Context: A subset (approximately 3%-5%) of patients with cystic fibrosis (CF) develops severe liver disease with portal hypertension.
Objective: To assess whether any of 9 polymorphisms in 5 candidate genes (alpha(1)-antitrypsin or alpha(1)-antiprotease [SERPINA1], angiotensin-converting enzyme [ACE], glutathione S-transferase [GSTP1], mannose-binding lectin 2 [MBL2], and transforming growth factor beta1 [TGFB1]) are associated with severe liver disease in patients with CF.
Design, Setting, And Participants: Two-stage case-control study enrolling patients with CF and severe liver disease with portal hypertension (CFLD) from 63 CF centers in the United States as well as 32 in Canada and 18 outside of North America, with the University of North Carolina at Chapel Hill as the coordinating site. In the initial study, 124 patients with CFLD (enrolled January 1999-December 2004) and 843 control patients without CFLD were studied by genotyping 9 polymorphisms in 5 genes previously studied as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 patients with CFLD (enrolled January 2005-February 2007) and 1088 with no CFLD.
Main Outcome Measures: Differences in distribution of genotypes in patients with CFLD vs patients without CFLD.
Results: The initial study showed CFLD to be associated with the SERPINA1 Z allele (odds ratio [OR], 4.72; 95% confidence interval [CI], 2.31-9.61; P = 3.3 x 10(-6)) and with TGFB1 codon 10 CC genotype (OR, 1.53; 95% CI, 1.16-2.03; P = 2.8 x 10(-3)). In the replication study, CFLD was associated with the SERPINA1 Z allele (OR, 3.42; 95% CI, 1.54-7.59; P = 1.4 x 10(-3)) but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (OR, 5.04; 95% CI, 2.88-8.83; P = 1.5 x 10(-8)).
Conclusions: The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater risk (OR, approximately 5) of developing severe liver disease with portal hypertension.
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http://dx.doi.org/10.1001/jama.2009.1295 | DOI Listing |
Dig Dis Sci
January 2025
Department of Internal Medicine and Center for Recovery Medicine, Allegheny General Hospital, 1307 Federal St Suite B300, Pittsburgh, PA, 15212, USA.
Background: Alcohol use disorder and alcohol-associated liver disease is increasing in the US, with subsequent and expected increases in morbidity and mortality due to these conditions.
Aims: To determine the impact of an educational intervention regarding alcohol use disorder on gastroenterology fellows.
Methods: A before-after survey study was carried out.
Dig Dis Sci
January 2025
Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, 70401, Taiwan.
Aim: Sarcopenic obesity (SO) is associated with adverse outcomes in diseased patients. This study aimed to examine the prevalence and risks associated with SO, with a focus on the impact of SO on cardiovascular risk in patients with MASLD.
Materials And Methods: In this cross-sectional study, patients with MASLD were prospectively enrolled.
Metab Brain Dis
January 2025
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark.
Background & Aims: Hepatic encephalopathy (HE), one of the most serious prognostic factors for mortality in alcohol-related cirrhosis (ALD cirrhosis), is not recorded in Danish healthcare registries. However, treatment of HE with lactulose, the universal first-line treatment, can be identified through data on filled prescriptions. This study aimed to investigate if lactulose can be used as a surrogate marker of HE.
View Article and Find Full Text PDFDiscov Oncol
January 2025
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Introduction: Colorectal cancer (CRC) is the second most common cause of cancer-related deaths globally. The gut microbiota, along with adenomatous polyps (AP), has emerged as a plausible contributor to CRC progression. This study aimed to scrutinize the impact of the FadA antigen derived from Fusobacterium nucleatum on the expression levels of the ANXA2 ceRNA network and assess its relevance to CRC advancement.
View Article and Find Full Text PDFClin Rheumatol
January 2025
Department of Rheumatology and Immunology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
Objectives: To investigate the clinical and laboratory features of Sjögren's syndrome-associated autoimmune liver disease (SS-ALD) patients and identify potential risk and prognostic factors.
Methods: SS patients with or without ALD, who visited Tongji Hospital between the years 2011 and 2021 and met the 2012 American College of Rheumatology (ACR) classification criteria for Sjögren's syndrome, were retrospectively enrolled. The clinical and laboratory data of the enrolled patients, including autoimmune antibodies, were collected and analyzed with principal component analysis, correlation analysis, LASSO regression, and Cox regression.
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