Medical Management of Chronic Liver Diseases in Children (Part I)

Abstract

The management of children with chronic liver disease (CLD) mandates a multidisciplinary approach. CLDs can be classified into 'potentially' curable, treatable non-curable, and end-stage diseases. Goals pertaining to the management of CLDs can be divided into prevention or minimization of progressive liver damage in curable CLD by treating the primary cause; prevention or control of complications in treatable CLD; and prediction of the outcome in end-stage CLD in order to deliver definitive therapy by surgical procedures, including liver transplantation. Curative, specific therapies aimed at the primary causes of CLDs are, if possible, best considered by a pediatric hepatologist. Medical management of CLDs in children will be reviewed in two parts, with part I (this article) specifically focusing on 'potentially' curable CLDs. Dietary modification is the cornerstone of management for galactosemia, hereditary fructose intolerance, and certain glycogen storage diseases, as well as non-alcoholic steatohepatitis. It is also essential in tyrosinemia, in addition to nitisinone [2-(nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione] therapy, as well as in Wilson disease along with copper-chelating agents such as D-penicillamine, triethylenetetramine dihydrochloride, and ammonium tetrathiomolybdate. Zinc and antioxidants are adjuvant drugs in Wilson disease. New advances in chronic viral hepatitis have been made with the advent of oral antivirals. In children, currently available drugs for the treatment of chronic hepatitis B virus infection are standard interferon (IFN)-α-2, pegylated IFN-α-2 (PG-IFN), and lamivudine. In adults, adefovir and entecavir have also been licensed, whereas telbivudine, emtricitabine, tenofovir disoproxil fumarate, clevudine, and thymosin α-1 are currently undergoing clinical testing. For chronic hepatitis C virus infection, the most accepted treatment is PG-IFN plus ribavirin. Corticosteroids, with or without azathioprine, remain the basic strategy for inducing remission in autoimmune hepatitis. Ciclosporin (cyclosporine) and other immune suppressants may be used for patients who do not achieve remission, or who have significant side effects, with corticosteroid/azathioprine therapy. The above therapies can prevent, or at least minimize, progression of liver damage, particularly if started early, leading to an almost normal quality of life in affected children.

Feasibility study for assessing liver fibrosis in paediatric and adolescent patients using real‐time shear wave elastography

“…Early diagnosis, follow‐up and progression of fibrosis in the liver are of great clinical importance. Historically, the tools used to assess the degree of hepatic fibrosis included clinical examination, blood tests, sonography and histology . Biopsy is considered the gold standard but has several limitations and risks; it yields a semi‐quantitative assessment that is subject to sampling error and interobserver variability and is an invasive technique often requiring general anaesthesia or sedation in children.…”

Acoustic radiation force impulse (ARFI) elastography for the noninvasive diagnosis of liver fibrosis in children

“…Children with chronic liver disease need regular monitoring of the progression of their liver disease [2]. Historically, the tools used have been clinical examination, blood tests, liver US and, in some cases, liver biopsy [3,4]. Biopsy is considered the gold standard, but comes with limitations and risks.…”

Current management options for tyrosinemia

“…18 In this condition, a moderate elevation of serum tyrosine is associated with severe involvement of the liver, kidneys, and central nervous system. 19 These findings are thought to arise from the accumulation of toxic metabolites of tyrosine, such as maleylacetoacetate, fumarylacetoacetate, succinyl-acetoacetate, and succinylacetone, which are highly reactive electrophilic toxic compounds and which bind to sulfhydryl groups, often leading to tissue injury.…”

“…It has improved the survival and quality of life of patients. 18,[73][74][75][76][77][78] The recommended starting dose of NTBC is 1 mg/kg/day, divided into two daily doses (Orfadin European Public Assessment Report [EPAR] product information, Orfadin package insert). 19,79 Recently, it has been reported that doses lower than 1 mg/kg/day have also been effective in the treatment of HTT-I.…”