Clinical Gastroenterology and Hepatology最新文献

Background & aims: Crohn's disease (CD) has emerged as a global disease, with the fastest rise in incidence in Asia. The impact of immigration (reflecting early-life exposure to one environment and later life to another) on disease phenotype, behavior, and seropositivity has not been examined previously.

Methods: We phenotyped a cohort of U.S.-residing (immigrant) South Asian patients with CD (SA-CD) and control subjects from 3 U.S. hospitals compared with native SA-CD and control subjects from India and Singapore. These cohorts were compared with a prospective cohort of 1679 U.S.-born White patients with CD (White-CD). Detailed disease phenotype, treatment, acculturation, environmental exposures, and serologies were ascertained.

Results: Our study consisted of 260 immigrant SA-CD and control subjects, 198 native SA-CD and control subjects, and 1679 White-CD. Both native (59%; P = .02) and immigrant (55%; P = .15) SA-CD demonstrated male predominance compared with White-CD (49%). The mean age at diagnosis for second-generation immigrants (17.7 years) was significantly lower than first-generation immigrants (34 years), native SA-CD (31.7 years) and White-CD (27.7 years); the age at diagnosis was also younger in Western/bicultural-identifying compared with Asian-identifying immigrants (P < .05). Second-generation patients with CD were more likely to have B1 disease compared with native and first-generation SA-CD (odds ratio, 3.48; P = .007). Immigrant patients with CD had higher frequency of perianal involvement compared with native SA-CD and White-CD. However, native-SA-CD more commonly had stricturing disease. The immigrant SA-CD cohort had higher CBir1 flagellin antibody (49%) and anti-outer membrane porin C antibody (19%) positivity rates than anti-Saccharomyces cerevisiae antibody (13%).

Conclusions: Our international, multicenter study identified both commonalities as well as unique differences in disease phenotype, behavior, serological patterns, and environmental factors by geography and immigrant status. We highlight the importance of changing environment on CD phenotypic expression.

Background & aims: Cholestatic liver diseases are a heterogeneous group of conditions that can remain unexplained despite a comprehensive diagnostic assessment. Genetic disorders may underlie many of these unexplained adult-onset cholestasis cases. However, genetic testing in adults has been focused on genes linked to progressive familial intrahepatic cholestasis (PFIC). This study evaluated the diagnostic utility of whole exome sequencing (WES) by targeting a broader set of genes beyond PFIC genes.

Methods: Adults with unexplained cholestatic liver disease from one tertiary center underwent WES. Pathogenic and rare damaging variants in candidate cholestatic and liver disease genes were prioritized, and genotype-phenotype correlations were conducted.

Results: Twenty-one patients with three distinct cholestatic phenotypes (recurrent lithiasis, intrahepatic cholestasis, and primary sclerosing cholangitis with unusual features) were included. WES yielded a genetic diagnosis of inherited cholestatic or liver disorder mimicking the cholestatic phenotype in 5 cases (23.8%). ABCB4 was the causative gene in 2 cases (40.0%), whereas genes outside the PFIC spectrum (ABCC2, PPOX, APOB) accounted for the other 3 (60.0%).

Conclusions: This study highlights the value of WES in the diagnostic workup of adult-onset cholestatic liver disease and expands our understanding of its genetic landscape, paving the way for larger-scale studies.

Background & aims: Clostridioides difficile infection (CDI) poses a significant health risk to immunocompromised hosts due to the increased risk of severe infection and recurrence. Microbiota-based therapies have emerged as a promising strategy for CDI, but safety and efficacy in immunocompromised populations remain underexplored.

Methods: A comprehensive literature search across Ovid MEDLINE, Ovid EMBASE, Clinicaltrials.gov, and Scopus from inception until December 16, 2024, identified studies meeting inclusion criteria, covering fecal microbiota transplantation (FMT) for recurrent CDI (rCDI) in immunocompromised individuals, including those on immunosuppressants, transplant recipients, undergoing chemotherapy, and with advanced HIV. Case reports and studies not separately reporting outcomes in immunocompromised patients were excluded. Statistical analysis was performed using random-effects models to account for heterogeneity among studies.

Results: A total of 44 studies (31 full-text articles, 13 abstracts) were included, comprising 3476 participants, of whom 1208 were immunocompromised. The population included solid organ transplant recipients (n = 219), patients with cancer on chemotherapy (n = 101), hematopoietic stem cell transplant recipients (n = 29), and advanced HIV patients (n = 11). The most common FMT route was colonoscopy (n = 12 studies), followed by upper gastrointestinal routes, capsules, and rectal retention enemas. The clinical resolution rate after a single FMT was 75.3% (95% confidence interval [CI], 71.7%-78.6%), increasing to 87.4% (95% CI, 84.8%-89.6%) with consecutive treatments. The recurrence rate was 23.9% (95% CI, 19.2%-29.4%), and the serious adverse event rate was 10.1% (95% CI, 6.7%-14.8%).

Conclusions: The safety and effectiveness outcomes of FMT in mild to moderately immunocompromised populations for rCDI are comparable to those in immunocompetent cohorts.

Background & aims: Although the clinical burden of metabolic dysfunction-associated steatohepatitis (MASH) is well-known, its economic burden is less well-described. We estimated MASH's economic burden in several regions of the world including the United States (U.S.), Germany, Spain, France, Italy, the United Kingdom (UK), Japan, Saudi Arabia, and Brazil over the next 2 decades.

Methods: A 1-year cycle Markov model projected MASH progression from 2021 to 2040, incorporating 2020 prevalent cases and annual incident cases (2021-2040). Transition probabilities were derived from the literature, calibrated using national estimates of prevalence rates for type 2 diabetes and obesity, and adjusted against observed incidences of decompensated cirrhosis, hepatocellular carcinoma, and liver transplants. MASH-related direct costs, productivity losses, and quality-of-life were updated annually based on projected disease stage. Future economic burdens were adjusted using country-specific inflation rates from the International Monetary Fund.

Results: MASH prevalence is projected to increase (2021-2040): United States (6.71%-7.41%), Germany (4.43%-4.97%), Spain (4.50%-5.38%), France (4.04%-4.50%), Italy (4.58%-5.37%), United Kingdom (4.75%-5.21%), Japan (3.67%-5.02%), Brazil (7.19%-7.52%), and Saudi Arabia (7.39%-7.50%). The prevalence of advanced MASH (F3- compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and liver transplantations) is expected to increase by ≥20% in all countries. Direct annual medical costs are projected to more than double, increasing from $34.97 to $78.59 billion in the United States, $0.83 to $1.82 billion in Germany, $1.48 to $3.50 billion in Spain, $1.28 to $2.90 billion in France, $1.34 to $3.00 billion in Italy, $2.18 to $5.29 billion in the United Kingdom, $1.20 to $2.33 billion in Japan, $3.41 to $9.81 billion in Brazil, and $1.72 to $3.96 billion in Saudi Arabia. Work productivity losses are projected to more than double in most countries, and health-related quality of life will decline modestly as the burden of advanced disease increases CONCLUSIONS: Without intervention, the clinical, economic, and quality-of-life burden of MASH is projected to increase across most regions of the world. These findings highlight the urgent need for both national and global strategies to reduce the negative impact of MASH on individuals and society.