Next-generation sequencing of pancreatic cyst wall specimens obtained using micro-forceps for improving diagnostic accuracy.

Pancreatic cysts are common incidental findings, with an estimated prevalence of 13% to 15% in imaging done for other reasons. Diagnosis often relies on collection of cyst fluid, but tissue sampling using micro-forceps may allow for a more reliable diagnosis and higher yield of DNA for next-generation sequencing (NGS). The primary aim was to assess the performance of NGS in identifying mucinous cyst.

Study design for development of novel safety biomarkers of drug-induced liver injury by the translational safety biomarker pipeline (TransBioLine) consortium: a study protocol for a nested case-control study.

A lack of biomarkers that detect drug-induced liver injury (DILI) accurately continues to hinder early- and late-stage drug development and remains a challenge in clinical practice. The Innovative Medicines Initiative's TransBioLine consortium comprising academic and industry partners is developing a prospective repository of deeply phenotyped cases and controls with biological samples during liver injury progression to facilitate biomarker discovery, evaluation, validation and qualification.In a nested case-control design, patients who meet one of these criteria, alanine transaminase (ALT) ≥ 5 × the upper limit of normal (ULN), alkaline phosphatase ≥ 2 × ULN or ALT ≥ 3 ULN with total bilirubin > 2 × ULN, are enrolled.

Biomarkers of Type IV Collagen Turnover Reflect Disease Activity in Patients with Early-Stage Non-Alcoholic Fatty Liver (NAFL).

Background: Identification of progressive liver disease necessitates the finding of novel non-invasive methods to identify and monitor patients in need of early intervention. Investigating patients with early-liver injury may help identify unique biomarkers. Early-liver injury is characterized by remodeling of the hepatocyte basement membrane (BM) of the extracellular matrix.

Identification and characterisation of a rare variant underlying hereditary non-alcoholic fatty liver disease.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a complex trait with an estimated prevalence of 25% globally. We aimed to identify the genetic variant underlying a four-generation family with progressive NAFLD leading to cirrhosis, decompensation, and development of hepatocellular carcinoma in the absence of common risk factors such as obesity and type 2 diabetes.

Methods: Exome sequencing and genome comparisons were used to identify the likely causal variant.

PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease.

Background & Aims: Fibroblast activity is a key feature of fibrosis progression and organ function loss, leading to liver-related complications and mortality. The fibrogenesis marker, PRO-C3, has been shown to have prognostic significance in relation to fibrosis progression and as a treatment efficacy marker. We investigated whether PRO-C3 was prognostic for clinical outcome and mortality in two distinct cohorts of compensated cirrhosis.

Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans.

Diagnosis of drug-induced liver injury (DILI) and its distinction from other liver diseases are significant challenges in drug development and clinical practice. Here, we identify, confirm, and replicate the biomarker performance characteristics of candidate proteins in patients with DILI at onset (DO; n = 133) and follow-up (n = 120), acute non-DILI at onset (NDO; n = 63) and follow-up (n = 42), and healthy volunteers (HV; n = 104). Area under the receiver operating characteristic curve (AUC) for cytoplasmic aconitate hydratase, argininosuccinate synthase, carbamoylphosphate synthase, fumarylacetoacetase, fructose-1,6-bisphosphatase 1 (FBP1) across cohorts achieved near complete separation (range: 0.

Plasma Sphingoid Base Profiles of Patients Diagnosed with Intrinsic or Idiosyncratic Drug-induced Liver Injury.

Sphingolipids are exceptionally diverse, comprising hundreds of unique species. The bulk of circulating sphingolipids are synthesized in the liver, thereby plasma sphingolipid profiles represent reliable surrogates of hepatic sphingolipid metabolism and content. As changes in plasma sphingolipid content have been associated to exposure to drugs inducing hepatotoxicity both in vitro and in rodents, in the present study the translatability of the preclinical data was assessed by analyzing the plasma of patients with suspected drug-induced liver injury (DILI) and control subjects.

Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated.

Background & Aims: The risk of significant liver fibrosis from prolonged methotrexate (MTX) exposure has been estimated at around 5%, prompting intensive monitoring strategies. However, the evidence is derived from retrospective studies that under-reported risk factors for liver disease. We evaluated the risk of long-term MTX therapy on liver fibrosis in a longitudinal cohort study using two non-invasive markers.

A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry.

Background & Aims: No multi-national prospective study of drug-induced liver injury (DILI) has originated in Europe. The design of a prospective European DILI registry, clinical features and short-term outcomes of the cases and controls is reported.

Methods: Patients with suspected DILI were prospectively enrolled in the United Kingdom, Spain, Germany, Switzerland, Portugal and Iceland, 2016-2021.

Development of Food Group Tree-Based Analysis and Its Association with Non-Alcoholic Fatty Liver Disease (NAFLD) and Co-Morbidities in a South Indian Population: A Large Case-Control Study.

Background: Non-alcoholic fatty liver disease (NAFLD) is a global problem growing in parallel to the epidemics of obesity and diabetes, with South Asians being particularly susceptible. Nutrition and behaviour are important modifiers of the disease; however, studies to date have only described dietary patterns and nutrients associated with susceptibility to NAFLD.

Methods: This cross-sectional case-control study included 993 NAFLD patients and 973 healthy controls from Trivandrum (India).

Comprehensive Comparative Analysis of Standard Validated, Genetic, and Novel Biomarkers to Enhance Prognostic Risk-Stratification in Patients With Hepatitis C Virus Cirrhosis.

Introduction: Risk-stratifying patients with hepatitis C virus (HCV) cirrhosis according to medium-term prognosis will inform clinical decision-making. It is unclear which biomarkers/models are optimal for this purpose. We quantified the discriminative ability of 14 diverse biomarkers for prognosis prediction over a 4-year time.

Integrins as a drug target in liver fibrosis.

As the worldwide prevalence of chronic liver diseases is high and continuing to increase, there is an urgent need for treatment to prevent cirrhosis-related morbidity and mortality. Integrins are heterodimeric cell-surface proteins that are promising targets for therapeutic intervention. αv integrins are central in the development of fibrosis as they activate latent TGFβ, a known profibrogenic cytokine.

Chronic liver disease in homeless individuals and performance of non-invasive liver fibrosis and injury markers: VALID study.

Background/aims: Community-based assessment and management of chronic liver disease (CLD) in people who are homeless (PWAH) remain poorly described. We aimed to determine prevalence/predictors of CLD in PWAH and assess the performance of non-invasive liver fibrosis and injury markers.

Methods: The Vulnerable Adult LIver Disease (VALID) study provided a "one-stop" liver service based at homeless hostels.

Effects of an isoenergetic low Glycaemic Index (GI) diet on liver fat accumulation and gut microbiota composition in patients with non-alcoholic fatty liver disease (NAFLD): a study protocol of an efficacy mechanism evaluation.

Introduction: A Low Glycaemic Index (LGI) diet is a proposed lifestyle intervention in non-alcoholic fatty liver diseases (NAFLD) which is designed to reduce circulating blood glucose levels, hepatic glucose influx, insulin resistance and de novo lipogenesis. A significant reduction in liver fat content through following a 1-week LGI diet has been reported in healthy volunteers. Changes in dietary fat and carbohydrates have also been shown to alter gut microbiota composition and lead to hepatic steatosis through the gut-liver axis.

Reliable computational quantification of liver fibrosis is compromised by inherent staining variation.

Biopsy remains the gold-standard measure for staging liver disease, both to inform prognosis and to assess the response to a given treatment. Semiquantitative scores such as the Ishak fibrosis score are used for evaluation. These scores are utilised in clinical trials, with the US Food and Drug Administration mandating particular scores as inclusion criteria for participants and using the change in score as evidence of treatment efficacy.

Gut Microbial Profile Is Associated With Residential Settings and Not Nutritional Status in Adults in Karnataka, India.

Undernutrition is a leading contributor to disease and disability in people of all ages. Several studies have reported significant association between nutritional status and gut microbiome composition but other factors such as demographic settings may also influence the adult microbiome. The relationship between undernourishment and gut microbiome in adults has not been described to date.

MR Measures of Small Bowel Wall T2 Are Associated With Increased Permeability.

Background: Increased small bowel permeability leads to bacterial translocation, associated with significant morbidity and mortality. Biomarkers are needed to evaluate these changes in vivo, stratify an individual's risk, and evaluate the efficacy of interventions. MRI is an established biomarker of small bowel inflammation.

In Severe Alcoholic Hepatitis, Serum Keratin-18 Fragments Are Diagnostic, Prognostic, and Theragnostic Biomarkers.

Introduction: Up to 40% of patients with severe alcoholic hepatitis (AH) die within 6 months of presentation, making prompt diagnosis and appropriate treatment essential. We determined the associations between serum keratin-18 (K18) and histological features, prognosis, and differential response to prednisolone in patients with severe AH.

Methods: Total (K18-M65) and caspase-cleaved K18 (K18-M30) were quantified in pretreatment sera from 824 patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial (87 with suitable histological samples) and disease controls.

Accurate non-invasive diagnosis and staging of non-alcoholic fatty liver disease using the urinary steroid metabolome.

Background: The development of accurate, non-invasive markers to diagnose and stage non-alcoholic fatty liver disease (NAFLD) is critical to reduce the need for an invasive liver biopsy and to identify patients who are at the highest risk of hepatic and cardio-metabolic complications. Disruption of steroid hormone metabolic pathways has been described in patients with NAFLD.

Aim(s): To assess the hypothesis that assessment of the urinary steroid metabolome may provide a novel, non-invasive biomarker strategy to stage NAFLD.

The Evaluation and Use of a Food Frequency Questionnaire Among the Population in Trivandrum, South Kerala, India.

Dietary record tools such as food frequency questionnaire (FFQ) and food diaries (FD) are the most commonly used choices for assessing dietary intakes in most large-scale epidemiological studies. The authors developed a self-administered 360-item food frequency questionnaire (FFQ) to assess dietary intakes amongst a population-based cohort in South Kerala. In the validation study ( = 460), the data were collected using FFQs that were administered on three different occasions which were then compared to 7-day food records.

Lower gut microbiome diversity and higher abundance of proinflammatory genus are associated with biopsy-proven nonalcoholic steatohepatitis.

There is increasing evidence for the role of gut microbial composition in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH) is the most serious form of NAFLD where inflammation causes liver damage that can progress to cirrhosis. We have characterized the gut microbiome composition in UK patients with biopsy-proven NASH (n = 65) and compared it to that in healthy controls (n = 76).

Genetic Variation in HSD17B13 Reduces the Risk of Developing Cirrhosis and Hepatocellular Carcinoma in Alcohol Misusers.

Background And Aims: Carriage of rs738409:G in patatin-like phospholipase domain containing 3 (PNPLA3) is associated with an increased risk for developing alcohol-related cirrhosis and hepatocellular carcinoma (HCC). Recently, rs72613567:TA in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) was shown to be associated with a reduced risk for developing alcohol-related liver disease and to attenuate the risk associated with carriage of PNPLA3 rs738409:G. This study explores the risk associations between these two genetic variants and the development of alcohol-related cirrhosis and HCC.

Cohort profile: the Trivandrum non-alcoholic fatty liver disease (NAFLD) cohort.

Purpose: The Trivandrum non-alcoholic fatty liver disease (NAFLD) cohort is a population-based study designed to examine the interaction between genetic and lifestyle factors and their association with increased risk of NAFLD within the Indian population.

Participants: Between 2013 and 2016, a total of 2222 participants were recruited to this cohort through multistage cluster sampling across the whole population of Trivandrum-a district within the state of Kerala, South India. Data were collected from all inhabitants of randomly selected households over the age of 25.