Please select the eligibility criteria that correspond to the clinical trial below.
Title: Granulocyte Colony Stimulating Factor (G-CSF) to Treat Acute-on-chronic Liver Failure: A Multicentre Randomized Trial
Brief Summary: Multicentre, open, randomised, and controlled trial conducted in patients diagnosed with acute on chronic liver failure (ACLF) who meet inclusion/exclusion criteria.The objective of GRAFT-trial is to evaluate efficacy and safety of subcutaneously administered granulocyte colony-stimulating factor (G-CSF) in patients with ACLF. All patients will receive standard medical care for ACLF according to the guidelines. Patients in the experimental arm additional receive subcutaneous injections of G-CSF.


Options:
A: Inclusion Criteria:

* Decompensated Cirrhosis of liver irrespective of etiology

Exclusion Criteria:

* Acute on chronic liver failure (fulfilling either APASL or CANONIC criteria of ACLF)
* Splenic diameter of more than 18 cm
* Concomitant HCC or other active malignancy
* Upper gastrointestinal bleeding in the previous 7 days
* Portal vein thrombosis
* Severe renal dysfunction as defined by creatnine \> 1.5mg/dl
* Severe cardiac dysfunction
* Uncontrolled diabetes (Hb A 1c ≥ 9) or diabetic retinopathy
* Acute infection or disseminate intravascular coagulation
* Active alcohol abuse in last 3 months
* Known hypersensitivity to G-CSF
* HIV co-infection
* Pregnancy
* Refusal to give informed consent
B: Inclusion Criteria:

* All patients who were known to have cirrhosis of liver with portal hypertension, now decompensated with ascites/ jaundice/ bleed/ HE/ HRS

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
C: Inclusion Criteria:

• Decompensated Cirrhosis of liver irrespective of etiology

Exclusion Criteria:

* Acute on chronic liver failure (fulfilling either APASL or CANONIC criteria of ACLF)
* Splenic diameter of more than 18 cm
* Concomitant HCC or other active malignancy
* Upper gastrointestinal bleeding in the previous 7 days
* Portal vein thrombosis
* Severe renal dysfunction as defined by creatnine \> 1.5mg/dl
* Severe cardiac dysfunction
* Uncontrolled diabetes (HbA1c ≥ 9) or diabetic retinopathy
* Acute infection or disseminate intravascular coagulation
* Active alcohol abuse in last 3 months
* Known hypersensitivity to G-CSF
* HIV co-infection
* Pregnancy
* Refusal to give informed consent
* Those opting for liver transplant
D: Inclusion Criteria:

1. Acute-on-chronic liver failure (ACLF) according to the consensus criteria recently defined by the CANONIC study group \[Moreau 2013\]. Patients with acute decompensation of cirrhosis \[defined as acute development of one or more of the following: ascites (onset and/or worsening), hepatic encephalopathy (onset and/or worsening), gastrointestinal haemorrhage, bacterial infection\] are classified as ACLF if one of the following applies:

   * single kidney failure (serum creatinine level ≥ 2 mg/dl) or
   * single failure of one of the following organ systems: liver, coagulation, circulation, or respiration, together with a serum creatinine level ranging from 1.5 to \< 2.0 mg/dl and/or mild to moderate hepatic encephalopathy or
   * single cerebral failure together with serum creatinine level ranging from 1.5 to \< 2.0 mg/dl or
   * two or more organ failures. Organ failures are defined according to the CLIF-C OFs \[Jalan 2014\].
2. Age ≥ 18 years, male or female
3. Written informed consent from patient, legal or authorized representative or a confirmation of justification of trial participation by an independent medical consultant PLEASE NOTE: In case of confirmation by the independent medical consultant a deferred informed consent from patient, legal or authorized representative has to be given

Exclusion Criteria:

1. Prior not curatively treated or active malignancies
2. Sickle cell disease
3. septic shock, defined by the following symptom complex: bacteraemia AND SIRS AND shock
4. WBC-count of \> 50 x 109/L
5. Known HIV infection
6. Known intolerance to filgrastim
7. Suspected lack of compliance
8. Pregnant or nursing women
9. Fertile women (within two years of their last menstruation) without appropriate contraceptive measures (implanon, injections, oral contraceptives, intrauterine devices, partner with vasectomy) while participating in the trial (participants using a hormone-based method have to be informed of possible effects from the trial medication on contraception).
10. Participation in other interventional trials

Answer: D