Helena Cortez-Pinto - Academia.edu (original) (raw)

Papers by Helena Cortez-Pinto

Research paper thumbnail of Global Epidemiology of Non-Alcoholic Fatty Liver Disease-Meta-Analytic Assessment of Prevalence, Incidence and Outcomes

Hepatology (Baltimore, Md.), Jul 28, 2015

NAFLD is a major cause of liver disease worldwide. We estimated the global prevalence, incidence,... more NAFLD is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression and outcomes of NAFLD and NASH. Pubmed/MEDLINE were searched from 1989-2015 for terms involving epidemiology and progression of NAFLD. selected groups (only morbidly obese or diabetics or pediatric), no data on alcohol consumption or other liver diseases. Incidence of HCC, cirrhosis, overall mortality and liver-related mortality were determined. NASH required histologic criteria. All studies were reviewed by 3 independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication and study population. We used random-effects models to provide point estimates (95% CI) of prevalence, incidence, mortality and incidence rate ratios, and meta-regression with sub-group analysis to account for heterogeneity. Out of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. Global prevalence of NAFLD is 25.24% (22.10-28.65) with hi...

Research paper thumbnail of Clinical relevance of liver histopathology and different histological classifications of NASH in adults

Expert review of gastroenterology & hepatology, Jan 26, 2017

Nonalcoholic fatty liver disease (NAFLD) encompasses simple steatosis and steatohepatitis (NASH) ... more Nonalcoholic fatty liver disease (NAFLD) encompasses simple steatosis and steatohepatitis (NASH) with or without fibrosis/cirrhosis and hepatocellular carcinoma. NAFLD occurs epidemically in most areas of the world, contributes to cardiovascular events and liver-related mortality and therefore exacts a major economic toll. Areas covered: Here we summarize what clinicians should know about NAFLD histopathology in adults. We report on the individual histological features and scoring systems of NAFLD: the NAFLD activity score (NAS) introduced by the NASH-Clinical Research Network, the 'Fatty Liver Inhibition of Progression' algorithm and Steatosis, Activity, and Fibrosis (SAF) score. Pros and cons of histological classifications in NASH are discussed. Special emphasis is given to liver histopathology in some high-risk patient groups, such as those with severe obesity and type 2 diabetes. Moreover, we also examine the relationship between liver histopathology and clinical featur...

Research paper thumbnail of The EASL–Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality

The Lancet, 2021

The EASL-Lancet Commission: Protecting the next generation of Europeans against liver disease com... more The EASL-Lancet Commission: Protecting the next generation of Europeans against liver disease complications and premature mortality Frontpage sentence: "The liver is a window to the 21 st century health of the European population."

Research paper thumbnail of Hepatic steatosis in patients coinfected with human immunodeficiency virus/hepatitis C virus: A meta-analysis of the risk factors

Hepatology, 2010

Hepatic steatosis (HS) is frequent in patients with hepatitis C virus (HCV) infection, occurring ... more Hepatic steatosis (HS) is frequent in patients with hepatitis C virus (HCV) infection, occurring in 40%-80%, associating with metabolic and virus-related factors, namely, genotype 3 and viral load. Human immunodeficiency virus (HIV) infection and antiretroviral treatment seem to be risk factors for HS. Several studies addressed this issue in coinfected patients, with discrepant results. A meta-analysis was performed on the HS risk factors in coinfected patients. Eligible studies were identified through structured keywords including coinfection, HCV, HIV, and steatosis in relevant databases including PubMed. Pooled odds ratios (ORs) and confidence limits (CIs) were obtained with the random-effects model and the DerSimonian-Laird method. Twelve studies, including 1,989 coinfected patients, were selected. Twenty percent were infected with HCV genotype 3. The overall prevalence of HS was 50.8% (23%-72%). Four studies also included 1,540 HCV monoinfected patients, not showing an increased risk for HS in coinfected patients (OR 1.61, 95% CI 0.84-3.10, P 5 0.151). In coinfected patients, HS was associated with higher body mass index (

Research paper thumbnail of Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification Biomarkers of NAFLD

Frontiers in Medicine, 2021

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whe... more Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome.Materials and Methods: Leptin, adiponectin, and IGF-1 serum levels were measured by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and healthy-liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD, 31 controls) and correlated with clinical data, histology, genetic parameters, and serum metabolomics.Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p < 0.0001). The leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In the discovery cohort, adiponectin was ...

Research paper thumbnail of Non-alcoholic steatohepatitis: From cell biology to clinical practice

Journal of Hepatology, 2006

Research paper thumbnail of Defining comprehensive models of care for NAFLD

Nature Reviews Gastroenterology & Hepatology, 2021

There is a need for effective models of care for patients with nonalcoholic fatty liver disease (... more There is a need for effective models of care for patients with nonalcoholic fatty liver disease (NAFLD). In this Expert Recommendation, Lazarus et al. discuss seven examples of comprehensive NAFLD models of care, and produce eight recommendations aimed at policymakers and practitioners.

Research paper thumbnail of Non-alcoholic fatty liver disease and insulin resistance: From bench to bedside

Diabetes & Metabolism, 2013

Non-alcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease in the d... more Non-alcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease in the developed countries. There is also growing evidence from basic and clinical research that NAFLD has a strong relationship to insulin resistance, which is a key factor in the development of type 2 diabetes. The aim of this review is to summarize the recent important findings linking NAFLD and insulin resistance. Lipid accumulation, particularly of diacylglycerol, appears to be of major importance in this process. Mitochondrial dysfunction, through decreased mitochondrial biogenesis, increases oxidative stress, and ageing also plays an important role. Finally, endoplasmic reticulum stress and inflammation also probably contribute to the development of insulin resistance via mechanisms that are still not well understood. Clinical aspects of NAFLD, such as its diagnosis and management, are also investigated in this review.

Research paper thumbnail of Noninvasive diagnosis of nonalcoholic fatty liver disease using serum biomarkers

Hepatology, 2007

Another mechanism for coffee's apparent effect may be through the lowering of hepatic iron reserv... more Another mechanism for coffee's apparent effect may be through the lowering of hepatic iron reserves, which is a well known proinflammatory hepatic carcinogen. A study of dietary factors modulating iron stores in free-living elderly populations using a sample of The Framingham Heart Study participants revealed that while supplemental iron, dietary vitamin C, and alcohol were positively associated with serum ferritin, coffee intake had a negative association. 9 In summary, coffee drinking pattern may be a surrogate marker of a clinical state of enhanced detoxification or clearance of hepatic carcinogens. Studies in this direction are needed before we conclude that coffee drinking will reduce risk of HCC by 40%.

Research paper thumbnail of Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal

World journal of hepatology, Jan 8, 2015

To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) meta... more To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnic-geographical differential frequencies (≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele fr...

Research paper thumbnail of Non-alcoholic fatty liver disease: what the clinician needs to know

World journal of gastroenterology : WJG, Jan 28, 2014

Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the West... more Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about one fifth of affected subjects are at risk of developing the progressive form of the disease, non-alcoholic steatohepatitis with fibrosis. Even in the latter, liver disease is slowly progressive, though, since it is so prevalent, it is already the third cause of liver transplantation in the United States, and it is predicted to get to the top of the ranking in few years. Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality. The literature and amount of published papers on NAFLD is increasing as fast as its prevalence, which makes it difficult to keep updated in this topic. This review aims to summarize the latest knowledge on NAFLD, in order to help clinicians understanding its pathogenesis an...

Research paper thumbnail of Alterations in Liver ATP Homeostasis in Human Nonalcoholic Steatohepatitis

JAMA, 1999

Context The mechanisms that drive progression from fatty liver to steatohepatitis and cirrhosis a... more Context The mechanisms that drive progression from fatty liver to steatohepatitis and cirrhosis are unknown. In animal models, obese mice with fatty livers are vulnerable to liver adenosine triphosphate (ATP) depletion and necrosis, suggesting that altered hepatic energy homeostasis may be involved. Objective To determine if patients with fatty liver disease exhibit impaired recovery from hepatic ATP depletion. Design Laboratory analysis of liver ATP stores monitored by nuclear magnetic resonance spectroscopy before and after transient hepatic ATP depletion was induced by fructose injection. The study was conducted between July 15 and August 30, 1998. Setting University hospital. Patients Eight consecutive adults with biopsy-proven nonalcoholic steatohepatitis and 7 healthy age-and sex-matched controls. Main Outcome Measure Level of ATP 1 hour after fructose infusion in patients vs controls. Results In patients, serum aminotransferase levels were increased (P = .02 vs controls); albumin and bilirubin values were normal and clinical evidence of portal hypertension was absent in both groups. However, 2 patients had moderate fibrosis and 1 had cirrhosis on liver biopsy. Mean serum glucose, cholesterol, and triglyceride levels were similar between groups but patients weighed significantly more than controls (P = .02). Liver ATP levels were similar in the 2 groups before fructose infusion and decreased similarly in both after fructose infusion (P = .01 vs initial ATP levels). However, controls replenished their hepatic ATP stores during the 1-hour follow-up period (PϽ.02 vs minimum ATP) but patients did not. Hence, patients' hepatic ATP levels were lower than those of controls at the end of the study (P = .04). Body mass index (BMI) correlated inversely with ATP recovery, even in controls (R = −0.768; P = .07). Although BMI was greater in patients than controls (P = .02) and correlated strongly with fatty liver and serum aminotransferase elevations, neither of the latter 2 parameters nor the histologic severity of fibrosis strongly predicted hepatic ATP recovery. Conclusions These data suggest that recovery from hepatic ATP depletion becomes progressively less efficient as body mass increases in healthy controls and is severely impaired in patients with obesity-related nonalcoholic steatohepatitis.

Research paper thumbnail of How to diagnose NAFLD in 2016

Journal of Hepatology, 2016

Research paper thumbnail of SY04EASL-ESBRA Joint Symposium on Alcoholic Liver DISEASESY04-1EPIDEMIOLOGY of Alcoholic Liver Disease in Europe

Alcohol and Alcoholism, 2015

Europe is the region of the world with the largest consumption of alcohol in the World, according... more Europe is the region of the world with the largest consumption of alcohol in the World, according to the WHO report 2014. This consumption associates with a very heavy economical burden, with alcohol-attributable costs that have been estimated at about 125 billion euros in the European Union for 2003. Furthermore, the proportion of alcohol-attributable deaths relative to all deaths is the highest in WHO European Region. Worldwide, alcohol is the leading cause of liver diseases including cirrhosis, and it is also the most common cause (responsible for 33 to 45%) of hepatocellular carcinoma (HCC) in several countries of Europe and USA. The last decade has witnessed an increase in alcoholrelated cirrhosis in several countries such as Estonia, in Denmark and UK, directly relating to the increase in alcohol consumption, since 1990s in those countries. Another evidence of the high prevalence of alcoholic liver disease in Europe is that it represents one-third of liver transplantation due to liver cirrhosis, although there is evidence that patients with liver disease due to alcohol are less frequently transplanted. Furthermore, alcohol is also a very important contributing factor to other liver diseases, such as viral hepatitis, accelerating progression and increasing the risk for HCC, although difficult to quantify its contribution. Consequently, measures are needed to reduce consumption. It has been shown that the more effective measures are increasing taxation/ price, reducing availability, and reducing advertising in media, mostly publicity targeting young people.

Research paper thumbnail of Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups

Digestive and Liver Disease, 2015

An improved understanding of nonalcoholic fatty liver disease epidemiology would lead to identify... more An improved understanding of nonalcoholic fatty liver disease epidemiology would lead to identifying those groups of individuals at high risk for developing chronic liver disease and extra-hepatic complications thus contributing to more effective case finding of nonalcoholic fatty liver disease among selected groups of individuals. We aimed to illustrate the epidemiology of nonalcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published through May 2015 using relevant and pertinent keywords "nonalcoholic fatty liver disease" and "diabetes", "obesity", "hyperlipidemia", "familial heterozygous hypobelipoproteinemia", "hypertension", "metabolic syndrome", "ethnicity", "family history" or "genetic polymorphisms". We found that age, sex and ethnicity are major physiologic modifiers of the risk of nonalcoholic fatty liver disease, along with belonging to "nonalcoholic fatty liver disease families" and carrying risk alleles for selected genetic polymorphisms. Metabolic syndrome, diabetes, obesity, mixed hyperlipidaemia and hypocholesterolemia due to familial hypobetalipoproteinaemia are the major metabolic modifiers of nonalcoholic fatty liver disease risk. Compared to these metabolic conditions, however, arterial hypertension appears to carry a relatively more modest risk of nonalcoholic fatty liver disease. A better understanding of the epidemiology of nonalcoholic fatty liver disease may result in a more liberal policy of case finding among high-risk groups.

Research paper thumbnail of A position statement on NAFLD/NASH based on the EASL 2009 special conference

Journal of Hepatology, 2010

Research paper thumbnail of Epidemiological modifiers of non-alcoholic fatty liver disease: focus on high-risk groups

Digestive and Liver Disease, 2015

An improved understanding of nonalcoholic fatty liver disease epidemiology would lead to identify... more An improved understanding of nonalcoholic fatty liver disease epidemiology would lead to identifying those groups of individuals at high risk for developing chronic liver disease and extra-hepatic complications thus contributing to more effective case finding of nonalcoholic fatty liver disease among selected groups of individuals. We aimed to illustrate the epidemiology of nonalcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published through May 2015 using relevant and pertinent keywords "nonalcoholic fatty liver disease" and "diabetes", "obesity", "hyperlipidemia", "familial heterozygous hypobelipoproteinemia", "hypertension", "metabolic syndrome", "ethnicity", "family history" or "genetic polymorphisms". We found that age, sex and ethnicity are major physiologic modifiers of the risk of nonalcoholic fatty liver disease, along with belonging to "nonalcoholic fatty liver disease families" and carrying risk alleles for selected genetic polymorphisms. Metabolic syndrome, diabetes, obesity, mixed hyperlipidaemia and hypocholesterolemia due to familial hypobetalipoproteinaemia are the major metabolic modifiers of nonalcoholic fatty liver disease risk. Compared to these metabolic conditions, however, arterial hypertension appears to carry a relatively more modest risk of nonalcoholic fatty liver disease. A better understanding of the epidemiology of nonalcoholic fatty liver disease may result in a more liberal policy of case finding among high-risk groups.

Research paper thumbnail of EASL Clinical Practical Guidelines: Management of Alcoholic Liver Disease

Burden of ALD Burden of alcohol-related disease and injury Alcohol consumption is responsible for... more Burden of ALD Burden of alcohol-related disease and injury Alcohol consumption is responsible for 3.8% of global mortality and 4.6% of disability-adjusted life-years (DALYs) lost due to premature death [4]. The attributable burden in Europe, with 6.5% of all deaths and 11.6% of DALYs attributable to alcohol, is the highest proportion of total ill health and premature deaths due to alcohol of all WHO regions [4,5]. Europe shows particularly large sex differences in burden: the deaths attributable to alcohol being 11.0% and 1.8% for men and women, respectively. The young account for a disproportionate amount of this disease burden, with an alcohol-associated mortality over 10% and 25% of female and male youth, respectively [6]. Burden of ALD in Europe The burden of compensated alcohol cirrhosis among the general population and heavy drinkers is not well known. The development of non-invasive methods to detect significant liver fibrosis (e.g., elastography, serum markers) should help in elucidating this issue. A recent study in France indicates that alcohol abuse accounts for up to one third of liver fibrosis cases [7]. The best comparative proxy for the burden of ALD is mortality from liver cirrhosis as a whole, although as discussed later this has its limitations. Mortality rates from liver cirrhosis vary considerably between European countries [8] with a 15-fold variation between the highest and lowest national rates [9]. However, Europe is essentially divided into two, with Eastern European states tending to have higher rates than the others [8]. Time trends in liver cirrhosis mortality over the past 30 years show very heterogeneous patterns between countries. About half

Research paper thumbnail of Treatment and prognostic factors in patients with hepatocellular carcinoma

Introduction: Hepatocellular carcinoma is a leading cause of death from cancer worldwide. Surviva... more Introduction: Hepatocellular carcinoma is a leading cause of death from cancer worldwide. Survival of patients depends on tumor extension and liver function, but yet there is no consensual prognostic model. Aims: To evaluate the influence on survival of pretreatment parameters (clinicolaboratorial, liver function, tumor extension, Okuda and Cancer of the Liver Italian program (CLIP) staging) and treatment modalities. Methods: We retrospectively analyzed 207 patients, diagnosed between 1993 and 2003. The initial treatment was: surgery-six patients; radiofrequency ablation-21; percutaneous ethanol injection-29; transarterial chemoembolization-49; tamoxifen-49; supportive care alone-53. Factors determining survival were assessed by Kaplan-Meier method and Cox regression models. Results: Median survival was 24 months. In univariate analysis, Child-Pugh classification and Model for end-stage liver disease (MELD) score, portal vein thrombosis (PVT), tumor size, number of lesions, Okuda and CLIP scores were all associated with prognosis (Po0.001). a-Fetoprotein levels were not predictive of survival. Independent predictors of survival were ascites, bilirubin, PVT and therapeutic modalities (Po0.001). In early stage hepatocellular carcinoma (HCC), survival was similar for both percutaneous ablation modalities, either radiofrequency or ethanol injection (P 5 NS). In advanced HCC, survival was better in patients receiving tamoxifen than supportive care alone (Po0.001). Conclusion: This study reinforces the importance of baseline liver function (Child-Pugh classification and MELD score) in the survival of patients with HCC, although staging systems allowed the stratification of patients in different prognostic groups. Ascites, bilirubin and PVT were independent pretreatment predictors of survival. All treatments influenced the patient's outcome, whether in early or advanced stages.

Research paper thumbnail of Epidemiological modifiers of non-alcoholic fatty liver disease: focus on high-risk groups

Digestive and Liver Disease, 2015

An improved understanding of non-alcoholic fatty liver disease epidemiology would lead to identif... more An improved understanding of non-alcoholic fatty liver disease epidemiology would lead to identification of individuals at high risk of developing chronic liver disease and extra-hepatic complications, thus contributing to more effective case finding of non-alcoholic fatty liver disease among selected groups. We aimed to illustrate the epidemiology of non-alcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published until May 2015 using relevant and pertinent keywords &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;nonalcoholic fatty liver disease&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;diabetes&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;obesity&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;hyperlipidaemia&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;familial heterozygous hypobetalipoproteinaemia&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;hypertension&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;metabolic syndrome&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;ethnicity&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;family…

Research paper thumbnail of Global Epidemiology of Non-Alcoholic Fatty Liver Disease-Meta-Analytic Assessment of Prevalence, Incidence and Outcomes

Hepatology (Baltimore, Md.), Jul 28, 2015

NAFLD is a major cause of liver disease worldwide. We estimated the global prevalence, incidence,... more NAFLD is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression and outcomes of NAFLD and NASH. Pubmed/MEDLINE were searched from 1989-2015 for terms involving epidemiology and progression of NAFLD. selected groups (only morbidly obese or diabetics or pediatric), no data on alcohol consumption or other liver diseases. Incidence of HCC, cirrhosis, overall mortality and liver-related mortality were determined. NASH required histologic criteria. All studies were reviewed by 3 independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication and study population. We used random-effects models to provide point estimates (95% CI) of prevalence, incidence, mortality and incidence rate ratios, and meta-regression with sub-group analysis to account for heterogeneity. Out of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. Global prevalence of NAFLD is 25.24% (22.10-28.65) with hi...

Research paper thumbnail of Clinical relevance of liver histopathology and different histological classifications of NASH in adults

Expert review of gastroenterology & hepatology, Jan 26, 2017

Nonalcoholic fatty liver disease (NAFLD) encompasses simple steatosis and steatohepatitis (NASH) ... more Nonalcoholic fatty liver disease (NAFLD) encompasses simple steatosis and steatohepatitis (NASH) with or without fibrosis/cirrhosis and hepatocellular carcinoma. NAFLD occurs epidemically in most areas of the world, contributes to cardiovascular events and liver-related mortality and therefore exacts a major economic toll. Areas covered: Here we summarize what clinicians should know about NAFLD histopathology in adults. We report on the individual histological features and scoring systems of NAFLD: the NAFLD activity score (NAS) introduced by the NASH-Clinical Research Network, the 'Fatty Liver Inhibition of Progression' algorithm and Steatosis, Activity, and Fibrosis (SAF) score. Pros and cons of histological classifications in NASH are discussed. Special emphasis is given to liver histopathology in some high-risk patient groups, such as those with severe obesity and type 2 diabetes. Moreover, we also examine the relationship between liver histopathology and clinical featur...

Research paper thumbnail of The EASL–Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality

The Lancet, 2021

The EASL-Lancet Commission: Protecting the next generation of Europeans against liver disease com... more The EASL-Lancet Commission: Protecting the next generation of Europeans against liver disease complications and premature mortality Frontpage sentence: "The liver is a window to the 21 st century health of the European population."

Research paper thumbnail of Hepatic steatosis in patients coinfected with human immunodeficiency virus/hepatitis C virus: A meta-analysis of the risk factors

Hepatology, 2010

Hepatic steatosis (HS) is frequent in patients with hepatitis C virus (HCV) infection, occurring ... more Hepatic steatosis (HS) is frequent in patients with hepatitis C virus (HCV) infection, occurring in 40%-80%, associating with metabolic and virus-related factors, namely, genotype 3 and viral load. Human immunodeficiency virus (HIV) infection and antiretroviral treatment seem to be risk factors for HS. Several studies addressed this issue in coinfected patients, with discrepant results. A meta-analysis was performed on the HS risk factors in coinfected patients. Eligible studies were identified through structured keywords including coinfection, HCV, HIV, and steatosis in relevant databases including PubMed. Pooled odds ratios (ORs) and confidence limits (CIs) were obtained with the random-effects model and the DerSimonian-Laird method. Twelve studies, including 1,989 coinfected patients, were selected. Twenty percent were infected with HCV genotype 3. The overall prevalence of HS was 50.8% (23%-72%). Four studies also included 1,540 HCV monoinfected patients, not showing an increased risk for HS in coinfected patients (OR 1.61, 95% CI 0.84-3.10, P 5 0.151). In coinfected patients, HS was associated with higher body mass index (

Research paper thumbnail of Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification Biomarkers of NAFLD

Frontiers in Medicine, 2021

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whe... more Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome.Materials and Methods: Leptin, adiponectin, and IGF-1 serum levels were measured by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and healthy-liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD, 31 controls) and correlated with clinical data, histology, genetic parameters, and serum metabolomics.Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p < 0.0001). The leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In the discovery cohort, adiponectin was ...

Research paper thumbnail of Non-alcoholic steatohepatitis: From cell biology to clinical practice

Journal of Hepatology, 2006

Research paper thumbnail of Defining comprehensive models of care for NAFLD

Nature Reviews Gastroenterology & Hepatology, 2021

There is a need for effective models of care for patients with nonalcoholic fatty liver disease (... more There is a need for effective models of care for patients with nonalcoholic fatty liver disease (NAFLD). In this Expert Recommendation, Lazarus et al. discuss seven examples of comprehensive NAFLD models of care, and produce eight recommendations aimed at policymakers and practitioners.

Research paper thumbnail of Non-alcoholic fatty liver disease and insulin resistance: From bench to bedside

Diabetes & Metabolism, 2013

Non-alcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease in the d... more Non-alcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease in the developed countries. There is also growing evidence from basic and clinical research that NAFLD has a strong relationship to insulin resistance, which is a key factor in the development of type 2 diabetes. The aim of this review is to summarize the recent important findings linking NAFLD and insulin resistance. Lipid accumulation, particularly of diacylglycerol, appears to be of major importance in this process. Mitochondrial dysfunction, through decreased mitochondrial biogenesis, increases oxidative stress, and ageing also plays an important role. Finally, endoplasmic reticulum stress and inflammation also probably contribute to the development of insulin resistance via mechanisms that are still not well understood. Clinical aspects of NAFLD, such as its diagnosis and management, are also investigated in this review.

Research paper thumbnail of Noninvasive diagnosis of nonalcoholic fatty liver disease using serum biomarkers

Hepatology, 2007

Another mechanism for coffee's apparent effect may be through the lowering of hepatic iron reserv... more Another mechanism for coffee's apparent effect may be through the lowering of hepatic iron reserves, which is a well known proinflammatory hepatic carcinogen. A study of dietary factors modulating iron stores in free-living elderly populations using a sample of The Framingham Heart Study participants revealed that while supplemental iron, dietary vitamin C, and alcohol were positively associated with serum ferritin, coffee intake had a negative association. 9 In summary, coffee drinking pattern may be a surrogate marker of a clinical state of enhanced detoxification or clearance of hepatic carcinogens. Studies in this direction are needed before we conclude that coffee drinking will reduce risk of HCC by 40%.

Research paper thumbnail of Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal

World journal of hepatology, Jan 8, 2015

To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) meta... more To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnic-geographical differential frequencies (≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele fr...

Research paper thumbnail of Non-alcoholic fatty liver disease: what the clinician needs to know

World journal of gastroenterology : WJG, Jan 28, 2014

Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the West... more Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about one fifth of affected subjects are at risk of developing the progressive form of the disease, non-alcoholic steatohepatitis with fibrosis. Even in the latter, liver disease is slowly progressive, though, since it is so prevalent, it is already the third cause of liver transplantation in the United States, and it is predicted to get to the top of the ranking in few years. Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality. The literature and amount of published papers on NAFLD is increasing as fast as its prevalence, which makes it difficult to keep updated in this topic. This review aims to summarize the latest knowledge on NAFLD, in order to help clinicians understanding its pathogenesis an...

Research paper thumbnail of Alterations in Liver ATP Homeostasis in Human Nonalcoholic Steatohepatitis

JAMA, 1999

Context The mechanisms that drive progression from fatty liver to steatohepatitis and cirrhosis a... more Context The mechanisms that drive progression from fatty liver to steatohepatitis and cirrhosis are unknown. In animal models, obese mice with fatty livers are vulnerable to liver adenosine triphosphate (ATP) depletion and necrosis, suggesting that altered hepatic energy homeostasis may be involved. Objective To determine if patients with fatty liver disease exhibit impaired recovery from hepatic ATP depletion. Design Laboratory analysis of liver ATP stores monitored by nuclear magnetic resonance spectroscopy before and after transient hepatic ATP depletion was induced by fructose injection. The study was conducted between July 15 and August 30, 1998. Setting University hospital. Patients Eight consecutive adults with biopsy-proven nonalcoholic steatohepatitis and 7 healthy age-and sex-matched controls. Main Outcome Measure Level of ATP 1 hour after fructose infusion in patients vs controls. Results In patients, serum aminotransferase levels were increased (P = .02 vs controls); albumin and bilirubin values were normal and clinical evidence of portal hypertension was absent in both groups. However, 2 patients had moderate fibrosis and 1 had cirrhosis on liver biopsy. Mean serum glucose, cholesterol, and triglyceride levels were similar between groups but patients weighed significantly more than controls (P = .02). Liver ATP levels were similar in the 2 groups before fructose infusion and decreased similarly in both after fructose infusion (P = .01 vs initial ATP levels). However, controls replenished their hepatic ATP stores during the 1-hour follow-up period (PϽ.02 vs minimum ATP) but patients did not. Hence, patients' hepatic ATP levels were lower than those of controls at the end of the study (P = .04). Body mass index (BMI) correlated inversely with ATP recovery, even in controls (R = −0.768; P = .07). Although BMI was greater in patients than controls (P = .02) and correlated strongly with fatty liver and serum aminotransferase elevations, neither of the latter 2 parameters nor the histologic severity of fibrosis strongly predicted hepatic ATP recovery. Conclusions These data suggest that recovery from hepatic ATP depletion becomes progressively less efficient as body mass increases in healthy controls and is severely impaired in patients with obesity-related nonalcoholic steatohepatitis.

Research paper thumbnail of How to diagnose NAFLD in 2016

Journal of Hepatology, 2016

Research paper thumbnail of SY04EASL-ESBRA Joint Symposium on Alcoholic Liver DISEASESY04-1EPIDEMIOLOGY of Alcoholic Liver Disease in Europe

Alcohol and Alcoholism, 2015

Europe is the region of the world with the largest consumption of alcohol in the World, according... more Europe is the region of the world with the largest consumption of alcohol in the World, according to the WHO report 2014. This consumption associates with a very heavy economical burden, with alcohol-attributable costs that have been estimated at about 125 billion euros in the European Union for 2003. Furthermore, the proportion of alcohol-attributable deaths relative to all deaths is the highest in WHO European Region. Worldwide, alcohol is the leading cause of liver diseases including cirrhosis, and it is also the most common cause (responsible for 33 to 45%) of hepatocellular carcinoma (HCC) in several countries of Europe and USA. The last decade has witnessed an increase in alcoholrelated cirrhosis in several countries such as Estonia, in Denmark and UK, directly relating to the increase in alcohol consumption, since 1990s in those countries. Another evidence of the high prevalence of alcoholic liver disease in Europe is that it represents one-third of liver transplantation due to liver cirrhosis, although there is evidence that patients with liver disease due to alcohol are less frequently transplanted. Furthermore, alcohol is also a very important contributing factor to other liver diseases, such as viral hepatitis, accelerating progression and increasing the risk for HCC, although difficult to quantify its contribution. Consequently, measures are needed to reduce consumption. It has been shown that the more effective measures are increasing taxation/ price, reducing availability, and reducing advertising in media, mostly publicity targeting young people.

Research paper thumbnail of Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups

Digestive and Liver Disease, 2015

An improved understanding of nonalcoholic fatty liver disease epidemiology would lead to identify... more An improved understanding of nonalcoholic fatty liver disease epidemiology would lead to identifying those groups of individuals at high risk for developing chronic liver disease and extra-hepatic complications thus contributing to more effective case finding of nonalcoholic fatty liver disease among selected groups of individuals. We aimed to illustrate the epidemiology of nonalcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published through May 2015 using relevant and pertinent keywords "nonalcoholic fatty liver disease" and "diabetes", "obesity", "hyperlipidemia", "familial heterozygous hypobelipoproteinemia", "hypertension", "metabolic syndrome", "ethnicity", "family history" or "genetic polymorphisms". We found that age, sex and ethnicity are major physiologic modifiers of the risk of nonalcoholic fatty liver disease, along with belonging to "nonalcoholic fatty liver disease families" and carrying risk alleles for selected genetic polymorphisms. Metabolic syndrome, diabetes, obesity, mixed hyperlipidaemia and hypocholesterolemia due to familial hypobetalipoproteinaemia are the major metabolic modifiers of nonalcoholic fatty liver disease risk. Compared to these metabolic conditions, however, arterial hypertension appears to carry a relatively more modest risk of nonalcoholic fatty liver disease. A better understanding of the epidemiology of nonalcoholic fatty liver disease may result in a more liberal policy of case finding among high-risk groups.

Research paper thumbnail of A position statement on NAFLD/NASH based on the EASL 2009 special conference

Journal of Hepatology, 2010

Research paper thumbnail of Epidemiological modifiers of non-alcoholic fatty liver disease: focus on high-risk groups

Digestive and Liver Disease, 2015

An improved understanding of nonalcoholic fatty liver disease epidemiology would lead to identify... more An improved understanding of nonalcoholic fatty liver disease epidemiology would lead to identifying those groups of individuals at high risk for developing chronic liver disease and extra-hepatic complications thus contributing to more effective case finding of nonalcoholic fatty liver disease among selected groups of individuals. We aimed to illustrate the epidemiology of nonalcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published through May 2015 using relevant and pertinent keywords "nonalcoholic fatty liver disease" and "diabetes", "obesity", "hyperlipidemia", "familial heterozygous hypobelipoproteinemia", "hypertension", "metabolic syndrome", "ethnicity", "family history" or "genetic polymorphisms". We found that age, sex and ethnicity are major physiologic modifiers of the risk of nonalcoholic fatty liver disease, along with belonging to "nonalcoholic fatty liver disease families" and carrying risk alleles for selected genetic polymorphisms. Metabolic syndrome, diabetes, obesity, mixed hyperlipidaemia and hypocholesterolemia due to familial hypobetalipoproteinaemia are the major metabolic modifiers of nonalcoholic fatty liver disease risk. Compared to these metabolic conditions, however, arterial hypertension appears to carry a relatively more modest risk of nonalcoholic fatty liver disease. A better understanding of the epidemiology of nonalcoholic fatty liver disease may result in a more liberal policy of case finding among high-risk groups.

Research paper thumbnail of EASL Clinical Practical Guidelines: Management of Alcoholic Liver Disease

Burden of ALD Burden of alcohol-related disease and injury Alcohol consumption is responsible for... more Burden of ALD Burden of alcohol-related disease and injury Alcohol consumption is responsible for 3.8% of global mortality and 4.6% of disability-adjusted life-years (DALYs) lost due to premature death [4]. The attributable burden in Europe, with 6.5% of all deaths and 11.6% of DALYs attributable to alcohol, is the highest proportion of total ill health and premature deaths due to alcohol of all WHO regions [4,5]. Europe shows particularly large sex differences in burden: the deaths attributable to alcohol being 11.0% and 1.8% for men and women, respectively. The young account for a disproportionate amount of this disease burden, with an alcohol-associated mortality over 10% and 25% of female and male youth, respectively [6]. Burden of ALD in Europe The burden of compensated alcohol cirrhosis among the general population and heavy drinkers is not well known. The development of non-invasive methods to detect significant liver fibrosis (e.g., elastography, serum markers) should help in elucidating this issue. A recent study in France indicates that alcohol abuse accounts for up to one third of liver fibrosis cases [7]. The best comparative proxy for the burden of ALD is mortality from liver cirrhosis as a whole, although as discussed later this has its limitations. Mortality rates from liver cirrhosis vary considerably between European countries [8] with a 15-fold variation between the highest and lowest national rates [9]. However, Europe is essentially divided into two, with Eastern European states tending to have higher rates than the others [8]. Time trends in liver cirrhosis mortality over the past 30 years show very heterogeneous patterns between countries. About half

Research paper thumbnail of Treatment and prognostic factors in patients with hepatocellular carcinoma

Introduction: Hepatocellular carcinoma is a leading cause of death from cancer worldwide. Surviva... more Introduction: Hepatocellular carcinoma is a leading cause of death from cancer worldwide. Survival of patients depends on tumor extension and liver function, but yet there is no consensual prognostic model. Aims: To evaluate the influence on survival of pretreatment parameters (clinicolaboratorial, liver function, tumor extension, Okuda and Cancer of the Liver Italian program (CLIP) staging) and treatment modalities. Methods: We retrospectively analyzed 207 patients, diagnosed between 1993 and 2003. The initial treatment was: surgery-six patients; radiofrequency ablation-21; percutaneous ethanol injection-29; transarterial chemoembolization-49; tamoxifen-49; supportive care alone-53. Factors determining survival were assessed by Kaplan-Meier method and Cox regression models. Results: Median survival was 24 months. In univariate analysis, Child-Pugh classification and Model for end-stage liver disease (MELD) score, portal vein thrombosis (PVT), tumor size, number of lesions, Okuda and CLIP scores were all associated with prognosis (Po0.001). a-Fetoprotein levels were not predictive of survival. Independent predictors of survival were ascites, bilirubin, PVT and therapeutic modalities (Po0.001). In early stage hepatocellular carcinoma (HCC), survival was similar for both percutaneous ablation modalities, either radiofrequency or ethanol injection (P 5 NS). In advanced HCC, survival was better in patients receiving tamoxifen than supportive care alone (Po0.001). Conclusion: This study reinforces the importance of baseline liver function (Child-Pugh classification and MELD score) in the survival of patients with HCC, although staging systems allowed the stratification of patients in different prognostic groups. Ascites, bilirubin and PVT were independent pretreatment predictors of survival. All treatments influenced the patient's outcome, whether in early or advanced stages.

Research paper thumbnail of Epidemiological modifiers of non-alcoholic fatty liver disease: focus on high-risk groups

Digestive and Liver Disease, 2015

An improved understanding of non-alcoholic fatty liver disease epidemiology would lead to identif... more An improved understanding of non-alcoholic fatty liver disease epidemiology would lead to identification of individuals at high risk of developing chronic liver disease and extra-hepatic complications, thus contributing to more effective case finding of non-alcoholic fatty liver disease among selected groups. We aimed to illustrate the epidemiology of non-alcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published until May 2015 using relevant and pertinent keywords &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;nonalcoholic fatty liver disease&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;diabetes&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;obesity&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;hyperlipidaemia&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;familial heterozygous hypobetalipoproteinaemia&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;hypertension&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;metabolic syndrome&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;ethnicity&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;family…