Liver Transplantation Trends and Outcomes for Hereditary Hemorrhagic Telangiectasia in the United States

Abstract

Background. Liver arteriovenous malformations (AVM) in hereditary hemorrhagic telangiectasia (HHT) can necessitate liver transplantation. There is limited data on HHT patients undergoing liver transplantation (LT) in the United States. Methods. Two sources of data were used: (1) Scientific Registry of Transplant Recipients (SRTR) database (1998-2016) (2) Single center liver transplant database (Mayo Clinic Rochester, MN). The aims of this study were (1) to determine trends in LT for HHT-related liver involvement in the United States using the SRTR database; (2) to identify clinical characteristics, indications, and outcomes for LT in HHT. Results. Thirty-nine HHT patients were listed for LT in the SRTR database from 1998-2016 to 1998-2001 (n = 1); 2002-2005 (n = 4); 2006-2010 (n = 10), and 2011-2016 (n = 24). Twenty-four underwent LT at a median age of 47.5 years (interquartile range, 37.0-58.5 years). Median calculated MELD score at time of LT was 8.0 (interquartile range, 7.0-9.5), and 75% received an exception MELD score. Two status-1 patients died during transplant surgery. Nineteen (86%) patients were alive after a median post-LT follow-up of 48 months, whereas 2 patients were lost to follow-up. Five of the aforementioned HHT patients underwent LT at Mayo Clinic, 4 with high output cardiac failure, and 1 with biliary ischemia. All 5 were alive at the time of last follow-up with good graft function and resolution of heart failure. Conclusions. Outcomes after LT for HHT patients are excellent with 86% survival after a median follow-up of 48 months and resolution of heart failure. LT listing for HHT has increased in substantially in more recent eras.

Gender differences in hereditary hemorrhagic telangiectasia severity

“…Moreover, 14 (60.8%) out of 23 of patients with high-output heart failure and all cases (n = 12) of isolated symptomatic biliar disease from the European Liver Transplant Registry were females, similar to our observation [24]. In fact, decompensated high output cardiac failure and biliary complications are the most frequent causes of liver transplantation [24,[32][33][34]. Similar to previous studies, among patients with genotype data available from our cohort, those at high risk of harboring clinically significant liver disease had ACVRL1 mutation [6,19].…”

“…In fact, the Simple Clinical Scoring Index included female gender as a risk factor for developing clinically significant hepatic involvement [19]. This female predominance in prevalence and severity of liver involvement is in agreement with the four published series of HHT patients with liver transplantation, where between 83.3 and 92.8% of the patients were women [24,[32][33][34]. Moreover, 14 (60.8%) out of 23 of patients with high-output heart failure and all cases (n = 12) of isolated symptomatic biliar disease from the European Liver Transplant Registry were females, similar to our observation [24].…”

Hepatic Arteriovenous Malformation: The Search for a PTEN Mutation!

“…LT offers successful therapy for HHT with liver involvement: 10-year patient survival rate reaches 86%. (2) PTEN loss of function leads to AVM by two mechanisms: one directly attributable to a PTEN mutation and another that involves genes that modulate PTEN activity. Several studies have shown that PTEN negatively regulates the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway by reversing the action of PI3K.…”

Pulmonary Abnormalities in Liver Disease: Relevance to Transplantation and Outcome

“…Improvement in cardiac function and normalization of hemodynamics have been demonstrated in patients with HHT transplanted for HOHF ( 15‐17 ) (Table 2).…”