IM - ORIGINAL Liver involvement in hereditary hemorrhagic telangiectasia: can breath test unmask impaired hepatic first-pass effect? Marcello Candelli • Maurizio Pompili • Patrizia Suppressa • Gennaro M. Lenato • Giulia Bosco • Gian Ludovico Rapaccini • Antonio Gasbarrini • Arnaldo Scardapane • Carlo Sabba ` Received: 29 June 2010 / Accepted: 22 January 2011 / Published online: 9 February 2011 Ó SIMI 2011 Abstract Hepatic arteriovenous malformations (HAVMs) in hereditary hemorrhagic telangiectasia (HHT) have long been considered to have scarce clinical significance in most cases. Nevertheless, data are lacking regarding the influence of HAVMs on the liver first-pass effect on drugs in HHT patients. To gain insight into the effect of HAVMs on hepatic drug clearance by means of two specific 13 C-labeled probes, namely the 13 C-methacetin and 13 C-aminopyrine, 46 HHT patients and 44-matched healthy controls were enrolled. The liver first-pass effect was studied by the 13 C-based breath test using methacetin and aminopyrine. The methacetin breath test showed statistically significant reduced metabolism rates (p \ 0.0001) in HHT when compared with controls, both in patients with and without CT-detectable HAVMs, and when expressed both as cumulative 13 C-percentage dose per hour and as 13 C-per- centage peak after 15 min. In contrast, no significant dif- ference was found between HHT and controls regarding aminopyrin metabolism rates. In HHT, 13 C%-methacetin breath test values are significantly lower than those found in normal subjects, probably due to the effect of hepatic shunts. A reduced perfusion and an impaired hepatic metabolism might affect hepatic drug clearance in HHT. Therefore, an appropriate dosage adjustments should be considered when high-hepatic-metabolism drugs are administered to HHT patients. Keywords Methacetin breath test Á Hepatic arteriovenous malformations Á Hereditary hemorrhagic telangiectasia Á First-pass effect Abbreviations HHT Hereditary hemorrhagic telangiectasia HAVMs Hepatic arteriovenous malformations 13 C-%P15 Percentage 13 CO 2 peak value after 15 min 13 C-%CPH Percentage 13 CO 2 cumulative dose per hour data Introduction Hereditary hemorrhagic telangiectasia (HHT) is a genetic autosomal dominant disorder with an estimated prevalence of 1:5–8/10,000 individuals [1, 2]. The disease HHT is characterized by a vascular dysplasia involving arteriove- nous malformations that consist in direct connections between a feeding arteriole and a draining dilatated venule, without the interposed capillary bed [3]. Although the pathogenesis of the disease is not clearly understood, mutations in at least two different genes (ENG and ALK1) are responsible for the HHT1 and HHT2 phenotype, respectively, and account for 80–93% of cases [4, 5]. M. Candelli Department of Emergency Medicine, Catholic University of Sacred Heart, Rome, Italy M. Pompili Á G. Bosco Á G. L. Rapaccini Á A. Gasbarrini Department of Internal Medicine, Catholic University of Sacred Heart, Rome, Italy P. Suppressa Á G. M. Lenato Á C. Sabba `(&) Geriatric Unit and Rare Disease Center, Department of Internal Medicine and Public Health, University of Bari ‘‘A. Moro’’, Policlinico, P.zza Giulio Cesare, 11, 70124 Bari, Italy e-mail: c.sabba@dimimp.uniba.it A. Scardapane Department of Radiological Diagnostics, University of Bari ‘‘A. Moro’’, Bari, Italy 123 Intern Emerg Med (2012) 7:323–329 DOI 10.1007/s11739-011-0531-9