Serum levels of the protein factor of fertility (PFF) were measured by immunoenzymatic assay with a sensitivity of 4 ng/ml. The normal concentration of PFF was within 8–20 ng/ml in males and 20–40 ng/ml in females. Elevated levels of PFF – from 50 to 400 ng/ml – were found in patients with ovarian tumors (19%), cancer of the uterine body (25%) and tumors of the uterine cervix (37%).

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Blood level of transforming growth factor beta 1 (TGF-β1) is associated with liver function and immune homeostasis, which suggests it as a potential biomarker for immunosuppressant tacrolimus dose requirement at liver transplantation (LT).Aim.To evaluate diagnostic efficacy of TGF-β1 blood level at determination of individual tacrolimus dose requirement in children at LT.Materials and methods.89 children with end stage liver disease aged from 3 to 73 months were examined. Children underwent living related LT, then the recipients received 2–3 component immunosuppressive therapy, including tacrolimus. Blood concentration of tacrolimus and TGF-β1 was measured by ELISA.Results.TGF-β1 blood level in children before LT was significantly lower than in healthy children: 3.7 (1.3–8.4) and 19.3 (12.6–25.5) ng/ml, p = 0.001. A month after LT, its concentration increased to 8.1 (1.8–15.3) ng/ml (p = 0.02). A year after LT, the cytokine level remained higher than before transplantation: 6.6 (1.9–12.6) ng/ml, p = 0.01. TGF-β1 level did not correlate with tacrolimus blood concentration, determined 12 hours after the last administration of the drug, neither a month, nor a year after transplantation. At the same time, the cytokine level one month after LT was associated with a tacrolimus daily dose one year after the operation (r = –0.23, p = 0.04). In the recipients, who received smaller daily doses (0.4–2.5 mg) of tacrolimus, TGF-β1 level was higher than in those receiving large doses (3.0–6.0 mg) of the drug: 9.1 (2.6–16.2) ng/ml vs. 4.2 (1.3–9.2) ng/ ml, p = 0.04. Evaluation of diagnostic efficacy of the TGF-β1 level as a test for the detection of tacrolimus dose requirement showed that the area under the ROC curve (AUC) was 0.66 ± 0.07; 95% CI [0.53–0.79], the sensitivity and specificity of the test were 60 and 74% at threshold value 6.7 ng/ml. Relative risk of higher tacrolimus dose requirement was 3.14 ± 0.48; 95% CI [1.24–7.96].Conclusion.TGF-β1 blood level in one month after LT less than 6.7 ng/ml is 3 times higher risk factor of tacrolimus dose requirement more than 3.0 mg per day. The likehood of the test is 66%, the sensitivity and specificity – 60 and 74%.

Introduction. To prevent post-transplant complications associated with unbalanced immunosuppression, objective indicators reflecting the state of the immune system and associated with the immunosuppressant dose are required. In pediatric liver transplantation, an important indicator of hepatocellular function and restoration of anthropometric characteristics is insulin-like growth factor 1 (IGF-1), which exhibits both nonspecific and selective immunomodulator properties.Objective: to assess the correlation between growth hormone and IGF-1 levels and tacrolimus dose and blood concentrations in pediatric liver recipients and to determine the possibility of using the IGF-1 level in selecting the drug dose required to achieve its target concentration in the blood. Materials and methods. We examined 156 children aged from 2 to 105 (median – 8) months with liver cirrhosis of various etiology, who received liver from a living related donor. The concentration of growth hormone and IGF-1 was determined in blood plasma before, one month, and one year after transplantation using the enzyme-linked immunosorbent assay. Tacrolimus residual concentration was measured in the patient’s whole blood by immunochemical method.Results. Growth hormone levels in the blood of pediatric liver recipients did not correlate with the dose or concentration of immunosuppressant tacrolimus one month or one year after transplantation, whereas the IGF-1 content was directly related to tacrolimus dose one year later (r = 0.41, p = 0.001), but not a month after surgery. The correlation coefficient was higher in uncomplicated post-transplant recipients (r = 0.51, p = 0.002) than in those with complications (r = 0.26, p = 0.17). The diagnostic efficiency of the IGF-1 level as an objective criterion for selecting the tacrolimus dose required to achieve its target blood concentration was 0.80 ± 0.11; 95% CI [0.58–1.00] (p = 0.007). In recipients with blood IGF-1 levels ≥115.7 ng/mL, the probability of prescribing a tacrolimus dose ≥0.25 mg/kg/day was 14 times higher than in children with lower blood IGF-1 levels. The estimated accuracy of the test was 83%, positive predictive value was 71%, and negative predictive value was 85%.Conclusion. The IGF-1 level was found to correlate with tacrolimus dose in liver transplant recipients one year after transplantation. The diagnostic efficiency of IGF-1 as a potential indicator for choosing the tacrolimus dose required to achieve its target blood concentration is 80%, which suggests further study of the test to assess the effectiveness of immunosuppression and selection of an individual immunosuppressant dose.

The problem of non-invasive monitoring of the liver condition is particularly relevant in liver transplantation among young children. Transforming growth factor beta 1 (TGF-β1) is a pleiotropic cytokine with a profibrogenic and immunosuppressive effect that can have a definite effect on the liver transplant functioning.Aim. To determine the diagnostic efficacy of TGF-β1 in blood when assessing the risk of developing graft dysfunction in liver recipient children. Materials and methods. 95 children aged 3 to 73 months with liver cirrhosis of various etiologies were surveyed. All the patients underwent liver transplantation (LT) from a living related donor. The TGF-β1 concentration in plasma was determined using ELISA on average 3 ± 2 days prior to liver transplantation and in the early post-transplant period.Results. The level of TGF-β1 in the blood of children with liver cirrhosis was lower than in healthy children (p = 0.001). LT was accompanied by an increase in the TGF-β1 content in the blood of recipients (p = 0.001). The incidence of graft dysfunction in the early postoperative period correlated with the pre-transplantation level of TGF-β1 (r = 0.40, p = 0.00), which was lower in recipients with developed graft dysfunction than in patients without dysfunction (1.7 ± 1.3 ng/ml versus 6.7 ± 5.3 ng/ml, p = 0.001). The analysis of the test diagnostic efficiency showed that the area under the ROC curve (AUC) was 0.85 ± 0.05, 95 % CI 0.75–0.94, the sensitivity of the method was 83 %, its specificity was 77 %. When the marker value was less than the threshold (2.2 ng/ml), the relative risk of developing graft dysfunction was 11.4 ± 0.7, 95 % CI 2.7-48.7. The accuracy of the method, the positive predictive value and the negative predictive value of the results were 78, 83 and 77 %, respectively. Conclusion. The level of TGF-β1 in the blood of liver recipient children before transplantation below 2.2 ng/ml increases the risk of developing graft dysfunction in the early postoperative period 11-fold. Measuring the TGF-β1 level in the blood prior to liver transplantation makes it possible to identify recipients with 85 % chance of developing a graft dysfunction.