Seronegative hepatitis C virus infection in Polish blood donors-Virological characteristics of index donations and follow-up observations.

Nucleic acid testing (NAT) was implemented in Poland in 1999 for screening of plasma for fractionation and for all blood donors in 2002. To analyze seronegative NAT-positive samples representing hepatitis C virus (HCV) window-period (WP) in the years 2000 to 2016 and to determine infection outcome. We analyzed results of 17 502 739 donations screened in minipools (6-48) or individually. Index samples underwent viral load (VL) quantification, genotyping and Ag, and anti-HCV re-testing using chemiluminescence (CMIA), electrochemiluminescence (ECLIA), and fourth-generation enzyme-linked immunosorbent assay (IV EIA) assays. HCV-seronegative infections were identified in 126 donations (7.2/mln donations; 95% confidential intervals, 6.0-8.6). Frequency of NAT yields was decreasing over time. Of the initial 126 seronegative index cases 106 were retested: 32.1% were reactive in IV EIA, 11.3% in ECLIA, and 1.9% in CMIA. The lowest VL correlated with absent anti-HCV and HCV Ag, while VL was highest when the antigen was detectable and then it decreased when anti-HCV appeared at a level detectable by sensitive third generation tests while retesting. The proportion of genotype 1 was 38.9% in samples positive only for HCV RNA and 71.4% in samples that were anti-HCV reactive in re-testing. In parallel, genotype 3 frequency was 50% in the former group and 21% in the latter. NAT is an effective measure to limit HCV transmission by transfusion and IV EIA seems to have higher clinical sensitivity than ECLIA. Samples representing likely successive phases of early HCV infection were characterized by different genotype distribution probably due to very early elimination of genotype 3.

Factors associated with hepatitis C prevalence differ by the stage of liver fibrosis: A cross-sectional study in the general population in Poland, 2012-2016.

BACKGROUND & AIMS: There is a considerable burden of hepatitis C in Europe related to the lack of prompt diagnosis. We aimed to estimate the prevalence and related risk factors of HCV infections by the stages of liver fibrosis, using non-invasive methods, to understand testing needs in Poland. METHODS: A cross-sectional study was conducted in 2012-2016 adopting a stratified random sampling of primary health care units followed by systematic sampling of patients within each unit. Study participants filled a questionnaire and donated blood for laboratory HCV testing. Additionally, the results of liver function tests and platelet count were collected to calculate APRI and FIB-4 scores. Cases were classified according to the level of fibrosis: 'significant fibrosis' (APRI≥0.7 or FIB4≥1.45) and 'no significant fibrosis' (APRI<0.7 and FIB4<1.45). RESULTS: Of 21 875 study participants, 102 were HCV-RNA positive. Prevalence of HCV infections and significant fibrosis was estimated at 0.47% (95% CI 0.38% - 0.57%) and 0.12% (0.08% - 0.17%), respectively. Cases with significant fibrosis accounted for 51.6% (33.4%-69.9%) in men and 34.4% (17.3%-51.4%) in women. There was no correlation between the HCV prevalence and age. Blood transfusion prior to 1992 strongly predicted significant fibrosis as did the history of injecting drug use (IDU) and ever having an HCV-infected sexual partner in men and caesarean sections in women. Factors associated with HCV infection without significant fibrosis were tattooing in men and younger age in women. We acknowledge limited possibility to study the associations between IDU and ever having HCV-infected sexual partner, given small sample sizes for these exposures. CONCLUSIONS: As no clear birth cohort affected by HCV could be identified, risk factor-based screening in the general population should be considered, taking into account the association between the increased risk of liver fibrosis and the history of transfusion prior to 1992 and caesarean sections.

What affects response rates in primary healthcare-based programmes? An analysis of individual and unit-related factors associated with increased odds of non-response based on HCV screening in the general population in Poland.

OBJECTIVES: Response rate in public health programmes may be a limiting factor. It is important to first consider their delivery and acceptability for the target. This study aimed at determining individual and unit-related factors associated with increased odds of non-response based on hepatitis C virus screening in primary healthcare. DESIGN: Primary healthcare units (PHCUs) were extracted from the Register of Health Care Centres. Each of the PHCUs was to enrol adult patients selected on a random basis. Data on the recruitment of PHCUs and patients were analysed. Multilevel modelling was applied to investigate individual and unit-related factors associated with non-response. Multilevel logistic model was developed with fixed effects and only a random intercept for the unit. Preliminary analysis included a random effect for unit and each of the individual or PHCU covariates separately. For each of the PHCU covariates, we applied a two-level model with individual covariates, unit random effect and a single fixed effect of this unit covariate. SETTING: This study was conducted in primary care units in selected provinces in Poland. PARTICIPANTS: A total of 242 PHCUs and 24 480 adults were invited. Of them, 44 PHCUs and 20 939 patients agreed to participate. Both PHCUs and patients were randomly selected. RESULTS: Data on 44 PHCUs and 24 480 patients were analysed. PHCU-level factors and recruitment strategies were important predictors of non-response. Unit random effect was significant in all models. Larger and private units reported higher non-response rates, while for those with a history of running public health programmes the odds of non-response was lower. Proactive recruitment, more working hours devoted to the project and patient resulted in higher acceptance of the project. Higher number of personnel had no such effect. CONCLUSIONS: Prior to the implementation of public health programme, several factors that could hinder its execution should be addressed.

Hepatitis C virus epidemiology and prevention in Polish and Swiss population - similar and contrasting experiences.

OBJECTIVE: The aim of the study was to review available data on HCV in Poland and Switzerland, in order to compare the two European countries with respect to epidemiological situation and efficiency of the response systems. MATERIALS AND METHOD: A search of registries, published and grey literature was performed to assemble data on prevalence, rate of detection of new cases, identified risk factors for transmission, mortality due to HCV, prevalence of HCC and the consequent liver transplantations, as well as data on treatment in Poland and Switzerland. RESULTS: Overall, the prevalence of anti-HCV antibodies was similar, not exceeding 1%. However, the major transmission routes of HCV infections were different: medical procedures in Poland and drug injections in Switzerland. By combining the available information it was also possible to demonstrate important differences in efficiency of the response systems. There was approximately 1 new diagnosis per 100 estimated undiagnosed cases in the population in Poland per year, compared to 6 in Switzerland, and the treatment rate per 100 estimated active infections was 2 and 4, respectively. CONCLUSIONS: Scaling up of the diagnosis and treatment is necessary in both countries; however, the means to achieve this might differ, taking into account the higher concentration of the infections in risk groups in Switzerland than in Poland.

Epidemiology of HCV infection in Central and Eastern Europe.

AIM OF STUDY: is the estimation of prevalence of HCV infection in fourteen Central and Eastern European countries (CEEC). MATERIAL AND METHODS: This review describes the comparative data of persons possessing anti-HCV antibodies and persons with HCV viremia (% of population and number) in fourteen Central and Eastern European countries (CEEC). The study was performed according to data on the ≥15 years of age populations obtained from the Statistical Offices of the countries. RESULTS: The prevalence of anti-HCV in populations varied between 0.27 and 3.5%. The lowest values were reported from Kosovo, Hungary, Germany and the Czech Republic; 0.3-0.6%. The highest values of anti-HCV antibodies were noted in Latvia, Lithuania and Romania; 2.4, 2.85 and 3.5%, respectively. From eight countries the percentages of persons with HCV viremia were available (0.2-3.5%). CONCLUSIONS: The paper gives an estimate of the number of people infected with HCV in the general population of 8 countries from the CSEEC region. This number is approximately ~1.16 million.

Current views on the persistence of immunity following hepatitis B vaccination.

This paper presents current views on the persistence of immunity following vaccination against hepatitis B. Very high effectiveness of hepatitis B vaccination has been reported in a number of studies worldwide. Standard vaccination with approved schedule induces protective antibody titers in healthy newborns, children, adolescents and adults in more than 96% and 90% of cases, respectively. A number of studies have also confirmed the occurrence of anamnestic response to a booster injection of HB vaccine even after 20 years following primary immunization. From the numerous studies transpires that cellular response following hepatitis B vaccination persists longer compared to humoral response. Irrespective of gradual decline and loss of anti-HBs antibodies, adequately performed primary immunization in healthy persons ensures long-term protection against acute and chronic stages of hepatitis B. In fact, T and B lymphocytes, whose responsiveness prevails the presence of anti-HBs antibodies in serum, are true markers of immunity. A special attention should be given to persons with secondary immunodeficiencies or immunosuppressed patients whose immunization against hepatitis B raises difficulties.

[HCV inection in pregnancy]. / Zakazenia wirusem HCV u kobiet w ciazy.

The prevalence of anti-HCV antibodies in pregnant women ranges from 0.1% to 3.6% worldwide. In Poland, one work was published on the prevalence of HCV antibodies in pregnant women. Based on studies conducted by Aniszewska et al. in 544 women, the percentage of anti-HCV antibodies was estimated at 2.02%. Since 2011, the NIPH-NIH performs "Preliminary programme of routine HCV testing among pregnant women" within the Swiss-Polish Cooperation Programme, co-financed by the Ministry of Health, with the aim to, i.a. estimate the prevalence of HCV infection in the population of pregnant women. The transmission of the virus from mother to fetus is now considered to be the most common route leading to infections in children and infants. According to available data, the risk of vertical transmission from infected mother is relatively low and ranges from 1.8% to 5%. Transmission of HCV can occur both in the prenatal period as well as during the labor. Irrespective of the numerous studies on the transmission of the virus from mother to child, its mechanism has not been completely understood. Exclusively the factors favoring this route of infection are known. The main risk factor for vertical transmission is the presence of viral RNA in maternal peripheral blood. Other risk factors include: the presence of viral RNA in PBMC, HIV coinfection, significant increase in ALT in a year preceding pregnan- cy and during labor in women infected with HCV, extended time between the rupture of membranes and delivery as well as female gender of the baby. The impact of amniocentesis and cesarean delivery as risk factors for vertical transmission of HCV are still discussed. Breastfeeding by mothers infected with HCV is safe and does not lead to transmission of infection to the baby. As ribavirin and interferon, which are used in therapeutic regimens, cannot be administered during pregnancy, it is important to perform testing for HCV prior to a planned pregnancy. This gives the opportunity to cure the infection and eliminate the vertical route of HCV transmission.

[Methods of testing potential inhibitors of hepatitis C in Huh-7.5 cell line]. / Metody badania potencjalnych inhibitów wirusa zapalenia watroby typu C w linii komórkowej Huh-7.5.

INTRODUCTION: According to WHO reports, there are 130-170 million persons chronically infected with hepatitis C virus on a global scale. There is no effective vaccine against HCV, and the current standard of chronic hepatitis C therapy has limited efficiency and undesirable side effects. Current studies are focused on searching for a new therapeutic agents, which are specifically targeted against the virus. The aim of the study was to develop a methodology for testing the activity and cytotoxicity of potential helicase inhibitors (derivatives of anthracycline antibiotics) in Huh-7.5 cell line infected with HCV. METHODS: The Huh-7.5 cell line was infected with the JFH1 (Japanese Fulminant Hepatitis) RNA by lipofection. The cytotoxicity of anthracycline antibiotics was measured by Cell Proliferation Kit II(XTT), after 1, 2, 3, 4 and 24 hours after incubation with tetrazolium salt XTT. The activity ofanthracycline antibiotics was examined by Real-Time PCR method. RESULTS: The study allowed to optimize the conditions of cytotoxicity and activity studies of anthracycline antibiotics. CONCLUSIONS: Huh-7.5 cell line infected with HCV is a robust cell culture model for screening new antivirals against HCV.

[Professor Adam Nowoslawski (1925-2012)--founder of the Polish School of Immunopathology]. / Profesor Adam Nowoslawski (1925-2012)--twórca Polskiej Szkoly Immunopatologii.

Professor dr med. Adam Nowoslawski, has died at age of 87, on February 3, 2012, the founder of the Polish school of immunopathology, member of Polish Academy of Sciences and of Polish Academy of Art and Sciences. Professor was born on April 30, 1925 in Rzeszów (SE Poland). During the Second World War he took part in the anti-nazi resistance movement; he was the soldier of the 'Baszta' regiment of the Home Army. Subsequently, he was imprisoned in the Pawiak and concentration camps: Majdanek and Buchenwald. The medical studies he has completed at Warsaw Medical Academy between 1946-1951. The degree of doctor of medicine Prof. Adam Nowoslawski has obtained in 1963, habilitation degree in the field of immunopathology--in 1966; the title of Professor he has obtained in 1980. His scientific achievements consist of 170 publications, including 101 original papers. His publications were quoted in several American books for students and physicians. Topics of his early papers concerned the immunopatogenesis ofPneumocystis carinii--induced pneumonia in premature babies, immunopatogenesis of rheumatoid arthritis, and the origin of rheumatoid factor. The enormous role in the field of hepatology played research on the virus of hepatitis B. These studies dealt with the discovery of HB core antigen which had the cellular localization different from HB surface antigen and with the parameters of the immune response to infection. Papers published on this topic were the mostly quoted in the literature and earned him national awards. The activity of Prof. Adam Nowoslawski in the field of HIV/AIDS prevention was honored by the special prize of the Minister of Health. Professor was the honorary member of the two Societies: Polish Society of Pathologists and Polish Society of Hepatology. He was also the member of International Association for the Study of the Liver and International Academy of Pathology. Prof. Adam Nowoslawski received the national medals: Polonia Restituta Crosses, Gold Medal for the Merits of the Country Defense, and the 'Auschwitz' Cross. He was also the recipient of the medals: Copernicus (1997) and Gloria Medicinae (2001).

RNA-HCV viral load in serum, peripheral blood mononuclear cells and liver in children with chronic hepatitis C.

The liver is the major site of hepatitis C virus (HCV) infection and replication. However, HCV may infect and replicate in extrahepatic sites as well. Several investigators have demonstrated that peripheral blood mononuclear cells (PBMCs) are the major extrahepatic milieu of infection and viral replication. The aim of the study was to investigate the correlation between RNA-HCV level in serum. PBMCs and liver in children with chronic viral hepatitis C (CHC). The impact of RNA-HCV level on the sustained virological response (SVR) after therapy was also determined. Study was carried out in the group of 10 children with CHC, age 8 to 17 years. Antiviral therapy was implemented in all patients with pegylated interferon alpha (Peg-lFNalpha) 2a or 2b and ribavirin during 48 weeks. The following tests were performed prior the therapy: basic laboratory parameters, histology of liver biopsy, RNA-HCV viral load in serum, PBMCs and in liver. The behavior of HCV-RNA viral load in serum, PBMCs and liver in children with CHC did not present strict mutual relations. However, the positive correlation between serum and PBMCs viral load (r = 0.47) and negative correlation between PBMCs and liver viral load (r = -0.47) was demonstrated. Although no statistically significant results were found, some trends of relationship in viral load between various body compartments were present. Given the aforementioned results, it is clear that more data are needed, mostly more numerous groups of patients, especially those whose influence of RNA-HCV viral load had a major impact on the antiviral treatment.

[HCV replication in Huh-7.5 cell line]. / Replikacja wirusa HCV w linii komórkowej Huh-7.5.

INTRODUCTION: Infection with hepatitis C virus is a serious worldwide health problem. Since its discovery in 1989, the development of a cell culture system for HCV has been a major goal for scientists worldwide. In 2005 the first tissue culture that led to the production of HCV particles (2a genotype) has been created. The aim of the study was to determine viral RNA level in an infectious HCV cell culture system. METHODS: Huh-7.5 cell line was infected with the JFH1 (Japanese Fulminant Hepatitis) RNA by lipofection. The level of HCV RNA was measured in supernatant of the cell culture by Real-Time PCR method. RESULTS: HCV RNA was detected in the supernatant of Huh-7.5 cell line infected with the use ofJFH 1 RNA and lipofectamin. The maximal level of HCV RNA (3.69 x 10(9) copies/ml) was detected 96h after transfection. After about 30 days oftransfection, HCV RNA was on the stable level (10(7)-10(8)). CONCLUSIONS: Huh-7.5 cell line infected with HCV form a robust cell culture model of HCV infection. HCV replicates on high levels in Huh-7.5, which is the crucial event for the investigation of new antivirals in in vitro model.

[Prevalence of anti-HCV antibodies among adults in Poland--results of cross-sectional study in general population]. / Rozpowszechnienie przeciwcial anty-HCV wsród osób doroslych w Polsce--wyniki badania przekrojowego w populacji ogólnej.

UNLABELLED: According to WHO data, there are 130-170 million hepatitis C virus (HCV) infected persons world-wide. Data on the prevalence of HCV infection in Poland is still insufficient. OBJECTIVE: The aim of study was to determine the prevalence of HCV infection in the general population in Poland and to characterize the positive predictive value of the ELISA screening test. MATERIAL AND METHODS: A total of 4822 persons aged 18+ and hospitalized on surgical, trauma-orthopedic and laryngological wards in Lubelskie, Mazowieckie, Swietokrzyskie, Warminsko-Mazurskie and Wielkopolskie voivodeships were enrolled into the study. The scheme of cluster sampling was applied. Hospitals wards were selected randomly from Health Care Units Registers. Detection of anti-HCV antibodies was performed using the 4th generation qualitative ELISA test (Dia Sorin, Murex). All positives samples were subject to further testing by Western Blot and retested by ELISA. According to ELISA test producers instructions, samples that were repeatedly reactive were considered as positive (reactive). Using the confirmation test (Western Blot), antibodies directed against specific antigens of HCV (C1, C2, E2, NS3, NS4, NS5) were determined. To determine the prevalence of HCV infections, repeatedly reactive ELISA samples, confirmed by Western Blot (WB) were used. In order to estimate the prevalence of anti-HCV antibodies in general population, indirect standardization according to age groups (<30, 30-49, 50-69, >or =70), gender and place of residence (urban/rural) was employed. RESULTS: Initially positive ELISA test results were obtained in 92/4822 patients (1.91%) and repeatedly positive results--in 46/4822 patients (0.95%). The presence of anti-HCV was confirmed by WB in 54/4822 (1.12%), which constituted 58.7% (54/92) of single-reactive samples and 95.7% (44/46) of double-reactive samples. The positive results of Western Blot were obtained for 10 samples, which were not repeatedly reactive in ELISA test. The standardized prevalence of anti-HCV antibodies amounted to 0.86% (95% CI: 0.59-1.14%). Positive predictive value for a single reactive ELISA test accounted for 47.8% (95% CI: 37.4-58.2%). CONCLUSIONS: Given the low predictive value of the single-positive ELISA, performance of repeated ELISA tests, even for epidemiological purpose, would be recommended.

Infections caused by RSV among children and adults during two epidemic seasons.

Respiratory Syncytial Virus (RSV) is one of the most common causes of lower respiratory tract infections in young children, immunocompromised patients (children and adults), patients with chronic respiratory diseases and elderly people. Reinfections occur throughout the life, but the severity of disease decreased with subsequent infection. The aim of this study was to analyze the frequency of RSV infections in two selected subpopulations: young children (below 5 y.) and adults with chronic respiratory diseases (25-87 y.). Nasopharyngeal swabs (334) collected from October 2008 to March 2010 were examined. The presence of RSV genome was determined by RT-PCR and the presence of RSV antigen by quick immunochromatographic test. Positive results of RT-PCR were found in 45.2% of all swabs: 48.6% samples in 2008; 41.5% in 2009; 50.8% in 2010. The highest frequency of RSV-positive samples was in fall-winter months, but differences in RSV epidemic seasons were found. In the first season (2008-2009) an increased number of RSV infections was observed from November 2008, but in the second season--from January 2010. Generally, the frequency of RSV-positive RT-PCR among children was 53%, among adults 25%. The highest difference was observed in the first three-month period of 2010. RT-PCR positive samples were found in 68.5% of children and 5.9% of adults. However, the RSV antigen was found in 44.4% of samples collected from adults in this period. Our results indicate that the contribution of RSV infections during epidemic season of respiratory tract infections in Poland was really high among children and adults.

Is interleukin-8 an additional to histopathological changes diagnostic marker in HCV-infected patients with cryoglobulinemia?

PURPOSE: The aim of this study was to analyze histopathological changes in the liver and serum inflammatory cytokine level in hepatitis C virus (HCV)-infected patients with and without cryoglobulinemia. METHODS: The study group consisted of 34 patients with chronic hepatitis C, confirmed by serological and virological markers. Ten out of 34 patients had cryoglobulinemia. The control group consisted of 21 healthy persons. Liver biopsy specimens of HCV-infected patients were evaluated by light microscopy using the grade and the stage according to Batts and Ludwig classification. The quantitative measurements of IL-1ß, IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor in sera were performed by flow cytometry. RESULTS: The mean age of HCV-infected patients with cryoglobulinemia was higher than age of HCV-infected patients without cryoglobulinemia. Microscopic examination of liver biopsy specimens revealed necroinflammatory activity slightly more prominent in patients with cryoglobulinemia. The most prominent inflammatory changes connected with abundant lymphoid aggregates in most of the examined portal tracts and piecemeal necroses were diagnosed in patients with several extrahepatic manifestations, such as cutaneous manifestations, nephrotic syndrome, polyneuropathy, and arthropathy. Liver fibrosis was similar in patients with and without cryoglobulinemia. CONCLUSIONS: The serum levels of all proinflammatory cytokines, especially IL-8, were significantly higher in the patients with cryoglobulinemia in comparison with the patients without cryoglobulinemia and healthy persons. All microscopic features did not correlate with the level of any investigated proinflammatory cytokines.

[Evaluation of quality of HIV diagnostic procedures in Poland]. / Ocena jakosci procedur diagnostycznych zwiazanych z zakazeniem HIV w Polsce.

UNLABELLED: The aim of this work was quality assessment of HIV diagnostic procedures in Poland, including human and technical resources as well as laboratory practice. Sixty questionnaires were distributed among diagnostic centers to obtain qualitative data. Basing on the survey data serological control using coded panels of HIV-1/2 samples was performed. Thirty-one filled questionnaires were received (50.8%). Surveyed laboratories perform from 350 to 5500 serological screening tests per year. In most of laboratories fourth generation assays are available, while Blood Donation Centers screen the blood both with serological assays and by HIV-RNA detection. Sanitary and Epidemiological Stations and academic laboratories hold the ISO/IEC 17025 or IS0 9001:2001 accreditation, five of the surveyed centers participate in Labquality assurance and two in Quality Control in Molecular Diagnostics programs. Data of control serological testing were received from 21 centers. In the quality control assessment 194 analyses were performed with 91 true negative, 2 false negative, 96 true positive and 5 false positive results. False negative rate of % and false positive rate of 5.2% was noted for this study. CONCLUSIONS: Currently, virtually no guidelines related to the HIV-diagnostics quality assurance and control in Poland are in delineated. Development of the national unified quality control system, basing on the central institution is highly desirable. National certification within the frames of the quality control and assurance program should be mandatory for all the diagnostic labs, and aim at improvement of reliability of the result distributed among clinicians and patients.

[Inhibitors of hepatitis C virus--current standards and status of investigations]. / Inhibitory wirusa zapalenia watroby typu C--aktualne standardy oraz stan badan.

The current standard of chronic hepatitis C therapy is the combined use of pegylated IFN-alpha 2a (PegIFN-alpha) and rybavirin (RBV). The new form of interferon, IFN-alpha 2b, was also introduced with no better results. Overall, the effectiveness of therapy with the use of the above scheme is not satisfactory. Thus the search for new therapeutic agents for hepatitis C is ongoing. These studies have the goal to find new preparations inhibiting the replication cycle of HCV. The new analogue of RBV, eg. tarybavirin was introduced, with lesser side effects, but the same effectiveness. The activity of new agents relies upon the inhibition of the most important enzymes of the HCV replication cycle: RNA polymerase, protease and helicase. Polymerase NS5 inhibitors are divided into nucleoside (R-7128) and nonnucleoside (ANA-598, GS 9190, VCH-759, VX-222). The intensive studies on the R-7128 analogue are ongoing. The effects of action of particular compounds in the I and II studies were summarized. The promised prodrug is nonnucleoside polymerase inhibitor, ANA-598 which when administrated to patients, gave 75% SVR. The combined administration of the newly described agents is the basis of specifically targeted antiviral therapies for HCV (STAT-C). These therapies allow to achieve better effectiveness of treatment, its shortening, the diminishment and limitation of side effects.

[Inhibitors of hepatitis C virus--therapeutic possibilities]. / Inhibitory wirusa zapalenia watroby typu C--mozliwosci terapeutyczne.

The search for new drugs against HCV contains new ways to obtain pro-drugs which inhibit translation and block viral proteins, and inhibit host proteins important in HCV-induced pathogenesis. This group of agents are serine protease NS3 inhibitors (telaprevir, boceprevir, R-7227, TMC-435, SCH 900518, GS-9256). The most advanced studies are developed with telaprevir and boceprevir; at present their effect in combined therapy with PegIFN-alpha and RBV in the III clinical phase is tested. The sustained viral response (SVR) was achieved at the level of 60-75%. This group of agents contains also inhibitors of NS5A domain, e.g. PPI-461 which shows antiviral and cytotoxic activity. The following prodrugs are NS3 helicase inhibitors, e.g. p14 peptide, whose IC50 equals 725 nM. Studies are continued on viral entry inhibitors (ITX-5061), therapeutic vaccines (IC-41, civaci, TG-4040, CT-1011, GI-5005) and immunomodulating preparations (ANA-773, IMO-3649, NOV-205). The agents acting on host proteins are a.o. cyclophilin inhibitors. The most advanced studies concern DEBIO 025 preparation which after phase I and II, underwent phase III of clinical studies in February 2010. Since 5 years there is a possibility to investigate the effects of these comounds in vitro with the use of Huh-7 line infected with HCV. These investigations allow to estimate the antiviral effectiveness and cytotoxicity of agents, and resistance of viral strains.

[Prof. Wlodzimierz Kurylowicz (MD) (1910-1991)--100th anniversary of birthday]. / Prof. Dr hab. med. Wlodzimierz Kurylowicz (1910-1991)--na stulecie urodzin.

The death of Professor Wlodzimierz Kurylowicz on February 21, 1991 at the age of 80 was a great loss that is especially felt by all those who have been involved in the research of antibiotics. He is remembered as one of pioneers of the antibiotic era. Prof. W. Kurylowicz was born September 26, 1910 in Lvov. He received his MD from the Jan Kazimierz University in Lvov. Following posts as an Associate Professor of Microbiology at Lvov and as a research bacteriologist at the National Institute of Hygiene in Warsaw he became a Professor of Microbiology at that Institute. He was Director of the Institute from 1964 to 1980. More than 270 of this works regarded such topics as: antibiotic biogenesis and biosynthesis, numerical taxonomy of Streptomyces spp., evaluation of BCG and microbial fine structure. Prof. W. Kurylowicz was a recipient of the National Prize Award for scientific guidance in construction of the first antibiotic industry in Poland, and the National Prize Award for the co-authorship of the monograph "Antibiotics - Origin, Nature and Properties". He was also recipient of Doctorates honoris causa of: Nicolas Copernicus Medical University in Poland; University of Oslo; University of Lille; Medical University of Debrecen, Hungary; University of Liège, Belgium; Federal University of Pernambuco, Recife, Brazil; University of Quèbec, Canada; University of Münster, Germany.

Anti-preS responses influence the anti-HBs response in newborns after vaccination with the third generation Sci-B-Vac vaccine.

We analysed the specificity and significance of the antibody response towards the linear preS1 sequence that has been shown to represent the "hepatocyte binding site" comprising amino acids preS1 (21-47) or the specific preS2 (131-140) antibody response to the "polymerised albumin receptor" in relation to the antibody response to hepatitis B surface antigen during immunisation of healthy children with the preS-containing Sci-B-Vac vaccine. Twenty-eight healthy newborns received three doses of the Sci-B-Vac vaccine according to a 0-, 1-, and 6-month scheme. Seventeen (61%) of the 28 newborns had detectable levels of anti-preS1 (21-47) antibodies and 14 (50%) were anti-preS2 (131-140) reactive at 6 and/or 9 months after initiation of the vaccination. The mean levels of anti-HBs were significantly higher in the anti-preS2 (131-140) non-reactive (24580+/-7815IU/l, mean+SEM) compared with the reactive sera (7287+/-2317IU/l, p<0.025). The highest anti-HBs levels were found in newborns who exhibited reactivity towards the aa 21-47 of the preS1 but lacked anti-preS2 (131-140) reactivity.