Fatty Liver Disease for the PA Exam
Fatty Liver Disease for the Physician Assistant Licensing Exam
Overview
- Fatty liver disease is characterized by excess fat accumulation in hepatocytes and includes two major categories:
- Non-alcoholic fatty liver disease (NAFLD): Occurs in the absence of significant alcohol consumption.
- Alcoholic liver disease (ALD): Linked to chronic alcohol intake.
Non-Alcoholic Fatty Liver Disease (NAFLD)
Pathophysiology
- NAFLD is associated with insulin resistance and is closely linked to metabolic syndrome (obesity, type 2 diabetes, dyslipidemia).
- Insulin resistance increases fatty acid delivery to the liver, enhancing fat storage.
- Non-alcoholic steatohepatitis (NASH): A subset of NAFLD, characterized by inflammation, hepatocyte injury, and fibrosis.
- Oxidative stress and lipotoxicity play roles in the progression from simple steatosis to NASH.
Risk Factors
- Obesity: Particularly visceral (central) obesity.
- Type 2 diabetes mellitus (T2DM): Strongly associated with NAFLD and fibrosis progression.
- Dyslipidemia: Elevated triglycerides and low HDL levels.
- Metabolic syndrome: Increases the risk of NAFLD.
Clinical Features
- Most patients are asymptomatic and diagnosed incidentally.
- Symptoms, if present, include fatigue and right upper quadrant (RUQ) discomfort.
- Hepatomegaly may be detected on physical examination.
Diagnosis
- Imaging:
- Ultrasound: Common initial test, showing increased echogenicity (bright liver).
- Liver biopsy: Gold standard for differentiating between simple steatosis and NASH.
- Steatosis: Fat droplets within hepatocytes.
- NASH: Ballooning degeneration, inflammation, and fibrosis.
- Laboratory tests:
- Mild elevations in ALT and AST with an AST:ALT ratio <1.
- Elevated gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) may also be seen.
Complications
- NAFLD can progress to cirrhosis and increases the risk of hepatocellular carcinoma (HCC).
- Cardiovascular disease: The most common cause of death in NAFLD patients due to its association with metabolic syndrome.
Alcoholic Liver Disease (ALD)
Pathophysiology
- ALD is caused by chronic alcohol consumption, leading to fat accumulation, oxidative stress, and cytokine release, which cause hepatocyte damage.
- The disease spectrum includes simple steatosis, alcoholic hepatitis, and cirrhosis.
Clinical Features
- Alcoholic hepatitis: Presents with jaundice, fever, RUQ pain, and tender hepatomegaly.
- Spider angiomata, palmar erythema, and ascites may be seen in advanced ALD.
Diagnosis
- AST:ALT ratio >2 is highly suggestive of ALD.
- Liver biopsy: Shows steatosis, Mallory bodies, and neutrophilic infiltration.
Complications
- ALD can progress to cirrhosis, which is associated with portal hypertension, ascites, and variceal bleeding.
- Risk of hepatocellular carcinoma increases in cirrhotic patients.
Management
NAFLD
- Lifestyle modification:
- Weight loss: A target reduction of 7-10% of body weight is recommended to improve steatosis and NASH.
- Diet: Low-calorie, low-carbohydrate diets such as the Mediterranean diet.
- Pharmacotherapy:
- Pioglitazone (a thiazolidinedione) improves liver histology in NASH.
- Vitamin E: Antioxidant therapy in non-diabetic patients with NASH.
ALD
- Alcohol cessation is the cornerstone of management.
- Corticosteroids: Used in severe alcoholic hepatitis to reduce liver inflammation.
- Nutritional support: Critical in malnourished patients, often with thiamine deficiency.
Key Points
- NAFLD is associated with insulin resistance and metabolic syndrome, and can progress to non-alcoholic steatohepatitis (NASH), which may lead to cirrhosis and hepatocellular carcinoma (HCC).
- ALD is caused by chronic alcohol use and can range from simple steatosis to alcoholic hepatitis and cirrhosis.
- AST:ALT ratio >2 is a hallmark of ALD, whereas NAFLD typically has an AST:ALT ratio <1.
- Management of NAFLD centers on weight loss and lifestyle changes, while ALD requires alcohol cessation and may involve corticosteroids for severe alcoholic hepatitis.