Obesity and abnormal liver function tests

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Chapter 39 OBESITY AND ABNORMAL LIVER FUNCTION TESTS

KEY POINTS

• Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver function tests in the Western world.
• NAFLD encompasses the spectrum of liver disease from bland steatosis to steatosis with inflammation and variable degrees of fibrosis (non-alcoholic steatohepatitis).
• NAFLD is associated with a variety of clinical conditions including obesity, hyperlipidaemia and hyperglycaemia, which are all, in turn, associated with the presence of insulin resistance.
• A proportion of patients with non-alcoholic steatohepatitis (NASH) progress to cirrhosis, hepatic decompensation and hepatocellular carcinoma.
• The main therapeutic modality is lifestyle change, including slow, steady weight loss and exercise.
• Lipid-lowering agents and oral antidiabetic agents that make hepatocytes more insulin sensitive are the main therapeutic agents used to manage NASH.
• Patients with NAFLD are at increased risk of type 2 diabetes mellitus and cardiovascular mortality.

INTRODUCTION

Fatty liver or steatosis refers to the accumulation of fat within the liver. The fatty liver disorders are the most common cause of disturbances of liver function tests in the Western world. While there are several causes of fatty liver, including that of excessive consumption of alcohol (see Chapter 40), the commonest cause is that of insulin resistance usually (but not always) associated with one or a combination of obesity, hyperlipidaemia and/or hyperglycaemia. Non-alcoholic fatty liver disease (NAFLD) is the term used to describe steatosis unrelated to excessive alcohol consumption. NAFLD is a form of metabolic liver disease nearly always associated with insulin resistance and very often with the metabolic, or insulin resistance (IR), syndrome.

NAFLD encompasses the entire pathological spectrum from bland steatosis to decompensated cirrhosis. It therefore includes:

• Steatosis
• Non-alcoholic steatohepatitis (fatty liver is accompanied by hepatocyte inflammation and liver cell injury [hepatitis]), with or without fibrosis
• Cirrhosis.

The term non-alcoholic steatohepatitis (NASH) is defined by histological features resembling those of alcoholic hepatitis that are present in patients who have not consumed excessive quantities of alcohol. Most studies define the latter as alcohol consumption less than 20 g per day (i.e. less than 2 standard alcoholic drinks per day).

Prevalence

The commonest cause of unexplained liver function test abnormalities is associated with the fatty liver disorders. The prevalence of such unexplained liver function abnormalities (most commonly an elevated alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) in patients with NAFLD is approximately 7%–20% of the adult population (based on American studies). It is thought that 2%–3% of adults have NASH, and that approximately 20% of these patients with NASH are at risk for developing cirrhosis and subsequently dying from end-stage liver disease. There are, to date, no Australian prevalence data, but prevalence is thought to be similar based on the knowledge of the prevalence of underlying insulin resistance and obesity. Given the significance of obesity and diabetes as risk factors, and the fact that these conditions are increasing in prevalence, it is estimated that the prevalence of NASH is likely to increase in the coming decades.

Risk factors

NAFLD is associated with central adiposity, obesity, hyperlipidaemia (particularly hypertriglyceridaemia, insulin resistance, the metabolic syndrome and type 2 diabetes—all conditions associated with insulin resistance (see Table 39.1). In addition, NAFLD is associated with rapid weight loss, particularly that observed after jejunoileal bypass surgery (Table 39.2).

TABLE 39.1 When to think about the insulin resistance syndrome

• Obesity (central)
• Hypertension
• Hyperlipidaemia
• Microalbuminuria
• Type 2 diabetes or a family history of type 2 diabetes
• Polycystic ovary syndrome
• Hyperuricaemia

TABLE 39.2 Non-alcoholic fatty liver disease (NAFLD) and its clinical associations

• Type 2 diabetes (including family history) or the insulin resistance syndrome
• Rapid and profound weight loss
• Some forms of obesity reduction surgery
• Dyslipidaemia, particularly hypertriglyceridaemia
• Gallstone disease
• Polycystic ovary syndrome
• Gout
• Family history of NAFLD

Natural history and prognosis

In the absence of steatohepatitis, NAFLD does not appear to cause fibrosis or progressive liver disease. In contrast, NASH may be associated with disease progression. The proportion of patients with NAFLD in the community who have cirrhosis is not known. Among those referred to liver clinics and selected for liver biopsy, the proportion with significant fibrosis is in the range of 20%–45%. NASH is a slowly progressing liver disorder. Factors associated with more severe disease include obesity, type 2 diabetes, age over 45 years and hypertriglyceridaemia. The role of gender is contentious. Some, studies have suggested that female gender is an independent risk factor for more severe liver disease.

Only those with advanced liver disease are likely to develop significant liver-related morbidity and mortality. Among those with cirrhosis, there is a risk of decompensation and liver failure.

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