Synchronous cryptogenic liver cirrhosis and idiopathic pulmonary fibrosis: a clue to telomeres involvement on line pubblication 03-Oct-2012Hepatology-

Background: Cryptogenic liver cirrhosis (CC) and Idiopathic pulmonary fibrosis (IPF) are chronic, progressive diseases with poor prognosis that share inflammation and fibrosis of target organs as common pathogenetic mechanisms. Both are included in the spectrum of syndrome of telomeres shortening. We describe a case of synchronous diagnosis of IPF and CC associated with a novel mutation in telomerase reverse transcriptase (hTERT). Subjects and Design: The proband was a 48-year-old active smoker, formerly obese, woman with type-2 diabetes mellitus. IPF and CC had a rapid and negative course. Her large family had an excess of type-2 diabetes and chronic liver disease and a high prevalence of different cancers, premature menopause and osteoporosis. In this family, we suggested an implication of telomeres shortening. Results: Sequencing and mutation analysis of hTERT and hTR demonstrated the presence of a novel hTERT mutation (L153M) and of a hTERT polymorphism (A305A). The patient was a carrier of both mutation and polymorphism, which were observed also in other family members. The relevance of L153M variant was confirmed by protein sequence alignment and by the prediction program PolyPhen. Furthermore, leukocyte telomeres length was significantly shorter in family members compared to age-matched healthy controls (0.94 ± 0.45 vs 1.37 ± 0.63; p=0.007). Conclusions: this is the first description of the coexistence of CC and IPF associated with a novel telomerase mutation not in the setting of dyskeratosis congenita. This case report gives further evidence of telomeres involvement in liver disease progression and suggests a possible link between NASH and CC through telomeres shortening.