Search

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

Objective: Cirrhotic cardiomyopathy (CCM) is associated with increased morbidity and mortality in patients with liver cirrhosis. Yet, it remains an under-diagnosed entity. Further, its relation to the severity of cirrhosis is contradictory. We conducted this study on an Indian population to determine the cardiac dysfunctions in cirrhosis of the liver and correlations with etiologies and cirrhosis severity. Methods: This study enrolled patients with diagnosed liver cirrhosis without any cardiac disease or conditions affecting cardiac function. All participants were evaluated clinically, electrocardiographically, and echocardiographically. Cirrhosis severity was assessed by scores from the Model for End-stage Liver Disease (MELD) and Child–Turcotte–Pugh (CTP) tests. Cirrhotic cardiomyopathy was defined as diastolic dysfunction and/or systolic dysfunction with QT prolongation. Results: Ninety-six patients were evaluated, and CTP-A stage of cirrhosis was found in 23 (24%), CTP-B in 42 (43.8%), and CTP-C in 31 (32.3%) cases. Systolic dysfunction was most frequent (P=0.014), and left ventricular ejection fraction was significantly reduced (P=0.001) in CTP-C stage of cirrhosis. Cirrhotic cardiomyopathy was found in 39.6% (n=38) of patients; CCM patients had significantly higher CTP scores (9.6±2.6 versus 8.3±2.3, P=0.012) as well as MELD scores (19.72±4.9 versus 17.41±4.1, P=0.015) in comparison to patients without CCM. Conclusion: Cirrhotic cardiomyopathy has a positive relationship with the severity of cirrhosis. Systolic function declines with the severity of cirrhosis, and overt systolic dysfunction can be present, particularly in the advanced stage of cirrhosis of the liver.

BackgroundDiastolic dysfunction (DD), one of the earliest signs of cirrhotic cardiomyopathy (CCM), is included in the revised 2019 CCM criteria. Nonetheless, relevant research regarding the effects of revised DD on post-liver transplantation (LT) outcomes remains limited.MethodsThis retrospective study enrolled patients who underwent LT for decompensated cirrhosis, from January 2018 to March 2021. Patients were divided into DD and non-DD groups. Clinical data were collected. Patients were followed up with, for at least 1 year post-LT; cardiovascular adverse events (AEs) and survival status were recorded. Risk factors were identified using 1:2 propensity score matching (PSM), after adjusting for confounding factors. The caliper value was set to 0.02.ResultsOf 231 patients, 153 were diagnosed with DD (male, 81.8%; mean age, 51.5 ± 9.5 years). Nineteen patients with DD died within 1 year, post-LT. After PSM, 97 and 60 patients were diagnosed with and without DD, respectively. Patients with DD had longer intensive care unit (ICU) stays, higher perioperative cardiovascular AEs, and higher mortality rates than those without DD. In a multivariate analysis, interventricular septum (IVS), left atrial volume index (LAVI), and potassium levels were independent prognostic factors of perioperative cardiovascular AEs, while a decreased early diastolic mitral annular tissue velocity (e’), increased neutrophil-to-lymphocyte ratio (NLR) and tumor markers were predictors of mortality within 1 year post-LT after PSM (P

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.

We report the case of a 36‑year‑old male who was referred to us with a provisional diagnosis of ethanol‑related acute on chronic liver failure with ascites, encephalopathy, and altered liver function tests (LFTs). The patient underwent a living donor liver transplant. Posttransplant, he had an uneventful recovery till postoperative day (POD) day 7 when he developed tachycardia and low‑grade fever. The immunosuppression has to be withheld till POD 26. The patient later developed deranged LFT and an initial liver biopsy showed features of acute cellular rejection. He also had ongoing tachycardia; thus, immunosuppression was withheld. Subsequent to that patient developed rapid progression from progressive early to chronic rejection (CR) within 78 days posttransplant. The patient initially responded to antithymocyte globulin, but finally succumbed to fungal infection. CR usually occurs over 6 months posttransplant. The occurrence of CR was noted very early in the index patients. This case highlights the importance of a basic step‑wise approach to a case post liver transplant. It also highlights the importance of specialized liver histopathology aiding in early diagnosis. [ABSTRACT FROM AUTHOR]

Objective: Liver cirrhosis, which is considered as the terminal stage of liver diseases, has become life-threatening among non-communicable diseases in the world. Viral hepatitis (hepatitis B and C) is the major risk factor for the development and progression of chronic liver cirrhosis. The asymptomatic stage of cirrhosis is considered as the compensated cirrhosis whereas the symptomatic stage is considered as decompensated cirrhosis. The latter stage is characterized by complex disorder affecting multiple systems of liver organ with frequent hospitalization. In this paper, we formulate system of fractional differential equations of chronic liver cirrhosis with frequent hospitalization to investigate the dynamics of the disease. The fundamental properties including the existence of positive solutions, positively invariant set, and biological feasibility are discussed. We used generalized mean value theorem to establish the existence of positive solutions. The Adams-type predictor-evaluate-corrector-evaluate approach is used to present the numerical scheme the fractional erder model. Results: Using the numerical scheme, we simulate the solutions of the fractional order model. The numerical simulations are carried out using MATLAB software to illustrate the analytic findings. The analysis reveals that the number of decompensated cirrhosis individuals decreases when the progression rate and the disease's past states are considered. [ABSTRACT FROM AUTHOR]

Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) are used for diagnosis of liver fibrosis and steatosis. This study aimed to noninvasively evaluate hepatic steatosis and fibrosis in liver transplant recipients using CAP and LSM and the impact on survival of patients. In a prospective study, adult liver transplant recipients were included. CAP and LSM obtained during transient elastography (TE) were used for assessment of hepatic steatosis and fibrosis. Patients were followed during 4 years for mortality as the main outcome after liver transplantation. From 296 patients, 24.7% and 25% of liver transplant recipients had liver steatosis and fibrosis in CAP and LSM, respectively. In multivariable Cox regression analysis, etiology of liver disease (NASH versus non-NASH) (HR: 3.125; 95% CI: 1.594–6.134; p = 0.001), and post-transplant diabetes mellitus (PTDM) (HR: 2.617; 95% CI: 1.396–4.926; p = 0.003) were associated with hepatic steatosis after liver transplantation. In multivariable Cox regression analysis, liver fibrosis was an independent predictor of mortality after liver transplantation (HR: 4.926; 95%CI: 1.779–13.513; p = 0.002). CAP and LS measurement during TE are useful methods for diagnosis of hepatic steatosis and fibrosis in liver transplant recipients. LS measurement might predict long-term survival of patients. [ABSTRACT FROM AUTHOR]

Purpose of Review: Our understanding of beta blockers in liver cirrhosis has transformed over the last 40 years. However, questions remain over their safety in acute decompensation and acute on chronic liver failure. Since these conditions are associated with significant morbidity and mortality, a critical appraisal of recent literature is imperative to help guide clinicians. Recent Findings: The latest BAVENO guidelines now recommend carvedilol in all patients with clinically significant portal hypertension to prevent decompensation. There is significant data which shows safety of beta blocker use in decompensated cirrhosis but concerns remain in refractory ascites. There is also a short-term mortality benefit demonstrated in acute on chronic liver failure. Summary: With the latest guidelines and recent evidence, it seems beta blocker use will continue to increase. Future studies should aim to identify biomarkers that can determine who will benefit from beta blockers and help guide therapy. [ABSTRACT FROM AUTHOR]

Purpose of Review: The development of acute failure of the kidneys in the context of decompensated cirrhosis represents one of the most challenging scenarios in clinical medicine due to the severity and complexity of the coexistence of those 2 illnesses. Thus, managing those cases can be cumbersome. Recent Findings: While the state of advanced cirrhosis and portal hypertension can lead to a unique type of acute kidney injury (AKI)—hepatorenal syndrome type 1 (HRS-1)—a number of other etiologies can cause AKI, such as prerenal or cardiorenal insults, acute tubular injury, and other parenchymal entities. As a result, medical management of AKI in cirrhosis should be dictated by the driving cause of AKI. Summary: Intravenous albumin is the preferred volume expander for hypovolemic states. Decongestive therapies are indicated in tense ascites-associated abdominal compartment syndrome and/or cardiorenal syndrome type 1. Vasoconstrictor therapy aimed to a specific rise in mean arterial pressure constitutes the cornerstone of the management of HRS-1. Most tubular causes of AKI are managed with supportive care, whereas other tubulointerstitial and glomerular conditions may warrant other interventions such as drug discontinuation, immunosuppression, or antimicrobial/antiviral therapy. Ultimately, AKI unresponsive to medical management may progress, and patients may ultimately necessitate renal replacement therapy (RRT) to sustain life. However, RRT must be carefully considered in this patient population taking in consideration eligibility for liver transplantation, life expectancy, risks and morbidity associated with RRT, and patients' wishes and those of their families or support network. [ABSTRACT FROM AUTHOR]

Background: We developed a nationwide database that stores data of patients with primary liver cancer (PLC) and decompensated cirrhosis (DC) on an admission basis.Methods: A database was constructed using the National Clinical Database, a nationwide registry platform for various diseases in Japan. Mutual data exchange was possible with the Nationwide Follow-up Survey of Primary Liver Cancer in Japan by the Liver Cancer Study Group of Japan. The stored data on the admission of patients with PLC, DC, or both, included treatment details as well as patient characteristics.Results: A total of 37,705 admissions (29,489 PLC, 10,077 DC, and 1862 for both) in 21,376 patients from 224 hospitals were analyzed. The proportions of patients with hepatitis B, hepatitis C, and non-viral etiology were 11.9%, 36.2%, and 42.6%, respectively, in PLC, and 7.5%, 23.8%, and 55.0%, respectively, in DC. The mean ages (± standard deviation) on admission with PLC and DC were 73 ± 10 and 68 ± 13 years, respectively. The Barcelona Clinic Liver Cancer (BCLC) stage for PLC was 0, A, B, C, and D in 22.0%, 17.1%, 29.6%, 15.1%, and 5.1%, respectively. Treatment modalities for PLC were resection, ablation, transarterial chemoembolization, and systemic therapy in 18.4%, 22.8%, 33.7%, and 11.4%, respectively. A vasopressin receptor V2 antagonist was used in 38.2% in addition to conventionally used loop diuretics and aldosterone antagonists for DC.Conclusions: The distribution of treatment options for PLC on admission differed from that of the initial treatment. Newly introduced drugs are widely used in patients with DC. [ABSTRACT FROM AUTHOR]

Transjugular intrahepatic porto-systemic shunt (TIPS) ameliorates renal function in type-2 hepatorenal syndrome (HRS). Available evidence is based on 'old' HRS diagnostic criteria, and not on the current definition of HRS – chronic kidney disease (HRS-CKD). Among patients who underwent TIPS for refractory ascites over the last 12 years, we investigated clinical and renal function evolution of those with HRS-CKD. among 212 patients, 41 with HRS-CKD were included. Renal function was evaluated for 12 months after TIPS, along with management of ascites and transplant-free survival (TFS). renal function significantly improved already one week after TIPS [serum creatinine (sCr): 1.37 ± 0.23 vs 1.94 ± 0.54 mg/dl, p < 0.001]; the amelioration was maintained during the whole follow-up and was observed in every CKD stage, defined according to baseline estimated Glomerular Filtration Rate (eGFR). sCr and eGFR became comparable between different CKD stages after only one week, whilst significantly different at baseline. TIPS led to a remarkable improvement in the control of ascites in all CKD stages and no significant differences in TFS were recorded. TIPS led to an early, substantial and persistent improvement in renal function in patients with HRS-CKD, irrespective of their baseline CKD stage. [ABSTRACT FROM AUTHOR]

Background and aims: Recent studies have debated the utility of beta-blockers to prevent variceal hemorrhage (V.H.) in cirrhosis patients with ascites. We aimed to evaluate the safety and efficacy of propranolol (PPL) compared to endoscopic variceal ligation (EVL) for V.H. primary prevention in patients with ascites. Methods: Cirrhosis patients with ≥ grade 2 ascites and varices needing primary prophylaxis were randomly assigned to receive either PPL (n = 80) or EVL (n = 80). Patients were followed monthly until 12 months or transplant or death. The primary endpoint was 12-month transplant-free-survival (TFS). Secondary endpoints were the incidence of V.H., acute kidney injury (AKI), and control of ascites. Results: Baseline characteristics were similar between the groups. PPL-group had a lower 12-month TFS (76.0% vs. 89.7%; p = 0.02) as compared with EVL-group. Mean arterial pressure ≤ 82 mmHg and MELD-sodium were the independent predictors of mortality. Incidence of VH was comparable between PPL and EVL-groups [6 (7.5%) vs. 2 (2.5%), p = 0.13]. In PPL vs. EVL-group, more patients had worsening of ascites (15% vs. 5%; p = 0.03), developed refractory ascites (13.7% vs.3.7%; p = 0.02), relapse of ascites (37.1% vs. 16.4%, p < 0.01), and AKI (26.2% vs. 12.5%; p = 0.02). Side effects were comparable between the two groups. Conclusions: Primary VH-prophylaxis with PPL is associated with lower survival, poor control of ascites, and increased risk of AKI in cirrhosis patients with ≥ grade 2 ascites. PPL and EVL are equally effective in preventing V.H. Serial monitoring of blood pressures and renal functions is needed in cirrhosis patients with ascites on PPL (NCT02649335). [ABSTRACT FROM AUTHOR]

Background & Aims: Sarcopenia, a prevalent condition, significantly impacts the prognosis of patients with decompensated cirrhosis (DC). Serum fibroblast growth factor 21 (FGF21) levels are significantly higher in DC patients with sarcopenia. Satellite cells (SCs) play a role in aging- and cancer-induced sarcopenia. Here, we investigated the roles of FGF21 and SCs in DC-related sarcopenia as well as the underlying mechanisms., Methods: We developed two DC mouse models and performed in vivo and in vitro experiments. Klotho beta (KLB) knockout mice in SCs were constructed to investigate the role of KLB downstream of FGF21. In addition, biological samples were collected from patients with DC and control patients to validate the results., Results: Muscle wasting and impaired SC myogenesis were observed in the DC mouse model and patients with DC. Elevated circulating levels of liver-derived FGF21 were observed, which were significantly negatively correlated with skeletal muscle mass/skeletal muscle index. Liver-secreted FGF21 induces SC dysfunction, contributing to sarcopenia. Mechanistically, FGF21 in the DC state exhibits enhanced interactions with KLB on SC surfaces, leading to downstream phosphatase and tensin homolog upregulation. This inhibits the protein kinase B (PI3K/Akt) pathway, hampering SC proliferation and differentiation, and blocking new myotube formation to repair atrophy. Neutralizing circulating FGF21 using neutralizing antibodies, knockdown of hepatic FGF21 by adeno-associated virus, or knockout of KLB in SCs effectively improved or reversed DC-related sarcopenia., Conclusions: Hepatocyte-derived FGF21 mediates liver-muscle crosstalk, which impairs muscle regeneration via the inhibition of the PI3K/Akt pathway, thereby demonstrating a novel therapeutic strategy for DC-related sarcopenia., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: An updated summary of the research profile of nutrition for the last 30 years for decompensated cirrhosis is lacking. This study aimed to explore the literature on nutrition for decompensated cirrhosis, draw a visual network map to investigate the research trends, and provide suggestions for future research. The Web of Science database retrieves the literature on nutrition for decompensated cirrhosis between 1994 and 2024., Methods: We used the cooperative, co-occurrence, and co-citation networks in the CiteSpace knowledge graph analysis tool to explore and visualize the relevant countries, institutions, authors, co-cited journals, keywords, and co-cited references., Results: We identified 741 articles on nutrition for decompensated cirrhosis. The number of publications and research interests has generally increased. The USA contributed the largest number of publications and had the highest centrality. The University of London ranked first in the number of articles issued, followed by the University of Alberta and Mayo Clinic. TANDON P, a "core strength" researcher, is a central hub in the collaborative network. Of the cited journals, HEPATOLOGY had the highest output (540, 15.3%)., Conclusions: Over the past three decades, the focus of research on nutrition in decompensated cirrhosis has shifted from "hepatic encephalopathy, intestinal failure, metabolic syndrome, and alcoholic hepatitis" to "sarcopenia and nutritional assessment." In the future, nutritional interventions for sarcopenia should be based on a multimodal approach to address various causative factors. Its targeted treatment is an emerging area that warrants further in-depth research.

Background: Liver cirrhosis is a prominent global contributor to mortality, and hyponatremia is a common complication in patients with decompensated chronic liver disease (DCLD). Hyponatremia is characterized by kidney impairment when eliminating solute-free water. The presence of contradictory findings in existing literature prompted this study., Objective: The objective of this study was to determine the prevalence of hyponatremia in patients with DCLDs presenting at a tertiary care hospital., Methodology:  This six-month cross-sectional study was performed at the Allied Institute of Medical Sciences Teaching Hospital in Gujranwala, Pakistan, from January 2022 to June 2022. A total of 133 patients were selected as subjects. Researchers took blood samples from these patients and sent the samples to the hospital pathology lab for evaluation of serum sodium levels. If sodium levels were ≤130 mmol/L, the patient was considered to have hyponatremia. All information was recorded on proforma., Results:  The mean age of patients was 47.68 ± 12.89 years. Overall, 80 (60.15%) were male, and 53 (39.85%) female. The mean BMI of patients was 23.20 ± 3.11 kg/m 2 and the average duration of DCLD was 7.24 ± 4.12 years. Among participants, 48 (36.09%) patients had hyponatremia, whereas 85 (63.91%) did not have hyponatremia. The mean sodium level was 132.39 ± 11.37 mEq/L. Stratified analysis based on patient age revealed that among patients aged 21-45 years, 27 (45.8%) had hyponatremia, whereas, in the group aged 46-70 years, 21 (28.4%) had hyponatremia with a p-value < 0.05. Stratification of the basis of BMI, among underweight patients, all eight (100%) had hyponatremia, whereas of overweight patients, 14 (31.1%) had hyponatremia. This difference was statistically significant (p < 0.05)., Conclusion: The prevalence of hyponatremia was notably elevated among individuals suffering from DCLD. Age and BMI were the most common risk factors for hyponatremia among subjects with DCLD. This study recommends that patients with DCLD should have their serum sodium levels screened at regular intervals to prevent complications, including encephalopathy, which occurs particularly in younger and underweight DCLD patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Gujranwala Medical College/Teaching Hospital, Gujranwala, Pakistan issued approval 377/22. 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, Azam et al.)

Background & Aims: Chronic hepatitis C-related decompensated cirrhosis is associated with lower sustained virologic response (SVR)-12 rates and variable regression of disease severity after direct-acting antiviral agents. We assessed rates of SVR-12, recompensation (Baveno VII criteria), and survival in such patients., Methods: Between July 2018 and July 2023, patients with decompensated chronic hepatitis C-related cirrhosis after direct-acting antiviral agents treatment were evaluated for SVR-12 and then had 6-monthly follow-up., Results: Of 6516 patients with cirrhosis, 1152 with decompensated cirrhosis (age 53.2 ± 11.5 years; 63% men; Model for End-stage Liver Disease-Sodium [MELD-Na]: 16.5 ± 4.6; 87% genotype 3) were enrolled. SVR-12 was 81.8% after 1 course; ultimately SVR was 90.8% after additional treatment. Decompensation events included ascites (1098; 95.3%), hepatic encephalopathy (191; 16.6%), and variceal bleeding (284; 24.7%). Ascites resolved in 86% (diuretic withdrawal achieved in 24% patients). Recompensation occurred in 284 (24.7%) at a median time of 16.5 (interquartile range, 14.5-20.5) months. On multivariable Cox proportional hazards analysis, low bilirubin (aHR, 0.6; 95% confidence interval [CI], 0.5-0.8; P < 0.001), INR (aHR, 0.2; 95% CI, 0.1-0.3; P < 0.001), absence of large esophageal varices (aHR, 0.4; 95% CI, 0.2-0.9; P = 0.048), or gastric varices (aHR, 0.5; 95% CI, 0.3-0.7; P = 0.022) predicted recompensation. Portal hypertension progressed in 158 (13.7%) patients, with rebleed in 4%. Prior decompensation with variceal bleeding (aHR, 1.6; 95% CI, 1.2-2.8; P = 0.042), and presence of large varices (aHR, 2.9; 95% CI, 1.3-6.5; P < 0.001) were associated with portal hypertension progression. Further decompensation was seen in 221 (19%); 145 patients died and 6 underwent liver transplantation. A decrease in MELDNa of ≥3 was seen in 409 (35.5%) and a final MELDNa score of <10 was seen in 335 (29%), but 2.9% developed hepatocellular carcinoma despite SVR-12., Conclusions: SVR-12 in hepatitis C virus-related decompensated cirrhosis in a predominant genotype 3 population led to recompensation in 24.7% of patients over a follow-up of 4 years in a public health setting. Despite SVR-12, new hepatic decompensation evolved in 19% and hepatocellular carcinoma developed in 2.9% of patients. (ClinicalTrials.gov, Number: NCT03488485)., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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.

Background: The clinical features and factors affecting the prognostic survival of hepatic hydrothorax (HH) are currently unknown.Methods: We conducted a retrospective cohort study of 131 patients with HH using the Kaplan-Meier method and Cox proportional hazards regression analysis to assess factors influencing the prognosis of HH.Results: A total of 131 patients were enrolled: the male to female ratio was 80:51 (1.59:1), and the mean age was 52.76 ± 11.88 years. Hepatitis B cirrhosis was the main cause of HH, and abdominal distention and dyspnea were the most common clinical signs. Ascites was present in varying amounts in all patients and was the most common decompensated complication, with pleural effusions mostly seen on the right side (107/131; 82%), followed by the left side (16/131; 12%) and bilateral effusions (8/131; 6%). For overall survival without transplantation, the estimated median survival time was 21 (95% confidence interval [CI]:18-25) months, and survival rates at 6 months, 1 year, and 2 years were 77.2%, 62.4%, and 29.7%, respectively. After controlling for covariates that were associated with liver-related mortality in the univariate analysis, males (hazard ratio [HR]: 1.721, 95% CI: 1.114-2.658, P = 0.005) and combined hepatic encephalopathy (HR: 2.016, 95% CI: 1.101-3.693, P = 0.001) were found to be associated with an increase in liver-related mortality.Conclusions: In this cohort of HH patients without liver transplantation, male sex and hepatic encephalopathy were associated with a higher risk of liver-related death. [ABSTRACT FROM AUTHOR]

Background: Eradication of hepatitis C virus (HCV) from chronic HCV-infected patients could improve liver function and prevent hepatocarcinogenesis in the long term. Eradication of HCV by direct-acting antivirals (DAAs) also leads to dynamic immunological changes. We report a case of recurrent coronavirus disease 2019 (COVID-19) that developed immediately after combination treatment with DAAs for HCV infection and decompensated cirrhosis. Case Report: A 55-year-old male was started on a 12-week treatment with combination of HCV NS5A inhibitor velpatasvir and HCV NS5B polymerase inhibitor sofosbuvir. HCV RNA became undetectable after six weeks of treatment and was undetectable at the end of the treatment (EOT). Twelve days after the EOT, we diagnosed the patient with COVID-19 pneumonia, admitted him to our hospital and he was discharged two weeks later. One week after his discharge, he visited our hospital again, was diagnosed with recurrent COVID-19 pneumonia readmitted for a second time. Four days after second admission, cardiac arrest occurred, however, he recovered from severe COVID-19 and achieved sustained virological response and his liver function improved. Conclusion: In the COVID-19 era, while attention should be paid to the occurrence or exacerbation of infection, including COVID-19, interferon-free DAA combination therapy should be performed for HCV-infected individuals. [ABSTRACT FROM AUTHOR]

Background and Aims: Due to increasing knowledge of the "gut–liver axis", there has been growing interest regarding the use of fecal microbiota transplant in the management of chronic liver disease. There are limited data available and current guidelines are mostly based on expert opinions. We aim to perform the first systematic review investigating safety and efficacy of fecal microbiota transplant particularly among high-risk decompensated cirrhosis patient populations. Methods: Literature search was performed using variations of the keywords "fecal microbiota transplant" and "cirrhosis" on PubMed/Medline from inception to 3 October 2021. The resulting 116 articles were independently screened by two authors. In total, 5 qualifying studies, including 2 randomized control trials and 3 retrospective case series, were found to meet established eligibility criteria and have adequate quality of evidence to be included in this review. Results: Of the total 58 qualifying patients, there were 2 deaths post fecal microbiota transplant, 1 of which could not rule out being related (1.7%). Among the remaining 56 participants, 8 serious adverse events were reported, of which 2 could not rule out being related (3.6%). The success rate of fecal microbiota transplantation in treating recurrent Clostridioides difficile infection among patients with decompensated cirrhosis was 77.8%. The success rate when used as investigational treatment for hepatic encephalopathy was 86.7%, with multiple studies reporting clinically significant improvement in encephalopathy testing scores. Conclusions: We found a marginally higher rate of deaths and serious adverse events from fecal microbiota transplant in our patient population compared with the average immunocompetent population, where it was previously found to have 0 deaths and SAE rate of 2.83%. The efficacy when used for recurrent C.difficile infection was 77.8% and 87% in the decompensated cirrhotic and general populations, respectively. Studies on efficacy in novel treatment of hepatic encephalopathy have been promising. This study concludes that fecal microbiota transplant use in decompensated cirrhosis patients should be used with caution and preferably be limited to research purposes until better data are available. [ABSTRACT FROM AUTHOR]

Ascites is a common complication of decompensated liver cirrhosis, and yet relatively little is known about its biochemical composition. We conducted two metabolomic investigations, comparing the profile of ascites from 33 cirrhotic patients and postoperative peritoneal drainage fluid from 33 surgical patients (Experiment 1). The profile of paired ascites and plasma was also compared in 17 cirrhotic patients (Experiment 2). Gas chromatography–mass spectrometry-based metabolomics identified 29 metabolites that significantly characterized ascites fluid, whether postoperative drainage fluid or plasma were used as controls. Ten elevated amino acids (glutamine, proline, histidine, tyrosine, glycine, valine, threonine, methionine, lysine, phenylalanine) and seven diminished lipids (laurate, myristate, palmitate, oleate, vaccenate, stearate, cholesterol) largely comprised the cirrhotic ascites metabolomic phenotype that differed significantly (adjusted p < 0.002 to 0.03) from peritoneal drainage fluid or plasma. The pattern of upregulated amino acids in cirrhotic ascites did not indicate albumin proteolysis by peritoneal bacteria. Bidirectional clustering showed that the more severe the cirrhosis, the lower the lipid concentration in ascitic fluid. The metabolomic compartment of ascites in patients with decompensated cirrhosis is characterized by increased amino acids and decreased lipids. These novel findings have potential relevance for diagnostic purposes. [ABSTRACT FROM AUTHOR]

Although proposed for the first time several decades ago, the possibility that long-term human albumin could be effective for the treatment of patients with cirrhosis and ascites has become a topic of scientific and clinical discussion in the last decade. Long-term albumin administration represents a completely different treatment perspective compared to acute or short-term uses of albumin. Results from the ANSWER and the MACHT studies indicate that long-term albumin treatment can be effective, safe and able to modify the course of the disease provided that albumin is given at a sufficient dose and for a sufficient time to restore physiological levels and functions of the circulating molecule, which are compromised, at least partially, in patients with decompensated cirrhosis. Further clinical studies and randomised trials are warranted to confirm the clinical benefits of long-term albumin therapy. Important areas for further research include determining the precise target population, the biomarkers of response, the optimal dose and frequency of albumin infusions, the stopping rules, and the cost-effectiveness of treatment in different healthcare systems across the world, particularly in those where the logistical issues and costs related to the periodic intravenous infusions may represent an important limitation to the implementation of this innovative approach in clinical practice. In this review, we will critically analyse the available data on long-term albumin treatment, focusing on the differences that exist between studies, the controversial issues and the future perspectives. [ABSTRACT FROM AUTHOR]

A growing body of research suggests that evidence-based interventions can tackle high rates of hospital readmissions among patients with decompensated cirrhosis. Care bundles are a prime example of an evidence-based intervention to reduce hospital readmissions through documentation and communication. In this pilot study, a comprehensive baseline audit of electronic medical records of 497 discharges for 175 patients was conducted to assess the current standards of care on discharge from Blacktown Hospital, Australia, and the scope for introducing a care bundle. Our results demonstrated suboptimal discharge communication in a number of areas: Only 54% of decompensated cirrhosis patients had a follow-up appointment pre-scheduled at discharge. Despite alcohol being identified as a key cause of cirrhosis in 60% of patients, a review by alcohol services was conducted on only 24.9% of patients. Moreover, a general lack of focus on patient education and health literacy was identified. In conclusion, our pilot study has highlighted areas for improvement in the standard of care provided to this cohort of patients. Implementation of a standardized care bundle could address the current shortfalls, improve the standard of care and refocus discharge planning to address health literacy and education in patients admitted with a decompensated liver. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle index (SMI), the gold standard for sarcopenia, cannot measure muscle strength and requires specialized software and training. Hand-grip strength (HGS) measurement is cheap, requires minimal training and directly reflects muscle strength. We assessed the performance of HGS as a screening tool for sarcopenia in male patients with decompensated cirrhosis (DC). Methods: Consecutive male DC patients (n=155) were enrolled. Baseline liver functions, etiologic work-up and anthropometric measurements were done. SMI was determined from computed tomography (CT) images at L3 level using ImageJ software. Sarcopenia was diagnosed using SMI cut-off <42 cm2/m2 as suggested by the Indian National Association for Study of the Liver. HGS was assessed using a hand-grip dynamometer. Diagnostic performance of HGS for discriminating sarcopenia was described using receiver operating characteristic (ROC) analysis. Diagnostic performance of different HGS cut-offs was assessed. Findings were internally validated using bootstrapping. Results: Mean HGS and SMI were 25.73 ± 5.94 kg and 47.72 ± 8.71 cm2/m2, respectively. HGS showed modest correlation with SMI (tau: 0.31, p <0.001). Sarcopenia was seen in 41 (26.5%) patients. Age and HGS were independent predictors of sarcopenia on multivariate analysis. Area under the ROC curve (AUROC) of HGS for detecting sarcopenia was 0.73 (p<0.001). Optimal cut-off for using HGS as a screening tool was ≤31 kg (sensitivity: 37/41 [90.2%]; specificity: 29/114 [25.4%]; positive predictive value [PPV] : 37/122 [30.3%]; and negative predictive value [NPV]: 29/33 [87.9%]). Conclusion: Prevalence of sarcopenia in Indian male patients with DC is 26.5%. HGS is an independent predictor of sarcopenia and can be used as a screening tool to stratify the need for confirmatory CT-based assessment of sarcopenia. [ABSTRACT FROM AUTHOR]

Background: Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with compensated (C-cirrhosis) and decompensated cirrhosis (D-cirrhosis) are limited. Methods: In this prospective multicenter study, adult participants with C-cirrhosis and D-cirrhosis were enrolled and received two doses of inactivated whole-virion COVID-19 vaccines. Adverse events were recorded within 14 days after any dose of vaccination, and serum samples of enrolled patients were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. Risk factors for negative neutralizing antibody were analyzed. Results: In total, 553 patients were enrolled from 15 centers in China, including 388 and 165 patients with C-cirrhosis and D-cirrhosis. The vaccines were well tolerated, most adverse reactions were mild and transient, and injection site pain (23/388 [5.9%] vs 9/165 [5.5%]) and fatigue (5/388 [1.3%] vs 3/165 [1.8%]) were the most frequently local and systemic adverse events in both the C-cirrhosis and D-cirrhosis groups. Overall, 4.4% (16/363) and 0.3% (1/363) of patients were reported Grades 2 and 3 alanine aminotransferase (ALT) elevations (defined as ALT > 2 upper limit of normal [ULN] but ≤ 5 ULN, and ALT > 5 ULN, respectively). The positive rates of COVID-19 neutralizing antibodies were 71.6% (278/388) and 66.1% (109/165) in C-cirrhosis and D-cirrhosis groups. Notably, Child–Pugh score of B and C levels was an independent risk factor of negative neutralizing antibody. Conclusions: Inactivated COVID-19 vaccinations are safe with acceptable immunogenicity in cirrhotic patients, and Child–Pugh score of B and C levels is associated with hyporesponsive to COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Background: Safety data reported from the large-scale clinical trials of the coronavirus disease 2019 (COVID-19) vaccine are extremely limited in patients with decompensated cirrhosis. The vaccination campaign in this specific population could be difficult due to uncertainty about the adverse events following vaccination. We aimed to assessed the COVID-19 vaccination rate, factors associated with unvaccinated status, and the adverse events following vaccination in patients with decompensated cirrhosis. Methods: This is a retrospective study from Ruijin Hospial (Shanghai, China) on an ongoing prospective cohort designed for long-term survival analysis of decompensated cirrhotic patients who recovered from decompensating events or acute-on-chronic liver failure (ACLF) between 2016 and 2018. We assessed the COVID-19 vaccination rate, the number of doses, type of vaccine, safety data, patient-reported reasons for remaining unvaccinated, factors associated with unvaccinated status, and the adverse events of COVID-19 vaccine. Binary logistic regression was used for identifying factors associated with unvaccinated status. Results: A total of 229 patients with decompensated cirrhosis without previous SARS-CoV-2 infection participated (mean age, 56 ± 12.2 years, 75% male, 65% viral-related cirrhosis). Mode of decompensation were grade II‒III ascites (82.5%), gastroesophageal varices bleeding (7.9%), hepatic encephalopathy (7.9%). Eighty-five participants (37.1%) received at least one dose of vaccination (1 dose: n = 1, 2 doses: n = 65, 3 doses: n = 19) while 62.9% remained unvaccinated. Patient-reported reasons for remaining unvaccinated were mainly fear of adverse events (37.5%) and lack of positive advice from healthcare providers (52.1%). The experience of hepatic encephalopathy (OR = 5.61, 95% CI: 1.24–25.4) or ACLF (OR = 3.13, 95% CI: 1.12–8.69) and post-liver transplantation status (OR = 2.47, 95% CI: 1.06–5.76) were risk factors of remaining unvaccinated independent of residential areas. The safety analysis demonstrated that 75.3% had no adverse events, 23.6% had non-severe reactions (20% injection-site pain, 1.2% fatigue, 2.4% rash) and 1.2% had a severe event (development of acute decompensation requiring hospitalization). Conclusions: Patients with decompensated cirrhosis in eastern China are largely remained at unvaccinated status, particularly those with previous episodes of ACLF or hepatic encephalopathy and liver transplantation recipients. Vaccination against COVID-19 in this population is safe. [ABSTRACT FROM AUTHOR]

Cirrhosis-associated immune dysfunction (CAID) contributes to disease progression and organ failure development. We interrogated immune system function in nonseptic compensated and decompensated cirrhotic patients using the TruCulture whole blood stimulation system, a novel technique that allows a more accurate representation than traditional methods, such as peripheral blood mononuclear cell culture, of the immune response in vivo. Thirty cirrhotics (21 decompensated and 9 compensated) and seven healthy controls (HCs) were recruited. Whole blood was drawn directly into three TruCulture tubes [unstimulated to preloaded with heat-killed Escherichia coli 0111:B4 (HKEB) or lipopolysaccharide (LPS)] and incubated in dry heat blocks at 37°C for 24 h. Cytokine analysis of the supernatant was performed by multiplex assay. Cirrhotic patients exhibited a robust proinflammatory response to HKEB compared with HCs, with increased production of interferon-γ-induced protein 10 (IP-10) and IFN-λ1, and to LPS, with increased production of IFN-λ1. Decompensated patients demonstrated an augmented immune response compared with compensated patients, orchestrated by an increase in type I, II, and III interferons, and higher levels of IL-1β, IL-6, and IL-8 post-LPS stimulation. IL-1β, TNF-α, and IP-10 post-HKEB stimulation and IP-10 post-LPS stimulation negatively correlated with biochemical markers of liver disease severity and liver disease severity scores. Cirrhotic patients exposed to bacterial products exhibit an exaggerated inflammatory response orchestrated by IFNs, IL-6, and IL-8. Poststimulation levels of a number of proinflammatory cytokines negatively correlate with markers of liver disease severity raising the possibility that the switch to an immunodeficient phenotype in CAID may commence earlier in the course of advanced liver disease. [ABSTRACT FROM AUTHOR]

Background: Endothelial damage is one of the pathogenic conditions of acute pulmonary embolism (APE). The essential role of angiogenin, ribonuclease A family, member 2 (Ang-2) in APE remains unclear. This study aimed to investigate the predictive value of Ang-2 in the clinical outcomes of patients with APE. Methods: Plasma Ang-2 levels were measured by an enzyme-linked immunosorbent assay kit using a DuoSet methodology in 118 APE patients and 53 healthy controls. Baseline data relevant to mortality over time were obtained from hospital databases or by patient's follow-up (median follow-up time: 25.0 ± 13.2 months). The main outcome was all-cause mortality. Results: Plasma Ang-2 level was significantly higher in APE patients than in healthy controls (p < 0.001). Patients dying during the first 30 days presented higher baseline levels of Ang-2 than the survivors (p < 0.001). Patients dying during the follow-up also showed higher baseline levels of Ang-2 than the survivors (p < 0.001). The multivariable logistic regression analysis showed that the N-terminal propeptide of B-type natriuretic peptide (NTproBNP) [odds ratio (OR): 19.8; 95% CI: 1.5 - 255.8; p = 0.022] and Ang-2 (OR: 9.9; 95% CI: 1.4 - 70.5; p = 0.022) emerged as independent predictors of the 30-day mortality. Furthermore, the multivariable Cox's regression identified plasma Ang-2 [hazards ratio (HR): 1.35; 95% CI: 1.10 - 1.66; p = 0.004] as an independent predictor of long-term mortality in patients with APE. Conclusions: A high circulating level of Ang-2 can be considered as an independent predictor for the poor outcome of APE and may serve as a biomarker for the risk stratification in patients with APE. [ABSTRACT FROM AUTHOR]

Abstract Background Insulin is highly recommended for diabetes management in persons with liver cirrhosis. However, few studies have evaluated its long-term effects in these persons. We conducted this study to compare the risks of mortality, liver-related complications, and cardiovascular events in persons with type 2 diabetes mellitus (T2DM) and compensated liver cirrhosis. Methods From January 1, 2000, to December 31, 2012, we selected 2047 insulin users and 4094 propensity score-matched nonusers from Taiwan’s National Health Insurance Research Database. Cox proportional hazard models were used to assess the risks of outcomes. Results The mean follow-up time was 5.84 years. The death rate during the follow-up period was 5.28 and 4.07 per 100 person-years for insulin users and nonusers, respectively. In insulin users, the hazard ratios and 95% confidence intervals (CIs) of all-cause mortality, hepatocellular carcinoma, decompensated cirrhosis, hepatic failure, major cardiovascular events, and hypoglycemia were 1.31 (1.18–1.45), 1.18 (1.05–1.34), 1.53 (1.35–1.72), 1.26 (1.42–1.86), 1.41 (1.23–1.62), and 3.33 (2.45–4.53), respectively. Conclusions This retrospective cohort study indicated that among persons with T2DM and compensated liver cirrhosis, insulin users were associated with higher risks of death, liver-related complications, cardiovascular events, and hypoglycemia compared with insulin nonusers.

Abstract Background The development of direct-acting antivirals (DAA) for HCV has revolutionized the treatment of HCV, including its treatment in patients with HIV coinfection. The aim of this study was to compare the changes in liver function between coinfected and monoinfected patients with cirrhosis who achieved HCV eradication by DAA. Methods Patients with pre-treatment diagnosis of HCV liver cirrhosis, consecutively enrolled in the multicenter PITER cohort, who achieved a sustained virological response 12 weeks after treatment cessation (SVR12) were analysed. Changes in Child-Pugh (C-P) class and the occurrence of a decompensating event was prospectively evaluated after the end of DAA treatment. Cox regression analysis was used to evaluate factors independently associated with changes in liver function following viral eradication. Results We evaluated 1350 patients, of whom 1242 HCV monoinfected (median follow-up 24.7, range 6.8–47.5 months after viral eradication) and 108 (8%) HCV/HIV coinfected (median follow-up 27.1, range 6.0–44.6). After adjusting for age, sex, HCV-genotype, HBsAg positivity and alcohol use, HIV was independently associated with a more advanced liver disease before treatment (C-P class B/C vs A) (OR: 3.73, 95% CI:2.00–6.98). Following HCV eradication, C-P class improved in 17/20 (85%) coinfected patients (from B to A and from C to B) and in 53/82 (64.6%) monoinfected patients (from B to A) (p = 0.08). C-P class worsened in 3/56 coinfected (5.3%) (from A to B) and in 84/1024 (8.2%) monoinfected patients (p = 0.45) (from A to B or C and from B to C). Baseline factors independently associated with C-P class worsening were male sex (HR = 2.00; 95% CI = 1.18–3.36), platelet count

Pasteurella multocida is a gram-negative bacterium that colonizes domestic animals. It is commonly implicated in bite and scratch wounds, potentially resulting in cellulitis, superficial abscesses, osteomyelitis, or peritonitis. Rarely, it can lead to bacteremia and septic shock in high-risk patients. We present an atypical presentation of Pasteurella multocida bacteremia and sepsis in a patient with stage 4 decompensated cirrhosis. The patient presented with melena and altered mental status with CT imaging showing a heterogeneous nodular liver along with an enlarged portal vein, gastric varices, and ascites consistent with decompensated cirrhosis. The patient was initially managed with intravenous (IV) octreotide and pantoprazole, blood and platelet transfusions, and broad-spectrum antibiotics. Upper endoscopy showed diffuse non-bleeding esophageal and gastric varices, which required band ligation and continued IV octreotide therapy. The infection resolved after a 7-day course of IV ceftriaxone.

Irene Perez,1 Fabian J Bolte,1 William Bigelow,1 Zachary Dickson,2 Neeral L Shah2 1Department of Internal Medicine, University of Virginia, Charlottesville, VA, USA; 2Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA, USACorrespondence: Neeral L ShahDivision of Gastroenterology and Hepatology, University of Virginia, PO. Box 800708, West Complex – 2nd Floor, Charlottesville, VA, 22908, USA, Tel +1 434-297-7206Fax +1 434-244-7586Email neeral.shah@virginia.eduAbstract: According to the Centers for Disease Control and Prevention, chronic liver disease and cirrhosis is the 11th leading cause of death in the United States. Common causes of chronic liver disease include alcohol, viral hepatitis, and non-alcoholic steatohepatitis (NASH). Inflammation is a critical driver in the progression of liver disease to liver fibrosis and ultimately cirrhosis. While the severity of chronic liver disease extends over a continuum, the management is more easily differentiated between compensated and decompensated cirrhosis. In this review, we discuss pathophysiology, clinical features and management of common complications of liver cirrhosis based on literature review and the current clinical practice guidelines of the American Association for the Study of Liver Diseases (AASLD).Keywords: cirrhosis, chronic liver disease, end-stage liver disease, decompensated cirrhosis, compensated cirrhosis, hepatorenal syndrome

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

Abstract Background Liver cirrhosis is the irreversible fibrosis of the liver and causes refractory ascites and hepatic encephalopathy, which might not respond to treatment. Living donor liver transplantation (LDLT) is an effective treatment for patients with cirrhosis. However, post-LDLT patients are prone to muscle atrophy and sarcopenia. Therefore, physiotherapy of post-LDLT patients is essential for preventing the progression of sarcopenia. Recently, rehabilitation using neuromuscular electrical stimulation (NMES) has been reported to be useful for preventing the progression of sarcopenia. Similarly, nutrition therapy is essential for post-LDLT patients because these patients frequently experience malnutrition. However, the effects of combined NMES and nutrition therapy on post-LDLT patients remain unknown. Methods/design This open-label, randomized, parallel-group study will compare the effects of combined therapy with NMES and branched-chain amino acids (BCAA) with those of NMES alone in patients with decompensated cirrhosis after LDLT. After LDLT, 50 patients with decompensated cirrhosis will be randomly assigned to receive NMES with BCAA or NMES without BCAA. The duration of the intervention will be 3 months. To analyze the change in skeletal muscle mass, InBody 770 body composition and body water analysis and ultrasonography will be performed before LDLT and 4 weeks and 12 weeks post-LDLT. The primary endpoint is changes in the skeletal muscle mass from baseline to 3 months. Important secondary endpoints are the changes in the skeletal muscle mass from baseline to 1 month and changes in the quadriceps strength from baseline to 1 month. Discussion The results of this study are expected to provide evidence regarding the effect of NMES combined with BCAA therapy on the skeletal muscle of post-LDLT patients. Trial registration Japan Registry of Clinical Research jRCTs071190051 . Registered on February 26, 2020.

Abstract Background and Aim Acute kidney injury (AKI) is a common complication of chronic liver disease (CLD). We performed a prospective study to evaluate the risk factors and spectrum of AKI among decompensated cirrhosis (DC) patients and the impact of AKI on survival. Methods This study was conducted in consecutive DC patients hospitalized in SCB Medical College between December 2016 and October 2018. AKI was defined as per ICA criteria. Demographic, clinical, and laboratory parameters and outcomes were compared between patients with and without AKI. Results A total of 576 DC subjects were enrolled, 315 (54.69%) of whom had AKI; 34% (n = 106) had stage 1A, 28% (n = 90) stage 1B, 21% (n = 65) stage 2, and 17% (n = 54) stage 3 AKI. Alcohol was the predominant cause of CLD (66.7%). In 207 (65.7%) patients, diuretic/lactulose/nonsteroidal anti‐inflammatory drugs use was noted, and infection was present in 190 (60.3%) patients. Compared to those without AKI, patients with AKI had higher leucocyte count, higher serum urea and creatinine, higher Child‐Turcotte‐Pugh, higher Model of End‐Stage Liver Disease (MELD) scores (P

Background: Physicians caring for patients with cirrhosis should recognize the acute or chronic character of renal disease; the causes of renal injury; the clinical conditions leading concomitantly to acute kidney injury (AKI) and liver dysfunction, and the prognostic factors associated with the progression of AKI. Hypovolemia (due to diuretics, hemorrhage, diarrhea), acute tubular necrosis, sepsis, nephrotoxic agents (such as non steroidal anti-inflammatory drugs, aminoglycosides radiological contrasts) and hepatorenal syndrome-type 1 are the most common causes of AKI in cirrhotic patients. Aim of the Work: The aim of this study was to evaluate urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) as a diagnostic biomarker for different causes of acute kidney injury in liver cirrhosis. Patients and Methods: This was a cross sectional study done in patients with liver cirrhosis hospitalized at the Gastroenterology Department of the Ain shams university hospital. Results: We found that in the comparison between HRS and AKI regarding HB, WBCs, Platelets, ALT, AST, Albumin, INR, Bilirubin, Urea, Creatinine, Na, Urinary Cr, Urinary Na and FeNa%, there was highly statistically significant difference found between two groups regarding Urinary Na and Fe Na%, Platelets, AST, Bilirubin and Na, and there was no statistically significant difference found between two groups regarding HB, WBCs, ALT, Albumin, INR, Urea, Creatinine and Urinary Cr. While in the Correlation between NGAL With Age, HB, WBCs, Platelets, ALT, AST, Albumin, INR, Bilirubin, Urea, Creatinine, Na, Urinary Cr, Urinary Na and FeNa%, we found that there was Non statically significant correlation Between NGAL, Age, HB, WBCs, Platelets, ALT, Albumin, INR, Bilirubin, Urea, Creatinine, Na and Urinary Cr, and there was statically significant Negative correlation Between NGAL, Urinary Na and FeNa%, and there was statically significant positive correlation Between NGAL and AST. Conclusion: It is well known that development of acute kidney injury (AKI) increases mortality in hospitalized cirrhotic patients; therefore many novel markers have been studied for early detection, differential diagnosis and prognosis in cirrhotic patients with AKI. NGAL is a newly identified member of the lipocalin family that is significantly expressed in injured epithelial cells. It can lead to rapid increases in NGAL secretion from glomeruli, thus increasing NGAL concentrations in the urine. In addition, its concentration often increases within 2 h of kidney injury. Urinary NGAL has the ability to differentiate between AKI types in patients with cirrhosis. This could improve risk stratification for patients admitted to the hospital with cirrhosis, perhaps leading to early ICU admission, transplant evaluation, and prompt initiation of HRS therapy and early management of AKI. These findings, if confirmed in larger cohorts, could lead to the development of biomarker algorithms to rapidly identify patients with HRS and ATN and accurately predict prognosis. [ABSTRACT FROM AUTHOR]

Liver cirrhosis is often associated with type 2 diabetes (T2D), but research on treatment of T2D in cirrhotic patients is scarce. We investigated the long-term outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with T2D and cirrhosis. Using propensity score matching, we selected 467 matched pairs of GLP-1 RA users and nonusers from the National Health Insurance Research Database of Taiwan from January 1, 2008, to December 31, 2019. Multivariable-adjusted Cox proportional hazards models were used to compare the outcomes between GLP-1 RA users and nonusers. The mean follow-up time was 3.28 and 3.06 years for GLP-1 RA users and nonusers, respectively. The rates of death were 27.46 and 55.90 per 1000 person-years for GLP-1 RA users and nonusers, respectively. The multivariable-adjusted models showed that GLP-1 RA users had lower risks of mortality (adjusted hazard ratio [aHR], 0.47; 95% confidence interval [CI], 0.32–0.69), cardiovascular events (aHR, 0.6; 95% CI, 0.41–0.87), decompensated cirrhosis (aHR, 0.7; 95% CI, 0.49–0.99), hepatic encephalopathy (aHR, 0.59; 95% CI, 0.36–0.97), and liver failure (aHR, 0.54; 95% CI, 0.34–0.85) than nonusers. A longer cumulative duration of GLP-1 RA use had a lower risk of these outcomes than GLP-1 RA nonuse. This population-based cohort study showed that GLP-1 RA users exhibited a significantly lower risk of death, cardiovascular events, decompensated cirrhosis, hepatic encephalopathy, and liver failure in patients with T2D and compensated liver cirrhosis. Additional studies are needed to confirm our results. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Various therapies and drugs have been developed to extend the life expectancy of patients with liver cirrhosis. The prolonged prognosis of cirrhotic patients may change the final cause of death in the future. Deep bleeding into the muscle is an uncommon but potentially life-threatening complication of liver cirrhosis. Case report: A 53-year-old man had undergone transjugular intrahepatic portosystemic shunt treatment for refractory ascites, which successfully controlled it for three years. However, he had started drinking again and experienced acute-on-chronic liver failure. He also had severe back pain. Abdominal computed tomography showed hyperdensities in the retroperitoneum and right pleural cavity. Despite blood infusion, he died from acute-on-chronic liver failure. A pathological autopsy revealed bleeding from the iliopsoas and right diaphragmatic muscle simultaneously, evident from the presence of red blood cells located between the muscle sheaths. Disruption of the small vessels in the skeletal muscle fibers was inferred. Conclusion: This is a critical case that underscores the significance of improving available knowledge based on the cause of final death of the patients with cirrhosis, who now have a good long-term prognosis owing to the latest medical developments. [ABSTRACT FROM AUTHOR]

Acute-on-chronic liver failure (ACLF) is a distinct clinical syndrome, characterized by acute decompensation (AD) of liver cirrhosis, severe systemic inflammation, intra- and extrahepatic organ failures, and a high short-term mortality. Liver transplantation (LT) is a potentially life-saving treatment for patients with decompensated liver cirrhosis and, due to the high mortality rates, particularly for ACLF patients. In the last decade, a plethora of studies has produced compelling evidence in favor of LT in ACLF, demonstrating high post-LT survival rates and excessive waitlist mortality. The importance of LT in these patients is underscored by the fact that no specific therapy for ACLF is available yet, rendering expeditious life-saving LT to be the only feasible treatment option for some ACLF patients. This review aims to provide an overview on pathophysiology, clinical trajectory, and clinical management of ACLF and to delineate the current literature regarding perspectives and limitations of LT as a life-saving treatment option for ACLF patients. [ABSTRACT FROM AUTHOR]

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 < 0.0001), liver-related mortality (HR 0.40, 95% CI 0.17-0.96, p = 0.04), non-liver-related mortality (HR 0.17, 95% CI 0.06-0.49, p = 0.001), liver transplantation (HR 0.17, 95% CI 0.05-0.54, p = 0.003), and hepatocellular carcinoma (HR 0.52, 95% CI 0.29-0.93, p = 0.03).Conclusion: Treatment with direct antiviral agents is associated with reduced risk for mortality. The sustained virological response was 88%. Thus, direct antiviral agents treatment should be considered for any patient with HCV-related decompensated cirrhosis.Trial Registration:  ClinicalTrials.gov registry number: NCT01953458. [ABSTRACT FROM AUTHOR]

Background: For patients with hepatitis C virus (HCV)-related decompensated cirrhosis, poor prognosis was documented due to the development of portal hypertension-related complications and hepatocellular carcinoma. Sofosbuvir-based direct-acting antiviral agents (DAAs) has revolutionized the treatment landscape of HCV, particularly in this subpopulation. To date, real-world efficacy, tolerability, and safety profiles for Taiwanese HCV-related decompensated cirrhosis treated by DAAs have not been reported. Methods: Between December 2015 and June 2020, 50 consecutive HCV-related Child-Turcotte-Pugh (CTP) classes B or C cirrhotics treated by sofosbuvir-based DAAs (with daclatasvir: 7, with ledipasvir: 32, with velpatasvir: 10, with ledipasvir then shifted to velpatasvir: 1) were enrolled. Forty-seven (94%) patients used DAAs in combination with low-dose ribavirin. SVR12 was defined by undetectable HCV RNA (<15 IU/mL) at treatment end and 12 weeks after the completion of therapy. Results: The mean age of the enrolled patients was 68.1 ± 11.2 years, 18% of the patients were CTP class C, and the baseline HCV RNA level was 5.42 ± 1.2 log10 IU/mL. The genotype distribution was as follows: 1a: 3; 1b: 34; 2: 9; 6: 3; and one patient with an unclassified HCV genotype. After DAAs treatment, the rates of undetectable HCV RNA at week 4 and at the end of the treatment were 88.9% and 98.0%, respectively. Subjective adverse events were reported by 42.0% of the patients, but they were generally mild and could be relieved by medications. One patient did not finish therapy due to sepsis with multiple organ dysfunction. The overall SVR12 rate was 96.0% (CTP class B: 97.6%, CTP class C: 88.9%). A significant improvement in hepatic functional reserve was noted after successful antiviral therapy. Conclusion: For patients with HCV-related decompensated cirrhosis, which has been considered a contraindication for interferon-based therapy, sofosbuvir-based all-oral DAAs provided high treatment efficacy, acceptable safety, and good tolerability. [ABSTRACT FROM AUTHOR]