Clinical and genetic definition of serum bilirubin levels for the diagnosis of Gilbert syndrome and hypobilirubinemia.

Background And Aims: Gilbert syndrome (GS) is genotypically predetermined by UGT1A1*28 homozygosity in Europeans and is phenotypically defined by hyperbilirubinemia using total bilirubin (TB) cutoff ≥1mg/dL (17 μmol/L). The prevalence of illnesses associated with GS and hypobilirubinemia has never been studied prospectively. As TB varies with UGT1A1*28 genotyping, sex, and age, we propose stratified definitions of TB reference intervals and report the prevalence of illnesses and adjusted 15 years survival.

Prospective direct comparison of non-invasive liver tests in outpatients with type 2 diabetes using intention-to-diagnose analysis.

Background: No prospective diagnostic studies have directly compared widespread non-invasive liver tests in patients with type 2 diabetes (T2D) using the intention-to-diagnose method for each of the three main histological features of metabolic dysfunction associated steatotic liver disease - namely fibrosis, metabolic dysfunction-associated steatohepatitis (MASH), and steatosis.

Aims: To compare the performance of nine tests using the intention-to-diagnose rather than the standard method, which would exclude non-evaluable participants METHODS: Biopsy was used as the reference with predetermined cut-offs, advanced fibrosis being the main endpoint. The Nash-FibroTest panel including FibroTest-T2D, SteatoTest-T2D and MashTest-T2D was optimised for type 2 diabetes.

Hepatocyte-derived biomarkers predict liver-related events at 2 years in Child-Pugh class A alcohol-related cirrhosis.

Background & Aims: In patients with compensated alcohol-related cirrhosis, reliable prognostic biomarkers are lacking. Keratin-18 and hepatocyte-derived large extracellular vesicle (lEV) concentrations reflect disease activity, but their ability to predict liver-related events is unknown.

Methods: We measured plasma keratin-18 and hepatocyte lEV concentrations in 500 patients with Child-Pugh class A alcohol-related cirrhosis.

External Validation of LCR1-LCR2, a Multivariable Hepatocellular Carcinoma Risk Calculator, in a Multiethnic Cohort of Patients With Chronic Hepatitis B.

Background And Aims: The liver cancer risk test (LCR1-LCR2) is a multianalyte blood test combining proteins involved in liver cell repair (apolipoprotein A1, haptoglobin), hepatocellular carcinoma (HCC) risk factors (gender, age, gamma glutamyl transpeptidase), a marker of fibrosis (alpha2-macroglobulin), and alpha-fetoprotein, a specific marker of HCC. The aim was to externally validate LCR1-LCR2 in hepatitis B.

Methods: Preincluded patients were from the Hepather cohort, a multicenter, multiethnic prospective study in 6071 patients.

Clinical Interest of Serum Alpha-2 Macroglobulin, Apolipoprotein A1, and Haptoglobin in Patients with Non-Alcoholic Fatty Liver Disease, with and without Type 2 Diabetes, before or during COVID-19.

In patients with non-alcoholic fatty liver disease (NAFLD) with or without type 2 diabetes mellitus (T2DM), alpha-2 macroglobulin (A2M), apolipoprotein A1 (ApoA1), and haptoglobin are associated with the risk of liver fibrosis, inflammation (NASH), and COVID-19. We assessed if these associations were worsened by T2DM after adjustment by age, sex, obesity, and COVID-19. Three datasets were used: the “Control Population”, which enabled standardization of protein serum levels according to age and sex (N = 27,382); the “NAFLD-Biopsy” cohort for associations with liver features (N = 926); and the USA “NAFLD-Serum” cohort for protein kinetics before and during COVID-19 (N = 421,021).

Validation of the Performance of A1HPV6, a Triage Blood Test for the Early Diagnosis and Prognosis of SARS-CoV-2 Infection.

Background And Aims: Apolipoprotein A1 (A1) and haptoglobin (HP) serum levels are associated with the spread and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We have constructed and validated a multivariable risk calculator (A1HPV6) integrating A1, HP, alpha2-macroglobulin, and gamma glutamyl transferase to improve the performances of virological biomarkers.

Methods: In a prospective observational study of hospitalized patients with nonsevere SARS-CoV-2 infection, A1HPV6 was constructed in 127 patients and validated in 116.

Baveno VI criteria as a prognostic factor for clinical complications in patients with compensated cirrhosis.

Background: Combination of liver stiffness measurement and platelets count is a tool to safely rule out varices needing treatment (VNT) in patients with compensated advanced chronic liver disease (cACLD).

Aims: to evaluate 4-year liver-related complications and survival in low-risk patients according to Baveno VI criteria.

Methods: we conducted a monocentric retrospective analysis of prospectively collected data of all consecutive patients, with cirrhosis (LSM≥12.

External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic HCV.

Background & Aims: The Liver Cancer Risk test algorithm (LCR1-LCR2) is a multianalyte blood test combining proteins involved in liver cell repair (apolipoprotein-A1 and haptoglobin), known hepatocellular carcinoma (HCC) risk factors (sex, age, and gamma-glutamyl transferase), a marker of fibrosis (alpha2-macroglobulin) and alpha-fetoprotein (AFP), a specific marker of HCC. The aim was to externally validate the LCR1-LCR2 in patients with chronic HCV (CHC) treated or not with antivirals.

Methods: Pre-included patients were from the Hepather cohort, a multicentre prospective study in adult patients with CHC in France.

Subclinical proximal tubulopathy in hepatitis B: The roles of nucleot(s)ide analogue treatment and the hepatitis B virus.

Background: The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity, such as estimated glomerular filtration rate (eGFR) and phosphatemia, are late markers of proximal tubulopathy. Multiple early markers are available, but no consensus exists on their use.

Aim: To determine the 24 mo prevalence of subclinical proximal tubulopathy (SPT), as defined with early biomarkers, in treated untreated hepatitis B virus (HBV)-monoinfected patients.

Performance of serum apolipoprotein-A1 as a sentinel of Covid-19.

Background: Since 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia. We have assessed the performance of serum apolipoprotein-A1, the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19.

Methods: We compared the daily mean serum apolipoprotein-A1 during the first 34 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in the USA (212,297 serum) and in France (20,652 serum) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (266,976 and 28,452 serum, respectively).

Hepatitis C Clearance by Direct-Acting Antivirals Impacts Glucose and Lipid Homeostasis.

Background: Chronic hepatitis C virus (HCV) infections are causally linked with metabolic comorbidities such as insulin resistance, hepatic steatosis, and dyslipidemia. However, the clinical impact of HCV eradication achieved by direct-acting antivirals (DAAs) on glucose and lipid homeostasis is still controversial. The study aimed to prospectively investigate whether antiviral therapy of HCV with DAAs alters glucose and lipid parameters.

Transportation and handling of blood samples prior to ammonia measurement in the real life of a large university hospital.

Background: Hyperammonemia is neurotoxic and as such can be a medical emergency. Preanalytical factors greatly influence the blood ammonia concentration results.

Aims And Methods: Ammonia concentrations measured in the real life setting of a large hospital after pneumatic transport of blood samples and various time periods before centrifugation were compared to those based on the indications of the reagent manufacturer.

Origin, HDV genotype and persistent viremia determine outcome and treatment response in patients with chronic hepatitis delta.

Background & Aims: HDV infection causes severe chronic liver disease in individuals infected with HBV. However, the factors associated with poor prognosis are largely unknown. Thus, we aimed to identify prognostic factors in patients with HDV infection.

Input of serum haptoglobin fucosylation profile in the diagnosis of hepatocellular carcinoma in patients with non-cirrhotic liver disease.

Background: Haptoglobin bifucosylated tetra-antennary glycan have been identified in patients with early stage hepatocellular carcinoma, but its specificity according to the presence or not of cirrhosis has never been assessed. The aims of this study were to determine if haptoglobin bifucosylated tetra-antennary glycan (1) could be a marker of HCC in patients without cirrhosis; (2) could increase the performance of standard alpha-fetoprotein (AFP) or recent blood tests for HCC detection, i.e.

Clinical validation of the FLIP algorithm and the SAF score in patients with non-alcoholic fatty liver disease.

Background & Aims: Histological classifications used to diagnose/stage non-alcoholic fatty liver disease (NAFLD) are based on morphology, with undetermined clinical correlates and relevance. We assessed the clinical relevance of the fatty liver inhibition of progression (FLIP) algorithm and the steatosis, activity, and fibrosis (SAF) scoring system.

Methods: One hundred and forty consecutive patients with suspected NAFLD and a separate validation cohort of 78 patients enrolled in a therapeutic trial, all with central reading of liver biopsy, were included.

Evaluation of Point Shear Wave Elastography Using Acoustic Radiation Force Impulse Imaging for Longitudinal Fibrosis Assessment in Patients with HBeAg-Negative HBV Infection.

Background: Accurate assessment of hepatic fibrosis in patients with chronic HBeAg-negative Hepatitis B is of crucial importance not only to predict the long-term clinical course, but also to evaluate antiviral therapy indication. The aim of this study was to prospectively assess the utility of point shear wave elastography (pSWE) for longitudinal non-invasive fibrosis assessment in a large cohort of untreated patients with chronic HBeAg-negative hepatitis B virus (HBV) infection.

Methods: 407 consecutive patients with HBeAg-negative HBV infection who underwent pSWE, transient elastography (TE) as well as laboratory fibrosis markers, including fibrosis index based on four factors (FIB-4), aspartate to platelet ratio index (APRI) and FibroTest, on the same day were prospectively followed up for six years.

Performance of liver biomarkers, in patients at risk of nonalcoholic steato-hepatitis, according to presence of type-2 diabetes.

Objective: There is a controversy about the performance of blood tests for the diagnostic of metabolic liver disease in patients with type-2-diabetes in comparison with patients without type-2-diabetes. These indirect comparisons assumed that the gold-standard is binary, whereas fibrosis stages, steatosis and nonalcoholic-steato-hepatitis (NASH) grades use an ordinal scale. The primary aim was to compare the diagnostic performances of FibroTest in type-2-diabetes vs.

Identification of an Endoglin Variant Associated With HCV-Related Liver Fibrosis Progression by Next-Generation Sequencing.

Despite the astonishing progress in treating chronic hepatitis C virus (HCV) infection with direct-acting antiviral agents, liver fibrosis remains a major health concern in HCV infected patients, in particular due to the treatment cost and insufficient HCV screening in many countries. Only a fraction of patients with chronic HCV infection develop liver fibrosis. While there is evidence that host genetic factors are involved in the development of liver fibrosis, the common variants identified so far, in particular by genome-wide association studies, were found to have limited effects.

Intestinal failure-associated liver disease in patients with short bowel syndrome: Evaluation by transient elastography.

Objective: Patients with short bowel syndrome (SBS) receiving long-term parenteral nutrition (PN) are at risk for intestinal failure-associated liver disease (IFALD). The aim of the present study was to evaluate dynamic changes of liver fibrosis and steatosis within 12 mo by transient elastography (TE), including controlled attenuation parameter (CAP) in a cohort of patients with SBS receiving long-term PN.

Methods: Twenty-five adult patients with SBS and PN requirement for ≥3 mo consecutively were included and prospectively followed.

LCR1 and LCR2, two multi-analyte blood tests to assess liver cancer risk in patients without or with cirrhosis.

Background: No blood test has been shown to be effective in the prediction of primary liver cancer in patients without cirrhosis.

Aim: To construct and internally validate two sequential tests for early prediction of liver cancer. These tests enable an algorithm which could improve the performance of the standard surveillance protocol recommended (imaging with or without AFP), limited to patients with cirrhosis.

The diagnostic performance of a simplified blood test (SteatoTest-2) for the prediction of liver steatosis.

Background: Serum biomarkers of steatosis such as the SteatoTest are recommended for large-scale screening studies, because imaging is less accessible and more expensive.

Aims: The primary aim of this retrospective analysis of prospective studies was to construct a new SteatoTest-2 that was not inferior to the reference first-generation SteatoTest, but that did not include BMI or bilirubin, as these two components can increase test variability because of the assessment of weight and height and in case of Gilbert syndrome or hemolysis, respectively.

Patients And Methods: Five different subsets of 2997 patients with biopsies were evaluated for test construction and validation, and four to assess the prevalence of steatosis in target populations with increasing risks of steatosis.