2. “My Journey Back to Kashmir” 1995 2005

3. MARS ® for Acute Liver Failure Prof. M. S. Khuroo Director Digestive Diseases Centre Khyber Medical Institute Srinagar Kashmir

4. Acute Liver Failure ALF is a devastating syndrome with high mortality Emergency liver transplantation offers the only chance of survival for ALF For logistic reasons, only 10% of ALF patients are transplanted As ALF is potentially reversible, liver support system has a potential for use as a temporary measure until spontaneous recovery or bridge to transplantation

5. Liver Support Systems Bioartificial i. ELAD ii. HepatAssist device Artificial i. Charcoal hemoperfusion ii. BioLogic-DT iii. MARS

6. Molecular Adsorbent Recirculating System (MARS ® )

7. MARS ® : specifications Requirements: monitor, kit (disposable), dialysis machine, albumin Tr. Modules: Intermittent (6-8 hr) or continuous Flow rates: blood, albumin, dialysate Cost: initial : i. device £16,000, contract £1600/yr ii. Running/session: disposables £1,100; albumin £ 200 (£3,900 to 10,400 for 3 to 8sessions)

8. MARS ® : detoxifying capacity Albumin bound bilirubin, Bile acids, tryptophan, fatty acids, aromatic amino acids, TNF alfa, interleukin 6, copper, benzodiazepines Water soluble ammonia, creatinine, urea

9. MARS ® : systemic effects in ALF Hemodynamic: i. increase in vascular resistance index, MAP ii. decrease in cardiac index, heart rate, oxygen delivery iii. no change in lactate & pH Intracranial (animal model): i. decrease in brain water & intracranial pressure ii. Improvement in lactate, glutamate & energy metabolism

10. MARS ® for ALF Indications: HE grade 2, increased ICP, ischemic hepatitis (bilirubin >8mg/dl), HRS, cholestasis, fulminant Wilson's Contraindications: MAP<55, active bleeding, severe coagulopathy, DIC Aim’s: full recovery, bridge to transplant Tr. Module: continuous, intermittent if condition improves

11. MARS ® for ALF: registry report (may 2003) Number of patients: 85 Etiology: acetaminophen, hypoxic, Wilson's, HV In hospital survival: 48 (56.9%) Transplanted: 15 (16.9%) Complications: bleeding, coagulopathy, hypotension, fever, anemia Safety profile: generally good

12. Liver Support Systems & Liver Failure: meta-analysis Systems assessed: all known Patients: ALF & AoCLF Trials (sample size): 12 (244/238) Mortality: all :101/123 (RR, 0.86; CI, 0.65-1.12) ns ALF: 72/83 (RR, 0.95; CI, 0.1-1.29) ns AoCLF: 29/40 (RR, 0.67; CI, 0.51-0.90)* Kjaegard et al, JAMA 2003

13. Khuroo et al, Liver transplantation 2004 MARS & Liver Failure: meta-analysis

14. MARS for Acute liver Failure MARS is a extremely exciting device which does detoxify albumin bound and water soluble toxins MARS corrects many hemodynamic abnormalities in patients with ALF Uncontrolled case studies have shown that MARS can be used in ALF to improve survival or bridge to transplant There are insufficient RCT to assess the role of MARS in ALF

15. MARS for Shopping Is there life in MARS: not known Should you rush to buy MARS: no Should institutions in India have MARS for trials: yes, for free/under grants Has MARS a role in other clinical situations: possibly yes, needs further data Is MARS cost effective for our community: not known