• Liver is enlarged in initial phases, decreased in size in advanced disease
• Splenomegaly
• Ascites and/or peripheral edema
• Altered mental status, decreased consciousness, asterixis in patients with hepatic encephalopathy
• Muscle wasting, palmar erythema, vascular spiders, gynecomastia, axillary hair loss, testicular atrophy, fetor hepaticus
• Dupuytren contractures, parotid gland enlargement, peripheral neuropathy in alcoholic patients

Laboratory Tests

• Serum aspartate aminotransferase (AST): frequently elevated, but levels > 300 U/L uncommon
• Serum alanine aminotransferase (ALT): may be relatively low (AST/ALT > 2)
• Prothrombin time: frequently prolonged
• Serum albumin levels: decreased
• Total serum globulin concentration: increased in advanced cirrhosis
• Alkaline phosphatase: moderately increased; markedly increased in patients with biliary disease
• Blood count
  • Leukopenia and thrombocytopenia may be present
  • Normocytic anemia; may be microcytic, hypochromic, macrocytic, or hemolytic
• Serum cholesterol and triglyceride levels: may be increased in biliary obstruction; low in advanced cirrhosis
• Blood glucose: glucose intolerance and diabetes mellitus may be present
• Serum sodium; hyponatremia is common
• Respiratory alkalosis may be present with low serum bicarbonate and high serum chloride
• Serum magnesium and phosphate levels: hypomagnesemia and hypophosphatemia
• Creatinine and urea blood levels: elevated in renal failure in patients with ascites
• Viral serologies to identify causative agent
• α-Fetoprotein serum levels: at diagnosis and every 6 mo to detect early hepatocellular carcinoma (HCC); mild elevations are common in cirrhosis

Imaging

• Real-time ultrasound
  • Demonstrates morphologic characteristics of cirrhosis
    • Irregular/nodular liver edges
    • Altered liver structure
    • Signs of portal hypertension, such as portocollateral veins
  • Detects hepatic steatosis, ascites, splenomegaly, and portal vein thrombosis
  • Rules out extrahepatic causes of jaundice
  • Detects early HCC
• Color flow Doppler ultrasound
  • Shows portal hemodynamics
  • Detects hepatic tumors and tumor vascularization
• Dynamic studies using CT and MRI: useful in assessing cirrhosis and diagnosing hepatic tumors; expensive
• Endoscopy: to assess presence and size of esophageal varices

Liver Biopsy

• Not always necessary if clinical picture, labs, imaging suggest cirrhosis
• Unequivocally establishes diagnosis
• Helps determine cause and extent of liver damage Percutaneous biopsy for most patients; transjugular biopsy for those with severe coagulopathy (INR > 1.5 and/or platelet count < 50,000/mm³)
• Use with caution in patients with ascites or severe obesity
• Subject to sampling error, especially in macronodular cirrhosis
• Histologic findings
  • Extensive fibrosis and regenerative nodules
  • Periportal lymphocyte infiltration suggests HCV-induced cirrhosis
  • Mallory bodies, polymorphonuclear leukocyte infiltration, and steatosis indicate alcohol-induced cirrhosis and/or nonalcoholic steatohepatitis (NASH)
  • Biliary involvement indicates primary biliary cirrhosis (PBS)
  • Massive iron deposition indicates hemochromatosis

---

back to top

Best Therapy

• Adequate caloric and protein intake
• Mild exercise, including walking and swimming
• Surgery and general anesthesia carry increased risks
• Zinc sulfate (50–200 mg/day) for zinc deficiency
• Topical testosterone for male patients with hypogonadism
• Calcium and vitamin D for patients at high risk for osteoporosis
• Aminobisphosphonates for decreased bone mineralization
• Vaccination against hepatitis A, hepatitis B, pneumococci, and influenza
• Avoid hepatotoxic medications (acetaminophen considered safe at dosages < 3 g/day)
• Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) and nephrotoxic antibiotics (e.g., aminoglycosides) in patients with ascites
• Pegylated interferon plus ribavirin
  • Consider for patients with compensated cirrhosis due to hepatitis C virus (HCV) infection
  • For patients with decompensated cirrhosis awaiting orthotopic liver transplantation (OLT), initiate several months before OLT to prevent graft reinfection
  • Response lower than in noncirrhotic patients
  • May worsen existing anemia and/or thrombocytopenia
  • Pegylated interferon
    • Dose:
      • Alpha 2a, 180 µg/wk S.C.; cost/mo: $1,700
      • Alpha 2b: 1.5 µg/kg/wk S.C.; cost/mo: $2,700
    • Ribavirin
      • Dose: 800–1,200 mg/day p.o.; cost/mo: $1,100-$1,600
    • Orthotopic liver transplantation
      • 1-year survival rate, 85%; 5-year survival rate, > 70%
      • Indications
        • Hepatocellular liver disease
          • Serum bilirubin > 3 mg/dl
          • Serum albumin < 2.5 g/dl
          • Prothrombin time >5 sec above control
        • Cholestatic liver disease
          • Serum bilirubin > 5 mg/dl
          • Intractable pruritus
          • Progressive bone disease
          • Recurrent bacterial cholangitis
        • Both hepatocellular and cholestatic liver disease
          • Recurrent or severe hepatic encephalopathy
          • Refractory ascites
          • Spontaneous bacterial peritonitis
          • Recurrent portal hypertensive bleeding
          • Progressive malnutrition
          • Hepatorenal syndrome
        • Hepatocellular carcinoma (< 3 nodules; no nodule > 5 cm; no portal invasion)
      • Contraindications
        • Severe cardiovascular or pulmonary disease
        • Active drug or alcohol abuse
        • Malignancy outside the liver
        • Sepsis
        • Psychosocial problems jeopardizing posttransplant care

Pruritus

• Cholestyramine, 4 g/day; cost/mo: $40
• Ursodeoxycholic acid, 10 mg/kg/day; cost/mo: $140
• Naltrexone, 50 mg/day; cost/mo: $100
• Rifampicin, 10 mg/kg/day; cost/mo: $100
• Ondansetron, 8 mg q. 12 hr; cost/mo: $2,200

HBV-Related Cirrhosis

• Lamivudine: may improve or stabilize liver disease in some patients; resistance can develop with prolonged treatment
  • Dose: 100 mg/day
  • Cost/mo: $230
• Adefovir: active against wild-type and lamivudine-resistant HBV
  • Dose: 10 mg/day
  • Cost/mo: $610
• Entecavir: active against wild-type and lamivudine-resistant HBV
  • Dose: 0.5–1.0 mg/day
  • Cost/mo: $660-$1,310

Alcohol-Induced Cirrhosis

• Abstinence from alcohol
• Nutritional support
• Colchicine of questionable benefit

Superimposed Alcoholic Hepatitis

• Glucocorticoid: alternative therapy; improves short-term survival in high-risk subgroup
  • Methylprednisolone, 32–40 mg/day for 4 wk, then tapered for 1–2 wk; cost/mo: $200
• Pentoxifylline: alternative therapy; improves short-term survival
  • Dose: 400 mg q. 8 hr
  • Cost/mo: $20

Primary Biliary Cirrhosis

• Ursodeoxycholic acid: relieves pruritus and improves biochemical blood test results, may delay need for liver transplantation
  • Dose: 13–15 mg/kg/day
  • Cost/mo: $230

Cirrhosis Due to Autoimmune Hepatitis

• Use immunosuppressant therapy with caution because it may favor infections

Cirrhosis Due to Genetic Metabolic Diseases

• Hemochromatosis
  • Phlebotomy
• Wilson Disease
  • Copper chelators (e.g., D-penicillamine, trientine)
  • Zinc

The authors have no commercial relationships with manufacturers of products or providers of services discussed in this module.

---

back to top

Best References

Blei AT: Lancet 365:1383, 2005 [PMID 15836876]

Bosch J, et al: Semin Hematol 41:8, 2004 [PMID 14872414]

Cardenas A, et al: J Hepatol 42(suppl):S124, 2005 [PMID 15777567]

Gines P, et al: N Engl J Med 350:1646, 2004 [PMID 15084697]

Wright TL: Hepatology 36:S185, 2002 [PMID 12407593]

August 2006