Minimal Hepatic Encephalopathy in Hereditary Hemorrhagic Telangiectasian

NCT ID: NCT03586115

Last Updated: 2020-11-03

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-01-08
• Study Completion Date: 2020-04-30

Brief Summary

HHT or Rendu-Osler-Weber disease is a genetic disease with an autosomal dominant inheritance pattern, characterized by widespread telangiectases that can involve several organs including the intestinal tract and the liver. Liver involvement by HHT is characterized by widespread diffuse liver vascular malformations that give origin to arteriovenous, arterioportal and portovenous shunts. The prevalence of hepatic involvement in HHT can reach 78%. Less commonly, patients may also develop porto-systemic encephalopathy (PSE). However, there are no studies on the possibility that patients with HHT might develop mHE, a highly plausible hypothesis considering the presence of diffuse macroscopic and microscopic porto-systemic shunt in this pathological condition.

Detailed Description

Hepatic encephalopathy (HE) is a potentially reversible disorder characterized by neuropsychiatric abnormalities and motor disturbances that range from mild alterations of cognitive and motor functions to coma and death (1-2). This condition has been linked to the combination of gut flora alterations, which increase the production of gut-derived toxins such as ammonia and indoles, and porto-systemic shunts, leading to endotoxemia associated to systemic and cerebral inflammation (3-4). The subclinical expression of HE is defined minimal hepatic encephalopathy (mHE) (5-7). The latter condition is characterized by the presence of various quantifiable neurophysiological and neuropsychological deficits that are only recognized by the use of specific diagnostic tools such as the paper-and-pencil tests and its variants as well as critical flicker frequency (CFF) (8-11).

The visual test based on CFF measures the frequency (Hz) when impression of fused light turns to a flickering one (5,11). This neurophysiological test has an elevated specificity and reproducibility, with only little biases due to training effects and daytime variability (7,11-13). CFF has also shown the ability to predict the risk of developing overt HE in cirrhotics undergoing transjugular intrahepatic portosystemic shunt (TIPS) (14,15).

HHT or Rendu-Osler-Weber disease is a genetic disease with an autosomal dominant inheritance pattern, characterized by widespread telangiectases that can involve several organs including the intestinal tract and the liver (16). There are two main types of the disease, HHT1 and HHT2, which are caused respectively by mutations in ENG gene on chromosome 9 coding for endoglin for HHT1and mutations in ACVRL1 gene on chromosome 12 for HHT2 (17,18). These two types of the disease account for most clinical cases but mutations in MADH4 gene on chromosome 5 (encodingSMAD4), have been recently described, and a new type HHT3 has been reported (17). HHT2 is associated with a high rate of liver involvement (18).

Liver involvement by HHT is characterized by widespread diffuse liver vascular malformations that give origin to arteriovenous, arterioportal and portovenous shunts. The prevalence of hepatic involvement in HHT can reach 78% (19). Less commonly, patients may also develop porto-systemic encephalopathy (PSE) (20). However, there are no studies on the possibility that patients with HHT might develop mHE, a highly plausible hypothesis considering the presence of diffuse macroscopic and microscopic porto-systemic shunt in this pathological condition.

Conditions

Hepatic Encephalopathy; Minimal Brain Dysfunction

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Patients with Hereditary telangectasia

In addition to all laboratory analyses and imaging studies required to evaluate the disease, hepatic elastometry and critical flicker frequency assessment will be performed.

Critical flicker frequency assessment

Intervention Type: DEVICE

All patients will undergo critical flicker frequency assessment to evaluate the presence of minimal hepatic encephalopaty. In addition, hepatic elastometry will be assessed to evaluate the presence of advanced liver fibrosis.

Interventions

Critical flicker frequency assessment

All patients will undergo critical flicker frequency assessment to evaluate the presence of minimal hepatic encephalopaty. In addition, hepatic elastometry will be assessed to evaluate the presence of advanced liver fibrosis.

Intervention Type: DEVICE

Other Intervention Names

Hepatic elastometry

Eligibility Criteria

Inclusion Criteria

• In this study all patients with hereditary hemorragic telangectasia carrying micro or macro porto-systemic vascular shunts will be enrolled.

Exclusion Criteria

• Actual or previous presence of overt HE (West-Haven criteria) (1,2), gastrointestinal bleeding in the previous 2 weeks, significant comorbidities such as cardiac, respiratory or renal failure; previous transjugular intrahepatic portosystemic shunt, electrolyte imbalance as hyponatremia (Na<125 mg/dl), neurological diseases, color blindness or severe visual disturbances (cataracts, diabetic retinopathy), hepatocellular carcinoma or other malignancies, use of psychotropic drugs in the week prior to the study. Patients with advanced liver disease will also be excluded. Diagnosis of cirrhosis or advanced liver fibrosis will be based on: a) histological evaluation documented at any time before enrollment, b) liver transient elastography and c) a combination of clinical, laboratory and abdominal ultrasound parameters established a priori (Barone M et al. Digestive and Liver Disease 2018;50:496-500).

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Bari

OTHER

Sponsor Role: lead

Responsible Party

Michele Barone

Clinical professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

michele barone, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Bari

Locations

Policlinic Hospital

Bari, , Italy

Countries

Italy

References

Barone M, Shahini E, Iannone A, Viggiani MT, Corvace V, Principi M, Di Leo A. Critical flicker frequency test predicts overt hepatic encephalopathy and survival in patients with liver cirrhosis. Dig Liver Dis. 2018 May;50(5):496-500. doi: 10.1016/j.dld.2018.01.133. Epub 2018 Jan 31.

Reference Type: BACKGROUND

PMID: 29530628 (View on PubMed)

Other Identifiers

Policlinic Hospital 4, Bari

Identifier Type: -

Identifier Source: org_study_id