Highlights
- •Hepatic vascular malformations (HVMs) observed in HHT include portosystemic shunts.
- •The presence of radiologically undetectable HVMs is reported in the literature.
- •HVMs can cause portosystemic encephalopathy (PSE).
- •Using specific neurological tests we identified subclinical PSE in HHT patients.
- •These neurological tests should be adopted in HHT surveillance protocols.
Abstract
Background. Portosystemic shunts in Hereditary Haemorrhagic Telangiectasia (HHT) are often overlooked
by conventional imaging although they could reduce hepatic clearance of gut-derived
toxins.
Aims. To evaluate, the presence of subclinical neurological alterations (SNAs), that we
named “minimal portosystemic encephalopathy” (mPSE) in HHT patients without advanced
liver disease (ALD).
Methods. In this cross sectional study, consecutive HHT outpatients were firstly screened
by critical flicker frequency (CFF) test (abnormal ≤39Hz), and the simplified animal
naming test (S-ANT1) (abnormal <15) was used to confirm the diagnosis of mPSE. Furthermore, we evaluated
the effect of lactulose administration on mPSE. Multi-slice CT, cerebral dynamic magnetic
resonance, laboratory analyses and transient elastography were also used.
Results. None of the 37 enrolled patients showed portosystemic shunts at imaging techniques.
However, 33 patients had normal CFF values (CFF-) and 4 displayed CFF alterations
(37.0±0.7Hz, CFF+). The S-ANT1 confirmed an impaired neurological performance (10.2±2.8) in CFF+ patients thus confirming
the presence of mPSE. Noteworthy, lactulose administration determined a CFF increase
(39.1±0.4Hz) and S-ANT1 normalization in these patients. Neither mPSE- nor mPSE+ patients had ALD and showed
similar demographic, clinical and laboratory parameters. Finally, no mPSE+ patient
showed radiologically-detectable brain vascular malformations or other brain abnormalities
at imaging.
Conclusions. HHT patients represent a human model of mPSE secondary to portosystemic shunts escaping
radiological detection. mPSE evaluation should be incorporated in HHT surveillance
protocols since it can affect both health-related/social aspects and pharmacokinetics
of orally administered drugs with a narrow therapeutic index and high hepatic first-pass
uptake.
Graphical abstract
Graphical Abstract
Key words
Abbreviations:
HHT (Hereditary Haemorrhagic Telangiectasia), HVMs (hepatic arteriovenous malformations), CFF (critical flicker frequency), MSCT (multi-slice computed tomography), MRA (magnetic resonance angiography), HE (hepatic encephalopathy), mHE (minimal hepatic encephalopathy), mPSE (minimal portosystemic encephalopathy), SNAs (subclinical neurological alterations), ALD (advanced liver disease), S-ANT1 (simplified animal naming test.)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: May 18, 2021
Accepted:
April 26,
2021
Received in revised form:
April 24,
2021
Received:
January 18,
2021
Identification
Copyright
© 2021 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
