Cirrhosis, Liver Failure
Conditions
Brief summary
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..
Detailed description
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.
Interventions
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
Sponsors
Study design
Eligibility
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite endpoint that includes the incidence specified infections: | Two years | 1. Spontaneous bacterial peritonitis 2. Urinary tract infections: 3. Pneumonia 4. Skin and soft tissue infections 5. Spontaneous bacteremia 6. Endocarditis 7. Tuberculosis 8. Infectious colitis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of hospital stay | Two years | The length of hospital stay after the admission with diagnosed infection or contraction of infection during hospital stay |
| The usage of antibiotics required for treatment of a diagnosed infection | Two years | — |
| The incidence of adverse effects | 2 years | — |
Other
| Measure | Time frame |
|---|---|
| Changes in lymphocyte subpopulations | 6 months |
| Change in the phagocytic activity of macrophages | 6 months |
| Changes in the levels of immunomodulators - IL-6, TNF alpha | 6 months |
| Changes in the levels of imunoglobulins IgA, IgG, IgM, IgD, IgE | 6 months |
| Changes in the capacity for oxidative burst in macrophages | 6 months |
| Changes in the complement levels and activation pathways activity | 6 months |
Countries
Slovakia