Effect of n acetylcysteine (NAC) in hypoxia induced liver injury (HILI)–a randomized placebo control clinical trial

Abstract

Objectives: HILI is common with a prevalence of 10% in US. Transient shift of intra hepatic hemodynamic compromise leads to tissue hypoxia and induces hypoxia induced protein (HIP), heat shock protein 70 (HSP24, 70), Endothelial reticular stress (ER) leading to reperfusion injury (RI). Dramatic rise of transaminases, drastic reversal with restoration of perfusion in weeks follows. In cirrhotics HILI requires liver transplantation. This study evaluated spontaneous recovery and salvage in HILI utilizing NAC. Methods: Sixty patients (n=60) with mean arterial pressure (MAP) < 35% and normal LFTs at baseline. Group A (n=28) chronic liver disease (CLD)[ alcohol-11/28(39%), NASH-9/28(32%), Hepatitis C-4/28(14%), hepatitis B-2/28(7%), PBC-1/28 (3%), AIH-1/28(3%). Group B (n=32) [respiratory failure-12/32(37%), CHF-8/32(25%), CVA-2/32(6%), sepsis-6/32(19%), post op-4/32(12%)]. Randomized into Placebo group- A1 (14) & B1 (16) and IV NAC for 48 hours - A2 (14) & B2 (16). Serum Transaminases, Bilirubin, INR, Creatinine and MELD score at 0, 3rd, 6th, 9th and 12th days with MAP and modified Sequential Organ Failure Assessment (SOFA) Score. All patients were allowed standard of care (SOC) and resuscitations if needed. Exclusions: Organ transplant, Septic shock, Hemodialysis, cancer, acute myocardial Infarct, Tylenol injury, acute viral hepatitis and organ trauma. Results: Placebo groups A1, B1: Normalized A1-[LFTs- on 3rd day-(7%), 6th day-(21%), 9th day-(36%) and 12th day-(21%). 1/14(7%) died]. B1(CLD)[ LFTs 3rd day-(19%) 6th (44%) 9 th(25%),2/16(6%) died of sepsis] NAC Groups A2[normalized LFTs 3rd (57%)6th day-(43%) 9 th day (25%), (7%)-one died ] B2 (CLD)[Normalized LFTs- 3rd day-(63%), 6th day-(25%) 9 th1/16(6%), one died]. Conclusion: This Study postulates that IV NAC (A2, B2) has efficient spontaneous recovery and salvage in non-CLD sub group B2 (63%)>A2 (57%) in day 3, in CLD NAC (A2)> placebo (A1) clinical recovery over placebo at 3rd day, (44%) over (36%) - 6th day. Larger trial need to establish the routine usage of IV NAC in HILI.