Liver transplantation in pediatrics: Indications, contraindications, and pretransplant management

Biliary atresia (BA) is a cholestatic liver disease of children that progresses to hepatic fibrosis. BA is the main indication of pediatric liver transplantation (LTx). Histopathological markers in liver biopsies could be useful for predicting progression to end-stage disease.

To establish histopathological or immunohistochemical markers in liver biopsies of BA patients and correlate those markers with prognosis.

Histological analysis of biliary alterations and morphometric assessment of liver fibrosis were performed, in addition to indirect immunofluorescence assays (IF) for type I, III, IV and V collagens in initial and final liver biopsies of 36 patients with BA who underwent Kasai hepatoportoenterostomy (KPE) and LTx in the last 20 years at a single center.

Histopathological markers had no correlation with evolutive time until LTx. The perisinusoidal deposition of type III and V collagens was more prominent in the initial biopsies (p < 0.01), whereas deposition of type I and IV collagens indicated progression (p < 0.01). Patients with large amounts of perisinusoidal type I collagen in the initial biopsies had worse progression time curves until LTx (p = 0.04).

Morphometric assessment of perisinusoidal deposition of type I collagen by IF in the initial biopsy can correlate with progression time to LTx in post-surgical BA.

Liver transplantation is regarded as an effective treatment for Wilson’s disease (WD), and recently has been shown to improve not only hepatic but also neurologic manifestations. Conventional auxiliary liver transplantation for WD is orthotopic liver transplantation and heterotopic liver transplantation. But the conventional procedure could not avoid the problem of space, functional competition, hemodynamic variation. Here we report a case of heterotopic auxiliary living-donor liver transplantation (HALDLT) to treat WD. We modified the operation to have a splenectomy, implant graft into the splenic fossa. The patient recovered well after the transplantation and has been symptom-free during a 5-year follow-up. This modified operation is more safe and simple. HALDLT might be an effective treatment for WD patients with splenomegaly.

Progressive familial intrahepatic cholestasis (PFIC) is a family of rare childhood diseases that was universally fatal until the development of liver transplant. In the last 20 years, the use of nontransplant surgery to treat PFIC has become the standard of care. There are various surgical techniques that have been performed. There are no reviews evaluating the outcome of these operations.

A systematic search of the literature for articles evaluating the outcome of nontransplant surgical interventions in PFIC patients was performed. Data from these studies was abstracted and summarized.

No trials have been performed addressing nontransplant surgical interventions in PFIC patients. We analyzed 11 case series and case reports. Generally, patients had successful outcomes (81%) with cessation of progression of disease and resolution of symptoms. Treatment failures were often associated with more advanced disease.

There is no evidence to demonstrate a superiority of one type of nontransplant surgical intervention in PFIC patients. We propose the development of a registry and standardization of outcomes measurements to allow improved comparison of results.

Hereditary tyrosinemia type I (HTI), also referred to as hepatorenal tyrosinemia, is the most severe metabolic disorder of the tyrosine degradation pathway. HTI is caused by a deficiency in fumarylacetoacetate hydrolase (FAH), the last enzyme of the pathway, which catalyzes the conversion of fumarylacetoacetate (FAA) in fumarate and acetoacetate. HTI presents into two main clinical types, acute and chronic. The acute form, with early onset at birth or soon after, is mainly characterized by severe liver failure associated with cirrhosis, hepato- and splenomegaly, abnormal blood coagulation and hypoglycemia leading to death in the first months of life. Renal tubular dysfunctions such as Fanconi syndrome and rickets have also been considered signs of HTI. In the chronic form, onset is insidious and progress is less aggressive. However, renal manifestations, mainly proximal tubulopathy, are prominent. Patients show impaired renal tubular reabsorptive function leading to Fanconi syndrome characterized by renal tubular acidosis, generalized aminoaciduria, hypophosphatemic vitamin D-resistant rickets and growth retardation. In vivo reversion of inherited somatic mutations has been reported in a number of inherited diseases, such as adenosine deaminase deficient severe combined immuno deficiency, Wiskott-Aldrich and Bloom syndromes, epidermolysis bullosa, Fanconi anemia, and HTI. It is in HTI, however, that reversion has been shown to occur most frequently. A mosaic pattern of FAH expression was observed in hepatic regenerative nodules of ›85% of studied patients. DNA analysis performed on FAH immunopositive liver nodules showed correction of the HTI-causing mutation in one allele. The treatment currently used in HTI patients is administration of the drug (2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3 cyclohexanedione) (NTBC) combined with a low-protein diet.