Enhanced diagnosis and prognosis of severe alcoholic hepatitis using novel metabolomic biomarkers.

AIM: Differentiating alcoholic hepatitis (AH) from acute decompensation of alcoholic cirrhosis (DC) is challenging, as the presentation and biochemistry are similar. We aimed to identify potential metabolomic biomarkers to differentiate between AH and DC, and to predict short-term mortality. METHODS: We included consecutive biopsy proven AH and DC patients, which were managed according to current guidelines and followed up until the end of the study. Untargeted metabolomics was assessed in all patients at baseline. Specific analyses were successively performed to identify potential biomarkers, which were further semi-quantitatively analysed against relevant clinical endpoints. RESULTS: Thirty-four patients with AH and 37 with DC were included. UHPLC-MS analysis identified 83 molecules potentially differentiating between AH and DC. C16-Sphinganine-1P (S1P) was the most increased, whereas Prostaglandin E2 (PGE2) was the most decreased. The PGE2/S1P ratio < 1.03 excellently discriminates between AH and DC: AUC 0.965 (p < 0.001), Se 90%, Sp 100%, PPV 0.91, NPV 1, and diagnostic accuracy 95%. This ratio is not influenced by the presence of infection (AUC 0.967 vs. 0.962), correlates with the Lille score at 7 days (r = -0.60; P = 0.022) and tends to be lower in corticosteroid non-responders as compared with patients who responded [0.85(±0.02) vs. 0.89(±0.05), P = 0.069]. Additionally, decreased ursodeoxycholic acid levels are correlated with MELD and Maddrey scores and predict mortality with a 77.27% accuracy (NPV = 100%). CONCLUSION: This study suggests the PGE2 (decreased)/S1P (increased) ratio as a biomarker to differentiate AH from DC. The study also finds that low levels of ursodeoxycholic acid could predict increased mortality in AH.

Non-Invasive Biomarkers for Differentiating Alcohol Associated Hepatitis from Acute Decompensation in Patients with ALD.

Alcohol-associated hepatitis (AH) is the most severe form of alcohol-related liver disease. The natural course of alcohol-related liver disease is influenced by heavy alcohol consumption and abstinence periods. Differentiating between AH and decompensated cirrhosis (DC) could be extremely challenging in clinical practice due to clinical and bioclinical similarities. The severity of AH is made on bioclinical grounds, the severe form necessitating corticotherapy treatment. Liver biopsy is still the standard of care for establishing the diagnosis in atypical presentations. The pathogenesis of AH is an interplay between gene expression, cytokine dysregulation, the immune system and the gut microbiota. Non-invasive tests are increasingly and widely used for the purpose of early diagnosis and reliable prognostication. The non-invasive tests are emerging in concordance with disease pathogenesis. In this review, we describe the non-invasive tools that can distinguish AH from DC. We outline the available cut-offs and their performance in diagnosis and prognosis, as well as in assessing the treatment response to corticotherapy. Promising circulating biomarkers like keratin 18, microRNAs and sphingolipids will be in the review.

Validation and Performance of Chronic Liver Disease Questionnaire (CLDQ-RO) in the Romanian Population.

BACKGROUND AND AIMS: Health-related quality of life is an essential part of managing chronically ill patients, including patients with chronic liver disease. Various methods are used to try to assess the quality of life ranging from generic to disease-specific questionnaires. Some of the results may reveal a novel connection to the disease's evolution, which is observed directly by the patient. This study aimed to validate and assess the chronic liver disease questionnaire (CLDQ-RO) performance in the Romanian population. METHODS: A two-phase study was designed. The first phase consisted of linguistic validation of CLDQ-RO (translation and piloting), while in the second phase, the questionnaire was applied to patients with various chronic liver diseases. Statistical validation (reliability, structural, and construct validity) was performed using SPSS v20.0, and statistical significance was considered p<0.05. RESULTS: The CLDQ-RO was applied to 231 patients with chronic liver disease (14.3% with chronic hepatitis, 35.5% with compensated cirrhosis, and 50.2% with decompensated cirrhosis). The questionnaire showed excellent overall reliability (Cronbach's alpha=0.93) and good structural and construct validity, with most of the items in CLDQ-RO fitting in the domains of the original version of the questionnaire. There was a significant decrease in the overall score of the CLDQ-RO with the progression of disease (p<0.001), indicating a substantial impact of the decompensation event on health-related quality of life. Regarding the type of decompensation, ascites accurately predicted a lower quality of life (p=0.004). CONCLUSIONS: The CLDQ-RO is a valid and disease-specific method for assessing patients' health-related quality of life with liver disease. Among the decompensation events, it seems that ascites seriously impacts the quality of life.