G-CSF Plus NAC In Severe Alcoholic Hepatitis

Patients with severe alcoholic hepatitis, admitted to Department of Hepatology PGIMER, Chandigarh from July 2014 to December 2016 will be included in the study. METHODS This will be an open label trial. A randomization code is generated by random number table. The patients will be randomized to receive standard medical therapy of pentoxifylline only as control and combination therapy of Pentoxifylline with NAC and G-CSF as cases. There will be one control and two cases as below: 1\) Pentoxifylline (control) 2) Pentoxifylline+G-CSF (case 1) 3) Pentoxifylline+G-CSF +NAC (case2) A) Pentoxifylline 400 mg thrice daily for 28 days A) Pentoxifylline 400 mg thrice daily for 28 days plus G-CSF 5 mcg/kg every 12 hourly for consecutive 5 days A) Pentoxifylline 400 mg thrice daily for 28 days plus G-CSF 5 mcg/kg every 12 hourly for 5 days plus NAC 300 mg/kg on day 1 (150 mg/kg in 250 ml of 5% dextrose over a minute of 30 minutes,50 mg/kg in 500ml 5% dextrose over a period of 4 hours, 100mg /kg in 1000 ml of 5% dextrose over a period of 16 hours ) and on day 2 through 5 100mg /kg/day in 1000ml of glucose solution. This will be a single time therapy. Patients will be admitted in the department of hepatology and will be assessed everyday clinically as well as by laboratory tests during therapy to assess safety and effects of treatment. 1. Total leukocytes count will be assessed daily. 2. Circulating CD 34 positive cells will be measured on day 0 and 6 of G-CSF therapy. 3. In addition, ultrasonography will be performed at day 1 and 6 in order to evaluate difference in spleen size and portal vein flow. 4. Biochemical, coagulation, and hematological parameters (Liver function tests, Renal Function Tests, Prothrombin Time, International Normalised Ratio, etc.) will be monitored periodically, daily for 1 week, then weekly for 1month and monthly for three month. All patients will be followed at weekly interval for 1 month and then monthly for 3 months. Outcome: Primary Objectives: Survival at 3 months Secondary Objectives: Mobilisation of CD34 positive cells in peripheral blood. Clinical/biochemical improvement in liver function profile. Improvement in prognostic scores-Maddrey's Discriminant function, MELD score, and Child score. Safety and efficacy of G-CSF and NAC in alcoholic hepatitis