Prevalence of fatty liver is high in the Western hemisphere. In the US it is 20%,17 while studies from Japan and Italy show prevalence of fatty liver in the general population ranging from 3-58%.18
Identifying those at risk
Prevalence increases with obesity and it is an established fact that diets rich in fat and high in calories lead to obesity and insulin resistance.
Patients with diabetes mellitus are at risk as well. In a study involving 100 patients with type-2 diabetes from India, it was seen that 49% had fatty liver on ultrasound.19 Another study from Cleveland, USA involving 132 patients with fatty liver, revealed that 33% had type-2 diabetes.20
Fatty liver is the hepatic manifestation of the metabolic syndrome. It’s severity is directly proportionate to the severity of insulin resistance. This is considered to be the key factor
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(GGT) and serum ferritin may also be elevated and occasionally serum bilirubin is mildly elevated.
Ultrasonographic findings of fatty liver include increased hepatic parenchymal echotexture and vascular blurring. The ability to detect fatty liver at sonography is markedly decreased if the fat content of liver is <30% of liver weight.24 CT is more specific for the diagnosis. CT attenuation of liver is decreased in fatty liver. Hepatic parenchymal attenuation >10 Hounsfield units lower than that of spleen in a non-contrast enhanced CT film suggests the diagnosis of fatty liver. After administration of intra-venous contrast, the liver to spleen attenuation differential is >20 Hounsfield units.24 MRI is superior to CT scan for the diagnosis of fatty liver, but none of the above three imaging modalities can provide information about the stage of hepatic fibrosis.24
Liver biopsy remains gold standard for diagnosis of fatty liver. It can also distinguish between hepatic steatosis and steatohepatitis and assess degree of hepatic fibrosis. Characteristic histopathological changes in fatty liver include macro-vesicular steatosis and in the presence of steatohepatitis, hepatocyte ballooning, Mallory’s hyaline, scattered inflammation and pericellular fibrosis.25
Goal of treatment
The goal of treatment is to prevent development of cirrhosis and it’s complications. Weight reduction is the primary treatment as the majority of patients with fatty liver are obese and improved glycaemic control is important in those who have type-2 diabetes.
Weight loss improves insulin sensitivity and prevents the onset of type-2 diabetes. However rapid weight loss >1.6 kg/week is not recommended as this can cause exacerbation of portal inflammation and fibrosis. Exercise should be combined where possible and this also improves insulin sensitivity.
Drugs for weight reduction include the pancreatic lipase inhibitor orlistat, which promotes weight loss by inducing dietary fat malabsorption and sibutramine, a serotonin-noradrenaline uptake inhibitor that induces a sense of satiety and increases metabolism.
Bariatric surgery is indicated in patients with morbid obesity. Surgical techniques include gastric banding, gastric bypass and bilio-pancreatic diversion.
Insulin sensitising agents such as metformin and the thiazolidinediones are a main focus of pharmacological treatment, as insulin resistance is central to the pathogenesis of fatty liver. A small pilot study in which 15 patients with fatty liver received metformin at a dose of 20mg/kg for one year, demonstrated improvement in serum ALT and AST levels and insulin sensitivity during the first three months of treatment.
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leading to accumulation of fat within hepatocytes through increased fatty acid uptake and synthesis and impaired fatty acid storage or export by hepatocytes.
Fatty liver progresses from NAFL through NASH to cirrhosis with upto 10% of NASH patients going on to develop cirrhosis.21 The ‘two hit’ hypothesis states that a second insult (eg. oxidative stress, hepatitis C, alcohol etc.) to fatty liver is needed for progression.22
Progression of cirrhosis due to fatty liver is similar irrespective of aetiology and there is risk of development of liver cancer.
Diagnosis of fatty liver
Typically fatty liver is associated with serum AST and serum ALT values <250 U/L and/or modest elevation of serum alkaline phosphatase. Serum ALT or AST> 300 U/L usually suggest an alternate pathology. An AST/ALT ratio >2 is suggestive of alcoholic liver disease, while AST/ALT ratio <1 suggests fatty liver. Values between 1 and 2 may be seen in both these conditions.23 Serum gamma glutamyl transferase
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