Faculty Bibliography

BACKGROUND & AIMS/OBJECTIVE:The health-related quality of life (HRQoL) during pregnancy has not been well-lidated in mothers with chronic hepatitis B (CHB). We aim to compare patient-reported outcomes (PROs) in CHB mothers with those of healthy mothers during pregnancy. METHODS:Between 4/16/2023 and 7/31/2023, we invited consecutive CHB and healthy mothers to complete the self-administered 36-item Short Form Survey (SF-36) and the Chronic Liver Disease Questionnaire (CLDQ) for PRO assessment. Pairwise comparisons of PRO scores between groups were performed using chi-square tests. Covariates for worse PROs were further analyzed by the multiple linear regression model to identify the independent predictors RESULTS: Among 257 participants (CHB: healthy control was 100:157), the mean (SD) age was 29.6 (3.4), and the majority completed the PRO assessment at the gestational weeks of 16-24. When compared to healthy mothers, CHB mothers had a significant impairment of PROs in the CLDQ domain of worry (6.97±0.16 vs 5.83±0.99, p<0.05) and the SF-36 domain of social functioning (95.33±10.00 vs 91.67±16.37, p<0.05). The subgroup analyses in CHB mothers showed HBV DNA >200,000 IU/mL associated with significantly worse PROs. The multivariate analyses identified CHB infection, severe nausea or vomiting, poor living conditions, and spousal negative attitude as independent predictors of HRQoL impairment. CONCLUSION/CONCLUSIONS:This study suggests that CHB infection during pregnancy negatively impacted HRQoL, particularly in worry and social functioning domains. CHB infection was an independent predictor for PRO impairments. Further integration of monitoring and intervention on HRQoL impairment should be considered when managing CHB mothers during pregnancy.

OBJECTIVE/UNASSIGNED:This study aimed to identify distinct intestinal microbiota associated with hepatocellular carcinoma (HCC) and to construct a predictive model for HCC. METHODS/UNASSIGNED:A case-control study was conducted including patients with chronic hepatitis B (CHB), liver cirrhosis (LC), HCC, and healthy controls (HC). Fecal 16S rDNA sequences were analyzed using bioinformatics approaches. Specific intestinal microbiota were identified through stratified analysis, and a predictive model was subsequently constructed. RESULTS/UNASSIGNED:were increased irrespective of liver disease stage. By combining microbiota profiles with clinical indicators, we developed a predictive nomogram that achieved an AUC of 0.865 in the training cohort and 0.848 in the external validation cohort. CONCLUSION/UNASSIGNED:Intestinal microbiota were associated not only with liver disease stage but also with the occurrence of HCC itself. Characteristic microbiota may serve as effective biomarkers for predicting HCC.

BACKGROUND:In two phase 3 studies, tenofovir alafenamide (TAF) showed non-inferior efficacy versus tenofovir disoproxil fumarate (TDF), with more favourable renal and bone safety in patients with chronic hepatitis B (CHB). AIMS/OBJECTIVE:Here, we report the studies' final 8-year results. METHODS:CHB patients (hepatitis B e antigen [HBeAg]-negative and HBeAg-positive) were randomised (2:1) to double-blind TAF 25 mg/day or TDF 300 mg/day for up to 3 years, followed by open-label (OL) TAF through year 8. Virological, biochemical, serological and fibrosis responses, and safety, including bone and renal parameters, were evaluated. Resistance to TAF was assessed annually by deep sequencing of polymerase/reverse transcriptase and by phenotyping. RESULTS:and hip/spine BMD observed during double-blind TDF improved after switching to OL TAF. No patients developed resistance to TAF. CONCLUSION/CONCLUSIONS:Long-term TAF treatment exhibited favourable safety and tolerability with high rates of viral suppression and no development of resistance. CLINICALTRIALS/RESULTS:gov numbers NCT01940341 and NCT01940471.

Hepatitis E virus (HEV) poses a serious threat to both public health and animal food safety, thereby highlighting the demands for rapid, sensitive, and easy-to-use detection. This study aimed to develop a One-Pot assay using CRISPR/Cas13a for detecting HEV RNA, suitable for point-of-care testing (POCT) in resource-limited settings. CRISPR/Cas13a combined with reverse transcription polymerase chain reaction (RT-PCR) and reverse transcription recombinase-aided amplification (RT-RAA) was applied to a One-Pot assay device. Additionally, a large cohort of HEV-infected patient (154) and animal (104) specimens was utilized for validation. The RT-PCR/RT-RAA + CRISPR/Cas13a assays for HEV RNA detection (genotypes: HEV-1, HEV-3, and HEV-4) were established, optimized, and validated, achieving a limit of detection (LoD) of 1 copy/μL and 100% specificity. In the application validation for HEV infection, the positive rates of the RT-PCR + CRISPR and RT-RAA + CRISPR assays were 98.6% and 89.6% for patients, and 96.6% and 88.8% for animals, respectively, which were superior to those of RT-qPCR. Furthermore, sample rapid lysis, reagent lyophilization, and the One-Pot device were integrated to construct a One-Pot assay with an LoD of 10² copies/μL. Despite slight decreases in sensitivity, the One-Pot assay significantly reduces the assay time to 35 min, making it easy to perform, minimizing contamination, and meeting the requirements for screening. We developed a One-Pot assay of HEV RNA using the CRISPR/Cas13a which effectively realizes a POCT test and maximizes the impetus for POCT implementation and shows potential as a valuable tool for detecting and monitoring HEV infection.

INTRODUCTION/BACKGROUND:This systematic scoping review aimed to synthesize existing research findings on the clinical manifestations in patients with nonalcoholic fatty liver disease (NAFLD) and sarcopenia. METHODS:Adhering to scoping review guidelines, we comprehensively searched five databases for literature on sarcopenia's clinical manifestations in NAFLD patients from December 2013 to December 2023, meticulously compiling and synthesizing the findings. RESULTS:A total of 312 articles were identified, with 9 studies included in the final review. Of these, 90% were cross-sectional investigations, with 70% from Asian cohorts. Comparative analysis between patients solely afflicted with NAFLD and those additionally experiencing sarcopenia revealed discernible trends. Individuals with both conditions tended to be older, have a higher body mass index, and show a higher prevalence among females, underscoring the influence of unhealthy lifestyles and obesity. Furthermore, comorbidities like metabolic syndrome, hypertension, and diabetes have been implicated in sarcopenia manifestation among NAFLD patients. Nonetheless, the lack of standardized diagnostic criteria and patterns poses an ongoing clinical challenge for this subgroup. CONCLUSIONS:Our review highlights distinct clinical characteristics evident in NAFLD patients with sarcopenia. However, comprehensive investigations remain scarce, impeding accurate early detection and intervention. Future research should prioritize bridging these gaps and fostering enhanced clinical management strategies.

OBJECTIVE:International guidelines recommend maternal tenofovir disoproxil fumarate (TDF) therapy accompanied by infant immunoprophylaxis to prevent HBV mother-to-child transmission (MTCT) in highly viremic mothers. However, pooled analyses for tenofovir alafenamide (TAF) effects and comparisons between the two regimens are lacking. DESIGN/METHODS:In this meta-analysis, pairs of independent reviewers performed multiple database searches from inception to March 31, 2024, and extracted data from cohort studies and RCTs in highly viremic mothers. The outcomes of interest were the reduction of MTCT and safety in the TDF-treated, TAF-treated, and control groups. RESULTS:We included 31 studies with 2,588 highly viremic mothers receiving TDF, 280 receiving TAF, and 1,600 receiving no treatment. Compared to the control, TDF therapy reduced the MTCT rate in infants aged 6-12 months (risk ratio: 0.10, 95% confidence interval 0.07-0.16). Pairwise meta-analysis between TAF and TDF revealed similar effects on reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.16-7.61). Network meta-analysis showed the equal efficacy of the two regimens in reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.15-7.65). The surface under the cumulative ranking curve revealed TDF as the best regimen compared with TAF (probability ranking: 0.77 vs. 0.72), while receiving a placebo during pregnancy had the lowest efficacy (probability ranking 0.01). There were no safety concerns for mothers and infants in all regimens. CONCLUSION/CONCLUSIONS:Compared to placebo or no treatment, maternal TDF and TAF prophylaxis are equally effective and without safety concerns in reducing MTCT in highly viremic mothers.

BACKGROUND AND AIM/OBJECTIVE:To identify individuals with metabolic dysfunction-associated steatohepatitis (MASH) or "at-risk" MASH among patients with metabolic dysfunction-associated steatotic liver disease (MASLD), three noninvasive models are available with satisfactory efficiency, which include magnetic resonance imaging [MRI]- AST (MAST), FibroScan-AST (FAST score), and magnetic resonance elastography [MRE] plus FIB-4 (MEFIB). We aimed to evaluate the most accurate approach for diagnosing MASH or "at-risk" MASH. METHODS:We included 108 biopsy-proven MASLD patients who underwent simultaneous assessment of MRE, MRI proton density fat fraction (MRI-PDFF), and FibroScan scans. Compared with the histological diagnosis, we analyzed the AUC of each model and assessed the accuracy. RESULTS:Our study cohort consisted of 64.8% of MASH and 25.9% of "at-risk" MASH. When analyzing the performance of each model for the diagnostic accuracy of MASH, we found that the AUC [95% CI] of MAST was comparable to FAST (0.803 [0.719-0.886] vs 0.799 [0.707-0.891], P = 0.930) and better than MEFIB (0.671 [0.571-0.772], P = 0.005). Similar findings were observed in the "at-risk" MASH patients. The AUCs [95% CI] for MAST, FAST, and MEFIB were 0.810 [0.719-0.900], 0.782 [0.689-0.874], and 0.729 [0.619-0.838], respectively. The models of MAST and FAST had comparable AUCs (P = 0.347), which were statistically significantly higher than that of MEFIB (P = 0.041). Additionally, the cutoffs for diagnosis of MASH were lower than "at-risk" MASH. CONCLUSION/CONCLUSIONS:MAST and FAST performed better than MEFIB in diagnosing "at-risk" MASH and MASH using lower cutoff values. Our findings provided evidence for selecting the most accurate noninvasive model to identify patients with MASH or at-risk MASH.