efficacy of granulocyte colony-stimulating factor and erythropoetin for patients with acute-on-chronic liver failure

Conditions: Acute on Chronic Hepatic Failure

Summary: 50 patients of acute-on-chronic liver failure (aclf) will be enrolled and randomized into g-csf+epo or placebo arms treatment protocol to administer g-csf (in prefilled syringe) at a dose of 5 µg/kg s/c at days 1, 2, 3, 4, 5 and then every 3rd day till day 28 (total 12 doses), along with darbopoetin alpha 100 mcg/ week (in prefilled syringe) for 4 weeks (total 4 doses). standard medical therapy included as per requirement lactulose, bowel wash, albumin, terlipressin, antibiotics (if indicated) will be continued and recorded. pentoxiphylline in alcoholic hepatitis and tenofovir in hep b reactivation controls: standard medical therapy will be given along with placebo in similar prefilled syringes. follow up physical examination will be done daily, after 1 week and at 4 weeks, at 2 months, at 3 months and at 6 months cbc on alternate day for 1 week, at end of 1 week and then at end of 4 weeks , at 2 months, at 3 months and at 6 months kft on alternate day for 1 week, at end of 1 week and then at end of 4 weeks, at 2 months, at 3 months and at 6 months lft along with pt/inr on alternate day for 1 week, at end of 1 week and then at end of 4 weeks, at 2 months, at 3 months and at 6 months afp at baseline, after 4 weeks, at 3 months and at 6 months liver regenerative potential efficacy testing at baseline and after 4 weeks

50 patients of aclf will be enrolled and randomized into g-csf+epo or placebo arms baseline investigations: * hematology * cbc, prothrombin time and inr * peripheral smear, retics * biochemistry * liver function testing, afp * kidney function test * etiology of acute event: * infectious etiology: igm anti hav, igm anti hev, igm anti hbc ( if hbsag +ve), igm anti hdv ( if hbsag +ve), hev rna * non infectious etiology: alcohol binging in last 4 weeks, hepatotoxic drugs, ana (\>1: 80), igg , surgeries in past 4 weeks, acute variceal bleed within 4 weeks * etiology of underlying chronic liver disease : * infectious etiology: total antihbc, anti hcv, hcv rna, hbv dna * non infectious etiology: autoimmune markers, copper studies, iron studies, homa ir, fbs ascitic fluid analysis ( wherever its possible) ugi endoscopy imaging usg abdomen with doppler for spleno-portal axis cect- triple phase upper abdomen liver regenerative potential efficacy testing (wherever it is possible) histology ( by transjugular liver biopsy) liver dendritic cells ( cd11c, cd40, cd 54, cd 123, bdca 2 staining) by flow cytometry cd 34+ cells and cd 133+ cells measurement in hepatic venous blood, peripheral blood and liver biopsy by flow cytometry markers of proliferation like ki- 67, proliferating cell nuclear antigen (pcna) in hepatic venous blood and liver biopsy markers of angiogenesis like vegf, v wf in hepatic venous blood measurement of hepatic venous pressure gradient ( hvpg) treatment protocol to administer g-csf (in prefilled syringe) at a dose of 5 µg/kg s/c at days 1, 2, 3, 4, 5 and then every 3rd day till day 28 (total 12 doses), along with darbopoetin alpha 100 mcg/ week (in prefilled syringe) for 4 weeks (total 4 doses). standard medical therapy included as per requirement lactulose, bowel wash, albumin, terlipressin, antibiotics (if indicated) will be continued and recorded. pentoxiphylline in alcoholic hepatitis and tenofovir in hep b reactivation controls: standard medical therapy will be given along with placebo in similar prefilled syringes. follow up physical examination will be done daily, after 1 week and at 4 weeks, at 2 months, at 3 months and at 6 months cbc on alternate day for 1 week, at end of 1 week and then at end of 4 weeks , at 2 months, at 3 months and at 6 months kft on alternate day for 1 week, at end of 1 week and then at end of 4 weeks, at 2 months, at 3 months and at 6 months lft along with pt/inr on alternate day for 1 week, at end of 1 week and then at end of 4 weeks, at 2 months, at 3 months and at 6 months afp at baseline, after 4 weeks, at 3 months and at 6 months liver regenerative potential efficacy testing at baseline and after 4 weeks

Eligibility criteria:
inclusion criteria: all consecutive patients with acute hepatic insult manifesting as jaundice (sr. bil. ≥ 5 mg/dl) and coagulopathy (inr≥1.5), complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease exclusion criteria: * age \ 75 years * autoimmune disorders * hcc * sepsis ( any culture positive: blood, urine, any other obvious source of infection: uti, sbp) * multi organ failure * grade 4 he * hiv seropositivity / pregnancy * essential hypertension * patients being taken up for transplant * refusal to participate in the study

Keywords: acute-on-chronic liver failure aclf cirrhosis acute hepatitis