Stefano Bellentani - Academia.edu (original) (raw)

Papers by Stefano Bellentani

The Lancet Gastroenterology & Hepatology, Aug 1, 2017

BMC Gastroenterology, Nov 28, 2018

Background: The estimation of the burden of disease attributable to fatty liver requires studies ... more Background: The estimation of the burden of disease attributable to fatty liver requires studies performed in the general population. Methods: The Bagnacavallo Study was performed between October 2005 and March 2009. All the citizens of Bagnacavallo (Ravenna, Italy) aged 30 to 60 years as of January 2005 were eligible. Altered liver enzymes were defined as alanine transaminase > 40 U/l and/or aspartate transaminase > 37 U/l. Results: Four thousand and thirty-three (58%) out of 6920 eligible citizens agreed to participate and 3933 (98%) had complete data. 393 (10%) of the latter had altered liver enzymes and 3540 had not. After exclusion of subjects with HBV or HCV infection, liver ultrasonography was available for 93% of subjects with altered liber enzymes and 52% of those with normal liver enzymes. The prevalence of fatty liver, non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) was 0.74 (95%CI 0.70 to 0.79) vs. 0.35 (0.33 to 0.37), 0.46 (0.41 to 0.51) vs. 0.22 (0.21 to 0.24) and 0.28 (0.24 to 0.33) vs. 0.13 (0.11 to 0.14) in citizens with than in those without altered liver enzymes. Ethanol intake was not associated and all the components of the metabolic syndrome (MS) were associated with fatty liver. All potential risk factors were associated with a lower odds of normal liver vs. NAFLD while they were unable to discriminate AFLD from NAFLD. Conclusions: Fatty liver as a whole was highly prevalent in Bagnacavallo in 2005/9 and was more common among citizens with altered liver enzymes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Apr 5, 2023

Background: Non-Alcoholic Fatty Liver (NAFL) is a spectrum of liver diseases (LD) that ranges fro... more Background: Non-Alcoholic Fatty Liver (NAFL) is a spectrum of liver diseases (LD) that ranges from benign fatty infiltration of the liver to cirrhosis and hepatic failure. Hepatic ultrasound (US) and serum alanine aminotransferase (ALT) are often used as markers of NAFL. Our aim is to describe prevalence of NAFL and associated findings on ultrasound (US) and biochemical parameters in a population of children and adolescents with obesity at the Children's Hospital of Eastern Ontario. Methods: Children with Obesity (BMI >95th percentile) ages 8-17 years presenting to the Endocrinology and Gastroenterology clinics, without underlying LD were prospectively recruited from 2009 to 2012. Fasting lipid profile, HOMA IR) and serum adiponectin levels were measured. NAFL was defined as ALT > 25 and >22 IU/mL (males and females respectively) and/or evidence of fatty infiltration by US. Logistic regression was performed to assess associations. Results: 97 children with obesity included in the study (Male 43%). Mean age was 12.9 ± 3.2 years (84% were older than 10 y). Mean BMI-Z score was 3.8 ± 1.4. NAFL was identified in 85%(82/97) of participants. ALT was elevated in 61% of patients. Median triglyceride (TG) level was higher in children with NAFL(1.5 ± 0.9 vs. 1.1 ± 0.5 mmol/L, p = 0.01). Total cholesterol, HDL, LDL and Non HDL cholesterol were similar in both groups(p = 0.63, p = 0.98, p = 0.72 and p = 0.37 respectively). HOMA IR was ≥3.16 in 53% of children(55% in those with NAFL and 40% in those without NAFL). Median serum adiponectin was 11.2 μg/ml(IQR 7.3-18.3) in children with NAFL vs. 16.1 μg/ ml(IQR 9.0-21.9) in those without NAFL(p = 0.23). Liver US was reported as normal in 30%, mild fatty infiltration in 38%, moderate in 20% and severe in 12%. TG were significantly higher(1.5 mmol/L vs. 1.0 mmol/L, p < 0.01) and HDL-C was lower(1.0 mmol/L vs. 1.1 mmol/L, p = 0.05) in children with moderate and severe NAFL by US. BMI-Z score, HOMA IR, serum adiponectin and HDL levels were not associated with NAFL, however TG were significantly associated(OR = 3.22 (95% CI: 1.01-10.25, p = 0.04)). Conclusion: NAFL is highly prevalent in obese children and youth. Elevated TG levels are associated with NAFL; these findings may serve as a noninvasive screening tool to help clinicians identify children with obesity needing liver biopsy and/or more aggressive therapeutic interventions.

Hepatology, Nov 1, 1988

The hepatic cytosolic estrogen receptor content was measured in liver samples from patients with ... more The hepatic cytosolic estrogen receptor content was measured in liver samples from patients with normal livers and from patients with nonalcoholic cirrhosis, alcoholic cirrhosis and alcoholic hepatitis. The estrogen receptor content of normal liver was 5.2 +/- 3.5 fmoles per mg of cytosolic protein. Levels which were not significantly different from this were found in the samples from patients with nonalcoholic cirrhosis (2.1 +/- 2.0 fmoles per mg of cytosolic protein). The cytosolic estrogen receptor content in the livers of patients with alcoholic cirrhosis who were abstaining was 4.2 +/- 3.6 fmoles per mg of cytosolic protein, but it increased to 10.4 +/- 4.9 fmoles per mg of protein in the livers of patients with alcoholic cirrhosis who were drinking, to 17.3 +/- 8.7 fmoles per mg of protein in the livers of patients with alcoholic hepatitis with cirrhosis and to 22.7 +/- 15.7 fmoles per mg of protein in the livers of patients with alcoholic hepatitis without cirrhosis. Alcohol abuse appeared, therefore, to induce an increase in the estrogen receptor content of human liver, especially in patients who were drinking and had histological evidence of acute liver damage (alcoholic hepatitis). The increase in hepatic estrogen receptor which we have observed may be involved in the molecular mechanisms underlying the feminization of the liver in alcoholic males.

European Journal of Clinical Nutrition, Dec 6, 2006

Objective: To evaluate predictors of non-alcoholic fatty liver disease (NAFLD) in obese children.... more Objective: To evaluate predictors of non-alcoholic fatty liver disease (NAFLD) in obese children. Design: Cross-sectional study. Subjects: Two hundred and sixty-eight obese children not consuming alcohol and without hepatitis B or C were consecutively studied at an auxology clinic. Measurements: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl-transferase (GGT), cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, uric acid, glucose, glucose during oral glucose tolerance testing (OGTT), insulin, insulin during OGTT, insulin resistance as estimated by homeostasis model assessment (HOMA), C-reactive protein (CRP), and systolic and diastolic blood pressure were measured. Fatty liver was diagnosed by ultrasonography using standard criteria. Univariable and multivariable logistic regression was used to evaluate predictors of NAFLD. All predictors except gender and pubertal status were modeled as continuous variables. Results: NAFLD was detected in 44% of obese children. At univariable analysis, male gender, Z-score of body mass index (BMI) (Z-BMI), ALT, AST, GGT, triglycerides, uric acid, glucose, glucose during OGTT, insulin, insulin during OGTT, HOMA, CRP and systolic blood pressure were predictors of NAFLD, whereas HDL-cholesterol and late-pubertal status were predictors of the normal liver. At multivariable analysis, however, only Z-BMI, ALT, uric acid, glucose during OGTT and insulin during OGTT were independent predictors of NAFLD. Conclusion: Z-BMI, ALT, uric acid, glucose during OGTT and insulin during OGTT are independent predictors of NAFLD in Italian obese children, with most of the prediction explained by ALT and Z-BMI.

Clinical liver disease, Oct 1, 2016

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Dec 29, 2006

New techniques such as these employing isolated perfused liver, isolated hepatocytes, and, more r... more New techniques such as these employing isolated perfused liver, isolated hepatocytes, and, more recently, membrane vesicles and hepatocyte couplets have increased our understanding of hepatic transport processes. The isolated perfused liver is the most complicated model used to study liver transport, because all aspects of hepatic architecture participate in the process. Highly purified canalicular and/or basolateral rat liver membrane vesicle preparations are very useful for exploring transport function in various domains of the plasma membrane and for identifying and isolating putative membrane carriers. Isolated hepatocytes are simple to prepare and are useful especially in studying uptake function of the hepatocyte. One limitation of this model is that isolated liver cells in suspension lose their polarity; thus, it is impossible to examine canalicular excretion processes. This problem has been partially solved by the use of hepatocyte couplets [12, 31]. However, this technique is technically demanding and does not lend itself to quantification of water or solute flux.

Springer eBooks, 2017

Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine/chemokine that is an impor... more Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine/chemokine that is an important component of the innate immune response. Recent studies have identified multiple roles for MIF in the progression and resolution of different stages of inflammatory and fibrotic response to liver injury. Here we review the basic functions of MIF and its cognate and non-cognate receptors in hepatic injury and repair, with an emphasis on alcoholic and nonalcoholic liver disease. Specific functions of MIF and its receptors in hepatocytes, Kupffer cells (the resident macrophage in the liver), and hepatic stellate cells are discussed in the context of hepatocyte injury, inflammatory responses and fibrogenesis. Finally, we analyze the potential for MIF as a therapeutic target for hepatic inflammatory and fibrotic diseases.

Microbes and Infection, Nov 1, 2000

In spite of the large diffusion of hepatitis C virus (HCV) infection and its high association wit... more In spite of the large diffusion of hepatitis C virus (HCV) infection and its high association with liver disease, the epidemiology of HCV in Italy is still unclear. This review collects all the data available on the prevalence and incidence of HCV infection in Italy and compares them with those reported in other countries.

The Lancet, Dec 1, 1982

To investigate the susceptibility of chronic symptomless HBsAg carriers to the hepatotoxic effect... more To investigate the susceptibility of chronic symptomless HBsAg carriers to the hepatotoxic effect of ethanol 296 such carriers were followed up for 3 1/2 years with repeated biochemical and clinical examinations. A control group of HBsAg-negative blood donors matched by age, sex, occupation, duration and type of ethanol intake, and state of nutrition were followed up for the same period. Chronic symptomless HBsAg carriers seemed to be at risk of hepatic abnormalities when drinking an amount of ethanol which was harmless for HBsAg-negative subjects (less than 80 g). It may therefore be advisable to suggest complete abstinence from ethanol for HBsAg carriers.

Gut, Sep 1, 1999

Background-Several retrospective and prospective studies report an increased prevalence of non-or... more Background-Several retrospective and prospective studies report an increased prevalence of non-organ-specific autoantibodies (NOSAs) in patients with hepatitis C virus (HCV) related chronic liver disease (CLD). Some of the data so far available are controversial and the true prevalence of NOSAs in the general population is still not known. Aim-To explore the prevalence of NOSAs, their relation to diVerent HCV genotypes, and the presence and severity of CLD in the general population of Northern Italy. Patients-All 226 anti-HCV positive and 87 hepatitis B surface antigen (HBsAg) positive patients of the Dionysos cohort study were analysed and compared with sex and age matched cases (226) negative for both anti-HCV antibody and HBsAg selected from the same cohort. Methods-Sera tested for the presence of NOSAs (anti-nuclear antibody (ANA), anti-smooth muscle antibody (SMA), and anti-liver/kidney microsomes type 1 antibody (LKM1)) were screened by indirect immunofluorescence at a 1:40 serum dilution. HCV RNA and HCV genotypes were also determined by nested polymerase chain reaction (PCR) of the 5' non-coding region and by PCR amplification of the core region with type specific primers. Results-The overall prevalence of NOSA reactivity was significantly higher in anti-HCV positive subjects than in both normal and pathological controls (25% v 6% and 7% respectively, p<0.05). ANA, SMA, and LKM1 occurred in 16, 10, and 1.3% of cases respectively. No specific association between NOSAs and a specific HCV genotype was found. NOSAs were found more often associated with more than one genotype (35.7%) and with untypable genotypes (34.6%), although the association was not statistically significant. NOSAs were associated with HCV RNA and CLD but not with the presence of cirrhosis and/or hepatocellular carcinoma. On univariate analysis, NOSA reactivity was independently associated with abnormal alanine aminotransferase (p<0.01) and-glutamyltranspeptidase levels (p<0.05). The risk for the presence of NOSAs was 5.1 times higher in anti-HCV subjects than in controls. Conclusions-In the general population the prevalence of NOSAs is higher in anti-HCV positive subjects than in normal or disease controls. Moreover NOSAs are associated with CLD and with a more active disease in terms of alanine aminotransferase activity.

Hepatology, Jan 14, 2016

; on behalf of the HCC-NAFLD Italian Study Group* Nonalcoholic fatty liver disease (NAFLD) repres... more ; on behalf of the HCC-NAFLD Italian Study Group* Nonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome and may evolve into hepatocellular carcinoma (HCC). Only scanty clinical information is available on HCC in NAFLD. The aim of this multicenter observational prospective study was to assess the clinical features of patients with NAFLD-related HCC (NAFLD-HCC) and to compare them to those of hepatitis C virus (HCV)-related HCC. A total of 756 patients with either NAFLD (145) or HCV-related chronic liver disease (611) were enrolled in secondary care Italian centers. Survival was modeled according to clinical parameters, lead-time bias, and propensity analysis. Compared to HCV, HCC in NAFLD patients had a larger volume, showed more often an infiltrative pattern, and was detected outside specific surveillance. Cirrhosis was present in only about 50% of NAFLD-HCC patients, in contrast to the near totality of HCV-HCC. Regardless of tumor stage, survival was significantly shorter (P 5 0.017) in patients with NAFLD-HCC, 25.5 months (95% confidence interval 21.9-29.1), than in those with HCV-HCC, 33.7 months (95% confidence interval 31.9-35.4). To eliminate possible confounders, a propensity score analysis was performed, which showed no more significant difference between the two groups. Additionally, analysis of patients within Milan criteria submitted to curative treatments did not show any difference in survival between NAFLD-HCC and HCV-HCC (respectively, 38.6 versus 41.0 months, P 5 nonsignificant) Conclusions: NAFLD-HCC is more often detected at a later tumor stage and could arise also in the absence of cirrhosis, but after patient matching, it has a similar survival rate compared to HCV infection; a future challenge will be to identify patients with NAFLD who require more stringent surveillance in order to offer the most timely and effective treatment.