Medical management of chronic liver diseases (CLD) in children (part II): focus on the complications of CLD, and CLD that require special considerations

Abstract

Treatment of the causes of many chronic liver diseases (CLDs) may not be possible. In this case, complications must be anticipated, prevented or at least controlled by the best available therapeutic modalities. There are three main goals for the management of portal hypertension: (i) prevention of the first episode of variceal bleeding largely by non-selective β-adrenoceptor antagonists, which is not generally recommended in children; (ii) control of bleeding by using a stepwise approach from the least to most invasive strategies; (iii) and prevention of re-bleeding using bypass operations, with particular enthusiasm for the use of meso-Rex bypass in the pediatric population. Hepatic encephalopathy management also consists of three main aspects: (i) ruling out other causes of encephalopathy; (ii) identifying and treating precipitating factors; and (iii) starting empiric treatment with drugs such as lactulose, rifaximin, sodium benzoate, and flumazenil. Treatment of mild ascites and peripheral edema should begin with the restriction of sodium and water, followed by careful diuresis, then large-volume paracentesis associated with colloid volume expansion in severe cases. Empiric broad spectrum antimicrobial therapy should be used for the treatment of spontaneous bacterial peritonitis, bacterial and fungal sepsis, and cholangitis, after taking appropriate cultures, with appropriate changes in therapy after sensitivity testing. Empirical therapies continue to be the standard practice for pruritus; these consist of bile acid binding agents, phenobarbital (phenobarbitone), ursodeoxycholic acid, antihistamines, rifampin (rifampicin), and carbamazepine. Partial external biliary diversion can be used in refractory cases. Once hepatorenal syndrome is suspected, treatment should be initiated early in order to prevent the progression of renal failure; approaches consist of general supportive measures, management of concomitant complications, screening for sepsis, treatment with antibiotics, use of vasopressin analogs (terlipressin), and renal replacement therapy if needed. Hepatopulmonary syndrome and portopulmonary hypertension are best managed by liver transplantation. Provision of an adequate caloric supply, nutrition, and vitamin/mineral supplements for the management of growth failure, required vaccinations, and special care for ensuring psychologic well-being should be ensured. Anticoagulation might be attempted in acute portal vein thrombosis. Some CLDs, such as extrahepatic biliary atresia (EHBA), Crigler-Najjar syndrome, and Indian childhood cirrhosis, require special considerations. For EHBA, Kasai hepatoportoenterostomy is the current standard surgical approach in combination with nutritional therapy and supplemental fat and water soluble vitamins, minerals, and trace elements. In type 1 Crigler-Najjar syndrome, extensive phototherapy is the mainstay of treatment, in association with adjuvant therapy to bind photobilirubin such as calcium phosphate, cholestyramine, or agar, until liver transplantation can be carried out. Treating Indian childhood cirrhosis with penicillamine early in the course of the disease and at doses similar to those used to treat Wilson disease decreases the mortality rate by half. New hopes for the future include extracorporeal liver support devices (the molecular adsorbent recirculating system [MARS®] and Prometheus®), hepatocyte transplantation, liver-directed gene therapy, genetically engineered enzymes, and therapeutic modalities targeting fibrogenesis. Hepapoietin, a naturally occurring cytokine that promotes hepatocyte growth, is under extensive research.