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Background and Aims: Mother‐to‐child‐transmission (MTCT) of hepatitis B virus (HBV) may still occur despite birth‐dose HBV vaccinations when pregnant women are positive for hepatitis B surface antigen (HBsAg) with high viral loads (HBV DNA ≥ 200 000 IU/mL). A pilot integrated model nurse clinic (IMNC) was started in 2020 to implement the pre‐emptive antiviral therapy with tenofovir disoproxil fumarate (TDF). We aimed to evaluate the performance of IMNC on uptake of TDF. Methods: This was a territory‐wide retrospective cohort of all consecutive HBsAg‐positive women of child‐bearing age with pregnancy records in public hospitals 2019–2022. Demographic characteristics, liver biochemistries and virologic parameters, and TDF use were collected. Concurrently, data from a prospective audit in Union Hospital, the private hospital with the highest number of deliveries in Hong Kong, from June 2022 to May 2023 were compared. Results: The prevalence rate of HBV DNA ≥ 200 000 IU/mL in pregnant women with available HBV DNA records was 29.2% (66/226) in 2019, 27.3% (99/363) in 2020, 15.9% (125/784) in 2021 and 17.2% (117/679) in 2022 (p <.001), out of 2052 pregnant women who had their HBV DNA checked within 1 year prior to delivery. An increasing uptake rate of TDF by highly viraemic pregnant women (i.e. ≥ 200 000 IU/mL) was noted after the commencement of IMNC in public hospitals, with 67% (45/67) in 2019, 83% (88/106) in 2020, 91% (117/128) in 2021 and 89% (149/167) in 2022. Moreover, all highly viraemic pregnant women from Union Hospital received TDF. Continuous use of TDF was associated with a reduced risk of postpartum biochemical flare. Conclusions: IMNC increases the uptake of antiviral treatment in pregnant women at risk of MTCT of HBV. IMNC contributes to hepatitis elimination through a structured care plan to prevent MTCT of HBV. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B (CHB) is endemic to Asia and is a leading cause of liver‐related morbidity. The prevalence of concomitant CHB and hepatic steatosis (HS) is increasing in Asia. Non‐invasive tests (NITs) including FIB‐4, NFS and APRI assess fibrosis in populations with a single aetiology, but not in subjects with concomitant CHB and HS. Aim: To explore the accuracy of NITs in predicting advanced fibrosis in patients with concomitant CHB and HS. Methodology: This multicentre study of CHB patients who underwent liver biopsy explored clinical characteristics of these subjects, stratified by presence of HS. Fibrosis scores from NITs were compared against histological fibrosis stage in CHB subjects with and without HS. Results: 2262 subjects were enrolled, 74.5% were males, and the mean age was 39.5 years ±11.8 SD. 984 (44.4%) had HS, 824 (36.4%) had advanced fibrosis. In the CHB group, the AUROC for advanced fibrosis were 0.65 (95% CI 0.62–0.69) for FIB‐4 and 0.63 (95% CI 0.60–0.66) for APRI. The specificities were 0.94 for FIB‐4 greater than 3.25 and 0.81 for APRI greater than 1.5. In the CHBHS group, the AUROC for advanced fibrosis were 0.67 (95% CI 0.63–0.71) for FIB‐4, 0.60 (95% CI 0.56–0.64) for APRI and 0.65 (95% CI 0.61–0.69) for NFS. The specificities were 0.95 for FIB‐4 greater than 3.25, 0.88 for APRI greater than 1.5 and 0.99 for NFS greater than 0.675. Conclusion: The performance of NITs to exclude advanced fibrosis did not differ greatly regardless of HS. FIB‐4 and NFS have the best negative predictive values of 0.80 and 0.78, respectively, to exclude advanced fibrosis in CHBHS subjects. [ABSTRACT FROM AUTHOR]

Cell-free DNA (cfDNA) fragmentation is nonrandom, at least partially mediated by various DNA nucleases, forming characteristic cfDNA end motifs. However, there is a paucity of tools for deciphering the relative contributions of cfDNA cleavage patterns related to underlying fragmentation factors. In this study, through non-negative matrix factorization algorithm, we used 256 5' 4-mer end motifs to identify distinct types of cfDNA cleavage patterns, referred to as "founder" end-motif profiles (F-profiles). F-profiles were associated with different DNA nucleases based on whether such patterns were disrupted in nuclease-knockout mouse models. Contributions of individual F-profiles in a cfDNA sample could be determined by deconvolutional analysis. We analyzed 93 murine cfDNA samples of different nuclease-deficient mice and identified six types of F-profiles. F-profiles I, II, and III were linked to deoxyribonuclease 1 like 3 (DNASE1L3), deoxyribonuclease 1 (DNASE1), and DNA fragmentation factor subunit beta (DFFB), respectively. We revealed that 42.9% of plasma cfDNA molecules were attributed to DNASE1L3-mediated fragmentation, whereas 43.4% of urinary cfDNA molecules involved DNASE1-mediated fragmentation. We further demonstrated that the relative contributions of F-profiles were useful to inform pathological states, such as autoimmune disorders and cancer. Among the six F-profiles, the use of F-profile I could inform the human patients with systemic lupus erythematosus. F-profile VI could be used to detect individuals with hepatocellular carcinoma, with an area under the receiver operating characteristic curve of 0.97. F-profile VI was more prominent in patients with nasopharyngeal carcinoma undergoing chemoradiotherapy. We proposed that this profile might be related to oxidative stress. [ABSTRACT FROM AUTHOR]

Background: It is uncertain whether biological therapies would increase the risk of hepatitis among patients with past hepatitis B virus (HBV) infection. This study aimed to evaluate the risk of alanine aminotransferase (ALT) flare in patients with past HBV infection while using biological therapies. Methodology: Patients who received biological therapies for ≥3 months from 2000 to 2019 were identified from a population‐based database in Hong Kong. Patients with past HBV infection were compared with a control group without prior HBV exposure. The primary endpoint was development of ALT flare within 5 years of starting biological therapies, defined as ALT >80 IU/L. Results: There were 2471 and 2394 patients with and without past HBV infection respectively. There was a non‐significant increase in risk of ALT flare among the HBV‐exposed group (27.6% vs. 23.7%, p =.055). In multivariable analysis, using prednisolone‐equivalent dose of >20 mg daily, male sex and concomitant immunosuppressants were risk factors for ALT flare. The risk of ALT flare was significantly higher with anti‐CD20 when compared to other biological agents (36.1% vs. 14.5%, p <.01), but was not significantly different among anti‐tumour necrosis factor, anti‐cytokine, Janus kinase inhibitors and T cell/B cell inhibitors or anti‐integrin (15.2% vs. 14.6% vs. 11.7% vs. 11.1%, p =.82). Among patients with documented hepatitis B surface antigen seroreversion, 96% were on anti‐CD20. Conclusions: Our study further supports the current suggestion of prophylactic anti‐viral before starting anti‐CD20 in HBV‐exposed patients. While other biological therapies appear to have a lower risk for ALT flare, this result needs further confirmation. [ABSTRACT FROM AUTHOR]

Cell-free DNA (cfDNA) fragmentation patterns contain important molecular information linked to tissues of origin. We explored the possibility of using fragmentation patterns to predict cytosine-phosphate-guanine (CpG) methylation of cfDNA, obviating the use of bisulfite treatment and associated risks of DNA degradation. This study investigated the cfDNA cleavage profile surrounding a CpG (i.e., within an 11-nucleotide [nt] window) to analyze cfDNA methylation. The cfDNA cleavage proportion across positions within the window appeared nonrandom and exhibited correlation with methylation status. The mean cleavage proportion was ~twofold higher at the cytosine of methylated CpGs than unmethylated ones in healthy controls. In contrast, the mean cleavage proportion rapidly decreased at the 1-nt position immediately preceding methylated CpGs. Such differential cleavages resulted in a characteristic change in relative presentations of CGN and NCG motifs at 5' ends, where N represented any nucleotide. CGN/NCG motif ratios were correlated with methylation levels at tissue-specific methylated CpGs (e.g., placenta or liver) (Pearson's absolute r > 0.86). cfDNA cleavage profiles were thus informative for cfDNA methylation and tissue-of-origin analyses. Using CG-containing end motifs, we achieved an area under a receiver operating characteristic curve (AUC) of 0.98 in differentiating patients with and without hepatocellular carcinoma and enhanced the positive predictive value of nasopharyngeal carcinoma screening (from 19.6 to 26.8%). Furthermore, we elucidated the feasibility of using cfDNA cleavage patterns to deduce CpG methylation at single CpG resolution using a deep learning algorithm and achieved an AUC of 0.93. FRAGmentomics-based Methylation Analysis (FRAGMA) presents many possibilities for noninvasive prenatal, cancer, and organ transplantation assessment. [ABSTRACT FROM AUTHOR]

Background and Aim: Whether 5‐aminosalicylic acid (ASA) can be stopped in patients with stable ulcerative colitis (UC) remains unclear. We aimed to examine whether 5‐ASA can be safely withdrawn in UC patients who have been in corticosteroid‐free clinical remission for ≥ 1 year. Methods: This is a retrospective cohort study using territory‐wide healthcare database in Hong Kong. Primary outcome was development of UC flare, defined as new corticosteroid use or UC‐related hospitalizations within 5 years. UC patients on oral 5‐ASA ≥ 2 g daily for ≥ 1 year with C‐reactive protein (CRP) < 10 mg/dL and no 5‐ASA dosage escalation, UC‐related hospitalization or corticosteroid use in the past year were included. Patients on biological agents were excluded. Patients were classified as "stopping" if 5‐ASA was withdrawn for ≥ 90 days within follow‐up period. We performed multivariable Cox regression models adjusting for demographics, blood parameters and immunosuppressants used. Adjusted hazard ratio (aHR) with 95% confidence interval (CI) was reported comparing stopping and continuous‐use groups. Results: A total of 1408 patients were included with a median follow‐up duration of 41.8 months (interquartile range [IQR]: 17.2–60.0 months). Stopping 5‐ASA was not associated with an increased risk of UC flare (aHR 0.91; 95% CI 0.64–1.31; P = 0.620). A higher CRP levels at the time of stopping 5‐ASA (aHR 1.15; 95% CI: 1.01–1.30; P = 0.037) were associated with increased risk of flare. Conclusion: Stopping 5‐ASA in UC patients in corticosteroid‐free remission for ≥ 1 year was not associated with increased risk of flare. Future prospective trials should evaluate the role of stopping 5‐ASA in stable UC patients. [ABSTRACT FROM AUTHOR]

Background & Aims: How adiposity influences the effect of genetic variants on non‐alcoholic fatty liver disease (NAFLD) in the Asian population remains unclear. We aimed to study the association between genetic risk variants and susceptibility/severity of NAFLD in the lean, overweight and obese individuals. Methods: Nine hundred and four community subjects underwent proton‐magnetic resonance spectroscopy and transient elastography examination. Lean (<23 kg/m2), overweight (23‐24.9 kg/m2) and obesity (≥25 kg/m2) were defined according to the body mass index cut‐offs for Asians. NAFLD was defined as intrahepatic triglycerides ≥5%. PNPLA3, TM6SF2, MBOAT7 and 9 other gene polymorphisms were analysed by rhAMPTM SNP assays. Results: Five hundred and twenty‐nine (58.5%), 162 (17.9%) and 213 (23.6%) subjects were lean, overweight and obese, respectively. The prevalence of NAFLD was 12.4%, 41.4% and 59.1% in the three groups (P <.001). Amongst those with NAFLD, lean subjects (30.3%) were more likely to carry the PNPLA3 rs738409 GG genotype than overweight (17.9%) and obese subjects (17.4%) (P =.003). Compared with the CC genotype, the GG genotype was associated with the greatest increase in the risk of NAFLD in lean subjects (odds ratio [OR] 6.04), compared with overweight (OR 3.43, 95% CI [1.06, 11.14]) and obese subjects (OR 2.51, 95% CI [0.93, 6.78]). Additionally, the TM6SF2 rs58542926 TT genotype was associated with reduced serum triglycerides only in lean subjects. A gene‐BMI effect was not observed for the other gene polymorphisms. Conclusions: The PNPLA3 rs738409 gene polymorphism has a greater effect on liver fat in Asian lean individuals than in overweight or obese ones. [ABSTRACT FROM AUTHOR]

We conducted a territory wide survey to investigate the epidemiology, risk factors, and clinical outcomes of Clostridioides difficile infection (CDI) among hospitalized patients in Hong Kong. A total of 17,105 cases of CDI were identified, of which 15,717 (91.9%) were healthcare-associated and 1,025 (6.0%) were community-associated. Although CDI incidence increased substantially from 2006 to 2017, it plateaued in 2018 and 2019. The 30-day mortality rates decreased from 20.1% in 2015 to 16.8% in 2019, whereas the 60-day recurrence rates remained constant at ≈11% during the study period. Cross-correlation statistic showed significant correlations between incidence trend and overall antimicrobial drug use (r = 0.865, p<0.001), which has decreased as a result of an antibiotic stewardship program initiated in 2017. Our data suggest a turning point in C. difficile epidemiology that could be related to the changing pattern of antimicrobial drug use. [ABSTRACT FROM AUTHOR]