liver cirrhosis

Cirrhosis of the Liver – Technical but useful

Cirrhosis of the Liver

Ramón Bataller, M.D.
Pere Ginès, M.D.
Institut de Malalties Digestives i Metabòliques, Hospital Clinic, Barcelona, Spain

Definition/Key Clinical Features

    A diffuse disorganization of normal hepatic structure by extensive fibrosis associated with regenerative nodules
    High morbidity and mortality
    Advanced disease is usually irreversible
    Insidious onset of symptoms
    Generalized weakness, anorexia, malaise, weight loss
    Loss of skeletal muscle mass
    Symptoms may be absent or minor in “compensated” cirrhosis
    Symptoms of hepatocellular dysfunction and portal hypertension

        Progressive jaundice, skin hyperpigmentation, pruritus, xanthelasmas
        Bleeding from gastroesophageal varices
        Neuropsychiatric symptoms
        Coagulopathy, mucosal bleeding in advanced disease
        Fat-soluble vitamin deficiency
        Nervous system, heart, and pancreatic symptoms in alcohol-related liver disease


        Gastrointestinal bleeding
        Hepatorenal syndrome
        Spontaneous bacterial peritonitis
        Hepatopulmonary syndrome
        Hepatic encephalopathy
        Hepatocellular carcinoma

Differential Diagnosis

    Hepatic encephalopathy
        Intracranial lesions
        Central nervous system infections
        Other metabolic causes of encephalopathy
        Toxic encephalopathy from alcohol or drugs
        Postseizure encephalopathy
        Psychiatric disorders

Best Tests

Physical Examination

    Liver is enlarged in initial phases, decreased in size in advanced disease
    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 countSerum cholesterol and triglyceride levels: may be increased in biliary obstruction; low in advanced cirrhosis
        Leukopenia and thrombocytopenia may be present
        Normocytic anemia; may be microcytic, hypochromic, macrocytic, or hemolytic
    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


    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 ultrasoundDynamic studies using CT and MRI: useful in assessing cirrhosis and diagnosing hepatic tumors; expensive
        Shows portal hemodynamics
        Detects hepatic tumors and tumor vascularization
    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

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
                Alpha 2a, 180 µg/wk S.C.; cost/mo: $1,700
                Alpha 2b: 1.5 µg/kg/wk S.C.; cost/mo: $2,700
                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%
                    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)
                Severe cardiovascular or pulmonary disease
                Active drug or alcohol abuse
                Malignancy outside the liver
                Psychosocial problems jeopardizing posttransplant care


    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

    Wilson Disease
        Copper chelators (e.g., D-penicillamine, trientine)