Grand Rounds: Hepatic Manifestations of Telomere Biology Disorders.
J Hepatol. 2018 May 11;:
Authors: Patnaik MM, Kamath PS, Simonetto DA
Clinical Case A 51 year old Caucasian male was referred for evaluation of variceal bleeding. Laboratory tests were remarkable for mild thrombocytopenia and moderate alkaline phosphatase elevation. Synthetic liver function was well preserved. Abdominal computed tomography scan revealed moderate splenomegaly, gastric varices, and normal hepatic contour. A transjugular liver biopsy was performed revealing findings of nodular regenerative hyperplasia (NRH) with no significant fibrosis or necroinflammatory activity. Hepatic venous pressure gradient was elevated at 31 mmHg, consistent with clinically-significant portal hypertension. The clinical course was complicated by refractory gastric variceal bleeding requiring a surgical porto-systemic shunt. Approximately 7 years after the initial presentation, the patient developed progressive dyspnea and a diagnosis of idiopathic pulmonary fibrosis (IPF) was made. Contrast-enhanced echocardiogram was not suggestive of hepatopulmonary syndrome or portopulmonary hypertension. Given this new diagnosis a telomere biology disorder (TBD) was suspected. A flow-FISH (fluorescent in situ hybridization) analysis for telomere length assessment revealed telomere lengths below the first percentile in both lymphocytes and granulocytes. Next generation sequencing analysis identified a heterozygous mutation involving the hTERT gene (Histidine983Threonine). The lung disease unfortunately progressed in the subsequent two years, leading to his demise 9 years after his initial presentation with portal hypertension. During those 9 years two brothers also developed IPF.
PMID: 29758336 [PubMed – as supplied by publisher]