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Acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) are life-threatening syndromes that can develop at the end-stage of chronic hepatitis B virus (HBV) infection. Both ACLF and DC are complicated by hepatic and extrahepatic pathogeneses. To better understand the compartment-specific metabolic modulations related to their pathogenesis, HBV-DC, HBV-ACLF patients, and controls (30 each) were analyzed by metabolomics using portal (Port), hepatic vein (Hep), and peripheral (Peri) serum. Compartment ratios of metabolites (Ratio Hep/Port , Ratio Peri/Hep , and Ratio Port/Peri ) were calculated. The liver tissues (10 per group) were analyzed using transcriptomics and metabolomics. An additional 75 patients with ACLF, 20 with DC, and 20 with liver cirrhosis (LC) were used to confirm oxlipid dysregulation. Both multi-omics datasets suggest suppressed energy, amino acid, and pyrimidine metabolism in the ACLF/DC liver. The serum metabolomic variations were contributed primarily by disease rather than sampling compartments, as both HBV-ACLF and HBV-DC patients demonstrated abnormal profiles of amino acids and peptides, indoles, purines, steroids, and benzimidazoles. In ACLF/DC patients, impaired hepatic metabolism resulted in a highly correlated hepatic and portal vein serum metabolome and release of inflammatory lipids and heme metabolites from the liver. HBV-ACLF showed higher Ratio Peri/Hep of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher Ratio Port/Peri of gut microbial metabolites. An inflammatory oxlipid outburst was confirmed in the early stages of HBV-ACLF. The inflammatory effects of the selected oxlipids were confirmed in monocytes. These findings support a synergy between liver-specific mechanisms and systemic inflammation in ACLF/DC development, and that pro-inflammatory oxlipids are metabolic signatures of early HBV-ACLF.

A fixed-dose combination of sofosbuvir/velpatasvir (SOF/VEL) plus weight-based ribavirin (RBV) for 12 weeks is recommended for the treatment of patients with hepatitis C virus (HCV)-associated decompensated cirrhosis. However, large global studies, while confirming the effectiveness of SOF/VEL in a broad range of patients, often exclude these patients. This Phase 2, single-arm, open-label study in adult patients with HCV-associated decompensated cirrhosis in France and the USA aimed to provide further data on the safety and efficacy of SOF/VEL plus RBV for 12 weeks in this population. Patients were treated with a fixed-dose combination of SOF 400 mg/VEL 100 mg plus weight-based RBV once daily for 12 weeks. The inclusion criteria were chronic HCV infection (≥6 months), quantifiable HCV RNA at screening, Child–Turcotte–Pugh class B or C cirrhosis, and liver imaging within 6 months of Day 1 to exclude hepatocellular carcinoma. Among 32 patients who initiated treatment, 78.1% achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Failure to achieve SVR12 was due to non-virologic reasons (investigator discretion, n = 1; death, n = 6). All 25 patients in the per-protocol population achieved SVR12 and all but one achieved sustained virologic response 24 weeks after the end of treatment. Adverse events (AEs) were as expected for a patient population with advanced liver disease. All Grade 3–4 and serious AEs and deaths were deemed unrelated to treatment. In patients with HCV-associated decompensated cirrhosis, SOF/VEL plus RBV achieved high SVR12 rates and was generally well tolerated.

Abstract Background In HCV-infected patients with advanced liver disease, the direct antiviral agents-associated clinical benefits remain debated. We compared the clinical outcome of patients with a previous history of decompensated cirrhosis following treatment or not with direct antiviral agents from the French ANRS CO22 HEPATHER cohort. Methods We identified HCV patients who had experienced an episode of decompensated cirrhosis. Study outcomes were all-cause mortality, liver-related or non-liver-related deaths, hepatocellular carcinoma, liver transplantation. Secondary study outcomes were sustained virological response and its clinical benefits. Results 559 patients met the identification criteria, of which 483 received direct antiviral agents and 76 remained untreated after inclusion in the cohort. The median follow-up time was 39.7 (IQR: 22.7–51) months. After adjustment for multivariate analysis, exposure to direct antiviral agents was associated with a decrease in all-cause mortality (HR 0.45, 95% CI 0.24–0.84, p = 0.01) and non-liver-related death (HR 0.26, 95% CI 0.08–0.82, p = 0.02), and was not associated with liver-related death, decrease in hepatocellular carcinoma and need for liver transplantation. The sustained virological response was 88%. According to adjusted multivariable analysis, sustained virological response achievement was associated with a decrease in all-cause mortality (HR 0.29, 95% CI 0.15–0.54, p

Abstract Background and Aim Long‐term human albumin (HA) infusions improve survival in cirrhotic patients with diuretic resistant ascites. We aimed to determine whether there is a significant benefit in a more unwell real‐world cohort. Methods This is a single‐center retrospective cohort study. Patients received outpatient HA between April 2017 and June 2021. Inclusion criteria were age ≥18 years, cirrhosis with ascites, and received at least 1 month of HA. Patients with significant comorbidities and ongoing alcohol use were not excluded. Outcomes assessed were transjugular intrahepatic portosystemic shunt (TIPS)/transplant‐free survival (TTFS), and biochemical and prognostic outcomes. Results Twenty‐four patients were included. Median age was 59.5 years. Seven were female (29.2%). Etiology included were alcohol (50%), non‐alcoholic steatohepatitis (16.7%), and viral/alcohol (12.5%). Median model for end‐stage liver disease‐sodium (MELD‐Na) was 18.5, with Child–Pugh scores (CPS) A (4.2%), B (50%), and C (45.8%). Improvements in serum sodium (P = 0.014), albumin (P = 0.003), and CPS (P = 0.017) were observed. Reduction in hospitalizations (P = 0.001), particularly portal hypertensive related admissions was observed (relative risk 0.39; 95% confidence interval [CI] 0.21–0.69, P = 0.003), needed to treat 2.09 (95% CI 1.25–3.67). There was a reduction in total paracentesis requirements (P = 0.005). On multivariate analysis, type 2 diabetes mellitus significantly increased risk of TIPS/transplant/death (hazard ratio 6.16; 95% CI 1.23–30.84, P = 0.027). Median TTFS improved in patients with a change in MELD‐Na ≤1 at 1 month: 29.4 months versus 7.7 months (P = 0.011). Conclusion Outpatient HA infusions decrease portal hypertensive related hospital admissions, improve serum sodium, albumin levels, and CPS. Type 2 diabetes mellitus and change in MELD‐Na score help discriminate those likely to benefit most.

Background: COVID-19 has rapidly become a major health emergency worldwide. The characteristic, outcome, and risk factor of COVID-19 in patients with decompensated cirrhosis remain unclear. Methods: Medical records were collected from 23 Chinese hospitals. Patients with decompensated cirrhosis and age- and sex-matched non-liver disease patients were enrolled with 1:4 ratio using stratified sampling. Results: There were more comorbidities with higher Chalson Complication Index (p < 0.001), higher proportion of patients having gastrointestinal bleeding, jaundice, ascites, and diarrhea among those patients (p < 0.05) and in decompensated cirrhosis patients. Mortality (p < 0.05) and the proportion of severe ill (p < 0.001) were significantly high among those patients. Patients in severe ill subgroup had higher mortality (p < 0.001), MELD, and CRUB65 score but lower lymphocytes count. Besides, this subgroup had larger proportion of patients with abnormal (PT), activated partial thromboplatin time (APTT), D-Dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBL) and Creatinine (Cr) (p < 0.05). Multivariate logistic regression for severity shown that MELD and CRUB65 score reached significance. Higher Child-Pugh and CRUB65 scores were found among non-survival cases and multivariate logistic regression further inferred risk factors for adverse outcome. Receiver Operating Characteristic (ROC) curves also provided remarkable demonstrations for the predictive ability of Child-Pugh and CRUB65 scores. Conclusions: COVID-19 patients with cirrhosis had larger proportion of more severely disease and higher mortality. MELD and CRUB65 score at hospital admission may predict COVID-19 severity while Child-Pugh and CRUB65 score were highly associated with non-survival among those patients.

Objective The aim of this study was to ascertain whether red cell distribution width-to-albumin ratio (RAR) is associated with survival in hepatitis B virus (HBV)–associated decompensated cirrhosis (DC) patients. Methods A cohort of 167 patients with confirmed HBV-DC was enrolled in our study. Demographic characteristics and laboratory data were obtained. The main endpoint was mortality at 30 days. The receiver operating characteristic curve and multivariable regression analysis were used to assess the power of RAR for predicting prognosis. Results Mortality at 30 days was 11.4% (19/167). The RAR levels were higher in the nonsurvivors than the survivors, and elevated RAR levels were clearly associated with poor prognosis. Moreover, the predictive powers of RAR and Model for End-Stage Liver Disease score were not obviously different. Conclusion Our data indicate that RAR is a novel potential prognostic biomarker of mortality in HBV-DC. [ABSTRACT FROM AUTHOR]

The 2021 Chronic Kidney Disease Epidemiology Collaboration equation [CKD-EPI 2021] is a race-neutral equation recently developed and rapidly implemented as a reference standard to estimate glomerular filtration rate(GFR). However, its role in cirrhosis has not been examined especially in low GFR. We analyzed the performance of CKD-EPI 2021 compared to other equations with protocol-measured GFR (mGFR) in cirrhosis. We analyzed 2090 unique adult patients with cirrhosis undergoing protocol GFR measurements using iothalamate clearance from 1985 to 2015 when listed for liver transplantation at Baylor University in Dallas and Fort Worth, Texas. Using mGFR as a reference standard, the CKD-EPI 2021 was compared to CKD-EPI 2012, Modification of Diet in Renal Disease-4, Modification of Diet in Renal Disease-6, Royal Free Hospital, and GFR Assessment in Liver disease overall and in certain subgroups (ascites, mGFR ≤ 30 mL/min/1.73 m 2 , diagnosis, Model for End-Stage Liver Disease and gender). We examined bias (difference between eGFR and mGFR), accuracy (p30: eGFR within ± 30% of mGFR) and agreement between eGFR and mGFR categories. CKD-EPI 2021 had the second lowest bias across the entire range of GFR after GFR Assessment in Liver disease (6.6 vs. 4.6 mL/min/1.73 m 2 , respectively, p < 0.001). The accuracy of CKD-EPI 2021 was similar to CKD-EPI 2012 (p30 = 67.8% vs. 67.9%, respectively) which was higher than the other equations ( p < 0.001). It had a similar performance in patients with ascites, by diagnoses, Model for End-Stage Liver Disease subgroups, by gender, and in non-Black patients. However, it had a relatively higher overestimation in mGFR ≤ 30 mL/min/1.73 m 2 than most equations (18.5 mL/min/1.73m 2 , p < 0.001). Specifically, 64% of patients with mGFR ≤ 30 mL/min/1.73m 2 were incorrectly classified as a less severe CKD stage by CKD-EPI 2021. In Blacks, CKD-EPI 2021 underestimated eGFR by 17.9 mL/min/1.73 m 2 , which was higher than the alternate equations except for Royal Free Hospital ( p < 0.001). The novel race-neutral eGFR equation, CKD-EPI 2021, improves the GFR estimation overall but may not accurately capture true kidney function in cirrhosis, specifically at low GFR. There is an urgent need for a race-neutral equation in liver disease reflecting the complexity of kidney function physiology unique to cirrhosis, given implications for organ allocation and dual organ transplant., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Transjugular intrahepatic portosystemic shunt (TIPS) is a medical procedure that has been used to manage variceal bleeding and ascites in patients with cirrhosis. It can prevent further decompensation and improve the survival of high-risk decompensated patients. Recent research indicates that TIPS could increase the possibility of recompensation of decompensated cirrhosis when it is combined with adequate suppression of the causative factor of liver disease. However, the results of the studies have been based on retrospective analysis, and further validation is required by conducting randomized controlled studies. In this context, we highlight the limitations of the current studies and emphasize the issues that must be addressed before TIPS can be recommended as a potential recompensating tool., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

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OBJECTIVE: Prognostic models proposed for cirrhotic patients' survival have not been satisfactorily investigated in the Vietnam population, especially in the medium-term period. PATIENTS AND METHODS: In this prospective study, we enrolled a total of 904 patients admitted to Hepato-Gastroenterology Center, Bach Mai Hospital from December 2019 to November 2021 and calculated their CP, MELD, MELD-Na score, IMELD, Refit MELD, and Refit MELD-Na after 2-year follow-up to compare their survival prognosis. RESULTS: The mean age of the patients was 53.8 ±10.8 years, and males constituted 91%. Compared with the surviving group, deceased patients had statistically significant lower albumin, higher INR, serum bilirubin, and creatinine levels with higher means of all prognostic scores. RefitMELD score had the highest AUC (0.768), followed by MELD (0.766), and the lowest belonged to RefitMELDNa (0.669). CONCLUSIONS: In conclusion, deceased patients had significantly higher values of Child-Pugh score and all MELD-based scores than survival. RefitMELD is the most reliable scoring system to predict 2-year mortality in patients with decompensated liver cirrhosis. [ABSTRACT FROM AUTHOR]

BackgroundPatient portals are a common electronic medical record tool that allow for the asynchronous exchange of health information between patients and their health care teams. Patients can leverage patient portals to perform tasks such as viewing test results, reviewing clinical notes, and messaging their health care team. The impact of patient portal use on clinical outcomes in cirrhosis is unknown. ObjectiveIn this study, we evaluated the relationship between patient portal use patterns and readmissions in cirrhosis. MethodsWe identified 131 patients with decompensated cirrhosis with an index cirrhosis-related admission between May 1, 2018, and May 1, 2019. We then examined patient portal enrollment and use data during the 6-month period preceding the study period. Portal functions evaluated included sending a message, reading a message, and reading a test result. Use was categorized as active (sending a message) and passive (reading a message or test result) and was further stratified as no, moderate, or frequent use based on the frequency of portal function use compared to the mean. The primary outcomes were 90-day and overall readmissions, adjusted for age, model for end-stage liver disease–sodium, alcohol-related cirrhosis etiology, ascites, and hepatic encephalopathy. Portal functions assessed included sending a message, reading a message, and reading a result; the total number of times a portal function was performed was divided by the number of months the patient was enrolled in the patient portal during the 6-month period. ResultsThe study population was 50.4% (66/131) female, with a mean age of 58 years. Enrollment in the patient portal was 63.4% (83/131), and there was no significant difference in enrollment based on clinical or demographic characteristics. For the entire cohort, 14.5% (19/131) and 22.1% (29/131) of patients were moderate and frequent active users, respectively. Of those enrolled in the patient portal, 97.6% (81/83) of patients were moderate or frequent passive users for both reading a message and reading a test result. Moderate active users had less 90-day readmissions (odds ratio 0.77, 95% CI 0.60-1.00) and overall readmissions (subdistribution hazard ratio 0.42, 95% CI 0.21-0.84), compared to nonactive users. There was no relationship between readmissions and passive use. ConclusionsPassive use of the patient portal is very high but is not associated with the risk of readmissions in people with decompensated cirrhosis. However, moderately active use of the patient portal is associated with a reduced risk of readmissions. Further work is needed to identify possible confounders and refine key use behaviors that may be protective with regard to the risk of readmission in this population.

Objective: To determine the incidence of decompensated cirrhosis and associated risk factors in people hospitalised with non-alcoholic fatty liver disease (NAFLD) or non- alcoholic steatohepatitis (NASH) with or without cirrhosis. Design: Retrospective cohort study; analysis of linked Queensland Hospital Admitted Patient Data Collection, Queensland Registry of Births, Deaths and Marriages, and Queensland Cancer Register data. Setting, participants: Queensland residents aged 20 years or older admitted to Queensland hospitals with NAFLD/NASH during 1 July 2009 - 31 December 2018. Main outcome measures: Progression to decompensated cirrhosis (ascites, hepatic encephalopathy, or oesophageal variceal bleeding). Results: We included data for 8006 patients in our analysis (10 082 admissions), including 4632 women (58%) and 2514 people with diabetes mellitus (31%); median follow- up time was 4.6 years (interquartile range, 2.7-7.2 years). Three hundred and fifty- one people (4.4%) experienced decompensated cirrhosis during the follow- up period. Of the 6900 people without cirrhosis, 4.5% (95% confidence interval [CI], 3.6-5.7%) experienced decompensated cirrhosis within ten years (mean, 0.5% per year; 95% CI, 0.4-0.6% per year); risk of progression was greater for people aged 70 years or older (v 20-39 years: adjusted hazard ratio [aHR], 4.7; 95% CI, 2.0-11.0) and those who had extrahepatic cancers (aHR, 5.0; 95% CI, 3.0-8.2), history of major cardiovascular events (aHR, 1.9; 95% CI, 1.2-3.1), or diabetes mellitus (aHR, 2.8; 95% CI, 2.0-3.9). Of the 1106 people with cirrhosis, 32.4% (95% CI, 27.2-38.3%) experienced decompensated cirrhosis within ten years (mean, 5.5% per year; 95% CI, 4.8-6.3% per year); risk of progression was greater for those with portal hypertension (aHR, 1.8; 95% CI, 1.3-2.7), extrahepatic cancer (aHR, 1.8; 95% CI, 1.1-2.9), or diabetes mellitus (aHR, 1.5; 95% CI, 1.1-2.0). Compared with people who had neither cirrhosis nor diabetes mellitus, the risk of decompensation was greater for people with cirrhosis (aHR, 10.7; 95% CI, 7.6-15.0) or cirrhosis and diabetes mellitus (aHR, 14.4; 95% CI, 10.1-20.6). Conclusions: Given the greater risk of progression to cirrhosis decompensation in people with diabetes mellitus, a disorder common in people with NAFLD/NASH, identifying advanced fibrosis and providing appropriate treatment for averting disease progression is vital. [ABSTRACT FROM AUTHOR]

Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03–1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84–3.58) for Native American race vs European American race In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment. [Display omitted] Acutely decompensated cirrhosis is a rapid deterioration of patient health leading to nonelective hospital admission. Among patients with acutely decompensated cirrhosis, differences in upstream factors, in particular, genetic ancestry (race) may be associated with differences in health outcomes, such as acute-on-chronic liver failure (characterized by the presence of organ failures) and short-term death (ie, death without liver transplantation within 28 days after presentation). To address these questions, the availability of a comprehensive set of data collected in a recently completed prospective cohort of 1274 Latin American patients nonelectively hospitalized for acutely decompensated cirrhosis was leveraged. Increasing Native American genetic ancestry (and Native American race) was independently associated with increased odds of acute-on-chronic liver failure at presentation, after adjustment for other covariates. Native American genetic ancestry (and its proxy Native American race) are underrepresented in the current acute-on-chronic liver failure medical literature. [ABSTRACT FROM AUTHOR]

In patients with decompensated cirrhosis, sarcopenia and frailty are prevalent. Although several definitions exist for these terms, in the field of hepatology, sarcopenia has commonly been defined as loss of muscle mass, and frailty has been broadly defined as the phenotypic manifestation of the loss of muscle function. Prompt recognition and accurate assessment of these conditions are critical as they are both strongly associated with morbidity, mortality, poor quality of life and worse post-liver transplant outcomes in patients with cirrhosis. In this review, we describe the complex pathophysiology that underlies the clinical phenotypes of sarcopenia and frailty, their association with decompensation, and provide an overview of tools to assess these conditions in patients with cirrhosis. When available, we highlight data focusing on patients with acutely decompensated cirrhosis, such as inpatients, as this is an area of unmet clinical need. Finally, we discuss management strategies to reverse and/or prevent the development of sarcopenia and frailty, which include adequate nutritional intake of calories and protein, as well as regular exercise of at least moderate intensity, with a mix of aerobic and resistance training. Key knowledge gaps in our understanding of sarcopenia and frailty in decompensated cirrhosis remain, including best methods to measure muscle mass and function in the inpatient setting, racial/ethnic variation in the development and presentation of sarcopenia and frailty, and optimal clinical metrics to assess response to therapeutic interventions that translate into a reduction in adverse outcomes associated with these conditions.

Effective antiviral therapy can significantly improve the long-term prognosis of HBV-related decompensated patients, and re-compensation may be achieved in part of the patients. To explore the re-compensation of ascites after HBV suppression and the risk factors, the clinical outcomes of 196 consecutive patients with HBV-related first decompensated cirrhosis of ascites treated with nucleos(t)ide analogue (NUC) were analyzed retrospectively. Among these patients, the median serum HBV DNA level was 5.0 (IQR, 3.0-6.0) log10 IU/mL before treatment. Most patients were given NUC with high barrier to resistance including ETV (152), TDF (1) and TAF (1). Initial combination of LAM plus ADV and LdT plus ADV was used in 41 patients and 1 patients, respectively. After NUC treatment, the percentage of patients with ascites regression was 77.6%, 81.4%, 70.5%, 93.8%, 80.8% at 12, 24, 36, 48, 60 months, respectively (P

Competing Interests: The authors declare that they have no conflict of interest.

Yue Zhang,&ast; Peng Chen,&ast; Wang Zhang, Chenkai Huang,&ast; Xuan Zhu&ast; Department of Gastroenterology, Jiangxi Province and Jiangxi Clinical Research Center for Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuan Zhu; Chenkai Huang, Department of Gastroenterology, Jiangxi Province and Jiangxi Clinical Research Center for Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email waiyongtg@163.com; hckroy@163.comBackground: Acute decompensated cirrhosis (AD) is related to high medical costs and high mortality. We recently proposed a new score model to predict the outcome of AD patients and compared it with the common score model (CTP, MELD and CLIF-C AD score) in the training and validation sets.Materials and Methods: A total of 703 patients with AD were enrolled from The First Affiliated Hospital of Nanchang University between December 2018 and May 2021. These patients were randomly assigned to the training set (n=528) and validation set (n=175). Risk factors affecting prognosis were identified by Cox regression analysis and then used to establish a new score model. The prognostic value was determined by the area under the receiver operating characteristic curve (AUROC).Results: A total of 192 (36.3%) patients in the training cohort and 51 (29.1%) patients in the validation cohort died over the course of 6 months. A new score model was developed with predictors including age, bilirubin, INR, WBC, albumin, ALT and BUN. The new prognostic score (0.022×Age + 0.003×TBil + 0.397×INR + 0.023×WBC- 0.07×albumin + 0.001×ALT + 0.038×BUN) for long-term mortality was superior to three other scores based on both training and internal validation studies.Conclusion: This new score model appears to be a valid tool for assessing the long-term survival of AD patients, improving the prognostic value compared with the CTP, MELD and CLIF-C AD scores.Keywords: new score, prognosis, CTP score, MELD score, CLIF-C AD score

Background and aimsHepatic Hydrothorax (HH) is one of the complications in patients with decompensated cirrhosis and its impact and role in the prognosis of patients with decompensated cirrhosis are not yet clear. Thus, this study aimed to determine the role of HH in patients with decompensated cirrhosis and the long-term impact on their mortality.Materials and methodsA retrospective study analyzed 624 patients with ascites without pleural effusion in decompensated cirrhosis and 113 patients with HH. Propensity scores were calculated based on eight variables, and the HH and non-HH groups were matched in a 1:1 ratio. The effect and role of HH on the prognosis of patients with decompensated cirrhosis was analyzed using the Kaplan–Meier method and Cox proportional hazards regression model.ResultsA total of 737 patients were included. Out of 113 HH patients, 106 could be matched to 106 non-HH patients. After matching, baseline characteristics were well-balanced. The multifactorial Cox proportional hazards model indicated that hepatic encephalopathy and HH were independent risk factors affecting prognostic survival in patients with decompensated cirrhosis (P < 0.01), with risk ratios and 95% confidence intervals (CI) of 2.073 (95% CI: 1.229–3.494, P < 0.01) and 4.724 (95% CI: 3.287–6.789, P < 0.01), respectively. Prognostic survival was significantly worse in the HH group compared to patients in the non-HH group, with mortality rates of 17.9, 30.1, and 59.4% at 6 months, 1 year, and 2 years in the HH group, compared to 0.9, 3.8, and 5.6% in the non-HH group, respectively. The estimated median survival time was 21 (95% CI: 18–25) months in the HH group and 49 (95% CI: 46–52) months in the non-HH group (P < 0.001).ConclusionHepatic hydrothorax is significantly associated with higher mortality in patients with decompensated cirrhosis and is a highly negligible independent decompensated event affecting their prognosis.

Aim Methods Results Conclusions Echocardiography is necessary for portopulmonary hypertension diagnosis, and identifying patients with cirrhosis who require it is challenging. In this study, we aimed to investigate the utility of the total bile acid (TBA) levels as a screening tool for identifying patients with decompensated cirrhosis who should undergo echocardiography for portopulmonary hypertension diagnosis.We evaluated 135 patients with decompensated cirrhosis who underwent liver transplantation. Subsequently, factors contributing to tricuspid regurgitation pressure gradient (TRPG) elevation (≥30 mmHg) were analyzed using preoperative data, including the TBA levels.The median age of patients was 58 years (61 women), and 45 and 90 patients had Child–Turcotte–Pugh grades of B and C, respectively. The median TRPG level was 21 mmHg, and 17 patients (12.6%) showed TRPG elevation. Multiple logistic regression analysis revealed that elevated TBA (odds ratio 4.322; p = 0.013) and main pulmonary artery diameter ≥33 mm (odds ratio 4.333; p = 0.016) were significantly associated with TRPG elevation. The TBA cut‐off value (167.7 μmol/L) showed a high diagnostic performance, with 70.6% sensitivity and 64.4% specificity. Ursodeoxycholic acid (UDCA) administration increased the TBA levels dose‐dependently. Analysis stratified by UDCA use revealed that in patients not taking UDCA (n = 59), elevated TBA levels and younger age significantly contributed to TRPG elevation. However, in those taking UDCA (n = 76), this contribution disappeared, suggesting that UDCA consumption reduced TBA levels' efficiency in diagnosing TRPG elevation.The TBA levels may be a potential screening tool for TRPG elevation; however, caution is warranted when interpreting cases treated with UDCA. [ABSTRACT FROM AUTHOR]

Introduction There are limited therapeutic options to efficiently treat patients with decompensated liver cirrhosis. This trial aims to explore the efficacy and safety of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for the treatment of patients with decompensated liver cirrhosis.Methods and analysis This study is an open-label, dose-escalation, one-armed phase I trial. A single injection of UC-MSCs will be administered in a predetermined dose in each cohort (5.0×107, 1.0×108, 1.5×108 or 2.0×108 cells) according to the ‘3+3’ rule. The primary evaluation measures will include the incidence of adverse events and the change in the Model for End-stage Liver Disease (MELD) score from baseline to the 28th day. Secondary evaluation measures will be evaluated at baseline and at each follow-up point. These measures will include the change in the MELD score from baseline to each follow-up point, the incidence of each complication associated with decompensated cirrhosis, liver transplant-free survival and the incidence of liver failure, among other relevant measures. All patients will be followed up for 24 months. This study will evaluate whether the use of UC-MSCs to treat patients with decompensated liver cirrhosis is safe and tolerable.Ethics and dissemination The study has been approved by the Chinese People’s Liberation Army General Hospital (Approval#: 2018-107-D-4). Once conducted, the results from the study will be published in a peer-reviewed journal.Trial registration number NCT05227846.

Objective: To develop a model that integrates radiomics features and clinical factors to predict upper gastrointestinal bleeding (UGIB) in patients with decompensated cirrhosis., Methods: 104 decompensated cirrhosis patients with UGIB and 104 decompensated cirrhosis patients without UGIB were randomized according to a 7:3 ratio into a training cohort ( n  = 145) and a validation cohort ( n  = 63). Radiomics features of the abdominal skeletal muscle area (SMA) were extracted from the cross-sectional image at the largest level of the third lumbar vertebrae (L3) on the abdominal unenhanced multi-detector computer tomography (MDCT) images. Clinical-radiomics nomogram were constructed by combining a radiomics signature (Rad score) with clinical independent risk factors associated with UGIB. Nomogram performance was evaluated in calibration, discrimination, and clinical utility., Results: The radiomics signature was built using 11 features. Plasma prothrombin time (PT), sarcopenia, and Rad score were independent predictors of the risk of UGIB in patients with decompensated cirrhosis. The clinical-radiomics nomogram performed well in both the training cohort (AUC, 0.902; 95% CI, 0.850-0.954) and the validation cohort (AUC, 0.858; 95% CI, 0.762-0.953) compared with the clinical factor model and the radiomics model and displayed excellent calibration in the training cohort. Decision curve analysis (DCA) demonstrated that the predictive efficacy of the clinical-radiomics nomogram model was superior to that of the clinical and radiomics model., Conclusion: Clinical-radiomics nomogram that combines clinical factors and radiomics features has demonstrated favorable predictive effects in predicting the occurrence of UGIB in patients with decompensated cirrhosis. This helps in early diagnosis and treatment of the disease, warranting further exploration and research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, He, Yang, Zhu, Li, Lei, Tang and Peng.)

Among patients with decompensated cirrhosis, serum creatinine (sCr) is biased by sex, frailty, and hepatic synthetic function, while Cystatin C (cysC) is not. We found that sCr would better associate with waitlist mortality and that the difference between cysC and sCr (cysCsCr diff ) would quantify this bias and be independently associated with outcomes. We measured cysC levels at ambulatory liver transplant visits among 525 consecutive patients seen at our center. We defined the cysCsCr diff as the difference between cysC minus sCr. We compared demographics and clinical characteristics in patients with low, intermediate, and high cysCsCr diff , divided by tertile. We used Cox regression to compare the association between sCr and cysC and waitlist mortality and demonstrate the independent association between cysCsCr diff and waitlist mortality. In Cox regression, cysC was significantly more associated with waitlist mortality than sCr ( p < 0.001). We found that as compared to those with a low cysCsCr diff , those with an intermediate or high cysCsCr diff were more likely to be female, have ascites, have higher frailty, and have higher MELD 3.0 scores ( p < 0.05 for all). Compared to those with a low cysCsCr diff , we found that those in the intermediate and high groups were more likely to die during follow-up (low: 6% vs. intermediate: 8% vs. high: 11%, p = 0.007). We found that after adjusting for the components of the MELD 3.0 score, each 1-point increase in the cysCsCr diff was associated with 1.72× (1.27-2.32) the hazard of waitlist mortality. Our study demonstrates that not only is cysC more associated with waitlist mortality than sCr, but that cysCsCr diff represents a novel independent metric associated with waitlist mortality., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Introduction, aim, and objective: Despite recent evidence suggesting the blood creatinine level is a significant predictor of survival in liver cirrhosis patients, the conventional Child-Pugh (CP) score has held a longstanding position as a valuable prognostic indicator in cirrhotic individuals. This study aimed to compare the predictive capabilities of the modified CP score and the traditional CP score in decompensated cirrhosis patients to evaluate their prognostic power. The objective of this study was to assess the prognostic value of the modified and traditional CP scores in individuals with decompensated cirrhosis by assessing their predictive accuracy., Methods: A total of 100 patients diagnosed with decompensated cirrhosis participated in this prospective study. Each patient's Child-Pugh score and class were determined using admission data, with scores ranging from 5 to 15. Serum creatinine was incorporated as the sixth variable to compute the modified CP score, which ranges from 5 to 19., Results: The percentages of individuals aged 16-30, 31-40, 41-50, 51-60, and above 60 years were as follows: 16.0%, 29.0%, 26.0%, and 11.0%, respectively. The patients had a mean age of 44.71 years and a standard deviation of 13.40 years. Out of the 100 patients studied, 26% were female and 74% were male. Fifty-two percent of patients had mild hepatic encephalopathy, while 24% had moderate encephalopathy and 24% had severe encephalopathy. In cases of moderate and severe hepatic encephalopathy, the creatinine-modified Pugh score showed a considerably large area under the curve (AUC=0.852) on the receiver operating characteristics (ROC) curve., Conclusion:  When blood creatinine is taken into account, it can enhance the Child-Pugh classification's prognostic usefulness. This is especially true for patients with moderate to severe hepatic encephalopathy, where serum creatinine is a key factor in accurately predicting both survival and complications associated with cirrhosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee of Sarojini Naidu Medical College, Agra issued approval #SNMC/IEC/THESIS/2023/175. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kumar et al.)

Introduction: Infections in patients with cirrhosis are associated with high morbidity and mortality. Rifaximin is an antibiotic used to treat and prevent hepatic encephalopathy (HE); however, it has been suggested that it may play a crucial role in reducing infections in these populations., Aim: To evaluate the role of rifaximin in preventing frequent cirrhosis-related infections [spontaneous bacterial peritonitis, pneumonia, urinary tract infection (UTI), and bacteremia], Clostridioides difficil e infection, and all-cause mortality, as well as determining adverse effects and adherence to the drug., Methods: A retrospective cohort study was conducted on decompensated cirrhotic patients with history of HE between January 2017 and November 2022 at a university center. Patients with cirrhosis, regardless of their etiology and severity, were included in the study, encompassing both hospitalized and outpatient cases. The statistical analysis included adjusted general linear models, Poisson regressions, and propensity score matching., Results: We included 153 patients. The mean age in the cohort was 60.2 ± 12.3 years and 67 (43.8%) were women. The main cause of cirrhosis was metabolic dysfunction-associated steatotic liver disease 52 (38%), and the median Model of End-Stage Liver Disease sodium was 16.5 (7-32). In the cohort, 65 (45%) patients used rifaximin. The mean follow-up was 32 months. Eighty-five patients with infectious events were recorded, and a total of 164 infectious events were registered. The main infectious events were UTIs (62, 37.8%) and pneumonia (38, 23.2%). The use of rifaximin was associated with lower infection rates, displaying an incidence rate ratio (IRR) of 0.64 [95% confidence interval (CI) (0.47-0.89); p  = 0.008]. However, no discernible impact on mortality outcome was observed [IRR 1.9, 95% CI (0.9-4.0); p  = 0.09]. There were no reported adverse effects, and no patient discontinued the therapy due to adverse effects., Conclusion: The use of rifaximin significantly reduces infections in patients with cirrhosis and HE. Despite rifaximin was associated with a decreased all-cause mortality, this impact was not statistically significant in the adjusted analysis., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

The progression of cirrhosis with clinically significant portal hypertension towards decompensated cirrhosis remains clinically challenging and the evolution towards acute-on-chronic liver failure (ACLF), with one or more extrahepatic organ failures, is associated with very high mortality. In the last decade, significant progress has been made in the understanding of the mechanisms leading to decompensation and ACLF. As portal hypertension advances, bacterial translocation across an impaired gut barrier culminates in endotoxaemia, systemic inflammation and cirrhosis-associated immune dysfunction (CAID). Gut-derived systemic inflammation and CAID have become the logical targets for innovative therapies that prevent hepatic decompensation episodes and the progression to ACLF.Furthermore, classification of disease and biomarker discovery to personalise care have advanced in the field. This review discusses progress in biomarker discovery and personalisation of treatment in decompensated cirrhosis and ACLF., Competing Interests: Competing interests: RH and ALG as an editor of the journal or an Editorial Board Member. JT has received speaking and/or consulting fees from Versantis, Gore, Boehringer-Ingelheim, Falk, Grifols, Genfit and CSL Behring., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

There is a paucity of information related to the usefulness of corticosteroid therapy in autoimmune hepatitis (AIH) with decompensated cirrhosis. In this study, we sought to determine the therapeutic effect of corticosteroids in this special group of AIH patients. Eighty-two AIH patients with decompensated cirrhosis were included through a retrospective analysis from January 2009 to September 2015. Sixty-four patients were treated with corticosteroids while 18 patients did not receive any corticosteroids. Clinical, laboratory, and histological characteristics and outcomes were analyzed comparing corticosteroid-treated and untreated groups. Patients that did not receive corticosteroids were older than corticosteroid-treated patients and had a worse survival. In corticosteroid-treated group, 40 of 64 patients reverted to compensated state and 15 patients remained decompensated, while 9 patients experienced liver-related death or transplantation. Patients who reverted to compensated state had significantly greater ALT, AST, GGT, white blood cell count, and platelet levels at presentation. Changes (Δ) in total bilirubin (TBIL) and MELD scores at day 7 after starting corticosteroid therapy revealed favorable predictive effects of treatment outcomes. Survival was significantly greater in patients with a ΔTBIL

Background: Few randomized trials have evaluated the effect of postdischarge interventions for patients with liver cirrhosis. This study assessed the effects of a postdischarge intervention on readmissions and mortality in patients with decompensated liver cirrhosis., Methods: We conducted a randomized controlled trial at a specialized liver unit. Adult patients admitted with complications of liver cirrhosis were eligible for inclusion. Participants were allocated 1:1 to standard follow-up or a family-focused nurse-led postdischarge intervention between December 1, 2019, and October 31, 2021. The 6-month intervention consisted of a patient pamphlet, 3 home visits, and 3 follow-up telephone calls by a specialized liver nurse. The primary outcome was the number of readmissions due to liver cirrhosis., Results: Of the 110 included participants, 93% had alcohol as a primary etiology. We found no significant differences in effects in the primary outcomes such as time to first readmission, number of patients readmitted, and duration of readmissions or in the secondary outcomes like health-related quality of life and 6- and 12-month mortality. A post hoc exploratory analysis showed a significant reduction in nonattendance rates in the intervention group (RR: 0.28, 95% CI: 0.13-0.54, p=0.0004) and significantly fewer participants continuing to consume alcohol in the intervention group (p=0.003). After 12 months, the total number of readmissions (RR: 0.76, 95% CI: 0.59-0.96, p=0.02) and liver-related readmissions (RR: 0.55, 95% CI: 0.36-0.82, p=0.003) were reduced in the intervention group., Conclusions: A family-focused postdischarge nursing intervention had no significant effects on any of the primary or secondary outcomes. In a post hoc exploratory analysis, we found reduced 6-month nonattendance and alcohol consumption rates, as well as reduced 12-month readmission rates in the intervention group., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Patients with cirrhosis are susceptible to develop bacterial infections that trigger acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Infections with multidrug-resistant organisms (MDRO) are associated with deleterious outcome. MDRO colonisation frequently proceeds MDRO infections and antibiotic therapy has been associated with MDRO colonisation., Aim: The aim of the study was to assess the influence of non-antibiotic medication contributing to MDRO colonisation., Methods: Three hundred twenty-four patients with AD and ACLF admitted to the ICU of Frankfurt University Hospital with MDRO screening were included. Regression models were performed to identify drugs associated with MDRO colonisation. Another cohort (n = 129) from Barcelona was included to validate. A third multi-centre cohort (n = 203) with metagenomic sequencing data of stool was included to detect antibiotic resistance genes., Results: A total of 97 patients (30%) were identified to have MDRO colonisation and 35 of them (11%) developed MDRO infection. Patients with MDRO colonisation had significantly higher risk of MDRO infection than those without (p = 0.0098). Apart from antibiotic therapy (odds ratio (OR) 2.91, 95%-confidence interval (CI) 1.82-4.93, p < 0.0001), terlipressin therapy in the previous 14 days was the only independent covariate associated with MDRO colonisation in both cohorts, the overall (OR 9.47, 95%-CI 2.96-30.23, p < 0.0001) and after propensity score matching (OR 5.30, 95%-CI 1.22-23.03, p = 0.011). In the second cohort, prior terlipressin therapy was a risk factor for MDRO colonisation (OR 2.49, 95% CI 0.911-6.823, p = 0.075) and associated with risk of MDRO infection during follow-up (p = 0.017). The validation cohort demonstrated that antibiotic inactivation genes were significantly associated with terlipressin administration (p = 0.001)., Conclusions: Our study reports an increased risk of MDRO colonisation in patients with AD or ACLF, who recently received terlipressin therapy, while other commonly prescribed non-antibiotic co-medications had negligible influence. Future prospective trials are needed to confirm these results., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Aetiological therapy improves liver function and may enable hepatic recompensation in decompensated cirrhosis., Aims: We explored the potential for recompensation in patients with decompensated primary biliary cholangitis (PBC) - considering a biochemical response to ursodeoxycholic acid (UDCA) according to Paris-II criteria as a surrogate for successful aetiological treatment., Methods: Patients with PBC were retrospectively included at the time of first decompensation. Recompensation was defined as (i) resolution of ascites and hepatic encephalopathy (HE) despite discontinuation of diuretic/HE therapy, (ii) absence of variceal bleeding and (iii) sustained liver function improvement., Results: In total, 42 patients with PBC with decompensated cirrhosis (age: 63.5 [IQR: 51.9-69.2] years; 88.1% female; MELD-Na: 13.5 [IQR: 11.0-15.0]) were included and followed for 41.9 (IQR: 11.0-70.9) months after decompensation. Seven patients (16.7%) achieved recompensation. Lower MELD-Na (subdistribution hazard ratio [SHR]: 0.90; p = 0.047), bilirubin (SHR per mg/dL: 0.44; p = 0.005) and alkaline phosphatase (SHR per 10 U/L: 0.67; p = 0.001) at decompensation, as well as variceal bleeding as decompensating event (SHR: 4.37; p = 0.069), were linked to a higher probability of recompensation. Overall, 33 patients were treated with UDCA for ≥1 year and 12 (36%) achieved Paris-II response criteria. Recompensation occurred in 5/12 (41.7%) and in 2/21 (9.5%) patients with vs. without UDCA response at 1 year, respectively. Recompensation was linked to a numerically improved transplant-free survival (HR: 0.46; p = 0.335). Nonetheless, 4/7 recompensated patients presented with liver-related complications after developing hepatic malignancy and/or portal vein thrombosis and 2 eventually died., Conclusions: Patients with PBC and decompensated cirrhosis may achieve hepatic recompensation under UDCA therapy. However, since liver-related complications still occur after recompensation, patients should remain under close follow-up., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)