Comparison of 6 tests for diagnosing minimal hepatic encephalopathy and predicting clinical outcome: A prospective, observational study.

BACKGROUND AND AIMS: Current guidelines recommend the assessment for minimal HE in patients with liver cirrhosis. Various efforts were made to find tools that simplify the diagnosis. Here, we compare the 6 most frequently used tests for their validity and their predictive value for overt hepatic encephalopathy (oHE), rehospitalization, and death. APPROACH AND RESULTS: One hundred thirty-two patients with cirrhosis underwent the Portosystemic Encephalopathy-Syndrome-Test yielding the psychometric hepatic encephalopathy score (PHES), Animal Naming Test (ANT), Critical Flicker Frequency (CFF), Inhibitory Control Test (ICT), EncephalApp (Stroop), and Continuous Reaction Time Test (CRT). Patients were monitored for 365 days regarding oHE development, rehospitalization, and death. Twenty-three patients showed clinical signs of HE grade 1-2 at baseline. Of the remaining 109 neurologically unimpaired patients, 35.8% had abnormal PHES and 44% abnormal CRT. Percentage of abnormal Stroop (79.8% vs. 52.3%), ANT (19.3% vs. 51.4%), ICT (28.4% vs. 36.7%), and CFF results (18.3% vs. 25.7%) changed significantly when adjusted norms were used for evaluation instead of fixed cutoffs. All test results correlated significantly with each other ( p <0.05), except for CFF. During follow-up, 24 patients developed oHE, 58 were readmitted to the hospital, and 20 died. Abnormal PHES results were linked to oHE development in the multivariable model. No other adjusted test demonstrated predictive value for any of the investigated endpoints. CONCLUSIONS: Where applicable, the diagnosis of minimal HE should be made based on adjusted norm values for the tests, exclusively. The minimal HE tests cannot be equated with one another and have an overall limited value in predicting clinical outcomes.

High Prevalence and Clinical Relevance of Intrapulmonary Vascular Dilatations in Patients Undergoing TIPS Implantation.

BACKGROUND & AIMS: Considerate patient selection is vital to ensure the best possible outcomes after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, data regarding the impact of intrapulmonary vascular dilatations (IPVDs) or hepatopulmonary syndrome (HPS) on the clinical course after TIPS implantation is lacking. Hence, this study aimed to investigate the relevance of IPVD and HPS in patients undergoing TIPS implantation. METHODS: Contrast enhanced echocardiography and blood gas analysis were utilized to determine presence of IPVD and HPS. Multivariable competing risk analyses were performed to evaluate cardiac decompensation (CD), hepatic decompensation (HD), and liver transplant (LTx)-free survival within 1 year of follow-up. RESULTS: Overall, 265 patients were included, of whom 136 had IPVD and 71 fulfilled the HPS criteria. Patients with IPVD had lower Freiburg index of post-TIPS survival (FIPS) scores, lower creatinine, and more often received TIPS because of variceal bleeding. Presence of IPVD was associated with a significantly higher incidence of CD (hazard ratio [HR], 1.756; 95% confidence interval [CI], 1.011-3.048; P = .046) and HD (HR, 1.841; 95% CI, 1.255-2.701; P = .002). However, LTx-free survival was comparable between patients with and without IPVD (HR, 1.081; 95% CI, 0.630-1.855; P = .780). Patients with HPS displayed a trend towards more CD (HR, 1.708; 95% CI, 0.935-3.122; P = .082) and HD (HR, 1.458; 95% CI, 0.934-2.275; P = .097) that failed to reach statistical significance. LTx-free survival did not differ in those with HPS compared with patients without HPS, respectively (HR, 1.052; 95% CI, 0.577-1.921; P = .870). CONCLUSION: Screening for IPVD before TIPS implantation could help to further identify patients at higher risk of CD and HD.

Folic acid supplementation is associated with a decreased mortality and reduced hospital readmission in patients with decompensated alcohol-related liver cirrhosis.

BACKGROUND AND AIMS: Thiamine and folic acid malnutrition is highly frequent in patients with decompensated alcohol-related liver cirrhosis (aLC). Current guidelines therefore recommend vitamin supplementation in these patients. However, implementation and its impact on the clinical outcome remains unknown. Therefore, we aimed to analyze the use of thiamine and folic acid and their effects on mortality and morbidity in patients with decompensated aLC. METHODS: A number of 289 consecutive patients with decompensated aLC who received a paracentesis at Hannover Medical School between 2011 and 2023 were retrospectively investigated. The use of folic acid and thiamine-containing supplements was assessed in the discharge medication. Patients were followed for up to one year regarding liver transplant (LTx)-free survival and the incidence of hepatic encephalopathy, infections and hepatic decompensation requiring rehospitalization. RESULTS: Median baseline MELD was 15, median age 56.6 years. 73.0% (n = 211) were male patients. At hospital discharge, thiamine-containing supplements and folic acid were prescribed to 48.1% (n = 139) and 18.0% (n = 52) patients, respectively. Neither thiamine nor folic acid prescription were linked to improved clinical outcomes within 90 days. However, folic acid intake was associated with a higher one-year LTx-free survival (HR = 0.48; p = 0.04) in the multivariable analysis. Furthermore, folic acid substitution was linked to a decreased risk of rehospitalization within one year (HR = 0.55; p = 0.01) in the multivariable competing risk model. In contrast, thiamine prescription did neither affect LTx-free survival nor the here investigated liver-related complications. CONCLUSION: Folic acid, but not thiamine substitution was linked to an improved outcome in patients with decompensated aLC.

No value of non-selective beta-blockers after TIPS-insertion.

BACKGROUND AND AIMS: Non-selective beta-blockers (NSBB) are a well-established treatment in patients with clinically significant portal hypertension. However, their potential role after insertion of a transjugular intrahepatic portosystemic shunt (TIPS) still needs to be determined. Of note, recent studies suggested that favourable anti-inflammatory effects of NSBB might be independent from pressure reduction. This study aimed to evaluate whether NSBB-treatment is associated with amelioration of systemic inflammation (SI), hepatic decompensation and survival after TIPS-insertion. METHODS: In a retrospective study comprising 305 consecutive patients, we investigated the impact of NSBB-intake at TIPS-placement on periinterventional cirrhosis-associated complications and continued NSBB-treatment after discharge on complications including hepatic decompensation and mortality during 1-year follow-up, employing multivariable competing-risk-analyses. In a prospective cohort including 45 patients, we performed a comprehensive analysis of SI analysing 48 soluble inflammatory markers (SIMs) at baseline plus 3 and 6 months after TIPS-insertion. RESULTS: Overall, 175 (57.4%) patients received NSBB-therapy prior to TIPS-insertion; upon discharge, this decreased to 131 (22.9%), with 36 (27.5%) discontinuing NSBB within 1-year follow-up. Neither NSBB-therapy at TIPS-insertion nor treatment-continuation after discharge were associated with lower risks for hepatic decompensation, individual cirrhosis-associated complications or mortality neither in the periinterventional period nor during follow-up. Similarly, in the prospective cohort NSBB-intake was not linked to lower levels or a more prominent change of WBC, CRP or any other SIM at any of the investigated time points. CONCLUSION: NSBB-therapy at the time of TIPS-insertion and its (dis-)continuation afterwards seems to have no significant impact on SI, development of hepatic decompensation and survival.

Predicting overt hepatic encephalopathy after TIPS: Value of three minimal hepatic encephalopathy tests.

Background & Aims: Hepatic encephalopathy (HE) is a frequent and severe complication in patients after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, risk factors for post-TIPS HE remain poorly defined. Minimal HE (mHE) is a well-known risk factor for overt HE in patients with cirrhosis without TIPS. We aimed to evaluate three tools frequently used for diagnosing mHE for their dynamic changes and their predictive value for overt HE after TIPS. Methods: We prospectively recruited 84 consecutive patients before TIPS insertion and monitored them for 180 days for post-TIPS HE. Before TIPS insertion, the patients underwent the portosystemic encephalopathy (PSE) syndrome test, the animal naming test (ANT), and the critical flicker frequency (CFF). Patients were retested after TIPS insertion. Results: The majority of patients were male (67.9%), and the predominant indication for TIPS was refractory ascites (75%). Median age was 59 years, model for end-stage liver disease score was 12, and 66.3%, 64.6%, and 28.4% patients had evidence for mHE according to the PSE syndrome test, ANT, and CFF, respectively. Overall, 25 patients developed post-TIPS HE within 180 days after TIPS insertion. Post-TIPS incidence of overt HE was 22.2, 28.6, 45.5, and 55.6% in those with no, one, two, and three pathological tests at baseline, respectively. However, none of the three tests was significantly associated with post-TIPS HE. Of note, mean performance in all tests remained stable over time after TIPS insertion. Conclusions: PSE syndrome test, ANT and CFF, which are frequently used for diagnosing mHE have limited value for predicting HE after TIPS insertion. We could not find evidence that TIPS insertion leads to a psychometric decline in the long term. Impact and implications: This prospective observational study compared three diagnostic tests for mHE and showed the limited value of these tests for predicting overt HE in patients with cirrhosis undergoing TIPS insertion. In addition, the results suggest that cognitive performance generally remains stable after TIPS insertion. These results are important for physicians and researchers involved in the management of patients with cirrhosis undergoing TIPS procedures. The study's findings serve as a starting point for further investigations on the development of more effective strategies for predicting and managing post-TIPS HE. Clinical trial number: ClinicalTrials.gov NCT04801290.