S2693 Outcome of Hepatitis C Virus-Positive Liver Transplantation for Telomere-Mediated HPS-Noncirrhotic Portal Hypertension After Bone Marrow Transplantation: A Case Report

Abstract

INTRODUCTION: Short telomere syndromes are disorders caused by germline mutations in genes regulating telomere maintenance. Their phenotypes and severity vary and depend on the extent of telomere shortening. Dyskeratosis congenita (DC) is a prototypic short telomere syndrome, characterized by bone marrow failure, liver disease (noncirrhotic portal hypertension, cryptogenic cirrhosis), pulmonary fibrosis and an increased risk of malignancy. With contemporary hematopoietic stem cell transplantation (HSCT) regimens, non-cirrhotic portal hypertension with hepatopulmonary syndrome (HPS) is the most common morbidity. We describe successful HCV-positive liver transplantation (LT) for telomere-mediated noncirrhotic portal hypertension with HPS after HSCT. CASE DESCRIPTION/METHODS: A 27-year-old female with DC complicated by noncirrhotic portal hypertension and HPS underwent LT at age 25, from a 23-year-old, HCV-positive, female donor. The recipient was diagnosed with bone marrow failure and DC at age 17. At that time, telomere length was below the 1st age-adjusted percentile, but she had no identifiable mutation. She underwent a non-myeloablative HSCT at age 19. Three years later, she presented with progressive dyspnea and was found to have stigmata of portal hypertension and intrapulmonary shunt. A trans-jugular liver biopsy confirmed the absence of significant fibrosis with a hepatic venous pressure gradient of 10 mmHg. Her dyspnea continued to progress with minimal evidence of parenchymal pulmonary fibrosis but worsening HPS. She was on 10 L oxygen prior to LT with room air PO2 55 mmHg, qualifying for UNOS upgrade to MELD 29. Liver explant pathology revealed focal parenchymal nodularity and absence of significant fibrosis. She had a prolonged recovery due to respiratory failure and malnutrition, which she recovered from and completely weaned off oxygen four months post-LT. She was successfully treated for HCV post-LT. She had recurrent low-level CMV viremia and presumed mild graft rejection episode. Sixteen months post-LT, she continues to be on room air with stable lung and liver graft function. DISCUSSION: The natural history of short telomere syndromes is marked by progressive noncirrhotic portal hypertension with HPS, a frequent long-term complication after HSCT. We report a successful LT and reversal of hypoxemia after an HCV-positive LT in a patient with DC. Sequential transplant may be feasible option for post-HSCT patients who develop end-stage liver disease.