-
Hepatology Communications Oct 2023NAFLD is the most common chronic liver disease worldwide, characterized by lipid accumulation in the liver, and usually evolves from steatohepatitis to fibrosis,... (Review)
Review
NAFLD is the most common chronic liver disease worldwide, characterized by lipid accumulation in the liver, and usually evolves from steatohepatitis to fibrosis, cirrhosis, or even HCC. Its incidence is rapidly rising in parallel with the increasing prevalence of obesity and metabolic syndrome. Current therapies are limited to lifestyle changes including dietary intervention and exercise, in which dietary modification exerts an important part in losing weight and preventing NAFLD. In this review, we briefly discuss the roles and mechanisms of dietary components including fructose, non-nutritive sweeteners, fat, proteins, and vitamins in the progression or prevention of NAFLD. We also summarize several popular dietary patterns such as calorie-restricted diets, intermittent fasting, ketogenic diets, Mediterranean diets, and dietary approach to stop hypertension diets and compare the effects of low-fat and low-carbohydrate diets in preventing the development of NAFLD. Moreover, we summarize the potential drugs targeting metabolic-related targets in NAFLD.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Carcinoma, Hepatocellular; Liver Neoplasms; Nutrients
PubMed: 37756016
DOI: 10.1097/HC9.0000000000000234 -
Best Practice & Research. Clinical... Oct 2023Faecal hemoglobin concentrations (f-Hb) can be quantitated using faecal immunochemical test for haemoglobin (FIT) analytical systems. FIT are of proven value and widely... (Review)
Review
Faecal hemoglobin concentrations (f-Hb) can be quantitated using faecal immunochemical test for haemoglobin (FIT) analytical systems. FIT are of proven value and widely used in colorectal cancer (CRC) screening. Several factors affect f-Hb including sex, age, deprivation, geographical region, and FIT system. Thus, FIT data may not be transferable. Women are disadvantaged in programmes using a single f-Hb threshold for all participants, but risk scoring or sex stratified thresholds could be used to minimise this problem. In addition, low but detectable f-Hb, below the threshold, implies future risk of CRC. In several countries, where colonoscopy resources are constrained, FIT are now accepted as of added value in assessment of patients presenting in primary or secondary care with symptoms, although some serious colorectal disease is missed. Elevated f-Hb in the absence of any discernible colorectal lesions is common and has been found in several diseases with a systemic inflammatory component, including circulatory, respiratory, digestive, neuropsychological, blood and endocrine diseases, and others. There is growing evidence for the value of f-Hb in post-polypectomy surveillance, potentially saving costs and colonoscopy. There may be a role for FIT systems which have lower limits of detection than currently available methods. The faecal material remaining in FIT specimen collection devices could be used for further studies, including assessment of the microbiome. The estimation of f-Hb is now a mature investigative tool but further research will undoubtedly expand applications of value.
Topics: Humans; Female; Colorectal Neoplasms; Feces; Occult Blood; Hemoglobins; Colonoscopy; Early Detection of Cancer; Sensitivity and Specificity
PubMed: 37852705
DOI: 10.1016/j.bpg.2023.101833 -
Acta Gastro-enterologica Belgica 2023
Review
Topics: Humans; Eosinophilic Esophagitis; Esophagitis; Enteritis; Gastritis; Eosinophilia
PubMed: 38240548
DOI: 10.51821/86.4.12001 -
United European Gastroenterology Journal Nov 2023
Topics: Humans; Acute-On-Chronic Liver Failure; Liver Cirrhosis; Severity of Illness Index
PubMed: 37921760
DOI: 10.1002/ueg2.12482 -
Journal of Hepatology Aug 2023Autoimmune liver diseases are siloed into three syndromes that define clinical practice. These classifiers can, and are, challenged by variant presentations across all... (Review)
Review
Autoimmune liver diseases are siloed into three syndromes that define clinical practice. These classifiers can, and are, challenged by variant presentations across all ages, something inevitable to disease definitions that rely on interpreting (inherently variable) semi-quantitative/qualitative clinical, laboratory, pathological or radiological findings. Furthermore this categorisation is premised on an ongoing absence of definable disease aetiologies. Clinicians thus encounter individuals with biochemical, serological, and histological manifestations that are common to both primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH), often labelled as 'PSC/AIH-overlap'. In childhood the term 'autoimmune sclerosing cholangitis (ASC)' may be used, and some propose this to be a distinct disease process. In this article we champion the concept that ASC and PSC/AIH-overlap are not distinct entities. Rather, they represent inflammatory phases of PSC frequently manifesting earlier in the disease course, most notably in younger patients. Ultimately, disease outcomes remain similar to those of a more classical PSC phenotype observed in later life. Thus, we argue that it is now time to align disease names and descriptions used by clinicians across all patient subpopulations, to help unify care. This will enhance collaborative studies and ultimately contribute to rational treatment advances.
Topics: Humans; Hepatitis, Autoimmune; Cholangitis, Sclerosing; Liver Diseases; Syndrome
PubMed: 36870613
DOI: 10.1016/j.jhep.2023.02.030 -
United European Gastroenterology Journal Oct 2023Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction.
OBJECTIVE
Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed.
METHODS
We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) compared to 9931 population-based controls from the University of Michigan Health and Retirement Study; and (ii) 402 GP cases compared to 48,340 non-gastroparesis controls from the Michigan Genomics Initiative. Associations for 5,811,784 high-quality SNPs were tested on a total of 880 GP patients and 58,271 controls, using logistic mixed models adjusted for age, sex, and principal components. Gene mapping was obtained based on genomic position and expression quantitative trait loci, and a gene-set network enrichment analysis was performed. Genetic associations with clinical data were tested in GpCRC patients. Protein expression of selected candidate genes was determined in full thickness gastric biopsies from GpCRC patients and controls.
RESULTS
While no SNP associations were detected at strict significance (p ≤ 5 × 10 ), nine independent genomic loci were associated at suggestive significance (p ≤ 1 × 10 ), with the strongest signal (rs9273363, odds ratio = 1.4, p = 1 × 10 ) mapped to the human leukocyte antigen region. Computational annotation of suggestive risk loci identified 14 protein-coding candidate genes. Gene-set network enrichment analysis revealed pathways potentially involved in immune and motor dysregulation (p ≤ 0.05). The GP risk allele rs6984536A (Peroxidasin-Like; PXDNL) was associated with increased abdominal pain severity scores (Beta = 0.13, p = 0.03). Gastric muscularis expression of PXDNL also positively correlated with abdominal pain in GP patients (r = 0.8, p = 0.02). Dickkopf WNT Signaling Pathway Inhibitor 1 showed decreased expression in diabetic GP patients (p = 0.005 vs. controls).
CONCLUSION
We report preliminary GWAS findings for GP, which highlight candidate genes and pathways related to immune and sensory-motor dysregulation. Larger studies are needed to validate and expand these findings in independent datasets.
Topics: Humans; Genome-Wide Association Study; Gastroparesis; Genetic Predisposition to Disease; Abdominal Pain
PubMed: 37688361
DOI: 10.1002/ueg2.12453 -
Journal of Clinical GastroenterologyTo better understand the characteristics, treatment approaches, and outcomes of patients with esophageal lichen planus (ELP).
GOALS
To better understand the characteristics, treatment approaches, and outcomes of patients with esophageal lichen planus (ELP).
BACKGROUND
ELP is a rare, often unrecognized and misdiagnosed disorder. Data on this unique patient population are currently limited to small, single-center series.
STUDY
A multicenter, retrospective descriptive study was conducted of adults diagnosed with ELP over a 5-year period, between January 1, 2015, and October 10, 2020, from 7 centers across the United States.
RESULTS
Seventy-eight patients (average age 65 y, 86% female, 90% Caucasian) were included. Over half had at least 1 extraesophageal manifestation. Esophageal strictures (54%) and abnormal mucosa (50%) were frequent endoscopic findings, with the proximal esophagus the most common site of stricture. Approximately 20% had normal endoscopic findings. Topical steroids (64%) and/or proton pump inhibitors (74%) dominated management; endoscopic response favored steroids (43% vs. 29% respectively). Almost half of the patients required switching treatment modalities during the study period. Adjunctive therapies varied significantly between centers.
CONCLUSIONS
Given its at times subtle clinical and endoscopic signs, a high index of suspicion and biopsy will improve ELP diagnosis, especially in those with extraesophageal manifestations. Effective therapies are lacking and vary significantly. Prospective investigations into optimal treatment regimens are necessary.
Topics: Adult; Humans; Female; Aged; Male; Esophageal Diseases; Retrospective Studies; Prospective Studies; Lichen Planus; Esophageal Stenosis; Steroids
PubMed: 37436831
DOI: 10.1097/MCG.0000000000001885 -
IScience Nov 2023Digestive disorders are a significant contributor to the global burden of disease and seriously affect human quality of life. Research has already confirmed the presence...
Digestive disorders are a significant contributor to the global burden of disease and seriously affect human quality of life. Research has already confirmed the presence of pleiotropic genetic loci among digestive disorders, and studies have explored shared genetic factors among pan-cancers, including various malignant digestive disorders. However, most cross-phenotype studies within the digestive tract system have been limited to a few traits, with no systematic coverage of common benign and malignant digestive disorders. Here, we analyzed data from the UK Biobank to investigate 21 digestive disorders, exploring the genetic correlations and causal relationships between diseases, as well as the common genetic factors and potential biological pathways driving these relationships. Our findings confirmed the extensive genetic correlation and causal relationship between digestive disorders, providing important insights into the genetic etiology, causality, disease prevention, and clinical treatment of diseases.
PubMed: 37965154
DOI: 10.1016/j.isci.2023.108238 -
British Journal of Hospital Medicine... Mar 2024Volvulus describes the twisting of the intestine or colon around its mesentery. Intestinal obstruction and/or ischaemia are the most common complications of volvulus.... (Review)
Review
Volvulus describes the twisting of the intestine or colon around its mesentery. Intestinal obstruction and/or ischaemia are the most common complications of volvulus. Within the gastrointestinal tract, there is a preponderance towards colonic volvulus. The sigmoid is the most commonly affected segment, followed by the caecum, small intestine and stomach. Distinguishing between the differing anatomical locations of gastrointestinal volvulus can be challenging, but is important for the management and prognosis. This article focuses on the main anatomical sites of gastrointestinal volvulus encountered in clinical practice. The aetiology, presentation, radiological features and management options for each are discussed to highlight the key differences.
Topics: Humans; Intestinal Volvulus; Intestinal Obstruction; Colon, Sigmoid; Intestine, Small; Radiography
PubMed: 38557088
DOI: 10.12968/hmed.2023.0295 -
Journal of Hepatology Dec 2023Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD) is the fastest growing cause of hepatocellular carcinoma (HCC) worldwide. However,...
BACKGROUND & AIMS
Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD) is the fastest growing cause of hepatocellular carcinoma (HCC) worldwide. However, whether family members of individuals with MASLD also share an increased risk of developing HCC is unknown.
METHODS
This nationwide multigenerational cohort study involved family members of all Swedish adults diagnosed with biopsy-proven MASLD (1969-2017), and matched general population comparators. Using the Swedish Multi-generation Register, we identified 38,018 first-degree relatives (FDRs: parents, siblings, offspring) and 9,381 spouses of patients with MASLD, as well as 197,303 comparator FDRs and 47,572 comparator spouses. We used Cox proportional hazards models to calculate adjusted hazard ratios (aHRs) for HCC, major adverse liver outcomes (cirrhosis, decompensated liver disease or liver transplantation), liver-related mortality, extrahepatic cancer, and non-liver-related mortality.
RESULTS
Over a median of 17.6 years, the rate of the primary outcome HCC was higher in MASLD FDRs vs. comparator FDRs (13 vs. 8/100,000 person-years [PY]; aHR 1.80, 95% CI 1.36-2.37). The HCC risk was further increased in FDRs of individuals with liver fibrosis/cirrhosis (aHR 2.14, 95% CI 1.07-4.27; P = 0.03). MASLD FDRs also had higher rates of major adverse liver outcomes (73 vs. 51/100,000 PY; aHR 1.52, 95% CI 1.36-1.69) and liver-related mortality (20 vs. 11/100,000 PY; aHR 2.14, 95% CI 1.67-2.74). MASLD FDRs with any concomitant chronic liver condition experienced accelerated progression of liver disease (aHR 1.47, 95% CI 1.29-1.67). MASLD spouses were at higher risks of major adverse liver outcomes (86 vs. 74/100,000 PY; aHR 1.23, 95% CI 1.01-1.51) and liver-related mortality (25 vs. 19/100,000 PY; aHR 1.93, 95% CI 1.15-3.23), but not of HCC (aHR 1.43, 95% CI 0.87-2.35).
CONCLUSIONS
There is distinct familial clustering of adverse liver-related outcomes in families of individuals with biopsy-proven MASLD, with higher relative risks of HCC, progressive liver disease, and liver-related mortality, but absolute risks are low.
IMPACT AND IMPLICATIONS
Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly termed NAFLD) clusters in families with high genetic susceptibility and shared environmental risk factors, but the risks of developing hepatocellular carcinoma and other major liver-related outcomes in family members of individuals with MASLD are largely unknown. This large nationwide multigenerational cohort study involving family members (first-degree relatives and spouses) of individuals with biopsy-proven MASLD and of matched general population comparators found slightly increased risks of hepatocellular carcinoma in first-degree relatives, and of developing cirrhosis and liver-related mortality in all family members of individuals with biopsy-proven MASLD. The findings of this study provide large-scale evidence to inform clinical practice guidelines for recommendations on the early identification of individuals at higher risk of liver-related morbidity and mortality.
Topics: Adult; Humans; Carcinoma, Hepatocellular; Cohort Studies; Non-alcoholic Fatty Liver Disease; Liver Neoplasms; Liver Cirrhosis
PubMed: 37647992
DOI: 10.1016/j.jhep.2023.08.018