Treatment of Essential Thrombocythemia with Anagrelide Is Associated with an Increased Risk of Worsened Kidney Function.

BACKGROUND AND PURPOSE: When choosing a cytoreduction method for patients suffering from essential thrombocythemia (ET), it is important to know the safety profile of the medicine used. Few articles have been published about the effects of hydroxycarbamide (hydroxyurea, HU) and anagrelide (ANA) on renal function in ET patients. This study is the largest analysis of nephrotoxicity of cytoreductive drugs used in ET therapy so far, which additionally includes risk factors for the progression of kidney disease and coexisting genetic mutation. EXPERIMENTAL APPROACH: The retrospective study included 310 patients diagnosed with ET. Demographic data, comorbidities, Cr, and estimated glomerular filtration rate (eGFR) were all taken into account prior to diagnosis and after 6 months of HU and ANA treatment. KEY RESULTS: A statistically significant difference was found between Cr and eGFR levels at baseline and after 6 months of treatment (p < 0.001). The applied treatment (HU and ANA) had the greatest impact on kidney function. ANA significantly increased the risk of worsening renal function in contrary to hydroxycarbamide after 6 months of treatment (eGFR change: median +1 mL/min/1.73 m2 [interquartile range (IQR) (-4)-(+7)] in the HU group vss. median -13 mL/min/1.73 m2 [IQR (-18)-(-6)] in the ANA group, odds ratio [OR] 7.92 95% confidence interval [95% CI] [4.17-15.08], p < 0.001). Lowering of eGFR <60 mL/min/1.73 m2 occurred in 31 patients (31.0%) from the ANA group and 10 people (4.8%) treated with HU (p = 0.000). In 1 patient from the ANA group, >50% decrease in eGFR was observed. The chance for an increase in Cr levels was higher in people with pre-existing arterial hypertension (OR 1.92 CI = 95% [1.21-3.05], p = 0.006). Sex, type of mutation found (JAK2 V617F or CALR), and previous renal impairment did not affect renal function after 6 months of treatment. In addition, there was no difference in the efficacy of ET treatment between HU and ANA (p = 0.998). CONCLUSIONS AND IMPLICATIONS: The observations indicate that ANA should be used in patients with ET with great caution and taking into account the risk of worsened kidney function.

Interferon-free therapy as the cause of white matter tracts and cerebral perfusion recovery in patients with chronic hepatitis C.

The purpose of this study was to assess cerebral microstructural and perfusion changes in patients with chronic hepatitis C virus (HCV) infection before and after interferon-free therapy, using advanced magnetic resonance (MR) techniques. Eleven HCV-positive patients underwent diffusion tensor imaging (DTI) and perfusion-weighted imaging (PWI) using a 1.5T MR unit, before and 24 weeks after completion of interferon-free therapy. DTI fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained from 14 white matter tracts. PWI values of relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were assessed from 8 areas, including basal ganglia, and cortical and white matter locations. In HCV-positive patients therapy with ombitasvir, paritaprevir boosted with ritonavir and dasabuvir, with or without ribavirin, was scheduled. Cognitive tests were used to assess cognitive function. We found increased FA values after interferon-free therapy compared to values obtained before treatment in HCV patients in almost all white matter tracts. We also observed elevated rCBV values in basal ganglia after therapy. There were significant correlations between improvement in the score of cognitive tests and increased FA values in both inferior fronto-occipital fascicles and left posterior cingulum after treatment. Liver fibrosis regression in elastography, APRI and improvement in cognitive tests were observed. This is the first report of interferon-free therapy as the cause of white matter tracts recovery as well as cerebral perfusion improvement in HCV-infected patients, indicating better functioning of frontal lobes after interferon-free treatment.

Imported malaria caused by Plasmodium falciparum ­ case report

INTRODUCTION: Malaria is caused by the Plasmodium spp. which are spread through Anopheles mosquitoes. Disease is not endemic in Poland currently but can be brought from other countries, mostly from Africa and Asia. The main sign of the disease is fever with shivers repeated periodically. There is highly effective chemoprophylaxis available and treatment, which should be given quickly CASE REPORT: A 35-year-old man have worked monthly in Nigeria since two years. He was using Malarone chemoprophylaxis, but contrary to recommendations. Patient presented to a hospital after four days of having fever in a medium-serious state. He reported three similar incidents in the past. Physical examination revealed hepatomegaly, depressive state, oliguria and diarrhoea. Lab tests showed DIC with thrombocytopenia, renal injury, liver injury, hypoalbuminemia. ECG indicated myocardial ischemia. Malaria Rapid Test and blood smear confirmed Plasmodium falciparum infection with 9,9% parasitemia. When antimalarial treatment was given, patient condition improved, but after three days in hospital he got pneumonia as a complication of malaria ­ antibiotic admission was committed. Moreover, quinine caused temporary deafness and serological tests revealed chronic HBV infection. After 23-days of hospitalisation the patient was discharged in a good condition. A month later patient went to follow-up and only mild anaemia was shown. CONCLUSIONS: This case shown that even such severe disease like malaria can be cured well without serious complications if patient will be diagnosed quickly. Moreover patient's experience and respecting symptoms improve prognosis. There also should be stronger emphasis on the role of chemoprophylaxis ­ patient did not use it properly, so it did not have to prevent development of malaria.

Risk of occupational exposure to the HBV infection in non-clinical healthcare personnel.

BACKGROUND: Occupational risk of blood-borne infections is investigated mostly among nurses and doctors, studies concerning non-clinical health personnel (nCHP) being rare. The analysis of the occupational exposure to the hepatitis B virus (HBV) infection and the history of vaccination against the HBV in the nCHP group has been the aim of the study. MATERIAL AND METHODS: A retrospective analysis of 458 cases of the occupational exposure to biological agents was conducted: group I - doctors (N = 121, 28%), group II - nursing staff (N = 251, 55%), group III - nCHP (N = 86, 19%). RESULTS: In the group III the source was usually unknown (group: I - 0.83%, II - 11.16%, III - 86.05%, p < 0.001), and the proportion of individuals vaccinated against hepatitis B before the exposure was the lowest (group: I - 98.35%, II - 97.19%, III - 77.91%, p < 0.001). In this group most exposures resulted from injuries caused by needles/sharps deposited in waste sacks (60%) or anywhere outside of the medical waste container (5%). The possibility of the HBV infection risk during the exposure was found in 25 cases and was significantly more frequent in the group III. The qualification for the HBV post-exposure prophylaxis was also significantly more frequent in the group III. CONCLUSIONS: The exposure to the occupational risk of the HBV infection also concerns the non-clinical healthcare personnel. The non-clinical healthcare personnel comprises one of the main groups of the HBV post-exposure recipients. It is essential to determine the causes of the low hepatitis B vaccination coverage in the nCHP and consider introduction of mandatory vaccination in this group in Poland. Med Pr 2016;67(3):301-310.

Transmitted HIV drug resistance in antiretroviral-treatment-naive patients from Poland differs by transmission category and subtype.

OBJECTIVES: The surveillance of HIV-transmitted drug resistance mutations (t-DRMs), including temporal trends across subtypes and exposure groups, remains a priority in the current management of the epidemic worldwide. METHODS: A cross-sectional analysis of 833 treatment-naive patients from 9 of 17 Polish HIV treatment centres. Partial pol sequences were used to analyse drug resistance with a general time reversible (GTR)-based maximum likelihood algorithm used for cluster/pair identification. Mutation frequencies and temporal trends were investigated. RESULTS: t-DRMs were observed in 9% of cases (5.8% for NRTI, 1.2% NNRTI and 2.0% PI mutations) and were more common among heterosexually infected (HET) individuals (13.4%) compared with MSM (8.3%, P = 0.03) or injection drug users (IDUs; 2.9%, P = 0.001) and in MSM compared with IDUs (P = 0.046). t-DRMs were more frequent in cases infected with the non-B variant (21.6%) compared with subtype B (6.6%, P < 0.001). With subtype B a higher mutation frequency was found in MSM compared with non-MSM cases (8.3% versus 1.8% for IDU + HET, P = 0.038), while non-B variants were associated with heterosexual exposure (30.4% for HET versus 4.8% for MSM, P = 0.019; versus 0 for IDU, P = 0.016). Trends in t-DRM frequencies were stable over time except for a decrease in NNRTI t-DRMs among MSM (P = 0.0662) and an NRTI t-DRM decrease in HET individuals (P = 0.077). With subtype B a higher frequency of sequence pairs/clusters in MSM (50.4%) was found compared with HET (P < 0.001) and IDUs (P = 0.015). CONCLUSIONS: Despite stable trends over time, patterns of t-DRMs differed notably between transmission categories and subtypes: subtype B was associated with MSM transmission and clustering while in non-B clades t-DRMs were more common and were associated with heterosexual infections.

Asymptomatic Human Immunodeficiency Virus-1 Infection with High CD4+ T Cell Count Does Not Alter Iron Metabolism or Hepcidin Levels: The Pilot Study.

INTRODUCTION: The purpose of the study was to assess hepcidin levels and iron metabolism in otherwise healthy human immunodeficiency virus-1 (HIV-1)-infected males and the influence of antiretroviral therapy on hepcidin production, as data in this group are scarce. METHODS: A total of 89 HIV-1-infected males, 42 on effective antiretroviral therapy (ART)-group A, 47 treatment-naïve-group B, and 27 healthy controls-group C, were enrolled. Erythrocytes parameters, iron metabolism parameters, hepcidin, highly sensitive C-reactive protein (hsCRP), interleukin 6 (IL-6), and soluble transferrin receptor (sTfR) levels were assessed. Conditions related to inflammatory activity, systemic metabolic diseases and iron supplementation were exclusion criteria. Convenience sampling was used. RESULTS: Median age in HIV-1 group was 33 years, and 27 years in the control group. Median CD4+ T-cell count was 724 cells/µl in group A, and 488 cells/µl in group B (p = 0.0000). Nadir CD4+ T-cell count was 397 cells/µl in group A and 475 cells/µl in group B (p = 0.0001). Median value of HIV-1 viral load (VL) in group B was 16 900 copies/mL. The hepcidin value was lower in group A than in groups B (p = 0.0008) or C (p = 0.0004), without differences between groups B and C. The hepcidin value correlated with ferritin in groups A (r2 = 0.16; p = 0.008) and B (r2 = 0.39; p = 0.000), but not in group C (r2 = 0.11; p = 0.09). In group A, the hepcidin value correlated with current CD4+ count (r = 0.48, p = 0.0012), but there was no correlation in group B. There were no correlations of hepcidin values with CD4+ T cell nadir in group A (p = 0.371) or in group B (p = 0.477); ART period (p = 0.614); VL in group B (p = 0.71). No abnormalities of iron metabolism, hsCRP, IL-6, or sTfR were noted. CONCLUSIONS: Asymptomatic HIV-1 infection does not cause clinically important iron metabolism alterations or increased hepcidin production. Hepcidin values decrease on effective antiretroviral therapy.

Dual infection of urinary tract with Enterocytozoon bieneusi and Encephalitozoon cuniculi in HIV/AIDS patients

Microsporidia are emerging pathogens which cause an opportunistic infections in immunocompromised patients, especially those with AIDS. Intestinal microsporidiosis is the most recognized infection, whereas urinary tract infections caused by microsporidia are rarely paid attention to either due to their subclinical course or diagnostic difficulties. In this report dual microsporidial infection of urinary tract, caused by Enterocytozoon bieneusi and Encephalitozoon cuniculi was described in HIV/AIDS patients under cART therapy. Since microsporidiosis can cause severe complications or even death in immunosuppressed patients, our results suggest that microsporidial infection should be included in routine investigation of HIV-positive patients, even asymptomatic.

Evaluation of brain volume alterations in HCV-infected patients after interferon-free therapy: A pilot study.

The study was performed to evaluate cerebral volume changes in HCV-infected subjects before and after interferon-free therapy with direct-acting antiviral agents (DAA). We aimed also to estimate the impact of successful DAA therapy on the neuropsychological state of patients. Eleven HCV genotype 1 (GT1) patients treated with ombitasvir/paritaprevir (boosted with ritonavir) and dasabuvir, with or without ribavirin underwent brain magnetic resonance (MR) before and 24 weeks after completion of therapy. All patients achieved sustained viral response. Precise automatic parcellation was made using the fully-available software FreeSurfer 6.0. Statistically significant volume deceleration six months after treatment was found in the subcallosal cingulate gyrus, transverse frontopolar gyri and sulci, anterior segment of the circular sulcus of the insula and horizontal ramus of the anterior segment of the lateral sulcus. After DAA therapy we found statistically significant improvement in the performance of all three tasks of the Rey Complex Figure Test that permits the evaluation of different functions (attention, planning, working,memory). Additionally, significant amelioration in Percentage Conceptual Level Responses in The Wisconsin Card Sorting Test (a neurocognitive test for assessing intellectual functioning) was also discovered. Successful interferon-free therapy may lead to transient cerebral atrophy, probably by reducing neuroinflammation and oedema. This is the first pilot study of the alterations in brain volume after successful interferon-free therapy in chronic HCV patients. Longitudinal follow-up study is needed to observe further effects of therapy on cerebral structures volume changes.

Visual and brainstem auditory evoked potentials in HCV-infected patients before and after interferon-free therapy - A pilot study.

INTRODUCTION: The aim of this study was to investigate brain bioelectrical activity disturbances in HCV-positive patients before and 24 weeks after interferon-free therapy (DAA), using visual (VEP) and brainstem (BAEP) evoked potentials and advanced magnetic resonance techniques. MATERIALS AND METHODS: 11 HCV-infected patients (6 women, 5 men, mean age 51 years old) and 30 healthy controls, sex and age-matched, were studied. Clinical neurological examinations, VEP, BAEP, diffusion tensor imaging (DTI) and perfusion weighted imaging (PWI) were performed. RESULTS: 11 patients achieved a sustained viral response, and liver fibrosis regression in APRI and in elastography were observed. The mean P100 latency was significantly shorter in HCV-patients after therapy compared to the values before treatment (p<0.05). The mean wave BAEP V latency and I-V interpeak latency were significantly longer in the HCV-infected patients before therapy compared to HCV-patients after therapy. CONCLUSIONS: This study confirms that treatment with DAA in patients with chronic HCV infection positively affects the bioelectrical activity of the brain. An increase in the amplitude of EP after treatment indicates an improvement in the activity of the cerebral cortex. EP examination may be a useful method of assessing the function of the nervous system before and after antiviral treatment.

[Cytokine assessment in untreated hepatitis C virus infected patients and during interferon alpha +ribavirine therapy]. / Badanie wybranych cytokin w surowicy krwi pacjentów z przewleklym zapaleniem watroby typu C nieleczonych oraz leczonych interferonem alfa i rybawiryna.

UNLABELLED: Many articles concerning the hepatitis C virus (HCV) infection emphasize the role of cytokines Th1- and Th2-dependent. The aim of our study was to assess the changes in the concentration of cytokines (IL-2, IFN-gamma, IL-4, IL-10) determined by ELISA test in serum of HCV infected patients treated with interferon alpha (IFN-alpha) and ribavirine. RESULTS: The cytokine levels in HCV patients (n = 40) were similar to levels observed in healthy volunteers (p > 0.05). During IFN-alpha and ribavirine therapy no statistically significant changes in cytokine levels were observed in patients who achieved sustained virological response (SVR) compared to unsuccessfully treated patients (p > 0.05). CONCLUSIONS: 1. Serum is not useful compartment to determinate level of cytokines by ELISA method in chronic hepatitis C. 2. The measurement of cytokine levels using ELISA test was not confirmed to be useful in monitoring and assessment of the therapy results in HCV infected patients.

[Diagnostic and therapeutic aspects of hepatitis C virus induced thrombocytopenia (HCV-TP)]. / Aspekty diagnostyczne i terapeutyczne maloplytkowosci indukowanej zakazeniem wirusem C zapalenia watroby (HCV-TP).

Hepatitis C virus induced thrombocytopenia (HCV-TP) is a problematic disorder for diagnosis and treatment both for the infectious diseases specialists and hematologists. In the relation we decided to the present most up-to date views upon the HCV-TP patomechanism and systematized the diagnostic methods and therapeutic possibilities.

Stage of liver fibrosis in patients with congenital bleeding disorders and infected with hepatitis C virus.

INTRODUCTION: Hepatitis C virus (HCV) is the major cause of chronic liver disease in patients with hemophilia. However, since liver biopsy should not be routinely used in these patients, the accurate assessment of the stage of fibrosis has been limited so far. OBJECTIVES: The aim of this study was to determine the stage of liver fibrosis in HCV­infected patients with hemophilia by using noninvasive methods of fibrosis assessment, and to analyze the influence of risk factors on liver fibrosis. PATIENTS AND METHODS: The study included 71 HCV­infected patients with hemophilia and other congenital bleeding disorders. Patients were divided into 3 groups: HCV-RNA negative after successful treatment, HCV-RNA negative after spontaneous elimination of infection, and HCV­RNA positive. Liver fibrosis was measured with shear wave elastography and FibroTest. The risk factors for liver fibrosis were analyzed, including demographic factors, HCV genotype, coinfections, and comorbidities. RESULTS: Cirrhosis or significant fibrosis (METAVIR score >F2) was observed in 26.8% of the patients. The stage of fibrosis was associated with age and estimated duration of infection (P <0.001). Active and past HBV infection did not affect fibrosis. The stage of liver fibrosis was lower in patients with spontaneous clearance of HCV (P = 0.007). CONCLUSIONS: Patients in our study had a similar stage of liver fibrosis to that reported by other studies on hemophilia. The older age and long duration of infection are the main risk factors for advanced fibrosis. Noninvasive methods such as shear wave elastography and FibroTest may allow a proper assessment of the fibrosis stage in hemophilia patients, particularly when used together and in correlation with other clinical parameters. They may also be useful in other groups of HCV­infected patients.

[Neuropsychiatric symptoms related to interferon alpha]. / Objawy neuropsychiatryczne w trakcie leczenia interferonem alfa.

Neuropsychiatric symptoms are commonly related to interferon alpha treatment. The paper summarises the current knowledge about their aetiology, course, and treatment. Interferon alpha is a cytokine with antiviral and antineoplasmatic activity. It is commonly used in the treatment of chronic hepatitis C and B, malignant melanoma, Kaposi sarcoma, renal cancers, and some haematological malignancies. Treatment with interferon alpha is associated with depressive symptoms, cognitive disturbances, chronic fatigue syndrome, dysphoria, anxiety symptoms, anorexia, mania and psychotic states. Up to a half of the patients need psychiatric consultations, 10-25% of them need psychiatric treatment. Neuropsychiatric symptoms are the results of direct affection of CNS by interferon and induced cytokines. They increase hypothalamic-pituitary-adrenal (HPA) activity, alter thyroid function and lead to a behavioural syndrome called 'sickness behaviour'. Moreover interferon induces the activity of 2, 3 indoloamine dioxygenase, the enzyme which converts tryptophan into kynurenine, leads to a reduced level of tryptophan, and thus to a reduced level of central serotonin and to an increased level of neurotoxic kynurenine metabolites. Interferon also affects central opioid receptors and changes dopaminergic and noradrenergic neurotransmission. Serotonin selective reuptake inhibitors (SSRI), other antidepressants i.e. nortriptyline, benzodiazepines, naltrexone, and neuroleptics (for maniac and psychotic states) are used to treat interferon associated psychiatric symptoms. Psychological therapy may also be useful, as well as psychoeducation and behavioural interventions.

[Depressive symptoms during treatment with interferon alpha for HCV infection--preliminary report]. / Objawy depresyjne w trakcie leczenia interferonem alfa z powodu zakalenia HCV--doniesienie wstepne.

BACKGROUND: Interferon alpha, used in hepatitis C virus (HCV) infection causes many neuropsychiatric side effects: emotional disturbances, chronic fatigue, cognitive impairment, and psychotic states. They overlap with emotional disturbances and cognitive impairment caused by chronic HCV infection. AIM: To assess prevalence and severity of depressive symptoms in patients treated with interferon alpha due to HCV infection. METHODS: A total of 44 persons (27 men, 17 women) aged from 21 to 61 years old (median 45 years) treated due to chronic hepatitis were examined. They were treated with pegylated interferon alfa 2a and ribavirin. All of them underwent liver biopsy to assess liver inflammation, fibrosis, and steatosis as well as completed Eysenck's neuroticism questionnaire. Then, before treatment and after 12 weeks, they underwent biochemical and psychiatric examination. Biochemical examination included aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (G-GT), and HCV RNA. Psychiatric examination included Beck Depression Inventory (BDI), Hamilton Depressive Rating Scale (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS), and the SF-36 questionnaire. Diagnoses of depression were made basing on PSE questionnaire from Schedules of Clinical Assessment in Neuropsychiatry (SCAN version 2.0). RESULTS: Depressive disorders were diagnosed in 3 (6.8%) subjects before treatment and in 5 (11.4%) subjects after 12 weeks of treatment. A statistically significant increase of depressive rates was observed (medians: HDRS 6/11.5; MADRS 4/10; BDI 8/10.5). Quality of life dropped significantly in some SF - 36 scales: physical functioning, general health, vitality, and social functioning. Depressive ratings were independent of biochemical parameters (AST, ALT, G-GT), HCV RNA, liver inflammation, fibrosis, steatosis level, and HCV genotype. Ratings of neuroticism highly influenced all depressive ratings. Rise of depressive ratings was independent of neither any initial biochemical parameters nor the neuroticism level. CONCLUSIONS: Interferon alpha increases the severity of depressive symptoms. The rise is probably caused by biological activity of interferon and independent of initial ratings of depression.

Co-Infection of the Hepatitis C Virus With Other Blood-Borne and Hepatotropic Viruses Among Hemophilia Patients in Poland.

BACKGROUND: The prevalence of HCV infection in people with hemophilia is substantially higher than that in the general population (63% - 98%). Multiple transfusions and substitutive therapy have also been linked to a high risk of HBV and HIV transmission. However, the prevalence of other blood-borne viral infections in this population is less well known. OBJECTIVES: This study aimed to assess the prevalence of co-infection with HBV and other blood-borne viruses in Polish HCV-infected hemophiliacs. METHODS: Seventy-one individuals, the majority of whom were male (94.36%), who had congenital bleeding disorders (60 had hemophilia A, five had hemophilia B, and six had other factor deficiencies) and HCV infection, which was defined as the presence of positive anti-HCV antibodies, were included in this study. The study group was divided into two subgroups according to the year in which blood donors were first tested for HBsAg in Poland. The serological markers were screened using commercially available enzyme immunoassays according to the manufacturer's instructions. The molecular tests were performed using real-time PCR technology with commercial assays according to the manufacturer's instructions. RESULTS: The spontaneous elimination rate of HCV RNA was 29.6%. The HCV genotype 1 was detected in 28 patients (65.1%), genotype 2 in one patient (2.3%), genotype 3 in 11 patients (25.6%), genotype 4 in two patients (4.7%), and a mixed infection with genotypes 1 and 4 was detected in one person (2.3%). Fifty-three patients (74.6%) were anti-HBc positive. Among the seven HBsAg(+) patients, three individuals were HBV-DNA positive. No occult hepatitis B was detected. In six HBsAg positive patients, the HCV RNA was positive, while one patient was also infected with HIV. The prevalence rate of past infection with HAV in the study group was 30.9%, with a tendency for a higher prevalence in older patients. The prevalence of CMV and EBV infection was high and similar to that seen in the general population. All the patients were HGV and HTLV-1 negative. CONCLUSIONS: The diagnostics and management of infections with hepatotropic viruses, particularly HBV, are neglected in hemophilic patients. All patients with coagulation disorders and a history of exposure to non-inactivated blood products should be screened for blood-borne infections. The prevalence of other potentially blood-borne viral infections exhibited a pattern similar to that observed in the general population.

Distribution and time trends of HIV-1 variants in Poland: Characteristics of non-B clades and recombinant viruses.

The spread of HIV-1 subtypes varies considerably both worldwide and within Europe, with non-B variants commonly found across various exposure groups. This study aimed to analyse the distribution and temporal trends in HIV-1 subtype variability across Poland. For analysis of the subtype distribution, 1219 partial pol sequences obtained from patients followed up in 9 of 17 Polish HIV treatment centres were used. Subtyping was inferred using the maximum likelihood method; recombination was assessed using the bootscanning and jumping profile hidden Markov model methods. Subtype B dominated in the studied group (n=1059, 86.9%); in 160 (13.1%) sequences, non-B variants were present [A1 (n=63, 5.2%), D (n=43, 3.5%), C (n=22, 1.8%), and F1 (n=2, 0.2%)]. In 25 (2.1%) cases circulating recombinant forms (CRFs) were found. Five A1 variants (0.4%) were unique AB recombinant forms (URF) not previously identified in Poland. Non-B clades were notably more common among females (n=73, 45.6%, p<0.001) and heterosexual individuals (n=103, 66.5%, p<0.001) and less frequent among men who have sex with men (MSM) (n=27, 17.42%, p<0.001). HIV-1 viral load at diagnosis was higher among non-B cases [median: 5.0 (IQR: 4.4-5.6)] vs. [median: 4.8 (IQR: 4.3-5.4) log copies/ml for subtype B (p<0.001)] with a lower CD4(+) lymphocyte count at baseline [median: 248 (IQR: 75-503) for non-B vs. median: 320 (IQR: 125-497) cells/µl for subtype B; p<0.001]. The frequency of the non-B subtypes proved stable from 2008 (11.5%) to 2014 (8.0%) [OR: 0.95 (95% CI: 0.84-1.07), p=0.4], with no temporal differences for exposure groups, gender, age and AIDS. Despite the predominance of subtype B, the variability of HIV in Poland is notable; both CRFs and URFs are present in the analysed population. Non-B variants are associated with heterosexual transmission, more advanced HIV disease and have stable temporal frequencies.

[Experimental therapy in HCV infection]. / Terapia eksperymentalna zakazenia HCV.

PEGInterferon and ribavirin combination therapy is a gold standard in hepatitis C treatment. However it is not efficacious in all cases. Therefore, many studies are conducted to identifying additional drugs and therapeutic regimens, which might be more affordable. The progress in development of HCV culture systems (e.g.replicon) is crucial for successful therapeutic intervention in viral life-cycle (viral NS5B polymerase and NS3/4A protease inhibitors, antisense nucleotides, ribozymes, siRNA). Other classes of immunomodulatory/antiviral agents and new interferon formulation have also been considered for IFN-based therapy also. On the other hand immunomodulatory pathways are attractive target for novel anti-HCV therapy. Combination therapy targeting different aspects will be probably in the future successful option in hepatitis C treatment.

[Neuropsychiatric disorders in HCV-infected people--own observations]. / Zaburzenia neuropsychiatryczne u osób zakazonych HCV--obserwacje wlasne.

UNLABELLED: Neuropsychiatric symptoms are commonly associated with chronic hepatitis C virus infection and its treatment. There are no Polish studies concerned this problem in patients during combination therapy (interferon and ribavirin). AIM: to examine the mood disorders an quality of life during the first 12 weeks of therapy. METHODS: The following research instruments were used: the Present State Examination (PSE), The Beck Depression Inventory, The Montgomery Asberg Depression Rating Scale, SF-36, Hamilton Depression Rating Scale. ALT, AST, GGT activity, HCV viral load and genotype, histological activity index of the liver was also measured. RESULTS: A group of 94 untreated patients (M=, K=) with hepatitis C was examined. 44 of them was examined secondly after 12 week of combination therapy. Depression disorders was observed in 4% pts before treatment and in 11% after 12 weeks therapy. In the group untreated patients there was two statistically significant correlations: between examined neuropsychiatric disorders and HCV viral load and necroinflammatory activity in the liver. CONCLUSIONS: The mood disorders are not so common in the patients with hepatitis C and could have biological etiology. The interferon based therapy increase the frequency and intensity of them.

[The role of therapeutic use of interleukin-2 in HIV infection]. / Rola i zastosowanie terapeutyczne interleukiny 2 w zakazeniu HIV.

Interleukin-2 (IL-2) is a cytokine produced by lymphocytes T CD4+, T CD8+ and NK cells. IL-2 increases the number of lymphocytes T and prolongs their survival and has extensive immunomodulatory effect. High levels of IL-2 are observed during asymptomatic phase of HIV infection (TH-1 dependent cytokine) and low levels are observed during progression of immunodeficiency. IL-2 inhibits apoptosis of CD4+ T cells, improves NK cells activity, has influence on production of soluble antiviral factor (CAF) which inhibits viral activity etc. That is why IL-2 has been introduced to the treatment of HIV infection along with highly active antiretroviral therapy (HAART). High T CD4+ cells count predicts long survival of HIV infected individual. Phase III clinical trials concerning IL-2 are now performed and the preliminary results are promising. Polish centers also take part in the ESPRIT study. Adverse events of various severity are seen in patients under treatment (anti inflammatory drugs are required). The symptoms usually resolve within a few days after IL-2 therapy is stopped.