Fatty Liver Disease for USMLE Step 3
Fatty Liver Disease for the USMLE Step 3
Overview
- Fatty liver disease includes Non-Alcoholic Fatty Liver Disease (NAFLD) and Alcoholic Liver Disease (ALD), both marked by excess fat accumulation in the liver.
- NAFLD occurs in the absence of significant alcohol consumption, while ALD is caused by chronic alcohol use.
Non-Alcoholic Fatty Liver Disease (NAFLD)
Pathophysiology
- NAFLD is the hepatic manifestation of metabolic syndrome and includes:
- Simple steatosis: Fat accumulation without significant inflammation.
- Non-alcoholic steatohepatitis (NASH): Fat accumulation with inflammation, hepatocyte injury, and fibrosis, which may progress to cirrhosis.
- The primary drivers of NAFLD are insulin resistance and lipotoxicity.
- Insulin resistance leads to increased free fatty acid delivery to the liver, promoting steatosis.
- Oxidative stress contributes to hepatocyte damage in NASH.
Risk Factors
- Obesity: Particularly central (visceral) obesity.
- Type 2 diabetes mellitus (T2DM): Strongly associated with fibrosis progression in NAFLD.
- Dyslipidemia: Elevated triglycerides and low HDL cholesterol levels.
- Metabolic syndrome: A combination of obesity, hypertension, hyperglycemia, and dyslipidemia.
Clinical Features
- Most patients are asymptomatic and diagnosed incidentally via imaging or abnormal liver function tests.
- Symptoms, if present, include fatigue, right upper quadrant (RUQ) discomfort, or nonspecific abdominal pain.
- Physical findings may include hepatomegaly.
Diagnosis
- Imaging:
- Ultrasound: Shows increased liver echogenicity (bright liver) due to fat infiltration.
- Transient elastography (FibroScan): Measures liver stiffness to estimate fibrosis.
- Liver biopsy: The gold standard for distinguishing between simple steatosis and NASH, and assessing fibrosis.
- Lab tests:
- Elevated ALT and AST levels, typically with an AST:ALT ratio <1.
- Gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) may also be elevated.
Complications
- NASH can progress to cirrhosis and increases the risk of hepatocellular carcinoma (HCC).
- Cardiovascular disease is the most common cause of death in NAFLD patients due to underlying metabolic syndrome.
Management
- Lifestyle modification:
- Weight loss: A reduction of 7–10% of body weight is recommended to improve liver histology.
- Diet: Low-calorie and low-carbohydrate diets, such as the Mediterranean diet, are beneficial.
- Pharmacotherapy:
- Pioglitazone: Improves liver histology in NASH, especially in patients with T2DM.
- Vitamin E: Used in non-diabetic patients with NASH for its antioxidant properties.
- Bariatric surgery: May be considered for patients with morbid obesity and NAFLD who do not respond to conservative measures.
Alcoholic Liver Disease (ALD)
Pathophysiology
- ALD results from chronic alcohol consumption, leading to fat accumulation in hepatocytes, oxidative stress, and proinflammatory cytokine release, which cause inflammation and fibrosis.
- ALD includes simple steatosis, alcoholic hepatitis, and cirrhosis.
Clinical Features
- Alcoholic hepatitis: Presents with jaundice, fever, RUQ pain, and tender hepatomegaly.
- Physical findings of advanced disease may include ascites, spider angiomata, and palmar erythema.
Diagnosis
- AST:ALT ratio >2 is characteristic of ALD.
- Liver biopsy: Shows steatosis, Mallory bodies, and neutrophilic infiltration in alcoholic hepatitis.
Complications
- ALD can progress to cirrhosis, which increases the risk of portal hypertension, hepatic encephalopathy, and hepatocellular carcinoma.
Management
- Alcohol cessation is the cornerstone of treatment and can reverse early-stage liver damage.
- Corticosteroids: Used in severe alcoholic hepatitis to reduce inflammation and improve short-term outcomes.
- Nutritional support: Often needed, especially in malnourished patients.
Key Points
- NAFLD is associated with metabolic syndrome and can progress to NASH, increasing the risk of cirrhosis and hepatocellular carcinoma (HCC).
- ALD results from chronic alcohol consumption and can progress from simple steatosis to alcoholic hepatitis and cirrhosis.
- AST:ALT ratio >2 is characteristic of ALD, while NAFLD usually has an AST:ALT ratio <1.
- Treatment of NAFLD centers on weight loss and lifestyle modification, while ALD requires alcohol cessation and, in severe cases, corticosteroids for alcoholic hepatitis.