Role of intravenous N-Acetyl cysteine (NAC) with steroid in acute alcoholic hepatitis (AAH) with high morbidity score: A randomized open label prospective clinical pilot trial

P Patrick Basu, MD, MRCP, FACG, AGAF, Niraj J Shah, MD, Richard Huang, Medical, Student, LIJ, Ravi Siriki, MD, Md Ashfique, MD, Sakina Farhat, MD. 1. Columbia University College of Physicians and Surgeons, NY 2. NSLIJHS/ Hofstra North Shore LIJ School of Medicine, NY 3. James J. Peters VA Medical Center, Mount Sinai School of Medicine, NY.

Objective: Acute alcoholic hepatitis is a severe clinical state with significant morbidity and impending mortality in 28 days of about 49% with systemic involvement and acute liver failure. Recent meta-analysis provokes therapeutic controversies of use of corticosteroid or even liver transplantation (in some countries) based on the severity score. Established standard of care (SOC) is absolute abstinence, proper nutrition with multivitamins. AAH is a condition of immune induced massive liver injury due to recruitment of liver designated CD3, CD4 and CD8; resulting in intra hepatic oxidative insult, depleting mEOS system altering Redox and depleting the salvage precursor Glutathione – thus activating the Th2 pathway up regulating the entire cascade of cytokines (IL1, IL2, IL6, IL8, IL10, TNF α) causing massive inflammation; mainly intra hepatic oxidative insult with preexisting nutritionally depleted liver.

Method: Forty five (n=45) patients with AAH were randomized. Age 32-58 (mean 46), race Hispanic 21, (Male 18, Female 3), Caucasian 18 (male 9, Female 9), African American 6 (Male 5, female 1), mean BMI 24%, Mean Alcohol daily consumption 80 grams/day. Total years of Alcohol consumption mean 14 years. DF 56%, Lilies score > 0.67, ABCI ( Albumin, Total Direct Bilirubin, creatinine and INR) > 9, mean MELD 24 and mean HOMA 0.9

Group A (n=15): I.V Methyl Prednisolone, i.v. Vitamin C 500 mg + Pentoxifylline 400 mg orally for 4 days followed by Prednisone 60 g orally for 30 days
Group B (n =15): I.V NAC + IV Vitamin C 500 mg + Pentoxifylline 400mg for 4 days followed by Prednisone 60 g orally for 30 days
Group C (n=15): IV Methyl Prednisolone + IV NAC + Pentoxifylline 400 mg for 4 days followed by Prednisone 60 g orally for 30 days

All received 2 grams of salt/day. 3000 cal/day and 120 grams of vegetable protein with BCCA orally.

Labs {Quest Lab at NJ}: Day 0, 4, 7, 14, 21, 30 – TB, AST, ALT, creatinine, CBC, BMP, LFT, Ammonia. Day 0, 14 and 21- Insulin, IL6, IL8, IL12, TNF α, MELD score
Sonogram: Day 0 and Day 30
Body weight: day 0 and 21

Exclusion criteria: GI bleed, HE, Sepsis, Cirrhosis, HIV, HCV, HBV, HCC, shock, Platelet count < 50 k

Results: See table

Conclusion: This clinical pilot study postulates adding IV NAC to the SOC in AAH with DF > 32% having a better efficacy with accelerated bilirubin response that enabled to continue steroid therapy with faster recovery time. Larger trial warrants validation.