» Information pour les spécialistes  » Hépatologie Pédiatrique  » Prise en charge des hépatopathies chroniques de l’enfant : prurit, hypertension portale, encephalopathie



Whatever its original cause, pediatric chronic liver disease will eventually lead to liver insufficiency, liver cirrhosis, and may be associated to profound cholestasis. Cholestasis may be associated to pruritus, malabsorption, malnutrition, and growth retardation. Liver cirrhosis leads to portal hypertension, ascitis, and gastrointestinal bleeding . Cholangitis and systemic bacterial infections are common in children with portoenterostomies. Rarer complications of chronic liver disease include progressive hypoxia due to hepatopulmonary shunts, or even more rarely pulmonary hypertension (Table I).


Patients presenting these complications usually become candidates to orthotopic liver transplantation. It is the task of the pediatrician to identify the right timing to decide liver transplantation and to bring these patients in the best condition to the surgical procedure, in order to enhance the success of transplantation (1).





Pruritus is most severe in children with progressive familial intrahepatic cholestasis (PFIC) , Alagille patients, familial cholestasis associated to MDR3 gene expression defect (15), and sclerosing cholangitis. Patients with biliary atresia may also experience pruritus, but usually less severe.


Pruritus and cholestasis are improved by ursodeoxycholic acid treatment (10 mg/kg TDS) in a proportion of PFIC patients (16) and sclerosing cholangitis , but it is not really efficient in pruritus associated to biliary atresia. In PFIC patients with low gamma glutamyl transferase activity as well as in PFIC with high GGT (type MDR3 deficiency) , ursodeoxycholic acid treatment was able to normalize liver function tests in 40 to 50 % of the children, and to improve tests in another 20% to 25%. These biochemical improvements were accompanied by regression of hepatosplenomegaly and disappearance or improvement of pruritus , and may hence avoid liver transplantation in a proportion of these patients (16).


Partial biliary diversion has also been proposed for treatment of cholestasis and pruritus in PFIC patients, and might be efficient provided that the patient has not established cirrhosis at the time of surgery (17). This surgery is not easily accepted by the families because of the permanent stomia. Well designed studies still lack to demonstrate the efficacy of this therapeutic approach. However, unless large multicentric reports do not confirm efficiency of this therapeutic approach, partial biliary diversion should be proposed prior to transplantation, in view of its reversibility . Patients with partial biliary diversion should take additional bicarbonate orally, in view of the possible marked loss of bicarbonate in the bile.


In our experience, neither ursodeoxycholic acid treatment nor partial biliary diversion were really efficient in children who had no bile acid detected in bile, despite abundant bile flow. Deficiency of bile salt transport may be indicative of PFIC1 (18), and bile salt dosage in gallbladder bile might indicate which children may or not respond to biliary diversion. Continuous improvements in the classification and genetic identification of the various types of PFIC may in the future help the clinician to identify candidates to biliary diversion. Finally, ursodeoxycholic acid has been shown efficient to improve clinical and biochemical parameter in liver disease associated to cystic fibrosis (19), and preliminary data suggest that this improvement is accompanied by a slower rate of progression to cirrhosis. Ursodeoxycholic acid is widely used in various conditions associated to mild or moderate cholestasis, including liver transplant recipients.


Rifampicin at the dose of 4 to 10 mg/kg/day is probably the most efficient anti-pruritus drug, and has the advantage over phenobarbital to not interfer with intellectual capacity and development (20).


Cholestyramine may help by its intraluminal bile salts chelating effect , but it also interfers with fat absorption.


When pruritus is so severe that it interfers with social life, development and causes a miserable life, transplantation should be proposed for the purpose of relieving pruritus, even if there is no associated life threatening problem. Pruritus and cholestasis without liver insufficiency and without portal hypertension is regularly the reason for transplantation in Alagille and PFIC patients.



This rare complication can be observed in any chronic liver disease in children, and is characterized by progressive hypoxia leading to deep cyanosis due to intra-pulmonary shunting. Attention should be paid to early signs of hypoxia when following a child with chronic liver disease and/or portal hypertension. There is no medical treatment, and this should be considered as an absolute indication of liver transplantation. Nitric oxide may have a temporary beneficial effect to improve oxemia in the early phase after liver transplantation, by increasing perfusion of ventilated lung units (30-32).



Encephalopathy is a late complication in chronic pediatric liver disease, but this observation should take into account the difficulty to detect encephalopathy at its early stage, in children more than in adults. There is no elaborated clinical testing to evaluate mild encephalopathy in infants, and clinicians mainly rely on consciousness and electro-encephalographic findings. Ammonium levels are not directly related to encephalopathy, and protein restriction should not be based on this biochemical parameter only in absence of encephalopathy. Encephalopathy is precipitated by intercurrent complications such as gastrointestinal bleeding, sepsis, meconial ileus (cystic fibrosis patients). Its treatment includes protein restriction, bowel decontamination and lactulose.

It should be reminded that any drug with CNS effect, including  central anti emetics,  are contra indicated: patients with liver insufficiency often experience  worsening encephalopathy  due to iatrogenic causes.




Complications des maladies hépatiques chroniques de l'enfant