Chapter 7 Fatty liver and nonalcoholic steatohepatitis
1 Hepatic steatosis, or the accumulation of triglyceride droplets in hepatocytes, is found in one third to one half of all adults in the United States and can be a cause of elevated serum aminotransferase levels (typically less than 250 U/L).
2 Steatosis without significant inflammation or fibrosis on biopsy is a benign hepatic condition, although it is a sign of insulin resistance and risk for development of cardiovascular disease and diabetes mellitus.
3 Steatosis associated with necroinflammatory changes identified on a liver biopsy specimen, called nonalcoholic steatohepatitis (NASH) when alcohol consumption is minimal or none, can cause progressive hepatic fibrosis, cirrhosis, and liver failure.
4 Nonalcoholic fatty liver disease (NAFLD) is the umbrella term that includes both steatosis without inflammation and NASH.
5 A liver biopsy is warranted to diagnose NASH or other causes of occult liver disease when elevated aminotransferase levels are unexplained, especially in the patient with obesity or type 2 diabetes mellitus.
6 Hepatic steatosis is reliably identified by imaging techniques when the degree of fatty infiltration is substantial. Ultrasonography reveals increased liver echogenicity, whereas noncontrast computed tomography (CT) imaging reveals decreased liver density compared with the spleen.
7 Focal steatosis is a variant typically detected incidentally during sonographic or CT imaging of the abdomen. The appearance is usually characteristic, although biopsy confirmation is occasionally required to exclude malignancy when the imaging appearance is atypical.
Overview
Terminology
1. Nonalcoholic fatty liver disease is a term used to describe excessive liver triglyceride accumulation when alcohol consumption is minimal (less than two to four drinks daily).
2. No uniformly accepted term exists for NAFLD that is not NASH; terms such as benign steatosis, simple steatosis, and nonalcoholic fatty liver (NAFL) are commonly used.
3. NASH is diagnosed when a liver biopsy specimen shows steatosis and characteristic necroinflammatory changes in a patient who has fewer than two to four drinks daily; the presence of fibrosis is not required, but characteristic perisinusoidal fibrosis supports a diagnosis of steatohepatitis.
Pathogenesis
Increased Peripheral Mobilization of Fatty Acids
1. Adipose tissue releases free fatty acids in response to cyclic adenosine monophosphate (cAMP)–mediated signaling from glucagon, epinephrine, and adrenocorticotropic hormone; released fatty acids are transported to the liver bound to albumin in the circulation.
2. Insulin is a major inhibitory signal that normally prevents adipose tissue lipolysis after meals; adipocyte insulin resistance allows inappropriate postprandial lipolysis in adipose tissue with release of free fatty acids into the circulation.
Impaired Hepatic Catabolism of Fatty Acids
1. Impaired mitochondrial beta-oxidation of fatty acids is a major factor in alcoholic steatosis and has also been shown to contribute to the development of NASH.
2. Factors that cause microvesicular steatosis may do so through impaired mitochondrial function (e.g., valproic acid, alcohol, and acute fatty liver of pregnancy).
Impaired Synthesis of Triglyceride and its Secretion as Very-Low-Density Lipoproteins from the Liver
2. Fatty acid esterification to triglyceride ensures that the level of fatty acids within hepatocytes remains low, thus averting cellular injury from fatty acid metabolites.
3. Monounsaturated fatty acids (MUFAs) are needed to make triglyceride; impaired MUFA synthesis in the liver may predispose to lipotoxicity.
5. Any deficiency or metabolic aberration that interferes with any one of these steps can cause accumulation of hepatic triglyceride and hepatic steatosis.
Clinical Features
Symptoms
1. Patients with benign steatosis or nonalcoholic steatohepatitis (NASH) are usually asymptomatic, whereas patients with alcoholic hepatitis are nearly always symptomatic.
2. Right upper quadrant pain or fullness of varying severity occurs in approximately one third of patients with nonalcoholic fatty liver disease (NAFLD); liver capsule distention probably underlies the pain.
Physical Findings
1. Hepatomegaly is common but can be difficult to detect on physical examination of the obese patient.
2. Signs of chronic liver disease such as spider telangiectasias, muscle wasting, jaundice, and ascites point to the presence of cirrhosis.
Risk Factors
3. Type 2 diabetes mellitus
NAFLD is unusual in type 1 diabetes mellitus unless glycemic control is poor or the patient is also obese and insulin resistant.
NAFLD is unusual in type 1 diabetes mellitus unless glycemic control is poor or the patient is also obese and insulin resistant.
