P23 Impact of Alcoholic Etiology of Liver Cirrhosis Upon mHE Diagnostics

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Introduction: It is unclear whether the etiology of liver cirrhosis has any impact upon tests that are used for diagnosing minimal hepatic encephalopathy (mHE). Alcohol abuse is one of the most frequent causes of liver cirrhosis. Since alcohol is neurotoxic in itself, patients with alcohol-related cirrhosis might perform worse in mHE tests than those with other etiologies despite similar severity of liver disease. Hence, in this study we compare the test results of patients with pure alcohol-related cirrhosis (ARC) with those with non-alcohol related cirrhosis (nARC) in 6 mHE tests. Methods: A number of 184 patients with liver cirrhosis were included in this study. After a neurological examination, the patients underwent the following tests: PSE-Syndrome Test yielding the PHES (cut-off <-4), Animal Naming Test (ANT, cut-off <23 or Z-Score <-1.3), Critical Flicker Frequency (CFF, cut-off <39 Hz), Inhibitory Control Test (ICT, cut-off >24 weighted lures), EncephalApp (Stroop, cut-off >190 sec) and Continuous Reaction Time Test (CRT cut-off <1.9). The order of the test procedure changed with each patient. Results: Overall, 89 patients had ARC and 95 nARC. Median age was 57; 67.4% of patients were male. 15.2% exhibited HE grade 1-2 at the time of testing and 34.8% had a history of overt HE. Median MELD and Child-Pugh-Score was 12 and 7, respectively. 63% were on medication for HE prophylaxis. The 2 patient groups were comparable in baseline characteristics and did not significantly differ regarding test results (Table 1). However, there was a trend for worse results in the ARC group for Digit Symbol Test (DST), Serial Dotting Test (SDT), PHES and Stroop, while the nARC group performed worse in the CRT (Figure 1). In multivariable analysis, adjusted for MELD, age, education, HE prophylaxis, HE grade 1-2 at time of testing and white blood cell count, nARC was associated with higher risk for abnormal results in CRT (OR: 2.3, P=0.018). Conclusion: Our findings suggest that etiology of liver disease has an impact upon the results of tests commonly used for diagnosing mHE. This emphasizes the importance of acknowledging the multifactorial origin of cognitive alterations in patients with liver cirrhosis. Table 1. - Baseline characteristics of tested patients with alcohol and non-alcohol related cirrhosis All patients Alcohol-related cirrhosis Non-alcohol related cirrhosis P-value Number of patients N=184 N=89 N=95 Age 57 (50-64) 57 (52-63) 58 (49-64) 0.849 Sex male 124 (67.4%) 65 (73%) 59 (62.1%) 0.119 TIPS at baseline 40 (21.7%) 23 (25.8%) 17 (17.9%) 0.214 Diabetes 48 (26.1%) 21 (23.6%) 27 (28.4%) 0.282 Previous-oHE-episodes 64 (34.8%) 29 (32.6%) 35 (36.8%) 0.642 Years of school education 10 (9-11) 10 (9-11) 10 (9-11) 0.989 HE grade 1-2 at time of testing 28 (15.2%) 16 (18%) 12 (12.6%) 0.412 Any HE prophylaxis 116 (63%) 64 (71.9%) 52 (54.7%) 0.022 Cognitive testing PHES -4 ((-7)-(-1)) -4 ((-8)-(-2)) -3 ((-6)-(-1)) 0.320 DST pathological (<-2) 80 (43.5%) 44 (49.4%) 36 (37.9%) 0.137 NCT-A pathological (<-2) 47 (25.5%) 24 (27%) 23 (24.2%) 0.736 NCT-B pathological (<-2) 46 (25%) 24 (27%) 22 (23.2%) 0.611 SDT pathological (<-2) 52 (28.3%) 29 (32.6%) 23 (24.2%) 0.252 LT-time pathological (<-2) 20 (10.9%) 9 (10.1%) 11 (11.6%) 0.816 LT-errors pathological (<-2) 22 (12%) 9 (10.1%) 13 (13.7%) 0.502 PHES pathological (<-4) 77 (41.8%) 42 (47.2%) 35 (36.8%) 0.179 CRT Index 1.818 (1.393-2.314) 1.988 (1.282-2.356) 1.747 (1.449-2.240) 0.458 CRT pathological (<-1.9) 98 (53.3%) 42 (47.2%) 56 (58.9%) 0.139 Stroop Off+OnTime (sec) 186.177 (161.400-215.899) 192.443 (161.914-219.276) 183.122 (161.328-205.289) 0.267 Stroop pathological (>190 sec) 92 (50%) 51 (57.3%) 41 (43.2%) 0.076 ANT (animals/minute) 22 (18-27) 22 (18-28) 22 (18-26) 0.268 ANT Z-Score (normalized by age, education & sex) -0.35 ((-1.21)-0.55)) -0.24 ((-1.12)-0.61) -0.49 ((-1.33)-0.38) 0.338 ANT (<23 animals) pathological 99 (53.8%) 46 (51.7%) 53 (55.8%) 0.657 ANT Z-Score (<-1.3) pathological 44 (23.9%) 18 (20.2%) 26 (27.4%) 0.301 ICT weighted lures (=Lures/Target Accuracy2) 19.42 (10.49-34.3) 18.97 (10.49-33.77) 20.35 (10.41-38.52) 0.994 ICT pathological (>24 weighted lures) 86 (46.7%) 40 (44.9%) 46 (48.4%) 0.66 CFF (Hz, corrected for SD) 41.45 (38-46.64) 41.18 (38-45.8) 41.66 (37.9-47.4) 0.832 CFF pathological (<39 Hz) 57 (31%) 26 (29.2%) 31 (32.6%) 0.367 Lab values MELD 12 (9-17) 12 (9-16) 12 (10-18) 0.347 Child-Pugh-Score 7 (6-9) 8 (6-9) 7 (6-9) 0.079 Sodium (mmol/l) 136 (134-139) 136 (133-138) 137 (135-139) 0.011 Creatinine (µmol/l) 87 (71-108) 88 (71-119) 85 (69-104) 0.087 CRP (mg/l) 8.2 (2.7-19.2) 8.5 (2.7-19.3) 7.5 (2.6-20.2) 0.94 CHE (kU/l) 3.11 (2.11-4.46) 2.87 (1.88-4.59) 3.26 (2.35-4.25) 0.491 Bilirubin (µmol/l) 29 (15-54) 24 (13-46) 31 (19-66) 0.04 Albumin (g/l) 33 (32-34) 34 (32-35) 32 (31-33) 0.132 White blood cells (tsd/µl) 4.9 (3.8-7) 6 (4.6-8) 4.2 (3.2-6.4) <0.001 Platelets (tsd/µl) 95 (61-139) 115 (74-170) 80 (60-115) <0.001 Hemoglobin (g/dl) 11.1 (9.5-13.2) 11 (8.9-13.4) 11.2 (10.2-13.4) 0.515 INR 1.26 (1.13-1.41) 1.25 (1.07-1.4) 1.29 (1.16-1.43) 0.128 All continuous variables are presented as median and IQR, t-test for normative distributed values, Mann-Whitney-U for not normative distributed values, Chi-Square for dichotomous values.Abbreviations: TIPS: transjugular intrahepatic portosystemic shunt, HE: hepatic encephalopathy, PHES: Portosystemic Hepatic Encephalopathy Score, DST: Digit-Symbol Test, NCT: Number-Connection Test, SDT: Serial-Dotting Test, LT: Line-Tracing Test, CRT: Continuous Reaction Time Test, ANT: Animal Naming Test, Stroop: EncephalApp, ICT: Inhibitory Control Test, CFF: Critical Flicker Frequency, CHE: Cholinesterase, CRP: C-reactive protein, INR: International normalized ratio, MELD: Model for end-stage liver disease. Figure 1.: Percentage of pathological results in the 6 tests applied for diagnosing mHE in patients with alcohol-related (ARC) or non-alcohol related (nARC) liver cirrhosis.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.