==== Front Saudi J GastroenterolSaudi J GastroenterolSJGSaudi Journal of Gastroenterology : Official Journal of the Saudi Gastroenterology Association1319-37671998-4049Medknow Publications & Media Pvt Ltd India 29956688SJG-24-21110.4103/sjg.SJG_122_18Original ArticleNonalcoholic fatty liver disease burden – Saudi Arabia and United Arab Emirates, 2017–2030 Alswat Khalid 1*Aljumah Abdulrahman A 23*Sanai Faisal M 14*Abaalkhail Faisal 56Alghamdi Mohamed 7Al Hamoudi Waleed K 15Al Khathlan Abdullah 8Al Quraishi Huda 9Al Rifai Ahmed 10Al Zaabi Mohamed 11Babatin Mohamed A 12Estes Chris 13Hashim Almoutaz 14Razavi Homie 131 Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia2 Hepatology Division, Department of Hepatobiliary Sciences and Organ Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia3 King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia4 Gastroenterology Unit, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia5 Department of Liver Transplantation and Hepatobiliary-Pancreatic Surgery, Division of Organ Transplant Center, King Faisal Specialist Hospital and Research Center-Riyadh, Alfaisal University, Riyadh, Saudi Arabia6 Department of Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia7 Department of Medicine, Gastroenterology Unit, King Fahd Military Medical Complex, Dhahran, Saudi Arabia8 Gastroenterology Section, Department of Medicine, King Fahad Medical City, Riyadh, Saudi Arabia9 Gastroenterology Unit, Rashid Hospital, Dubai, United Arab Emirates10 Gastroenterology Division, Mafraq Hospital, Abu Dhabi, United Arab Emirates11 Department of Gastroenterology, Zayed Military Hospital, Abu Dhabi, United Arab Emirates12 Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia13 Center for Disease Analysis, Lafayette, Colorado, USA14 Department of Internal Medicine, Jeddah University, Jeddah, Saudi ArabiaAddress for correspondence: Dr. Homie Razavi, Center for Disease Analysis, 1120 W. South Boulder Rd., Ste. 102, Lafayette, Colorado, USA. E-mail: hrazavi@cdafound.org* These authors contributed equally as first authors Jul-Aug 2018 24 4 211 219 Copyright: © 2018 Saudi Journal of Gastroenterology2018This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.Background/Aim: Due to epidemic levels of obesity and type 2 diabetes mellitus (DM), nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) will be driving factors in liver disease burden in the coming years in Saudi Arabia and United Arab Emirates (UAE). Materials and Methods: Models were used to estimate NAFLD and NASH disease progression, primarily based on changes in adult prevalence rates of adult obesity and DM. The published estimates and expert interviews were used to build and validate the model projections. Results: In both countries, the prevalence of NAFLD increased through 2030 parallel to projected increases in the prevalence of obesity and DM. By 2030, there were an estimated 12,534,000 NAFLD cases in Saudi Arabia and 372,000 cases in UAE. Increases in NASH cases were relatively greater than the NAFLD cases due to aging of the population and disease progression. Likewise, prevalent cases of compensated cirrhosis and advanced liver disease are projected to at least double by 2030, while annual incident liver deaths increase in both countries to 4800 deaths in Saudi Arabia and 140 deaths in UAE. Conclusions: Continued high rates of adult obesity and DM, in combination with aging populations, suggest that advanced liver disease and mortality attributable to NAFLD/NASH will increase across both countries. Reducing the growth of the NAFLD population, along with potential therapeutic options, will be needed to reduce liver disease burden. Keywords: Burden of diseasecardiovascular diseasecirrhosisdecompensated cirrhosishealthcare resource utilizationhepatocellular carcinomametabolic syndromenonalcoholic fatty livernonalcoholic fatty liver diseasenonalcoholic steatohepatitisobesitytype 2 diabetes mellitus ==== Body INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) is a leading cause of advanced liver disease in multiple regions,[123] and is characterized by excessive liver fat in the absence of other causes.[45] Overweight/obesity, type 2 diabetes mellitus (DM), and metabolic syndrome are the most important risk factors for NAFLD.[46] Morbidity related to NAFLD and resulting nonalcoholic steatohepatitis (NASH) is likely to increase dramatically in the coming decades, especially in the Gulf countries, where there is already an epidemic of obesity[7] and DM.[8] For this analysis, NAFLD cases were classified into two groups: NAFL (steatosis only) and NASH, where inflammation can progress to liver fibrosis, which is the primary risk factor for development of decompensated cirrhosis and hepatocellular carcinoma (HCC),[9] as well as liver-related mortality.[10] Increasing age, obesity, and DM have been consistently identified as risk factors for fibrosis progression and cirrhosis.[6] Most liver-related outcomes occur with the development of significant fibrosis and cirrhosis. HCC usually develops in patients with cirrhosis secondary to NASH; however, HCC can occur in noncirrhotic NASH patients.[11] NASH with end-stage liver disease is increasingly listed as an indication for liver transplantation.[1213] There is a pressing need to understand the current and future burden of NAFLD-related liver disease. A model of disease burden allows for more efficient allocation of limited healthcare resources and assists in the development of national strategies. Several recent analyses assessed the disease and economic burden associated with NASH[141516] based on the existing literature. In addition, a recently developed dynamic model of NAFLD progression for the United States overcomes several limitations in data availability.[17] In this analysis, we report the development of such a model for two countries, Saudi Arabia and UAE, based on the changing trends for obesity and DM in this region. MATERIALS AND METHODS A Markov model was constructed for Saudi Arabia and UAE. Fibrosis progression rates were back-calculated using surveillance data[17] and adjusted for the relative prevalence of obesity in each country.[6] Progression rates to HCC, decompensated cirrhosis, and liver-related death were based on published estimates.[17] The populations in each country were tracked beginning in 1950. As described below, trends for adult prevalence of obesity and DM were used to estimate the annual number of new NAFLD cases over time and track cases by METAVIR fibrosis stage, with progression to advanced liver disease and liver-related death [Figure 1]. Figure 1 NAFLD progression model Inputs: For both countries, indexed articles and nonindexed sources, including national data reports, were utilized. A literature search was conducted to identify reported estimates of NAFLD or NASH prevalence,[18192021] including reports of advanced liver disease attributable to NAFLD or NASH. National estimates for adult prevalence of obesity (body mass index (BMI) ≥30 kg/m2) and DM were also incorporated in the analysis. In addition to literature review, a Delphi process was used to incorporate expert input based on interviews to identify key model inputs and review outputs against available estimates of disease burden. The proposed model calculated the NAFLD population by fibrosis stage and NASH status (NAFL or NASH). Progression of disease through fibrosis and liver disease stages [Figure 1] was calculated with adjustment for all-cause mortality (including background, excess cardiovascular disease (CVD), and liver-related mortality). New NAFLD cases: Annual changes in the number of new cases were back-calculated based on the adult prevalence of obesity and DM for which more robust data exist than those for NAFLD. For obesity, the fastest growth in prevalence was estimated to occur prior to the greatest relative increases in NAFLD prevalence, while the fastest growth in DM prevalence was estimated to occur after the greatest increase in NAFLD at the general population level. National estimates of obesity for Saudi Arabia and UAE were available through published estimates.[722232425] For both countries, relative changes in obesity were estimated using global burden of disease estimates for adult obesity in Saudi Arabia in 1980, 1990, 2000, and 2013, due to the availability of estimates at different time points.[23] Similar estimates were available for UAE, but were partially based on studies in limited populations that may not be representative of the national population. Published[26272829] and unpublished data were used to estimate changes in adult prevalence of DM in Saudi Arabia. While longitudinal diabetes data for UAE were sparse, it was assumed that increases over time would follow the trends observed for Saudi Arabia. NAFLD prevalence: It was assumed that 30% of individuals aged ≥15 years of age in 2015 experienced NAFLD. After adjustment for lower prevalence in the population aged <15 years, the all ages prevalence was estimated at 24.8% (Saudi Arabia) and 23.7% (UAE). For the age and gender distribution of the NAFLD population, data from general population studies in multiple countries were used where prevalence is 1.3 times higher in males as compared to females and there is increasing prevalence with age.[303132] Prevalence studies often did not include younger age groups, and it was assumed that prevalence rates would decrease with decreasing age. One study of NAFLD prevalence in Saudi Arabia used computed tomography (CT) scan data from 100 adult hospital patients in 2012, and reported 18–54% NAFLD depending on the criteria applied.[33] A study of 230 DM patients at Jazan General Hospital in 2013 reported overall prevalence of 47.8%. Among these patients, there was slightly higher prevalence in males (49.1%) than females (46.3%), and prevalence was 52.9% among the middle-aged population (ages 40–59 years).[34] NASH status: NASH prevalence was based on reported estimates and fibrosis progression that varied by sex and age group. Given that inflammatory and fibrotic changes can regress in NAFLD patients,[9] it was assumed that up to 5% of NAFLD cases without NASH could be NASH regressors, with increasing fibrosis score modeled to have a lower probability of being a regressed NASH case. Therefore, a relatively small number of fibrotic cases (F1–F4) were classified as non-NASH NAFLD. The model assumed that approximately 15–20% of NAFLD cases would be classified as NASH in 2015.[353637] Fibrosis progression and NASH status were calibrated to US surveillance data for NASH-related HCC[17] and then extrapolated to other countries, with adjustments between countries based on relative rates of overweight/obesity and published odds of disease progression to advanced fibrosis.[6] For disease progression adjustment, obesity and overweight prevalence data from the Saudi Health Information Survey were used.[22] Due to demographic factors,[38] the proportion of NASH cases varies between countries, with overall aging of the population and increased overweight/obesity rates associated with increased proportion of NASH cases among the total NAFLD population. During initial model calibration to surveillance data for NAFLD-related HCC, it was assumed that 15–20% of NASH cases would be classified as ≥F3 in 2015.[39] In settings with younger affected populations and/or where the obesity epidemic began later, the proportion of NASH cases was lower. Similar to NASH status, some countries had a higher proportion of advanced fibrosis cases due to the advanced age of the overall population, as well as the timing of the growth in obesity and DM prevalence that began at different time points. Population: The United Nations population database was used to estimate population for Saudi Arabia. Because UAE has a very high population of expatriate individuals (approximately 90% of total population), the NAFLD model for UAE only considered Emirati citizens. Estimates of the citizen population were available for 1975–2005[40] through national databases. It was assumed that the age and gender distribution of the Emirate population would mirror the Saudi Arabia population in 1950 and 2050,[38] and the population data were linearly interpolated for 1951–1974 and 2006–2050, when national data by citizen status were unavailable. Mortality: Background deaths were based on data from the United Nations population database for both Saudi Arabia and UAE[38] divided by population estimates by age group and gender from the same database.[38] Background rates were adjusted to account for incrementally increased mortality related to CVD.[414243] A standard mortality ratio 1.15 [uncertainty range: 1.00–1.31] was applied to all background mortality rates in all years of the model.[414243] While incremental CVD mortality may increase with severity of liver disease and vary by age group, data were largely unavailable, and a constant multiplier was applied. Liver-related mortality was calculated separately as part of liver disease progression modeling. Liver-related deaths were calculated as a progression rate among prevalent HCC, decompensated cirrhosis, and liver transplant cases. Transplants: Annual transplant data by indication are sparse for Saudi Arabia and UAE. Using the total annual transplant data, along with expert input for total transplants,[44] it was assumed that up to 25% of current liver transplants could be attributable to NASH. These estimates were used to validate the model outputs and informed by studies showing that numerous transplants indicated for cryptogenic or idiopathic cirrhosis are NAFLD-related based on obesity rates in these populations.[1345] Given the uncertainties around transplant demand and availability, it was assumed that the annual number of NAFLD-related transplants would remain constant through 2030. This was a conservative estimate, as data already suggest that the proportion of NAFLD-related transplants is increasing in areas of high obesity.[13] Uncertainty and sensitivity analysis: Uncertainty analyses were conducted for the models. Beta-PERT distributions[46] were defined for key model inputs, including total NAFLD prevalence, excess background mortality multipliers, and fibrosis transition probabilities. Monte-Carlo simulation was conducted using Crystal Ball® (11.1.3708.0 by Oracle®), an Excel® add-in, to estimate 95% uncertainty intervals (UI). Sensitivity analyses were conducted to identify the inputs that accounted for the greatest variation in modeled outcomes. Prevalent NAFLD and NASH cases in 2017 and 2030 with 95% UI are shown in Figures 2 and 3. Figure 2 Distribution of NAFLD population by fibrosis stage – 2017 and 2030 Figure 3 Distribution of NASH population by fibrosis stage – 2017 and 2030 RESULTS NAFLD population: The total 2017 NAFLD prevalence was estimated at 8,451,000 (25.7%) in Saudi Arabia and 255,000 (25.0%) in UAE [Table 1]. By 2030, the total NAFLD population was projected to increase 48% in Saudi Arabia to 12,534,000 and 46% in UAE to 372,000 cases [Figure 2], with overall prevalence rates estimated at 31.7 and 30.2%, respectively. The number of prevalent cases with NAFLD-related compensated cirrhosis was projected to increase 262% during 2017–2030 in Saudi Arabia, from 55,900 to 202,100 cases, while such cases increased 232% in UAE from 1710 to 5700 cases in 2030 [Figure 4]. Table 1 2017 Model Forecasts - Saudi Arabia and United Arab Emirates, 2017 and 2030 Figure 4 Prevalent NAFLD, NAFL (simple steatosis and regressed NASH), and NASH cases – 2015-2030 NAFL population: The NAFL population was assumed to be cases with steatosis only that never progressed to NASH, with a relatively small number of cases that were formerly NASH and would experience disease regression. In 2017, the NAFL population was estimated at 7,078,000 in Saudi Arabia (83.6% of all NAFLD cases) and increased to 9,846,000 cases in 2030 (78.6% of all NAFLD cases), a 39% increase. In UAE, the NAFL population was estimated to increase 37% from 213,600 cases in 2017 (83.6% of all NAFLD cases) to 293,400 cases in 2030 (78.9% of all NAFLD cases) [Figure 2]. NASH population: The number of NASH cases in 2017 was estimated at 1,373,000 in Saudi Arabia and 41,800 in UAE, equivalent to 16.2 and 16.4% of the total NAFLD populations, respectively. General population: NASH prevalence in 2017 was estimated at 4.2% (Saudi Arabia) and 4.1% (UAE). In Saudi Arabia, NASH cases were projected to increase 96% to 2,688,000 cases in 2030, while NASH increased 87% in UAE to 78,300 cases [Figure 3]. Among NASH cases in Saudi Arabia, 185,500 were estimated to have F3/F4 fibrosis or advanced liver disease (decompensated cirrhosis or HCC), encompassing approximately 13.5% of all NASH cases [Figure 3] and 0.56% of the total population (all ages). By 2030, this number was expected to increase 216% to 586,000 cases, and account for 21.8% of all NASH cases. In UAE, there were 5670 such cases in 2017, equivalent to 13.6% of total NASH and 0.56% of the total population. By 2030, these cases increased 191% to 16,500 cases, or 21.1% of total NASH. Decompensated cirrhosis and HCC: In Saudi Arabia, incident decompensated cirrhosis was projected to increase by 273%, from 1830 cases in 2017 to 6840 cases in 2030, while cumulative incidence during 2017–2030 was estimated at 55,500 cases [Figure 5]. In UAE, incident decompensation was estimated at 60 cases in 2017, increasing 241% to 190 cases in 2030, while cumulative incidence was estimated at 1620 cases. Figure 5 Incident decompensated cirrhosis, HCC and liver-related deaths among prevalent NAFLD population – 2015–2030 Prevalent HCC cases related to NAFLD increased 209% in Saudi Arabia, from 580 cases in 2017 to 1790 cases in 2030, while such cases increased 181% in UAE from 18 to 51 prevalent cases during 2017–2030. In Saudi Arabia, incident HCC cases increased by 199% during 2017–2030 from 300 to 890 cases [Figure 5]. UAE was projected to have an increase of 178% from 9 incident cases in 2017 to 25 incident cases in 2030. Cumulative incidence of HCC during 2017–2030 was estimated at 7860 cases in Saudi Arabia and 230 cases in UAE. Mortality: In the total NASH population in Saudi Arabia in 2017, there were 1810 deaths classified as excess cardiovascular and 1220 liver-related deaths. In UAE, NASH deaths in 2017 included 80 excess cardiovascular deaths and 40 liver-related deaths (1.5%). By 2030, annual liver-related deaths were estimated at 4800 deaths in Saudi Arabia (295% increase from 2017) and 140 deaths in UAE (270% increase). By 2030, liver-related mortality was estimated to comprise 4.4% of all deaths in the total NAFLD population in Saudi Arabia and 2.9% of such deaths in UAE [Figure 5]. DISCUSSION Levels of obesity and diabetes in Saudi Arabia and UAE are on par with the high levels observed in Western countries.[7] The burden of NAFLD-related liver disease may reach very high levels in the Gulf countries, which have relatively young populations, potentially implying relatively lower rates of advanced liver disease in the near term and potentially large increases in disease burden in the coming decades. Pediatric and adolescent obesity in Saudi Arabia,[4748] UAE,[49] and other Arab countries[50] is already at epidemic levels and increasing rapidly. There may be an age impact of developing NAFLD in young populations with resulting NASH that may require a liver transplant at an earlier age.[51] In the coming decade, NASH will likely be the leading indication for liver transplantation in Gulf countries, due to a reduced burden of viral hepatitis, in combination with skyrocketing obesity rates. Increasing prevalence of obesity and diabetes will reduce the potential pool of donors as well. One study in the region reports that approximately 25% of potential donors were excluded due to diabetes or BMI > 28 kg/m2.[52] Both literature review and expert interviews were utilized to design the model and validate model outputs. For changes over time in obesity levels, estimates from the global burden of disease study were used, as data were available at four time points.[23] Data from the Saudi Health Information Survey[22] were used in adjustments of disease progression,[6] as these data were considered representative of the long-term populations of both countries. For both countries, if the national obesity prevalence levels off, it is estimated that the prevalence of NAFLD will also level off. The proportion of NASH subjects among the NAFLD population is likely to increase in the coming decades due to aging populations, even if adult obesity prevalence remains at the current high levels without further increase. The results of modeling have potential to inform healthcare systems. Effective strategies are needed to prevent and treat NAFLD/NASH in order to avert a marked increase in the incidence of end-stage liver disease and related mortality. A future with increasing disease burden is supported by recent data demonstrating the growing contribution of NASH toward demand for liver transplantation.[113] Another important result of the modeling is the rapid increase in the number of individuals with cirrhosis, especially decompensated cirrhosis due to NASH. Data from multiple countries demonstrate that the proportion of HCC attributed to NAFLD is growing rapidly.[153] Among 235 HCC patients presenting at a Saudi medical center during 2009–2011, the majority were overweight/obese (mean BMI = 27.6 ± 5.9 kg/m2) and had NAFLD risk factors, including 57.9% with DM, 52.3% with hypertension, and 12.8% with dyslipidemia. Among the HCC cases, 21.7% were classified as cryptogenic cirrhosis,[54] which potentially includes cases attributable to NAFLD.[13] A further impact of the growing burden of NAFLD in Saudi Arabia and UAE is increasing incidence and prevalence of HCC. This analysis calculated mortality among NAFLD cases with classification as background, excess CVD and liver-related mortality. Large increases in liver-related mortality will be associated with increasing numbers of cirrhotic cases within a growing NASH population. Aging of the population is a risk factor for more advanced disease[6] and the progression of disease to advanced stages of NASH.[49] Given the long course of the disease, the burden of liver-related morbidity and mortality will continue to increase for decades. This emphasizes the necessity of identifying NAFLD cases, especially persons with clinically significant fibrosis, who may be candidates for therapy. Limitations of this study included those inherent to modeling a condition with a long course of disease in countries with large expatriate populations. Data from the UAE National Diabetes and Lifestyle Study show that expatriates in UAE experience Western levels of obesity and diabetes, similar to the Emirati population.[25] However, it is unknown how many expatriate individuals will develop NAFLD while in the UAE or for what duration of the disease they will be residents of UAE. Saudi Arabia also has a high proportion of expatriate individuals included in their population, but they do not constitute a majority of the population. A limitation of modeling is a lack of data from general population studies measuring hepatic steatosis and fibrosis with consistent methods. Some estimates are based on data collected years ago, and likely do not reflect current disease burden, given increases in obesity and DM. Many studies conducted NAFLD screening using ultrasound, which only reliably detects steatosis of >20%, failing to identify a significant proportion of the NAFLD population.[5] While the model adjusted for the greater current magnitude of obesity and DM, there has been a dramatic increase in childhood obesity in recent decades, and the onset of DM at younger ages is expected,[55] suggesting a longer course of disease with potentially greater risk to develop end-stage liver disease. The largest relative increase in diabetes prevalence over the past two decades has occurred among adults aged ≥ 65 years,[56] with increased age also a predictor of advanced fibrosis.[6] A lack of consistent diagnostic measures means that reported NAFLD prevalence rates vary between studies,[14] and NASH can be histologically detected in some NAFLD cases with normal liver enzyme measures.[57] NAFLD is asymptomatic among most stages, and typically there is a long period between incident steatosis and a diagnosis of liver disease. However, staging of fibrosis alone can be a useful predictor of long-term outcomes.[5859] Noninvasive tests such as transient elastography are relatively easy to perform, and have been shown to reliably predict the degree of liver fibrosis,[6061] but still have not been approved for this purpose. CONCLUSION This analysis confirms a large and growing burden of disease associated with NAFLD and NASH, in tandem with a global pandemic of obesity.[62] The World Health Organization has called for a halt to the increase in diabetes and obesity at the global level,[63] with sustainable development goal 3.4 calling for a reduction by one-third in premature mortality from noncommunicable diseases by 2030. There is an urgent need to address the factors contributing to obesity in the Eastern Mediterranean Region, including dietary factors and inactivity,[64] and to meet World Health Organization goals to stop the increase in noncommunicable disease.[63] Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. ==== Refs REFERENCES 1 Younossi ZM Otgonsuren M Henry L Venkatesan C Mishra A Erario M Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009 Hepatology 2015 62 1723 30 26274335 2 Sanyal A Poklepovic A Moyneur E Barghout V Population-based risk factors and resource utilization for HCC: US perspective Curr Med Res Opin 2010 26 2183 91 20666689 3 Loomba R Sanyal AJ The global NAFLD epidemic Nat Rev Gastroenterol Hepatol 2013 10 686 90 24042449 4 Chalasani N Younossi Z Lavine JE Diehl AM Brunt EM Cusi K The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology Gastroenterology 2012 142 1592 609 22656328 5 EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease Diabetologia 2016 59 1121 40 27053230 6 Angulo P Hui JM Marchesini G Bugianesi E George J Farrell GC The NAFLD fibrosis score: A noninvasive system that identifies liver fibrosis in patients with NAFLD Hepatology 2007 45 846 54 17393509 7 DeNicola E Aburizaiza OS Siddique A Khwaja H Carpenter DO Obesity and public health in the Kingdom of Saudi Arabia Rev Environ Health 2015 30 191 205 26351801 8 Abuyassin B Laher I Diabetes epidemic sweeping the Arab world World J Diabetes 2016 7 165 74 27114755 9 Singh S Allen AM Wang Z Prokop LJ Murad MH Loomba R Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: A systematic review and meta-analysis of paired-biopsy studies Clin Gastroenterol Hepatol 2015 13 643 54.e1 9 quiz e39-40 24768810 10 Dulai PS Singh S Patel J Soni M Prokop LJ Younossi Z Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis Hepatology 2017 65 1557 65 28130788 11 White DL Kanwal F El-Serag HB Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review Clin Gastroenterol Hepatol 2012 10 1342 59.e2 23041539 12 Wong RJ Aguilar M Cheung R Perumpail RB Harrison SA Younossi ZM Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States Gastroenterology 2015 148 547 55 25461851 13 Wong RJ Cheung R Ahmed A Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S Hepatology 2014 59 2188 95 24375711 14 Younossi ZM Koenig AB Abdelatif D Fazel Y Henry L Wymer M Global epidemiology of non-alcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence and outcomes Hepatology 2016 64 73 84 26707365 15 Younossi ZM Henry L Economic and quality-of-life implications of non-alcoholic fatty liver disease Pharmacoeconomics 2015 33 1245 53 26233836 16 Younossi ZM Zheng L Stepanova M Henry L Venkatesan C Mishra A Trends in outpatient resource utilizations and outcomes for Medicare beneficiaries with nonalcoholic fatty liver disease J Clin Gastroenterol 2015 49 222 7 24637730 17 Estes C Razavi H Loomba R Younossi Z Sanyal AJ Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease Hepatology 2018 67 123 33 28802062 18 el-Hassan AY Ibrahim EM al-Mulhim FA Nabhan AA Chammas MY Fatty infiltration of the liver: Analysis of prevalence, radiological and clinical features and influence on patient management Br J Radiol 1992 65 774 8 1393413 19 Al-hamoudi W El-Sabbah M Ali S Altuwaijri M Bedewi M Adam M Epidemiological, clinical, and biochemical characteristics of Saudi patients with nonalcoholic fatty liver disease: A hospital-based study Ann Saudi Med 2012 32 288 92 22588441 20 Ahmed MH Noor SK Bushara SO Husain NE Elmadhoun WM Ginawi IA Non-alcoholic fatty liver disease in Africa and Middle East: An attempt to predict the present and future implications on the healthcare system Gastroenterology Res 2017 10 271 9 29118867 21 Gasim GI Elshehri FM Kheidr M Alshubaily FK ElZaki EM Musa IR The use of computed tomography in the diagnosis of fatty liver and abdominal fat distribution among a Saudi population Open Access Maced J Med Sci 2017 5 762 5 29104685 22 Memish ZA El Bcheraoui C Tuffaha M Robinson M Daoud F Jaber S Obesity and associated factors—Kingdom of Saudi Arabia, 2013 Prev Chronic Dis 2014 11 E174 25299980 23 Ng M Fleming T Robinson M Thomson B Graetz N Margono C Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: A systematic analysis for the Global Burden of Disease Study 2013 Lancet 2014 384 766 81 24880830 24 Reid M The weight of affluence Bull World Health Organ 2010 88 86 7 20428361 25 Sulaiman N Elbadawi S Hussein A Abusnana S Madani A Mairghani M Prevalence of overweight and obesity in United Arab Emirates Expatriates: The UAE National Diabetes and Lifestyle Study Diabetol Metab Syndr 2017 9 88 29118852 26 Al Dawish MA Robert AA Braham R Al Hayek AA Al Saeed A Ahmed RA Diabetes Mellitus in Saudi Arabia: A Review of the Recent Literature Curr Diabetes Rev 2016 12 359 68 26206092 27 Alotaibi A Perry L Gholizadeh L Al-Ganmi A Incidence and prevalence rates of diabetes mellitus in Saudi Arabia: An overview J Epidemiol Glob Health 2017 7 211 8 29110860 28 Al-Rubeaan K Al-Manaa H Khoja T Ahmad N Al-Sharqawi A Siddiqui K The Saudi Abnormal Glucose Metabolism and Diabetes Impact Study (SAUDI-DM) Ann Saudi Med 2014 34 465 75 25971818 29 Bahijri SM Jambi HA Al Raddadi RM Ferns G Tuomilehto J The Prevalence of Diabetes and Prediabetes in the Adult Population of Jeddah, Saudi Arabia--A Community-Based Survey PLoS One 2016 11 e0152559 27035920 30 Lazo M Hernaez R Eberhardt MS Bonekamp S Kamel I Guallar E Prevalence of nonalcoholic fatty liver disease in the United States: The Third National Health and Nutrition Examination Survey, 1988-1994 Am J Epidemiol 2013 178 38 45 23703888 31 Caballeria L Pera G Auladell MA Toran P Munoz L Miranda D Prevalence and factors associated with the presence of nonalcoholic fatty liver disease in an adult population in Spain Eur J Gastroenterol Hepatol 2010 22 24 32 19730384 32 Fan JG Farrell GC Epidemiology of non-alcoholic fatty liver disease in China J Hepatol 2009 50 204 10 19014878 33 Alshumrani GA Shawky KA Assiri YI Algathradi MA Mahfouz AA Mostafa OA Fatty Liver Disease among Adults in Southwestern Saudi Arabia Med J Cairo Univ 2013 81 205 9 34 Elmakki E Aqeely H Bani I Omer H Solan Y Taher A Nonalcoholic Fatty Liver Disease (NAFLD) in Saudi Patients with T2DM in Jazan Region: Prevalence and Associated Factors BJMMR 2015 5 872 9 35 Ground KE Liver pathology in aircrew Aviat Space Environ Med 1982 53 14 8 7055484 36 Grant LM Lisker-Melman M Nonalcoholic fatty liver disease Ann Hepatol 2004 3 93 9 15505593 37 Williams CD Stengel J Asike MI Torres DM Shaw J Contreras M Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: A prospective study Gastroenterology 2011 140 124 31 20858492 38 United Nations. Department of Economic Social Affairs Population Division World population prospects: The 2015 revision 2016 New York United Nations 39 Kleiner DE Brunt EM Van Natta M Behling C Contos MJ Cummings OW Design and validation of a histological scoring system for nonalcoholic fatty liver disease Hepatology 2005 41 1313 21 15915461 40 UAE Open Data Portal. Population by Age Groups, Gender and Nationality 2017 [updated 2017] Last accessed on 2018 Mar 02 Available from: http://data.bayanat.ae/en_GB/dataset/population-by-age-groups-gender-and-nationality 41 Stepanova M Rafiq N Makhlouf H Agrawal R Kaur I Younoszai Z Predictors of All-Cause Mortality and Liver-Related Mortality in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) Dig Dis Sci 2013 58 3017 23 23775317 42 Byrne CD Targher G NAFLD: A multisystem disease J Hepatol 2015 62 1 Suppl S47 64 25920090 43 Targher G Byrne CD Lonardo A Zoppini G Barbui C Nonalcoholic Fatty Liver Disease and Risk of Incident Cardiovascular Disease: A Meta-Analysis of Observational Studies J Hepatol 2016 65 589 600 27212244 44 IRODaT. International Registry on Organ Donation and Transplantation 2017 [cited 2017] Last accessed on 2018 Mar 02 Available from: http://www.irodat.org/?p=database 45 OrganProcurement and Transplantation Network (OPTN). OPTN data as of October 28 2016 2016 [updated 2016] Last accessed on 2018 Mar 02 Available from: https://optn.transplant.hrsa.gov/data/ 46 Malcolm DG Roseboom JH Clark CE Fazar W Application of a technique for research and development program evaluation Oper Res 1959 7 646 69 47 Al-Muhaimeed AA Dandash K Ismail MS Saquib N Prevalence and correlates of overweight status among Saudi school children Ann Saudi Med 2015 35 275 81 26497706 48 Shaikh MA Al Sharaf F Shehzad K Shoukat F Naeem Z Al Harbi S Prevalence and trends of overweight and obesity amongst Saudi school children, a study done by using three noninvasive methods Int J Health Sci (Qassim) 2016 10 381 7 27610061 49 Ng SW Zaghloul S Ali H Harrison G Yeatts K El Sadig M Nutrition transition in the United Arab Emirates Eur J Clin Nutr 2011 65 1328 37 21772317 50 Musaiger AO Al-Mannai M Al-Haifi AR Nabag F Elati J Abahussain N Prevalence of overweight and obesity among adolescents in eight Arab countries: Comparison between two international standards (ARABEAT-2) Nutr Hosp 2016 33 567 27759971 51 Alkhouri N Hanouneh IA Zein NN Lopez R Kelly D Eghtesad B Liver transplantation for nonalcoholic steatohepatitis in young patients Transpl Int 2016 29 418 24 26402655 52 Al-Hamoudi W Abaalkhail F Bendahmash A Allam N Hegab B Elsheikh Y The impact of metabolic syndrome and prevalent liver disease on living donor liver transplantation: A pressing need to expand the pool Hepatol Int 2016 10 347 54 26341515 53 Weinmann A Koch S Niederle IM Schulze-Bergkamen H Konig J Hoppe-Lotichius M Trends in epidemiology, treatment, and survival of hepatocellular carcinoma patients between 1998 and 2009: An analysis of 1066 cases of a German HCC Registry J Clin Gastroenterol 2014 48 279 89 24045276 54 Aljumah AA Kuriry H AlZunaitan M Al Ghobain M Al Muaikeel M Al Olayan A Clinical presentation, risk factors, and treatment modalities of hepatocellular carcinoma: A single tertiary care center experience Gastroenterol Res Pract 2016 2016 1989045 27525001 55 Alberti G Zimmet P Shaw J Bloomgarden Z Kaufman F Silink M Type 2 diabetes in the young: the evolving epidemic: The international diabetes federation consensus workshop Diabetes Care 2004 27 1798 811 15220270 56 Cheng YJ Imperatore G Geiss LS Wang J Saydah SH Cowie CC Secular changes in the age-specific prevalence of diabetes among U.S. adults: 1988-2010 Diabetes Care 2013 36 2690 6 23637354 57 Fracanzani AL Valenti L Bugianesi E Andreoletti M Colli A Vanni E Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: A role for insulin resistance and diabetes Hepatology 2008 48 792 8 18752331 58 Angulo P Bugianesi E Bjornsson ES Charatcharoenwitthaya P Mills PR Barrera F Simple noninvasive systems predict long-term outcomes of patients with nonalcoholic fatty liver disease Gastroenterology 2013 145 782 9.e4 23860502 59 Angulo P Kleiner DE Dam-Larsen S Adams LA Bjornsson ES Charatcharoenwitthaya P Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease Gastroenterology 2015 149 389 97.e10 25935633 60 Yoneda M Yoneda M Mawatari H Fujita K Endo H Iida H Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD) Dig Liver Dis 2008 40 371 8 18083083 61 Loomba R Wolfson T Ang B Hooker J Behling C Peterson M Magnetic resonance elastography predicts advanced fibrosis in patients with nonalcoholic fatty liver disease: A prospective study Hepatology 2014 60 1920 8 25103310 62 Afshin A Forouzanfar MH Reitsma MB Sur P Estep K Lee A Health effects of overweight and obesity in 195 countries over 25 years N Engl J Med 2017 377 13 27 28604169 63 World Health Organization Global action plan for the prevention and control of noncommunicable diseases 2013–2020 2013 Geneva World Health Organization 64 Musaiger AO Overweight and obesity in the Eastern Mediterranean Region: Can we control it? East Mediterr Health J 2004 10 789 93 16335765