Predictors of liver cirrhosis and hepatocellular carcinoma among perioperative survivors of the Fontan operation

Abstract

ObjectiveFontan-associated liver disease (FALD) is widely recognised as a common complication in patients long after the Fontan operation. However, data on the predictors of FALD that can guide its screening and management are lacking. The present study aimed to identify the predictors of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) in post-Fontan patients.MethodsThis was a multi-institutional retrospective cohort study. Clinical data of all perioperative survivors of Fontan operation before 2011 who underwent postoperative catheterisation were collected through a retrospective chart review.ResultsA total of 1117 patients (538 women, 48.2%) underwent their first Fontan operation at a median age of 3.4 years. Postoperative cardiac catheterisation was conducted at a median of 1.0 year. During a median follow-up period of 10.3 years, 67 patients (6.0%) died; 181 (16.2%) were diagnosed with liver fibrosis, 67 (6.0%) with LC, 54 (4.8%) with focal nodular hyperplasia and 7 (0.6%) with HCC. On multivariable analysis, high central venous pressure (CVP) (HR, 1.28 (95% CI 1.01 to 1.63) per 3 mm Hg; p=0.042) and severe atrioventricular valve regurgitation (HR, 6.02 (95% CI 1.53 to 23.77); p=0.010) at the postoperative catheterisation were identified as independent predictors of LC/HCC.ConclusionsPatients with high CVP and/or severe atrioventricular valve regurgitation approximately 1 year after the Fontan operation are at increased risk of developing advanced liver disease in the long term. Whether therapeutic interventions to reduce CVP and atrioventricular valve regurgitation decrease the incidence of advanced liver disease requires further elucidation.

Congestive Hepatopathy: A Case of Fontan-Associated Liver Disease and Review of Literature

“…Although some degree of liver dysfunction seems to be inevitable in this patient population, risk factors for rapid progression include other etiologies of liver pathology such as alcohol use and nonalcoholic fatty liver disease 14 . High central venous pressure and severe atrioventricular valve regurgitation have also been associated with increased risk of cirrhosis and hepatocellular neoplasm in this patient population 20 . Advanced fibrosis is a relative contraindication to heart transplant, but combined heart-liver transplant has been successful 21–23 …”

“…14 High central venous pressure and severe atrioventricular valve regurgitation have also been associated with increased risk of cirrhosis and hepatocellular neoplasm in this patient population. 20 Advanced fibrosis is a relative contraindication to heart transplant, but combined heart-liver transplant has been successful. [21][22][23] FIGURE 3.…”

Update on combined heart and liver transplantation: evolving patient selection, improving outcomes, and outstanding questions

“…Initially described by Elder et al [18] in 2013, a VAST score at least 2 was associated with multifold increased risk for major adverse event in Fontan patients including need for heart transplant, development of hepatocellular carcinoma (HCC), or death [18]. Finally, a strong correlation exists between elevated central venous pressures indicative of Fontan failure and clinically significant FALD [19 ▪▪ ].…”

Heartbeat: not all patients with primary mitral regurgitation are the same

“…However, these patients are at risk of progressive liver disease. In a multicenter retrospective study of 1117 patients with a Fontan procedure (mean age at surgery 3.4 years) followed from 7 to 16 years, mortality was 6% and a diagnosis of liver disease was common—16% developed fibrosis, 6% cirrhosis, 5% focal nodular hyperplasia and 0.6% hepatocellular carcinoma 5. Although the time interval between surgery and the diagnosis of liver disease averaged 14 years, findings at cardiac catheterisation performed 1 year after surgery predicted subsequent liver disease, specifically a high central venous pressure (HR, 1.28 (95% CI 1.01 to 1.63) per 3 mm Hg; p=0.042) and severe atrioventricular valve regurgitation (HR, 6.02 (95% CI 1.53 to 23.77); p=0.010).…”