Transfer Factor Efficacy in the Management of Cirrhosis-associated Immune Dysfunction (IMUNO-HEGITO7)

Prospective Randomized Single-blind Study on Transfer-factor in Acute Decompensation of Advanced Chronic Liver Disease and Acute-on-chronic Liver Failure.

This study is aimed to assess the efficacy of Human derived Transfer factor ( T-lymphocytes homogenate that contains small molecular weight (10 kDa) molecules: various IFNs, ILs, chemokines, endorfins, heat shock proteins) in decreasing rate and/or severity of infections in acute or chronic decompensations of liver cirrhosis and acute on chronic liver failure..

Most of mortality from advanced chronic liver disease (ACLD) is mediated by so- called specific complications of end-stage liver disease (ESLD); one of the most important is infection (25-30%). Infection is responsible for considerable proportion of ESLD-related mortality. Important in pathogenesis of infections in ESLD is CAIDS (cirrhosis - associated immune dysfunction syndrome), recently re-named to CAID (Cirrhosis-Associated Immune Deficit). TRANSFER FACTOR (TF) is supposed to act at several points in CAID - cascade. This gave rise to hypothesis, that TF could be of benefit in AD/ACLF. Characteristics of TF It has been shown that transmission fo T-Lymphocyte reactivity is transmissible not only by T-cells alone, but also by hommogenate of peripheral white blood cells. Later it became clear that for the transmission of cellular immunity is responsible dialysable fraction of T-lymphocytes homogenate (with small molecular weight of 10 kDa; consists of amino acids, small peptides, nucleotides etc). This homogenate was named Transfer - factor (TF). One dose of lyophilized drug contains: Leucocyti dialysatum 200 x 10 6 (contains various IFNs, ILs, chemokines, endorfins, heat shock protein etc) stimulates T H 1 response induces production of IL-1, IL-2 activates chemotaxis of immunocompetent cells increases fagocytic activity activates antigen-presentation by APCs The aim of this study is to assess the efficacy of transfer factor in decreasing rate and/or severity of infections in ACLF.

Aqua pro injectione 4 mL ampules for subcutaneous administration in the same time points as in the active arm

One dose (the content of one amp.) of lyophilised drug contains: Leucocyte dialysatum 200 x 10 to the power of 6 (Lyophilized dialysate from 200 million leukocytes) pH = 7.8 to 9 after reconstitution (dissolving) of drug To be administered subcutaneously as follows: 12 doses TF in total: 3 x TF in first week: day 1,3,5 2 x TF in week 2: day 8 , 11 1 xTF in week 3 and 4 : day 15, 22 1 x TF once a month up to 6 month

12 doses in total: 3 doses in first week: day 1,3,5 2 doses in week 2: day 8 , 11 1 dose in week 3 and 4 : day 15, 22 1 dose once a month up to 6 month

Spontaneous bacterial peritonitis Urinary tract infections: Pneumonia Skin and soft tissue infections Spontaneous bacteremia Endocarditis Tuberculosis Infectious colitis

The length of hospital stay after the admission with diagnosed infection or contraction of infection during hospital stay

Inclusion Criteria: admission to hospital at participating liver units or ICUs or internal medicine wards with acute decompensation (AD) of advanced chronic liver disease or acute-on-chronic liver failure according to CLIF - C criteria ability to provide informed consent, Exclusion Criteria: disapproval lymphoproliferative disorders liver transplantation in the past pregnancy suspected. chronic infection in risk locations CNS peritoneum Known virus-related immune deficiency malignancy severe heart failure (NYHA >= III) severe lung disease (COPD, GOLD>3)