Session Title: Category 2b. CIRRHOSIS AND ITS COMPLICATIONS: b. CLINICAL ASPECTS
Presentation Date: Apr 15, 2010
PERSISTENT DEFICIT IN LEARNING OF RESPONSE INHIBITION FOLLOWING ONSET OF OVERT HEPATIC ENCEPHALOPATHY IN CIRRHOSIS
J. Bajaj1*, D.M. Heuman1, C. Schubert2, D.P. Gibson3, J.B. Wade3, A. Topaz1, D. Bell1, R.T. Stravitz1, R.K. Sterling1, A.J. Sanyal1
1Gastroenterology, Hepatology and Nutrition, 2Biostatistics, 3Psychology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA. *email@example.com
Introduction: Acute mental status changes of overt hepatic encephalopathy (OHE) are generally reversible, but OHE episodes may be associated with chronic neurological damage.
Aim was to determine if cognitive function deteriorates after OHE by evaluating psychometric performance of pts with/without prior OHE both retrospectively (cross sectional) & prospectively.
Cross-sectional: Pts with OHE, minimal HE (MHE) & no MHE (nMHE) were tested & compared.
Prospective: Pts without prior OHE were tested and followed prospectively. Of these a group developed OHE and was retested after clinical resolution while the remaining were retested without OHE development. A psychometric battery (PB), including number connection A/B, digit symbol & block design tests) was given with inhibitory control test (ICT; high lures indicate poor response inhibition). ICT has identical halves, therefore learning can be studied. Improvement (reduction) in lures between 1st/2nd ICT halves(ΔL:1-2) was evaluated as a measure of learning ability for response inhibition. All OHE pts were adherent on lactulose and had normal mental status(mini-mental score>25).
Cross-sectional: 226 pts(120 MHE,52 OHE,54 nMHE,57 yrs,75%men,69%HCV,MELD 9) were included. OHE and MHE subjects performed worse on all tests compared to nMHE (p< 0.0001). Positive ΔL:1-2 showed learning capacity for response inhibition in nMHE(1.7) & MHE(1.9) but not in OHE (0.2, p=0.003).
Prospective: 15 pts(54yrs,12 men,80%HCV) developed OHE & were tested 36±25 days after the episode (total 4±2 mths apart) while 44 (55 yrs,32 men,74% HCV) did not develop OHE and were retested 4±3 mths apart. PB remained similar to baseline in both groups. Overall lure response worsened after OHE (12 vs18, p=0.0001) & ΔL:1-2 declined from 3.0 pre-OHE to 0.3 post-OHE, p=0.001, indicating loss of learning. Pre-OHE,14 of 15 (93%) pts had ΔL:1-2 ≥1, compared to only 2 (13%) post-OHE(p=0.0001). In the pts who remained OHE-free on follow-up, no change in lures or ΔL:1-2 (2.4 vs 2.7 p=0.3) was seen, indicating intact learning.
Conclusion: Learning of response inhibition as demonstrated by ICT (ΔL:1-2) is present in nMHE & MHE, but is lost following onset of OHE despite lactulose treatment. This feature of ICT may represent a sensitive measure to detect chronic neurocognitive impairment in OHE.