Liver cirrhosis
Dose-escalation phase I single-centre study with 3+3 design: 3 patients will receive the same dose, if no dose-limiting toxicity recorded dose will be escalated to the second group of 3 patients until maximum tolerated dose. Followed by randomised controlled single centre phase II study of autologous activated macrophage infusion versus standard medical care. Macrophages will be infused via peripheral vein for the duration of 30 minutes. Participants will be randomised 1:1 via computer system based on a minimisation algorithm using the key variable aetiology of disease. No blinding will be possible but efficacy data will be analysed at the end of the trail to avoid bias.
1. Age 17-65 2. Liver cirrhosis 3. Model for End-Stage Liver Disease (MELD) score 10-16 4. Aetiology liver disease: ALRD, NAFLD, PBC, hemochromatosis, alpha 1 anti trypsin deficiency, previous Hep C with SVR
1. Refusal or inability to give informed consent to participate in the study 2. Other cause of chronic liver disease/cirrhosis not included in listed aetiologies – this is left to the clinical judgement of the investigator based on previous investigations and trial screening 3. Portal hypertensive bleeding; active episode of bleeding requiring hospitalisation in the last 3 months where varices have not been eradicated by banding 4. Ascites unless, in the opinion of the investigator, the ascites is minimal and well controlled with no increase to diuretic therapy in last 3 months 5. Encephalopathy; current or requiring hospitalisation for treatment in last 3 months 6. Hepatocellular carcinoma – uncertain cases to be discussed at local hepatobiliary multidisciplinary meeting, dysplastic or indeterminate nodules to be excluded, regenerative or other nodules to be included at discretion of MDM 7. Previous diagnosis of hepatocellular carcinoma 8. Previous organ transplant or previous recipient of tissue 9. Listed for liver transplantation 10. Any situation that in the Investigators' opinion may interfere with optimal study participation such as alcohol or drug abuse, domicile too distant from study site, potential non-compliance or inability to co-operate 11. Presence of clinically relevant acute illness that in the opinion of the investigator might compromise the participant’s safe participation in the study 12. Presence or history of cancer within past 5 years with exception of adequately treated localised skin carcinoma, in situ cervical cancer or solid malignancy surgically excised in total without recurrence for 5 years 13. Pregnancy or breastfeeding