Efficacy of Granulocyte Colony-stimulating Factor and Erythropoetin for Patients With Acute-on-chronic Liver Failure
Efficacy of Granulocyte Colony-stimulating Factor and Erythropoetin for Patients With Acute-on-chronic Liver Failure
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
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 <12 or > 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