DIALIVE 2.0 Liver Dialysis for ACLF in adults with cirrhosis

Inclusion Criteria:

* Adults aged 18-70 years, with a diagnosis of ACLF grade 2-4 (according to A-TANGO ACLF criteria, APPENDIX 1)
* ACLF non-responsive to SoC for up to 48 hours prior to developing grade 2-4 ACLF.
* Inclusion within 10 days from the onset of A-TANGO ACLF grade ≥ 2.

Exclusion Criteria:

* A-TANGO ACLF grade ≥2 for more than 10 days prior to inclusion
* Pregnancy
* Co-infection with HIV and AIDS defining illness i.e. CD4+ T-cell count below 200 cells/µL, a CD4+ T-cell percentage of total lymphocytes of less than 15%, or one of the defining illnesses such as PCP, Kaposi's sarcoma, CMV, Candidiasis etc.
* Bacterial infection or sepsis unresponsive to treatment with antimicrobials for 48 hours indicated by (a) persistent pyrexia (b) rising white cell count, creactive protein and lactate (c) persistently positive cultures for bacteria or fungi and/or (d) worsening clinical state indicated by escalating requirement for fluid resuscitation, increasing vasopressors requirements or increasing organ support.
* Invasive fungal infection (clinical or radiological evidence, not solely biomarker positivity such as BDG or galactomannan)
* Acute or sub-acute liver failure in the absence of cirrhosis
* Post-hepatectomy liver failure or primary non-function following transplantation
* Previous liver transplant
* Severe thrombocytopaenia (absolute platelet count \<20,000/mm3 at screening) or evidence of rapid decline in platelet count (\> 50% reduction within the preceding 24 hrs)
* INR \>3.0, unless sustained correction for \>24 hours following FFP/PCC treatment
* Severe disseminated intravascular coagulopathy (DIC)
* Persistent haemodynamic instability as defined by:

  (i) Norepinephrine(NE) dose \>0.5µg/kg/min, or, (ii) If a second pressor is used, a composite Norepinephrine equivalence index (NEEI) of dose \>0.5µg/kg/min (iii) Arterial lactate level \>4mmol/L despite 24 hours of adequate fluid resuscitation and pressor therapy
* Severe respiratory failure: PaO2/FiO2 (P/F) ≤ 200 mmHg or 27kPa
* Established on renal replacement therapy for longer than 24 hours prior to inclusion
* A-TANGO WCC ACLF score \>64 (APPENDIX 1)
* Significant and/or uncontrolled bleeding (participants can be enrolled 48 hours after bleeding is controlled)
* Active or prior history of non hepatic malignancy unless adequately treated or in complete remission for five or more years
* HCC outside of Milan criteria.
* Acute, extensive, portal vein thrombosis extending to and occluding superior mesenteric vein
* Major systemic illness, aside from liver disease, that in the opinion of the investigator would preclude the participant from participating in the study (e.g. coronary artery disease, cerebrovascular disease, chronic pulmonary disease, chronic kidney disease, serious psychiatric disease)
* Pre-existing chronic kidney disease (CKD) defined as eGFR (estimated glomerular filtration rate) \<30 mL/min for 3 months or longer prior to screening
* Severe frailty (Clinical Frailty Scale, CFS\>5)
* Severe malnourishment (BMI\<18)
* Participants not considered appropriate for full active treatment including organ support
* Participants who have a "do not attempt cardio-pulmonary resuscitation" order in place
* Any participant who has received an investigational drug or device within 30 days, or who is scheduled to receive another investigational drug or device during the course of the study (concomitant observational studies are allowed)
* Uncontrolled seizures
* Evidence of new intracranial pathology such as cerebral hemorrhage or infarction.
* Participants diagnosed with Creutzfeldt-Jakob disease.
* Participants unable to consent for themselves, unless a legal representative/consultee is appointed and approved as dictated by local and national legislation.
* Known allergy to heparin, or type II thrombocytopaenia caused by heparin (HIT syndrome type II).
* In the opinion of the investigator, recruitment to the the study would be unsafe for the participant.