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Abstract Background Hyponatremia portends a poor prognosis in decompensated cirrhosis and is an independent predictor of mortality. Multiple modalities have been evaluated in the management of hyponatremia, including albumin infusion. However, the effect of albumin infusion on the resolution of hyponatremia is unclear. We conducted a systematic review to explore the available literature on the use of albumin infusion in hyponatremia. Methods We performed a comprehensive search up to 31st December 2022 using MEDLINE, EMBASE, and Scopus for studies reporting the effectiveness of albumin infusion in the resolution of hyponatremia. The impact of albumin infusion of any dose, administration frequency, and duration of therapy was recorded. The study protocol was prospectively registered (CRD42021245914). Results The literature search yielded 1322 references after duplicate removal. Only seven studies (three randomized trials, three cohort studies, and one case series) satisfied the predefined selection criteria after a full-text review. While hyponatremia was clearly defined as serum sodium 135 mEq/L). No differentiation was made between the types of hyponatremia. The strength of the albumin infusion used was 5% and 20%. All but one study reported significant improvement in hyponatremia with albumin infusion. A subgroup analysis showed albumin infusion improved 30-day survival (odds ratio 0.43, 95% CI 0.25–0.74, I 2 = 0.) No studies reported adverse events or the impact of concomitant associations (diuretic withdrawal, lactulose use, sepsis). Conclusion Despite available literature on the use of albumin infusion for the resolution of hyponatremia, the level of evidence remains low. Large prospective studies with pre-defined selection criteria and endpoints are required to generate the evidence.

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.

Neoplasms arising from the ampulla of Vater are exceedingly rare, and there is a paucity of literature regarding their diagnosis and management. Ampullary cancer typically presents with jaundice and signs of biliary obstruction. We present a case of ampullary adenocarcinoma with concomitant choledocholithiasis that proved complex and diagnostically challenging.

Abstract We aimed to explore the association between FFP transfusion and outcomes of DC patients with significant coagulopathy. A total of 693 DC patients with significant coagulopathy were analyzed with 233 patients per group after propensity score matching (PSM). Patients who received FFP transfusion were matched with those receiving conventional therapy via PSM. Regression analysis showed FFP transfusion had no benefit in 30-day (HR: 1.08, 95% CI 0.83–1.4), 90-day (HR: 1.03, 95% CI 0.80–1.31) and in-hospital(HR: 1.30, 95% CI 0.90–1.89) mortality, associated with increased risk of liver failure (OR: 3.00, 95% CI 1.78–5.07), kidney failure (OR: 1.90, 95% CI 1.13–3.18), coagulation failure (OR: 2.55, 95% CI 1.52–4.27), respiratory failure (OR: 1.76, 95% CI 1.15–2.69), and circulatory failure (OR: 2.15, 95% CI 1.27–3.64), and even associated with prolonged the LOS ICU (β: 2.61, 95% CI 1.59–3.62) and LOS hospital (β: 6.59, 95% CI 2.62–10.57). In sensitivity analysis, multivariate analysis (HR: 1.09, 95%CI 0.86, 1.38), IPTW (HR: 1.11, 95%CI 0.95–1.29) and CAPS (HR: 1.09, 95% CI 0.86–1.38) showed FFP transfusion had no beneficial effect on the 30-day mortality. Smooth curve fitting demonstrated the risk of liver failure, kidney failure and circulatory failure increased by 3%, 2% and 2% respectively, for each 1 ml/kg increase in FFP transfusion. We found there was no significant difference of CLIF-SOFA and MELD score between the two group on day 0, 3, 7, 14. Compared with the conventional group, INR, APTT, and TBIL in the FFP transfusion group significantly increased, while PaO2/FiO2 significantly decreased within 14 days. In conclusion, FFP transfusion had no beneficial effect on the 30-day, 90-day, in-hospital mortality, was associated with prolonged the LOS ICU and LOS hospital, and the increased risk of liver failure, kidney failure, coagulation failure, respiratory failure and circulatory failure events. However, large, multi-center, randomized controlled trials, prospective cohort studies and external validation are still needed to verify the efficacy of FFP transfusion in the future.

Malnutrition is common in patients with cirrhosis, eventually leading to sarcopenia and loss of bone mass. The aims of this study was the assessment of body composition (BC) and bone mineral density (BMD) in patients with decompensated cirrhosis and the prognostic impact on survival after transjugular intrahepatic portosystemic shunt (TIPS) implantation. BMD and BC of 107 patients with cirrhosis undergoing TIPS implantation were prospectively analyzed by dual-energy X-ray absorptiometry. The prevalence and predisposing risk factors for reduced BMD and sarcopenia were assessed. Impact on 12-month survival after TIPS implantation was evaluated. Sarcopenia was diagnosed in 48.6 % of the patients with a predominance of male patients (58.7% vs. 25.0 %, p = 0.001). 67.2 % had reduced BMD. Low BMI was independently associated with sarcopenia (OR 0.751 (95 % CI: 0.662;0.852), p < 0.001) and reduced BMD (OR 0.851 (0.773;0.937), p = 0.001). Patients with reduced BMD, but not sarcopenia, had impaired 12-month survival after TIPS-implantation (61.2% vs. 82.9 %, p = 0.030). Subgroup analysis showed that this was especially valid for female patients. Sarcopenia and reduced BMD are frequently observed in patients with decompensated cirrhosis. Reduced BMD negatively affects post-TIPS survival. Since malnutrition is a leading cause, assessment of nutritional status and specific treatment should be included in clinical practice. [ABSTRACT FROM AUTHOR]

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 (RatioHep/Port, RatioPeri/Hep, and RatioPort/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 RatioPeri/Hep of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher RatioPort/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.

Key Clinical Message We present a case of Cronkhite–Canada syndrome in a patient with decompensated cirrhosis who had successful induction of remission with nutritional supplementation alone. We propose that early institution of high‐protein, high‐energy enteral supplementation should be offered to all patients, especially those with compelling contraindications to immunosuppression.

Abstract Background/objectives Malnutrition coexisting with abdominal adipose tissue accumulation bring a double burden on prognosis. More recently, the Global Leadership Initiative on Malnutrition (GLIM) has reached a novel consensus concerning the diagnostic criteria, that is, a two-step modality combining nutritional risk screening and subsequent phenotypic/etiologic parameters for comprehensive evaluation in hopes of harmonizing the malnutrition diagnosis. We aimed to elucidate their synergistic impact among inpatients with decompensated cirrhosis concerning long-term mortality. Subjects/methods Malnutrition, visceral obesity, and visceral adiposity were defined by the Global Leadership Initiative on Malnutrition (GLIM), visceral fat area (VFA), and visceral to subcutaneous adipose tissue area ratio (VSR) on computed tomography, respectively. Accordingly, the patients were categorized into different groups given their nutritional status and visceral obesity/adiposity. Multivariate Cox regression was performed to identify independent risk factors associated with 1-year all-cause mortality. Kaplan–Meier curves with log-rank tests were compared among distinct groups. Results Totally, 295 patients were recruited. GLIM, VFA, and VSR identified 131 (44.4%), 158 (53.6%), and 59 (20%) patients with malnutrition, visceral obesity and visceral adiposity, respectively. Malnutrition coexisted with visceral obesity in 55 (MO group) relative to visceral adiposity in 40 patients (MA group). Multivariate Cox analysis showed that MA (hazard ratio: 2.48; 95% confidence interval: 1.06, 5.79; P = 0.036) was independently associated with dire outcome rather than MO. Moreover, patients with cirrhosis in the MA group had the worst survival status when compared with other groups (log-rank test: P

INTRODUCTION: To report outcomes of a 3-year quality improvement pilot study to improve advance directive (AD) completion. METHODS: The pilot consisted of champions, education, electronic health record templates, and workflow changes. We assessed changes, predictors, and effects of AD completion. RESULTS: The pilot led to greater (8.3%-36%) and earlier AD completion, particularly among those divorced, with alcohol-associated liver disease, and with higher Model of End-Stage Liver Disease-Sodium score. Decedents whose AD specified nonaggressive goals experienced lower hospital lengths of stay. DISCUSSION: Advance care planning initiatives are feasible and may reduce health care utilization among decedents requesting less aggressive care.

Introduction: In this multicenter clinical study, we aimed to investigate the efficacy and safety of the transhepatic arterial administration of granulocyte-colony stimulating factor (G–CSF)–mobilized autologous peripheral blood (PB)-CD34+ cells compared with standard therapy in patients with decompensated cirrhosis type C. Methods: Patients were randomly assigned (2:1) to the CD34+ cell transplant (CD34+ cell) or standard-of-care (SOC) group and followed up for 52 weeks. The primary endpoints were the non-progression rate of Child-Pugh (CP) scores at 24 weeks post-enrollment and the safety of the protocol treatment. Results: Fourteen patients (CD34+ cell group: 10; SOC group: 4) were enrolled. CP scores at 24 weeks had a non-progression rate of 90% in the CD34+ cell group and 100% in the SOC group, with no significant difference between groups. Importantly, 4 out of 10 patients in the CD34+ cell group exhibited an improvement from decompensated to compensated cirrhosis, whereas all patients in the SOC group remained in decompensated cirrhosis. With regard to secondary endpoints, a trend toward increased serum albumin levels in the CD34+ cell group was noted. Serious adverse events (SAEs) occurred in three patients in the CD34+ cell group and in one patient in the SOC group. No causal relationship was observed between all SAEs and G-CSF, leukapheresis, or cell transplantation in the CD34+ cell group. No patients died and no hepatocellular carcinoma occurred within the study period. Conclusions: PB-CD34+ cell infusion therapy may have the potential to circumvent the decompensated stage of cirrhosis, thus avoiding the need for liver transplantation.

Abstract Background Patient heterogeneity poses significant challenges for managing individuals and designing clinical trials, especially in complex diseases. Existing classifications rely on outcome-predicting scores, potentially overlooking crucial elements contributing to heterogeneity without necessarily impacting prognosis. Methods To address patient heterogeneity, we developed ClustALL, a computational pipeline that simultaneously faces diverse clinical data challenges like mixed types, missing values, and collinearity. ClustALL enables the unsupervised identification of patient stratifications while filtering for stratifications that are robust against minor variations in the population (population-based) and against limited adjustments in the algorithm’s parameters (parameter-based). Results Applied to a European cohort of patients with acutely decompensated cirrhosis (n = 766), ClustALL identified five robust stratifications, using only data at hospital admission. All stratifications included markers of impaired liver function and number of organ dysfunction or failure, and most included precipitating events. When focusing on one of these stratifications, patients were categorized into three clusters characterized by typical clinical features; notably, the 3-cluster stratification showed a prognostic value. Re-assessment of patient stratification during follow-up delineated patients’ outcomes, with further improvement of the prognostic value of the stratification. We validated these findings in an independent prospective multicentre cohort of patients from Latin America (n = 580). Conclusions By applying ClustALL to patients with acutely decompensated cirrhosis, we identified three patient clusters. Following these clusters over time offers insights that could guide future clinical trial design. ClustALL is a novel and robust stratification method capable of addressing the multiple challenges of patient stratification in most complex diseases.

Abstract Background Cirrhosis is associated with sarcopaenia and fat wasting, which drive decompensation and mortality. Currently, nutritional status, through body composition assessment, is not routinely monitored in outpatients. Given the deleterious outcomes associated with poor nutrition in decompensated cirrhosis, there is a need for remotely monitoring this to optimise community care. Methods A retrospective analysis was conducted on patients monitored remotely with digital sensors post hospital discharge, to assess outcomes and indicators of new cirrhosis complications. 15 patients had daily fat mass measurements as part of monitoring over a median 10 weeks, using a Withing’s bioimpedance scale. The Clinical Frailty Score (CFS) was used to assess frailty and several liver disease severity scores were assessed. Results 73.3% (11/15) patients were male with a median age of 63 (52–68). There was a trend towards more severe liver disease based on CLIF-Consortium Acute Decompensation (CLIF-C AD) scores in frail patients vs. those not frail (53 vs 46, p = 0.072). When the cohort was split into patients who gained fat mass over 8 weeks vs. those that lost fat mass, the baseline CLIF-C AD scores and WBC were significantly higher in those that lost fat (58 vs 48, p = 0.048 and 11.2 × 109 vs 4.7 × 109, p = 0.031). Conclusions This proof-of-principle study shows feasibility for remote monitoring of fat mass and nutritional reserve in decompensated cirrhosis. Our results suggest fat mass is associated with greater severity of acute decompensation and may serve as an indicator of systemic inflammatory response. Further prospective studies are required to validate this digital biomarker.

Background: Hepatitis B virus-related decompensated cirrhosis (HBV-DC) is a critical illness with a low survival rate. Timely identification of prognostic indicators is crucial for risk stratification and personalized management of patients. The present study aimed to investigate the potential of the D-dimer-to-platelet count ratio (DPR) as a prognostic indicator for HBV-DC. Methods: A retrospective review of medical records was conducted for 164 patients diagnosed with HBV-DC. Baseline clinical and laboratory characteristics were extracted for analysis. The endpoint was 30-day mortality. Disease severity was assessed by the Model for End-stage Liver Disease (MELD) score. A multivariate logistic regression model and receiver operating characteristic curve analysis (ROC) were used to evaluate the predictive value of DPR for mortality. Results: During the 30-day follow-up period, 30 (18.3%) patients died. Non-survivors exhibited significantly higher DPR values than survivors, and a high DPR had a strong association with increased mortality. Importantly, DPR was identified as an independent risk factor for mortality in HBV-DC patients after adjustments for confounding factors (Odds ratio = 1.017; 95% Confidence interval, 1.006–1.029; p = 0.003). The cut-off value of DPR as a predictor of mortality was>57.6 (sensitivity = 57%, specificity = 86%, p