**3. Results**

#### *3.1. Clinical Characteristics*

During the study period, 240 patients met the inclusion criteria. Most patients (57.1%) were female, and mean age was 53.6 ± 13.6 years. Clinical diagnosis of HHT was definitive according to the Curaçao criteria (meeting ≥ 3 criteria) in 229 (95.4%) patients and by a positive molecular test in the remaining 11 (4.6%) patients. A genetic test was carried out in 161 patients: 75 (45.2%) had *ENG* mutation, and 73 (43.9%) had *ACVRL1* mutation, with no mutation found in 13 (7.8%). After screening tests, 176 patients (73.3%) had visceral involvement: 67 (27.9%) with pulmonary AV fistula, 110 (45.8%) with hepatic VMs, 73 (30.4%) with other intraabdominal VM, and 10 (4.2%) with central nervous system involvement.

In 67 (27.9%) patients, GI disease was confirmed with the positive endoscopic study, while 28 (11.7%) patients had suggestive symptoms but a negative endoscopic study, and GI disease was unsuspected in the remaining 145 (60.4%) patients.

#### *3.2. Risk Factors for GI Involvement*

Patients with GI involvement were more likely to use tobacco and to have *ENG* mutation, lower hemoglobin values at diagnosis, lower minimal hemoglobin levels during follow-up, lower ferritin levels (<15 ug/L), and higher systolic pulmonary artery pressure (sPAP) at TTE than those with no GI involvement. Compared to patients with unsuspected GI involvement, those with GI involvement were older and were more likely to use tobacco or alcohol and to have more comorbidities, higher ESS, lower ferritin (<15 ug/L), minimal hemoglobin levels, and a higher cardiac index (CI) and sPAP at TTE (Table 1).


**Table 1.** Clinical characteristics and screening tests according to gastrointestinal involvement in 240 patients with hereditary hemorrhagic telangiectasia (HHT).


**Table 1.** *Cont*.

GI: Gastrointestinal; ACVRL1: Activin A receptor type II-like 1 gene; ENG: Endoglin gene; SD: Standard deviation; CI: Cardiac index; sPAP: Systolic pulmonary artery pressure; TTE: Transthoracic echocardiography; CNS: Central nervous system. *\** Comparison between GI involvement and unsuspected GI involvement groups.

After multivariate analysis, age (OR 1.07, 1.06–1.14, *p* = 0.033), *ENG* mutations (OR 5.7, 1.02–31.93 95% CI, *p* = 0.047), previous/current tobacco use (OR 7.8, 1.37–44.52 95% CI, *p* = 0.020), and hemoglobin values (OR 0.96, 0.93–0.96 95% CI, *p* = 0.033) were associated with GI involvement at endoscopy tests (Table 2). The ROC analysis showed a good predictive power of the associated risk factors for GI involvement (AUC = 0.834).

**Table 2.** Uni- andmultivariable logistic regression analyses for gastrointestinal bleedingin patients with HHT.


OR: odds ratio; 95% CI: 95% confidence intervals; *ACVRL1*: activin A receptor type II-like 1 gene; *ENG*: endoglin gene; ESS: epistaxis severity score.

#### *3.3. GI Involvement*

Telangiectasia was more frequently found in the stomach and duodenum. All but one patient with telangiectasia based on the esophagogastroduodenoscopy (EGD) also showed telangiectases in the colonoscopy (CS). Most patients (81.5%) with gastric or duodenal telangiectasia in EGD also had small intestine involvement at VCE. The size of telangiectases most commonly was ≤3 mm in all locations, and most patients had ≤10 telangiectases per location. Multiple (>10) telangiectases were mostly found in the jejunum and ileum.

Most patients with GI disease had hemoglobin levels < 8 g/dL and/or RBC transfusion requirements during follow-up (*n* = 44; 65.7%). These patients were older and with a higher ESS than the subgroup of patients without these conditions. No gender, epistaxis, age, or visceral involvement differences were found between any subgroups. Patients with hemoglobin levels < 8 g/dL and/or transfusion requirements had larger telangiectases (>3 mm) and needed APC therapy more often than the remaining patients with GI involvement, with no other differences in location or the number of telangiectases (Table 3).


**Table 3.** Clinical characteristics and endoscopic findings among patients with gastrointestinal involvement.

APC: argon plasma coagulation; EGD: esophagogastroduodenoscopy; EES: epistaxis severity score; CS: colonoscopy; *GI*: gastrointestinal; Hb: Hemoglobin; SD: standard deviation.
