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.

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.

Minor effect of patient education for alcohol cessation intervention on outcomes after acute fracture surgery: a randomized trial of 70 patients.

Background And Purpose: High alcohol intake is associated with increased risk of postoperative complications. Alcohol cessation intervention is recommended prior to elective surgery. We investigated short- and long-term effects of perioperative intensive alcohol intervention in relation to acute ankle fracture surgery.

Binge drinking induces an acute burst of markers of hepatic fibrogenesis (PRO-C3).

Background & Aims: Binge drinking is associated with an increased risk of liver disease. Morbidity and mortality of alcohol-related liver disease (ALD) is associated with collagen deposition in the hepatic extracellular matrix (ECM). However, the acute effects of binge drinking on ECM turnover are unknown.

Corrigendum to 'Level of MFAP4 in ascites independently predicts 1-year transplant-free survival in patients with cirrhosis' [JHEP Reports 3 (2021) 100287].

[This corrects the article DOI: 10.1016/j.jhepr.

Progressive alcohol-related liver fibrosis is characterised by imbalanced collagen formation and degradation.

Background: Liver fibrosis accumulation is considered a turnover disease, with formation exceeding degradation, although this hypothesis has never been tested in humans.

Aims: To investigate extracellular matrix (ECM) remodelling in a biopsy-controlled study of alcohol-related liver disease (ALD) patients.

Methods: We evaluated the relationship between formation and degradation of four collagens as a function of histological fibrosis, inflammation and steatosis in 281 patients with ALD and 50 matched healthy controls.

Diagnostic accuracy of routine liver function tests to identify patients with significant and advanced alcohol-related liver fibrosis.

Aims: Alcohol is the leading cause of cirrhosis, but most patients go undetected until decompensation occurs despite frequent contacts with the healthcare system. We aimed to evaluate the diagnostic accuracy of routine liver function tests compared with indirect and direct fibrosis markers and to assess doctors' abilities to diagnose significant and advanced alcohol-related liver fibrosis.

Methods: This study was a retrospective evaluation of liver function tests for diagnosing alcohol-related liver disease compared to indirect fibrosis tests, the ELF test, and transient elastography.

Comprehensive lipidomics reveals phenotypic differences in hepatic lipid turnover in ALD and NAFLD during alcohol intoxication.

Background & Aims: In experimental models, alcohol induces acute changes in lipid metabolism that cause hepatocyte lipoapoptosis and inflammation. Here we study human hepatic lipid turnover during controlled alcohol intoxication.

Methods: We studied 39 participants with 3 distinct hepatic phenotypes: alcohol-related liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), and healthy controls.

PRO-C3 and ADAPT algorithm accurately identify patients with advanced fibrosis due to alcohol-related liver disease.

Background: Alcohol is a main cause of preventable deaths and frequently leads to the development of alcohol-related liver disease. Due to the lack of diagnostics, patients are commonly diagnosed after developing clinical manifestations. Recently, the biomarker PRO-C3 was shown to accurately identify fibrosis due to non-alcoholic fatty liver disease.

Level of MFAP4 in ascites independently predicts 1-year transplant-free survival in patients with cirrhosis.

Background & Aims: Prognostic models of cirrhosis underestimate disease severity for patients with cirrhosis and ascites. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein linked to hepatic neoangiogenesis and fibrogenesis. We investigated ascites MFAP4 as a predictor of transplant-free survival in patients with cirrhosis and ascites.

Metabolic and Genetic Risk Factors Are the Strongest Predictors of Severity of Alcohol-Related Liver Fibrosis.

Background & Aims: Individual risk for developing alcohol-related liver disease (ALD) varies greatly. We hypothesized that metabolic risk factors and genetic polymorphisms predict severity of ALD.

Methods: Biopsy-controlled, cross-sectional study in patients with a history of excessive drinking.

Prediction of liver fibrosis severity in alcoholic liver disease by human microfibrillar-associated protein 4.

Background: Alcoholic liver disease (ALD) is a public health concern that is the cause of half of all cirrhosis-related deaths. Early detection of fibrosis, ideally in the precirrhotic stage, is a key strategy for improving ALD outcomes and for preventing progression to cirrhosis. Previous studies identified the blood-borne marker human microfibrillar-associated protein 4 (MFAP4) as a biomarker for detection of hepatitis C virus (HCV)-related fibrosis.

Spleen stiffness to liver stiffness ratio significantly differs between ALD and HCV and predicts disease-specific complications.

Background & Aims: Both liver stiffness (LS) and spleen stiffness (SS) are widely used to non-invasively assess liver fibrosis and portal hypertension, respectively. We aimed to identify the impact of disease etiology, namely the localization of inflammation (portal lobular), on the SS/LS ratio.

Methods: In this multicenter study, LS and SS were prospectively assessed in 411 patients with alcohol-related liver disease (ALD) or hepatitis C virus (HCV) using FibroScan® (Echosens, Paris); changes in these parameters were also studied in response to treatment (alcohol withdrawal, HCV therapy).

Dobutamine reverses the cardio-suppressive effects of terlipressin without improving renal function in cirrhosis and ascites: a randomized controlled trial.

Acute kidney injury and hepatorenal syndrome (HRS) are frequent complications in patients with cirrhosis and ascites. First-line treatment is terlipressin, which reverses HRS in ~40% of patients but also lowers cardiac output (CO). We aimed to investigate whether reversing the cardio-suppressive effect of terlipressin with the β-adrenoceptor agonist dobutamine would increase CO and thereby increase the glomerular filtration rate (GFR).

Heterologous production of the widely used natural food colorant carminic acid in Aspergillus nidulans.

The natural red food colorants carmine (E120) and carminic acid are currently produced from scale insects. The access to raw material is limited and current production is sensitive to fluctuation in weather conditions. A cheaper and more stable supply is therefore desirable.

Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography: an individual patient data meta-analysis.

Background: The value of transient elastography for the non-invasive diagnosis of alcohol-related liver fibrosis is subject to debate. We did an individual patient data (IPD) meta-analysis to determine specific diagnostic cutoff values for liver stiffness in alcohol-related fibrosis, and to assess the effect of aminotransferase concentrations, bilirubin concentrations, and presence of asymptomatic and non-severe alcoholic hepatitis on liver stiffness.

Methods: We searched for studies that included patients with alcohol-related liver disease, liver biopsy, and transient elastography, and with a statistical method for determining the diagnostic cutoffs for alcohol-induced liver fibrosis on the basis of the FibroScan results, in PubMed between Jan 1, 2000, and Sept 30, 2017.

On the biosynthetic origin of carminic acid.

The chemical composition of the scale insect Dactylopius coccus was analyzed with the aim to discover new possible intermediates in the biosynthesis of carminic acid. UPLC-DAD/HRMS analyses of fresh and dried insects resulted in the identification of three novel carminic acid analogues and the verification of several previously described intermediates. Structural elucidation revealed that the three novel compounds were desoxyerythrolaccin-O-glucosyl (DE-O-Glcp), 5,6-didehydroxyerythrolaccin 3-O-β-D-glucopyranoside (DDE-3-O-Glcp), and flavokermesic acid anthrone (FKA).

Antifibrotic and molecular aspects of rifaximin in alcoholic liver disease: study protocol for a randomized controlled trial.

Background: Alcoholic liver disease is the leading cause of cirrhosis worldwide. Due to an increase in alcohol overuse, alcoholic liver disease has become an increased burden on health care systems. Abstinence from alcohol remains the cornerstone of alcoholic liver disease treatment; however, this approach is hampered by frequent relapse and lack of specific therapy for treating advanced cases of liver disease.

Controlled attenuation parameter and alcoholic hepatic steatosis: Diagnostic accuracy and role of alcohol detoxification.

Background & Aims: Controlled attenuation parameter (CAP) is a novel non-invasive measure of hepatic steatosis, but it has not been evaluated in alcoholic liver disease. Therefore, we aimed to validate CAP for the assessment of biopsy-verified alcoholic steatosis and to study the effect of alcohol detoxification on CAP.

Methods: This was a cross-sectional biopsy-controlled diagnostic study in four European liver centres.

Accuracy of the Enhanced Liver Fibrosis Test vs FibroTest, Elastography, and Indirect Markers in Detection of Advanced Fibrosis in Patients With Alcoholic Liver Disease.

Background & Aims: Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3).

Methods: We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day.

Characterization of a membrane-bound C-glucosyltransferase responsible for carminic acid biosynthesis in Dactylopius coccus Costa.

Carminic acid, a glucosylated anthraquinone found in scale insects like Dactylopius coccus, has since ancient times been used as a red colorant in various applications. Here we show that a membrane-bound C-glucosyltransferase, isolated from D. coccus and designated DcUGT2, catalyzes the glucosylation of flavokermesic acid and kermesic acid into their respective C-glucosides dcII and carminic acid.