Covert Hepatic Encephalopathy Research Articles

Diagnostic role of serum brain-derived neurotrophic factor in HCV cirrhotic patients with minimal hepatic encephalopathy with and without schistosomiasis

Abstract Background Liver cirrhosis (LC) advances from an asymptomatic phase (compensated cirrhosis) to a symptomatic phase (decompensated cirrhosis). Up to 80% of patients with LC may experience minimal hepatic encephalopathy (MHE), which is the first stage of hepatic encephalopathy (HE). Due to the lack of serum indicators, the diagnosis of MHE is frequently based on neuropsychometric tests. Therefore, this study aimed to evaluate the role of brain-derived neurotrophic factor (BDNF) as a diagnostic marker for MHE in HCV cirrhotic patients with or without hepatic schistosomiasis. Patients and methods The study consisted of 60 patients with divided into 3 groups (20 patients with HCV-related LC with overt HE, 20 patients with HCV-related LC without overt HE, and 20 patients with HCV-related LC and hepatic schistosomiases co-infection without overt HE) as well as 20 healthy controls. Patients without overt HE were evaluated for MHE by psychometric tests (trail making tests A and B). Serum BDNF was measured in all patients as well as healthy controls. Results Serum BDNF was found to be significantly lower in patients with LC regardless of etiology than in healthy controls; however, no statistically significant difference was found between patients with and without overt HE. Upon subdivision of patients without overt HE into “normal” and “deficient” using psychometric tests, serum BDNF was found to be significantly lower in patients with overt as well as those with “deficient” psychometric tests (have MHE). Serum BDNF had a sensitivity of 65.85% and specificity of 84.62%, and positive predictive value (PPV) was 82.0%, and negative predictive value (NPV) was 70.0% for diagnosis of MHE. Conclusion Serum BDNF concentration was found to be significantly lower in patients with deficient psychometric tests having either overt or covert HE which suggests that serum BDNF can be used as a diagnostic marker for MHE.

Possible pathogenetic role of ammonia in liver cirrhosis without hyperammonemia of venous blood: The so-called latency period of abnormal ammonia metabolism.

Ammonia plays a crucial role in the pathogenesis of hepatic encephalopathy. Ammonia is also involved in many other pathological conditions seen in cirrhosis, such as sarcopenia, liver fibrosis, hepatocellular injury, immune dysfunction, and hyperammonemia. Furthermore, the ammonia level of the veins is a useful prognostic factor for cirrhosis. In cirrhosis without hyperammonemia of the vein, however, covert hepatic encephalopathy has been reported. This discrepancy is because of the anatomical features of ammonia metabolism. There are two systems in the body for detoxifying ammonia: one is the urea cycle in the liver, and the other is the glutamine synthesis pathway in skeletal muscle and other tissues. The blood processed in the liver's urea cycle is then transported via arteries to various organs. Further processing occurs in the brain and skeletal muscle's glutamine synthesis pathway before entering the veins. When the urea cycle function decreases in cirrhosis, the ammonia levels in the artery increase. In response, the glutamine synthesis pathway compensates by increasing the capacity to process ammonia. Therefore, the ammonia concentration in the veins downstream of skeletal muscles does not increase immediately. However, the brain and skeletal muscles, which receive arterial blood, might be exposed to high ammonia concentrations. In addition, branched-chain amino acids in venous blood decrease. This period is the transition phase from early- to late-phase cirrhosis, and understanding the pathophysiology during this stage is extremely important for preventing the progression of cirrhosis.

Covert hepatic encephalopathy is associated with aggressive disease progression and poor survival in patients with cirrhosis.

Covert hepatic encephalopathy (CHE) negatively affects the health-related quality of life and increases the risk of overt HE (OHE) in patients with liver cirrhosis. However, the impact of CHE on long-term patient outcomes remains controversial. This study aimed to explore the association between CHE and disease progression and survival among cirrhotic patients. This was a single-center prospective study that enrolled 132 hospitalized patients with cirrhosis, with an average follow-up period of 45.02 ± 23.06 months. CHE was diagnosed using the validated Chinese standardized psychometric hepatic encephalopathy score. CHE was detected in 35.61% cirrhotic patients. During the follow-up, patients with CHE had a higher risk of developing OHE (log-rank 5.840, P = 0.016), exacerbation of ascites(log-rank 4.789, P = 0.029), and portal vein thrombosis (PVT) (log-rank 8.738, P = 0.003). Cox multivariate regression analyses revealed that CHE was independently associated with the occurrence of OHE, exacerbation of ascites, and PVT. Furthermore, patients with progression of cirrhosis were more likely to be diagnosed as CHE (log-rank 4.462, P = 0.035). At the end of the follow-up, patients with CHE had a lower survival rate compared to those without CHE (log-rank 8.151, P = 0.004). CHE diagnosis (hazard ratio 2.530, P = 0.008), together with elder age and higher Child-Pugh score, were risk factors for impaired survival in cirrhotic patients. CHE is associated with disease progression and poor survival in patients with cirrhosis, indicating that CHE may serve as an independent predictor of poor prognosis among these patients.

Higher scores in the Clinical Frailty Scale are associated with covert and overt hepatic encephalopathy in patients with cirrhosis

BackgroundFrailty increases the vulnerability to internal and external stressors and may therefore be an indicator of a higher frequency of cirrhosis complications. We aimed to investigate the association of the Clinical Frailty Scale (CFS) with covert (CHE) and overt HE (OHE) development in patients with cirrhosis. MethodsThis study analyzed data of 228 patients with cirrhosis. Frailty was assessed using CFS. Patients were examined for the presence of CHE (using PHES) at study inclusion and followed for OHE. ResultsMedian CFS was 3 and 26 (11 %) patients were at least pre-frail (CFS>3). In multivariable logistic regression analysis in patients without a history of OHE (n = 195), a higher CFS was associated with the presence of CHE at baseline (OR 1.6, p = 0.039). During follow-up, 42 (18 %) patients developed an episode of OHE. In multivariable competing risk regression analyses, a higher CFS was independently associated with the development of an OHE episode in the total cohort (sHR 1.97, p < 0.001) and in the subcohort of patients without a history of OHE (sHR 1.88, p = 0.008). ConclusionCFS appears to be a reliable tool to identify patients at higher risk of HE in whom intensified monitoring and treatment may be justified.

Working Memory in Patients with Varying Degree of Hepatic Encephalopathy (HE): A Pilot EEG-fNIRS Study.

It is known that patients with covert hepatic encephalopathy (CHE) exhibit working memory abnormalities, but to date there is no study comparing patients with cirrhosis with/without CHE and controls with both electrophysiological and hemodynamic data collected at the same time.Here we collected behavioral [accuracy and reaction times (RTs), electrophysiological (evoked potentials) and hemodynamic (oxygenated and deoxygenated haemoglobin) correlates of an n-back task [formed by a control (0-back) condition, a low (1-back) and a high (2-back) working memory load conditions] in patients with cirrhosis with/without CHE: (1) at baseline (n = 21, males = 15, 58±8 yrs), and by comparison with controls (n = 21, males = 15, 57±11 yrs) and (2) after a 3-month course of rifaximin (n = 18, males = 12, 61±11 yrs), and by comparison to baseline.All patients showed slower RTs (p < 0.0001) and lower P2 amplitude compared with controls (p = 0.018); moreover, patients with CHE showed reduced accuracy (p < 0.0001) compared with controls, and patients without CHE showed higher oxygenated haemoglobin in the central dorsolateral prefrontal cortex in the 2-back compared with patients with CHE. Post-rifaximin, oxygenated haemoglobin increased in the central frontopolar cortex. In addition, in patients without CHE the RTs of the 2-back became comparable to those of the 0-back and P3 showed higher amplitude.In conclusion, the presence of cirrhosis seemed to have more effects than CHE on working memory at baseline. A course of treatment with rifaximin was more beneficial to patients without CHE, who probably had more room for improvement in this complex task.

QuickStroop Predicts Time to Development of Overt Hepatic Encephalopathy and Related Hospitalizations in Patients With Cirrhosis

Cirrhosis-related neurocognitive impairment caused by covert or minimal hepatic encephalopathy (CHE) affects psychosocial function, increases risk of overt hepatic encephalopathy (OHE) development, and worsens survival.1,2 However, detection in clinical practice is challenging.2 One modality used for screening and prediction of outcomes related to cirrhosis is the EncephalApp Stroop, but it can require up to 10 minutes. Furthermore, the assessment comprises of distinct stages of difficulty, with an easier "Off" stage and a more challenging "On" stage.3 To alleviate these concerns, QuickStroop, which takes <1 minute, was developed. This uses only the first 2 runs of the Off stage of the EncephalApp Stroop, where number signs presented in red, green, or blue need to be matched quickly to their respective colors.4 A prior study showed these versions were comparable cross-sectionally to diagnose CHE.4 However, the utility of QuickStroop to predict cirrhosis-related outcomes is unclear.5-7 Our aim was to determine the ability of QuickStroop to determine time to development of OHE and OHE-related hospitalizations, all-cause hospitalizations, and death in outpatients with cirrhosis.

P15 Higher Scores in the Clinical Frailty Scale Are Associated With Covert and Overt Hepatic Encephalopathy in Patients With Cirrhosis

P15 Higher Scores in the Clinical Frailty Scale Are Associated With Covert and Overt Hepatic Encephalopathy in Patients With Cirrhosis

P45 Multimodal Assessment of Covert Hepatic Encephalopathy and Its Outcome in a Prospective Cohort of Outpatients With Chronic Liver Disease

P45 Multimodal Assessment of Covert Hepatic Encephalopathy and Its Outcome in a Prospective Cohort of Outpatients With Chronic Liver Disease

Animal naming test is a simple and valid tool for detecting covert hepatic encephalopathy and predicting outcomes in Chinese-speaking regions: a preliminary study

Background and aims Hepatic encephalopathy (HE) implies high morbidity and mortality. The assessment of covert HE (CHE) [i.e. minimal HE (MHE) plus grade 1 HE] is often neglected in Taiwan. Therefore, the aim was to investigate the potential of the animal naming test (ANT1 and simplified ANT1 (S-ANT1)) for assessing CHE in Chinese-speaking regions, specifically Taiwan. Methods A prospective cohort study was conducted, comprising 65 cirrhotic patients and 29 healthy controls (relatives of the patients). Patients were followed up every three months and censored after two years or until death. Hospitalization for overt HE (OHE) and mortality were considered. All subjects underwent ANT1, psychometric HE score (PHES), and mini-mental state examination (MMSE). The patients underwent an electroencephalogram (EEG) to detect slowing indicative of MHE. Cut-off values for ANT1 and S-ANT1 were assessed by ROC analysis and Youden’s index, considering CHE as a reference. The prognostic values for OHE and OHE-free survival were assessed. Results Preliminary analysis confirmed that PHES ≤-4 is a good discriminant point for abnormal results. CHE was found in 29 patients: 9 had MHE (PHES ≤ -4 or altered EEG) and 20 had grade 1 HE. ANT1 and S-ANT1 were found to have diagnostic values for CHE: AUC = 0.807, 0.786; cut off: 18 and 19, respectively. ANT1 and S-ANT1 were found to have prognostic value for OHE, number of hospitalization episodes for OHE, and OHE recurrence-free survival. Conclusions ANT1 shows promise as a tool for CHE detection, quantification, and follow-up in Taiwan and other Chinese-speaking regions. Key messages The animal naming test (ANT1) is a simple and valid semantic fluency test that can be easily performed in outpatient or bedside settings in one minute and can also be used as a tool for covert hepatic encephalopathy (CHE) detection, quantification, and follow-up in Taiwan, other Chinese-speaking regions, and many other countries. The diagnostic value of ANT1 and S-ANT1 for CHE were found to be significant, with area under the receiver operating characteristic curve (AUROC) values of 0.807 and 0.786 respectively, and cut-off scores of 18 and 19. ANT1 and S-ANT1 have prognostic value for the first breakthrough of overt hepatic encephalopathy (OHE), number of hospitalization episodes for OHE, and OHE recurrence-free survival, independent of the MELD score.

WED-364 - Activation of the kynurenine pathway potentially underlies neurodegeneration in patients with covert hepatic encephalopathy

WED-364 - Activation of the kynurenine pathway potentially underlies neurodegeneration in patients with covert hepatic encephalopathy

WED-377 - Poorer results in the clinical frailty scale are associated with covert and overt hepatic encephalopathy in patients with cirrhosis

WED-377 - Poorer results in the clinical frailty scale are associated with covert and overt hepatic encephalopathy in patients with cirrhosis

Prevalence and Risk Factors of Covert Hepatic Encephalopathy in Cirrhotic Patients: A Multicenter Study in China.

We aimed to determine the prevalence of covert hepatic encephalopathy (CHE) in cirrhotic patients from China and to investigate its risk factors. A multicenter prospective observational study was conducted from January 2021 to March 2022 in 16 centers to investigate the impact factors of CHE and establish a prognostic model for CHE episodes. Totally 528 patients were enrolled in the analysis. Based on the anomalies of both PHES and Stroop test results, the prevalence of CHE was 50.4% (266/528), and the consistency between these two tests was 68.9%. Advanced age (OR = 1.043; 95% CI: 1.022-1.063, P < 0.001), low education level (OR = 0.891; 95% CI: 0.832-0.954, P = 0.001), poor Child-Pugh score (OR = 1.142; 95% CI: 1.029-1.464, P = 0.025), and high BUN concentration (OR = 1.126; 95% CI: 1.038-1.2221, P = 0.004) were associated with CHE episodes. According to the chronic Liver Disease Questionnaire (CLDQ), CHE patients had lower scores for abdominal symptoms and systemic symptoms (P < 0.001), which reflected the poor health-related quality of life (HRQoL). According to the stepwise Cox regression hazard model analysis, we established a nomogram for determining the probabilities of CHE episodes, and the AUC was 0.733 (95% CI: 0.679-0.788) in the training cohort and 0.713 (95% CI: 0.628-0.797) in the validation cohort. CHE was a common complication of cirrhosis in China. It is necessary to carry out more large-scale studies with longer follow-up periods to determine the natural history of Chinese CHE patients. This article is protected by copyright. All rights reserved.

Elevated serum levels of glial fibrillary acidic protein are associated with covert hepatic encephalopathy in patients with cirrhosis

Blood biomarkers facilitating the diagnosis of covert hepatic encephalopathy (CHE) in patients with cirrhosis are lacking. Astrocyte swelling is a major component of hepatic encephalopathy. Thus, we hypothesised that glial fibrillary acidic protein (GFAP), the major intermediate filament of astrocytes, might facilitate early diagnosis and management. This study aimed to investigate the utility of serum GFAP (sGFAP) levels as a biomarker of CHE. In this bicentric study, 135 patients with cirrhosis, 21 patients with ongoing harmful alcohol use and cirrhosis, and 15 healthy controls were recruited. CHE was diagnosed using psychometric hepatic encephalopathy score. sGFAP levels were measured using a highly sensitive single-molecule array (SiMoA) immunoassay. In total, 50 (37%) people presented with CHE at study inclusion. Participants with CHE displayed significantly higher sGFAP levels than those without CHE (median sGFAP, 163pg/ml [IQR 136; 268] vs. 106pg/ml [IQR 75; 153]; p <0.001) or healthy controls (p <0.001). sGFAP correlated with results in psychometric hepatic encephalopathy score (Spearman's ρ=-0.326, p <0.001), model for end-stage liver disease score (Spearman's ρ= 0.253, p= 0.003), ammonia (Spearman's ρ= 0.453, p= 0.002), and IL-6 serum levels (Spearman's ρ= 0.323, p= 0.006). Additionally, sGFAP levels were independently associated with the presence of CHE in multivariable logistic regression analysis (odds ratio 1.009; 95% CI 1.004-1.015; p <0.001). sGFAP levels did not differ between patients with alcohol-related cirrhosis vs. patients with non-alcohol-related cirrhosis or between patients with ongoing alcohol use vs. patients with discontinued alcohol use.Conclusions: sGFAP levels are associated with CHE in patients with cirrhosis. These results suggest that astrocyte injury may already occur in patients with cirrhosis and subclinical cognitive deficits and that sGFAP could be explored as a novel biomarker. Blood biomarkers facilitating the diagnosis of covert hepatic encephalopathy (CHE) in patients with cirrhosis are lacking. In this study, we were able to demonstrate that sGFAP levels are associated with CHE in patients with cirrhosis. These results suggest that astrocyte injury may already occur in patients with cirrhosis and subclinical cognitive deficits and that sGFAP could be explored as a novel biomarker.

Psychometric tests, critical flicker frequency, and inflammatory indicators in covert hepatic encephalopathy diagnosis.

Hepatic encephalopathy (HE) is a frequent complication of liver diseases. Systemic inflammation is key for HE pathogenesis. The main goal of the study was to investigate the role of psychometric tests, critical flicker frequency (CFF), and comparative evaluation of inflammatory indicators for the diagnosis of covert HE (CHE). The study was a prospective, nonrandomized, case-control study with a total of 76 cirrhotic patients and 30 healthy volunteers. The West Haven criteria were used to determine the occurrence of CHE in cirrhotic patients. Psychometric tests were applied to healthy and cirrhotic groups. CFF, venous ammonia, serum endotoxin, IL-6, IL-18, tumor necrosis factor alpha (TNF-α) levels, and hemogram parameters were evaluated for cirrhotic patients. CFF values and psychometric tests were found to accurately discriminate CHE positives from CHE negatives (p<0.05). When the control group was excluded, the digit symbol test and the number connection A test failed, unlike CFF and other psychometric tests. Using CFF, a 45 Hz cutoff value had 74% specificity and 75% sensitivity. Basal albumin levels (p=0.063), lymphocyte-to-monocyte ratio (LMR) (p=0.086), and neutrophil-to-lymphocyte ratio (p 0.052) were significant, albeit slightly, among CHE groups. Basal albumin levels had 50% sensitivity and 71% specificity when 2.8 g/dL was used as a cutoff value to determine CHE. Both psychometric tests and CFF can be useful in diagnosing CHE. Using cytokine and endotoxin levels seems to be inadequate to diagnose CHE. Using LMR and albumin levels instead of psychometric tests for diagnosing CHE can be promising.

Evolution of hepatic encephalopathy over time: ecological data from a tertiary referral centre for hepatology.

Few data on hepatic encephalopathy (HE) over time are available, thus our aim was to study its evolution in patients with varying degree of HE on first assessment. Eighty-six patients with cirrhosis (age=58±11 years; males=72) were evaluated 2-10 times for liver transplantation selection purposes, differential diagnosis or treatment optimization. The presence/severity of HE was assessed by clinical and neuropsychiatric indices [ Psychometric Hepatic Encephalopathy Score (PHES) and electroencephalography (EEG)] and the severity of liver disease by the Model for End-Stage Liver Disease (MELD) score. Treatment was instituted/modified after each evaluation. Amongst 23 unimpaired patients, 56/6% remained unimpaired, 35/3% developed covert HE, 9/0% developed overt HE on second/third evaluation. Amongst 32 patients with covert HE, 25/10% became unimpaired, 44/19% remained covert, 31/13% developed overt HE. Finally, amongst 32 patients with overt HE, 19/16% became unimpaired, 25/13 % became covert and 56/25% remained overt. PHES results improved in patients with overt HE and EEG worsened over time (despite remaining normal) in unimpaired patients. In patients with multiple evaluations, HE evolution was manifold and difficult to predict. HE evolution over time is variable and largely dependent on HE history/management. These data support the concept that HE is an essentially reversible condition.

A simple covert hepatic encephalopathy screening model based on blood biochemical parameters in patients with cirrhosis.

Covert hepatic encephalopathy (CHE) adversely affects clinical outcomes in patients with liver cirrhosis, although its diagnosis is difficult. This study aimed to establish a simple CHE screening model based on blood-related biochemical parameters. This retrospective study enrolled 439 patients who were assessed for CHE using a neuropsychiatric test between January 2011 and June 2019. A simple CHE (sCHE) score was calculated with hypoalbuminemia (≤ 3.5 g/dL) and hyperammonemia (≥ 80 μg/dL) as 1 point each. The association between sCHE score and CHE or overt hepatic encephalopathy (OHE) was assessed using logistic regression and Fine-Gray competing risk regression models. Of 381 eligible patients, 79 (21%) were diagnosed with CHE. The distribution of sCHE scores was 48% with 0 point, 33% with 1 point, and 19% with 2 points. Patients with sCHE score ≥ 1 point had a higher prevalence of CHE than those with sCHE score of 0 (27% vs. 14%, P = 0.002). A cut-off value of 1 point showed high discriminative ability for identifying CHE, with a sensitivity of 0.67, specificity of 0.56, positive predictive value of 0.27, and negative predictive value of 0.86. During the median follow-up period of 2.2 years, 58 (15%) patients developed OHE. Multivariate analysis showed that sCHE score ≥ 1 (sub-distribution hazard ratio [SHR], 2.69; 95% confidence interval [CI], 1.41-5.15) and CHE (SHR, 2.17; 95% CI, 1.26-3.73) independently predicted OHE. The sCHE score is a useful screening model for identifying patients with CHE and for predicting OHE occurrence.

Predicting which patients with cirrhosis will develop overt hepatic encephalopathy: Beyond psychometric testing.

It remains challenging to identify covert hepatic encephalopathy and predict progression to overt hepatic encephalopathy. Psychometric testing is a widely used diagnostic modality, but it is often inaccurate and difficult to implement in diverse populations, making it a less than ideal assessment. Alternatively, by using easily accessible data from the electronic health record, simple clinical assessment tools, and patient-reported outcomes, we may be better able to predict hepatic encephalopathy across multiple populations. Furthermore, incorporation of patient-reported outcomes into our diagnostic toolset not only aids detection of covert hepatic encephalopathy and prediction of overt hepatic encephalopathy, but also allows us to target therapies and track their impact. Herein, we outline a potential algorithm based on these easily integrated tools to promote patient risk-stratification and early therapeutic intervention.

A shortened Stroop test to identify covert hepatic encephalopathy and predict overt hepatic encephalopathy in patients with cirrhosis.

Covert hepatic encephalopathy (CHE) adversely affects the clinical outcomes of patients with cirrhosis but remains largely undiagnosed and untreated. Although the Stroop test is a useful method for CHE detection, a faster, simpler, and more accurate test is required to diagnose CHE. This prospective study aimed to develop a new shortened Stroop test that can detect CHE and predict overt hepatic encephalopathy (OHE) in Japanese patients with cirrhosis. Patients who underwent neuropsychological tests (NPT) and the Stroop test between November 2018 and December 2021 were enrolled and followed until OHE occurrence or March 2022. The discriminative ability of various run combinations in the off and on states to detect CHE was evaluated using the area under the receiver-operating characteristic curve (AUC) and compared with that of the total Stroop test time. Among the 227 eligible patients, the On1-2Time cutoff value of 44.4s had a comparable discriminative ability with the total Stroop test time to detect CHE, with an AUC of 0.791, a sensitivity of 0.827, and a specificity of 0.685. During a median follow-up period of 16months, 37 patients developed OHE. On1-2Time ≥ 44.4s (hazard ratio [HR], 3.93; 95% confidence interval [CI] 1.36-11.36) and serum albumin levels (HR, 0.28; 95% CI 0.11-0.67) were independently associated with OHE occurrence. The shortened Stroop test (On1-2Time) is equivalent to the total Stroop test not only for identifying CHE but also for estimating the risk of progression to OHE.

The impact of rifaximin on the hospital burden and infections in patients with hepatic encephalopathy: a retrospective observational study.

Advanced liver disease frequently culminates in hepatic encephalopathy (HE), which can be classified as covert or overt HE, with subtle or clinically obvious changes respectively. 30-40% of patients with cirrhosis develop overt HE, which negatively affects the patients' quality of life. Next to lactulose, rifaximin-α has been prescribed as a second line therapy to treat and reduce the risk of recurrence of overt HE. In this study, we aimed to evaluate the effect of rifaximin-α therapy, both on the number of occurring infections and on the evolution in hospital admissions of patients with overt HE. A total of 66 cirrhotic patients, treated for at least 6 months with rifaximin-α at AZ Maria Middelares, between October 1st 2014 and January 1st 2020, were included in the study analysis. Medical records of all patients were evaluated over a period of 6 months prior and after initiation of rifaximin-α therapy. Data analysis revealed that the included cirrhotic patients were severely ill, with a mean model for end-stage liver disease (MELD) score of 21, and a median Child Pugh score of 11. Among these patients, rifaximin-α treatment significantly downgraded the total number of infections, with a main effect on respiratory infections. Furthermore, rifaximin-α therapy led to a significant decrease in HE-related, as well as in other liver-related hospital admissions. This study confirms the potential value of rifaximin-aα in reducing the number of developing infections and hospital admissions in a severely ill cirrhotic patient population.

Systematic Review and Meta-Analysis on the Effects of Lactulose and Rifaximin on Patient-Reported Outcomes in Hepatic Encephalopathy.

Patients with hepatic encephalopathy (HE) suffer from significant symptoms and impaired quality of life. Improved understanding on the potential benefits of first-line HE therapies may aid patient-provider discussions regarding expected benefits of HE treatments. We aimed to perform a systematic review to assess the effects of lactulose and rifaximin on patient-reported outcomes (PROs). We searched MEDLINE, EMBASE, and Cochrane Library databases for randomized trials or prospective cohort studies using lactulose and/or rifaximin for the management of HE and assessing changes in PRO using PRO instruments. Physician reviewers independently reviewed titles, abstracts, and full texts and extracted data independently. We performed random-effects meta-analyses to examine the effects of lactulose and rifaximin on PROs. We identified 16 studies representing 1,376 patients that met inclusion criteria. Most studies assessed treatment of covert HE. In patients with covert HE, lactulose significantly improved overall patient-reported health-related quality of life measured by the Sickness Impact Profile with an estimated pooled mean difference of 6.92 (95% confidence interval: 6.66-7.18) and showed improvements in several subscales. Conversely, rifaximin demonstrated a nonstatistically significant mean difference in the total Sickness Impact Profile of 4.76 (95% confidence interval: -4.23 to 13.76), with strong evidence of heterogeneity between these studies. Studies examining other PRO instruments showed improvements in overall health-related quality of life, social functioning, and sleep from both lactulose and rifaximin. Patients with HE treated with lactulose or rifaximin reported improvements in important PROs. These results may inform provider-patient communication and help manage patient expectations regarding the potential benefits of HE therapies.