Educational pathways of childhood cancer survivors-a parental cohort.

PURPOSE: Using the International Standard Classification of Education (ISCED), we examined the educational and vocational pathways of two comparable, parental cohorts: childhood cancer survivors (CCS) and their siblings. Both cohorts had previously entered parenthood. The aim of the study was to elucidate whether childhood cancer and treatment affect the educational pathways chosen by parents who are former patients. METHODS: We analysed data that was collected from childhood cancer survivors and their siblings regarding their offspring's health within the FeCt Multicentre Offspring Study (conducted 2013-2016). We evaluated and compared the professional pathways of (i) all participating survivors and all participating siblings and those of (ii) survivors and their biological siblings. RESULTS: Overall information on parental gender, age, and education were available from 1077 survivors and 246 siblings (group (i)). The majority of participants were female with a mean age of 35.2 (survivor) and 37.9 (sibling) years at time of survey. For subgroup (ii), analysis information was available on 191 survivors and 210 siblings. Fathers achieved university degrees significantly more often than mothers (p = 0.003 (i), p < 0.001 (ii)). The distribution of professional education was not significantly different between cancer survivors and siblings in either cohort (i) or (ii). CONCLUSIONS: Regarding our research on the educational and vocational trajectory of CCS, patients can be reassured that family planning and vocational education are well compatible. Inequalities regarding gender-specific educational pathways remain to be addressed. IMPLICATIONS FOR CANCER SURVIVORS: CCS should monitor their fertility status regularly and, if necessary, cryopreserve germ cells or tissue in order to optimize their family planning. Educational opportunities should be pursued as desired and with confidence. Local as well as European aftercare programs can assist with family planning and education.

First-line immunosuppressive treatment in children with aplastic anemia: rabbit antithymocyte globulin.

Immunosuppressive therapy is the treatment of choice in children with acquired severe aplastic anemia (AA) and no HLA-matched family donor. The paper presents results of a multicenter study of 63 children with AA treated with rabbit antithymocyte globulin (r-ATG) and cyclosporine A as the first line treatment in the years 1996-2012. Therapeutic effects were evaluated at Days 112, 180, and 360. At Day 112, remission was achieved in 28 out of the 63 patients (44.4 %), complete remission in 10 patients (15.9 %), and partial remission in 18 (28.5 %). At Day 180, 31 patients (49.2 %) were in remission including 15 cases in complete (23.8 %), and 16 cases in partial remission (25.4 %). One year after therapy onset, 34 patients (64.9 %) were in remission including 24 patients (38.0 %) in complete and 10 (15.9 %) in partial remission. Relapse occurred in 4 patients, from 8 months up to 2 years and 2 months after remission. One child, 5 years after remission, was diagnosed with paroxysmal nocturnal hemoglobinuria. The estimated 10-year overall survival rate and 10-year event-free survival rate were 67 % and 57 %, respectively.

Comparison of contrast-enhanced ultrasonography with grey-scale ultrasonography and contrast-enhanced computed tomography in diagnosing focal fatty liver infiltrations and focal fatty sparing.

PURPOSE: Fatty liver infiltrations and fatty sparing impair diagnostic performance of grey-scale ultrasonography in differentiating malignant and benign focal liver lesions. In the study, we present our experience in diagnosing focal fatty liver infiltrations and focal fatty sparing with contrastenhanced ultrasonography (CEUS) in comparison to grey-scale ultrasonography and contrast-enhanced computed tomography (CECT). MATERIAL AND METHOD: The retrospective study group (n=82 patients), included 44 (53.7%) men, 38 (46.3%) women (aged 29- 81 years, mean 55.8 years) with 48 focal fatty liver infiltrations and 34 focal fatty sparing. All patients underwent grey-scale ultrasonography (US), CEUS using SonoVue® and CECT executed within the 7 days. RESULTS: With US, CEUS and CECT focal fatty liver infiltrations were diagnosed in 22, 46 and 44 cases, respectively. The following values were obtained: sensitivity - 45.8%, 95.8% and 91.7%, specificity - 100% for all, accuracy - 95.2%, 99.6% and 99.3%, respectively. Focal fatty sparing was diagnosed in 16, 31 and 30 cases, respectively. The following values were obtained: sensitivity - 47.1%, 91.2% and 88.2%, specificity - 99.8%, 100% and 100%, accuracy - 95.6%, 99.4% and 99.3%, respectively. No statistically significant differences were found in sensitivity of diagnosing focal fatty liver infiltrations and focal fatty liver sparing between CEUS and CECT. Sensitivity of grey-scale ultrasonography was significantly lower when compared to those of CEUS and CECT (p<0.001). CONCLUSION: CEUS is as sensitive as CECT in focal fatty infiltrations and focal fatty sparing diagnosing. However, CEUS provides more information than CECT about the vasculature and enhancement pattern of focal fatty liver infiltrations.

[New bioplastic materials for reconstructive surgery].

Results of creation and clinical application of bioplastic materials using specimens from the tissue bank of the Institute of Traumatology and Orthopedics are presented. The use of materials of the new generation, such as perfoost, alomatrix-implant, and osteomatrix, is illustrated by examples of the treatment of various bone diseases. High biocompatibility and efficiency, osteoconductive and osteoinductive properties of these materials are reported. Technical developments in modern bioimplantology are analysed with reference to their status in the Institute's tissue bank.

Concentrations of ssDNA in liver tissue and its correlation with sFas and sFasL in serum of patients infected with HBV, HCV, HCV and HIV.

PURPOSE: The concentration of nucleic acids that undergo apoptosis (ssDNA) determines the actual activity of programmed cell death. ssDNA concentrations in liver tissue of patients with chronic HBV, HCV and HCV and HIV infections were assessed. The concentration of this nucleic acid was analyzed in relation to the concentrations of serous apoptosis indicators, sFas and sFasL receptor proteins, the activity of inflammatory processes and fibrosis in liver tissue as well as HBV, HCV and HIV viraemia. PATIENTS: The study included 153 patients: 48 chronic HBV infected, 86 chronic HCV infected and 19 HCV and HIV infected. PATIENTS AND METHODS: The concentrations of HBV-DNA, HCV-RNA and HIV-RNA were determined by use of RT-PCR method. CD3+, CD4+ and CD8+ lymphocytes count were detected in HIV infected patients' blood by use of a flow cytometer. The concentration of ssDNA was determined by use of monoclonal antibodies and ELISA tests. The concentrations of sFas and sFasL in serum were determined by use of an immunoenzymatic method (ELISA). RESULTS: The concentration of ssDNA in liver tissue of both HCV and HBV infected patients was higher in comparison to those co-infected with HCV and HIV (1332 x 10(-6) g/mg, +/-664 x 10(-6); vs 1508 x 10(-6) microg/mg, +/-810 x 10(-6); vs 886 x 10(-6) microg/mg, +/- 388 x 10(-6); p < 0.004). No correlation between ssDNA concentration and HBV and HCV viraemia was observed. In patients infected with HCV genotype 3, the concentration of ssDNA was 1343 x 10(-6) microg/mg, +/-700 x 10(-6), comparable from patients infected with genotype 1, 296 x 10(-6) microg/mg, +/- 615 x 10(-6). The highest concentration of ssDNA in liver tissue was detected in HBV infected patients with low inflammatory activity (1645 x 10(-6) microg/mg, +/-987) and low fibrosis (1606 x 10(-6) microg/mg, +/- 876 x 10(-6). Mild inflammatory changes and low fibrosis were observed in all HCV and HIV infected patients. No correlation between ssDNA concentration in liver tissue and HIV viraemia (r = 0.03; p = 0.90), HCV, CD8+ and CD4+ count (r = -11; p = 0.66) was observed. The concentration of ssDNA among HCV and HIV infected patients correlated with the concentration of sFas in serum (r = 0.52; p < 0.02). CONCLUSIONS: HCV, HBV and HIV viraemias do not correlate with ssDNA concentration in liver tissue. In patients with HCV and HIV infections, CD4+ and CD3+ counts do not correlate with the concentration of ssDNA in liver tissue. HIV infection seems to inhibit apoptosis processes in liver tissue of HCV and HIV co-infected patients. In the case of HCV and HIV infections, the concentration of sFas in serum correlates with the concentration of ssDNA in liver tissue.

Mucosal gastrin cells and serum gastrin levels in children with Helicobacter pylori infection.

PURPOSE: Impaired control of gastric juice secretion is observed in chronic gastritis due to Helicobacter pylori (H. pylori) infection. G cells are stimulated by such cytokines as tumor necrosis factor (TNF-alpha), interferon gamma (IFN-gamma) and interleukin-8 (IL-8). The number of D cells producing somatostatin decreases simultaneously. An increase in gastrin levels could also depend on alkalization in G cell environment caused by bacterial urease. The aim of the study was to evaluate G cell counts in the antrum and gastrin levels in the serum of children with H. pylori infection and after bacterium eradication. MATERIAL AND METHODS: The study was performed in 106 patients. Children were divided into 3 groups with regard to the presence and course of H. pylori infection. Fifty nine children (55.7%) had chronic gastritis in the course of H. pylori infection with a positive titre of antibodies in IgG class against H. pylori; 29 children (27.3%) with past H. pylori infection, without bacterium colonization and gastritis but with a positive titre of antibodies in IgG class against H. pylori; 18 children (17%) with functional disorders of the gastrointestinal tract but without H. pylori infection. RESULTS: The quantitative analysis of gastrin cells in the antral mucosa of children performed by immunohistochemical method showed the highest gastrin cell count in group I with H. pylori infection (112.1 +/- 58.9 cell/mm2) and in group II with past H. pylori infection (105.3 +/- 73.1 cell/mm2). The serum gastrin level (92.9 +/- 41.6 microU/ml) was the highest in children with H. pylori infection. In controls, it was 70.0 +/- 15.3 microU/ml and could be compared to the results of children with past H. pylori infection. CONCLUSIONS: 1. The H. pylori infection plays a significant role in the stimulation of G cells increase and gastrin release in the blood serum in children. 2. The eradication of H. pylori infection is probably a main factor in gastric secretion down-regulation during gastritis in children.

Event-related cerebral potentials for the diagnosis of subclinical hepatic encephalopathy in patients with liver cirrhosis.

PURPOSE: Subclinical hepatic encephalopathy (SHE) seems to be a common problem in liver cirrhosis, however, studies assessing the pathogenesis of this disease remain unclear. Currently no gold standard exists for the diagnosis of this complex neuropsychiatric syndrome. The present study was undertaken firstly to examine the diagnostic usefulness of auditory event-related cerebral potentials (ERPs) in the detection of SHE, and secondly to compare it with that of the most validated psychometric test. MATERIAL AND METHODS: 22 patients with liver cirrhosis without overt hepatic encephalopathy and 28 healthy controls were studied, using auditory ERPs. In addition they underwent a battery of neuropsychological and laboratory tests. RESULTS: P300 latency analysis turned out that cirrhotics patients had significantly longer P300 latency than controls. The only neuropsychological test showing significant difference between clinical and control group was the similarities subtest of WAIS-R. CONCLUSIONS: The results of the present study suggest that ERPs are more sensitive method than psychometric tests in detecting early changes in the brain function of patients with cirrhosis and for this reason this neurophysiological method should be applied in clinical practice.

MR and 1H MR spectroscopy of the brain in patients with liver cirrhosis and early stages of hepatic encephalopathy.

BACKGROUND/AIMS: Hepatic encephalopathy is a serious problem in patients with liver cirrhosis and precise pathophysiological mechanisms responsible for encephalopathy are not fully understood. Magnetic resonance imaging and magnetic resonance spectroscopy can be used to detect specific morphological and metabolic abnormalities in the brain even in patients with early stages of hepatic encephalopathy. METHODOLOGY: Twenty patients with liver cirrhosis and 14 patients with grade I-II hepatic encephalopathy were studied with magnetic resonance and proton magnetic resonance spectroscopy. Localized magnetic resonance spectra were acquired in the parietal gray/white matter regions and basal ganglia. Control group consisted of 20 healthy volunteers. RESULTS: Frequency and degree of brain atrophy and bilateral signal hyperintensities in globus pallidus were similar in groups with liver cirrhosis and with encephalopathy. Decreased myoinositol, choline and increased glutamine levels were noted in both groups whereas N-acetylaspartate levels were unchanged. The statistically significant differences between cirrhotic and encephalopathic groups were observed only in myoinositol/creatine ratio in basal ganglia. There were no significant differences in metabolic concentrations between parietal and basal ganglia regions. CONCLUSIONS: Metabolic brain alterations occur earlier than clinical evidence of hepatic encephalopathy but there is no correlation between presence of symptoms encephalopathy and magnetic resonance and magnetic resonance spectroscopy findings.

Search for hepatitis delta virus (HDV) infection in hepatitis C patients in north-eastern Poland. Comparison with anti-HDV prevalence in chronic hepatitis B.

Hepatitis C virus and hepatitis D virus have been shown to suppress HBsAg synthesis. Thus it is possible that HDV infection occurs despite the lack of detectable HBsAg. The aim of our study was to (a) determine the prevalence of HDV infection in patients with chronic hepatitis C (b) compare it with the prevalence of HDV infection in HBsAg positive patients with hepatitis B. The study group consisted of 51 chronic hepatitis C patients, 30 HIV infected drug addicts (27 of them were also positive for anti-HCV) and 102 hepatitis B patients. The participants were tested for anti-HDV, anti-HCV and HBsAg. All anti-HCV positive patients were negative for anti-HDV. Four individuals with anti-HDV belonged to hepatitis B group and constituted 3.9% of all HBsAg positive subjects. We conclude that (a) there is currently no evidence of HDV infection among HCV infected patients in our region (b) hepatitis delta infection is rare in north-eastern Poland.

Immunological response in HIV-positive patients vaccinated against tick-borne encephalitis.

BACKGROUND: Vaccination against infectious diseases is a recommended preventive measure in patients with impaired immunity. The aim of the study was to estimate the immunogenicity of the vaccine against tick-borne encephalitis (TBE) in HIV-infected patients and to determine its safety for this group. PATIENTS AND METHODS: The TBE vaccine FSME-IMMUN-inject was tested on 29 HIV-positive patients and the response compared to that of 40 healthy controls. The vaccination protocol for the HIV-positive group was modified by the addition of a fourth dose according to a 0/1/2/9-month schedule. RESULTS: No serious adverse reactions were observed in patients with deficient immunity. A better response was obtained in HIV-infected patients with CD4 counts >or= 500/microl (55% of the patients had levels of IgG antibody > 126 VIEU/microl) than in those with CD4 counts of 200-499/microl (40%). However, the difference did not reach significance. 85% of healthy controls achieved protective antibody titers after a full course of vaccination. CONCLUSION: The correlation between post-vaccine seroconversion and CD4 lymphocyte count showed that the FSME-IMMUN-inject vaccine can be considered to be a CD4 cell-independent vaccine. The examinations carried out 1 year after the completed vaccination protocol showed maintenance of the anti-TBE response acquired after the third vaccination in healthy subjects and in HIV-infected patients.

[Identification of genes induced to chondrocytes by nitric oxide]. / Poisk i identifikatsiia genov, indutsiruemykh v khondrotsitakh pod deistviem okisi azota.

Nitric oxide (NO) acts as a short-lived paracrine factor and selectively activates transcription of certain genes. The spectrum of inducible genes was studied in primary chondrocytes. A cDNA library was obtained by subtraction hybridization with RNAs isolated from rabbit chondrocytes before and after treatment with nitrosoglutathione, an NO-generating agent. Some of the cloned cDNAs were homologous to known mammalian genes and human EST. NO-dependent transcriptional activation was demonstrated for the stromelysin 1 and cyclooxygenase 2 genes and, for the first time, for mcl1 coding for an apoptosis suppressor.

Activation of blood platelets in chronic hepatitis and liver cirrhosis P-selectin expression on blood platelets and secretory activity of beta-thromboglobulin and platelet factor-4.

BACKGROUND/AIMS: Blood platelets are cells that quite often undergo damage in chronic liver diseases. Endotoxemia and hyperkinetic circulation influence platelets in an active manner. The role of platelets in the development of hepatitis and liver fibrosis is speculative. The aim of the study was to determine the influence of chronic liver diseases on platelets morphologic parameters, their secretory activity and P-selectin expression. METHODOLOGY: The examination was completed in the group of 29 patients with chronic hepatitis and 27 with liver cirrhosis of postinflammatory etiology (HBV, HCV). Liver biopsies were carried out in all patients. Thirty-two healthy individuals were the control group. Platelets morphological parameters (number, volume, platelet crit, micro- and macrothrombocyte fraction) were estimated. beta-thromboglobulin concentration and platelet factor 4 in blood serum as well as P-selectin expression on resting platelets and after thrombin activation were also examined. RESULTS: Number, volume, and platelet crit decreased with the advancement of a liver disease. Megathrombocyte fraction increased inversely with the severity of liver damage. The concentration of beta-thromboglobulin and platelet factor 4 alpha-granule contents in blood serum was higher 2- and 7-times, respectively than in healthy controls. P-selectin expression on resting platelets was considerably higher. After stimulation with thrombin, P-selectin expression was equal (chronic hepatitis) or higher (liver cirrhosis) than in the control. CONCLUSIONS: There are changes of platelet morphological parameters, with accompanying megathrombocyte fraction increase that occur in chronic liver diseases. Thrombocytes in chronic liver diseases and liver cirrhosis are more activated. Platelet sensitivity to stimuli in these ailments is higher (liver cirrhosis) than in the healthy controls.

[Autoimmune thrombocytopenia in recurrent polietiological malaria (Plasmodium falciparum, Plasmodium vivax)]. / Autoimmunologiczna trombocytopenia w nawracajacej polietiologicznej malarii (Plasmodium falciparum, Plasmodium vivax).

Thrombocytopenia frequently appear in severe malaria. The reasons of low blood platelets count are different and its results of hypersplenism, subclinical course of intravascular coagulation (DIC). Thrombocytopenia from "consumption" is consequence of sequestration of blood platelets in blood vessels of lungs and cerebral. We examination 29 years old men, who was as forest worker in islands on Indonesia. He was treated with recurrent, poliethiological malaria (Plasmodium falciparum, Plasmodium vivar) and severe thrombocytopenia (17.0 G/L) without hepatosplenomegalia. Antiplatelet antibody was examined in blood serum by ELISA methods (GTI - PAKPLUS. In blood serum was detected IgG antibody agai nstglicoprotein receptors on surface of blood platelets GPIIb/IIIa, GPIV, GPIb/IX, GPV, GPIa/IIa. Chronic infections of Plasmodium may conduct to autoimmune destruction of blood platelets.

Bone marrow failure and hematological abnormalities in alcoholic liver cirrhosis.

Long term alcohol abuse may result in bone marrow damage and hematologic abnormalities. In the study we evaluated bone marrow and peripheral blood changes in patients with alcoholic cirrhosis. Although majority of the patients (91%) presented with hematologic abnormalities such as leukopenia, thrombocytopenia, low hemoglobin level, only mild alterations in bone marrow were observed. The hematopoietic tissue was of high cellularity with features of activation and moderate myelofibrosis.

Autoantibodies in chronic liver diseases.

177 patients with chronic liver disease, among 115 with chronic hepatitis and 61 with liver cirrhosis were subjected to the autoantibodies examinations (ANA, AMA, ASMA, APCA, LKM, ATA) by means of immunofluorescent method (IFA). 25% of cases showed autoantibodies of autoimmunological disease index titre (1:80). Autoantibodies occurred more frequently in woman (75%), mainly in the age of 40-60. Patients with hepatic cirrhosis revealed autoantibodies as frequently as other patients. Among patients infected with hepatotropic viruses (HBV, HCV) with chronic liver diseases, autoantibodies were present in 23-28% of cases and in patients with chronic liver diseases of non-infectious etiology, autoantibodies were observed in 25% of cases.

Peripheral blood T, B lymphocytes and NK cells in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is an autoimmune disease with progressive destruction of the bile ducts and cholestasis. The most of epithelial cells in the bile ducts has molecule MHC I and II class expression which induced intensive immunological reaction and produced antimitochondrial autoantibodies (AMA). It leads to the destruction of own cells in PBC. The main part in the development of the disease have T cells, B cells, and NK cells. We analyzed subpopulation of lymphocytes in peripheral blood in 16 patients with PBC by flow cytometry. We noted statistically significant increase of NK CD16+ + CD56+ cell value and activated T CD3+ + HLA DR+ cell value in peripheral blood in PBC. Slightly increase in the value of CD4+ cells and slightly decreased CD8+ cell value were observed. However, the CD4/CD8 ratio was elevated statistically and it was 2.3 (healthy subjects--1.7). Lymphocyte T and B subpopulations remained normal. The results showed that the main role in PBC is played by NK cells and activated T cells.

[Autoimmune thrombocytopenia in chronic liver disease]. / Autoimmunologiczna trombocytopenia w przewleklych chorobach watroby.

Thrombocytopenia (TP) often accompanies chronic liver diseases. The causes are numerous and include impaired production of blood platelets, spleen sequestration, and the immune factors, e.g. antiplatelet autoantibodies. ELISA (GTI-PAKPLUS) examinations were conducted in order to estimate the rate of autoimmune thrombocytopenia occurrence in patients with thrombocytopenia in the course of chronic hepatitis (10 patients) and liver cirrhosis (20 patients). Blood platelet activity was also evaluated as well as the expression of platelet glycoproteins (GPIIb, GPIIIa, and GPIX) in platelets of the patients and the controls. It was observed that autoimmune TP occurred in 30% of patients with liver cirrhosis and in 10% of patients with chronic hepatitis, in which anti-GPIIb/IIIa, GPIa/IIa, and HLA class I antibodies were detected. In all patients there occurred significant/marked platelet activation with CD61P expression. Thrombocytopenia in patients showed a similar activity after thrombin stimulation to that in healthy individuals. Expression on GPIIb platelet receptors was markedly increased and GPIX decreased in patients in comparison to the controls. There was no correlation between the occurrence of certain types of anti-platelet autoantibodies and the expression of GP on thrombocytes in these patients.

[Liver biopsy: the mandatory test in liver diagnosis in adults]. / Biopsja watroby--niezbedny element w diagnostyce chorób watroby u doroslych.

The aim of the study was clinical and morphological analysis patients with liver biopsy. In this work technique of percutaneous liver biopsy, indications, contraindications and complications were presented. Among 547 liver biopsy 56% patients was HCV infected and a 14% patient was HBV infected. Microscopic examination was performed the similar percentage the stage of inflammation and fibrosis. Among patients without viral infection (HBV and HCV) the most finding was steatosis and liver cirrhosis. Agreement of clinical diagnosis with results of microscopic investigations with reference to of inflammable changes carried out 90%, the less agreement with steatosis, cholestasis and hemosiderosis. In 30% patients after biopsy were pains in place executed of intervention and right arm for 6 hours. 0.5% of patients was sub capsular bleeding after intervention. We no observed dangerous complications after liver percutaneous biopsy. Liver biopsy is very important investigation in liver diagnosis, comparatively safety if contraindications are complains.

Platelet autoantibodies in liver cirrhosis and thrombocytopenia.

One of frequently occurring hematological disorders accompanying advanced liver diseases is thrombocytopenia (TP). Immunological disorders in patients with liver cirrhosis, loss of tolerance to own antigens, and the change of platelet antigenicity enable antiplatelet antibody formation under the influence of continuous activation. The aim of the study was to determine the rate of autoimmunological thrombocytopenia occurrence in patients with liver cirrhosis and TP. Antiplatelet autoantibody occurrence were determined in blood serum with the use of ELISA method in 15 patients with liver cirrhosis and TP (mean plt number 67.9 +/- 24.9 x 10(3)/microliter). Three patients (20%) presented anti-GPIIb/IIIa antibodies and 2 patients--anti-GPIa/IIa. These patients had liver failure (stage C according to Child-Pugh classification) and splenomegaly. Plt morphological parameters were also evaluated. The significant decrease of plt crit as well as the decrease of mean platelet volume (MPV) was observed in liver cirrhosis with thrombocytopenia. The increase of megathrombocyte population (MPV > 20fl) up to 5.5% of all plt was also observed. Megathrombocytes in healthy individuals were 2.25% of platelet population. Examinations confirmed that autoimmunological factors play an important role in the development of thrombocytopenia in liver cirrhosis.

Efficacy of interferon therapy on patients with HCV infection in dependence from the time of treatment.

Among 45 patients with chronic hepatitis C the efficiency of interferon alpha 2b treatment was evaluated. The efficiency of interferon therapy was determined after 6 months of treatment in the group of 28 patients (group I) treated for 6 months and 17 patients (group II) treated for 12 months. The side effects were investigated with respect to such a factor as time of treatment. 11 (39%) patients from group I had eliminated HCV RNA and 14 (50%) patients had normalized AlAT levels in the serum. Five (29%) patients from group II eliminated HCV RNA and 8 (47%) patients had normalized AlAT levels in the serum. The flu-like syndrome, thrombocytopenia, vision disorder, depression and somnolence were most often the side effects observed in treated patients. Proportionally to time of treatment vision disorder, depression and somnolence increased.