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NAFLD in Asia -As common and important as in the West
Abstract and Figures
NAFLD-regarded as a consequence of the modern sedentary, food-abundant lifestyle prevalent in the West-was recorded in Japan nearly 50 years ago and its changing epidemiology during the past three decades is well-documented. NAFLD, and its pathologically more severe form NASH, occur in genetically susceptible people who are over-nourished. Asian people are particularly susceptible, partly owing to body composition differences in fat and muscle. Community prevalence ranges between 20% (China), 27% (Hong Kong), and 15-45% (South Asia, South-East Asia, Korea, Japan and Taiwan). This Review presents emerging data on genetic polymorphisms that predispose Asian people to NAFLD, NASH and cirrhosis, and discusses the clinical and pathological outcomes of these disorders. NAFLD is unlikely to be less severe in Asians than in other populations, but the associated obesity and diabetes pandemics have occurred more recently in Asia than in Europe and the USA, and occur with reduced degrees of adiposity. Cases of cryptogenic cirrhosis and hepatocellular carcinoma have also been attributed to NAFLD. Public health efforts to curb over-nutrition and insulin resistance are needed to prevent and/or reverse NAFLD, as well as its adverse health outcomes of type 2 diabetes, cardiovascular events, cirrhosis and liver cancer.
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... NAFLD encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) with or without fibrosis, and cirrhosis (2). The global prevalence of NAFLD is approximately 25%, with variability observed across different regions, including 15-45% in Asian countries (3,4). In Pakistan, the prevalence estimates range between 14-47%, indicating a significant burden (5)(6)(7)(8). ...
Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of chronic liver disease worldwide, with a rising incidence in developing countries. In Pakistan, the estimated prevalence ranges from 14-47%. Studies have shown that NAFLD is also not uncommon among the non-obese lean population. Objective: The aim of this study was to evaluate the factors predictive of non-alcoholic fatty liver disease in a non-obese Pakistani population, defined by a body mass index (BMI) of less than 23 kg/m². Methods: This cross-sectional study was conducted at the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation from November 1, 2020, to October 31, 2021. A total of 194 patients with BMI < 23 kg/m² presenting with abdominal pain were included. Exclusion criteria were viral hepatitis, significant alcohol intake, hepatocellular carcinoma, or other malignancies. Data collection involved recording demographic information, medical history, and clinical parameters. Ultrasound abdomen examinations were performed after 8-10 hours of fasting to diagnose NAFLD. Clinical assessments included history of hypertension and smoking, and laboratory tests such as liver function tests, fasting blood sugar levels, and lipid profiles. The primary outcome was the presence of fatty liver on ultrasound. Statistical analysis was conducted using SPSS version 25.0. Continuous variables were analyzed using the Student t-test and categorical variables using the Chi-square test. Significant variables in univariate analysis underwent multivariate logistic regression to identify independent predictors of lean NAFLD. A p-value ≤ 0.05 was considered significant. Results: Out of the 194 patients, 107 (55.2%) were females. The mean age was 36.1 ± 9.6 years, and the mean BMI was 21 ± 1.7 kg/m². NAFLD was detected in 48 (24.7%) patients. Among the study population, 78 (40.2%) were hypertensive, 40 (20.6%) were diabetic, 49 (25.3%) were smokers, and 54 (27.8%) had increased triglyceride levels. Decreased HDL-C levels were observed in 72 (37.1%) patients. Univariate analysis identified hypertension (p ≤ 0.001), diabetes (p ≤ 0.001), smoking (p ≤ 0.001), hypertriglyceridemia (p ≤ 0.001), and decreased HDL-C levels (p ≤ 0.001) as significant factors. Multivariate logistic regression showed that diabetes (OR: 9.4, p = 0.037), smoking (OR: 46.4, p ≤ 0.001), hypertriglyceridemia (OR: 4.75, p = 0.016), and decreased HDL-C levels (OR: 36.8, p ≤ 0.001) were independently associated with lean NAFLD. Conclusion: Non-obese individuals with a BMI less than 23 kg/m² can develop NAFLD and related complications. The study identified diabetes, smoking, hypertriglyceridemia, and decreased HDL-C levels as significant predictors of lean NAFLD. Further studies are needed to enhance the understanding of the disease's risk factors and behavior in this population.
... 8 Although this sounded politically correct, this "theory" was soon debunked when data began to emerge that showed NAFLD to be as common, if not more prevalent, in rural and agrarian societies. 9,10 In the study published from the Eastern part of India two decades ago, in a predominantly rural population, it was found that one fourth of the subjects, people who were untouched by industrialization and affluence, had NAFLD. 9 The whole nomenclature bandwagon seems to be driven by myths only. ...
... 8 Although this sounded politically correct, this "theory" was soon debunked when data began to emerge that showed NAFLD to be as common, if not more prevalent, in rural and agrarian societies. 9,10 In the study published from the Eastern part of India two decades ago, in a predominantly rural population, it was found that one fourth of the subjects, people who were untouched by industrialization and affluence, had NAFLD. 9 The whole nomenclature bandwagon seems to be driven by myths only. ...
... Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver conditions that ranges from steatosis to nonalcoholic steatohepatitis with or without liver fibrosis [1]. The prevalence of NAFLD ranges from 11.4% to 44.5% in Taiwan [2] and from 20% to 27% in China and Hong Kong [3]. NAFLD is becoming an increasingly common indication for liver transplantation in the United States [4], with a similar increasing trend also noted in Europe [5]. ...
... In Western countries, it is estimated that one-third of the general population is affected by NAFLD which is associated with excess body weight and diabetes mellitus. Moreover, the disease is highly prevalent in the Middle East and the rate of incidence is growing in the Asian subcontinent and the Far East nations [7][8][9]. Altogether, NAFLD has become the most common chronic liver disorder with a worldwide prevalence of around 25% of the adult population that is recognized to be closely and bidirectionally related to components of metabolic syndrome [9,10]. ...
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent type of chronic liver disease. However, the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies. Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoetiology and suggest functional therapeutic and diagnostic options. Pyroptosis, ferroptosis, and necroptosis are the main subtypes of non-apoptotic regulated cell deaths (RCDs), each of which represents particular characteristics. Considering the complexity of the findings, the present study aimed to review these types of RCDs and their contribution to NAFLD progression, and subsequently discuss in detail the role of necroptosis in the pathoetiology, diagnosis, and treatment of the disease. The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer, hence it has potential in diagnostic and therapeutic approaches. Nevertheless, further studies are necessary.
... Studies observed that for every 5-unit increase in the body mass index (BMI) above 25 kg/m 2 , the mortality rate increased by 29% (7,8). The increasing prevalence of obesity and T2DM is associated with the rising trend of NAFLD, an emerging healthcare challenge in Asia that is prevalent in about a third of Iranian adults (9)(10)(11)(12). ...
Background
Iran is facing an epidemiological transition with the increasing burden of non-communicable diseases, such as obesity-related disorders and cardiovascular diseases (CVDs). We conducted a population-based prospective study to assess the prevalence and incidence rates of CVDs and obesity-related metabolic disorders and to evaluate the predictive ability of various CVD risk assessment tools in an Iranian population.
Method
We enrolled 5,799 participants in Amol, a city in northern Iran, in 2009–2010 and carried out the first repeated measurement (RM) after seven years (2016–2017). For all participants, demographic, anthropometric, laboratory, hepatobiliary imaging, and electrocardiography data have been collected in the enrollment and the RM. After enrollment, all participants have been and will be followed up annually for 20 years, both actively and passively.
Results
We adopted a multidisciplinary approach to overcome barriers to participation and achieved a 7-year follow-up success rate of 93.0% with an active follow-up of 5,394 participants aged 18–90 years. In the RM, about 64.0% of men and 81.2% of women were obese or overweight. In 2017, about 16.2% and 5.2% of men had moderate or severe non-alcoholic fatty liver disease, while women had a significantly higher prevalence of metabolic syndrome (35.9%), and type 2 diabetes mellitus (20.9%) than men. Of 160 deceased participants, 69 cases (43.1%) died due to CVDs over seven years.
Conclusion
The most prevalent obesity-related chronic disease in the study was metabolic syndrome. Across the enrollment and RM phases, women exhibited a higher prevalence of obesity-related metabolic disorders. Focusing on obesity-related metabolic disorders in a population not represented previously and a multidisciplinary approach for enrolling and following up were the strengths of this study. The study outcomes offer an evidence base for future research and inform policies regarding non-communicable diseases in northern Iran.
Background: Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health issue with a global prevalence that mirrors the rise in obesity and metabolic syndrome. Non-invasive diagnostic indices like the Waist to Height Ratio (WHtR) and the Fatty Liver Index (FLI) are crucial for early detection and management, offering an alternative to the invasive liver biopsy. These indices are particularly pertinent for populations with distinctive body compositions, such as those seen in Asian countries, where traditional measures like Body Mass Index (BMI) may not accurately reflect metabolic risk. Objective: To evaluate the efficacy of WHtR and FLI as non-invasive diagnostic tools for NAFLD in both lean and obese populations, and to identify the most reliable indicator for predicting the presence of fatty liver disease across different body compositions. Methods: This cross-sectional study was approved by the Ethical Review Board (ERC-771) and conducted at the Sindh Institute of Urology and Transplantation. It included 757 participants aged 18-70 years, with 559 lean and 298 obese individuals based on BMI classifications. Exclusion criteria included other forms of hepatitis, use of steatogenic medication, and significant gastrointestinal disorders. Diagnostic measures included abdominal ultrasonography performed by an expert radiologist and calculation of WHtR and FLI. Statistical analyses were performed using SPSS version 25, and diagnostic accuracy was assessed through sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Area Under the Receiver Operating Characteristic (AUROC) curves. Results: Fatty liver was detected in 49% of obese patients and 33% of lean patients. The obese cohort demonstrated a WHtR >0.63 with a diagnostic accuracy of 94.63%, whereas the FLI had a diagnostic accuracy of 83.6% for a cutoff >74. In lean patients, FLI >16.5 was more predictive of NAFLD with a diagnostic accuracy of 96.96%, as opposed to WHtR, which was less effective. The AUROC for WHtR and FLI in obese patients was 0.847 and 0.704, respectively, while in lean patients, the AUROC for FLI was 0.875, suggesting superior diagnostic performance over WHtR. Conclusion: The study confirms that WHtR and FLI are valuable non-invasive tools for predicting NAFLD, with WHtR being more effective in obese patients and FLI showing greater reliability in lean patients. These findings highlight the need for tailored approaches in diagnosing NAFLD according to body composition. Further large-scale, multicentric research is needed to generalize these diagnostic cut-offs.
Background and Aim
This study aimed to clarify the efficacy and safety of 48‐week pemafibrate treatment in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD) complicated by dyslipidemia.
Methods
A total of 110 patients diagnosed with MASLD complicated by dyslipidemia received pemafibrate at a dose of 0.1 mg twice daily for 48 weeks.
Results
The participants were 54 males and 37 females, with a median age of 63 (52–71) years. Besides improvement in lipid profile, significant reductions from baseline to 48 weeks of treatment were found in liver‐related enzymes, such as aspartate aminotransferase, alanine aminotransferase (ALT), gamma‐glutamyl transpeptidase, and alkaline phosphatase ( P < 0.001 for all). A significant decrease in the homeostasis model assessment‐insulin resistance (HOMA‐IR) was observed in patients with insulin resistance (HOMA‐IR ≥ 2.5) (4.34 at baseline to 3.89 at Week 48, P < 0.05). Moreover, changes in ALT were weakly correlated with those in HOMA‐IR ( r = 0.34; p < 0.05). Regarding noninvasive liver fibrosis tests, platelets, Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein, type IV collagen 7s, and the non‐alcoholic fatty liver disease fibrosis score significantly decreased from baseline to Week 48. Most adverse events were Grades 1–2, and no drug‐related Grade 3 or higher adverse events were observed.
Conclusion
This study demonstrated that 48‐week pemafibrate administration improved liver‐related enzymes and surrogate marker of liver fibrosis in patients with MASLD. The improvement of insulin resistance by pemafibrate may contribute to the favorable effect on MASLD complicated by dyslipidemia.
This guidance provides a data-supported approach to the diagnostic, therapeutic, and preventive aspects of NAFLD care. A "Guidance" document is different from a "Guideline." Guidelines are developed by a multidisciplinary panel of experts and rate the quality (level) of the evidence and the strength of each recommendation using the Grading of Recommendations, Assessment Development, and Evaluation (GRADE) system. A guidance document is developed by a panel of experts in the topic, and guidance statements, not recommendations, are put forward to help clinicians understand and implement the most recent evidence. This article is protected by copyright. All rights reserved.
Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.
Plasma lipids and lipoproteins, glucose tolerance, plasma insulin response to glucose load, and liver function were examined in 81 relatives of 12 index cases with primary endogenous hypertriglyceridemia, hyperinsulinemia, and hepatic steatosis, as well as in 90 nonrelatives, including the spouses, as controls. Insulin hypersecretion (with or without glucose intolerance), endogenous hypertriglyceridemia, and abnormal liver function suggesting hepatic steatosis were shown to exist in the relatives mostly in combined fashion. Correlation analysis and stepwise multiple regression analysis revealed that the combined disorder developed on the basis of obesity. The incidence of diabetes mellitus was significantly high in the relatives (14.8 per cent) as compared with the normal Japanese population (3.5 per cent).
Although the vertical transmission of the combined disorder was noted in almost all pedigrees, the frequency distribution analysis of insulin response, glucose tolerance, and plasma triglyceride showed the histograms of these variables similarly skewed to the right as compared with those in the controls, with no apparent bimodality.
In view of the hitherto suggested role of insulin in triglyceride metabolism, it is concluded that hyperinsulinemia coupled with obesity seems to be the basic trait of this form of familial hypertriglyceridemia and hepatic steatosis, though the mode of transmission remains to be elucidated.
Background: The frequent association of nonalcoholic fatty liver disease with components of the metabolic syndrome such as obesity, hyperglycemia, dyslipidemia, and hypertension is well known. However, no prospective study has examined the role of the metabolic syndrome in the development of this disease. Objective: To characterize the longitudinal relationship between the metabolic syndrome and nonalcoholic fatty liver disease. Design: A prospective observational study. Setting: A medical health checkup program in a general hospital. Participants: 4401 apparently healthy Japanese men and women, 21 to 80 years of age, with a mean body mass index (BMI) of 22.6 kg/m 2 (SD, 3.0). Measurements: Alcohol intake was assessed by using a questionnaire. Biochemical tests for liver and metabolic function and abdominal ultrasonography were done. Modified criteria of the National Cholesterol Education Program Adult Treatment Panel III were used to characterize the metabolic syndrome. Results: At baseline, 812 of 4401 (18%) participants had nonalcoholic fatty liver disease. During the mean follow-up period of 414 days (SD, 128), the authors observed 308 new cases (10%) of nonalcoholic fatty liver disease among 3147 participants who were disease-free at baseline and who completed a second examination. Regression of nonalcoholic fatty liver disease was found in 113 (16%) of 704 participants who had the disease at baseline and who completed a second examination. Men and women who met the criteria for the metabolic syndrome at baseline were more likely to develop the disease during follow-up (adjusted odds ratio, 4.00 [95% Cl, 2.63 to 6.08] and 11.20 [Cl, 4.85 to 25.87], respectively). Nonalcoholic fatty liver disease was less likely to regress in those participants with the metabolic syndrome at baseline. Limitations: Ultrasonography may lead to an incorrect diagnosis of nonalcoholic fatty liver disease in 10% to 30% of cases and cannot distinguish steatohepatitis from simple steatosis. Selfreported alcohol intake may cause bias. Because all of the participants were Japanese, generalizability to non-Japanese populations is uncertain. Conclusions: The metabolic syndrome is a strong predictor of nonalcoholic fatty liver disease.
Do you have patients referred to you suffering from NAFLD? Are you looking for an expert guide to the latest in clinical management? If so, this is the book for you, providing an expert and comprehensive analysis of NAFLD: what it is, why it happens, who is likely to suffer from it, and how to decide on the best management options for your patients. This book focuses clearly on providing first-rate clinical guidance as to the assessment, diagnosis and treatment of patients in the clinical setting, based wherever possible on the latest evidence and scientific understanding of disease mechanisms. With each chapter fully revised and updated with the very latest in AASLD, EASL and Asia-Pacific guidelines, this second edition provides: Four brand new chapters, including "NAFLD and cardiovascular risk factors" and "Non-invasive methods to determine severity of NAFLD/ NASH" A clear overview on the causative mechanisms of NAFLD Self-assessment via key points and multiple-choice questions throughout The very latest in clinical drug trials Analysis of NAFLD in relation to obesity, diabetes, high cholesterol and liver cancer A consideration of NAFLD importance in Asia (particularly including Japan and China) and South America, as well as Europe and North America.
AIM: To investigate the effect of lifestyle intervention on non-alcoholic fatty liver disease (NAFLD) in Chinese obese children.
METHODS: Seventy-six obese children aged from 10 to 17 years with NAFLD were enrolled for a one-month intervention and divided randomly into three groups. Group1, consisting of 38 obese children, was an untreated control group without any intervention. Group 2, consisting of 19 obese children in summer camp, was strictly controlled only by life style intervention. Group 3, consisting of 19 obese children, received oral vitamin E therapy at a dose of 100 mg/d. The height, weight, fasting blood glucose (FBG), fasting serum insulin (FINS), plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TCHO) and homeostasis model assent-insulin resistance (HOMA-IR) were measured at baseline and after one month. All patients were underwent to an ultrasonographic study of the liver performed by one operator who was blinded to the groups.
RESULTS: The monitor indices of BMI, ALT, AST, TG, TCHO and HOMA-IR were successfully improved except in group 1. BMI and ALT in group 2 were reduced more significantly than in group 3 (2.44 ± 0.82 vs 1.45 ± 0.80, P = 0.001; 88.58 ± 39.99 vs 63.69 ± 27.05, P = 0.040, respectively).
CONCLUSION: Both a short-term lifestyle intervention and vitamin E therapy have an effect on NAFLD in obese children. Compared with vitamin E, lifestyle intervention is more effective. Therefore, lifestyle intervention should represent the first step in the management of children with NAFLD.