TO TREAT ACUTE-ON-CHRONIC LIVER FAILURE; THE FIRST MULTICENTER RANDOMIZED TRIAL RITUXIMAB INITIATION, PRESCRIBING AND HEPATITIS B REACTIVATION: RETROSPECTIVE FIVE-YEAR REVIEW

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Background The acute-on-chronic liver failure (ACLF) is a severe complication of cirrhosis characterised by immune dysfunction and high mortality. Granulocyte-colony stimulating factor (G-CSF) mobilises immunomodulatory stem and immune cells and has been proposed as therapy for ACLF. We therefore conducted the first multicentre randomised trial. Methods In this prospective, controlled, open-label 2-armed study 176 patients with ACLF according to the EASL-CLIF criteria without malignancies or septic shock were randomised in 18 trial centres between 02/2016 and 01/2019 in a 1:1 ratio to receive either standard medical therapy (SMT) or SMT plus G-CSF (12 injections with 5mg/kg for 5days daily, then every 3 days). The primary efficacy endpoint was 90-day transplant free survival (TFS90).

Results
The 90-day transplant free survival was 34.1% in the G-CSF plus SMT group compared to 37.5% in the SMT group with a corresponding hazard ratio (HR) of 1.05 (95% CI 0.711; 1.551) (p=0.805). G.CSF had no effect on the 360-day transplant free survival [HR of 0.998 [95%CI 0.697;1.430 (p=0.992)] or overall survival [HR of 1.058 [95%CI 0.727;1.548 (p=0.768)]. There was no improvement of the CLIF-C OF score (p=0.757), MELD score (p=0.884) or the rate of bacterial infections (p=0.251) with G-CSF therapy. In subgroups of patients without infections [p=0.883], with alcohol related ACLF [p=0.875], or with ACLF defined by the APASL criteria [p=0.405] G-CSF also didn't improve survival. There were 61 serious adverse events (SAE) reported in the G-CSF+SMT group and 57 SAEs in the SMT group including seven drug-related serious adverse reactions under G-CSF therapy. The study was prematurely terminated due to futility. Conclusion This interim analysis of the first multicentre trial reveals that G-CSF has no therapeutic effect in ACLF, which is in obvious contrast to the results from smaller clinical trials published previously. As a consequence, the study was prematurely terminated due to futility after conditional power calculation.
Introduction Hepatitis B reactivation is a potentially life-threatening complication of immunosuppression in patients with serological evidence of current or past exposure to Hepatitis B Virus (HBV). Rituximab is a widely used B-cell depleting medication widely used to treat haematological cancers and rheumatological disease. The British Society of Rheumatology, British Society of Haematology and the European Association of Study of the Liver guidelines all recommend patients must all be assessed for HBV before rituximab initiation. This is a single-centre five-year retrospective review of our Trusts Rituximab prescribing and HBV screening. Methods We included all adult patients receiving rituximab between 1st October 2015 and 30th September 2020 at our Trust. Patients were identified using hospital pharmacy Rituximab prescribing logs. Indications, HBV screening bloods and outcomes were collected using electronic records (Allscripts, Telepath). Patients with incomplete or missing records were excluded. Results A total of 870 patients were included in this study. Seventy percent (n = 611) were for oncohaematological indications and 30% (n =258) for rheumatological. There were 606 patients newly initiated on Rituximab during the study period (table 1). HBV screening improved from 62% to 94% during the study period.
Eighteen patients were positive or equivocal for Hepatitis B core antibody and 1 for Hepatitis B Surface Antigen. Four patients were prescribed lamivudine prophylaxis, 2 Tenofovir and 1 entecavir. The other patients had no treatment or monitoring. Only 1 case was on adequate length of prophylaxis after being referred to the hepatobiliary service. There were no cases of hepatitis B reactivation in the study period. Conclusions A significant number of patients are not being screened for Hepatitis B core antibodies, despite local education programmes in 2016 and 2018. Low background rates of HBV in the local community may account for low levels of previous and current HBV infections. Education of prescribers, modifications to the initiation pharmacy checklists and simplification of computer request process should help to improve Hepatitis B screening in our patients and avoid potentially life threatening reactivation. Background Variceal haemorrhage is a major cause of morbidity and mortality in patients with chronic liver disease (CLD). Oesophagogastroduodenoscopy (OGD) is the gold standard for variceal screening. Baveno VI guidelines recommend that in patients with CLD a Liver Stiffness measurement (LSM) <10kPa may rule out compensated CLD and also recommend that patients with LSM <20kPa and a platelet count (PLT) of >150000 are at low risk of clinically significant varices (CSV) and may safely omit OGD for variceal surveillance.
Objectives Examine the utility of these cut offs in a cohort of patient with heterogeneous aetiology of CLD at a District General Hospital (DGH). Methods We interrogated electronic Transient Elastography (TE) records to identify patients who underwent TE between 06/2018 and 06/2019. For those with LSM >10kPa, electronic case note review was performed to identify those who underwent OGD within 12 months of their TE and had PLT available. Data were collected for endoscopic findings, PLT, aetiology of CLD and outcomes (variceal bleeding and mortality). CSV were defined as oesophageal varices (OV) described as grade 2 or above. We defined 'Baveno positive category' as patients with either LSM ! 20kPa and/or PLT £150000, 'Baveno negative category' were those with both LSM <20kPa and PLT>150000. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) for the detection of CSV were calculated. Overall sensitivity and specificity were 96.3% and 36.1% respectively.
22/229 (9.6%) of patients died. Mortality was significantly higher among patients in Baveno positive category. Only 1 patient in Baveno negative category died (0.43%), cause of death was not related to variceal bleed or hepatic decompensation.
Conclusion Our results show that in DGH cohort of heterogeneous aetiology of CLD, the Baveeno VI criteria can be safely used to avoid endoscopic screening for CSV. Mortality rate was significantly lower in patients in Baveno negative category and none experienced variceal bleed. Abstract P002 Table 1 Abstracts