Balloon catheter-assisted endoscopic resection for papillary adenoma of non-exposed protruded type (with video).

Papillary adenomas, known precursors to papillary adenocarcinoma, warrant close monitoring due to their malignant potential. Historically, surgical resection represented the mainstay of treatment for papillary adenomas with intraductal extension. However, recent advancements in endoscopic techniques have facilitated the adoption of endoscopic papillectomy as a minimally invasive alternative in carefully selected cases. We report a case of an 82-year-old woman with a diagnosis of papillary adenoma exhibiting intraductal extension. This was managed with a novel endoscopic technique, balloon catheter-assisted endoscopic resection. Due to the obscured intraductal component of the papillary mass, a balloon occlusion catheter was deployed within the common bile duct and used as traction to facilitate endoscopic visualization of the mass. Endoscopic resection via papillectomy was subsequently performed. Histopathological examination of the resected specimen revealed a villous adenoma with high-grade dysplasia. Serial endoscopic ultrasound examinations with targeted papillary biopsies were performed to monitor for disease recurrence.

Relationship between Helicobacter pylori infection, osteoporosis, and fracture.

Osteoporotic fracture is a prevalent noncommunicable disease globally, causing significant mortality, morbidity, and disability. As the population ages, the healthcare and economic burden of osteoporotic fracture is expected to increase further. Due to its multifactorial features, the development of osteoporotic fracture involves a complex interplay of multiple risk factors, including genetic, environmental, and lifestyle factors. Helicobacter pylori, which infects approximately 43% of the world's population, has been associated with increased fracture risk due to hypochlorhydria from atrophic gastritis and systemic inflammation from elevated pro-inflammatory cytokines. However, the potential impact of H. pylori infection and eradication on fracture risk remains contentious among various studies due to the study design and inadequate adjustment of confounding factors including baseline gastritis phenotype. In this review, we provided a comprehensive evaluation of the current evidence focusing on the underlying mechanisms and clinical evidence of the association between H. pylori infection and osteoporotic fracture. We also discussed the potential benefits of H. pylori eradication on fracture risk.

Vonoprazan Dual or Triple Therapy Versus Bismuth-Quadruple Therapy as First-Line Therapy for Helicobacter pylori Infection: A Three-Arm, Randomized Clinical Trial.

BACKGROUND: We compared efficacy of vonoprazan-dual or triple therapies and bismuth-quadruple therapy for treatment-naive Helicobacter pylori (HP) infection in Southern China, where primary resistance rates of clarithromycin and levofloxacin are >30%. METHODS: This was an investigator-initiated, three-arm, randomized clinical trial in Southern China. Between March 2022 and August 2023, treatment-naïve HP-infected adults were randomly assigned to receive one of three 14-day regimens (1:1:1 ratio): vonoprazan-dual (VA-dual; vonoprazan 20 mg twice daily and amoxicillin 1 g thrice daily), vonoprazan-triple (VAC-triple; vonoprazan 20 mg/amoxicillin 1 g/clarithromycin 500 mg twice daily), or bismuth-quadruple therapy containing bismuth, esomeprazole, tetracycline, and metronidazole. Primary outcome was noninferiority in HP eradication, evaluated by UBT 4-6 weeks post-treatment by intention-to-treat (ITT) and per-protocol (PP) analysis (based on subjects who completed 14-day treatment and rechecked UBT). Bonferroni-adjusted p-value of <0.017 was used to determine statistical significance. RESULTS: A total of 298 subjects (mean age: 35.7 ± 8.4 years; male: 134 [45.0%]; VC-dual: 100, VAC-triple: 98, bismuth-quadruple: 100) were enrolled, and 292 (98.0%) had UBT rechecked. ITT analysis showed that both VA-dual (eradication rate of 96.0%) and VAC-triple therapies (95.9%) were noninferior to bismuth-quadruple therapy (92.0%) (difference: 4.0%, 95% CI: -2.9% to 11.5%, p < 0.001; and 3.9%, 95% CI: -3.1% to 11.5%, p < 0.001, respectively). PP analysis also revealed noninferiority (96.7% or 96.7% vs. 97.4%, with difference: -2.9% and -2.9%, p = 0.009 and 0.010, respectively). The frequency of adverse events was 39.0%, 56.1%, and 71.0% in VA-dual, VAC-triple, and bismuth-quadruple therapies, respectively. CONCLUSIONS: VA-dual and VA-triple therapies are highly effective and noninferior to bismuth-quadruple therapy in Southern China. Given the lower adverse effects and fewer antibiotic use, VA-dual therapy is the preferred first-line treatment for HP infection. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=14131.

Glycaemic control is a modifiable risk factor for hepatocellular carcinoma and liver-related mortality in patients with diabetes.

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.

Effect of metabolic dysfunction-associated steatotic liver disease on BNT162b2 immunogenicity against the severe acute respiratory syndrome coronavirus 2 omicron variant.

BACKGROUND AND AIM: We aimed to investigate the effect of metabolic dysfunction-associated steatotic liver disease (MASLD) on three-dose BNT162b2 immunogenicity to the omicron variant. METHODS: Adult recipients of three doses of BNT162b2 were prospectively recruited between May and December 2021. The serology of the neutralizing antibody by live virus microneutralization (vMN) to the omicron variant was measured at baseline, day 180, and day 360 after the first dose. The primary outcome was seroconversion (vMN titer ≥ 10) at day 360. Exposure of interest was MASLD, defined as hepatic steatosis (controlled attenuation parameter ≥ 248 dB/m on transient elastography) plus at least one of five cardiometabolic risk factors. Subjects with prior COVID-19 were excluded. A multivariable logistic regression model was used to derive the adjusted odds ratio of seroconversion with MASLD by adjusting for age, sex, antibiotic use, and proton pump inhibitor use. RESULTS: One hundred forty-eight BNT162b2 recipients (male: 48 [32.4%]; median age: 51.0 years [interquartile range, IQR: 44.5-57.3]) were recruited. The median time from the first dose to the third dose was 8.5 months (IQR: 7.9-8.9). MASLD subjects had a lower seroconversion rate than non-MASLD ones (89.6% vs 99.0%; P = 0.007). MASLD was the only independent risk factor for seroconversion (adjusted odds ratio: 0.051, 95% confidence interval: 0.002-0.440). Subgroup analysis of immunogenicity at 4 months after the third dose shows significantly lower vMN titer (13.06 [IQR: 7.69-22.20] vs 33.49 [IQR: 24.05-46.53]; P = 0.004) and seroconversion rate (76.9% vs 97.4%; P = 0.016) in MASLD than non-MASLD subjects, but not within 4 months from the third dose (vMN titer: 46.87 [IQR: 33.12-66.02] vs 41.86 [IQR: 34.47-50.91], P = 0.240; seroconversion rate: 94.3% vs 100%, P = 0.131). CONCLUSION: Metabolic dysfunction-associated steatotic liver disease was a risk factor for poorer immunogenicity to the omicron variant, with a more pronounced waning effect compared among three-dose BNT162b2 recipients.

Baseline Gut Microbiota Was Associated with Long-Term Immune Response at One Year Following Three Doses of BNT162b2.

BACKGROUND: This study explored neutralizing IgG antibody levels against COVID-19 decline over time post-vaccination. We conducted this prospective cohort study to investigate the function of gut microbiota in the host immune response following three doses of BNT162b2. METHODS: Subjects who received three doses of BNT162b2 were recruited from three centers in Hong Kong. Blood samples were obtained before the first dose and at the one-year timepoint for IgG ELISA to determine the level of neutralizing antibody (NAb). The primary outcome was a high immune response (NAb > 600 AU/mL). We performed shotgun DNA metagenomic sequencing on baseline fecal samples to identify bacterial species and metabolic pathways associated with high immune response using linear discriminant analysis effect size analysis. RESULTS: A total of 125 subjects were recruited (median age: 52 years [IQR: 46.2-59.0]; male: 43 [34.4%]), and 20 were regarded as low responders at the one-year timepoint. Streptococcus parasanguinis (log10LDA score = 2.38, p = 0.003; relative abundance of 2.97 × 10-5 vs. 0.03%, p = 0.001), Bacteroides stercoris (log10LDA score = 4.29, p = 0.024; relative abundance of 0.14% vs. 2.40%, p = 0.014) and Haemophilus parainfluenzae (log10LDA score = 2.15, p = 0.022; relative abundance of 0.01% vs. 0, p = 0.010) were enriched in low responders. Bifidobacterium pseudocatenulatum (log10LDA score = 2.99, p = 0.048; relative abundance of 0.09% vs. 0.36%, p = 0.049) and Clostridium leptum (log10LDA score = 2.38, p = 0.014; relative abundance of 1.2 × 10-5% vs. 0, p = 0.044) were enriched in high responders. S. parasanguinis was negatively correlated with the superpathway of pyrimidine ribonucleotides de novo biosynthesis (log10LDA score = 2.63), which contributes to inflammation and antibody production. H. parainfluenzae was positively correlated with pathways related to anti-inflammatory processes, including the superpathway of histidine, purine, and pyrimidine biosynthesis (log10LDA score = 2.14). CONCLUSION: Among three-dose BNT162b2 recipients, S. parasanguinis, B. stercoris and H. parainfluenzae were associated with poorer immunogenicity at one year, while B. pseudocatenulatum and C. leptum was associated with a better response.

Synergistic association of sodium-glucose cotransporter-2 inhibitor and metformin on liver and non-liver complications in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease.

OBJECTIVE: Type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (diabetic MASLD) frequently coexist and worsen liver and non-liver outcomes, but effective pharmacological therapies are limited. We aimed to evaluate the long-term effect of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) on liver and non-liver outcomes among patients with diabetic MASLD. DESIGN: This population-based cohort study retrieved patients with diabetic MASLD from Merative Marketscan Research Databases (April 2013 and December 2021). The active comparator was other glucose-lowering drugs (oGLDs). Primary outcomes were liver complications including hepatocellular carcinoma (HCC) and liver cirrhosis, as well as non-liver complications including cardiovascular disease (CVD), chronic kidney disease (CKD) and non-liver cancer. Propensity score matching was applied and Cox regression models were conducted. RESULTS: Compared with oGLD, SGLT-2i users had significantly lower risk of HCC (HR 0.76, 95% CI 0.62 to 0.93), liver cirrhosis (HR 0.80, 95% CI 0.76 to 0.84), CVD (HR 0.82, 95% CI 0.79 to 0.85) and CKD (HR 0.66, 95% CI 0.62 to 0.70), non-liver cancer (HR 0.81, 95% CI 0.76 to 0.86). Compared with patients without metformin and SGLT-2i, a stepwise decreasing risk was observed in users of either metformin or SGLT-2i (HRs 0.76-0.97) and in users of both medications (HRs 0.58-0.79). The lower risk also was shown in liver decompensation, compensated cirrhosis, major CVD, end-stage renal disease and specific common cancers (HRs 0.61-0.84). CONCLUSION: In a nationwide cohort, SGLT-2i users were associated with a substantially lower risk of liver and non-liver complications than oGLD users among patients with diabetic MASLD. The risk was further reduced with concomitant metformin use.

Immediate postpartum cessation of tenofovir did not increase risk of virological or clinical relapse in highly viremic pregnant mothers with chronic hepatitis B infection.

Background & Aims: Peripartum prophylaxis (PP) with tenofovir disoproxil fumarate (TDF) is the standard of care to prevent mother-to-child transmission of chronic hepatitis B (CHB) infection in mothers who are highly viremic. We investigated the maternal and infant outcomes in a large Chinese cohort of TDF-treated CHB pregnant participants. Methods: In this prospective study, treatment-naive mothers with CHB and highly viremic (HBV DNA ≥200,000 IU/ml) but without cirrhosis were treated with TDF at 24-28 weeks of pregnancy. In accordance with Chinese CHB guidelines, TDF was stopped at delivery or ≥4 weeks postpartum. Serum HBV DNA and alanine aminotransferase were monitored every 6-8 weeks to determine virological relapse (VR). Infants received standard neonatal immunization, and HBV serology was checked at 7-12 months of age. Results: Among 330 participants recruited (median age 30, 82.7% HBeAg+, median HBV DNA 7.82 log IU/ml), TDF was stopped at delivery in 66.4% and at ≥4 weeks in 33.6%. VR was observed in 98.3%, among which 11.6% were retreated with TDF. Timing of TDF cessation did not alter the risk of VR (99.0 vs. 96.9%), clinical relapse (19.5 vs. 14.3%), or retreatment (12.6 vs. 10.1%) (all p > 0.05). A similar proportion of patients developed alanine aminotransferase flare five times (1.1 vs. 2.1%; p = 0.464) and 10 times (0.5 vs. 0%; p = 0.669) above the upper limit of normal (ULN) in the early withdrawal and late withdrawal groups, respectively. No infants developed HBsAg-positivity. Conclusions: PP-TDF and neonatal immunization were highly effective in preventing mother-to-child transmission of HBV in mothers who are highly viremic. Timing of cessation of PP-TDF did not affect the risk of VR or retreatment. Impact and Implications: In pregnant mothers with chronic hepatitis B infection who are started on peripartum tenofovir to prevent mother-to-child-transmission (MTCT), the optimal timing for antiviral withdrawal during the postpartum period remains unknown. This prospective study demonstrates that stopping tenofovir immediately at delivery, compared with longer treatment duration of tenofovir, did not lead to an increased risk of virological relapse, retreatment, or transmission of the virus to the baby. Shortening the duration of peripartum antiviral prophylaxis from 12 weeks to immediately after delivery can be considered. The immediate withdrawal of peripartum tenofovir, combined with standard neonatal immunization schemes, is 100% effective in preventing MTCT among pregnant mothers with CHB who are highly viremic, with a high rate of vaccine response in infants.

Proton pump inhibitors associated with severe COVID-19 among two-dose but not three-dose vaccine recipients.

BACKGROUND AND AIM: Proton pump inhibitors (PPIs) may increase the risk of COVID-19 among non-vaccinated subjects via various mechanisms, including gut dysbiosis. We aimed to investigate whether PPIs also affect the clinical outcomes of COVID-19 among vaccine recipients. METHODS: This was a territory-wide cohort study of 3 272 286 vaccine recipients (aged ≥ 18 years) of ≥ 2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior gastrointestinal surgery, immunocompromised status, and prior COVID-19. The primary outcome was COVID-19, and secondary outcomes included COVID-19-related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Covariates include age, sex, the Charlson Comorbidity Index, comorbidities, and concomitant medication use. Subjects were followed from index date (first dose of vaccination) until outcome occurrence, death, additional dose of vaccination, or March 31, 2022. Exposure was pre-vaccination PPI use (any prescription within 90 days before the index date). Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with PPI use. RESULTS: Among 439 154 PS-matched two-dose vaccine recipients (mean age: 65.3 years; male: 45.7%) with a median follow-up of 6.8 months (interquartile range: 2.6-7.9), PPI exposure was associated with a higher risk of COVID-19 (aIRR: 1.08; 95% confidence interval [95% CI]: 1.05-1.10), hospitalization (aIRR: 1.20; 95% CI: 1.08-1.33), and severe infection (aIRR: 1.57; 95% CI: 1.24-1.98). Among 188 360 PS-matched three-dose vaccine recipients (mean age: 62.5 years; male: 49.0%; median follow-up: 9.1 months [interquartile range: 8.0-10.9]), PPIs were associated with higher infection risk (aIRR: 1.11; 95% CI: 1.08-1.15) but not other outcomes. CONCLUSIONS: Although PPI use was associated with a higher COVID-19 risk, severe infection was limited to two-dose but not three-dose vaccine recipients.

Benefit and Harm of Aspirin on Mortality From Gastrointestinal Cancers Vs Bleeding in Helicobacter pylori-Eradicated Patients.

BACKGROUND & AIMS: We investigated the benefit-risk profile of aspirin on mortality reduction from chemoprevention of gastrointestinal (GI) cancer vs excess mortality from bleeding among Helicobacter pylori-eradicated patients, and its interaction with proton pump inhibitors (PPIs). METHODS: H pylori-eradicated patients (between 2003 and 2016), identified from a territory-wide database, were observed from the date of H pylori therapy until death or the end of the study (July 2020). Primary exposure was aspirin use as time-varying variable. The primary outcome was GI cancer-related (gastrointestinal, hepatobiliary, or pancreatic cancer) death and the secondary outcome was bleeding-related (gastrointestinal bleeding or intracranial bleeding) death. The adjusted hazard ratio (aHR) of outcomes was calculated by multivariable Cox model after adjusting for age, sex, comorbidities, and concomitant medications. The benefit-risk profile was expressed as the adjusted absolute risk difference of cancer-related deaths and bleeding-related deaths between aspirin users and nonusers. RESULTS: A total of 87,967 subjects were followed up for a median of 10.1 years, with 1294 (1.5%) GI cancer-related deaths and 304 (0.3%) bleeding-related deaths. Aspirin was associated with lower GI cancer-related mortality (aHR, 0.51; 95% CI, 0.42-0.61), but higher bleeding-related mortality (aHR, 1.52; 95% CI, 1.11-2.08). Among PPI users, the aHR of bleeding-related mortality with aspirin was 1.06 (95% CI, 0.70-1.63). For the whole cohort, the adjusted absolute risk difference between aspirin users and nonusers was 7 (95% CI, 5-8) fewer cancer-related and 1 (95% CI, 0.3-3) more bleeding-related death per 10,000 person-years. Among concomitant PPI-aspirin use, there were 9 (95% CI, 8-10) fewer cancer-related deaths per 10,000 person-years without an increase in bleeding-related deaths. CONCLUSIONS: GI cancer mortality benefit from aspirin outweighs bleeding-related mortality in H pylori-eradicated subjects, which is enhanced further by PPI use.

Optimal glycaemic control and the reduced risk of colorectal adenoma and cancer in patients with diabetes: a population-based cohort study.

OBJECTIVE: Whether varying degrees of glycaemic control impact colonic neoplasm risk in patients with diabetes mellitus (DM) remains uncertain. DESIGN: Patients with newly diagnosed DM were retrieved from 2005 to 2013. Optimal glycaemic control at baseline was defined as mean haemoglobin A1c (HbA1c)<7%. Outcomes of interest included colorectal cancer (CRC) and colonic adenoma development. We used propensity score (PS) matching with competing risk models to estimate subdistribution HRs (SHRs). We further analysed the combined effect of baseline and postbaseline glycaemic control based on time-weighted mean HbA1c during follow-up. RESULTS: Of 88 468 PS-matched patients with DM (mean (SD) age: 61.5 (±11.7) years; male: 47 127 (53.3%)), 1229 (1.4%) patients developed CRC during a median follow-up of 7.2 (IQR: 5.5-9.4) years. Optimal glycaemic control was associated with lower CRC risk (SHR 0.72; 95% CI 0.65 to 0.81). The beneficial effect was limited to left-sided colon (SHR 0.71; 95% CI 0.59 to 0.85) and rectum (SHR 0.71; 95% CI 0.57 to 0.89), but not right-sided colon (SHR 0.86; 95% CI 0.67 to 1.10). Setting suboptimal glycaemic control at baseline/postbaseline as a reference, a decreased CRC risk was found in optimal control at postbaseline (SHR 0.79), baseline (SHR 0.71) and both time periods (SHR 0.61). Similar associations were demonstrated using glycaemic control as a time-varying covariate (HR 0.75). A stepwise greater risk of CRC was found (Ptrend<0.001) with increasing HbA1c (SHRs 1.34, 1.30, 1.44, 1.58 for HbA1c 7.0% to <7.5%, 7.5% to <8.0%, 8.0% to <8.5% and ≥8.5%, respectively). Optimal glycaemic control was associated with a lower risk of any, non-advanced and advanced colonic adenoma (SHRs 0.73-0.87). CONCLUSION: Glycaemic control in patients with DM was independently associated with the risk of colonic adenoma and CRC development with a biological gradient.

Low Bone Mineral Density as a Risk Factor for Liver Cirrhosis: A Prospective Cohort Study.

CONTEXT: Bone metabolism interplays with liver metabolism, also known as the liver-bone axis. Osteoporosis is a common complication of cirrhosis, but whether bone mineral density (BMD) can predict cirrhosis development is unknown. OBJECTIVE: This study aims to investigate the relationship between BMD and the risk of incident cirrhosis in the Hong Kong Osteoporosis Study (HKOS). METHODS: BMD was measured at the lumbar spine, femoral neck, total hip, and trochanter of 7,752 participants by the dual-energy X-ray absorptiometer (DXA), and the incidence of cirrhosis and mortality were followed by linking to the territory-wide electronic health records database. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% CI. RESULTS: With a median follow-up of 18.43 years, 42 incident cirrhosis were identified. Higher BMD T-scores at the femoral neck, total hip and trochanter were significantly associated with a reduced risk of cirrhosis (femoral neck: HR 0.56, 95% CI 0.39 to 0.82; total hip: HR 0.60, 95% CI 0.44 to 0.82; trochanter: HR 0.63, 95% CI 0.46 to 0.88). Similar associations were observed in participants without risk factors of cirrhosis at the baseline and further adjusting for the baseline level of alkaline phosphatase, albumin, and alanine transaminase. Consistent relationships in multiple sensitivity analyses suggest the robustness of the results. CONCLUSION: Low BMD could be a novel risk factor and early predictor for cirrhosis, with consistent associations observed in multiple sensitivity analyses.

Association between Gut Microbiota Composition and Long-Term Vaccine Immunogenicity following Three Doses of CoronaVac.

BACKGROUND: Neutralizing antibody level wanes with time after COVID-19 vaccination. We aimed to study the relationship between baseline gut microbiota and immunogenicity after three doses of CoronaVac. METHODS: This was a prospective cohort study recruiting three-dose CoronaVac recipients from two centers in Hong Kong. Blood samples were collected at baseline and one year post-first dose for virus microneutralization (vMN) assays to determine neutralization titers. The primary outcome was high immune response (defined as with vMN titer ≥ 40). Shotgun DNA metagenomic sequencing of baseline fecal samples identified potential bacterial species and metabolic pathways using Linear Discriminant Analysis Effect Size (LEfSe) analysis. Univariate and multivariable logistic regression models were used to identify high response predictors. RESULTS: In total, 36 subjects were recruited (median age: 52.7 years [IQR: 47.9-56.4]; male: 14 [38.9%]), and 18 had low immune response at one year post-first dose vaccination. Eubacterium rectale (log10LDA score = 4.15, p = 0.001; relative abundance of 1.4% vs. 0, p = 0.002), Collinsella aerofaciens (log10LDA score = 3.31, p = 0.037; 0.39% vs. 0.18%, p = 0.038), and Streptococcus salivarius (log10LDA score = 2.79, p = 0.021; 0.05% vs. 0.02%, p = 0.022) were enriched in low responders. The aOR of high immune response with E. rectale, C. aerofaciens, and S. salivarius was 0.03 (95% CI: 9.56 × 10-4-0.32), 0.03 (95% CI: 4.47 × 10-4-0.59), and 10.19 (95% CI: 0.81-323.88), respectively. S. salivarius had a positive correlation with pathways enriched in high responders like incomplete reductive TCA cycle (log10LDA score = 2.23). C. aerofaciens similarly correlated with amino acid biosynthesis-related pathways. These pathways all showed anti-inflammation functions. CONCLUSION: E. rectale,C. aerofaciens, and S. salivarius correlated with poorer long-term immunogenicity following three doses of CoronaVac.

Effects of empagliflozin on liver fat in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus: A randomized, double-blind, placebo-controlled trial.

BACKGROUND AND AIMS: We investigated whether empagliflozin reduces hepatic steatosis in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus. APPROACH AND RESULTS: This was an investigator-initiated, double-blind, randomized, placebo-controlled trial recruiting adult subjects from the community. Eligible subjects without diabetes mellitus (fasting plasma glucose < 7 mmol/L and HbA1c < 6.5%) who had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 5% were randomly allocated to receive empagliflozin 10 mg daily or placebo (1:1 ratio) for 52 weeks (end of treatment, EOT). MRI-PDFF was conducted at baseline and EOT. The primary outcome was the difference in change of MRI-PDFF between the 2 groups at EOT. Secondary outcomes were hepatic steatosis resolution (MRI-PDFF < 5%), alanine aminotransferase drop ≥ 17 U/L, MRI-PDFF decline ≥ 30%, a combination of both, and changes of anthropometric and laboratory parameters at EOT. All outcomes were based on intention-to-treat analysis. Of 98 recruited subjects (median age: 55.7 y [IQR:49.5-63.4]; male:54 [55.1%]), 97 (empagliflozin:49, placebo:48; median MRI-PDFF:9.7% vs 9.0%) had MRI-PDFF repeated at EOT. The Empagliflozin group had a greater reduction in median MRI-PDFF compared to the placebo group (-2.49% vs. -1.43%; p = 0.025), with a nonsignificant trend of resolution of hepatic steatosis (44.9% vs. 28.6%; p = 0.094). There was no significant difference in alanine aminotransferase drop ≥ 17 U/L (16.3% vs. 12.2%; p = 0.564), MRI-PDFF drop ≥ 30% (49.0% vs. 40.8%; p = 0.417), and composite outcome (8.2% vs. 8.2%; p = 1.000). Empagliflozin group had a greater drop in body weight (-2.7 vs. -0.2 kg), waist circumference (-2.0 vs. 0 cm), fasting glucose (-0.3 vs. 0 mmol/L), and ferritin (-126 vs. -22 pmol/L) (all p < 0.05). CONCLUSIONS: Empagliflozin for 52 weeks reduces hepatic fat content in subjects with nondiabetic metabolic dysfunction-associated steatotic liver disease. (ClinicalTrials.gov Identifier: NCT04642261).

Mortality in patients with chronic hepatitis B treated with tenofovir or entecavir: A multinational study.

BACKGROUND AND AIM: The benefits of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in reducing the development of chronic hepatitis B (CHB)-related hepatocellular carcinoma remain controversial. Whether mortality rates differ between patients with CHB treated with ETV and those treated with TDF is unclear. METHODS: A total of 2542 patients with CHB treated with either ETV or TDF were recruited from a multinational cohort. A 1:1 propensity score matching was performed to balance the differences in baseline characteristics between the two patient groups. We aimed to compare the all-cause, liver-related, and non-liver-related mortality between patients receiving ETV and those receiving TDF. RESULTS: The annual incidence of all-cause mortality in the entire cohort was 1.0/100 person-years (follow-up, 15 757.5 person-years). Patients who received TDF were younger and had a higher body mass index, platelet count, hepatitis B virus deoxyribonucleic acid levels, and proportion of hepatitis B e-antigen seropositivity than those who received ETV. The factors associated with all-cause mortality were fibrosis-4 index > 6.5 (hazard ratio [HR]/confidence interval [CI]: 3.13/2.15-4.54, P < 0.001), age per year increase (HR/CI: 1.05/1.04-1.07, P < 0.001), alanine aminotransferase level per U/L increase (HR/CI: 0.997/0.996-0.999, P = 0.003), and γ-glutamyl transferase level per U/L increase (HR/CI: 1.002/1.001-1.003, P < 0.001). No significant difference in all-cause mortality was observed between the ETV and TDF groups (log-rank test, P = 0.69). After propensity score matching, no significant differences in all-cause, liver-related, or non-liver-related mortality were observed between the two groups. CONCLUSIONS: Long-term outcomes of all-cause mortality and liver-related and non-liver-related mortality did not differ between patients treated with ETV and those receiving TDF.