM diagnosis. By applying propensity score matching to balance covariates, we analysed glycaemic control via competing risk models with outcomes of interest being HCC and liver‐related mortality. Results: We identified 146,430 patients (52.2% males, mean age 61.4 ± 11.8 years). During a median follow‐up duration of 7.0 years, 1099 (0.8%) and 978 (0.7%) patients developed HCC and liver‐related deaths. Optimal glycaemic control, when compared to suboptimal glycaemic control, was associated with reduced risk of HCC (subdistribution hazard ratio [SHR] 0.70, 95% CI 0.61–0.79). The risk of HCC increased with incremental HbA1c increases beyond >7% (SHR 1.29–1.71). Significant associations with HCC were also found irrespective of age (SHR 0.54–0.80), sex (SHR 0.68–0.69), BMI <25 or ≥25 kg/m2 (SHR 0.63–0.75), smoking (SHR 0.61–0.72), hepatic steatosis (SHR 0.67–0.68) and aspirin/statin/metformin use (SHR 0.67–0.75). A lower risk of liver‐related mortality in relation to optimal glycaemic control was also observed (SHR 0.70, 95% CI 0.61–0.80). Conclusions: Glycaemic control is an independent risk factor for HCC and liver‐related mortality, and should be incorporated into oncoprotective strategies in the general DM population. [ABSTRACT FROM AUTHOR]

Cigarette smoking is associated with worse clinical outcomes in patients with chronic hepatitis B (CHB) infection, but the effects on hepatitis B surface antigen (HBsAg) seroclearance are unclear. This study aimed to investigate the effect of active smoking on HBsAg seroclearance (SC) and its impact on peripheral blood lymphocytes in patients with CHB infection. Longitudinal follow‐up data was retrieved in 7833 antiviral‐treated CHB subjects identified from a centralised electronic patient record database (Part 1). Phenotypic analysis of peripheral blood mononuclear cells (PBMCs) from 27 CHB‐infected patients (6 active smokers; 13 with SC) was performed by flow cytometry to assess programmed death‐1 (PD‐1) expression and proportion of regulatory T cells (CD4+CD25+CD127lo). Effector function of HBV‐specific T cells was examined by comparing granzyme B (GZMB) and transforming growth factor beta (TGFβ) production in undepleted PBMCs and Treg‐depleted PBMCs after 7 days in vitro stimulation with HBV envelope protein overlapping peptides (Part 2). Over a median follow‐up of 5 years, smoking was associated with lower probability of SC (aHR 0.70, 95% CI 0.57–0.87). PD‐1 expression was increased in CD4+ T cells, CD8+ T cells and CD20+ B cells among smokers compared to non‐smokers and positively correlated with pack years (all p < 0.05). Treg depletion led to partial functional recovery of HBV‐specific T cells, with significantly bigger magnitude in smokers (p = 0.0451, mean difference = 4.68%) than non‐smokers (p = 0.012, mean difference = 4.2%). Cigarette smoking is associated with lower chance of HBsAg seroclearance, higher PD‐1 expression on lymphocytes, and impairment of effector functions of HBV‐specific T cells in CHB. [ABSTRACT FROM AUTHOR]

Background and Aim Method Results Conclusion We assessed the effect of hepatitis B surface antigen (HBsAg) seroclearance (HBsAg‐loss) on liver fibrosis regression in patients with chronic hepatitis B (CHB) infection.CHB patients with recent documented HBsAg‐loss were age‐ and gender‐matched with treatment‐naïve HBeAg‐negative CHB infection. Paired assessment with transient elastography and enhanced liver fibrosis (ELF) measurements were performed and repeated at 3 years. Fibrosis regression was arbitrarily defined as decrease in ≥ 1 fibrosis stage by ELF, or combining with reduction > 30% in liver stiffness.A total of 142 HBsAg‐loss and 142 CHB subjects were recruited (median age 58.1 years, 51.4% male). A total of 1.8% (1.4% HBsAg‐loss vs 2.1% CHB) achieved combined endpoint of fibrosis regression at 3 years. When ELF‐only definition of fibrosis regression was used, 14.5% HBsAg‐loss and 16.9% CHB subjects achieved this endpoint, which was significantly associated with baseline ELF (hazard ratio (HR) 1.827, 95% confidence interval (CI) 1.085–3.075) and time since HBsAg‐loss (HR 2.688, 95% CI 1.257–5.748). While increasing time since HBsAg‐loss increased the proportion of ELF‐defined fibrosis regression, increasing age was also associated with significant fibrosis. Age of achieving HBsAg‐loss (ageSC) was independently associated with high baseline ELF values. Up to 52.3% and 63.8% subjects with ageSC > 50 had advanced fibrosis/cirrhosis at baseline and 3 years, respectively, compared with 5.9% and 20.6% in subjects with ageSC < 50.Fibrosis regression occurred in a minority of subjects achieving HBsAg‐loss, which was not significantly different compared with subjects with persistent overt CHB. Subjects after achieving HBsAg‐loss, especially among those with ageSC > 50, should receive ongoing surveillance for liver‐related complications. [ABSTRACT FROM AUTHOR]

Background and Aim: Spontaneous seroclearance of hepatitis B surface antigen (HBsAg) is a rare event that occurs in patients that are chronically infected with the hepatitis B virus. As the functional cure and ultimate treatment endpoint of chronic hepatitis B (CHB), HBsAg seroclearance is an important milestone in the natural history of CHB and serves great clinical value. This study aims to identify host and viral factors associated with HBsAg seroclearance. Methods: This is a retrospective study carried out in the Queen Mary Hospital, Hong Kong. By analyzing the plasma retrieved from the serum archive (collected during 2011–2021) of 100 CHB patients attending the hospital's liver clinic, the longitudinal cytokine profiles between the HBsAg‐losers and the control groups were compared. Results: Data revealed that plasma levels of IP‐10 were significantly lower at 3–5 years prior to HBsAg seroclearance compared with patients who remained HBsAg positive (P < 0.05). Receiver operating characteristic curve analysis reveals that plasma IP‐10 levels at multiple time points before HBsAg seroclearance return area under receivor‐operating characteristic curve (AUC) greater than 0.7. Plasma IP‐10 levels at 42.39 pg/mL produced an AUC = 0.723 with 74.0% sensitivity and 75.5% specificity to predict subsequent HBsAg seroclearance in the next 3–5 years. Low plasma IP‐10 identified 91.4% patients with quantitative HBsAg < 100 IU/mL who would subsequently develop HBsAg seroclearance, compared with 37% with higher plasma IP‐10 levels (P < 0.001). Conclusions: Low plasma levels of IP‐10 are associated with subsequent HBsAg seroclearance, suggesting potential clinical utilities of measurement of IP‐10 in predicting HBsAg seroclearance, especially among patients with low HBsAg. [ABSTRACT FROM AUTHOR]