Systematic review and meta-analysis on the adverse events of rimonabant treatment: Considerations for its potential use in hepatology

<p>Abstract</p> <p>Background</p> <p>The cannabinoid-1 receptor blockers have been proposed in the management of obesity and obesity-related liver diseases (fatty liver as NAFLD or NASH). Due to increasing number of patients to be potentially treated and the need to assess the advantage of this treatment in terms of risk/benefit, we analyze the side events reported during the treatment with rimonabant by a systematic review and meta-analysis of all randomized controlled studies.</p> <p>Methods</p> <p>All published randomized controlled trials using rimonabant <it>versus </it>placebo in adult subjects were retrieved. Relative risks (RR) with 95% confidence interval for relevant adverse events and number needed to harm was calculated.</p> <p>Results</p> <p>Nine trials (n = 9635) were considered. Rimonabant 20 mg was associated with an increased risk of adverse event (RR 1.35; 95%CI 1.17-1.56), increased discontinuation rate (RR 1.79; 95%CI 1.35-2.38), psychiatric (RR 2.35; 95%CI 1.66-3.34), and nervous system adverse events (RR 2.35; 95%CI 1.49-3.70). The number needed to harm for psychiatric adverse events is 30.</p> <p>Conclusion</p> <p>Rimonabant is associated with an increased risk of adverse events. Despite of an increasing interest for its use on fatty liver, the security profile and efficacy it is needs to be carefully assessed before its recommendation. At present the use of rimonabant on fatty liver cannot be recommended.</p

MBL2 Genetic Variants in HCV Infection Susceptibility, Spontaneous Viral Clearance and Pegylated Interferon Plus Ribavirin Treatment Response

Hepatitis C is disease that damages the liver, and it is caused by the hepatitis C virus (HCV). The pathology became chronic in about 80% of the cases due to virus persistence in the host organism. The standard of care consists of pegylated interferon plus ribavirin; however, the treatment response is very variable and different host/viral factors may concur in the disease outcome. The mannosebinding protein C (MBL) is a component of the innate immune system, able to recognize HCV and consecutively activating the immune response. MBL is encoded by MBL2 gene, and polymorphisms, two in the promoter region (H/L and X/Y) and three in exon 1 (at codon 52, 54 and 57), have been described as functionally influencing protein expression. In this work, 203 Italian HCV patients and 61 healthy controls were enrolled and genotyped for the five MBL2 polymorphisms mentioned above to investigate their role in HCV infection susceptibility, spontaneous viral clearance and treatment response. MBL2 polymorphisms were not associated with HCV infection susceptibility and with spontaneous viral clearance, while MBL2 O allele, O/O genotype, HYO haplotype and DP combined genotype (all correlated with low or deficient MBL expression) were associated with sustained virological response. Moreover, a meta-analysis to assess the role of MBL2 polymorphisms in HCV infection susceptibility was also performed: YA haplotype could be associated with protection towards HCV infection

MicroRNAs as Regulators of Neo-Angiogenesis in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a highly vascularized neoplasm. In the tumor niche, abundant angiogenesis is fundamental in providing nutrients for tumor growth and represents the first escape route for metastatic cells. Active angiogenesis, together with metastasis, are responsible for the reduction of recurrence-free survival of HCC. MicroRNAs (miRNAs) are small non-coding RNAs that have recently drawn attention in molecular targeted therapy or as diagnostic and prognostic biomarkers. MiRNA expression in HCC has been widely studied in the last decade. Some miRNAs have been found to be up- or down-regulated, besides association with apoptosis, metastasis progression and drug resistance have been found. This review article aims to summarize the angiogenetic process in tumor diseases and to update on what has been found in the vast world of HCC-related-miRNAs and, eventually, to report the latest finding on several miRNAs involved in HCC angiogenesis. We searched the state of the arts for the 12 miRNAs found to be involved with angiogenesis in HCC (miR-29b, miR-126-3p, miR-144-3p, miR-146a, miR-195, miR-199a-3p, miR-210-3p, miR-338- 3p, mir-491, mir-497, mir-638, mir-1301) and reported their main molecular targets and their overall effect in the sprouting of new vessels

The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population

BACKGROUND: Fatty liver (FL) is the most frequent liver disease in Western countries. We used data from the Dionysos Nutrition & Liver Study to develop a simple algorithm for the prediction of FL in the general population. METHODS: 216 subjects with and 280 without suspected liver disease were studied. FL was diagnosed by ultrasonography and alcohol intake was assessed using a 7-day diary. Bootstrapped stepwise logistic regression was used to identify potential predictors of FL among 13 variables of interest [gender, age, ethanol intake, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase (GGT), body mass index (BMI), waist circumference, sum of 4 skinfolds, glucose, insulin, triglycerides, and cholesterol]. Potential predictors were entered into stepwise logistic regression models with the aim of obtaining the most simple and accurate algorithm for the prediction of FL. RESULTS: An algorithm based on BMI, waist circumference, triglycerides and GGT had an accuracy of 0.84 (95%CI 0.81–0.87) in detecting FL. We used this algorithm to develop the "fatty liver index" (FLI), which varies between 0 and 100. A FLI < 30 (negative likelihood ratio = 0.2) rules out and a FLI ≥ 60 (positive likelihood ratio = 4.3) rules in fatty liver. CONCLUSION: FLI is simple to obtain and may help physicians select subjects for liver ultrasonography and intensified lifestyle counseling, and researchers to select patients for epidemiologic studies. Validation of FLI in external populations is needed before it can be employed for these purposes

Systematic review and meta-analysis on the adverse events of rimonabant treatment: Considerations for its potential use in hepatology

<p>Abstract</p> <p>Background</p> <p>The cannabinoid-1 receptor blockers have been proposed in the management of obesity and obesity-related liver diseases (fatty liver as NAFLD or NASH). Due to increasing number of patients to be potentially treated and the need to assess the advantage of this treatment in terms of risk/benefit, we analyze the side events reported during the treatment with rimonabant by a systematic review and meta-analysis of all randomized controlled studies.</p> <p>Methods</p> <p>All published randomized controlled trials using rimonabant <it>versus </it>placebo in adult subjects were retrieved. Relative risks (RR) with 95% confidence interval for relevant adverse events and number needed to harm was calculated.</p> <p>Results</p> <p>Nine trials (n = 9635) were considered. Rimonabant 20 mg was associated with an increased risk of adverse event (RR 1.35; 95%CI 1.17-1.56), increased discontinuation rate (RR 1.79; 95%CI 1.35-2.38), psychiatric (RR 2.35; 95%CI 1.66-3.34), and nervous system adverse events (RR 2.35; 95%CI 1.49-3.70). The number needed to harm for psychiatric adverse events is 30.</p> <p>Conclusion</p> <p>Rimonabant is associated with an increased risk of adverse events. Despite of an increasing interest for its use on fatty liver, the security profile and efficacy it is needs to be carefully assessed before its recommendation. At present the use of rimonabant on fatty liver cannot be recommended.</p

Behind the Decrease of Liver Stiffness After Successful Hepatitis C Virus Eradication with Direct-Acting Antiviral Agents

5N/AopenopenGiuffrè, Mauro; Masutti, Flora; Crosato, Ivo Maria; Luzzati, Roberto; Crocè, Lory SaveriaGiuffrè, Mauro; Masutti, Flora; Crosato, Ivo Maria; Luzzati, Roberto; Crocè, Lory Saveri

Rapid identification system of frontal dysfunction in subclinical hepatic encephalopathy

Introduction and aim. Liver disease is associated with cognitive dysfunction also at early stages, and minimal hepatic encephalopathy, affecting 20-70% of patients, is frequently under-recognized. The main purpose of this work was to demonstrate that a substantial number of patients, enrolled due to an acute confusional state in absence of a diagnosis of liver disease, suffers of hepatic encephalopathy.Material and methods. Before a diagnosis of a well-compensated liver diseases was performed, 410 patients with an acute confusional state were enrolled in this study.Results. Even in the presence of minimal alterations of hepatic function, the psychometric tests applied demonstrated early signs of cerebral frontal alteration. The alteration was associated with the severity of liver disease, paralleling the progression of the patient to minimal hepatic failure or chronic liver disease.Conclusions. These psychometric tests are essential to detect early and subclinical frontal failure. Frontal dysfunction may be a useful tool in the follow-up of these patients

Spleen Stiffness Probability Index (SSPI): A simple and accurate method to detect esophageal varices in patients with compensated liver cirrhosis.

Abstract Introduction and objectives Recent findings pointed out that even low-risk esophageal varices (EVs) are markers of severe prognosis. Accordingly, we analyzed spleen stiffness (SS) as a non-invasive method to predict EVs of any grade in a cohort of patients with compensated liver cirrhosis. Method We measured SS and liver stiffness (LS) using point-Shear-Wave Elastography (pSWE) with Philips Affiniti 70 system in 210 cirrhotic patients who had undergone endoscopic screening for EVs. We compared SS and LS predictive capability for EVs of any grade. Results SS was higher in cirrhotic patients with EVs if compared to patients without EVs (p Conclusion SS showed significantly higher performance than other parameters, proving to be the best non-invasive test in the screening of EVs: by directly applying SS cut-off of 31 kPa, our department could have safely avoided endoscopy in 36% of patients. Despite cut-off analyses, it was possible to create a probability model that could further stratify low-risk from high-risk patients (for any grade of EVs)

Analysis of p53 and ras gene mutations in hepatocellular carcinoma from a Western country

Objective: To evaluate the frequency of p53 tumour suppressor gene and H- and K-ras oncogene mutations in both neoplastic and distant cirrhotic non-neoplastic tissue in Italian patients with hepatocellular carcinoma (HCC). Patients: Ten men and four women (mean age 62 +/-7 years) with HCC associated with cirrhosis, who underwent resection. More than half the patients had a lesion over 3 cm in diameter and in 12 cases carcinoma was well differentiated. Methods: Exons 4 to 9 of p53 and codons 12, 13 and 61 of the H- and K-ras genes were analyzed by the polymerase chain reaction-single strand conformation polymorphism method in both neoplastic and non-adjacent cirrhotic tissue and in cell lines harbouring known mutations as positive controls. Results: No aberrant migrating fragments were observed in tumoral and cirrhotic non-neoplastic tissue. Conclusion: Our findings suggest that p53 mutation is a rare occurrence in HCC, at least in countries with a low incidence of this cancer. They also confirm that H- and K-ras mutations are infrequent in HCC and play a minimal role in hepatocarcinogenesis