Debulon E. Bell

Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test.

Patients with minimal hepatic encephalopathy (MHE) have impaired driving skills, but association of MHE with motor vehicle crashes is unclear. Standard psychometric tests (SPT) or inhibitory control test (ICT) can be used to diagnose MHE. The aim was to determine the association of MHE with crashes and traffic violations over the preceding year and on 1‐year follow‐up. Patients with cirrhosis were diagnosed with MHE by ICT (MHEICT) and SPT (MHESPT). Self and department‐of‐transportation (DOT)‐reports were used to determine crashes and violations over the preceding year. Agreement between self and DOT‐reports was analyzed. Patients then underwent 1‐year follow‐up for crash/violation occurrence. Crashes in those with/without MHEICT and MHESPT were compared. 167 patients with cirrhosis had DOT‐reports, of which 120 also had self‐reports. A significantly higher proportion of MHEICT patients with cirrhosis experienced crashes in the preceding year compared to those without MHE by self‐report (17% vs 0.0%, P = 0.0004) and DOT‐reports (17% vs 3%, P = 0.004, relative risk: 5.77). SPT did not differentiate between those with/without crashes. A significantly higher proportion of patients with crashes had MHEICT compared to MHESPT, both self‐reported (100% vs 50%, P = 0.03) and DOT‐reported (89% vs 44%, P = 0.01). There was excellent agreement between self and DOT‐reports for crashes and violations (Kappa 0.90 and 0.80). 109 patients were followed prospectively. MHEICT patients had a significantly higher future crashes/violations compared to those without (22% vs 7%, P = 0.03) but MHESPT did not. MHEICT (Odds ratio: 4.51) and prior year crash/violation (Odds ratio: 2.96) were significantly associated with future crash/violation occurrence. Conclusion: Patients with cirrhosis and MHEICT have a significantly higher crash rate over the preceding year and on prospective follow‐up compared to patients without MHE. ICT, but not SPT performance is significantly associated with prior and future crashes and violations. There was an excellent agreement between self‐ and DOT‐reports. (HEPATOLOGY 2009.)

Persistence of Cognitive Impairment After Resolution of Overt Hepatic Encephalopathy

BACKGROUND & AIMS In patients with cirrhosis, hepatic encephalopathy (HE) has acute but reversible as well as chronic components. We investigated the extent of residual cognitive impairment following clinical resolution of overt HE (OHE). METHODS Cognitive function of cirrhotic patients was evaluated using psychometric tests (digit symbol, block design, and number connection [NCT-A and B]) and the inhibitory control test (ICT). Improvement (reduction) in ICT lures and first minus second halves (DeltaL(1-2)) were used to determine learning of response inhibition. Two cross-sectional studies (A and B) compared data from stable cirrhotic patients with or without prior OHE. We then prospectively assessed cognitive performance, before and after the first episode of OHE. RESULTS In study A (226 cirrhotic patients), 54 had experienced OHE, 120 had minimal HE, and 52 with no minimal HE. Despite normal mental status on lactulose after OHE, cirrhotic patients were cognitively impaired, based on results from all tests. Learning of response inhibition (DeltaL(1-2) > or =1) was evident in patients with minimal HE and no minimal HE but was lost after OHE. In study B (50 additional patients who developed > or =1 documented OHE episode during follow-up), the number of OHE hospitalizations correlated with severity of residual impairment, indicated by ICT lures (r = 0.5, P = .0001), digit symbol test (r = -0.39, P = .002), and number connection test-B (r = 0.33, P = .04). In the prospective study (59 cirrhotic patients without OHE), 15 developed OHE; ICT lure response worsened significantly after OHE (12 before vs 18 after, P = .0003), and learning of response inhibition was lost. The 44 patients who did not experience OHE did not have deteriorations in cognitive function in serial testing. CONCLUSIONS In cirrhosis, episodes of OHE are associated with persistent and cumulative deficits in working memory, response inhibition, and learning.

The Multi-Dimensional Burden of Cirrhosis and Hepatic Encephalopathy on Patients and Caregivers

OBJECTIVES:Cirrhosis and hepatic encephalopathy (HE) can adversely affect survival, but their effect on socioeconomic and emotional burden on the family is not clear. The aim was to study the emotional and socioeconomic burden of cirrhosis and HE on patients and informal caregivers.METHODS:A cross-sectional study in two transplant centers (Veterans and University) of cirrhotic patients and their informal caregivers was performed. Demographics for patient/caregivers, model-for-end-stage liver disease (MELD) score, and cirrhosis complications were recorded. Patients underwent a cognitive battery, sociodemographic, and financial questionnaires. Caregivers were given the perceived caregiver burden (PCB; maximum=155) and Zarit Burden Interview (ZBI)-Short Form (maximum=48) and questionnaires for depression, anxiety, and social support.RESULTS:A total of 104 cirrhotics (70% men, 44% previous HE, median MELD 12, 49% veterans) and their caregivers (66% women, 77% married, relationship duration 32±14 years) were included. Cirrhosis severely impacted the family unit with respect to work (only 56% employed), finances, and adherence. Those with previous HE had worse unemployment (87.5 vs. 19%, P=0.0001) and financial status (85 vs. 61%, P=0.019) and posed a higher caregiver burden; PCB (75 vs. 65, P=0.019) and ZBI (16 vs. 11, P=0.015) compared with others. Cognitive performance and MELD score were significantly correlated with employment and caregiver burden. Veterans and non-veterans were equally affected. On regression, depression score, MELD, and cognitive tests predicted both PCB and ZBI score.CONCLUSIONS:Previous HE and cognitive dysfunction are associated with worse employment, financial status, and caregiver burden. Cirrhosis-related expenses impact the family units daily functioning and medical adherence. A multidisciplinary approach to address this burden is required.

Predictors of the recurrence of hepatic encephalopathy in lactulose-treated patients

Aliment Pharmacol Ther 31, 1012–1017

PROMIS computerised adaptive tests are dynamic instruments to measure health-related quality of life in patients with cirrhosis.

Aliment Pharmacol Ther 2011; 34: 1123–1132

Driving Simulation and Cognitive Testing Can Improve Insight Into Impaired Driving Skills in Cirrhotic Patients With MHE

Background/Aims: Episodes of bacterial translocation are associatedwith increased concentrations of endotoxin, which is able to prime and activate neutrophils and monocytes. Since variants of the nucleotide-binding oligomerization domain containing 2 (NOD2) gene impair the innate immune response and contribute to bacterial translocation, we hypothesized that the phagocyte resting burst is increased in patients with liver cirrhosis that carry NOD2 variants. Methods: The common NOD2 gene variants G908R, R702W, and 1007fs were determined in 35 non-infected patients with liver cirrhosis. The formation of reactive oxygen species in neutrophils and monocytes from these patients was monitored through the oxidation of dihydrorhodamine 123 to rhodamine by flow cytometry in whole blood and compared with that of 25 healthy controls. Results: The resting burst was increased in patients with liver cirrhosis compared to control subjects (P≤0.001). 8 of 35 cirrhotic patients were carriers of NOD2 variants. The spontaneous production of ROS in neutrophils (P=0.012) and monocytes (P=0.018) was increased in presence of a NOD2 mutation. A higher resting burst in neutrophils was also associated with a higher MELD score (r[s]= 0.388; P=0.023) and with Child-Pugh-Stage C (P=0.040). However, in a multivariate regression model only the presence of a NOD2 variant (P=0.019) and of ascites (P=0.016) were independent predictors of spontaneous ROS production in neutrophils (adjusted R2=0.231). Conclusion: The augmented neutrophil resting burst in patients with liver cirrhosis is further increased in presence of a NOD2 mutation which is suggestive of an increased bacterial translocation in these patients.