Liver failure (acute liver failure and acute decompensation of cirrhosis) Digestive System
Conditions
Interventions
Nivolumab (anti-PD1 antibody)
Non-CTIMP, physiological assessment in two groups of patients:
1. Patients (n = 19) with acute liver failure (ALF)
2. Patients (n=59) with acute decompensation of cirrho
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria – Group 1 (ALF): 1. Male and female patients aged 18 years or older at screening 2. Clinical diagnosis of acute liver failure: 2.1. Presence of jaundice (bilirubin > 40 uMol/L) 2.2. INR > 1.5 2.3. Any degree of encephalopathy 2.4. No history of cirrhosis or advanced chronic liver disease 3. Informed consent (provided by a relative or a professional legal representative when the patient lacks capacity) Inclusion criteria – Group 2 (AD): 1. Male and female patients aged 18 years or older at screening 2. Clinical diagnosis of acute decompensation of cirrhosis including acute-on-chronic liver failure characterised by at least one of: 2.1. Ascites 2.2. Spontaneous bacterial peritonitis 2.3. Encephalopathy (any degree) 2.4. Variceal haemorrhage 3. Evidence of cirrhosis based on any of the following: 4. Liver biopsy (at any time) 5. Elastography (at any time) FS >10 KPa 6. Radiological imaging (at any time) 7. Informed consent (provided by the patient or a relative or a professional legal representative when the patient lacks capacity)
Exclusion criteria
Exclusion criteria: 1. Candidates for liver transplantation within 2 months 2. Duration of clinically apparent jaundice >3 months before baseline visit 3. Evidence of acute viral hepatitis 4. Biliary obstruction 5. Hepatocellular carcinoma 6. Any known autoimmune disorder, including autoimmune-mediated liver failure 7. Previous treatment with any checkpoint inhibitor 8. Untreated sepsis 9. Evidence of current malignancy (except non-melanotic skin cancer) 10. Patients with known hypersensitivity or contraindications to anti-PD-L1 antibody (nivolumab or pembrolizumab) 11. Pregnant or lactating women 12. Currently enrolled in a CTIMP 13. Known HIV infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| HLA-DR expression on circulating monocytes measured using flow cytometry on day 15 compared to baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Monocyte phagocytosis measured using pH-Rodo uptake in flow cytometry on days 5, 10, 15 and 30 compared to baseline 2. HLA-DR expression on circulating monocytes measured using flow cytometry on days 5, 10, 15 and 30 compared to baseline 3. Incidence of clinically diagnosed infection during the 30 days of follow-up 4. Incidence of bacteraemia diagnosed on blood cultures during the 30 days of follow-up 5. Changes in lipopolysaccharide-induced tumour necrosis factor alpha secretion from monocytes measured by ELISA test on days 5 and 15 compared to baseline 6. Changes in circulating bacterial 16S-ribosomal DNA (16S-rDNA) at days 5 and 10 compared to baseline measured using real-time polymerase chain reaction assays | — |
Countries
England, United Kingdom
Contacts
Public ContactMark Thursz
Outcome results
None listed