Risk factors and serological markers of liver cirrhosis after Fontan procedure

Abstract

Liver cirrhosis (LC), which may result in hepatic failure or cancer, has been reported in patients after Fontan procedure. The purpose of this study was to clarify the frequency and histological characteristics of LC, and to evaluate the risk factors and serological markers of LC with Fontan circulation. Retrospective review of contrast-enhanced CT scans (CT) of the liver was carried out in 57 patients after Fontan procedure. Patients were divided into two groups: LC group (n = 31) and no LC group (n = 26). Age at Fontan procedure, duration after Fontan procedure, catheterization data, and history of failing Fontan circulation were compared between groups. Serological data including γ-GTP and hyaluronic acid were compared. Histology of autopsy specimens was assessed when available. Duration after Fontan procedure was significantly longer in LC group than no LC group. History of failing Fontan circulation was more frequent in LC group than in no LC group. There was no correlation between type of procedure (APC/Bjork/lateral tunnel/TCPC) and LC in this series. Serum hyaluronic acid, γ-GTP, and Forns index were significantly higher in LC group. Significant risk factors for LC were duration after Fontan procedure (>20 years). In autopsy specimens, histopathological changes of LC were observed predominantly in the central venous area. LC diagnosed with CT is frequent in patients long after Fontan procedure, especially after 20 years. Hyaluronic acid and γ-GTP could be useful markers to monitor the progression of liver fibrosis in Fontan patients.

Identification of liver fibrosis using the hepatic vein waveform in patients with Fontan circulation

“…Strikingly, Fontan patients showed HV waveform patterns similar to those commonly seen in CLD patients; therefore, the HV waveform changes were assumed to reflect the progression of liver fibrosis in Fontan patients. In fact, the phased changes in HV waveforms correlated with increases in hyaluronic acid and GGT levels and a decrease in platelet count, which associate with liver fibrosis progression in Fontan patients . Furthermore, the HV waveform change was most strongly associated with advanced liver fibrosis as defined by US and clinical features.…”

Liver Cirrhosis and/or Hepatocellular Carcinoma Occurring Late After the Fontan Procedure ― A Nationwide Survey in Japan ―

“…15 A long duration after the Fontan procedure (>20 years) is one of the risk factors for LC, and hyaluronic acid and γ -guanosine triphosphate ( γ -GTP) have been reported to be useful markers to evaluate the progression of liver fibrosis in patients undergoing the Fontan procedure. 16 The aim of the present study was to clarify the prevalence of LC and/or HCC after the Fontan procedure and to elucidate T he Fontan procedure is currently accepted as the final palliative surgery in patients with single ventricle physiology. However, the lack of a subpulmonary ventricle alters static resistance and dynamic impedance, resulting in a profound effect on the hepatic circulation.…”

A composite noninvasive index correlates with liver fibrosis scores in post-Fontan patients: Preliminary findings

“…Regardless the challenge of clinically following FALD's progression from no liver fibrosis to cirrhosis, a serial, reproducible, noninvasive, clinic‐based method would be preferable to techniques derived from invasive testing or computed tomography/magnetic resonance imaging procedures . Further, it is stable Fontan patients that would most be benefited by a reliable noninvasive tracking method for predicting the degree of hepatic fibrosis, as stable patients do not routinely undergo frequent invasive assessments.…”

“…In patients with infectious hepatitis, nonalcoholic fatty liver disease, and alcoholic liver disease, composite models comprised of laboratory values, patient characteristics, and hepatic elastography either by magnetic resonance or ultrasound, have been developed primarily to predict the presence of cirrhosis . However, to the best of our knowledge, there are only two post‐Fontan reports, with 10 patients each, that have compared liver biopsy findings with either magnetic resonance or ultrasound hepatic elastography . Nevertheless, in FALD patients, liver stiffness may not be directly related to fibrosis, as liver stiffness increases even with Glenn shunting, before Fontan completion .…”

“…Previous, large patient cohort studies report correlations between liver pathology and noninvasive methods, including composite models comprised of multiple patient variables, in those with infectious hepatitis, nonalcoholic fatty liver disease, and alcoholic liver disease . However, there are few reports comparing liver biopsy findings with noninvasive approaches in patients with Fontan associated liver disease (FALD); thus, there are no current, useful, clinic‐based, noninvasive methods that strongly correlate one with the other . This study reports our experience comparing post‐Fontan hepatic biopsy findings with a composite, noninvasive index derived from liver‐ultrasound, shear‐wave elastography (SWE) measurements, model for end‐stage liver disease excluding INR (MELD‐XI) scores, and time post‐Fontan.…”