The Epidemiology of Nonalcoholic Fatty Liver Disease: A Global Perspective

Mariana Lazo, M.D., M.Sc.; Jeanne M. Clark, M.D., M.P.H.


Semin Liver Dis. 2008;28(4):339-350. 

In This Article

Definition and Diagnosis of NAFLD

Strictly speaking, the definition of NAFLD remains clinicopathological with well-defined criteria of the patterns of liver injury[9]; thus the use of liver biopsy to confirm, diagnose, and stage the disease remains the best available method to clinicians. However, it is far from ideal. Liver biopsies are invasive and have the potential for sampling and interpretation error.[9,10,11] Thus, except for the studies conducted in bariatric surgical settings where a liver biopsy is performed almost routinely, the use of liver biopsy for epidemiologic study is limited.

Based on studies that reported the normal content of liver fat is 5% of the weight, the American Association for the Study of Liver Diseases (AASLD) has now accepted as a definition of NAFLD fat accumulation in the liver exceeding 5 to 10% by weight.[9]

However, for operational purposes, the majority of studies define NAFLD using surrogate indicators of the disease, such as elevated liver enzymes or imaging studies (ultrasound [US] or computed tomography [CT]) suggesting hepatic steatosis in persons who have negative serologic tests for viral hepatitis, autoimmune liver disease, and congenital causes of chronic hepatitis. Additionally, alcohol consumption is typically restricted to ≤ 14 units/week (20 g/day), a threshold considered to be below the traditional cutoff for alcohol-induced liver disease.[9] However, the specificity and sensitivity of liver enzymes is low,[12,13] and their results may vary considerably over time.[14] Ultrasound also has limited sensitivity when the degree of steatosis is < 30% and is considered highly operator-dependent.[15,16] In contrast to the somewhat qualitative results obtained using enzymes or ultrasound, proton-magnetic resonance spectroscopy (proton-MRS) represents the best noninvasive quantitative method to measure hepatic triglyceride (HT) content and has been used in a few published studies.[17] The major drawbacks of this method are its cost and the inability to distinguish simple steatosis from fibrosis.

Simply ruling out or excluding other causes of liver disease is complex because patients with NAFLD may have other liver diseases[18] and the presence of NAFLD may influence the outcome of those other conditions. Evidence suggests, for example, that NAFLD and obesity are risk factors for progression to fibrosis and cirrhosis in patients infected with hepatitis C.[19,20,21,22,23,24,25] Similar observations have been made in the context of hepatitis B,[26] HIV,[27] hemochromatosis, and even alcoholic liver disease.[18,28] The mechanism and implications of the association between NAFLD and other liver diseases are currently the subject of extensive investigation and are beyond the scope of this review. However, this issue highlights the uncertainties that exist on the current estimates of the prevalence and correlates of NAFLD.


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