Progression of liver disease and portal hypertension in dyskeratosis congenita and related telomere biology disorders

Abstract

Background and Aims: Dyskeratosis congenita (DC) and related telomere biology disorders (TBD) are characterized by very short telomeres and multisystem organ involvement including liver disease. Our study aimed to characterize baseline hepatic abnormalities in patients with DC/TBD and determine risk factors associated with liver disease progression. Approach and Results: A retrospective review was performed on a cohort of 58 patients (39 males) with DC/TBD who were prospectively evaluated at a single institute from 2002 to 2019. The median age at initial assessment was 18 (1.4–67.6) years, and median follow-up duration was 6 (1.4–8.2) years. Patients with autosomal or X-linked recessive inheritance and those with heterozygous TINF2 DC were significantly younger, predominantly male, and more likely to have DC-associated mucocutaneous triad features and severe bone marrow failure compared with autosomal dominant-non-TINF2 DC/TBD patients. Liver abnormality (defined at baseline assessment by laboratory and/or radiological findings) was present in 72.4% of patients with predominantly cholestatic pattern of liver enzyme elevation. Clinically significant liver disease and portal hypertension developed in 17.2% of patients during the 6-year follow-up; this progression was mainly seen in patients with recessive or TINF2-associated DC. Significant risk factors associated with progression included the presence of pulmonary or vascular disease. Conclusions: Our experience shows a high prevalence of cholestatic pattern of liver abnormality with progression to portal hypertension in patients with DC/TBD. Presence of pulmonary and/or vascular disease in patients with recessive or TINF2 DC was an important predictor of liver disease progression, suggesting the need for increased vigilance and monitoring for complications in these patients.

Liver disease and transplantation in telomere biology disorders: An international multicenter cohort

“…Our cohort demonstrates a similar broad spectrum of liver involvement in earlier studies. 5 , 6 , 17 – 19 Elevated liver enzymes are a common manifestation seen in the majority of patients. There was a relatively high prevalence of cirrhosis in our cohort (34%).…”

“…Liver disease in telomere biology disorders is common but poorly characterized. 5 , 6 , 17 A National Institutes of Health study found hepatic involvement in 40% of adult patients with TBD. 18 In the study, which included adults aged 29–50 years, the most common laboratory findings were liver enzyme elevations and cholestasis, and the most common imaging findings were increased hepatic echogenicity and hepatomegaly.…”

“…Liver disease in telomere biology disorders is common but poorly characterized 5,6,17 . A National Institutes of Health study found hepatic involvement in 40% of adult patients with TBD 18 .…”