The clinical spectrum of Fontan-associated liver disease: results from a prospective multimodality screening cohort

Abstract

Liver fibrosis and cirrhosis are a consequence of a Fontan physiology, and determine prognosis. It is unclear whether non-invasive assessment of liver pathology is helpful to provide clinically relevant information. The aims of this study were to assess the spectrum of Fontan-associated liver disease (FALD) and usefulness of non-invasive methods to assess biopsy confirmed liver fibrosis. MethodsHepatic screening of consecutive patients consisted of a blood panel, ultrasonography, elastography, contrast-enhanced MRI/CT, and liver biopsy (scored with Fontan specific fibrosis scores and collagen proportionate area; CPA). Fibrosis parameters, varices, ascites, and splenomegaly were measured on imaging. Results38/49 referred patients (27 ± 6.6 years, 73.7% male) underwent the complete screening protocol.Liver fibrosis on biopsy was present in all patients, and classified as severe (stage 3-4) in 68%. Median CPA was 22.5% (16.9-29.5) and correlated with individual fibrosis scores. ELF® and liver stiffness were elevated, but MELD-XI scores were low in all patients. Fibrosis severity neither correlated to ELF® and liver stiffness, nor to (semi-) quantitative fibrosis parameters on MRI/CT. Varices were present in 50% and hyper-enhancing nodules in 25% of patients, both independent of fibrosis stage, but varices were associated with higher CPA values. ConclusionThe FALD spectrum includes both hepatic congestion and severe fibrosis, with signs of portal hypertension and hyper-enhancing nodules as significant manifestations. Routine imaging, transient elastography and serum biomarkers are unable to accurately assess severity of liver fibrosis in this cohort. Future research should focus on validating new diagnostic tools with biopsy as the reference standard.

Hepatic magnetic resonance T1-mapping and extracellular volume fraction compared to shear-wave elastography in pediatric Fontan-associated liver disease

“…Our young study population had normal splenic MR relaxometry values, which argued against a general inflammatory state and could be interpreted as the absence of splenic congestion/fibrosis. In turn, this finding also indicated normal portal venous pressure, which suggested a less-advanced liver fibrosis stage that might be reversible [4,34,35].…”

Avaliação da frequência de nódulos hepáticos em pacientes submetidos ao procedimento de Fontan: o papel da ultrassonografia, tomografia computadorizada e ressonância magnética

“…O perfil populacional de pacientes incluídos no nosso estudo foi semelhante à maioria dos estudos publicados na literatura, dentre os quais a principal cardiopatia congênita relacionada ao PF foi atresia tricúspide e a principal cirurgia realizada foi ACPT com túnel extracardíaco (33,55,56) . O intervalo de tempo entre a realização do PF e a avaliação hepática variou bastante nos estudos disponíveis, entre 5 e 42 anos, com uma média estimada de 19 anos (23-25, 27, 29, 30, 32, 33, 42, 44, 55-79) .…”

“…Poterucha et al demonstraram que os níveis de GGT se correlacionaram com o grau de fibrose (62) . Porém, Munsterman et al não demonstraram diferença significativa entre pacientes com fibrose leve e acentuada (56) . No nosso estudo, apesar de grande parte dos pacientes apresentar aumento dos níveis de GGT, não observamos correlação estatisticamente significativa entre os níveis de GGT com a presença de nódulos ou com a rigidez hepática.…”

“…Já dentre os métodos seccionais com resultados discordantes, a frequência de NH variou entre 0,2% e 26% (24,29,30,55,56,62,66,68,82,83) . A menor frequência de 0,2% foi obtida no estudo de Kuwabara et al (55) Kiesewetter et al (24) e Serai et al (82) também obtiveram frequências menores de NH, 18,2% e 25%, porém o número de pacientes incluídos foi pequeno, o que pode justificar essa diferença de frequência.…”

“…Poterucha et al (62) incluíram 50 pacientes na análise retrospectiva e 26% dos pacientes apresentavam NH na RM. Já Munsterman et al (56) (27,30,42,61,62,84) .…”