Basics
Description
- Cirrhosis is the end stage of progressive hepatic necrosis, fibrosis, and regenerative nodule formation that may occur as a result of many different liver diseases.
- Results in distortion of liver architecture and compression of hepatic vascular and biliary structures
- In its advanced form, cirrhosis is irreversible and often requires liver transplantation for survival of the patient.
Epidemiology
- There are varying causes of cirrhosis; accordingly, no specific epidemiologic pattern can be identified.
- Cirrhosis due to chronic HCV infection, alcoholic liver disease, and nonalcoholic fatty liver disease (NAFLD) are the most common indications for liver transplantation in adults.
- Biliary cirrhosis due to biliary atresia is the most common indication for liver transplantation in children.
Genetics
- Many distinct genetic disorders can cause cirrhosis, such as Wilson disease and hereditary hemochromatosis.
- Human leukocyte antigen (HLA) associations have been identified in several autoimmune disorders, including sclerosing cholangitis and autoimmune hepatitis.
Diagnosis
History
- Compensated (latent) cirrhosis: asymptomatic, with no signs or symptoms of liver disease. Discovered incidentally either during routine physical examinations with an enlarged liver and/or palpable spleen or as a result of an investigation for an unrelated condition
- Decompensated (active) cirrhosis: As cirrhosis progresses, overt signs and symptoms may occur including failure to thrive, muscle weakness, fatigue, jaundice, pruritus, edema, abdominal pain, ascites, steatorrhea, spontaneous bleeding (i.e., epistaxis) or bruising, and deterioration in school performance or depression.
- In adults, decompensated cirrhosis is defined by the development of major complications: variceal hemorrhage, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension.
- Based on the varying etiologies, one should elicit pertinent historical features characteristic of specific problems:
- Exposure to infectious hepatitis, antecedent viral illnesses
- Exposure to hepatotoxins
- Family or personal history of genetic, metabolic, or autoimmune diseases
- Neurologic problems, deteriorating school performance, depression (Wilson disease)
Physical Exam
- General: poor growth, malnutrition, fever, cachexia, obesity (NAFLD)
- Skin: jaundice, flushing, pallor, cyanosis, palmar erythema, spider angiomata, fine telangiectasia (face and upper back), easy bruising
- Abdomen: ascites (distention, fluid wave, shifting dullness), caput medusa (prominent periumbilical veins), splenomegaly, rectal varices, hepatomegaly, or a shrunken liver
- Extremities: digital clubbing, hypertrophic osteoarthropathy, muscle wasting, peripheral edema
- Endocrine: gynecomastia, testicular atrophy, delayed puberty
- Central nervous system: asterixis, positive Babinski sign, mental status changes, hyperreflexia, muscle wasting
- Eyes: Kayser-Fleischer rings (Wilson disease)
Diagnostic Tests & Interpretation
Lab
Can be useful in determining the etiology and the severity of liver disease prior to a liver biopsy
- Tests of liver cell injury: alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH)
- Tests of synthetic function: albumin and other serum proteins, prothrombin time (PT), international normalized ratio (INR), partial thromboplastin time (prolonged in severe liver disease), ammonia, plasma and urine amino acids, serum lipids and lipoproteins, cholesterol and triglycerides
- Tests of cholestasis: fractionated bilirubin, alkaline phosphatase, γ-glutamyltransferase, cholesterol, serum and urine bile acids
- Tests of fibrosis: Serum markers may be useful to evaluate hepatic fibrosis noninvasively; however, these are still being investigated for clinical use.
- Miscellaneous disease-specific serum tests:
- Viral serologies: hepatitis B, hepatitis C, other viruses
- Wilson disease: serum ceruloplasmin, 24-hour urine copper, and slit-lamp exam for Kaiser-Fleischer rings
- α1-Antitrypsin deficiency: α1-Antitrypsin serum level and protease inhibitor (Pi) phenotype
- Autoimmune hepatitis: autoantibodies (antinuclear, anti-smooth muscle, anti-liver/kidney microsomal, anti-F-actin), serum immunoglobulins
- Hemochromatosis: serum iron, total iron binding capacity, ferritin
- Metabolic/genetic: fasting blood sugar, lactate, pyruvate, uric acid, sweat test, carnitine, creatine phosphokinase (CPK), porphyrins, serum amino acids, urine organic acids, urine reducing substances, urine succinylacetone, fatty acid degeneration products, α-fetoprotein
Imaging
- Ultrasound with Doppler images: Evaluate for anatomy of the liver and biliary tree and vessels, presence of ascites, signs of portal hypertension such as splenomegaly, varices, reversal of flow in portal vein.
- Hepatobiliary radioisotope scanning: Assess biliary patency in neonatal cholestasis.
- Cholangiography (magnetic resonance cholangiopancreatography [MRCP]: Assess for intra- and extrahepatic biliary disease (stones, choledochal cyst, sclerosing cholangitis).
- Angiography: CT or magnetic resonance angiography to evaluate for vascular anatomy and portosystemic shunts
- Noninvasive assessment of liver fibrosis: CT, MRI, elastography by ultrasound or MRI
Diagnostic Procedures/Other
- Liver biopsy
- Percutaneous needle biopsy, intraoperative wedge biopsy, transjugular liver biopsy
- Confirm the presence (stage), activity (grade), and type of cirrhosis.
- Various hepatic diseases that progress to cirrhosis have characteristic histologic findings. However, the process of cirrhosis may obscure the nature of the original insult, rendering morphologic and histologic classifications unhelpful.
- Hepatic venous pressure gradient (HPVG): rarely used in children but is the most accurate prognostic indicator of outcome in adults with cirrhosis.
- Cholangiography
- Intraoperative cholangiography: Assess for extrahepatic biliary atresia in neonates.
- Endoscopic retrograde cholangiopancreatography (ERCP): Assess for extrahepatic biliary disease in older patients where MRCP is not helpful or therapeutic interventions possible (i.e., stent placement).
Differential Diagnosis
- Biliary
- Extrahepatic biliary atresia
- Choledochal cyst
- Tumors
- Common bile duct and biliary lithiasis
- Alagille syndrome
- Biliary hypoplasia
- Sclerosing cholangitis
- Graft-versus-host disease
- Vanishing bile duct syndrome due to drugs (e.g., trimethoprim-sulfamethoxazole)
- Langerhans cell histiocytosis
- Hepatic
- Infectious hepatitis, including viral hepatitis B, C, D, other viruses
- Autoimmune hepatitis
- Nonalcoholic steatohepatitis (NASH)
- Drugs/toxins and alcohol
- Genetic/metabolic (examples for each category, not a complete list)
- Cystic fibrosis
- α1-Antitrypsin deficiency
- Congenital hepatic fibrosis
- Progressive familial intrahepatic cholestasis (PFIC)
- Wilson disease
- Hereditary hemochromatosis
- Carbohydrate defects: galactosemia, hereditary fructose intolerance, glycogen storage III and IV
- Amino acid defects: tyrosinemia
- Lipid storage diseases: Gaucher disease, Niemann-Pick type C
- Mitochondrial disorders: fatty acid oxidation defects, respiratory chain defects
- Peroxisomal disorders: Zellweger syndrome
- Porphyrias: erythropoietic protoporphyria
- Vascular
- Budd-Chiari syndrome
- Veno-occlusive disease
- Congestive heart failure
Treatment
Medication
First Line
- Fat-soluble vitamin supplementation: vitamins A, D, E, and K
- Diuretic therapy (furosemide, spironolactone) for patients with ascites
- Albumin infusions for patients with refractory ascites
- β-blockers have been shown to decrease portal pressure and reduce the risk of variceal bleeding in adults with portal hypertension.
- Antibiotics, if suspicious for spontaneous bacterial peritonitis (avoid nephrotoxic agents)
- Lactulose and rifaximin (adults) are used for patients with hepatic encephalopathy.
Surgery/Other Procedures
- Endoscopic variceal band ligation or sclerotherapy for variceal GI bleeding
- Paracentesis for refractory ascites or diagnosis of spontaneous bacterial peritonitis
- Portosystemic shunt placement (surgical or radiologic transjugular intrahepatic portosystemic shunting [TIPS] procedure) for complications of uncontrolled portal hypertension
- Liver transplantation
Ongoing Care
Diet
- Malnutrition is common in chronic liver diseases because of several metabolic derangements, fat malabsorption, anorexia, and increased energy requirements.
- Adequate caloric intake is critical and, often, will require supplemental nasogastric tube feedings.
- Some of the dietary fat should be provided as medium-chain triglycerides, which do not require bile for absorption.
- Fat-soluble vitamin levels should be monitored and supplemented, if necessary.
- Careful attention must also be paid to fluid and electrolyte balance; sodium restriction (<2 mEq/kg/day) may be necessary in the presence of ascites.
General Measures
Spleen guard and avoidance of abdominal trauma if significant splenomegaly
Prognosis
- The prognosis for cirrhosis leading to decompensation depends on the underlying cause.
- The underlying condition should be treated when possible (e.g., Wilson disease, autoimmune hepatitis).
- Poor prognostic features in children include prolonged INR unresponsive to vitamin K, ascites, malnutrition, low plasma cholesterol, elevated bilirubin level, and presence of hepatorenal syndrome.
Complications
- Malnutrition and growth failure
- Malabsorption (diarrhea, steatorrhea, fat-soluble vitamin deficiencies)
- Portal hypertension and variceal bleeding
- Chronic gastritis, peptic ulcer disease, gastroesophageal reflux
- Ascites
- Encephalopathy
- Hypersplenism (associated with anemia, thrombocytopenia, and neutropenia)
- Anemia
- Coagulopathy
- Hepatopulmonary syndrome (hypoxemia, cyanosis, dyspnea, digital clubbing)
- Hepatorenal syndrome (rapidly progressive renal failure in patients with cirrhosis)
- Bacterial infections, spontaneous bacterial peritonitis
- Hepatocellular carcinoma
Additional Reading
- Albilllos A, Garcia-Tsao G. Classification of cirrhosis: the clinical use of HVPG measurements. Dis Markers. 2011;31(3):121-128. [View Abstract]
- Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, et al. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut. 2009;58(11):1538-1544. [View Abstract]
- Kamath BM, Olthoff KM. Liver transplantation in children: update 2010. Pediatr Clin North Am. 2010;57(2):401-414. [View Abstract]
- Leonis MA, Balistreri WF. Evaluation and management of end-stage liver disease in children. Gastroenterology. 2008;134(6):1741-1751. [View Abstract]
- Lewindon PJ, Shepherd RW, Walsh MJ, et al. Importance of hepatic fibrosis in cystic fibrosis and the predictive value of liver biopsy. Hepatology. 2011;53(1):193-201. [View Abstract]
- Mencin AA, Lavine JE. Nonalcoholic fatty liver disease in children. Curr Opin Clin Nutr Metab Care. 2011;14(2):151-157.
- Poupon R, Chazouilleres O, Poupon RE. Chronic cholestatic diseases. J Hepatol. 2000;32(1)(Suppl):129-140. [View Abstract]
Codes
ICD09
- 571.5 Cirrhosis of liver without mention of alcohol
- 571.6 Biliary cirrhosis
- 751.61 Biliary atresia
ICD10
- K74.60 Unspecified cirrhosis of liver
- K74.5 Biliary cirrhosis, unspecified
- Q44.2 Atresia of bile ducts
SNOMED
- 19943007 Cirrhosis of liver (disorder)
- 1761006 Biliary cirrhosis (disorder)
- 77480004 Congenital biliary atresia (disorder)
FAQ
- Q: Will my child with cystic fibrosis develop cirrhosis?
- A: The medical literature suggests a 5-10% incidence of cirrhosis in children with cystic fibrosis. Children with cystic fibrosis liver disease who develop cirrhosis are at risk for complications of portal hypertension.
- Q: Will every child with cirrhosis need a liver transplant?
- A: If cause of cirrhosis cannot be treated, most children who develop cirrhosis will ultimately require a liver transplant.