Cirrhosis and Portal Hypertension

Snapshot

• A 50-year-old man presents to his primary care physician with yellowing skin and increased abdominal girth. He believes that he has gained weight and is worried about obesity. He also reports being concerned about increased breast size. He denies having a history of alcohol abuse, but when he is questioned further, he admits to drinking a bottle of vodka daily to cope with stressors in his life. On exam, he has spider angiomas on his abdomen, jaundice, and gynecomastia.

Introduction

• Overview
  • cirrhosis is a liver disease characterized by hepatic fibrosis, regenerative nodules, and dysfunction
  • portal hypertension is a complication of cirrhosis, resulting in increased pressure in the portal venous system
• Epidemiology
  • incidence
    • very common cause of death
  • risk factors
    • alcoholic liver disease (most common)
    • nonalcoholic steatohepatitis
    • chronic viral hepatitis
    • autoimmune hepatitis
    • hepatocellular carcinoma
    • primarily biliary cirrhosis
    • α1-antitrypsin deficiency
    • Wilson disease
    • hemochromatosis
• Pathogenesis
  • mechanism
    • chronic liver damage
      • results in regenerative nodules surrounded by bridging fibrosis
        • abnormal wound healing with continued connective tissue deposition, resulting in fibrosis
          • fibrosis mediated by stellate cells 
        • micronodular
          • nodules < 3 mm following metabolic insult
        • macronodular
          • nodules > 3 mm following hepatic necrosis
          • increased risk of hepatocellular carcinoma
      • results in damage to hepatic vasculature
        • fibrosis causes portal hypertension and shunting of portal and arterial blood
      • impaired liver biosynthetic function
        • decreased synthesis of albumin and other proteins
          • leads to decreased plasma oncotic pressure
    • portal hypertension 
      • increased portal hydrostatic pressure
      • causes dilation of venous plexuses at sites of portal-systemic anastomoses (e.g., esophageal varices)
      • regulatory response by the body (e.g., nitric oxide release) leads to splanchnic and systemic vasodilation, resulting in hypotension
        • stimulates ADH release by the posterior pituitary
        • low renal perfusion pressures cause activation of the renin-angiotensin-aldosterone system 
• Prognosis
  • Model for End-Stage Liver Disease (MELD) score
    • predicts 3-month mortality in patients with cirrhosis
    • creatinine
    • bilirubin
• INR

Presentation

• Symptoms
  • common symptoms
    • fatigue
    • weakness
    • weight loss
    • loss of appetite
    • pruritus
    • upper gastrointestinal bleeding
• Physical exam
  • inspection
    • mental status changes
    • signs of liver disease (BAD JPEGS)
      • Bleeding 
        • ↑ prothrombin time
      • Asterix
        • “flapping” tremor
      • Dupuytren contracture
      • Jaundice 
        • ↓ excretion of bilirubin
      • Palmar erythema
      • Encephalopathy
        • ↓ excretion of ammonia
      • Gynecomastia 
        • ↓ degradation of estrogen
      • Spider angiomata
        • ↓ degradation of estrogen
    • portal hypertension 
      • hepatosplenomegaly
      • caput medusa
• ascites

Imaging

• Computed tomography (CT) of abdomen  
  • indications 
    • other imaging studies are inconclusive
    • patients often undergo CT of the abdomen during workup to exclude other pathologies
  • findings
    • nodularity
    • hypertrophy
    • ascites
• Liver ultrasound
  • indications
    • all patients
  • findings
    • fibrosis
    • nodularity
    • increased echogenicity
    • atrophy or hypertrophy of liver lobes
• Transient elastography
  • indications
    • measures liver stiffness
    • all patients
  • findings
• hepatic fibrosis and increased stiffness

Studies

• Serum labs
  • multiple severity scores exist for cirrhosis but often include
    • ↑ liver enzymes
    • ↑ prothrombin time
      • treat with fresh frozen plasma or factor replacement
    • ↑ direct bilirubin
    • ↓ platelets
    • creatinine
  • determining etiology
    • hepatitis B and C serology
    • alpha-1 antitrypsin levels
    • antinuclear antibody
    • anti-smooth muscle titers
    • anti-mitochondrial antibody
    • ferritin
    • transferrin saturation levels
    • 24-hour copper level in the urine
    • ceruloplasmin
    • hemochromatosis genetic testing
• Invasive studies
  • liver biopsy   
    • indications
      • patients who cannot undergo transient elastography
• clinical presentation is not consistent with a diagnosis

Differential

• Acute viral hepatitis
  • key distinguishing factor
    • acute onset of symptoms with viral prodrome, nausea, vomiting, and abdominal pain
• lacks findings of chronic liver disease

Treatment

• Management approach
  • treat underlying cause if possible
• Lifestyle
  • diet with restricted sodium
    • indications
      • all patients with ascites
  • alcohol and smoking cessation
• Medical
  • antibiotic prophylaxis for spontaneous bacterial peritonitis
    • indications
      • cirrhosis and gastrointestinal bleeding or ascites
  • diuretics 
    • indications
      • patients with ascites
    • modalities
      • furosemide
      • spironolactone
  • vaccinations
    • indications
      • all patients
    • modalities
      • hepatitis A
      • hepatitis B
      • 23-valent pneumococcal vaccine
• Surgical
  • liver transplantation
    • indications
      • refractory liver cirrhosis
      • major complications
        • ascites
        • variceal bleeding
        • hepatic encephalopathy
  • portal shunting 
    • indications
• portal hypertension

Complications

• Hepatocellular carcinoma
  • screening
    • liver ultrasound and alpha-fetoprotein every 6 months
• Esophageal or gastric varices
  • screening
    • esophagogastroduodenoscopy (EGD)
• Spontaneous bacterial peritonitis