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• W3003987302 abstract "Watch a video presentation of this article Answer questions and earn CME Nonalcoholic fatty liver disease (NAFLD) is defined as cytoplasmic accumulation of fat in more than 5% of hepatocytes with or without inflammation when other causes of steatosis such as excessive alcohol consumption, viral hepatitis, genetic disorders, and drugs are ruled out. NAFLD encompasses a range of histological abnormalities. The mildest form, nonalcoholic fatty liver (NAFL), is characterized by simple steatosis without hepatocyte balloon degeneration, inflammation, or fibrosis. NAFL rarely progresses to cirrhosis. Nonalcoholic steatohepatitis (NASH) is a more severe form of NAFLD where steatosis is accompanied by balloon degeneration and lobular inflammation. NASH can progress to cirrhosis in up to 40% of patients.1 NAFLD is emerging as a leading cause of cirrhosis, liver failure, and hepatocellular carcinoma (HCC) around the globe. The global prevalence rate of NAFLD is around 25%.1 In the United States and Europe, NAFLD is expected to become the main indication for liver transplantation by 2030.2 In addition to liver-related morbidity and mortality, NAFLD is associated with increased incidence of cardiovascular and chronic kidney disease. Being the hepatic component of the metabolic syndrome (MetS), the prevalence of NAFLD parallels that of type 2 diabetes mellitus (T2DM) and obesity. Accordingly, overnutrition and a sedentary lifestyle are the major risk factors for NAFLD. However, irrespective of lifestyle, there are important interethnic differences in the susceptibility to NAFLD, which appear to be related to genetic factors.3 The Middle East is considered a high-prevalence region for NAFLD. It is estimated that around 30% of adults have NAFLD.1 This estimate is based on three studies (Table 1).4-6 Two of these studies were carried out on highly selected populations.4, 6 Hence the findings may not be extrapolated to the general population. A fourth report pertaining to the disease burden in Saudi Arabia and the United Arab Emirates (UAE) used a mathematical model that calculated the current and future prevalence of NAFLD, based mainly on the prevalence of diabetes and obesity in both countries.7 Despite these limitations, the notion that NAFLD is common in Middle East populations is supported by the high prevalence of obesity, T2DM, and the MetS (Fig. 1).8 Ten countries in the region are placed in the top 15 countries with the highest levels of obesity in the world.9 In some of these countries, obesity starts at a young age. For instance, in the Gulf Cooperation Council states (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the UAE), the prevalence rates of obesity among schoolchildren and adolescents range between 25% and 30%.10 Overweight and obese children are more likely to stay obese into adulthood and to experience obesity-related complications. In Kuwait, 22 out of 35 patients (63%) referred for liver transplantation in 2018-2019 had NASH-related cirrhosis (with permissions from Moataz Fathi, Ministry of Health, personal communication). These alarming statistics call for urgent action by government and nongovernment organizations to encourage the population to reduce the consumption of obesogenic diet and increase physical activity through education and legislation. The impact of such interventions should be monitored by conducting population-based cohort studies and establishing comprehensive national registries. NAFLD is usually asymptomatic. The diagnosis is based on: (1) documenting hepatic steatosis on imaging or histology, (2) lack of excessive consumption of alcohol, and (3) ruling out other causes of steatosis and/or chronic liver diseases (CLDs). Because the Middle East encompasses countries with variable resources, a cost-sensitive approach is recommended.11 The workup of NAFLD is based on history and physical examination, laboratory investigations, imaging, and liver biopsies (Table 2). Clinical assessment requires few resources and has the following goals: (1) identifying high-risk individuals; (2) excluding competing causes of CLD and hepatic steatosis, especially excessive alcohol intake; and (3) detecting signs of complications such as portal hypertension and hepatic decompensation. Laboratory investigations should include screening for diabetes mellitus (DM) and dyslipidemia. A low platelet count on complete blood count (CBC) can hint to the development of cirrhosis. Serum aminotransferases are inexpensive and readily available but can be “normal” in patients with NAFLD. American Association for the Study of Liver Diseases cutoffs should be used as reference values to enhance the sensitivity of transaminase levels in detecting liver disease. Several noninvasive scoring systems for assessing fibrosis, such as Fibrosis-4 score (FIB-4) and NAFLD Fibrosis Score, use transaminase levels. These scoring tools can help primary care providers select high-risk patients who need referral to specialized centers for further evaluation. When testing for competing causes of CLD, priority is given to ruling out chronic hepatitis B and C infections that are endemic to the region. Once viral hepatitis is excluded, consideration can be given to testing for less frequent causes of liver disease, such as autoimmune hepatitis, Wilson’s disease, and celiac disease, according to the clinical setting and availability of resources. Testing for genetic hemochromatosis is probably unwarranted because the responsible gene mutations are rare in ethnic groups residing in the Middle East. Imaging tools include ultrasound, computed tomography, and magnetic resonance imaging (MRI). Ultrasonography is the imaging modality of choice due to its low cost. MRI Proton Density Fat Fraction is the most accurate noninvasive imaging tool for the assessment of steatosis, but it is expensive and requires special expertise. Measurement of liver stiffness using transient elastography has been validated as a reliable tool in assessing fibrosis. However, in most Middle Eastern countries, this technology is available only in secondary or tertiary care settings. Finally, when noninvasive measures are inconclusive or competing liver diseases are suspected, liver biopsy is recommended. It is the gold standard in assessing steatosis, inflammation, and fibrosis, but is invasive and expensive. The detailed workup presented in Table 2 may not be tenable in all health care systems in the Middle East. Table 3 summarizes diagnostic options taking into consideration available resources.11 An important caveat is that in the Middle East, published data regarding the performance of the noninvasive diagnostic tools of hepatic fibrosis in the setting of NAFLD are still lacking. Fig. 2 illustrates a roadmap for the management of NAFLD.12 Low-risk patients with NAFLD can be managed in primary care facilities, whereas high-risk patients should be referred to specialist care. The mainstay of therapy of NAFLD is directed toward optimizing the treatment of the MetS by weight reduction, exercise, and pharmacological therapy of diabetes, dyslipidemia, and hypertension. Vitamin E and pioglitazone may be used in carefully selected patients.2 Morbidly obese patients (body mass index [BMI] > 40) and those with a BMI of 35 to 40 who have obesity-related complications may be considered for bariatric surgery. Patients with cirrhosis need monitoring for decompensation, portal hypertension, and HCC. NAFLD is a major cause of liver dysfunction in the Middle East. Several diagnostic pathways have been proposed, taking into consideration cost and local expertise. Once validated, these pathways can be used as part of a comprehensive action plan for early identification of individuals at risk, linkage to care, appropriate intervention, and follow-up." @default.
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• W3003987302 date "2019-12-01" @default.
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• W3003987302 title "The Burden and Clinical Care Pathways of Nonalcoholic Steatohepatitis in the Middle East" @default.
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