CMS200 - Wk 1

NAFLD Overview

• An umbrella term for a spectrum of conditions characterized by excessive fat accumulation in the liver, excluding secondary causes.
• Most common cause of liver disease in Canada, affecting ~20% of Canadians and ~37% of adult Americans.

Key Concepts

• Steatosis: Abnormal retention of fat within an organ.
• Hepatic Steatosis: Fat accumulation in the liver.
• Hepatitis: Inflammation of the liver.
• Steatohepatitis: Fat accumulation and inflammation of the liver.
• Fibrosis: Scarring.
• Cirrhosis: Permanent liver damage where scar tissue replaces liver cells.

NAFLD Progression

• Simple Steatosis (or Non-alcoholic fatty liver (NAFL)): 5% or greater hepatic steatosis without hepatocellular injury or fibrosis.
• Non-alcoholic steatohepatitis (NASH): 5% or greater hepatic steatosis with hepatocellular injury and inflammation, with or without fibrosis.
• NASH with hepatocellular carcinoma: Can progress from NASH.

Epidemiology

• Prevalence: 20-30% in western countries.
• NASH Prevalence: 3-5%.
• More common in obese/overweight adults, but can affect non-obese individuals.
• Average age at diagnosis: 50 years.
• Increasing prevalence in children due to rising childhood obesity: 3-10% in children.
• Ethnic disparities: Hispanics > Caucasians > African Americans.
• Sex disparities in Caucasians: Men > Women; No sex differences observed in Hispanics and African-Americans.

Risk Factors and Causes

• Principal Causes:
  • Obesity (40% of patients with NAFLD)
  • Diabetes mellitus (>20% of patients with NAFLD)
  • Dyslipidemia/hypertriglyceridemia (>20% of patients with NAFLD)
• Association with: Insulin resistance and metabolic syndrome.

Metabolic Syndrome

• Important questions to ask patients during history taking:
  • Family history of obesity or diabetes.
  • Lifestyle habits, including diet, exercise, and alcohol consumption.
  • Medications used.
  • Presence of any existing conditions like high blood pressure, high cholesterol, and cardiovascular disease.

NAFLD Timing and Clinical Course

• Slowly progressive disease: Silent liver disease when there is only steatosis.
• Early Stages (simple steatosis or NAFL) are reversible.
• Progression: NAFL → 20% develop NASH → 20% progress to cirrhosis → possible liver failure and liver cancer.
• Risk Factors for Advanced Hepatic Fibrosis and Cirrhosis:
  • Advanced age
  • Obesity
  • Diabetes mellitus
• Strongest predictor of progression: The degree of inflammation on the first liver biopsy.

NAFLD Complications

• Cardiovascular Disease
• Hepatocellular carcinoma: Annual risk 1-2%.
• End-stage liver disease and liver failure: Develops over 10 years in 45% of patients.
• Coexistence with other chronic liver conditions
• Cardiovascular risk factors contribute to mortality in those with end-stage liver cirrhosis and hepatocellular carcinoma.

Other Predicted Risks of NAFLD

• Cardiovascular events
• Chronic kidney disease
• Colorectal cancers
• Type 2 diabetes mellitus

NAFLD Signs and Symptoms

• Most patients are asymptomatic.
• Possible Presentations in early stages:
  • Fatigue
  • Malaise
  • Mild abdominal discomfort (right upper quadrant)
• Possible Presentations in advanced stages:
  • Nausea
  • Vomiting
  • Jaundice
  • Pruritis
  • Memory impairment
  • Easy bleeding
  • Loss of appetite
  • Hepatomegaly (in 75% of patients)
  • Spider angiomas
  • Signs of portal hypertension: edema, ascites, caput medusae
  • Palmar erythema
  • Gynecomastia - Dupuytren contracture - Petechiae

Detecting Hepatomegaly

• Physical exam findings:
  • Midclavicular liver span on percussion ≥ 10 cm: Sensitivity: 61-92%, Specificity: 30-43%
  • Palpable liver edge: Sensitivity: 39-71%, Specificity: 56-85%

Diagnosing Hepatocellular Disease in Patients with Jaundice

• Physical exam findings:
  • Spider angiomas: Sensitivity: 35-47%, Specificity: 88-97%
  • Palmar erythema: Sensitivity: 49%, Specificity: 95%
  • Dilated abdominal veins: Sensitivity: 42%, Specificity: 98%
  • Ascites: Sensitivity: 44%, Specificity: 90%
  • Palpable spleen: Sensitivity: 29-47%, Specificity: 83-90%
  • Palpable gallbladder: Sensitivity: 0%, Specificity: 69%
  • Palpable liver: Sensitivity: 71-83%, Specificity: 15-17%
  • Liver tenderness: Sensitivity: 37-38%, Specificity: 70-78%

Diagnosing Cirrhosis in Patients with Chronic Liver Disease

• Physical exam findings:
  • Spider angiomas: Sensitivity: 33-84%, Specificity: 48-98%
  • Palmar erythema: Sensitivity: 12-70%, Specificity: 49-98%
  • Gynecomastia: Sensitivity: 18-58%, Specificity: 92-97%
  • Reduction of body or pubic hair: Sensitivity: 24-51%, Specificity: 94-97%
  • Jaundice: Sensitivity: 16-44%, Specificity: 83-99%
  • Dilated abdominal wall veins: Sensitivity: 9-51%, Specificity: 79-100%