Previous Overt Hepatic Encephalopathy Research Articles

Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis

Neuropsychological and psychophysical tests are recommended to assess the risk of overt hepatic encephalopathy (OHE), but their accuracy is limited. Hyperammonaemia is central in the pathogenesis of OHE, but its predictive utility is unknown. In this study, we aimed to determine the role of neuropsychological or psychophysical tests and ammonia, and to develop a model (AMMON-OHE) to stratify the risk of subsequent OHE development in outpatients with cirrhosis. This observational, prospective study included 426 outpatients without previous OHE from three liver units followed for a median of 2.5 years. Psychometric hepatic encephalopathy score (PHES) <-4 or critical flicker frequency (CFF) <39 was considered abnormal. Ammonia was normalized to upper limit of normal (AMM-ULN) at the respective reference laboratory. Multivariable frailty competing risk and random survival forest analyses were performed to predict future OHE and to develop the AMMON-OHE model. External validation was carried out using 267 and 381 patients from two independent units. Significant differences were found in time-to-OHE (log-rank p <0.001) according to PHES or CFF and ammonia, with the highest risk in patients with abnormal PHES plus high AMM-ULN (hazard ratio 4.4; 95% CI 2.4-8.1; p <0.001 compared with normal PHES and AMM-ULN). On multivariable analysis, AMM-ULN but not PHES or CFF was an independent predictor of the development of OHE (hazard ratio 1.4; 95% CI 1.1-1.9; p= 0.015). The AMMON-OHE model (sex, diabetes, albumin, creatinine and AMM-ULN) showed a C-index of 0.844 and 0.728 for the prediction of a first episode of OHE in two external validation cohorts. In this study, we developed and validated the AMMON-OHE model, comprising readily available clinical and biochemical variables that can be used to identify outpatients at the highest risk of developing a first episode of OHE. In this study, we aimed to develop a model to predict which patients with cirrhosis are at risk of developing overt hepatic encephalopathy (OHE). Using data from three units and including 426 outpatients with cirrhosis, we developed the AMMON-OHE model - comprising sex, diabetes, albumin, creatinine and ammonia levels - which demonstrated good predictive ability. The AMMON-OHE model performs better than PHES and CFF to predict the first episode of OHE in outpatients with cirrhosis. This model was validated in 267 and 381 patients from two independent liver units. The AMMON-OHE model is available online for clinical use.

Minimal Hepatic Encephalopathy and Biejia-Ruangan Are Associated with First Hospital Readmission in Nonalcoholic Cirrhosis Patients.

Introductionand Aim. Patients with cirrhosis are often hospitalized repeatedly for a variety of complications. This retrospective study aimed to assess the effects of minimal hepatic encephalopathy (MHE) and Biejia-Ruangan (BR) on first hospital readmission in nonalcoholic cirrhosis patients without previous overt hepatic encephalopathy (OHE) or hepatocellular carcinoma (HCC). Materials and Methods. A total of 176 hospitalized patients with nonalcoholic cirrhosis were included in this retrospective study. Patients who were first admitted to Beijing Ditan Hospital of Capital Medical University from January 2017 to September 2019 were enrolled. The primary endpoint was their first liver-related hospital readmission. The risk factors for readmission were analyzed by Cox proportional hazard regression analysis. Results. A total of 176 nonalcoholic cirrhosis patients without previous OHE or HCC were included; 57 patients (32.4%) were diagnosed with MHE, and 63 patients (35.8%) were administered BR (2 g, three times a day). Multivariate analysis revealed that nonalcoholic cirrhosis patients with MHE (HR, 5.805; 95% CI, 3.007–11.206; x, P < 0.001) and a higher Model for End-Stage Liver Disease (MELD) score (HR, 1.145; 95% CI, 1.068–1.227; P < 0.001) had an increased risk of first hospital readmission, and patients treated with BR (HR, 0.318; 95% CI, 0.151–0.670; P=0.003) had a decreased risk of first hospital readmission. Conclusion. MHE increased the risk of hospital readmission in nonalcoholic cirrhosis patients without previous OHE or HCC, and this risk was decreased by BR administration.

Clinical, neuropsychological and neurophysiological indices and predictors of hepatic encephalopathy (HE)

Background & aims The occurrence of overt hepatic encephalopathy (HE) marks a significant progression in the natural history of liver disease. The aims of the present study were: 1) to describe a large cohort of patients with cirrhosis in terms of neuropsychological/neurophysiological HE indices, and 2) to test if the severity of liver disease and/or any such indices [Psychometric Hepatic Encephalopathy Score (PHES), Scan test, electroencephalography (EEG)] predicted mortality/HE risk in a subgroup of such cohort. Method 461 patients with cirrhosis (59±10 years; 345 males) were included; information on previous overt HE episodes was available in 407. Follow up information on mortality/HE-related hospitalization in 134/127, respectively. Information on previous overt HE episodes and both mortality and HE-related hospitalization over the follow up in 124. Results Patients with a history of overt HE (60%) had poorer liver function, worse neuropsychiatric indices, higher ammonia levels and higher prevalence of portal-systemic shunt. The risk of HE-related hospitalization over the follow up was higher in patients with higher MELD score and worse Scan performance. Mortality was higher in those with higher MELD. Amongst patients without a history of overt HE, those with worse PHES had higher HE risk. Amongst patients with a history, those with higher MELD, better PHES and worse Scan performance had higher HE risk. Conclusions In patients without previous overt HE episodes, neuropsychological and neurophysiological tests predict HE, while in those with previous overt HE episodes, HE development largely depends on the severity of liver dysfunction.

Clinical, neuropsychological and neurophysiological indices and predictors of hepatic encephalopathy (HE).

The occurrence of overt hepatic encephalopathy (HE) marks a significant progression in the natural history of liver disease. The aims of the present study were to: 1) describe a large cohort of patients with cirrhosis in terms of neuropsychological or neurophysiological HE indices, and 2) test if the severity of liver disease and/or any such indices [Psychometric Hepatic Encephalopathy Score (PHES), Scan test, electroencephalography (EEG)] predicted mortality/HE risk in a subgroup of such cohort. Four hundred and sixty-one patients with cirrhosis (59±10years; 345 males) were included; information on previous overt HE episodes was available in 407. Follow-up information on mortality/HE-related hospitalization in 134/127 respectively. Information on previous overt HE episodes and both mortality and HE-related hospitalization over the follow-up in 124. Patients with a history of overt HE (60%) had poorer liver function, worse neuropsychiatric indices, higher ammonia levels and higher prevalence of portal-systemic shunt. The risk of HE-related hospitalization over the follow-up was higher in patients with higher MELD score and worse Scan performance. Mortality was higher in those with higher MELD. Among patients without a history of overt HE, those with worse PHES had higher HE risk. Among patients with a history, those with higher MELD, better PHES and worse Scan performance had higher HE risk. In patients without previous overt HE episodes, neuropsychological and neurophysiological tests predict HE, while in those with previous overt HE episodes, HE development largely depends on the severity of liver dysfunction.

Muscle Alterations Are Associated With Minimal and Overt Hepatic Encephalopathy in Patients With Liver Cirrhosis.

Muscle alterations (myosteatosis and sarcopenia) are frequent in cirrhosis and related to some complications including overt hepatic encephalopathy (HE). The aim of our study was to investigate the relationship between muscle alterations and minimal HE (MHE) and their role in the risk of overt HE. Sixty-four patients with cirrhosis were administered the Psychometric Hepatic Encephalopathy Score and animal naming test to detect MHE. Computed tomography was used to analyze the skeletal muscle index and attenuation. The incidence of the first episode of HE, taking into account the competing risk nature of the data, was estimated. Myosteatosis was observed in 24 patients (37.5%), sarcopenia in 37 (58%), and MHE in 32 (50%). Both myosteatosis (62.5% versus 12.5%, P<0.001) and sarcopenia (84% versus 31%, P<0.001) were more frequent in patients with MHE. The variables independently associated with the presence of MHE were sarcopenia, previous overt HE, and myosteatosis. Thirty-one (48%) patients developed overt HE over 16.1±13 months; myosteatosis was detected in 68% and sarcopenia in 84% of them. Sarcopenia and myosteatosis were also independently associated with the development of overt HE. Venous ammonia was significantly higher in patients with sarcopenia (62.6±17.7 versus 41.4±16.1 μg/dL, P<0.001) and in patients with myosteatosis (65.2±19.2 versus 46.7±17.1 μg/dL, P<0.001) and inversely correlated to both parameters. Survival was significantly lower in malnourished patients compared to patients without myosteatosis or sarcopenia (P<0.001). Conclusion: Myosteatosis and sarcopenia, probably by reducing the handling of ammonia in the muscle, are independently associated with MHE and the risk of overt HE in patients with cirrhosis; in malnourished patients, the amelioration of nutritional status may be a goal to decrease both the prevalence of MHE and the incidence of overt HE.

Factors Affecting Psychological Burden on the Informal Caregiver of Patients With Cirrhosis: Looking Beyond the Patient

Cirrhosis leads to considerable morbidity and mortality, compromises quality of life, and often necessitates assistance in activities of daily living. An informal caregiver bears the psychological burden of coping with the needs of the patient and the knowledge of morbid prognosis of a loved one. This aspect is rarely recognized and almost never addressed in a clinical practice. This cross-sectional study assessed the factors influencing psychological burden of cirrhosis on the caregivers in a predominantly lower-middle socioeconomic class Indian population. Patients underwent psychometric tests [Psychometric Hepatic Encephalopathy Score (PHES)], and questionnaires for quantifying caregiver burden [Perceived Caregiver Burden (PCB) and Zarit Burden Interview (ZBI)] and assessing depression [Beck Depression Inventory (BDI)] and anxiety [Beck Anxiety Inventory (BAI)] were administered. One hundred patients with cirrhosis [70% male, 27% with past hepatic encephalopathy (HE), and 53% with minimal HE] and their caregivers (66% women, 81% spouse, 26.51 years of mean relationship) were evaluated. Caregiver burden scores were higher in patients with previous overt HE than in those without previous overt HE [PCB (74.63 vs. 66.15, P=0.001), ZBI (27.93 vs. 21.11, P= 0.023), BDI (11.63 vs. 8.96, P=0.082), and BAI (11.37 vs. 8.12, P= 0.027)]. Similarly, caregivers of patients with minimal HE had higher caregiver burden that those of patients who did not have minimal HE [PCB (70.74 vs. 65.85, P=0.027), ZBI (26 vs. 19.51, P= 0.015)]. Burden scores correlated well with each other and with liver disease severity scores and negatively correlated with socioeconomic status. Repeated hospital admissions, alcohol as etiology, and lower socioeconomic status were the independent predictors of caregiver burden. Higher perceived burden is common in caregivers of patients with cirrhosis. Repeated hospital admissions, alcoholism, and lower socioeconomic status influence caregiver burden.

Assessment of Potential Impact of Demographic and Baseline Disease Characteristics on Rifaximin Monotherapy versus Lactulose Combination Therapy for the Prevention of Overt Hepatic Encephalopathy (OHE) Recurrence

Introduction: Rifaximin 550 mg is indicated for prevention of OHE recurrence in adults. A phase 4, open-label noninferiority trial evaluated the impact of baseline parameters on the efficacy of rifaximin alone vs rifaximin + lactulose for OHE recurrence prevention. Methods: Adults with cirrhosis and a previous OHE episode now in remission (Conn score ≤1) were randomized to rifaximin 550 mg BID alone or rifaximin 550 mg BID + lactulose (self-titrated; 2-3 soft stools/d) for 6 months. Breakthrough HE (Conn score ≥2) was monitored monthly. Time to onset of an OHE episode (primary endpoint) was assessed overall and by baseline parameters: age (< 65 y; ≥65 y), sex, race, prior lactulose use, diabetes status, MELD score, Conn score (0; 1), Child-Pugh class, asterixis grade (0; ≥1), duration of HE remission before study entry (≤90 days; >90 days), time since first diagnosis of advanced liver disease (< 50 months; 50 months), time since first diagnosis of HE (< 15 months; ≥15 months), number of HE episodes during past 6 months (1; >1), and cirrhosis etiology. Noninferiority was demonstrated if the upper limit 2-sided, 95% CI of hazard ratio (HR) of rifaximin to rifaximin + lactulose was < 1.6. Results: 113 patients were treated in the rifaximin alone group; 108 in rifaximin + lactulose group. Overall population mean MELD score was 11.9, 39.8% and 55.7% were Child-Pugh A and B, respectively, and baseline parameters were similar between groups. Breakthrough HE was reported in fewer patients in rifaximin + lactulose (13.9%) vs rifaximin alone (24.8%) groups; rifaximin + lactulose reduced the risk of breakthrough HE over 6 months to a greater degree (rifaximin alone vs combination HR, 2.0; 95% CI, 1.0-3.7; P=0.04). Demographic and baseline characteristics evaluated did not substantially alter the risk profile with rifaximin alone vs rifaximin + lactulose. In some subgroups (ie, Child-Pugh A [HR, 0.7; 95% CI, 0.2-2.4; P=0.6], remission duration >90 days [HR, 0.9; 95% CI, 0.4-2.1; P=0.7], prior 6-month HE episodes >1 [HR, 0.9; 95% CI, 0.3-2.7; P=0.9]), rifaximin alone reduced the risk of breakthrough HE to a greater degree than rifaximin + lactulose (ie, HR < 1); however, differences were not significant. Conclusion: Rifaximin + lactulose therapy appears to be consistently efficacious in prevention of OHE recurrence vs rifaximin alone and was unaltered by baseline characteristics evaluated. These data support the generalizability of the primary endpoint results.

Validation study associating glutaminase promoter variations with hepatic encephalopathy in East Asian populations.

In a recent study, microsatellite variations (GCA tandem repeats) in the promoter region of the (kidney-type) glutaminase gene were associated with the development of hepatic encephalopathy (HE) in Spanish patients with cirrhosis. The objective of this study was to validate the relation between microsatellite variations in the glutaminase promoter region and the development of overt HE in Korean patients with liver cirrhosis. We performed a prospective cohort study of 154 cirrhotic patients who underwent a glutaminase microsatellite study without previous overt HE history at baseline. The primary end point was the first episode of overt HE. The microsatellite length was categorized into three groups based on its repeated number, with a cutoff value of 14; 65 (42.2%), 70 (45.5%), and 19 (12.3%) patients had the short-short, short-long, and long-long alleles, respectively. Over a median 3.5 years of follow-up (range = 0.1-4.4), overt HE developed in 28 patients (18.2%). The 3-year cumulative incidence of overt HE was 18.4%. Multivariate Cox model indicated that past hepatocellular carcinoma history, alcoholic etiology for cirrhosis, higher Model for End-Stage Liver Disease scores and their deterioration, and serum ammonium levels were independently associated with HE development. However, microsatellite length was not associated with the development of overt HE. In Korean patients with cirrhosis, microsatellite variations in the glutaminase promoter region were not associated with development of overt HE. Thus, additional studies are needed to identify other genetic factors related to glutaminase activity in Asians with overt HE.

Hepatic Encephalopathy in Patients With Non-Cirrhotic Portal Hypertension: Description, Prevalence and Risk Factors

Background: Hepatic encephalopathy (HE) is a common complication of cirrhosis but it's less studied in patients with non-cirrhotic portal hypertension (NCPH). Aims: To describe the prevalence of cognitive impairment (overt and covert HE) in NCPH patients and to identify the risk factors for its development. Methods: 51 patients with NCPH, 35 with chronic portal vein thrombosis (PVT) and 16 with idiopathic non-cirrhotic portal hypertension (INCPH), were evaluated for the presence of previous or present overt HE (OHE). The psychometric hepatic encephalopathy score and the SCAN battery were used to detect the presence of covert HE (CHE). 34 compensated cirrhotic patients were used as control. In NCPH patients, abdominal scans were performed to detect the presence of shunts. Results: None of the patients experienced OHE at evaluation while 5.7% of PVT and 12.5% of INCPH patients referred at least one documented episode of previous OHE, similarly to patients with cirrhosis (14.7%). Even if lower than in patients with cirrhosis (64.7%), a considerable proportion of patients with chronic PVT (34.3%) and INCPH (25%) had CHE (P = 0.008). The presence of a large portal-systemic shunt was the only factor significantly correlated to cognitive impairment in NCPH patients (Figure 1). Conclusion: HE is a tangible complication of NCPH and is mainly related to the presence of portal-systemic shunts (Table 1).Table 1Prevalence of MetabolitesMinimal, Previous, Overt HE and of Global Cognitive Impairments in the Patients Included in the Study.Cirrhosis (n = 34)Chronic PVT (n = 35)INCPH (n = 16)PMinimal HE (Phes and/or Scan)22 (64.7%)*12 (34.3%)4 (25.0%)0.008Overt HE0 (0.0%)0 (0.0%)0 (0.0%)NSPrevious HE5 (14.7%)2 (5.7%)2 (12.5%)NSCognitive impairment23 (67.6%)*13 (37.1%)5 (31.3%)0.012 Open table in a new tab The authors have none to declare.

Mo1022 Effect of Body Mass Index (BMI) on Functional Status of Patients With Cirrhosis Based on the Six-Minute Walk Test (6mwt)

Background & Aims: Hepatic encephalopathy (HE) represents a spectrum of neurocognitive impairment seen in cirrhotic patients and is considered to be fully reversible with treatment, however recent evidence suggests otherwise. This longitudinal study was carried out to evaluate the persistence of cognitive impairment in cirrhotics with prior overt HE (OHE) episode despite treatment. Methods: Of 213 patients screened, 107 patients who met the eligibility criteria were enrolled and 102 patients completed the study (52 patients without prior OHE episode and 50 patients with prior OHE). Among 102 patients included in the study, 86 were men and 16 were women; 67 (65.7%) patients had alcoholic etiology and 35 (34.3%) had non-alcoholic etiology (hepatitis B virus 6 patients, hepatitis C virus 4 patients, cryptogenic 14 patients, miscellaneous 11 patients). All patients underwent psychometric hepatic encephalopathy score (PHES) evaluation at 3 separate visits (Day 1, Day 3 and between 30 and 60 days, median 34). PHES ≤5 was considered abnormal and diagnostic of minimal HE (MHE). One point improvement in PHES between first and second evaluation was considered as a measure of learning. Results: Thirty-four (33.3%) of patients with cirrhosis of liver had MHE; 20 (40%) with prior episode and 14 (26.9%) without prior episode of OHE had MHE. Patients with previous OHE episode showed learning impairment in PHES on repetition on 3rd day [Day 1, mean -3.70 (95% confidence intervals -4.71 -2.68) versus Day 3, -4.02 (-5.06-2.97); P = 0.084] as compared to patients without prior OHE episode [Day 1, -2.26 (-3.13 -1.40) versus Day 3, -0.44 (-1.24 0.35); P <0.0001] irrespective of having MHE or not. In this study, 57 patients were learners, i.e., 1point improvement in PHES (55.8%) and 45 patients were non-learners (44.2%). Univariate analysis demonstrated that Child-Turcotte-Pugh score, lactulose and/or rifaximin therapy, presence of MHE and previous OHE episode were associated with learning impairment. Multivariate analysis demonstrated that only presence of previous episode of OHE (adjusted odds ratio [95%, confidence interval; 38.398, 9.192 160.4]; p <0.0001) significantly affected learning. Conclusions: This study conclusively demonstrated learning impairment in cirrhotic patients with previous episode of OHEdespite normalmental status. Improvement in PHES on repetition can be used as a measure of learning in future studies.

Persistence of cognitive impairment after resolution of overt hepatic encephalopathy.

Hepatic encephalopathy (HE) represents a spectrum of neurocognitive impairment seen in cirrhotic patients and is considered to be fully reversible with treatment; however, recent evidence suggests otherwise. This longitudinal study was carried out to evaluate the persistence of cognitive impairment in cirrhotics with prior overt HE (OHE) episode despite treatment. Of the 213 patients screened, 107 patients who met the eligibility criteria were enrolled and 102 patients completed the study (52 patients without prior OHE episode and 50 patients with prior OHE). All patients underwent psychometric hepatic encephalopathy score (PHES) evaluation at three separate visits (day 1, day 3, and between 30 and 60 days). A one-point improvement in PHES between the first and second evaluation was considered as a measure of learning. Patients with a previous OHE episode showed learning impairment in PHES on repetition on day 3 (P=0.084), whereas patients without a previous OHE episode demonstrated learning effect (P<0.0001) irrespective of whether they had minimal HE (MHE) or not. Univariate analysis demonstrated that Child-Turcotte-Pugh score, lactulose and/or rifaximin therapy, the presence of MHE, and a previous OHE episode were associated with learning impairment. Multivariate analysis demonstrated that only the presence of a previous episode of OHE (adjusted odds ratio 38.398; 95% confidence interval 9.192-160.4; P<0.0001) significantly affected learning. This study conclusively demonstrated learning impairment in cirrhotic patients with a previous episode of OHE despite normal mental status. Improvement in PHES on repetition may be a measure of learning.

The Stroop smartphone application is a short and valid method to screen for minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) detection is difficult because of the unavailability of short screening tools. Therefore, MHE patients can remain undiagnosed and untreated. The aim of this study was to use a Stroop smartphone application (app) (EncephalApp_Stroop) to screen for MHE. The app and standard psychometric tests (SPTs; 2 of 4 abnormal is MHE, gold standard), psychometric hepatic encephalopathy score (PHES), and inhibitory control tests (ICTs) were administered to patients with cirrhosis (with or without previous overt hepatic encephalopathy; OHE) and age-matched controls from two centers; a subset underwent retesting. A separate validation cohort was also recruited. Stroop has an "off" state with neutral stimuli and an "on" state with incongruent stimuli. Outcomes included time to complete five correct runs as well as number of trials needed in on (Ontime) and off (Offtime) states. Stroop results were compared between controls and patients with cirrhosis with or without OHE and those with or without MHE (using SPTs, ICTs, and PHES). Receiver operating characteristic analysis was performed to diagnose MHE in patients with cirrhosis with or without previous OHE. One hundred and twenty-five patients with cirrhosis (43 previous OHE) and 134 controls were included in the original cohort. App times were correlated with Model for End-Stage Liver Disease (Offtime: r = 0.57; Ontime: r = 0.61; P < 0.0001) and were worst in previous OHE patients, compared to the rest and controls. Stroop performance was also significantly impaired in those with MHE, compared to those without MHE, according to SPTs, ICTs, and PHES (all P < 0.0001). A cutoff of >274.9 seconds (Ontime plus Offtime) had an area under the curve of 0.89 in all patients and 0.84 in patients without previous OHE for MHE diagnosis using SPT as the gold standard. The validation cohort showed 78% sensitivity and 90% specificity with the >274.9-seconds Ontime plus Offtime cutoff. App result patterns were similar between the centers. Test-retest reliability in controls and those without previous OHE was good; a learning effect on Ontime in patients with cirrhosis without previous OHE was noted. The Stroop smartphone app is a short, valid, and reliable tool for screening of MHE.

White matter abnormalities correlate with neurocognitive performance in patients with HBV-related cirrhosis

BackgroundWhite matter (WM) abnormalities are common in cirrhotic patients and possibly contribute to hepatic encephalopathy (HE), a frequent neuropsychiatric complication of cirrhosis. However, little is known about these WM abnormalities and their relationship to neurocognitive deficits in patients with HBV-related cirrhosis. MethodsThree-dimensional T1-weighted magnetic resonance imaging and diffusion tensor imaging (DTI) scans were obtained from 67 patients with HBV-related cirrhosis and 40 controls. Voxel-based morphometry and voxel-based DTI were performed to detect macroscopic atrophy and damage to the microstructural integrity of the WM, respectively. Correlation analyses were performed to investigate the relationships between WM abnormalities and neurocognitive performances. ResultsPatients with cirrhosis exhibited significantly decreased WM volume and fractional anisotropy (FA) values, especially in the corpus callosum, thalamus, extra-nuclear area, sensorimotor area, fusiform gyrus, lingual gyrus, and frontal lobes. These abnormalities were more severe with increasing Child–Pugh stage, minimal HE, and previous overt HE. Changes in the corpus callosum, frontal lobe, sensorimotor area, internal capsule, and temporal–occipital lobes were correlated with poor neurocognitive performance. Also, the significantly decreased global WM volume and mean FA value were correlated with poor neurocognitive performances. ConclusionsDiffuse WM abnormalities are common in patients with HBV-related cirrhosis. Advanced liver disease and episodes of HE are two factors associated with WM abnormalities. The correlation between poor neurocognitive performance and WM abnormalities suggests that WM abnormalities may be one of mechanisms underlying neurocognitive deficits in patients with HBV-related cirrhosis.

Previous overt hepatic encephalopathy rather than minimal hepatic encephalopathy impairs health‐related quality of life in cirrhotic patients

It has been observed that overt hepatic encephalopathy (HE) is accompanied by a persistent cognitive defect, suggesting that HE may not be fully reversible. The health-related quality-of-life (HRQoL) has been shown to be impaired by cirrhosis, and, according to some reports, influenced by minimal HE. Little is known about the effect of previous HE on HRQoL. To investigate the relative impact of previous HE and minimal HE on HRQoL in a group of consecutively hospitalized cirrhotic patients. Seventy five consecutive cirrhotic patients were evaluated using the Psychometric HE Score (PHES) and simplified Psychometric HE Score (SPHES) to detect the presence of minimal HE and using SF-36 to assess the HRQoL, both corrected for age and education. Eighteen of them had previous bouts of overt HE. Minimal HE was significantly more frequent in patients with previous HE than in those without (p<0.001), independently on the method used for the diagnosis (PHES or SPHES). A deeper impairment in several domains of SF-36 was observed in patients with previous bouts of overt HE, in those with ascites, as well as in those with decompensated cirrhosis. At multivariate analysis, ascites, MELD score and previous HE were independently related to the mental-component-summary (MCS) of SF-36, whereas ascites was the only variable independently associated with the physical-component-summary (PCS) of SF-36. Minimal HE (independently on the method used for its diagnosis) impaired only one domain of SF-36. These data suggest that previous bouts of HE, despite their complete clinical resolution, play an independent role in producing a persistent impairment in HRQoL of cirrhotics.

Evidence of Persistent Cognitive Impairment After Resolution of Overt Hepatic Encephalopathy

The Inhibitory Control Test has been proposed as a tool to detect the persistence of cognitive defects after the resolution of overt hepatic encephalopathy (OHE). We tested learning abilities of cirrhotic patients using the Psychometric Hepatic Encephalopathy Score (PHES). One hundred six cirrhotic patients who agreed to be examined twice within 3 days were studied using the PHES. Twenty-seven patients had previous OHE; of the remaining 79 patients, 34 were affected by minimal HE and 45 were normal. Among patients without previous OHE, PHESs significantly improved at the second examination; this learning effect was present in the patients with or without minimal HE. To the contrary, learning ability was lost in patients with previous OHE. Even among the 8 patients with history of HE and normal PHESs in the first examination, repeated testing showed a lack of learning capacity. HE is not a fully reversible condition. Residual cognitive impairments should be evaluated by specific tests, based on patients' learning capacities.