Interferon-γ-inducible protein-10 in chronic hepatitis C: Correlations with insulin resistance, histological features & sustained virological response.

BACKGROUND & OBJECTIVES: One of the multiple factors contributing to virological response in chronic hepatitis C (CHC) is interferon-gamma-inducible protein-10 (IP-10). Its level reflects the status of interferon-stimulated genes, which in turn is associated with virological response to antiviral therapy. The aim of this study was to evaluate the role of serum IP-10 levels on sustained virological response (SVR) and the association of this parameter with insulin resistance (IR) and liver histology. METHODS: Two hundred and three consecutive biopsy proven CHC patients were included in the study. Serum levels of IP-10 were determined using ELISA method. IR was evaluated by homeostasis model assessment-IR (HOMA-IR). Histological features were assessed invasively by liver biopsy and noninvasively using FibroTest, ActiTest and SteatoTest. Predictive factors for SVR and their interrelations were assessed. RESULTS: A cut-off value for IP-10 of 392 pg/ml was obtained to discriminate between responders and non-responders. SVR was obtained in 107 patients (52.70%). Area under the receiver operating characteristic curve for SVR was 0.875 with a sensitivity of 91.6 per cent, specificity 74.7 per cent, positive predictive value 80.3 per cent and negative predictive value 88.7 per cent. Higher values of IP-10 were associated with increasing stages of fibrosis (P<0.01) and higher grades of inflammation (P=0.02, P=0.07) assessed morphologically and noninvasively through FibroTest and ActiTest. Significant steatosis and IR were also associated with increased levels of IP-10 (P=0.01 and P=0.02). In multivariate analysis, IP-10 levels and fibrosis stages were independently associated with SVR. INTERPRETATION & CONCLUSIONS: Our findings showed that the assessment of serum IP-10 level could be a predictive factor for SVR and it was associated with fibrosis, necroinflammatory activity, significant steatosis and IR in patients with chronic HCV infection.

Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility.

Irritable bowel syndrome with diarrhoea (IBS-D) and functional diarrhoea (FDr) are the two major functional bowel disorders characterized by diarrhoea. In spite of their high prevalence, IBS-D and FDr are associated with major uncertainties, especially regarding their optimal diagnostic work-up and management. A Delphi consensus was performed with experts from 10 European countries who conducted a literature summary and voting process on 31 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation criteria. Consensus (defined as >80% agreement) was reached for all the statements. The panel agreed with the potential overlapping of IBS-D and FDr. In terms of diagnosis, the consensus supports a symptom-based approach also with the exclusion of alarm symptoms, recommending the evaluation of full blood count, C-reactive protein, serology for coeliac disease, and faecal calprotectin, and consideration of diagnosing bile acid diarrhoea. Colonoscopy with random biopsies in both the right and left colon is recommended in patients older than 50 years and in presence of alarm features. Regarding treatment, a strong consensus was achieved for the use of a diet low fermentable oligo-, di-, monosaccharides and polyols, gut-directed psychological therapies, rifaximin, loperamide, and eluxadoline. A weak or conditional recommendation was achieved for antispasmodics, probiotics, tryciclic antidepressants, bile acid sequestrants, 5-hydroxytryptamine-3 antagonists (i.e. alosetron, ondansetron, or ramosetron). A multinational group of European experts summarized the current state of consensus on the definition, diagnosis, and management of IBS-D and FDr.

Transaminases: oldies but goldies. A narrative review.

Worldwide, patients are tested for acute and chronic diseases using a series of basic blood assays. The most common liver tests are serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), also called transaminases. These tests are indicators of hepatocellular injury and their increase requires further investigations. The aim of this descriptive review is to highlight and remind the importance of liver transaminases in daily practice. A systematic literature search of the main international databases was performed. We looked for papers that involved transaminases, either in the normal range or in case of increased level and focused on their use in clinical practice. A narrative review of this topic was written. Multiple studies have demonstrated that the presence of an elevated ALT was associated with increased liver-related mortality. The normal ALT level ranges from 29 to 33 IU/L in males and 19 to 25 IU/L in females. The investigations imposed by a high level of transaminases includes testing for viral hepatitis A, B, C and E, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for autoimmune hepatitis, hemochromatosis, Wilson's disease and alpha-1 antitrypsin deficiency. Hepatotoxic drugs consumption also should be excluded. Furthermore, the utility of transaminases is evident in the assessment of the outcome after treatment of each specific liver disease. Beside the role in the first diagnostic step of liver injuries, the utility of liver transaminases is also maintained during the follow-up of liver diseases and in their prognostic assessment.

Malnutrition and non-compliance to nutritional recommendations in patients with cirrhosis are associated with a lower survival.

BACKGROUND: Malnutrition is frequently encountered in patients with cirrhosis and appears to significantly impact their prognosis. While evaluating the burden of malnutrition in cirrhosis is gathering momentum, as suggested by multiple recently published reports, there is still a persistent scarcity of solid data in the field, especially with regards to the role of nutritional interventions. AIM: To assess the prevalence of malnutrition in patients with advanced cirrhosis and to evaluate its impact on survival. METHODS: One hundred and one consecutive patients with advanced cirrhosis were screened for malnutrition using the Subjective Global Assessment (SGA) criteria and the mid-arm circumference (MAC). Malnutrition was defined as SGA class B and C and MAC < 10th percentile. All patients were interviewed regarding their food intake using an adapted questionnaire. Subsequently, total energy intake was calculated and further subdivided in main nutrients. The data were then compared to the available recommendations at the time of analysis to assess adherence. RESULTS: 54/79 patients (68.4%) in the decompensated group had malnutrition, while only 3/22 patients (13.6%) were malnourished in the compensated group. After a median follow-up time of 27 mo (0-53), the overall mortality was 70%. Survival was significantly lower among patients with malnutrition. The mortality rates were 50% at 1 year and 63% at 2 years for the patients with malnutrition, compared to 21% at 1 year and 30% at 2 years for patients without malnutrition (P = 0.01). On multivariate analysis, the factors independently associated with mortality were age, creatinine level and adherence to the protein intake recommendations. The mortality was lower in patients with the appropriate protein intake: 8% at 1 year and 28% at 2 years in the adherent group, compared to 47% at 1 year and 56% at 2 years in the non-adherent group. CONCLUSION: The prevalence of malnutrition is high among patients with advanced cirrhosis and might be related in part to a low adherence to nutritional recommendations, especially with regards to protein intake.

Upper Gastrointestinal Sensitization And Symptom Generation.

Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders, and their diagnostic criteria are symptom-based, with the absence of anatomical and biochemical abnormalities of the gastrointestinal tract. Chronic visceral symptoms are common both in patients with an identifiable organic disease but also in FGID patients. Patients suffering from upper gastrointestinal functional disorders typically present with various symptoms such as early satiety, postprandial fullness, bloating, nausea, vomiting, and epigastric pain. Considering their increasing prevalence, difficulties in diagnosis, and low quality of life, FGIDs have become an emerging problem in gastroenterology. We aimed to provide an updated summary of pathways involved in visceral sensitization. We examined the recent literature searching for evidence of the most important studies about the mechanisms underlying gastrointestinal symptom generation and sensitization.

What's in Metabolomics for Alcoholic Liver Disease?

BACKGROUND AND AIMS: Current management of alcoholic liver disease (ALD), especially for alcoholic hepatitis (AH) is still driven by liver biopsy. Therefore, the identification of novel and accurate noninvasive biomarkers for the diagnosis and assessment of severity is important. Metabolomics, because it unravels changes closest to the phenotype, may represent the key for novel biomarkers. The aim of this study was to identify and characterize potential metabolomic biomarkers for diagnosis, staging and severity assessment of ALD. METHODS: 30 consecutive ALD patients and 10 healthy controls were included in this proof-of-concept cross-sectional study. Baseline assessment consisted in evaluation of Maddrey's Discriminant Function, Model for End-Stage Liver Disease (MELD) and ABIC scores as well as ASH-Test (Fibromax) as a surrogate for the confirmatory diagnosis of AH in suggestive clinical and biologic settings. Additionally, SOP metabolomics and lipidomics were performed from serum samples by liquid chromatography mass-spectrometry analysis. RESULTS: From the 127 and 135 serum/urine candidate metabolites initially identified, only 11/5 metabolites were characteristic for ALD patients. None of them correlated with alcohol intake, and only 5/1 metabolites could differentiate cirrhotic from non-cirrhotic patients. Of those, N-Lauroglycine (NLG) was the best for identifying cirrhosis (100% sensitivity and 90% negative predictive value, NPV) and decatrienoic acid (DTEA) was the best for assessing disease severity (evaluated by ABIC score) with 100% sensitivity and 100% NPV. CONCLUSION: Due to their high NPV, NLG and DTEA could be used in conjunction in ALD patients to exclude cirrhosis or a severe disease. If further validated, they could become biomarkers for better management and risk assessment in ALD.

Noninvasive Assessment of Liver Diseases using 2D Shear Wave Elastography.

There has been great interest in the development of non-invasive techniques for the diagnosis of liver fibrosis in chronic liver diseases, including ultrasound elastographic methods. Some of these methods have already been adequately studied for the non-invasive assessment of diffuse liver diseases. Others, however, such as two-dimensional Shear Wave Elastography (SWE), of more recent appearance, have yet to be validated and some aspects are for the moment incompletely elucidated. This review discusses some of the aspects related to two-dimensional SWE: the examination technique, the examination performance indicators, intra and interobserver agreement and clinical applications. Recommendations for a high-quality examination technique are formulated.