Clinical Gastroenterology and Hepatology最新文献

Background and aims: Females with Barrett's esophagus (BE) have a lower risk of neoplastic progression than males, but sufficiently powered risk analyses are lacking. This systematic review and meta-analysis of individual patient data (IPD) aimed to provide more robust evidence on neoplastic progression risk in females.

Methods: We conducted a systematic literature search of 3 electronic databases (Medline, Embase, Google Scholar) from inception until August 2023. Eligible studies (1) reported original data on progression from nondysplastic BE, indefinite for dysplasia, or low-grade dysplasia to high-grade dysplasia or esophageal adenocarcinoma; and (2) included female and male patients. IPD were quality controlled by 2 independent reviewers. The primary outcome was the association between sex and neoplastic progression risk, adjusted for risk factors using multivariable Cox regression analysis. Secondary outcomes were sex differences in time to progression and annual progression rate.

Results: IPD were obtained from 11 of 66 eligible studies, including 2196 (31%) females. Neoplastic progression risk was lower in females (hazard ratio for males vs females, 1.44; 95% confidence interval, 1.13-1.82) after adjusting for age, smoking, medication use, hiatal hernia, BE length, and baseline pathology. The annual progression rate was 0.88% in females vs 1.29% in males. Time to progression was similar in both sexes: 3.7 years (interquartile range, 2.1-7.7 years) in females and 4.2 years (interquartile range, 2.0-8.1 years) in males.

Conclusion: Although females had a lower neoplastic progression risk, sex differences were smaller than previously reported, and time to progression was similar for both sexes. Future research should focus on other factors than sex to identify low- and high-risk BE patients.

Background & aims: Cholelithiasis is the most well-recognized risk factor for gallbladder cancer (GBC), the predominant biliary-tract malignancy; however, credibility on other modifiable exposures remains uncertain. We performed a field-wide systematic review and meta-analysis on environmental factors associated with GBC.

Methods: We systematically searched Medline/PubMed and Embase up to May 8, 2023, to identify randomized and nonrandomized studies examining environmental factors for GBC. We conducted random-effects meta-analyses focusing on longitudinal studies. Evidence from case-control studies was considered complementary. Evidence credibility was graded by prespecified criteria including the random-effects estimate, 95% confidence interval (CI), P value, statistical heterogeneity, small-study effects, and robustness to unmeasured confounding.

Results: We identified 215 eligible primary studies and performed 350 meta-analyses across 7 domains: lifestyle, reproductive, metabolic, dietary, infections, interventions, and contaminants and occupational exposures. Based on longitudinal evidence, body mass index (relative risk [RR] _{per 5-unit increase}, 1.27; 95% CI, 1.21‒1.33), hip circumference (RR _{per 5-cm increase}, 1.16; 95% CI, 1.11‒1.22), infection of bile ducts (RR, 31.7; 95% CI, 24.8-40.6), high parity (RR, 1.48; 95% CI, 1.30‒1.68), obesity (RR, 1.70; 95% CI, 1.44‒2.01), overweight (RR, 1.28; 95% CI, 1.14‒1.43), waist circumference (RR _{per 5-cm increase}, 1.14; 95% CI, 1.10‒1.18), and waist-to-height ratio (RR _{per 0.1 increase}, 1.49; 95% CI, 1.36‒1.64) were robustly associated with increased GBC risk, whereas high education (RR, 0.63; 95% CI, 0.49‒0.82) was associated with reduced risk (moderate-to-high credibility). Another 39 significant associations showed lower credibility, including different exposure scenarios of tobacco smoking, alcohol consumption, and insufficient physical activity.

Conclusions: This study offers a detailed appraisal and mapping of the evidence on modifiable factors for GBC. Further high-quality prospective studies are essential to validate emerging associations and inform preventive strategies in high-incidence areas. (Systematic review registration: CRD42023434673.).

Background and aims: Prior antibiotic use may be a factor in the rising incidence of colorectal cancer seen in those under 50 years of age (early-onset colorectal cancer [EOCRC]); however, the few studies to examine this link have reported conflicting results. Therefore, we evaluated the association between oral antibiotic use in adulthood and EOCRC in a large integrated healthcare system in the United States.

Methods: A population-based nested case-control study was conducted among Kaiser Permanente Northern California patients 18-49 years of age diagnosed with EOCRC (adenocarcinoma of the colon or rectum) in 1998-2020 who had ≥2 years of continuous pharmacy benefit prior to diagnosis. Cases were matched 4:1 to healthy controls on birth year, sex, race and ethnicity, medical facility, and duration of pharmacy benefit. Antibiotic exposure >1 year before the diagnosis/index date was assessed using prescribing records. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals. A sensitivity analysis was performed among those with ≥10 years of continuous prescribing records.

Results: A total of 1359 EOCRC cases were matched to 4711 healthy controls. Antibiotic use in adulthood was not significantly associated with EOCRC in unadjusted or adjusted analyses (adjusted odds ratio, 1.04; 95% confidence interval, 0.94-1.26). No associations were seen for cumulative number of oral antibiotic dispensations or for any prior period of antibiotic exposure.

Conclusions: In a large U.S. healthcare setting, there was no conclusive evidence of an association between oral antibiotic use in adulthood and risk of EOCRC.

Background & aims: Metabolic dysfunction-associated steatohepatitis (MASH) and fibrotic MASH are significant health challenges. This multi-national study aimed to validate the acMASH index (including serum creatinine and aspartate aminotransferase concentrations) for MASH diagnosis and develop a new index (acFibroMASH) for non-invasively identifying fibrotic MASH and exploring its predictive value for liver-related events (LREs).

Methods: We analyzed data from 3004 individuals with biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD) across 29 Chinese and 9 international cohorts to validate the acMASH index and develop the acFibroMASH index. Additionally, we utilized the independent external data from a multi-national cohort of 9034 patients with MAFLD to examine associations between the acFibroMASH index and the risk of LREs.

Results: In the pooled global cohort, the acMASH index identified MASH with an area under the receiver operating characteristic curve (AUROC) of 0.802 (95% confidence interval [CI], 0.786-0.818). The acFibroMASH index (including the acMASH index plus liver stiffness measurement) accurately identified fibrotic MASH with an AUROC of 0.808 in the derivation cohort and 0.800 in the validation cohort. Notably, the AUROC for the acFibroMASH index was 0.835 (95% CI, 0.786-0.882), superior to that of the FAST score at 0.750 (95% CI, 0.693-0.800; P < .01) in predicting the 5-year risk of LREs. Patients with acFibroMASH >0.39 had a higher risk of LREs than those with acFibroMASH <0.15 (adjusted hazard ratio, 11.23; 95% CI, 3.98-31.66).

Conclusions: This multi-ethnic study validates the acMASH index as a reliable, noninvasive test for identifying MASH. The newly proposed acFibroMASH index is a reliable test for identifying fibrotic MASH and predicting the risk of LREs.

Background & aims: Whether gastric cancer (GC) precursor lesions progress to invasive cancer at similar rates globally remains unknown. We conducted a systematic review and meta-analysis to determine the progression of precursor lesions to GC in countries with low versus medium/high incidence.

Methods: We searched relevant databases for studies reporting the progression of endoscopically confirmed precursor lesions to GC. Studies were stratified by low (<6 per 100,000) or medium/high (≥6 per 100,000) GC incidence countries. Random-effects models were used to estimate the progression rates of atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia to GC per 1000 person-years.

Results: Among the 5829 studies identified, 44 met our inclusion criteria. The global pooled estimates of the progression rate per 1000 person-years were 2.09 (95% confidence interval, 1.46-2.99), 2.89 (2.03-4.11), and 10.09 (5.23-19.49) for AG, IM, and dysplasia, respectively. The estimated progression rates per 1000 person-years for low versus medium/high GC incidence countries, respectively, were 0.97 (0.86-1.10) versus 2.47 (1.70-2.99) for AG (P < .01), 2.37 (1.43-3.92) versus 3.47 (2.13-5.65) for IM (P = .29), and 5.51 (2.92-10.39) versus 14.80 (5.87-37.28) for dysplasia (P = .08). There were no differences for progression of AG between groups when high-quality studies were compared.

Conclusions: Similar progression rates of IM and dysplasia were observed among low and medium/high GC incidence countries. This suggests that the potential benefits of surveillance for these lesions in low-risk regions may be comparable with those of population-wide interventions in high-risk regions. Further prospective studies are needed to confirm these findings and inform global screening and surveillance guidelines.