Overall Bottom Line
- ESLD, is an irreversible condition that leads to imminent complete failure of the liver.
- Most chronic liver diseases of childhood result in cirrhosis characterized by widespread hepatic fibrosis and regenerative nodules. Diagnosis of cirrhosis is based on clinical, laboratory, imaging and histologic findings.
- PHT, acute variceal bleeding and hypersplenism, ascites, spontaneous bacterial peritonitis, encephalopathy, coagulopathy and malnutrition, are complications of decompensated cirrhosis.
- Bleeding esophageal varices are managed endoscopically (banding/sclerotherapy), medically (non-selective beta blockers, octreotide) or surgically (portosystemic shunts, TIPS or liver transplantation).
- Fluid and salt restriction with/without diuretics are effective in managing ascites.
- Spontaneous bacterial peritonitis should be diagnosed promptly by paracentesis and treated with antibiotics.
- Hepatic encephalopathy can be subtle in infants and managed with antibiotics, lactulose and low protein diet.
- Coagulopathy is managed with vitamin K and blood products prior to procedures.
- Malnutrition requires high caloric formulas containing medium-chain triglycerides and fat-soluble vitamin supplements.
- Patients with cirrhosis should be screened for HCC (periodic abdominal US and serum AFP level) and for hepatopulmonary syndrome (upright hypoxemia). Children with decompensated cirrhosis should be evaluated for liver transplantation.
Section 1: Background
Definition of disease
- ESLD is an irreversible condition that leads to imminent complete failure of the liver. The etiology of ESLD in children varies with age of presentation.
- In infants biliary atresia, parenteral nutrition-induced cholestasis, Alagille syndrome and metabolic syndromes are the main causes for ESLD. In older children and adolescents autoimmune hepatitis, cryptogenic cirrhosis, PSC or Wilson disease are the leading etiologies for ESLD.
- The main causes of chronic liver disease in children are presented in the table – Causes of liver disease in children that result in cirrhosis.
- ESLD can be with compensated and decompensated liver disease. In compensated liver disease, there may be no symptoms and the indication of liver disease may be incidental findings of liver/spleen or elevation of liver enzymes or direct bilirubin. Decompensated liver disease is characterized by clinical complications (jaundice, ascites, variceal bleeding) and laboratory findings of synthetic failure such as increased INR and hypoalbuminemia.
- The complications of ESLD in children include:
- PHT and variceal bleeding.
- Ascites.
- Bacterial infection, SBP.
- Hepatopulmonary syndrome and pulmonary hypertension.
- Hepatic encephalopathy.
- Coagulopathy.
- Malnutrition.
- Hepatorenal syndrome.
- Hepatocellular carcinoma.
- PHT and variceal bleeding.
Causes of liver disease in children that result in cirrhosis
| Infectious disease Chronic hepatitis B Chronic hepatitis C Herpes simplex disease Cytomegalovirus Genetic/metabolic disorders Alpha-1 antitrypsin deficiency Cystic fibrosis Galactosemia Tyrosinemia Wilson disease Hemochromatosis Glycogen storage disease type 3 Glycogen storage disease type 4 Progressive familial intrahepatic cholestasis type 1 (Byler disease) Progressive familial intrahepatic cholestasis type 2 Progressive familial intrahepatic cholestasis type 3 Zellweger Congenital disorders of glycosylation Non-alcoholic steatohepatitis | Toxic/drugs disorders Organic solvents Hepatotoxic drugs Hypervitaminosis A Total parenteral nutrition Vascular lesions Budd–Chiari syndrome Congenital heart failure Veno-occlusive liver disease Autoimmune diseases Autoimmune hepatitis PSC Biliary diseases Biliary atresia Alagille syndrome Choledochal cyst Congenital hepatic fibrosis Intrahepatic cystic biliary dilatation (Caroli disease) Idiopathic diseases Neonatal hepatitis Cryptogenic |
Section 2: Prevention
Not applicable for this topic.
Section 3: Diagnosis
- The diagnostic approach is provided in each of the following complications of chronic liver disease (including physical examination, laboratory parameters and imaging studies when relevant).
- PHT and variceal bleeding.
- Ascites.
- Bacterial infection, SBP.
- Hepatopulmonary syndrome and pulmonary hypertension.
- Hepatic encephalopathy.
- Coagulopathy.
- Malnutrition and nutrition support.
- Hepatorenal syndrome.
- Hepatocellular carcinoma.
- PHT and variceal bleeding.
Please note: as many of the complications of chronic liver disease appear in adults as well, an algorithm was provided only for nutrition and nutrition support part, which is unique for children.
Section 4: Treatment
- The treatment (medical/surgical) is provided in each of the different complications of chronic liver disease (see relevant chapters on complications of cirrhosis as listed under Section 3: Diagnosis, and under the individual headings in this chapter). A treatment algorithm was provided to the nutritional part which is unique to children.
Section 5: Special Populations
Not applicable for this topic.
Section 6: Prognosis
- The prognosis is provided in each of the different complications of chronic liver disease (see relevant chapters on complications of cirrhosis as listed under Section 3: Diagnosis, and under the individual headings in this chapter).
PHT and variceal bleeding
- PHT is defined by a portal venous pressure above 5 mmHg and an elevated pressure gradient between the portal vein and the inferior vena cava, which is measured by the HVPG above 10–12 mmHg.
- HPVG is elevated in cirrhosis and its response to pharmacotherapy may predict the recurrence of gastrointestinal bleeding.
Clinical manifestations
- Acute variceal bleeding is the presenting symptom of PHT in up to two-thirds of children.
- No particular peak age of presentation has been demonstrated and GIB was reported as early as 2 months of age.
- Splenomegaly may be first discovered on routine physical examination.
- Cytopenias (thrombocytopenia and/or leucopenia) may present as a result of hypersplenism which may cause petechiae and ecchymoses.
- Abdominal vascular marking may be prominent as a result of subcutaneous portocollateral shunting.
- Rectal varices and hypertensive rectopathy may be found.
- Peristomal varices are a common site of bleeding in children with short gut.
Diagnosis
- PHT should be suspected in any child with significant GIB or unexplained splenomegaly.
- Physical examination should focus on the liver, spleen, cutaneous markings and growth.
- Laboratory studies should examine cytopenias and the liver function.
- US with Doppler is the primary investigation of choice in children. Other imaging studies, such as triple phase CT, magnetic resonance venography and selective angiography may be helpful diagnostically in complex cases.
- The gold standard in the diagnosis of varices is EGD.
- Capsule endoscopy, a minimally invasive procedure that uses special video capsules, has a sensitivity of 63–100% for screening of esophageal varices and may be used in children older than 10 years.
- Gastroesophageal varices are an extension of the esophageal varices and isolated gastric varices occur in the absence of esophageal varices and are less common in children.
- Portal gastropathy was found in 25% of children with PHT.
Natural history
- Cirrhotic patients without varices develop them at a rate of 8% per year.
- GIB may occur in the first year of life. Patients with biliary atresia and bilirubin >4 mg/dL have lower survival after the first variceal bleeding without liver transplantation (LT). Complications of PHT are a leading cause of mortality in untreated biliary atresia.
- Mortality rate from variceal bleeding in children is 0–8% in published studies.
- Continuous bleeding at the time of EGD is a poor prognostic sign.
Therapy
- Approaches to the management of PHT in children are mostly descriptive and anecdotal and mostly adapted from the adult literature.
- The management of varices can be divided into pre-primary (before esophageal varices develop), primary (before GIB develops), secondary (before recurrent GIB) and acute variceal bleed.
- In patients with small varices who have not bled but are at increased risk of bleeding (progressive liver disease, esophageal varices with red wales), non-selective beta blockers (i.e. propranolol) are recommended in adults with scant data on efficacy in children. The dose is titrated to decrease the basal heart rate by 25% with a wide dosing range (0.6–8 mg/kg/day) two to four times a day.
- In patients with medium to large varices at high risk of bleeding, either beta blockers or endoscopic therapy (sclerotherapy or banding) may be recommended.
- The initial management of acute variceal bleeding is patient stabilization. Fluid and blood resuscitation is critical, with optimal hemoglobin in adults between 7 and 9 g/dL to avoid overfilling.
- Fresh frozen plasma, recombinant factor 7 and vitamin K may be of benefit in coagulopathic patients. Platelets should be given if the count is <50 000.
- Intravenous antibiotics are recommended to decrease the risk of severe infectious complications.
- Somatostatin (octreotide) or vasopressin should be considered the first line treatment of variceal bleeding. Octreotide is tolerated by children and was effective in treatment of GIB.
- EGD should be initiated once the diagnosis of acute variceal bleeding is suspected and endoscopic therapy performed.
- Variceal band ligation was found to achieve variceal eradication more quickly, with a lower rebleeding rate and fewer complications compared with sclerotherapy.
- Sclerotherapy, also effective in aborting variceal bleeding, is recommended in patients in whom banding is not technically feasible, especially children younger than 2 years, due to difficulty in passing the device.
- Surgical shunts and TIPS are effective rescue therapies. LT may be effective if a donor is found rapidly.
- Given the high rebleeding rate, secondary prophylaxis is recommended. Combination endoscopic plus beta blockers are warranted.
Ascites
- The accumulation of ascitic fluid is the product of a complex process involving hepatic, renal, systemic, hemodynamic and neurohormonal factors. PHT is key to the development of ascites and portal pressure below 12 mmHg in adults is rarely associated with ascites.
- Fluids and salt restriction to reduce ascites can be effective but may have a negative effect on growth unless balanced by high caloric concentrated formula.
- The diuretic of choice is the aldosterone antagonist, spironolactone (starting dose of 1 mg/kg, to be increased gradually up to 6 mg/kg/day). Furosemide (1–2 mg/kg) can be used to control the hyperkalemia (side-effects of spironolactone) and to promote strong and rapid response.
- Children, and especially infants, are vulnerable to the complications of ascites. Tense ascites may lead to extrahepatic organ dysfunction, including compromise of gastrointestinal, renal and pulmonary function.
- Abdominal paracentesis is indicated in non-responsive tense ascites that leads to severe extrahepatic organ dysfunction.
- A modest amount of ascites, as long as extrahepatic organ function is not compromised, is somewhat desired if the patient is to be considered for LT to allow for room for donor transplant organs and subsequent ease of fascial and skin closure with minimal intra-abdominal compression and compromise of donor organ vascular flow.
Related posts:
15: Hereditary Hemochromatosis
14: Primary Sclerosing Cholangitis
38: Liver Transplantation: A Pediatric Perspective
36: Approach to Jaundice in Infancy
53: Recurrent Disease Post-Liver Transplantation: Autoimmune Diseases, Hepatitis B and NASH
34: Diagnosis and Management of Acute Liver Failure: A Pediatric Perspective
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
