DESCRIPTION

• Progressive process of inflammation, cellular injury and necrosis, diffuse fibrosis, and formation of regenerative nodules
• Loss of lobular and vascular architecture
• Irreversible in advanced stages
• Intrahepatic portal hypertension owing to increased resistance at the sinusoid, compression of the central veins, and anastomosis between the arterial and portal systems
• 10th leading cause of death in US

ETIOLOGY

• Chronic alcohol abuse (most common cause in US)
• Chronic viral hepatitis, B or C (2nd most common cause in US)
• Autoimmune hepatitis
• Biliary cirrhosis, primary (PBC) or secondary (sclerosing cholangitis)
• Metabolic:
  • Hereditary hemochromatosis
  • Wilson disease
  • Porphyria
• Drugs:
  • Acetaminophen
  • Methotrexate
  • Amiodarone
  • Methyldopa
• Hepatic congestion:
  • Right-sided heart failure
  • Pericarditis
  • Budd–Chiari syndrome (hepatic venous outflow obstruction)
• Infiltrative:
  • Sarcoidosis
  • Amyloidosis
  • Nonalcoholic steatohepatitis (NASH)
  • Hepatocellular carcinoma, diffusely infiltrating
• Infections:
  • Brucellosis
  • Echinococcosis
  • Tertiary syphilis
  • Schistosomiasis

Pediatric Considerations

• Congenital
• Arteriohepatic dysplasia, biliary atresia, cystic fibrosis, α₁-antitrypsin deficiency
• Metabolic
• Fructosemia, tyrosinemia, galactosemia, glycogen storage diseases
• Infectious
• Congenital hepatitis B

[Outline]

• DESCRIPTION
• ETIOLOGY

SIGNS AND SYMPTOMS

• May be silent
• Insidious onset with nonspecific findings:
  • Malaise
  • Fatigue
  • Anorexia
  • Nausea and vomiting
  • Weight loss
  • Pruritus
  • Hyperpigmentation
• Jaundice
• Abdominal collateral circulation including caput medusae
• Hepatomegaly
• Splenomegaly
• Abdominal discomfort or tenderness
• Fever
• Fetor hepaticus
• Asterixis
• Hypotension
• Cruveilhier–Baumgarten murmur
• Renal insufficiency
• Spider telangiectasias
• Palmar erythema
• Dupuytren contractures
• Parotid and lacrimal gland enlargement
• Terry nails
• Muehrcke lines
• Clubbing
• Feminization:
  • Testicular atrophy
  • Impotence
  • Loss of libido
  • Gynecomastia
• Amenorrhea
• Complications:
  • When complications develop, patient is considered to have decompensated disease.
  • Ascites
  • Spontaneous bacterial peritonitis (SBP)
  • Hepatic encephalopathy (HE)—may be precipitated by:
    • GI bleed
    • Infections
    • Increased dietary protein
    • Hypokalemia
    • Sedatives
    • Constipation
    • Azotemia
    • Alkalosis
  • Variceal hemorrhage:
    • 1/3 of patients with variceal bleed.
    • Each bleeding episode carries a 33% mortality rate.
    • Hepatic venous pressure gradient > 12 mm Hg increases risk of bleed.
  • Portal hypertensive gastropathy or peptic ulcer disease
  • Hepatorenal failure:
    • Caused by decreased renal perfusion during severe decompensated cirrhosis
    • May be iatrogenic: Secondary to diuretics, NSAIDs, IV contrast, aminoglycosides, large-volume paracentesis
    • High mortality rate
  • Hepatopulmonary syndrome:
    • Intrapulmonary vascular dilation and hypoxia
    • Results in increased alveolar–arterial gradient

ESSENTIAL WORKUP

Detailed history and physical exam to search for clues to liver disease

DIAGNOSIS TESTS & INTERPRETATION

Lab

• CBC:
  • Anemia
  • Macrocytosis
  • Leukopenia and neutropenia
  • Thrombocytopenia
• Impaired liver function:
  • High bilirubin
  • Low albumin
  • High globulins
  • Prolonged PT
  • Varying degrees of DIC
  • Hypoglycemia
• Increased liver enzymes:
  • Aspartate alanine aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT)—reflect injury
  • Ratio of AST:ALT ≥2 in alcoholic liver disease
  • Alkaline phosphatase and 5'-nucleotidase reflect cholestasis.
  • γ-Glutamyltranspeptidase (GGT)
  • May be normal in inactive cirrhosis
• Electrolytes, BUN, and creatinine
• Hyponatremia:
  • Renal dysfunction and hepatorenal syndrome
• Arterial blood gases or pulse oximeter for:
  • Suspected pneumonia
  • CHF
  • Hepatopulmonary syndrome
• Search for cause:
  • Hepatitis B surface antigen
  • Hepatitis C antibody
  • Antinuclear antibody (ANA) and antismooth muscle antibody (autoimmune hepatitis)
  • Antimitochondrial antibody (PBC)
  • Serum iron, transferrin saturation, and ferritin (hemochromatosis)
  • Ceruloplasmin (Wilson disease)
  • α₁-Antitrypsin deficiency
  • Serum immune electrophoresis (high IgM in PBC)
  • Cholesterol (chronic cholestasis)
  • α-Fetoprotein (hepatocellular cancer)

Imaging

• US for liver architecture, biliary obstruction, ascites, portal vein thrombosis, splenomegaly
• CT scan to explore abnormal finding on ultrasound
• CXR for pleural effusion, cardiomegaly, and CHF

Diagnostic Procedures/Surgery

• Esophagogastroduodenoscopy (EGD) indicated for upper GI bleeding or variceal surveillance
• Variceal ligation or endoscopic sclerotherapy
• Paracentesis for significant ascites or SBP

DIFFERENTIAL DIAGNOSIS

• Ascites:
  • Increased right heart pressure
  • Hepatic vein thrombosis
  • Peritoneal malignancy/infection
  • Pancreatic disease
  • Thyroid disease
  • Lymphatic obstruction
• Upper GI bleeding:
  • Peptic ulcer disease
  • Gastritis
• Encephalopathy:
  • Metabolic
  • Toxic
  • Intracranial process

[Outline]

• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

PRE-HOSPITAL

• Naloxone, dextrose (or Accu-Chekk), and thiamine for altered mental status
• Reverse hypotension with IV fluids to prevent acute ischemic hepatic injury.

INITIAL STABILIZATION/THERAPY

Treat complications such as GI bleeding or HE.

ED TREATMENT/PROCEDURES

• For suspected variceal bleed:
  • IV proton pump inhibitors
  • IV octreotide-splanchnic vasoconstrictor
  • Reverse coagulopathy:
    • Fresh-frozen plasma 1 IU/hr until bleeding is controlled
    • Desmopressin (DDAVP)—improves bleeding time and prolonged PTT
  • Balloon tamponade with Sengstaken–Blakemore tube or a variant for variceal compression (rarely used anymore, prophylactic intubation recommended)
  • Emergent endoscopic sclerotherapy
• Initiate broad-spectrum antibiotics in suspected sepsis or SBP:
  • Cefotaxime
  • Ticarcillin–clavulanate
  • Piperacillin–tazobactam
  • Ampicillin–sulbactam
• Treat complicating conditions such as ascites, HE, SBP.
• Treat pruritus with:
  • Diphenhydramine 25–50 mg IM/IV q4h
  • Cholestyramine, ursodeoxycholic acid, or rifampin
  • Naloxone infusion 0.2 µg/kg/min for temporary relief for extreme cases
• β-Blocker (propranolol) for esophageal varices:
  • Titrated to pulse rate of 60 or 25% reduction of resting pulse
  • With or without isosorbide dinitrate
  • Decreases rebleeding rate
  • May delay or prevent occurrence of 1st bleed
• Relieve biliary obstruction (e.g., stricture) by endoscopic, radiologic, or surgical means.
• Provide nutritious diet, high in calories and adequate in protein (1 g/kg), unless there is complicating HE
• Consult transplantation coordinator whenever postliver transplantation patient presents to the ED with liver dysfunction, suspected sepsis, or possible treatment-related complication.

SPECIAL-THERAPY

• Hemochromatosis: Phlebotomy or deferoxamine (iron-chelating agent)
• Autoimmune hepatitis: Prednisone with or without azathioprine
• Chronic hepatitis B or C: α-Interferon (avoid in decompensated cirrhosis)
• PBC: Ursodeoxycholic acid
• Wilson disease: Penicillamine
• The only cure for most advanced cirrhosis is liver transplantation.

MEDICATION

• Azathioprine: 1–2 mg/kg PO daily
• Cefotaxime: 1–2 g q6–8h (peds: 50–180 mg/kg/d q6h) IV
• Cholestyramine: 4 g PO 1–6 times per day
• Desmopressin (DDAVP): 0.3 µg/kg in 50 mL saline infused over 15–30 min
• Dextrose: D₅₀W 1 amp (50 mL or 25 g; peds: D₂₅W 2–4 mL/kg) IV
• Naloxone: 0.2–2 mg (peds: 0.1 mg/kg) IV or IM initial dose
• Lactulose: 15–30 mL TID—goal is 2–3 stools per day
• Octreotide: 25–50 µg IV bolus followed by 50 µg/hr IV infusion
• Piperacillin–tazobactam: 3.375 g IV q6h (peds: 100–400 mg/kg/d div. q6–8h; renal dosing required)
• Prednisone: 40 mg (peds: 1–2 mg/kg) PO daily
• Propranolol: 40 (initial) to 240 mg (peds: 1–5 mg/kg/d) PO TID
• Rifampin: 600 mg (peds: 10–20 mg/kg) PO daily
• Thiamine: 100 mg (peds: 50 mg) IV or IM
• Ursodeoxycholic acid: 8–10 mg/kg/d TID

[Outline]

• PRE-HOSPITAL
• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• SPECIAL-THERAPY
• MEDICATION

DISPOSITION

Admission Criteria

• Acute decompensation or complicating conditions
• 1st presentation with clinically evident cirrhosis, unless close outpatient workup is possible
• Advanced grades HE, sepsis, active GI bleed, and hepatorenal and hepatopulmonary syndromes require ICU.
• Advanced stages of hepatocellular carcinoma

Discharge Criteria

Most patients with compensated cirrhosis can be treated as outpatients.

FOLLOW-UP RECOMMENDATIONS

GI for all new cases

[Outline]

• DISPOSITION
• FOLLOW-UP RECOMMENDATIONS

• Prognosis is highly variable.
• Patients present with a wide variety of signs and symptoms related to end-stage liver disease.
• New cases need full workup and GI consultation for management.
• Any complication puts patient in decompensated state.
• SBP symptoms are frequently vague:
  • Must have a high suspicion and low threshold for paracentesis when considering SBP

ICD9

• 571.2 Alcoholic cirrhosis of liver
• 571.5 Cirrhosis of liver without mention of alcohol
• 571.6 Biliary cirrhosis

ICD10

• K70.30 Alcoholic cirrhosis of liver without ascites
• K74.5 Biliary cirrhosis, unspecified
• K74.60 Unspecified cirrhosis of liver

[Outline]

• ICD9
• ICD10

• Feldman M. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 9th ed. Philadelphia, PA: WB Saunders; 2010.
• Goldberg E. Diagnostic Approach to the Patient with Cirrhosis. Wellesley, MA: UpToDate; 2012.
• Longo D, Fauci A, et al. Harrison's Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2011.
• Runyon BA. Management of adult patients with ascites due to cirrhosis. Hepatology. 2009;49(6):2087–2107.

See Also (Topic, Algorithm, Electronic Media Element)

• Ascites
• Hepatic Encephalopathy
• Hepatitis
• Spontaneous Bacterial Peritonitis
• Varices

Ahmed Nadeem

Paul J. Allegretti