Fatty Liver
Author:
Dawn Sears, MD;
Chief Editor:
Julian Katz, MDBackground

Fatty liver disease can range from
fatty liver alone (steatosis) to fatty liver associated with
inflammation (steatohepatitis). This condition can occur with the use of
alcohol (alcohol-related fatty liver) or in the absence of alcohol
(nonalcoholic fatty liver disease [NAFLD]). Fatty liver disease
is now the most common cause for elevated liver function tests in the
United States. This is mainly due to the ongoing obesity epidemic in the
United States. Fatty liver can be associated with the use of
alcohol. This may occur with as little as 10 oz of alcohol ingested per
week. Identical lesions also can be caused by other diseases or toxins. If
steatohepatitis is present but a history of alcohol use is not, the
condition is termed nonalcoholic steatohepatitis (NASH). Fatty change in
the liver results from excessive accumulation of lipids within
hepatocytes. Simple fatty liver is believed to be benign, but NASH can
progress to cirrhosis and can be associated with hepatocellular carcinoma.
The main risk factors for simple fatty liver (NAFLD) and NASH are
obesity, diabetes, high triglyceride levels, or a high fat diet.
Pathophysiology
Fatty liver is the accumulation of
triglycerides and other fats in the liver cells. In some patients, this
may be accompanied by hepatic inflammation and liver cell death
(steatohepatitis). Potential pathophysiological mechanisms
include the following: (1) decreased mitochondrial fatty acid
beta-oxidation, (2) increased endogenous fatty acid synthesis or
enhanced delivery of fatty acids to the liver, and (3) deficient
incorporation or export of triglycerides as very low-density
lipoprotein.

Epidemiology

Frequency
United States
Steatosis affects approximately 25-35% of the
general population. Steatohepatitis may be related to alcohol-induced
hepatic damage or may be unrelated to alcohol (ie, NASH). NASH has been
detected in 1.2-9% of patients undergoing routine liver biopsy. NAFLD is
found in over 80% of patients who are obese. Over 50% of patients
undergoing bariatric surgery have NASH.International

Danish
and Australian studies show less intense disease progression than
studies in the United States. Asian studies reveal NASH and NAFLD at
lower body mass indexes (BMIs).Mortality/Morbidity

A
natural history study from Olmsted County, Minnesota, revealed that 10%
more patients with NAFLD died versus control subjects over a 10-year
period. Malignancy and heart disease were the top 2 causes of death.
Liver-related disease was the third cause of death (13%), as compared to
the 13th cause of death (< 1%) for control subjects.

• Steatosis
  was once believed to be a benign condition, with rare progression to
  chronic liver disease. Steatohepatitis may progress to liver fibrosis
  and cirrhosis and may result in liver-related morbidity and mortality.
  
• Fibrosis
  or cirrhosis in the liver is present in 15-50% of patients with NASH.
  Approximately 30% of patients with fibrosis develop cirrhosis after 10
  years. Many cases of cryptogenic cirrhosis may represent so-called
  burnt-out NASH because a high proportion is associated with obesity,
  type II diabetes, or hyperlipidemia.
  
• Some
  patients with drug-induced fatty liver present dramatically with the
  rapid evolution of hepatic failure. Some patients with inborn errors of
  metabolism, such as tyrosinemia, may rapidly progress to cirrhosis.
  

Race

Fatty liver has been found across all races, but most of the research and the highest prevalence appear in the Caucasian race. A
small study evaluating fatty liver disease in the Indian population
found its association with the nonobese and its recovery with simple
lifestyle habits.^[3] However, obesity, when present, was a significant risk factor for NASH in Indians as well as in Koreans.^[2] Interestingly,
and as supported in the author’s clinical practice, Asian patients
often develop NAFLD and NASH at normal BMIs, but BMIs on the higher
range for a patient’s ethnicity. A diagnosis of cirrhosis in an
80-year-old, 5-foot, 110-lb Asian female, with a BMI of 21, is not
unusual.Mutations for hemochromatosis appear to put Caucasians at a higher risk of more advanced fibrosis.^[4] Sex

• As many as 75% of patients in initial reported studies were females.
  
• In more recent studies, 50% of patients are females.
  

Age

• Fatty liver occurs in all age groups.
  
• NAFLD
  is the most common liver disease among adolescents in the United
  States. Older age often is predictive of more severe grading of
  fibrosis.
  
• NASH is the third most common cause of
  chronic liver disease in adults in the United States (after hepatitis C
  and alcohol). It is now probably the leading reason for mild elevations
  of transaminases.
  
• NASH has recurred within 6 months after pediatric or adult liver transplant.^{[5, 6, 7]}
  
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