Risk Of Overt Hepatic Encephalopathy Research Articles

S1660 Rifaximin Monotherapy Is More Effective Than Lactulose Monotherapy for Reducing the Risk of Overt Hepatic Encephalopathy (OHE) Recurrence and All-Cause Mortality: An Analysis of Two Randomized Trials

S1660 Rifaximin Monotherapy Is More Effective Than Lactulose Monotherapy for Reducing the Risk of Overt Hepatic Encephalopathy (OHE) Recurrence and All-Cause Mortality: An Analysis of Two Randomized Trials

Reduced risk of overt hepatic encephalopathy and death after transjugular intrahepatic portosystemic shunt in patients with hepatic venovenous communications

PurposeHepatic venovenous communications (HVVC) is detectable in more than one-third of cirrhotic patients, where portal hypertension (PHT) tends to present more severely. We aimed to explore the prognostic implications of HVVC in patients with sinusoidal PHT treated by transjugular intrahepatic portosystemic shunt (TIPS). MethodThe multicenter data of patients (2020–2022) undergoing balloon-occluded hepatic venography during TIPS were retrospectively analyzed. Pre-TIPS total bile acids (TBA) levels in portal, hepatic and peripheral veins were compared between groups. The primary endpoint was the development of overt hepatic encephalopathy (HE) within one year after TIPS. Results183 patients were eligible and classified by the presence (n = 69, 37.7 %) or absence (n = 114, 62.3 %) of HVVC. The agreement between wedged hepatic venous pressure and portal venous pressure was poor in HVVC group (intraclass correlation coefficients [ICC]: 0.141, difference: 13.4 mmHg, p < 0.001), but almost perfect in non-HVVC group (ICC: 0.877, difference: 0.4 mmHg, p = 0.152). At baseline, patients with HVVC had lower Model for end-stage liver disease scores (p < 0.001), blood ammonia levels (p < 0.001), TBA concentrations in the hepatic (p = 0.011) and peripheral veins (p = 0.049) rather than in the portal veins (p = 0.516), and a higher portosystemic pressure gradient (p = 0.035), suggesting more effective intrahepatic perfusion in this group. Within 1-year post-TIPS, HVVC group had a lower incidence of overt HE (11.7 % vs. 30.5 %, p = 0.004, HR: 0.34, 95 % CI: 0.16–0.74, absolute risk difference [ARD]: −17.4) and an improved liver transplantation-free survival rate (97.1 % vs. 86.8 %, p = 0.021, HR: 0.16, 95 % CI: 0.05–0.91, ARD: −10.3). ConclusionsFor patients with sinusoidal PHT treated by TIPS, the presence of HVVC was associated with a reduced risk of overt HE and a potential survival benefit.

Body Compositions Correlate With Overt Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt: A Multicentre Cohort Study.

The relationship between body composition and the risk of overt hepatic encephalopathy (OHE) following transjugular intrahepatic portosystemic shunt (TIPS) needs to be investigated. Overall, 571 patients from 5 medical centers were included. To assess body compositions, we evaluated skeletal muscle indices, adipose tissue indices, sarcopenia, and myosteatosis at the third lumbar vertebral level. Univariate and Multivariate logistic regression analyses were performed to identify independent risk factors for post-TIPS OHE. An integrated score was then constructed using stepwise multiple regression analyses, with a cut-off value selected using the best Youden index. Finally, the Akaike information criterion (AIC) was performed to compare the integrated score and independent risk factors on their ability in predicting post-TIPS OHE. Sarcopenia and all skeletal muscle indices had limited associations with post-TIPS OHE. The index of the subcutaneous adipose tissue (SATI) (P=0.005; OR: 1.034, 95% CI: 1.010-1.058) and myosteatosis (297 cases, 52.01%, 125 with OHE, 42.09%; P=0.003; OR: 1.973; 95% CI: 1.262-3.084) were both ascertained as independent risk factors for post-TIPS OHE. The integrated score (ScoreALL=1.5760 + 0.0107 * SATI + 0.8579 * myosteatosis) was established with a cutoff value of -0.935. The akaike information criterion (AIC) of ScoreALL, SATI, and myosteatosis was 655.28, 691.18, and 686.60, respectively. SATI and myosteatosis are independent risk factors for post-TIPS OHE. However, the integrated score was more significantly associated with post-TIPS OHE than other skeletal muscle and adipose tissue factors.

Nutritional counseling improves mortality and prevents hepatic encephalopathy in patients with alcohol-associated liver disease.

Nutritional counseling improves malnutrition, which determines the prognosis of patients with chronic liver disease. In this study, we investigated the effects of nutritional counseling on mortality and the risk of overt hepatic encephalopathy (HE) in patients with alcohol-associated liver disease. In this retrospective cohort study, we included 211 patients with alcohol-associated liver disease who visited Gifu University Hospital between August 2008 and June 2023. Patients were classified into two groups according to the frequency of nutritional counseling by a registered dietitian. The primary outcomes were all-cause mortality and overt HE. Propensity score matching analysis was performed to adjust for potential confounders. Among the patients (median age 67years; 88% men; and median Model for End-Stage Liver Disease score, 9), 86 (39%) were in the high-frequency (≥2) nutritional counseling group. The high-frequency group had a significantly higher survival rate (46% vs. 25%) and a lower incidence of overt HE (16% vs. 27%) at 5years than the low-frequency group. Nutritional counseling was associated with a reduced risk of mortality (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.36-0.63) and overt HE (HR 0.64; 95% CI 0.42-0.99), independent of hepatocellular carcinoma and liver function reserve. After propensity score matching, nutritional counseling was still associated with a reduced risk of mortality (HR 0.34; 95% CI 0.19-0.59) and overt HE (HR 0.31; 95% CI 0.11-0.87). Nutritional counseling effectively improves mortality and prevents overt HE in patients with alcohol-associated liver disease, thereby proving essential for the management of these patients.

Myosteatosis is an independent risk factor for overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunting.

The relationship between skeletal muscle and adipose tissue compositions and risk of overt hepatic encephalopathy (OHE) following transjugular intrahepatic portosystemic shunt (TIPS) treatment needs to be investigated. A total of 282 patients were collected from two medical centres. The median time of follow-up was 48.23 + 1.36 months and the first-year results of all patients after TIPS therapy were collected. The muscle and adipose tissue indices were quantified at the third lumbar vertebra level. Sarcopenia and myosteatosis were defined according to previous researches. Receiver operating characteristic curves, chi-square test, univariate and multivariate logistic regression analyses were employed to investigate the potential association between muscle and adipose indices, sarcopenia, myosteatosis and the risk of developing post-TIPS OHE. All skeletal muscle indices, adipose tissue indices and sarcopenia had limited associations with post-TIPS OHE. Myosteatosis (148 cases, 52.5%, 55 with OHE, 37.2%) was identified as an independent risk factor for post-TIPS OHE. with P < 0.001 in Chi-square test, P < 0.001, odds ratio (OR): 2.854, 95% confidence interval (CI): 1.632-4.993 in univariate logistic regression analyses, and P = 0.007, OR: 2.372, 95% CI: 1.268-4.438 in multivariate logistic regression analyses, respectively. Our results showed that myosteatosis was proven as an independent risk factor for the development of post-TIPS OHE.

Identifying Minimal Hepatic Encephalopathy: A New Perspective from Magnetic Resonance Imaging.

Type C hepatic encephalopathy (HE) is a condition characterized by brain dysfunction caused by liver insufficiency and/or portal-systemic blood shunting, which manifests as a broad spectrum of neurological or psychiatric abnormalities, ranging from minimal HE (MHE), detectable only by neuropsychological or neurophysiological assessment, to coma. Though MHE is the subclinical phase of HE, it is highly prevalent in cirrhotic patients and strongly associated with poor quality of life, high risk of overt HE, and mortality. It is, therefore, critical to identify MHE at the earliest and timely intervene, thereby minimizing the subsequent complications and costs. However, proper and sensitive diagnosis of MHE is hampered by its unnoticeable symptoms and the absence of standard diagnostic criteria. A variety of neuropsychological or neurophysiological tests have been performed to diagnose MHE. However, these tests are nonspecific and susceptible to multiple factors (eg, aging, education), thereby limiting their application in clinical practice. Thus, developing an objective, effective, and noninvasive method is imperative to help detect MHE. Magnetic resonance imaging (MRI), a noninvasive technique which can produce many objective biomarkers by different imaging sequences (eg, Magnetic resonance spectroscopy, DWI, rs-MRI, and arterial spin labeling), has recently shown the ability to screen MHE from NHE (non-HE) patients accurately. As advanced MRI techniques continue to emerge, more minor changes in the brain could be captured, providing new means for early diagnosis and quantitative assessment of MHE. In addition, the advancement of artificial intelligence in medical imaging also presents the potential to mine more effective diagnostic biomarkers and further improves the predictive efficiency of MHE. Taken together, advanced MRI techniques may provide a new perspective for us to identify MHE in the future. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

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.

P9 Minimal Hepatic Encephalopathy Is Associated With an Increased Risk of Overt Hepatic Encephalopathy and Poorer Prognosis – A Multicenter Study

P9 Minimal Hepatic Encephalopathy Is Associated With an Increased Risk of Overt Hepatic Encephalopathy and Poorer Prognosis – A Multicenter Study

Overweight/Obesity Increases the Risk of Overt Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt in Cirrhotic Patients.

The purpose of this study was to investigate the effect of body mass index (BMI) on the prevalence of overt hepatic encephalopathy (OHE) after the transjugular intrahepatic portosystemic shunt (TIPS) procedure in decompensated cirrhotic patients. A retrospective observational cohort study of 145 cirrhotic patients receiving TIPS was carried out in our department from 2017 to 2020. The relationships between BMI and clinical outcomes including OHE, as well as risk factors of developing post-TIPS OHE, were analyzed. BMI was categorized as normal weight (18.5 ≤ BMI < 23.0 kg/m2), underweight (BMI < 18.5 kg/m2), and overweight/obese (BMI ≥ 23.0 kg/m2). Among the 145 patients, 52 (35.9%) were overweight/obese and 50 (34%) had post-TIPS OHE. Overweight/obese patients more frequently had OHE compared with normal weight patients (OR: 2.754, 95% CI: 1.236-6.140; p = 0.013). Overweight/obesity (p = 0.013) and older age (p = 0.030) were independent risk factors for post-TIPS OHE according to the logistic regression analysis. Kaplan-Meier curve analysis suggested that overweight/obese patients had the highest cumulative incidence of OHE (log-rank p = 0.0118). In conclusion, overweight/obesity and older age may raise the risk of post-TIPS OHE in cirrhotic patients.

Large Paraumbilical Vein Shunts Increase the Risk of Overt Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Placement.

Background: This study aimed to evaluate whether a large paraumbilical vein (L-PUV) was independently associated with the occurrence of overt hepatic encephalopathy (OHE) after the implantation of a transjugular intrahepatic portosystemic shunt (TIPS). Methods: This bi-center retrospective study included patients with cirrhotic variceal bleeding treated with a TIPS between December 2015 and June 2021. An L-PUV was defined in line with the following criteria: cross-sectional areas > 83 square millimeters, diameter ≥ 8 mm, or greater than half of the diameter of the main portal vein. The primary outcome was the 2-year OHE rate, and secondary outcomes included the 2-year mortality, all-cause rebleeding rate, and shunt dysfunction rate. Results: After 1:2 propensity score matching, a total of 27 patients with an L-PUV and 54 patients without any SPSS (control group) were included. Patients with an L-PUV had significantly higher 2-year OHE rates compared with the control group (51.9% vs. 25.9%, HR = 2.301, 95%CI 1.094−4.839, p = 0.028) and similar rates of 2-year mortality (14.8% vs. 11.1%, HR = 1.497, 95%CI 0.422−5.314, p = 0.532), as well as variceal rebleeding (11.1% vs. 13.0%, HR = 0.860, 95%CI 0.222−3.327, p = 0.827). Liver function parameters were similar in both groups during the follow-up, with a tendency toward higher shunt patency in the L-PUV group (p = 0.067). Multivariate analysis indicated that having an L-PUV (HR = 2.127, 95%CI 1.050−4.682, p = 0.037) was the only independent risk factor for the incidence of 2-year OHE. Conclusions: Having an L-PUV was associated with an increased risk of OHE after a TIPS. Prophylaxis management should be considered during clinical management.

Benefit of probiotics in preventing hepatic encephalopathy among patients with liver cirrhosis: an evidence-based case report

Background: Hepatic encephalopathy (HE) is a serious complication in patients with liver cirrhosis. Its pathogenesis involved the mechanism of HE including endotoxins, ammonia production and other neurotoxins by gut microflora. Probiotic exert potential benefit for gastrointestinal microflora. The use of probiotics may provide substantial benefit for the treatment of HE. Objective: This report aimed to evaluate the benefit of probiotics in preventing HE among liver cirrhosis patients. Methods: Literature searching with keywords of ‘liver cirrhosis’, ‘probiotics’, ‘hepatic encephalopathy’ along with its synonyms and related terms was implemented in Pubmed. Additional hand-search was implemented to obtain the relevant articles Result: Three meta-analyses showed that probiotics are effective to prevent HE development. All meta-analyses obtained similar results, in which the odds ratio (OR) obtained was ranging from 0.22 to 0.42. One randomized controlled trial (RCT) by Dhiman et al showed that probiotics treatment reduces the relative risk of overt HE by 33% compared to placebo. Conclusion: Probiotics administration exert potential to prevent the development of HE in the liver cirrhotic patients. The patient may benefit with the given of probiotics.

Racial and ethnic disparities in rifaximin use and subspecialty referrals for patients with hepatic encephalopathy in the United States

Rifaximin use in combination with lactulose is associated with a decreased risk of overt hepatic encephalopathy (HE). We sought to determine whether race and ethnicity were associated with rifaximin prescriptions. We examined data for a 20% random sample of United States Medicare enrollees with cirrhosis and hepatic encephalopathy treated with outpatient lactulose and Part D prescription coverage from 2011-2019. Beginning at the time of first diagnosis, we evaluated time to first prescription of rifaximin accounting for competing risks (Fine-Gray, yielding subdistribution hazard ratios [sHRs]) and cumulative rifaximin exposure using a gamma hurdle model (yielding exposure length ratios). We aimed to determine the association of race and ethnicity with each outcome, adjusting for demographics, clinical factors, and other features of clinical management. Overall, 29,095 patients were diagnosed with HE and treated with lactulose, of whom 13,272 were prescribed rifaximin. Compared to White patients, Black patients were least likely to receive any prescription for rifaximin (sHR 0.70; 95% CI 0.65-0.76). Asian and Hispanic patients were also less likely to receive rifaximin compared to White patients. Black patients also received fewer doses of rifaximin (exposure length ratio 0.90; 95% CI 0.82-0.98). Hispanic patients also received fewer doses (0.88; 95% CI 0.80-0.98). Out-of-pocket spending on rifaximin per person-year was higher for Black and Hispanic than White patients. Out-of-pocket medication spending was associated with reduced odds of filling a rifaximin prescription. Black and Hispanic patients were least likely to be referred to a gastroenterologist. In a national cohort of patients with HE, we observed stark racial and ethnic disparities in the use of rifaximin, an approved therapy for the improvement of HE-specific outcomes. Access to gastroenterologists and cost controls may reduce disparities. Hepatic encephalopathy is a serious problem that can affect people with cirrhosis. When someone develops hepatic encephalopathy, there are 2 main treatments. The first-line treatment is called lactulose. If episodes of hepatic encephalopathy happen on lactulose, another treatment called rifaximin is recommended. In this study, we found that compared to White patients, Black and Hispanic patients are less likely to be prescribed rifaximin, receive fewer rifaximin refills, spend more on rifaximin, and have less access to subspecialists who are familiar with rifaximin. We conclude that efforts to address the cost of rifaximin and access to gastroenterologists could help improve these disparities.

Development and Validation of Prognostic Models to Estimate the Risk of Overt Hepatic Encephalopathy After TIPS Creation: A Multicenter Study.

INTRODUCTION:Overt hepatic encephalopathy (HE) is a major complication of transjugular intrahepatic portosystemic shunt (TIPS). This study aimed to develop and validate prognostic models to identify patients at different risks of overt HE within 3 months after TIPS.METHODS:Two cohorts of patients with cirrhosis undergoing TIPS insertion were retrospectively included. In the derivation cohort of 276 patients, 3 models were established in increasing order of complexity: core model (age + Child-Pugh class), sarcopenia model (core model + sarcopenia), and full model (sarcopenia model + post-TIPS portal pressure gradient). All models were internally validated for discrimination and calibration and externally validated in an independent cohort of 182 patients.RESULTS:During a 3-month follow-up period, 61 (22.1%) and 33 patients (18.1%) developed overt HE in the derivation and validation cohort, and sarcopenia was associated with increased risk of the outcome. In the derivation cohort, the core model showed a c-statistic of 0.68 (95% confidence interval [CI] 0.61–0.75), and discrimination improved in the sarcopenia model (c-statistic 0.73; 95% CI 0.66–0.80). The full model that extended the core model with inclusion of sarcopenia and post-TIPS portal pressure gradient showed a significant improvement in discriminative ability (0.77; 95% CI 0.71–0.83; P = 0.001). Both sarcopenia and full model yielded comparable performances in the validation cohort.DISCUSSION:We developed and externally validated 2 prediction models applied before (sarcopenia model) and after TIPS (full model) to estimate the risk of post-TIPS overt HE. These tools could aid to select appropriate candidates for TIPS and guide postoperative management.

An Electronic Decision Support Intervention Reduces Readmissions for Patients With Cirrhosis.

Rifaximin use in combination with lactulose is associated with a decreased risk of overt hepatic encephalopathy (HE). We prospectively evaluated the impact of an interruptive electronic medical record alert to indicate rifaximin for patients with cirrhosis and HE on lactulose. The intervention was associated increased rifaximin utilization, particularly for nongastroenterology and hospitalist services odds ratio 1.20 95% confidence interval (1.09-1.31). For patients with HE, the intervention was associated with a lower readmission risk-adjusted subdistribution hazard ratio 0.63 95% confidence interval (0.48-0.82). An interruptive alert in the electronic ordering system was associated with a lower risk of readmissions.

Handgrip strength stratifies the risk of covert and overt hepatic encephalopathy in patients with cirrhosis.

Handgrip strength (HGS) is a simple and convenient method to assess nutrition status in patients with cirrhosis. This retrospective study aimed to investigate the utility of HGS for predicting patients with covert hepatic encephalopathy (CHE) and patients at high risk of overt hepatic encephalopathy (OHE). We reviewed 963 patients with cirrhosis and consequently enrolled eligible 270 patients. HGS was measured using a digital grip dynamometer. CHE was diagnosed using a computer-aided neuropsychiatric test. Factors associated with CHE were estimated using the logistic regression model. Predictors associated with OHE occurrence were analyzed using the Fine-Gray competing risk regression model. Of the 270 eligible patients, reduced HGS was observed in 102 (38%), reduced muscle mass in 107 (40%), and CHE in 53 (20%). Multivariate analysis showed that serum ammonia levels (odds ratio [OR], 2.23; 95% CI, 1.14-4.36; P = 0.014) and reduced HGS (OR, 3.68; 95% CI, 1.93-7.03; P < 0.001) were independently associated with CHE. During the median follow-up period of 24.5 months, 43 (16%) patients experienced OHE. After adjusting for possible confounding factors, multivariate analysis showed that reduced HGS (subdistribution hazard ratio, 2.36; 95% CI, 1.27-4.38; P = 0.007) was a significant predictor in the development of OHE. Patients with reduced HGS had a higher prevalence of CHE and a higher risk for OHE occurrence than those with normal HGS. The measurement of HGS could be a simple bedside modality to stratify the patients' risk for CHE and OHE.

S1014 The Modest Differential Effects of Rifaximin Alone vs Rifaximin Plus Lactulose on Intestinal Microbial Diversity and Composition in Patients With Cirrhosis

INTRODUCTION: Rifaximin, a nonsystemic antibiotic, is indicated in the United States for reducing the risk of overt hepatic encephalopathy (OHE) recurrence in adults and may be used alone or in combination with lactulose. This analysis employed genomic characterization to assess the impact of daily rifaximin alone or rifaximin + lactulose treatment on stool microbiota in patients with a history of OHE. METHODS: In a randomized, open-label trial, patients aged ≥18 y with cirrhosis and history of ≥1 OHE episode during the prior 6 months, currently in HE remission (Conn score ≤1), received rifaximin 550 mg twice daily (BID) or rifaximin 550 mg BID + lactulose (titrated to 2–3 soft stools/d) for 6 months. Stool samples were collected at screening (baseline) and month 6/end of treatment (EOT). Patients were randomly selected for the stool microbiota sequencing analysis substudy. Genomic characterization of microbiota was achieved using 16S rRNA bacterial deep gene sequencing. Metrics included stool microbiota richness (number of bacterial species in a sample, adjusted for different numbers of sequences observed from each sample), evenness (relative abundance of different species [range, 0–1; 1 = complete evenness]), and Shannon diversity index (richness and evenness [overall community complexity]). RESULTS: Sixty-six adults (mean age, 56.0 y; 68.2% male; mean body mass index, 31.7 kg/m2) were randomly selected for stool microbiota analysis (rifaximin alone [n = 34]; rifaximin + lactulose [n = 32]; demographics evenly matched). At baseline, measures of richness and evenness of stool microbiota and Shannon diversity index were similar for rifaximin alone and rifaximin + lactulose groups (Table 1). Stool microbiota richness did not significantly change from baseline to EOT in either group; no significant difference was observed between groups. Significant decreases from baseline to EOT were seen in evenness of stool microbiota and Shannon diversity index in the rifaximin alone group (P < 0.005 for both measures); greater reductions in these parameters were observed in the rifaximin alone group versus the rifaximin + lactulose group (P < 0.05 for both measures). CONCLUSION: Modest effects on stool microbiota diversity and evenness, with no effects on the absolute number of species, were observed in the rifaximin alone group. Concomitant lactulose may offset these effects, but further research is needed. Overall, data support that overall effects to stool microbiota during rifaximin treatment are modest in scope.Table 1

S1013 Lack of Colonic Microbial Cross-Resistance to Other Antibiotics in Patients Treated With Rifaximin Alone vs Rifaximin Plus Lactulose for Reducing the Risk of Overt Hepatic Encephalopathy (OHE) Recurrence

INTRODUCTION: Rifaximin is a nonsystemic antibiotic indicated for reducing the risk of OHE recurrence in adults. The risk of bacterial antibiotic resistance to rifaximin and cross-resistance to other antibiotics is thought to be low, possibly because of minimal systemic absorption. Data are limited on the potential impact of concomitant lactulose. This phase 4 substudy assessed rifaximin ± lactulose on antibiotic susceptibility of fecal bacteria in patients with cirrhosis and a history of overt HE. METHODS: Adults with cirrhosis and history of ≥1 OHE episode during previous 6 months, currently in OHE remission (Conn score ≤1) were randomized to receive open-label rifaximin 550 mg twice daily (BID) or rifaximin 550 mg BID + lactulose (titrated to 2-3 soft stools/d) for 6 months. Stool samples were collected at screening (baseline) and month 6/end of treatment (EOT). Patients were randomly selected for the fecal microbiota antibiotic susceptibility substudy. Bacteria were cultured using standard techniques; susceptibility to several antibiotics, depending on bacterium, was tested by broth or agar dilution methods; and minimum inhibitory concentrations (MIC) were determined. Control strains were included per lab SOP practices. RESULTS: Sixty-four patients (mean age, 55.8 y; 64.1% male) were included (rifaximin: n = 31; rifaximin + lactulose: n = 33). Overall, 376 bacterial isolates were identified: Enterobacteriaceae (36.2%), Enterococcaceae (27.7%), Bacteroidaceae (25.5%) families, Staphylococcaceae (7.2%), and Clostridiaceae (3.5%). Patients in each group had a similar distribution of bacterial families and species at baseline and EOT. Cross resistance to other antibiotics rarely developed (Table 1). CONCLUSION: Rifaximin ± lactulose for up to 6 months did not lead to clinically relevant changes to fecal microbial antibiotic susceptibility profiles. There was no indication of clinically relevant antibiotic resistance with the addition of lactulose to rifaximin therapy for the prevention of OHE recurrence. These data support the clinical safety profile of rifaximin + lactulose in adults with cirrhosis.Table 1

Incidence and Bedside Predictors of the First Episode of Overt Hepatic Encephalopathy in Patients With Cirrhosis.

Hepatic encephalopathy (HE) is associated with marked increases in morbidity and mortality for patients with cirrhosis. We aimed to determine the risk of and predictors for HE in contemporary patients. We prospectively enrolled 294 subjects with Child A-B (70% Child A) cirrhosis and portal hypertension without previous HE from July 2016 to August 2018. The primary outcome was the development of overt HE (grade >2). We assessed the predictive power of model for end-stage liver disease-sodium (MELD-Na) score, the Inhibitory Control Test, the Sickness Impact Profile score, and the Bilirubin-Albumin-Beta-Blocker-Statin score. We also derived a novel predictive model incorporating MELD-Na score, impact of cirrhosis on daily activity (Likert 1-9), frailty (chair-stands per 30 seconds), and health-related quality of life (Short-Form 8, 0-100). The cohort's median age was 60 years, 56% were men, and the median MELD-Na score was 9. During a follow-up of 548 ± 281 days, 62 (21%) had incident overt HE with 1-year probability of 14% ± 2%, 10% ± 2%, and 25% ± 5% for Child A and B. The best model for predicting the risk of overt HE included MELD-Na, Short-Form 8, impact on activity rating, and chair-stands within 30 seconds. This model-MELDNa-Actvity-Chairstands-Quality of Life Hepatic Encephalopathy Score-offered an area under the receiver operating curve (AUROC) for HE development at 12 months of 0.82 compared with 0.55, 0.61, 0.70, and 0.72 for the Inhibitory Control Test, Sickness Impact Profile, Bilirubin-Albumin-Beta-Blocker-Statin, and MELD-Na, respectively. The AUROC for HE-related hospitalization was 0.92. This study provides the incidence of HE in a well-characterized cohort of contemporary patients. Bedside measures such as activity, quality of life, and physical function accurately stratified the patient's risk for overt HE.

Prediction of overt hepatic encephalopathy by the continuous reaction time method and the portosystemic encephalopathy syndrome test in clinically mentally unimpaired patients with cirrhosis.

Predicting overt hepatic encephalopathy (OHE) is important because the condition is frequent, often requires hospitalization and is potentially preventable. The risk of OHE is related to pre-existing discrete cognitive defects, and for clinical practice it is recommended to apply two different psychometric tests to detect such deficits. We used the continuous reaction time test (CRT) and the portosystemic encephalopathy (PSE) syndrome test and examined their single and combined value for OHE prediction in cirrhosis patients. We studied 130 clinically mentally unimpaired cirrhosis patients by the two tests and followed them for an average of 38.5 months. The CRT measures velocity and stability of motor reaction times to 150 repeated auditory signals. The PSE is a five sub-set paper-and-pencil test battery evaluating cognitive and psychomotor processing, speed and vision-motor coordination. We collected data on episodes of OHE during follow-up. The clinical course was analysed in patient groups according to the outcome of each test and of both tests together. No anti-HE treatment was initiated except for cases with OHE. At baseline, the CRT test was abnormal in 74 patients and the PSE in 47. During follow-up 35 patients (27%) experienced 74 OHE events. 23 patients with abnormal CRT experienced OHE (prediction sensitivity 65%). The PSE predicted OHE in 14 patients (prediction sensitivity 40%). One or both tests were abnormal in 87/130 (67%) and this predicted OHE in 27 patients (21%) (prediction sensitivity 77%). The CRT test was clinically useful in identifying two-thirds of clinically mentally unimpaired cirrhosis patients who later experienced OHE, and the use of both the CRT and PSE showed satisfactory prediction by identifying three-fourths of later OHE cases.

Albumin infusion may decrease the incidence and severity of overt hepatic encephalopathy in liver cirrhosis.

Background: The role of human albumin infusion for the prevention and treatment of overt hepatic encephalopathy (HE) in liver cirrhosis remains unclear. Results: Among the 708 patients without pre-existing overt HE, albumin infusion significantly decreased the incidence of overt HE (4.20% versus 12.70%, P<0.001) and in-hospital mortality (1.70% versus 5.40%, P=0.008). Among the 182 patients with overt HE at admission or during hospitalization, albumin infusion significantly improved overt HE (84.60% versus 68.10%, P=0.009) and decreased in-hospital mortality (7.70% versus 19.80%, P=0.018). Meta-analysis of 6 studies found that albumin infusion might decrease the risk of overt HE (OR=1.63, P=0.07), but the difference was not statistically significant. Meta-analysis of 3 studies found that albumin infusion significantly improved overt HE (OR=2.40, P=0.04). Conclusions: Based on the results of our retrospective study and meta-analysis, albumin infusion might prevent from the occurrence of overt HE and improve the severity of overt HE in cirrhosis. Our retrospective study also suggested that albumin infusion improved the outcomes of cirrhotic patients regardless of overt HE. Methods: Cirrhotic patients consecutively admitted between January 2010 and June 2014 were considered in a retrospective study. A 1:1 propensity score matching analysis was performed. Additionally, publications regarding albumin infusion for the management of overt HE were systematically searched. Meta-analyses were performed by random-effect model. Odds ratio (OR) was calculated.