Elsevier

Annals of Epidemiology

Volume 17, Issue 11, November 2007, Pages 863-869
Annals of Epidemiology

Nonalcoholic Fatty Liver Disease

https://doi.org/10.1016/j.annepidem.2007.05.013Get rights and content

Nonalcoholic fatty liver disease (NAFLD) refers to the presence of hepatic steatosis not associated with a significant intake of ethanol. Insulin resistance is central to the pathogenesis of NAFLD; thus obesity, diabetes, and the metabolic syndrome are frequently associated with the disease. Consequently, as these metabolic conditions emerge as major health problems in Western society, it is now recognized that NAFLD is the most common chronic liver condition in the Western world. NAFLD is generally asymptomatic, although a minority of patients may present with evidence of progressive liver injury with complications of cirrhosis, liver failure, and hepatocellular carcinoma. Despite being common and potentially serious, relatively little is known about the natural history or prognostic significance of NAFLD. Although diabetes, obesity, and age are recognized risk factors for advanced liver disease, other significant factors leading to progressive liver injury remain to be identified. The treatment of NAFLD focuses upon modifying metabolic risk factors. Insulin-sensitizing and hepatoprotective drugs have been subjected to study trials, but as yet, no agent has conclusively been demonstrated to prevent disease progression. Management is further complicated by the inability to predict which patients will develop liver-related morbidity and thus benefit from treatment.

Section snippets

Epidemiology

The prevalence of NAFLD varies according to the sensitivity of the instrument used to detect hepatic steatosis. Magnetic resonance spectroscopy (MRS) and liver biopsy are the most sensitive techniques at detecting hepatic steatosis, whereas the sensitivity of ultrasound varies between 49% and 94%, being less sensitive with milder degrees of hepatic steatosis or with higher levels of body mass index (BMI) 6, 7. Abnormal liver enzymes not due to alcohol, viral hepatitis, or iron overload are

Pathophysiology

Accumulation of hepatic triglyceride results when lipid influx and de novo synthesis exceeds hepatic lipid export and utilization. Insulin resistance is an important driving force, which promotes lipolysis of peripheral adipose tissue which in turn increases free fatty acid (FFA) influx into the liver. Hyperinsulinemia and hyperglycemia also promote de novo lipogenesis as well as indirectly inhibit FFA oxidation 25, 26. Lipid export from the liver may also be impaired among individuals with

Natural History

Since the first description of NASH, it has been recognized that hepatic fibrosis may be progressive and result in cirrhosis with complications of hepatocellular carcinoma (HCC), liver failure, and liver-related death 37, 38. Overall, NAFLD appears to be a slowly progressive, with disease-related morbidity and mortality occurring in a minority of subjects. There appears to be, however, considerable variation in the course of the disease with rapid progression to end-stage liver disease being

NAFLD and Cryptogenic Cirrhosis

An important observation by Powell and colleagues (38) was that patients with NAFLD may lose histological evidence of hepatic steatosis as the disease progresses to cirrhosis. Thus the histological picture may resemble one of cryptogenic cirrhosis. Subsequently, examination of metabolic risk factors among patients with cryptogenic cirrhosis revealed a similar prevalence of obesity and diabetes compared to patients with NASH, but a higher prevalence compared to patients with cirrhosis from other

NAFLD and HCC

The occurrence of HCC among patients with NAFLD appears to be relatively low, between zero and 2% 38, 63. However, as NAFLD may affect up to 1 in 3 persons, the potential disease burden may be considerable. Although HCC has been documented to rarely occur in NAFLD in the absence of cirrhosis (64), the risk appears predominantly in the presence of cirrhosis. The risk of HCC in patients with NASH-related cirrhosis is difficult to quantify because of the relatively low numbers of patients,

Treatment

Patients diagnosed with NAFLD should undergo evaluation and treatment of accompanying metabolic risk factors, such as obesity, glucose intolerance, and dyslipidemia in order to modify risk of morbidity and mortality from vascular disease. Treatment strategies specific for NAFLD aim to improve insulin sensitivity and modify underlying metabolic risk factors; these strategies may also be devised to protect the liver from oxidative stress and further insults. Liver transplantation may be required

Conclusions

NAFLD is a common condition related to insulin-resistant states such as obesity and glucose intolerance. The individual risk of developing disease-related morbidity and mortality appears relatively low; however, the overall public health burden may be substantial, considering the high prevalence of the disease. Further natural history studies with adequate follow-up are required to clarify this further. In addition, research into disease pathogenesis will assist in identifying patients who are

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