Author:
Paul J.Allegretti
Rodney M.Fullmer
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
Etiology
- Chronic viral hepatitis C (most common cause in the U.S.)
- Chronic alcohol abuse (second most common cause in the U.S.)
- Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)
- Other: Chronic hepatitis B and /or D
- Metabolic:
- Hereditary hemochromatosis
- Wilson disease
- Porphyria
- Drugs:
- Hepatic congestion:
- Right-sided heart failure
- Pericarditis
- Budd-Chiari syndrome (hepatic venous outflow obstruction)
- Infiltrative/autoimmune:
- Sarcoidosis
- Amyloidosis
- Primary biliary cholangitis (PBC) or secondary (sclerosing cholangitis)
- 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
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Signs and Symptoms
- May be asymptomatic
- 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 and Muehrcke lines
- Clubbing
- Feminization:
- Testicular atrophy
- Impotence
- Loss of libido
- Gynecomastia
- Amenorrhea
- Complications:
- When complications develop, patient is considered to have decompensated disease
- Portal hypertension
- Ascites
- 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
- Spontaneous bacterial peritonitis (SBP)
- Hepatic encephalopathy (HE)—may be precipitated by:
- GI bleed
- Infections
- Increased dietary protein
- Hypokalemia
- Sedatives
- Constipation
- Azotemia
- Alkalosis
- 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
Test 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:
- 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
Prehospital
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:
- 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 mcg/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 first 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 mcg/kg in 50 mL saline infused over 20-30 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 t.i.d—goal is 2-3 stools per day
- Octreotide: 25-50 mcg IV bolus followed by 50 mcg/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 t.i.d
- Rifampin: 600 mg (peds: 10-20 mg/kg) PO daily
- Thiamine: 100 mg (peds: 50 mg) IV or IM
- Ursodeoxycholic acid: 13-15 mg/kg/d t.i.d
Disposition
Admission Criteria
- Acute decompensation or complicating conditions
- First 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
- BaconBR. Cirrhosis and its complications. In: JamesonJ, FauciAS, KasperDL, HauserSL, LongoDL, LoscalzoJ, eds. Harrison's Principles of Internal Medicine. 20th ed.New York, NY: McGraw-Hill.
- FeldmanM. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 10th ed.Philadelphia, PA: WB Saunders; 2015.
- GoldbergE. Cirrhosis in Adults: Etiologies, Clinical manifestations, and diagnosis. Wellesley, MA: UpToDate; 2017.
- RunyonBA. Management of adult patients with ascites due to cirrhosis: Update 2012 . Hepatology. 2009;49(6):2087-2107.
See Also (Topic, Algorithm, Electronic Media Element)