Treatment of HCV infection in Poland at the beginning of the interferon-free era-the EpiTer-2 study.

The aim of the EpiTer-2 study was to analyse patient characteristics and their medication for HCV infection in Poland at the beginning of the interferon-free era. Analysis of data of HCV infected patients treated during the initial period of availability of interferon-free regimens in Poland, who started therapy after 1 July 2015 and had available an efficacy evaluation report before 30 June 2017 was undertaken. A total of 2879 patients with chronic hepatitis C were entered, including 46% with liver cirrhosis. The most common was genotype 1b (86.8%). The study population was gender balanced, the majority of patients were overweight or obese and 69% presented comorbidities, with the highest prevalence that for hypertension. More than half of patients were retreated due to failure of previous therapy with pegylated interferon and ribavirin. Almost two-third of patients received current therapy with ombitasvir/paritaprevir/ritonavir±dasabuvir (OPrD) ±ribavirin. Other patients received mostly sofosbuvir-based regimens including combination with ledipasvir and pegylated interferon and ribavirin for genotype 3-infected patients. Efficacy of treatment in the whole study population measured as intent-to-treat analysis was 95%. The most frequent regimen, administered for patients infected with genotype 1b, was 12 weeks of OPrD, resulting in an SVR rate of 98%. At least one adverse event was reported in 38% of patients, and the death rate was 0.8%. In conclusion, data from the EpiTer-2 study confirmed the excellent efficacy and safety profile of the real-world experience with recently introduced therapeutic options for genotype 1 HCV infection, but demonstrated weakness of the current therapeutic programme regarding genotype 3 infections.

[The presence of antibodies to Borrelia burgdorferi associated with immunologic complexes in sera of foresters]. / Obecnosc przeciwcial dla Borrelia burgdorferi zwiazanych w kompleksy immunologiczne w surowicach lesników.

Binding of antibodies specific to Borrelia burgdorferi in circulating immune complexes can lead to false negative results in serological tests. The aim of our study was to determine the presence of IgM antibodies to Borrelia burgdorferi bound in immune complexes in 52 sera of foresters the National Park in Karkonosze. Free and bound in immune complexes IgM antibodies present in 6 (11.5%) examined sera. In 24 (46.2%) seronegative sera after dissociation of immune complexes IgM antibodies to spirochaeta were found. The rest of the examined seronegative sera we failed to find IgM antibodies to Borrelia burgdorferi. The diagnostic assay, such as antibody analysis of immune components is useful in establishing of the diagnosis of borreliosis in seronegative cases and monitoring of disease activity. That method should be introduced for routine diagnosis of Lyme disease.

[Therapeutic efficacy of low-dose alpha interferon therapy in liver cirrhosis associated with HBV]. / Skutecznosc terapeutyczna niskich dawek interferonu alfa w wyrównanej marskosci watroby zwiazanej z zakazeniem HBV.

The aim of this study was the assessment the efficacy and safety of therapy with interferon alpha (Intron A) administered s.c. 3 MU x 3/week for 12 weeks for patients with HBV related liver cirrhosis (Child's class A). Fifteen patients completed therapy and 12 months follow-up. At the end of follow-up sustained response to the therapy, defined by clearance of HBV-DNA, normalization of ALAT activity in serum and improvement in the liver histology was achieved in 46.6% of treated patients. Moreover, among few patients from group of nonresponders (patients without sustained clearance of HBV-DNA) decrease of HBV-DNA level, ALAT activity in serum and improvement in the liver histology were observed. Adverse effects of IFN alpha therapy were typical, but in any case were no necessity terminate the therapy.

[The interferon system in chronic brucellosis]. / Uklad interferonowy w przewleklej brucelozie.

The purpose of the paper was to evaluate activity of interferon system in a group of patients with chronic brucellosis. Trial was performed in 21 persons: 10-with active and 11-with non active disease. "Whole blood test" was used to induce interferon by peripheral blood leucocytes after stimulation with antigens: non specific (NDV, LPS, PHA + PMA) and specific (Brucella). There was no difference between examined and control groups in interferon induction by non specific factors. This indicates correct functions by interferon system in chronic brucellosis. Relatively, after stimulation by specific antigens 4-fold increase of endogenic interferon (alfa and gamma) was observed. These results suggest that chronic brucellosis (active and non active) in still immunologically active and pathological changes depend on delayed hypersensitivity. We conclude, that this method seems to be deciding diagnostic test in latent brucellosis.

[Epidemiological and clinical analysis of chronic brucellosis and new Brucella infections]. / Analiza epidemiologiczno-kliniczna brucelozy przewleklej i zakazen swiezych.

We analyzed clinically and epidemiologically 285 patients suffered from chronic brucellosis treated during 12 years. Especially we observed 51 persons with the infection called "brucellosis recens". Comparing both groups, we did not notice any statistically significant differences in the changes of organs and systems. This suggests greater influence of kind and frequency of exposition on pathologic changes than duration of illness.

Antigen-specific and nonspecific interferon response of peripheral blood leukocytes from patients with chronic brucellosis.

Thirty seven blood samples from 21 patients with chronic brucellosis were studied for interferon response to Brucella specific antigens and to the classical IFN inducers. Whole blood technique for IFN induction and bioassay with A549 cells challenged with EMC virus for IFN detection were used. Two different antigen preparations (BRU-1 and BRU-2) used for the serologic diagnosis of brucellosis, stimulated significantly (P less than 0.001) the synthesis of IFN-alpha and IFN-gamma in the whole blood cultures from the patients with chronic brucellosis but not from the control subjects. The detoxified antigen (brucellin) was inactive as the IFN inducer. BRU-1 and BRU-2 antigens induced also low levels of IFN-alpha + IFN-gamma in the short term cultures of the separated peripheral blood leukocytes (5-10 X 10(6) cells/ml) from healthy blood donors. This resembled stimulation of the leukocytes with LPS. Brucellin was inactive in the leukocyte culture. Despite the chronic infection lasting many years the brucellosis patients had apparently intact IFN system because the response of their leukocytes to NDV, PHA + PMA or LPS was not significantly different from that of the healthy blood donors. The importance of the relative balance of the IFN system for the pathogenesis of brucellosis is suggested and contrasted with IFN disfunction in the acquired immune deficiency syndrome.

Assessment of interferon production in patients with chronic nonviral diseases by whole blood or whole bone marrow techniques.

Hundred and fifty-four samples of heparinized blood from patients with chronic toxoplasmosis, chronic brucellosis, lung diseases, psychiatric affective disorders, healthy individuals and neonates, were obtained. The experimental material included also 14 bone marrow samples from patients with hematological diseases or lung cancer. The whole cell populations were treated with several classical IFN inducers and supernatants were assayed for IFN activity in human lung adenocarcinoma cell line A 549 using VSV or EMC viruses as challenge. The response of WBC to NDV or PHA + PMA was high and remarkably stable in majority of cases except listed below. The levels of IFN induced by LPS were low. The response of WBMC to IFN inducers closely resembled the response of WBC. Low IFN levels in samples of stimulated WBMC from some hematological patients were connected with low cellularity. WBC from psychiatric patients with affective disorders weakly responded to stimulation with NDV. This suggested an existence of deficiency of IFN alpha production connected with affective disorders. Also WBC from cord blood failed to react to PHA + PMA and were poorly responsive to NDV.