Hepatic venous pressure gradient predicts risk of hepatic decompensation and liver-related mortality in patients with MASLD.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of advanced chronic liver disease (ACLD). Portal hypertension drives hepatic decompensation and is best diagnosed by hepatic venous pressure gradient (HVPG) measurement. Here, we investigate the prognostic value of HVPG in MASLD-related compensated ACLD (MASLD-cACLD). METHODS: This European multicentre study included patients with MASLD-cACLD characterised by HVPG at baseline. Hepatic decompensation (variceal bleeding/ascites/hepatic encephalopathy) and liver-related mortality were considered the primary events of interest. RESULTS: A total of 340 patients with MASLD-cACLD (56.2% male; median age 62 [55-68] years, median MELD 8 [7-9], 71.2% with diabetes) were included. Clinically significant portal hypertension (CSPH: i.e., HVPG ≥10 mmHg) was found in 209 patients (61.5%). During a median follow-up of 41.5 (27.5-65.8) months, 65 patients developed hepatic decompensation with a cumulative incidence of 10.0% after 2 years (2Y) and 30.7% after 5 years (5Y) in those with MASLD-cACLD with CSPH, compared to 2.4% after 2Y and 9.4% after 5Y in patients without CSPH. Variceal bleeding did not occur without CSPH. CSPH (subdistribution hazard ratio [SHR] 5.13; p <0.001) was associated with an increased decompensation risk and a higher HVPG remained an independent risk factor in the multivariable model (adjusted SHR per mmHg: 1.12, p <0.001). Liver-related mortality occurred in 37 patients at a cumulative incidence of 3.3% after 2Y and 21.4% after 5Y in CSPH. Without CSPH, the incidence after 5Y was 0.8%. Accordingly, a higher HVPG was also independently associated with a higher risk of liver-related death (adjusted SHR per mmHg: 1.20, p <0.001). CONCLUSION: HVPG measurement is of high prognostic value in MASLD-cACLD. In patients with MASLD-cACLD without CSPH, the short-term risk of decompensation is very low and liver-related mortality is rare, while the presence of CSPH substantially increases the risk of both. IMPACT AND IMPLICATIONS: While the incidence of compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, insights into the impact of clinically significant portal hypertension (CSPH) on the risk of liver-related events in MASLD-cACLD remain limited. Based on the findings of this European multicentre study including 340 MASLD-cACLD patients, we could show that increasing HVPG values and the presence of CSPH in particular were associated with a significantly higher risk of first hepatic decompensation and liver-related mortality. In contrast, the short-term incidence of decompensation in patients with MASLD-cACLD without CSPH was low and the risk of liver-mortality remained negligible. Thus, HVPG measurements can provide important prognostic information for individualised risk stratification in MASLD-cACLD and may help facilitate the study of novel and promising treatment possibilities for MASLD.

Prediction of Mortality and Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Placement: Baseline and Longitudinal Body Composition Measurement.

PURPOSE: To investigate effects of baseline and early longitudinal body composition changes on mortality and hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: This is a case-control study with analysis of a TIPS registry (1995-2020) including data from patients with cirrhosis with computed tomography (CT) scans obtained within 1 month before and 3 months after TIPS. Core muscle area (CMA), macroscopic subcutaneous adipose tissue (mSAT), macroscopic visceral adipose tissue (mVAT) area, and muscle adiposity index (MAI) on CT were obtained. Multipredictor Cox proportional hazards models were used to assess the effect of body composition variables on mortality or HE. RESULTS: In total, 280 patients (158 men; median age, 57.0 years; median Model for End-stage Liver Disease-sodium [MELD-Na] score, 14.0) were included. Thirty-four patients had post-TIPS imaging. Median baseline CMA was 68.3 cm2 (interquartile range, 57.7-83.5 cm2). Patients with higher baseline CMA had decreased risks of mortality (hazard ratio [HR]: 0.82; P = .04) and HE (HR: 0.82; P = .009). It improved prediction of mortality over MELD-Na and post-TIPS right atrial pressure alone (confidence interval = 0.729). An increase in CMA (HR: 0.60; P = .043) and mSAT (HR: 0.86; P = .022) or decrease in MAI (HR: 1.50; P = .049) from before to after TIPS was associated with a decreased risk of mortality. An increase in mSAT was associated with an increased risk of HE (HR: 1.11; P = .04). CONCLUSIONS: CMA on CT scan 1 month before TIPS placement predicts mortality and HE in patients with cirrhosis. Changes in body composition on CT measured 3 months after TIPS placement independently predict mortality and HE.

Discharge Outcomes of Hospitalized Patients with New Onset Decompensated Cirrhosis.

INTRODUCTION: There are a lack of data describing outcomes and follow-up after hospital discharge for patients with newly diagnosed cirrhosis with complication on index admission. This study examines factors that influence outcomes such as readmission, follow-up, and mortality for patients with newly diagnosed cirrhosis. METHODS: We conducted a single-center retrospective chart review study of 230 patients with newly diagnosed cirrhosis from January 1st, 2020 through December 31st, 2021. We obtained demographics, clinical diagnoses, admission, and discharge MELD-Na, disposition, mortality, appointment requests rate, appointment show rate, and readmission. RESULTS: The primary complications on admission were GI bleed (27%), ascites (25.7%), and hepatic encephalopathy (HE) (10.4%). Overall, the median length of stay (LOS) was 6 days, and the readmission rate was 27%. Out of 230 patients, 25 (10.9%) patients died while hospitalized while another 43 (18.6%) died after initial discharge within the two-year study period. Although there was a significant reduction of the MELD-Na from admission to discharge (p < 0.05), admission MELD-Na did not correlate with LOS and discharge MELD-Na did not predict readmission. Patients with HE had the highest median LOS, while patients with ascites had the highest readmission rate. The median time to an appointment was 32 days. When comparing discharge destinations, most patients were discharged to home (63%), to facilities (13.9%), or expired (10.9%). The average appointment show rate was 38.5%, although 70% of patients had appointment requests. Readmission rate and mortality did not differ based on appointment requests. No significant differences in outcomes were observed based on race, sex, or insurance status. CONCLUSION: New diagnosis of decompensated was found to have high mortality and high readmission rates. Higher MELD-Na score was seen in patients who died within 30 days. Routine appointment requests did not significantly improve readmission, mortality, increase appointment show rate, or decrease time to appointment. A comprehensive and specialized hepatology-specific program may have great benefits after cirrhotic decompensation, especially for those with newly diagnosed cirrhosis.

Serum copeptin level is a biomarker associated with ascites retention and the formation of a portosystemic shunt in chronic liver disease.

BACKGROUND AND AIM: Copeptin is a stable cleavage product of the arginine vasopressin precursor and is equimolarly secreted with arginine vasopressin. We aimed to assess whether copeptin is the surrogate marker for complications related chronic liver disease (CLD) such as ascites, hepatic encephalopathy (HE), portosystemic shunts (PSSs), and all causes of mortality in CLD. METHODS: Serum copeptin was measured in 170 CLD patients upon hospital admission. The association of copeptin levels with liver enzymes, liver functional reserve, and clinical parameters was investigated. Cox proportional hazard regression, logistic regression, and Kaplan-Meier analyses were performed to evaluate the associations of copeptin and ascites, HE and PSS formation, and prognostic factors with short-term (1 year) and long-term (4 years) mortality. RESULTS: Serum copeptin levels were significantly correlated with liver and renal function, elevated in parallel with liver disease progression, and also associated with HE. Serum copeptin, albumin-bilirubin score and hepatocellular carcinoma were independent predictors of PSS formation and decreased rate of survival. Serum copeptin and albumin-bilirubin scores were independent predictors of ascites retention. The short-term and long-term cumulative mortality rate was significantly decreased in patients with serum copeptin >5.5 or >4.8 pmol/mL compared with patients in whom serum copeptin levels were <5.5 or <4.8 pmol/mL (P < 0.0001; P < 0.0001). CONCLUSIONS: Serum copeptin level is a predictor for ascites retention and HE and PSS formation associated with portal hypertension. Moreover, serum copeptin level may be useful in predicting the rate of survival in patients with CLD.

Disparities in Mortality and Health Care Utilization for 460,851 Hospitalized Patients with Cirrhosis and Hepatic Encephalopathy.

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) is a common cause of hospitalizations and readmissions for patients with decompensated cirrhosis. In this study, we proposed to investigate recent trends in in-hospital mortality and utilization for patients with cirrhosis and HE and to explore the effect of various sociodemographic, hospital, and clinical factors on mortality. METHODS: We performed an observational study using serial cross-sectional data from the 2009-2013 National Inpatient Sample to examine hospitalizations of patients with cirrhosis and HE. We collected data on in-hospital mortality, length of stay, and total hospital costs. We used negative binomial regression and logistic regression to investigate trends in utilization and multilevel modeling to examine the association between sociodemographic, hospital, and clinical factors and in-hospital mortality. RESULTS: The annual total number of hospitalizations from HE has steadily risen from 75,475 in 2009 to 106,915 in 2013 (P < 0.001). Annual in-hospital mortality (11.9-10.2%, P < 0.001) and length of stay (7.5-7.1 days, P = 0.015) have significantly decreased over this timeframe. The presence of septicemia, GI bleeding, and being uninsured were associated with 29.6%, 16.7%, and 15.7% of in-hospital death, respectively. Patients hospitalized in the South, Medicare beneficiaries, and patients hospitalized in the Midwest had a 9.8%, 9.2%, and 8.9% chance of dying in the hospital. CONCLUSION: The number of hospitalizations from HE has increased while in-hospital mortality has concomitantly decreased from 2009 to 2013. Both traditional risk factors (sepsis and GI bleeding) strongly influence the probability of in-hospital death. However, disparities in mortality by sociodemographic factors (insurance status and geography) also exist.

Long-term clinical outcome and survival predictors in patients with cirrhosis after 10-mm-covered transjugular intrahepatic portosystemic shunt.

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunts (TIPS) are successfully used in the management of portal hypertension (PH)-related complications. Debate surrounds the diameter of the dilation. The aim was to analyse the outcomes of and complications deriving from TIPS in patients with cirrhosis and identify predictors of survival. METHODS: This was a retrospective single-centre study, which included patients with cirrhosis who had a TIPS procedure for PH from 2009 to October 2018. Demographic, clinical and radiological data were collected. The Kaplan-Meier method was used to measure survival and predictors of survival were identified with the Cox regression model. RESULTS: A total of 98 patients were included (78.6% male), mean age was 58.5 (SD±/-9.9) and the median MELD was 13.3 (IQR 9.5-16). The indications were refractory ascites (RA), variceal bleeding (VB) and hepatic hydrothorax (HH). Median survival was 72 months (RA 46.4, VB 68.5 and HH 64.7) and transplant-free survival was 26 months. Clinical and technical success rates were 70.5% and 92.9% respectively. Age (HR 1.05), clinical success (HR 0.33), sodium (HR 0.92), renal failure (HR 2.46) and albumin (HR 0.35) were predictors of survival. Hepatic encephalopathy occurred in 28.6% of patients and TIPS dysfunction occurred in 16.3%. CONCLUSIONS: TIPS with 10-mm PTFE-covered stent is an effective and safe treatment for PH-related complications in patients with cirrhosis. Age, renal failure, sodium, albumin and clinical success are independent predictors of long-term survival.

Long-term outcomes in patients with decompensated alcohol-related liver disease, steatohepatitis and Maddrey's discriminant function <32.

BACKGROUND & AIMS: Patients with alcoholic hepatitis and a modified Maddrey's discriminant function (mDF) <32 have a low risk of short-term mortality. However, few data exist concerning long-term outcomes. The aims of this study were to evaluate 5-year survival rates and to identify predictive factors for long-term prognosis in this patient population. METHODS: We studied patients from 2 centers who were admitted for hepatic decompensation (ascites, hepatic encephalopathy, or jaundice) and who had histological findings of steatohepatitis and an mDF <32. Clinical and biological parameters were recorded at the time of liver biopsy and alcohol consumption was recorded during follow-up. We performed Cox proportional hazard survival analysis to identify factors associated with 5-year survival. RESULTS: One hundred and twenty-one patients were included (male: 64%, mean age: 51.5 ± 10.3 years, presence of cirrhosis: 84%). The median model for end-stage liver disease and mDF scores were 14 (IQR 11.7-16.1) and 19 (IQR 11.1-24), respectively. During follow-up, 30% of the patients remained abstinent. Survival rates at 1, 6, 12, 24, and 60 months were 96.7 ± 1.6%, 90.1 ± 2.7%, 80.8 ± 3.6%, 69.9 ± 4.3%, and 50.7 ± 4.9%, respectively. The majority of deaths (80%) were liver related. In multivariable analysis, encephalopathy at baseline and alcohol abstinence were predictive of 5-year survival. The 5-year survival rates of patients without and with encephalopathy at baseline were 60.5 ± 5.8% and 29.7 ± 8.0%, respectively, and the 5-year survival rates of abstinent and non-abstinent patients were 74.0 ± 8.0% and 40.9 ± 5.8%, respectively. CONCLUSIONS: The mortality rate of patients with alcoholic hepatitis and an mDF <32 is around 50% at 5 years. Hepatic encephalopathy at baseline and lack of alcohol abstinence impair long-term prognosis. New treatment strategies, including measures to ensure abstinence, are required. LAY SUMMARY: Patients with alcoholic hepatitis that is of intermediate severity have a low risk of short-term mortality but not much is known regarding long-term outcomes for these patients. This study clearly indicates that patients with intermediate disease characteristics have poor long-term outcomes. The presence of hepatic encephalopathy at the time of diagnosis and the absence of alcohol abstinence during follow-up are factors that predict poor long-term mortality.

Frailty Associated With Waitlist Mortality Independent of Ascites and Hepatic Encephalopathy in a Multicenter Study.

BACKGROUND & AIMS: Frailty is associated with mortality in patients with cirrhosis. We measured frailty using 3 simple tests and calculated Liver Frailty Index (LFI) scores for patients at multiple ambulatory centers. We investigated associations between LFI scores, ascites, and hepatic encephalopathy (HE) and mortality. METHODS: Adults without hepatocellular carcinoma who were on the liver transplantation waitlist at 9 centers in the United States (N = 1044) were evaluated using the LFI; LFI scores of at least 4.5 indicated that patients were frail. We performed logistic regression analyses to assess associations between frailty and ascites or HE and competing risk regression analyses (with liver transplantation as the competing risk) to estimate sub-hazard ratios (sHRs) of waitlist mortality (death or removal from the waitlist). RESULTS: Of study subjects, 36% had ascites, 41% had HE, and 25% were frail. The odds of frailty were higher for patients with ascites (adjusted odd ratio 1.56, 95% confidence interval [CI] 1.15-2.14) or HE (odd ratio 2.45, 95% CI 1.80-3.33) than for those without these features. Larger proportions of frail patients with ascites (29%) or HE (30%) died while on the waitlist compared with patients who were not frail (17% of patients with ascites and 20% with HE). In univariable analysis, ascites (sHR 1.52, 95% CI 1.14-2.05), HE (sHR 1.84, 95% CI 1.38-2.45), and frailty (sHR 2.38, 95% CI 1.77-3.20) were associated with waitlist mortality. In adjusted models, only frailty remained significantly associated with waitlist mortality (sHR 1.82, 95% CI 1.31-2.52); ascites and HE were not. CONCLUSIONS: Frailty is a prevalent complication of cirrhosis that is observed more frequently in patients with ascites or HE and independently associated with waitlist mortality. LFI scores can be used to objectively quantify risk of death related to frailty-in excess of liver disease severity-in patients with cirrhosis.

Proton Pump Inhibitors Are Associated With Minimal and Overt Hepatic Encephalopathy and Increased Mortality in Patients With Cirrhosis.

Minimal hepatic encephalopathy (MHE) is a subclinical cognitive impairment frequently observable in patients with cirrhosis. Proton pump inhibitors (PPIs) can contribute to small-bowel bacterial overgrowth, but no study has investigated the link between PPIs and MHE. We investigated the relationship between MHE and PPI use as well as the role of PPI use in the development of overt HE and survival. Consecutive patients with cirrhosis (n = 310) were included in the study and followed up for 14.1 ± 12.3 months. At entry, MHE was diagnosed when the Psychometric Hepatic Encephalopathy Score was ≤-4. Data were analyzed by logistic regression for the factors associated with MHE and by time-related models for overt HE development and survival. At inclusion, 131 out of 310 patients with cirrhosis (42%) were affected by MHE. One hundred and twenty-five patients (40%) were using PPIs. The variables independently associated with the presence of MHE were PPI use, previous overt HE, low albumin, low sodium, and age. During follow-up, the development of overt HE was higher (64% versus 25%, P < 0.001) and overall survival lower (41% versus 81%, P < 0.001) in PPI users than in nonusers. Variables independently associated with the development of overt HE were PPIs, history of overt HE, low albumin, MHE, and age, while variables independently associated with mortality were PPIs, development of overt HE, Model for End-Stage Liver Disease score, low sodium, and age. Conclusion: The study identifies a potentially removable factor associated with the presence of MHE and related to the development of overt HE and survival in patients with liver cirrhosis.

Cognitive Tests and Stool Frequency at Hospital Discharge Do Not Predict Outcomes in Hepatic Encephalopathy.

OBJECTIVES: Hepatic encephalopathy (HE) is associated with hospital readmissions and mortality. We sought to determine whether cognitive testing and stool frequency at discharge predicted 30-day readmission or death in cirrhotic patients admitted with overt HE. METHODS: We approached consecutive inpatients with cirrhosis and overt HE when they were within 48 hours of discharge. Patients underwent cognitive tests, including Psychometric Hepatic Encephalopathy Score (PHES), and stool frequency was documented. Chart review identified Model for End-Stage Liver Disease-sodium (MELD-Na) and the presence of non-HE extrahepatic organ failures. Cox proportional hazards models were used to evaluate predictors of time to the primary composite outcome of hospital readmission for HE or death within 30 days, censoring for liver transplantation. RESULTS: Of 51 patients consented and enrolled, 14 patients met the primary composite outcome. In unadjusted Cox models, 4 variables predicted HE readmission or death: MELD-Na (hazard ratio [HR] 1.10 [1.01-1.20], P = 0.03), respiratory failure (HR 4.26 [1.47-12.35], P = 0.008), total number of HE extrahepatic organ failures (HR 1.79 [1.12-2.88], P = 0.02), and score on a PHES subtest, Number Connection Test A (per 30 seconds; HR 1.25 [1.06-1.47], P = 0.01). PHES and 24-hour stool frequency did not predict the primary outcome. When controlling for MELD-Na, respiratory failure predicted the primary outcome (HR 3.67 [1.24-10.86], P = 0.02). CONCLUSION: Cognitive testing and stool frequency at discharge did not predict poor outcomes in patients admitted with HE, while respiratory failure appeared to be a strong predictor.

[Prognostic significance and economic burden of hepatic encephalopathy in liver cirrhosis in German hospitals based on G-DRG data]. / Mortalität und ökonomische Auswirkungen der hepatischen Enzephalopathie bei Leberzirrhose in deutschen Krankenhäusern auf der Basis von G-DRG-Kostendaten.

INTRODUCTION: Hepatic encephalopathy (HE) represents a frequent complication of liver cirrhosis with negative effects on patients' lives. The prevalence of clinical HE is estimated to be between 30-45 %. Regardless of its clinical and prognostic relevance HE is considered to be underdiagnosed. METHODS: Beyond a systematic analysis of mortality of HE, we investigated the economic impact and reimbursement situation for HE in patients with liver cirrhosis in Germany. For the retrospective analysis, anonymized data (2011-2015) concerning expenses and diagnoses (§â€Š21-4 KHEntgG) were obtained from 74 participating hospitals of the Diagnosis Related Groups (DRG) Project of the German Gastroenterological Association (DGVS). Furthermore, results were compared with case data from all German hospitals provided by the German Federal Authority on Statistics (Statistische Bundesamt (Destatis), Wiesbaden). RESULTS: In participating hospitals 59 093 cases with liver cirrhosis were identified of which 14.6 % were coded as having HE. Hospital mortality was threefold increased compared to cirrhosis-patients without HE (20.9 versus 7.5 %). Cases with cirrhosis as well as the proportion with HE increased over time. Compared to all patients with cirrhosis, reimbursement for HE patients produced a deficit (of up to 634 € for HE grade 4). DISCUSSION: Mortality is threefold increased in patients with cirrhosis when an additional HE is diagnosed. Hospitals participating in the DGVS-DRG-project coded 2 % more HE cases among their cirrhosis cases than the rest of hospitals either because of a selection bias for greater disease severity or because of better coding quality. At present, reimbursement for HE patients on the basis of F-DRG-system produced a deficit.

Association Between Portosystemic Shunts and Increased Complications and Mortality in Patients With Cirrhosis.

BACKGROUND & AIMS: Spontaneous portosystemic shunts (SPSS) have been associated with hepatic encephalopathy (HE). Little is known about their prevalence among patients with cirrhosis or clinical effects. We investigated the prevalence and characteristics of SPSS in patients with cirrhosis and their outcomes. METHODS: We performed a retrospective study of 1729 patients with cirrhosis who underwent abdominal computed tomography or magnetic resonance imaging analysis from 2010 through 2015 at 14 centers in Canada and Europe. We collected data on demographic features, etiology of liver disease, comorbidities, complications, treatments, laboratory and clinical parameters, Model for End-Stage Liver Disease (MELD) score, and endoscopy findings. Abdominal images were reviewed by a radiologist (or a hepatologist trained by a radiologist) and searched for the presence of SPSS, defined as spontaneous communications between the portal venous system or splanchnic veins and the systemic venous system, excluding gastroesophageal varices. Patients were assigned to groups with large SPSS (L-SPSS, ≥8 mm), small SPSS (S-SPSS, <8 mm), or without SPSS (W-SPSS). The main outcomes were the incidence of complications of cirrhosis and mortality according to the presence of SPSS. Secondary measurements were the prevalence of SPSS in patients with cirrhosis and their radiologic features. RESULTS: L-SPSS were identified in 488 (28%) patients, S-SPSS in 548 (32%) patients, and no shunt (W-SPSS) in 693 (40%) patients. The most common L-SPSS was splenorenal (46% of L-SPSS). The presence and size of SPSS increased with liver dysfunction: among patients with MELD scores of 6-9, 14% had L-SPSS and 28% had S-SPSS; among patients with MELD scores of 10-13, 30% had L-SPSS and 34% had S-SPSS; among patients with MELD scores of 14 or higher, 40% had L-SPSS and 32% had S-SPSS (P < .001 for multiple comparison among MELD groups). HE was reported in 48% of patients with L-SPSS, 34% of patients with S-SPSS, and 20% of patients W-SPSS (P < .001 for multiple comparison among SPSS groups). Recurrent or persistent HE was reported in 52% of patients with L-SPSS, 44% of patients with S-SPSS, and 37% of patients W-SPSS (P = .007 for multiple comparison among SPSS groups). Patients with SPSS also had a larger number of portal hypertension-related complications (bleeding or ascites) than those W-SPSS. Quality of life and transplantation-free survival were lower in patients with SPSS vs without. SPSS were an independent factor associated with death or liver transplantation (hazard ratio, 1.26; 95% confidence interval, 1.06-1.49) (P = .008) in multivariate analysis. When patients were stratified by MELD score, SPSS were associated with HE independently of liver function: among patients with MELD scores of 6-9, HE was reported in 23% with L-SPSS, 12% with S-SPSS, and 5% with W-SPSS (P < .001 for multiple comparison among SPSS groups); among those with MELD scores of 10-13, HE was reported in 48% with L-SPSS, 33% with S-SPSS, and 23% with W-SPSS (P < .001 for multiple comparison among SPSS groups); among patients with MELD scores of 14 or more, HE was reported in 59% with L-SPSS, 57% with S-SPSS, and 48% with W-SPSS (P = .043 for multiple comparison among SPSS groups). Patients with SPSS and MELD scores of 6-9 were at higher risk for ascites (40.5% vs 23%; P < .001) and bleeding (15% vs 9%; P = .038) than patients W-SPSS and had lower odds of transplant-free survival (hazard ratio 1.71; 95% confidence interval, 1.16-2.51) (P = .006). CONCLUSIONS: In a retrospective analysis of almost 2000 patients, we found 60% to have SPSS; prevalence increases with deterioration of liver function. SPSS increase risk for HE and with a chronic course. In patients with preserved liver function, SPSS increase risk for complications and death. ClinicalTrials.gov ID NCT02692430.

Early-Recurrent Overt Hepatic Encephalopathy Is Associated with Reduced Survival in Cirrhotic Patients after Transjugular Intrahepatic Portosystemic Shunt Creation.

PURPOSE: To investigate the role of early overt hepatic encephalopathy (OHE) as a clinical marker of prognosis in cirrhosis with a transjugular intrahepatic portosystemic shunt (TIPS) and to assess the relationship between recurrence of OHE and survival after TIPS. METHODS: From January 2012 to December 2013, a retrospective study of consecutive patients with cirrhosis and a TIPS was performed at a single institution. A total of 304 patients (196 males; mean age, 52 years) were enrolled during the study period. The mean Model for End-Stage Liver Disease (MELD) score was 11.6. Time-dependent Cox regression was applied to estimate the predictive ability of early OHE (within 3 months after TIPS) and the effect of its frequency on survival. RESULTS: During a median follow-up of 28.3 months, 115 patients experienced OHE after the TIPS procedure; of these, 54 had at least 2 OHE episodes. Long-term survival worsened in patients with early OHE (hazard ratio [HR] = 2.75; 95% confidence interval [CI]: 1.75-4.32; P < .001). When early OHE was further divided into early-recurrent and single OHE, death was more common in patients with early-recurrent OHE (P < .001) than in patients with early-single OHE (P = .24). After adjustment by MELD score, ascites, serum albumin, indication for TIPS, and age, patients with early-recurrent OHE had a lower probability of survival (HR = 2.91; 95% CI: 1.04-4.89; P < .001). Furthermore, landmark and propensity score analyses confirmed the predictive value of early-recurrent OHE. CONCLUSIONS: Early recurrence of OHE was associated with an increased risk of mortality for patients with cirrhosis who underwent TIPS.

Prognostic significance of minimal hepatic encephalopathy in patients with liver cirrhosis in Japan: A propensity score-matching analysis.

BACKGROUND AND AIM: Minimal hepatic encephalopathy (MHE) represents the mildest form of the hepatic encephalopathy spectrum. This study aimed to clarify the prognostic significance of MHE in cirrhotic patients. METHODS: This retrospective study evaluated 357 consecutive patients with liver cirrhosis. MHE was diagnosed using a neuropsychiatric test. A propensity score-matching analysis was employed to adjust significant differences in the baseline characteristics between patients with and without MHE. RESULTS: Of 269 eligible patients, 56 patients (21%) were diagnosed as having MHE. The Child-Pugh score, model for end-stage liver disease score, and serum ammonia levels were significantly increased, while serum albumin levels were reduced in patients with MHE. By contrast, no significant difference was found between the two groups in matched patients. During the median follow-up period of 13.4 months, 67 patients (24.9%) died. Overall survival rates were significantly lower in patients with MHE (median, 25.4 vs 48.8 months; P < 0.001). Multivariate analysis revealed that male sex (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.03-3.18; P = 0.038), stage III/IV hepatocellular carcinoma (HR, 6.32; 95% CI, 3.30-12.79; P < 0.001), the Child-Pugh score (HR, 1.35; 95% CI, 1.12-1.62; P = 0.002), and MHE (HR, 1.92; 95% CI, 1.09-3.29; P = 0.024) were independently associated with mortality in all patients as well as in matched patients. CONCLUSION: Minimal hepatic encephalopathy is associated with an increased risk of mortality in patients with liver cirrhosis, independent of hepatocellular carcinoma stage or Child-Pugh score.

Increasing Burden of Hepatic Encephalopathy Among Hospitalized Adults: An Analysis of the 2010-2014 National Inpatient Sample.

BACKGROUND: Hepatic encephalopathy (HE) is associated with substantial morbidity and mortality, contributing significant burden on healthcare systems. AIM: We aim to evaluate trends in clinical and economic burden of HE among hospitalized adults in the USA. METHODS: Using the 2010-2014 National Inpatient Sample, we identified adults hospitalized with HE using ICD-9-CM codes. Annual trends in hospitalizations with HE, in-hospital mortality, and hospital charges were stratified by the presence of acute liver failure (ALF) or cirrhosis. Adjusted multivariable regression models were evaluated for predictors of in-hospital mortality and hospitalization charges. RESULTS: Among 142,860 hospitalizations with HE (mean age 59.3 years, 57.8% male), 67.7% had cirrhosis and 3.9% ALF. From 2010 to 2014, total number of hospitalizations with HE increased by 24.4% (25,059 in 2010 to 31,182 in 2014, p < 0.001). Similar increases were seen when stratified by ALF (29.7% increase) and cirrhosis (29.7% increase). Overall in-hospital mortality decreased from 13.4% (2010) to 12.3% (2014) (p = 0.001), with similar decreases observed in ALF and cirrhosis. Total inpatient charges increased by 46.0% ($8.15 billion, 2010 to $11.9 billion, 2014). On multivariable analyses, ALF was associated with significantly higher odds of in-hospital mortality (OR 5.37; 95% CI 4.97-5.80; p < 0.001) as well as higher mean inpatient charges (122.6% higher; 95% CI + 115.0-130.3%; p < 0.001) compared to cirrhosis. The presence of ascites, hepatocellular carcinoma, and hepatorenal syndrome was associated with increased mortality. CONCLUSIONS: The clinical and economic burden of hospitalizations with HE in the USA continues to rise. In 2014, estimated national economic burden of hospitalizations with HE reached $11.9 billion.

A validated risk model for prediction of early readmission in patients with hepatic encephalopathy.

INTRODUCTION AND AIM: Hepatic encephalopathy (HE) is a common complication in cirrhotics and is associated with an increased healthcare burden. Our aim was to study independent predictors of 30-day readmission and develop a readmission risk model in patients with HE. Secondary aims included studying readmission rates, cost, and the impact of readmission on mortality. MATERIALS AND METHODS: We utilized the 2013 Nationwide Readmission Database (NRD) for hospitalized patients with HE. A risk assessment model based on index hospitalization variables for predicting 30-day readmission was developed using multivariate logistic regression and validated with the 2014 NRD. Patients were stratified into Low Risk and High Risk groups. Cox regression models were fit to identify predictors of calendar-year mortality. RESULTS: Of 24,473 cirrhosis patients hospitalized with HE, 32.4% were readmitted within 30 days. Predictors of readmission included presence of ascites (OR: 1.19; 95% CI: 1.06-1.33), receiving paracentesis (OR: 1.43; 95% CI: 1.26-1.62) and acute kidney injury (OR: 1.11; 95% CI: 1.00-1.22). Our validated model stratified patients into Low Risk and High Risk of 30-day readmissions (29% and 40%, respectively). The cost of the first readmission was higher than index admission in the 30-day readmission cohort ($14,198 vs. $10,386; p-value <0.001). Thirty-day readmission was the strongest predictor of calendar-year mortality (HR: 4.03; 95% CI: 3.49-4.65). CONCLUSIONS: Nearly one-third of patients with HE were readmitted within 30 days, and early readmission adversely impacted healthcare utilization and calendar-year mortality. With our proposed simple risk assessment model, patients at high risk for early readmissions can be identified to potentially avert poor outcomes.

Serial assessment of hepatic encephalopathy in patients hospitalised for acute decompensation of cirrhosis.

INTRODUCTION AND AIM: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis, but the clinical and prognostic significance of the progression of mental status in hospitalised cirrhotics is unknown. We aimed to investigate the prognostic significance of serial evaluation of HE in patients hospitalised for acute decompensation (AD) of cirrhosis. MATERIALS AND METHODS: Patients (n=293) were evaluated for HE (West-Haven criteria) at admission and at day-3 and classified in two groups: (1) Absent or improved HE: HE absent at admission and at day-3, or any improvement at day-3; (2) Unfavourable progression: Development of HE or HE present at admission and stable/worse at day-3. RESULTS: Unfavourable progression of HE was observed in 31% of patients and it was independently associated with previous HE, Child-Pugh C and acute-on-chronic liver failure (ACLF). MELD score and unfavourable progression of HE were independently associated with 90-day mortality. The 90-day Kaplan-Meier survival probability was 91% in patients with MELD<18 and absent or improved HE and only 31% in subjects with both MELD≥18 and unfavourable progression of HE. Unfavourable progression of HE was also related to lower survival in patients with or without ACLF. Worsening of GCS at day-3 was observed in 11% of the sample and was related with significantly high mortality (69% vs. 27%, P<0.001). CONCLUSION: Among cirrhotics hospitalised for AD, unfavourable progression of HE was associated with high short-term mortality and therefore can be used for prognostication and to individualise clinical care.

Establishment and evaluation of a model for predicting 3-month mortality in Chinese patients with hepatic encephalopathy.

Hepatic encephalopathy (HE) is a serious complication of liver disease. To establish a model for predicting 3-month mortality in patients with HE in China. This retrospective study included 609 patients with HE admitted to the Peoples' Hospital, Liaocheng City, China (August 2006 to January 2016). Patients were allocated to a modeling (n = 409) or validation (n = 200) group. Demographic/clinical characteristics, laboratory test results, Model for End Stage Liver Disease (MELD) score and Child-Turcotte-Pugh (CTP) score were extracted from medical records. A model for predicting death within 3 months after admission was established using logistic regression analysis (modeling group). Model validity (validation group) was assessed using receiver operating characteristic (ROC) curve analysis. 270/409(66.0%) patients died in the modeling group and 142/203(70.0%) died in the validation group. Compared with survivors, patients who died had more severe HE, and higher MELD score, CTP score, incidence of complications including hepatorenal syndrome (HRS) and upper gastrointestinal bleeding, and values for laboratory parameters including red blood cell count(RBC) and total bilirubin(TBIL)(P < 0.05). Regression analysis revealed RBC, TBIL, HE stage, HRS and upper gastrointestinal bleeding as independent factors associated with death (P < 0.05). The area under the ROC curve (AUC) for the model was 0.931.The model had a higher Youden index than MELD or CTP scores and predicted death in the validation group with a sensitivity of 83.1% and specificity of 93.4%. The established model has superior performance to MELD and CTP scores for predicting mortality in patients with HE.

Hepatic encephalopathy impacts the predictive value of the Fried Frailty Index.

Frailty is increasingly recognized as a predictor of poor outcomes in solid organ transplantation. The most widely utilized frailty tool, the Fried Frailty Index (FFI), includes patient-reported exhaustion, weight loss, and physical activity as well as measured walk speed and handgrip. Although hepatic encephalopathy (HE) is common among liver transplant candidates, data are lacking regarding its impact on the interpretation of frailty. We prospectively enrolled 685 patients with cirrhosis during their transplant evaluation, following them until death or transplantation. Our cohort was aged 54.5 ± 10.3 years, 60% male, with an average MELD score of 14.7 ± 6.3. A history of HE was present in 39%. Frailty was present in 41%, associated with higher MELD, low albumin, ascites, and HE. HE was associated with frail performance on three components of the FFI-grip (odds ratio 1.41 95% CI, 1.03-1.92), walk speed (1.56 95% CI, 1.14-2.15), and decreased energy (1.44 95% CI, 1.05-1.99). These three components were associated with transplant free survival in the whole cohort: energy (hazard ratio 1.67 95% CI, 1.25-2.28), grip (1.63 95% CI, 1.24-2.16), and walk speed (1.56 95% CI, 1.19-2.04). However, among patients with HE, the FFI was not associated with survival. HE plays a critical role in the frailty phenotype and the implications of frailty among patients with cirrhosis evaluated for liver transplantation.

Coil-Assisted Retrograde Transvenous Obliteration (CARTO): An Alternative Treatment Option for Refractory Hepatic Encephalopathy.

BACKGROUND: Overt hepatic encephalopathy (OHE) is a serious complication of liver dysfunction, which is associated with severe morbidity/mortality and healthcare resource utilization. OHE can be medically refractory due to spontaneous portosystemic shunts (SPSSs) and therefore a new treatment option for these SPSSs is critical. METHODS: This is a retrospective study of 43 patients with medically refractory OHE, who underwent CARTO (Coil-Assisted Retrograde Transvenous Obliteration) procedures between June 2012 and October 2016. The patient demographic characteristics, technical and clinical outcomes with an emphasis on HE improvement, and complications are reviewed and analyzed. RESULTS: The overall clinical success rate was 91% with a significant HE improvement. Eighty-one percent of patients had clinically significant improvement from OHE and 67% of patients had complete resolution of their HE symptoms during our follow-up period of 893 ± 585 days (range 36-1881 days, median 755.0 days). The median WH score improved from 3 (range 2-4) pre-CARTO to 1 (range 0-4) post-CARTO (p < 0.001). The median ammonia level significantly decreased from 134.5 pre-CARTO to 70.0 post-CARTO (p < 0.001) in 3 days. The overall mean survival was 1465.5 days (95% CI of 1243.0 and 1688.0 days). Only three patients had recurrent HE symptoms. There were 39.6% minor complication rate including new or worsened ascites and esophageal varices, and only 2.3% major complication rate requiring additional treatment (one patient with bleeding esophageal varices requiring treatment). No procedure-related death is noted. CONCLUSIONS: CARTO appears to be a safe and effective treatment option for refractory overt hepatic encephalopathy (OHE) due to spontaneous portosystemic shunts. CARTO could be an excellent addition to currently available treatment options for these patients.