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Patients hospitalized with decompensated cirrhosis and a serum albumin level of less than 30 g per liter were randomly assigned to daily albumin infusions to raise the albumin level to 30 g per liter or higher or to standard care. Albumin infusions did not reduce the incidences of infection, kidney dysfunction, and death. More serious adverse events occurred in the albumin group.

Background Transjugular intrahepatic portosystemic shunt (TIPS) has recently been reported to be effective in the treatment of cirrhotic patients with refractory ascites. However, the clinical utility of TIPS in the subset of refractory ascitic patients with good hepatic and renal function is uncertain. The aim of this study was to compare the efficacy of TIPS to that of large-volume paracentesis in cirrhotic patients with refractory ascites who have good hepatic and renal function. Methods Sixty cirrhotic patients with refractory ascites who presented with a Child-Pugh score of <11, serum bilirubin of <3 mg/dl and creatinine of <1.9 mg/dl were assigned randomly to TIPS (n = 30) or large-volume paracentesis plus albumin (n = 30). The primary endpoint was survival. The secondary endpoints were response to treatment and development of hepatic encephalopathy. Results The baseline characteristics were similar in the two groups. Seventeen patients treated with TIPS and 21 treated with paracentesis died during the study period. The cumulative probabilities of survival at 1 and 2 years were 80 and 64% in the TIPS group and 49 and 35% in the paracentesis group (p < 0.005). TIPS was significantly superior to paracentesis in the control of ascites (p < 0.005). Treatment failure was more frequent in the paracentesis group, whereas the frequency of hepatic encephalopathy was greater in the TIPS group. Conclusions In cirrhotic patients with refractory ascites who have good hepatic and renal function, TIPS improves survival and provides better control of ascites than large-volume paracentesis.

Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008–000625–19, and ClinicalTrials.gov, number NCT01288794. From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40–0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3–4 non-liver related adverse events. In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. Italian Medicine Agency.

The British Society of Gastroenterology in collaboration with British Association for the Study of the Liver has prepared this document. The aim of this guideline is to review and summarise the evidence that guides clinical diagnosis and management of ascites in patients with cirrhosis. Substantial advances have been made in this area since the publication of the last guideline in 2007. These guidelines are based on a comprehensive literature search and comprise systematic reviews in the key areas, including the diagnostic tests, diuretic use, therapeutic paracentesis, use of albumin, transjugular intrahepatic portosystemic stent shunt, spontaneous bacterial peritonitis and beta-blockers in patients with ascites. Where recent systematic reviews and meta-analysis are available, these have been updated with additional studies. In addition, the results of prospective and retrospective studies, evidence obtained from expert committee reports and, in some instances, reports from case series have been included. Where possible, judgement has been made on the quality of information used to generate the guidelines and the specific recommendations have been made according to the ‘Grading of Recommendations Assessment, Development and Evaluation (GRADE)’ system. These guidelines are intended to inform practising clinicians, and it is expected that these guidelines will be revised in 3 years’ time.

Malignant abdominal fluid (ascites) frequently develops in women with advanced high-grade serous ovarian cancer (HGSOC) and is associated with drug resistance and a poor prognosis 1 . To comprehensively characterize the HGSOC ascites ecosystem, we used single-cell RNA sequencing to profile ~11,000 cells from 22 ascites specimens from 11 patients with HGSOC. We found significant inter-patient variability in the composition and functional programs of ascites cells, including immunomodulatory fibroblast sub-populations and dichotomous macrophage populations. We found that the previously described immunoreactive and mesenchymal subtypes of HGSOC, which have prognostic implications, reflect the abundance of immune infiltrates and fibroblasts rather than distinct subsets of malignant cells 2 . Malignant cell variability was partly explained by heterogeneous copy number alteration patterns or expression of a stemness program. Malignant cells shared expression of inflammatory programs that were largely recapitulated in single-cell RNA sequencing of ~35,000 cells from additionally collected samples, including three ascites, two primary HGSOC tumors and three patient ascites-derived xenograft models. Inhibition of the JAK/STAT pathway, which was expressed in both malignant cells and cancer-associated fibroblasts, had potent anti-tumor activity in primary short-term cultures and patient-derived xenograft models. Our work contributes to resolving the HSGOC landscape 3 – 5 and provides a resource for the development of novel therapeutic approaches. Single-cell transcriptomics analysis of malignant ascites samples from patients with high-grade serous ovarian cancer reveals inter- and intra-patient heterogeneity in malignant cells, cancer-associated fibroblasts and macrophages.

Background Ascites remains the most common complication of cirrhosis and a frequent reason for hospitalisation in advanced chronic liver disease (ACLD). Ascites is associated with significant symptom burden, caregiver workload and poor health-related quality of life (HRQoL). Once refractory to treatment, median survival is poor. Many with refractory ascites (RA) will neither receive a transjugular intrahepatic portosystemic shunt (TIPS) nor a liver transplant. Palliative care remains underutilised and evidence-based interventions focused on improving HRQoL are clearly needed. The standard of care for RA is repeated hospital ascites drainage with large volume paracentesis (LVP). Our earlier feasibility randomised controlled trial (RCT) (REDUCe) showed acceptability of palliative tunnelled long-term abdominal drains (LTADs), as well as preliminary evidence of safety and efficacy. The current REDUCe2 trial is a definitive national study designed to assess the impact of palliative LTADs on HRQoL in patients with RA due to ACLD. Methods/design The REDUCe2 study is a pragmatic, multicentre, open-label, mixed-methods, superiority RCT being conducted in England, Scotland and Wales. Patients with RA secondary to ACLD who are ineligible for a liver transplant or TIPS will be randomised 1:1 to receive a LTAD or continue the current standard of care (LVP). Fortnightly home research visits will be conducted for 12 weeks in both arms. The primary outcome will be liver specific HRQoL assessed at 12 weeks using the Short Form Liver Disease Quality of Life questionnaire (SFLDQoL). Secondary outcomes include assessment of symptom burden (Ascites Questionnaire), health utilities (EQ-5D-5L tool), caregiver workload (Caregiver Roles and Responsibilities Scale—CRRS questionnaire), safety (including infection, acute kidney injury and other clinical outcomes), health resource utilisation and acceptability of the intervention by patients, caregivers and healthcare professionals. We aim to recruit a total of 310 patients (155 in each arm). Discussion Effective palliative care provision remains an unmet need in ACLD. The REDUCe2 study, the largest palliative interventional trial in the UK, aims to address this inequity for this vulnerable and underserved cohort. It has the potential to generate high quality evidence to optimise and enhance palliative care in RA. Trial registration ISRCTN26993825, date registered: 15/08/2022.

ObjectiveSatavaptan, a vasopressin V2 receptor antagonist, has been shown to improve the control of ascites in cirrhosis in short-term phase II studies. The aim of this study was to evaluate the efficacy and safety of satavaptan in three different populations of patients with cirrhosis and ascites.Methods1200 patients were included in three randomised double-blind studies comparing satavaptan with placebo in uncomplicated ascites (study 1: n=463 patients) and difficult-to-treat ascites, with and without concomitant diuretic treatment (studies 2 and 3: n=497 and n=240 patients, respectively).ResultsSatavaptan was not more effective than placebo in the control of ascites in any of the populations studied as estimated by the primary efficacy endpoints: worsening of ascites (study 1) and the cumulative number of large-volume paracenteses during 12 weeks (studies 2 and 3). Nevertheless, some of the secondary efficacy endpoints related to the treatment of ascites were met in the three studies, suggesting a slight advantage of satavaptan over placebo in delaying ascites formation. Moreover, satavaptan was more effective than placebo in improving the serum sodium concentration in patients with hyponatraemia. The incidence of major complications of cirrhosis during follow-up did not differ significantly between the satavaptan and placebo groups in the three studies. Overall, the rate of any treatment-related adverse events, serious treatment-related events and treatment-related events leading to permanent discontinuation of treatment did not differ significantly between the treatment groups. However, in study 2 mortality was higher in patients treated with satavaptan compared with placebo (HR 1.47; 95% CI 1.01 to 2.15); no significant differences in mortality between the two groups were observed in the other two studies. No specific cause for the increased mortality was identified. Most deaths were associated with known complications of liver cirrhosis.ConclusionSatavaptan, alone or in combination with diuretics, is not clinically beneficial in the long-term management of ascites in cirrhosis.