Quantification of alcohol intake in patients with steatotic liver disease and excessive alcohol intake.

Background & Aims: Quantifying alcohol intake is crucial for subclassifying participants with steatotic liver disease (SLD) and interpreting clinical trials of alcohol-related liver disease (ALD) and metabolic and alcohol-related liver disease (MetALD). However, the accuracy of self-reported alcohol intake is considered imprecise. We compared the diagnostic and prognostic utility of self-reported alcohol intake with blood-based biomarkers of alcohol intake: phosphatidylethanol (PEth) and carbohydrate-deficient transferrin (CDT).

Development, validation, and prognostic evaluation of LiverPRO for the prediction of significant liver fibrosis in primary care: a prospective cohort study.

Background: Clinically significant liver fibrosis is associated with future adverse events in patients with steatotic liver disease. We designed a software tool for detection of clinically significant liver fibrosis in primary care.

Methods: In this prospective cohort study, we developed and validated LiverPRO using six independent cohorts from Denmark, Germany, and England that included patients from primary and secondary care with steatotic liver disease related to alcohol or metabolic dysfunction.

Longitudinal Evaluation of Individuals With Severe Alpha-1 Antitrypsin Deficiency (Pi∗ZZ Genotype).

Background & Aims: Homozygous Pi∗Z mutation in alpha-1 antitrypsin (Pi∗ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To facilitate selection into clinical trials typically targeting only 1 organ, we systematically evaluated an international, multicenter, longitudinal, Pi∗ZZ cohort to uncover natural disease course and surrogates for future liver- and lung-related endpoints.

Methods: Cohort 1 recruited 737 Pi∗ZZ individuals from 25 different centers without known liver comorbidities who received a baseline clinical and laboratory assessment as well as liver stiffness measurement (LSM).

Alcohol consumption and liver phenotype of individuals with alpha-1 antitrypsin deficiency.

Background And Aims: Alpha-1 antitrypsin deficiency is an inherited disorder caused by alpha-1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver-related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium.

Methods: Reported alcohol consumption was evaluated in two cohorts: (i) the community-based United Kingdom Biobank (17 145 Pi*MZ, 141 Pi*ZZ subjects, and 425 002 non-carriers [Pi*MM]); and (ii) the European Alpha1 liver consortium (561 Pi*ZZ individuals).

Infections increase the risk of decompensation and death in patients with early alcohol-related liver disease.

Background & Aims: Infections are frequent in patients with cirrhosis and worsen prognosis. We evaluated the incidence of infections and their impact on decompensation and death in patients with early alcohol-related liver disease (ALD) during long-term follow-up.

Methods: We performed a prospective cohort study of patients in secondary care with a history of excess alcohol intake, no prior decompensation, and with liver biopsies along with clinical investigations conducted at baseline.

Validation of the new nomenclature of steatotic liver disease in patients with a history of excessive alcohol intake: an analysis of data from a prospective cohort study.

Background: Steatotic liver disease is a new overarching term that includes metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related steatotic liver disease (MetALD), and alcohol-related liver disease (ALD). We aimed to validate the prognostic importance of MASLD, MetALD, and ALD as steatotic liver disease subclasses.

Methods: Between April 18, 2013, and Sept 17, 2018, we prospectively recruited patients aged 18-75 years with current or previous excessive alcohol intake (>24 g/day for women and >36 g/day for men) for at least a year and no previous hepatic decompensation from the Department of Gastroenterology and Hepatology at Odense University Hospital (Odense, Denmark).

Screening for Fibrosis Promotes Lifestyle Changes: A Prospective Cohort Study in 4796 Individuals.

Background And Aims: Early detection of liver fibrosis is believed to promote lifestyle changes. We evaluated self-reported changes in alcohol intake, diet, exercise, and weight after participating in a screening study for liver fibrosis.

Methods: We conducted a prospective screening study of individuals at risk of alcohol-related liver disease (ALD) or metabolic dysfunction-associated steatotic liver disease (MASLD).

Alpha-1 Antitrypsin Augmentation and the Liver Phenotype of Adults With Alpha-1 Antitrypsin Deficiency (Genotype Pi∗ZZ).

Background & Aims: α1-Antitrypsin (AAT) is a major protease inhibitor produced by hepatocytes. The most relevant AAT mutation giving rise to AAT deficiency (AATD), the 'Pi∗Z' variant, causes harmful AAT protein accumulation in the liver, shortage of AAT in the systemic circulation, and thereby predisposes to liver and lung injury. Although intravenous AAT augmentation constitutes an established treatment of AATD-associated lung disease, its impact on the liver is unknown.

Impact of PNPLA3 I148M on alpha-1 antitrypsin deficiency-dependent liver disease progression.

Background And Aims: Genetic risk factors are major determinants of chronic liver disease (CLD) progression. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M polymorphism and alpha-1 antitrypsin (AAT) E342K variant, termed PiZ, are major modifiers of metabolic CLD. Both variants are known to affect metabolic CLD through increased endoplasmic reticulum stress, but their combined effect on CLD progression remains largely unknown.

Binge drinking episode causes acute, specific alterations in systemic and hepatic inflammation-related markers.

Background: Frequent binge drinking is a known contributor to alcohol-related harm, but its impact on systemic and hepatic inflammation is not fully understood. We hypothesize that changes in immune markers play a central role in adverse effects of acute alcohol intake, especially in patients with early liver disease.

Aim: To investigate the effects of acute alcohol intoxication on inflammation-related markers in hepatic and systemic venous plasma in people with alcohol-related liver disease (ArLD), non-alcoholic fatty liver disease (NAFLD) and healthy controls.

Using the ELF test, FIB-4 and NAFLD fibrosis score to screen the population for liver disease.

Background & Aims: There is a need for accurate biomarkers of fibrosis for population screening of alcohol-related and non-alcoholic fatty liver disease (ALD, NAFLD). We compared the performance of the enhanced liver fibrosis (ELF) test to the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS), using transient elastography as the reference standard.

Methods: We prospectively included participants from the general population, and people at risk of ALD or NAFLD.

Rifaximin-α for liver fibrosis in patients with alcohol-related liver disease (GALA-RIF): a randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Alcohol is the leading cause of liver-related mortality worldwide. The gut-liver axis is considered a key driver in alcohol-related liver disease. Rifaximin-α improves gut-barrier function and reduces systemic inflammation in patients with cirrhosis.

Effect of Calorie-Unrestricted Low-Carbohydrate, High-Fat Diet Versus High-Carbohydrate, Low-Fat Diet on Type 2 Diabetes and Nonalcoholic Fatty Liver Disease : A Randomized Controlled Trial.

Background: It remains unclear if a low-carbohydrate, high-fat (LCHF) diet is a possible treatment strategy for type 2 diabetes mellitus (T2DM), and the effect on nonalcoholic fatty liver disease (NAFLD) has not been investigated.

Objective: To investigate the effect of a calorie-unrestricted LCHF diet, with no intention of weight loss, on T2DM and NAFLD compared with a high-carbohydrate, low-fat (HCLF) diet.

Design: 6-month randomized controlled trial with a 3-month follow-up.

Serum keratin-18 detects hepatic inflammation and predicts progression in compensated alcohol-associated liver disease.

Alcohol-associated liver fibrosis accumulates over decades, driven by hepatic inflammation and cell death. We investigated the diagnostic accuracy of keratin-18 degradation, measured using serum M30 and M65 levels, and the ActiTest for hepatic inflammatory activity in patients with compensated alcohol-associated liver disease (ALD). Furthermore, we evaluated the prognostic accuracy of markers for liver-related events and all-cause mortality.

Only one-third of referrals for fatty liver disease are on time: real-world study reveals opportunities to avoid unnecessary and delayed referrals.

Background And Aims: Fatty liver disease is a global health concern, but in the absence of specific guidelines, current referral patterns differ according to the preferences of the general practitioners. Outpatient Gastroenterology clinics spend futile resources on liver-healthy patients while diagnosing decompensated patients delayed. We aimed to describe referral patterns to a regional outpatient Gastroenterology clinic.