Association Between Laboratory Values and Covert Hepatic Encephalopathy in Patients with Liver Cirrhosis: A Multicenter, Retrospective Study.

Deciphering the Spectrum of Low-Grade Hepatic Encephalopathy in Clinical Practice

Diagnosis of covert hepatic encephalopathy (CHE) is challenging and often neglected in clinical practice. The aim of this study was to develop an easy-to-perform score to predict CHE in patients with cirrhosis. For the development or validation cohort of the proposed clinical CHE score, 142 or 96 consecutive patients with cirrhosis were prospectively enrolled. The Psychometric Hepatic Encephalopathy Score was used to detect minimal hepatic encephalopathy. All patients were examined with the simplified animal naming test and were asked to complete the Chronic Liver Disease Questionnaire. We followed the TRIPOD guideline for development, validation, and reporting of the proposed score. The clinical covert hepatic encephalopathy score containing the variables-clinically detectable ascites, history of overt hepatic encephalopathy (OHE), albumin serum level, activity subdomain of the Chronic Liver Disease Questionnaire, and simplified animal naming test-discriminated best between patients with and without CHE. We generated 2 cutoff values for the identification of the high-, intermediate- (with need for additional specialized testing), and low-risk groups for CHE. By applying these cutoffs, the sensitivity, specificity, positive predictive value, and negative predictive value were 90%, 91%, 85%, and 94%, respectively. The AUC was 0.908 or 0.872 for the development or the validation cohort, respectively. Higher scores were further associated with poorer quality of life, and the high-risk group was predictive for first-time OHE within 180 days. We developed an easy-to-perform score to identify patients with cirrhosis at risk of CHE, which correlates with quality of life and risk of first-time OHE.

Minimal Hepatic Encephalopathy Is An Under Recognized Entity in Clinical Practice Of Bangladeshi Physicians

Background: Cirrhotic patient develops esophageal varix due to portal hypertension also increase the risk of developing encephalopathy. Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver disease that occurs in 30-40% of patients with cirrhosis. Minimal hepatic encephalopathy (MHE) is a state in which patients with cirrhosis of liver regardless of its cause show a number of quantifiable abnormal psychometric tests. This study aimed to see the association of severity of esophageal varix with Minimal Hepatic Encephalopathy in patients with Cirrhosis of Liver. Methods: This hospital based observational analytical study included 40 patients with Cirrhosis of liver admitted to the Department of Medicine, Rajshahi Medical College Hospital from July-December 2012. Complete history was taken either from patients or accompanying attendants. Thorough clinical examination was done. Relevant investigations report was collected. All the information’s were recorded on the fixed protocol. Collected data was classified, edited, coded and entered into the computer for statistical analysis by using SPSS. Results: Severity of liver disease according to Child-Pugh Grading, Grade-A was 02(5%), Grade-B was 30(75%) and Grade-C was 08(20%). Prevalence of number connection tests positive was 15(37.5%), line tracing test positive were 15(37.5%), serial dotting test positive were 16(40.0%) and two test positives were 15(37.5%). Association between line tracing test with Child-Pugh Grading, out of 15 positive line tracing test, 09 had Grade-B and 06 had Grade-C, p value was (p<0.05) that was statistically significant. Association between serial dotting tests with Child-Pugh Grading, out of 16 positive serial dotting tests, 09 had Grade- B and 07 had Grade- C, p value was (p<0.05) that was statistically significant. Association between psychometric tests with esophageal varix by Paquet’s grading, out of 40 patients 15 patients were grade-III, who were psychometric test positive groups and 16 patients were grade-III and 09 patients were grade-II who were psychometric test negative groups, p value was (p<0.05) statistically significant. In psychometric test positive groups mean duration of disease were 7.25(1.12) months and psychometric test negative groups were 5.09(1.99) months, p value were (<0.001) that was statistically significant. Conclusion: Minimal hepatic encephalopathy (MHE) is common in patients with stable cirrhosis of liver. There is a good relationship between MHE with advanced liver disease by Child-Pugh Grading. Esophageal varix with high grade severity is common in cirrhotic patients who have MHE and longer duration of disease.

BackgroundThe International Normalized Ratio (INR) is significantly associated with Hepatic Encephalopathy (HE) in patients with liver cirrhosis. However, the dose-response relationship between continuous INR changes and HE risk has not been clearly defined. Thus, our goal was to explore the continuous relationship between HE and INR among patients hospitalized with liver cirrhosis and to evaluate the role of the INR as a risk factor for HE in these patients.MethodsA total of 6,266 people were extracted from the Big Data Platform of the Medical Data Research Institute of Chongqing Medical University. In this study, unconditional logistic regression and restricted cubic spline (RCS) model were used to analyze the dose-response association of INR with HE. Alcoholic liver disease, smoking status, and drinking status were classified for subgroup analysis.ResultsThe prevalence of HE in the study population was 8.36%. The median INR was 1.4. After adjusting for alcoholic liver disease, age, smoking status, drinking status, total bilirubin, neutrophil percentage, total hemoglobin, aspartate aminotransferase, serum sodium, albumin, lymphocyte percentage, serum creatinine, red blood cell, and white blood cell, multivariate logistic regression analysis revealed that INR ≥ 1.5 (OR = 2.606, 95% CI: 2.072–3.278) was significantly related to HE risk. The RCS model showed a non-linear relationship between the INR and HE (non-linear test, χ2 = 30.940, P < 0.001), and an increased INR was an independent and adjusted dose-dependent risk factor for HE among patients with liver cirrhosis.ConclusionThis finding could guide clinicians to develop individualized counseling programs and treatments for patients with HE based on the INR risk stratification.

Background: Minimal Hepatic Encephalopathy, the mildest from of Hepatic Encephalopathy is characterized by subtle motor and cognitive deficits and impairs health related quality of life. Though the prevalence of Minimal Hepatic Encephalopathy in cirrhotic patient is high but awareness regarding MHE is yet not satisfactory. Moreover diagnosis of MHE, the cut off normative value for psychometric test is yet not established in Bangladesh. This is the first study in Bangladesh to find out the normative value for psychometric test and see the prevalence of Minimal Hepatic Encephalopathy in cirrhotic patient.Methods: Cross sectional study done in Department of Hepatology, BSMMU, Dhaka from July 2012 to June 2014. Total 150 patient of which 50 patient with cirrhosis and remaining 100 healthy individual were included in the study. By doing number connection test, Serial dotting test and line tracing test in healthy individual, first normative values for psychometric test was detected then these test was done on cirrhotic patient, whose 2 psychometric test result among 3 above normal value were enrolled as a case of Minimal Hepatic Encephalopathy. None of the patient previously diagnosed as any type of Hepatic Encephalopathy.Results: Cut off normative value for NCT, SDT, LTT is 52 seconds, 52 seconds and 84 seconds respectively (Mean+2SD). Prevalence of Minimal Hepatic Encephalopathy in this study was 66% and it is more prevalent in advanced cirrhosis.Conclusion: MHE is frequent in patient with liver cirrhosis, manifested even in patient with child pugh A liver cirrhosis. Every attention should be given to detect Minimal Hepatic Encephalopathy in patient with cirrhosis of liver well before the development of overt Hepatic Encephalopathy.J Bangladesh Coll Phys Surg 2018; 36(2): 59-63

We aimed to define the impact of the genetic background on overt hepatic encephalopathy (HE) in patients with liver cirrhosis by developing a combined clinical-genetic risk score. Patients suffering from liver cirrhosis from the outpatient clinics of 4 hospitals (n = 600) were included and followed up for at least 5 years until HE bouts, liver transplant, or death. Patients were genotyped for 60 candidate single nucleotide polymorphisms together with the microsatellite in the promoter region of the gene GLS. Single nucleotide polymorphisms rs601338 (FUT2), rs5743836 (TRL9), rs2562582 (SLC1A3), rs313853 (SLC1A5), and GLS microsatellite did predict independently the incidence and severity of overt HE and were included as genetic score. Competing risk analysis revealed that bilirubin (subhazard ratio [sHR] 1.30 [1.15-1.48], P < 0.001), albumin (sHR 0.90 [0.86-0.93], P < 0.001), genetic score (sHR 1.90 [1.57-2.30], P < 0.001), and previous episodes of overt HE (sHR 2.60 [1.57-4.29], P < 0.001) were independently associated to HE bouts during the follow-up with an internal (C-index 0.83) and external validation (C-index 0.74). Patients in the low-risk group had 5% and 12% risk of HE at 1 (log-rank 92.1; P < 0.001) and 5 (log-rank 124.1; P < 0.001) years, respectively, whereas 36% and 48% in the high-risk group. The genetic background influenced overt HE risk and severity. The clinical-genetic HE Risk score, which combined genetic background together with albumin, bilirubin, and previous episodes of overt HE, could be a useful tool to predict overt HE in patients with cirrhosis.

Clinical significance of measuring hepatic venous pressure gradient on transjugular liver biopsy for patients with pre-cirrhotic bridging fibrosis liver disease

Cryptococcus neoformans, an encapsulated fungus, is an important opportunistic pathogen that can cause meningitis in im-munocompromised patients. Since patients with cryptococcemia have high mortality, it is essential to make an early diagnosis and promptly initiate antifungal therapy. However, it is often very difficult to differentiate between cryptococcal meningitis and hepatic encephalopathy in patients with liver cirrhosis, and there is delay in making the diagnosis. Therefore, these patients have a particularly grave prognosis and consequently many patients die before culture results become available. In one study, starting antifungal therapy within 48 hours of the blood culture was associated with improved survival, but patients with liver cirrhosis were significantly less likely to receive antifungal therapy within 48 hours compared to those without liver cirrhosis. Recently, the authors experience a case of a 68-year-old woman with liver cirrhosis who presented with fever and a drowsy mental status. She had a previous history of having been admitted for infection-associated hepatic encephlopathy. Cryptococcal meningitis and cryptococcemia were diagnosed by spinal puncture and culture of cerebrospinal fluid. In spite of adequate treatment, the patient developed multi-system organ failure and eventually expired. Herein, we report a case of cryptococcal meningitis mimicking hepatic encephalopathy in a patient with liver cirrhosis.

ObjectivePatients with liver cirrhosis (LC) are at increased risk for bacterial infections. It is not fully understood how exposure to infections induces further development of hepatic encephalopathy (HE). This study estimated risks of infection associated with HE among patients with LC.MethodsA nested case-control study of 14,428 adult patients with LC was performed using the population-based Longitudinal Health Insurance Database 2000 in Taiwan. Cases were cirrhotic patients who developed HE during follow-up. Controls were matched to each case by age at LC diagnosis (±2 years), sex, Charlson Comorbid index score, year of LC, and follow-up time with a 1:1 ratio. A multivariate logistic regression model was used to determine and compare the odds of developing HE based on exposure to various risk factors, including site of infection, cirrhosis-related complications, Helicobacter pylori eradication therapy, and peptic ulcer bleeding. Patient survival was evaluated using the time-dependent Cox regression model.ResultsCirrhotic patients with HE (n = 714) and without HE (n = 714) were matched to compare risks. Infections and more frequent yearly infections were significantly associated with increased risk of HE. Independent predictors of HE included spontaneous bacterial peritonitis (aOR, 5.13; 95% CI, 3.03–8.69), sepsis (aOR, 2.54; 95% CI, 1.82–-3.53), and biliary tract infection (aOR, 2.03; 95% CI, 1.2–3.46), controlling for confounders.ConclusionFrequent infections are associated with increased risk of HE in cirrhotic patients. More frequent exposure to infection increases the risk of HE and mortality rates. Appropriate prevention of infection and the use of antibiotics for cirrhotic patients at risk for HE are needed.

The clinical classification of hepatic encephalopathy is largely subjective, which has led to difficulties in designing trials in this field. To review the current classification of hepatic encephalopathy and to develop consensus guidelines on the design and conduct of future clinical trials. A round table was convened at the 14th International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) meeting. Key discussion points were the nomenclature of hepatic encephalopathy and the selection of patients, standards of care and end-points for assessing the treatment and secondary prevention of hepatic encephalopathy. It was generally agreed that severity assessment of hepatic encephalopathy in patients with cirrhosis, whether made clinically or more objectively, should be continuous rather than categorical, and a system for assessing the SONIC (Spectrum of Neuro-cognitive Impairment in Cirrhosis) was proposed. Within this system, patients currently classified as having minimal hepatic encephalopathy and Grade I hepatic encephalopathy would be classified as having Covert hepatic encephalopathy, whereas those with apparent clinical abnormalities would continue to be classified as overt hepatic encephalopathy. Some aspects of the terminology require further debate. Consensus was also reached on the patient populations, standards of care and endpoints to assess clinical trial outcomes. However, some compromises had to be made as there is considerable inter- and intravariability in the availability of some of the more objective surrogate performance markers. The objectives of the round table were met. Robust, defendable guidelines for the conduct of future studies into hepatic encephalopathy have been provided. Outstanding issues are few and will continue to be discussed.

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

Proposal of Stroop test cut-off values as screening for neuropsychological impairments in cirrhosis: A Japanese multicenter study.

BACKGROUND: Rifaximin reduces the risk of overt hepatic encephalopathy (HE) in patients with advanced chronic liver disease (ACLD) and is associated with significant reductions in hospitalisations and 30‐day readmissions. This study examined clinical outcomes of patients listed for liver transplantation with a diagnosis of HE on rifaximin compared to those naïve to the drug. METHODS: Patient records of those listed for liver transplantation over a 2-year period were retrospectively reviewed. Patients were included if they had at least two episodes of overt HE resulting in hospitalisation or were encephalopathic at the time of assessment. Information collected included patient demographics, aetiology of liver disease, disease severity scoring at transplant listing, concomitant medications and medical co-morbidities. Emergency admissions whilst on the waiting list for complications of ACLD in addition to requirement for prioritisation (UKELD score ≥63), duration on the waiting list (days) and mortality on the waiting list were recorded. Univariate and multivariate regression analyses were performed on acute admission and complication data (related to sepsis, acute variceal bleeding (AVB), HE and complications of ascites) with rifaximin use as the independent variable. RESULTS: Of the 622 patients listed for transplantation, 101 were listed with HE. 66 patients were treated with rifaximin and 35 were naïve at listing. Median MELD score was similar (15 [14–16)] rifaximin-treated and 16 [14–18] rifaximin-naïve). The use of lactulose was not significantly different between groups. Patients on the waiting list treated with rifaximin had an independent association with reduced all-cause admissions (P = 0.037), episodes of spontaneous bacterial peritonitis (P = 0.008) and AVB (P = 0.026). Mean length of hospital stay was 9 (95% CI 6–12) in the rifaximin-treated group vs 14 days (95% CI 7–21) in the rifaximin-naïve group. Multivariate regression analysis demonstrated that rifaximin was independently associated with an increase in days to readmission (adjusted effect estimate 71, 95% CI 3–140 days, P = 0.037) and reduced likelihood of requirement for prioritisation on the waiting list (odds ratio 0.29; 95% CI 0.89–0.93, P = 0.037). CONCLUSION: Rifaximin prescribed for HE in patients listed for liver transplantation improved outcomes on the waiting list with a significant reduction in admissions related to spontaneous bacterial peritonitis, ascites and AVB and indicating potential beneficial impacts of rifaximin beyond HE in ACLD.

Cost-effectiveness of screening and treatment protocols for treating hepatic encephalopathy in patients diagnosed with dementia.