Prevalence and genotype distribution of human papillomavirus infection among HIV-infected men who have sex with men living in Lower Silesia, Poland.

Introduction: Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and is associated with the risk of anogenital and oropharyngeal cancers. Men who have sex with men (MSM) are at a high risk of HPV infection. However, little up-to-date data are available regarding the prevalence of HIV and HPV co-infection in MSM in Poland. Aim: To evaluate the prevalence, genotype distribution and risk factors for HPV infection among HIV-positive MSM living in Lower Silesia. Material and methods: A total of 54 HIV-positive and 28 HIV-negative MSM participated in the study. The polymerase chain reaction was performed to detect HPV from oral and anal swabs. A self-applied written questionnaire was conducted to collect sociodemographic and behavioural data. Results: The prevalence rates of oral and anal HPV infection were higher in HIV-infected MSM than in HIV-negative MSM. Statistical analysis showed that the prevalence of high oncogenic genotypes, HPV 16 and HPV 18, at the anal site was significantly higher in patients with lower CD4 cell counts, in addition, HPV 18 infection was significantly more frequent in patients with higher levels of HIV RNA. Moreover, HPV 33 and HPV 52 at the anal site were significantly more common in patients with lower nadir CD4. Conclusions: This is the first report of HPV infection among Polish HIV-infected MSM. Our results show that HIV-related immunodeficiency is associated with a higher prevalence of high-risk HPV infections, therefore early detection of HIV infection and initiation of antiretroviral therapy might reduce the risk of HPV-related diseases.

The role of anthranilic acid in the increase of depressive symptoms and major depressive disorder during treatment for hepatitis C with pegylated interferon-α2a and oral ribavirin.

Background: Tryptophan metabolism via the kynurenine pathway is considered the link between the immune and endocrine systems. Dysregulation of serotonergic transmission can stem from the direct influence of interferon-α on the activity of serotonergic receptors 5-HT1A and 5-HT2A, and from its indirect effect on tryptophan metabolism. Induction of the kynurenine pathway increases the concentration of neurotoxic kynurenine metabolites, and the activity of kynurenine derivatives is linked to the onset of depression. The aim of our study was to evaluate the relationships between depressive symptoms and kynurenine, tryptophan, anthranilic acid and kynurenic acid concentrations, indolamine 2,3-dioxygenase (IDO) activity and tryptophan availability to the brain. Methods: The study followed a prospective longitudinal cohort design. We evaluated 101 patients with chronic hepatitis C who were treated with pegylated interferon-α2a, and 40 controls who were awaiting treatment. We evaluated the relationships between total score on the Montgomery-Åsberg Depression Rating Scale and kynurenine, tryptophan, anthranilic acid and kynurenic acid concentrations, IDO activity and tryptophan availability to the brain. A logistic regression model was adapted for the diagnosis of major depressive disorder at each time point, taking into account changes in parameters of the kynurenine pathway between a given time point and the baseline measurement. Results: Of the treated patients, 44% fulfilled the criteria for major depressive disorder at least once during the 24 weeks of treatment. Anthranilic acid concentrations were significantly increased compared to baseline for all time points except week 2. Tryptophan availability showed a significant decrease (ß = -0.09, p = 0.01) only in week 12 of treatment. Over time, kynurenine, tryptophan and anthranilic acid concentrations, as well as IDO activity and tryptophan availability to the brain, were significantly associated with total score on the Montgomery-Åsberg Depression Rating Scale. A logistic regression model revealed that participants with decreased tryptophan availability to the brain at 12 weeks of treatment and participants with increased anthranilic acid concentrations at week 24 of treatment were at increased risk for diagnosis of major depressive disorder (odds ratios 2.92 and 3.59, respectively). Limitations: This study had an open-label design in a population receiving naturalistic treatment. Conclusion: The present study provides the first direct evidence of the role of anthranilic acid in the pathogenesis of inflammation-induced major depressive disorder during treatment for hepatitis C with pegylated interferon-α2a.

The effects of killer cell immunoglobulin-like receptor (KIR) genes on susceptibility to HIV-1 infection in the Polish population.

Killer cell immunoglobulin-like receptors (KIR) are the most polymorphic receptors of natural killer (NK) cells. Their activity diversifies the functions of NK cells in the antiviral immune response, so the presence of certain KIR may affect transmission of HIV-1. The aim of the study was to evaluate the influence of KIR genes on the susceptibility to HIV-1 infection in the Polish population depending on the route of exposure. We determined the frequencies of activating (2DS1, 2DS2, 2DS3, 2DS4f, 2DS4del, 2DS5, 3DS1) and inhibitory (2DL1, 2DL2, 2DL3, 2DL5, 3DL1) KIRs in HIV-1-positive patients (n = 459), individuals exposed to HIV-1 but uninfected (EU, n = 118) and in uninfected, healthy blood donors (BD, n = 98). Analysis was performed using stepwise logistic regression. Apart from KIRs, CCR5-∆32, and CCR2-64I, alleles were also analyzed, as we knew or suspected that these features could affect susceptibility to HIV infection. The regression confirmed the protective effect of CCR5-∆32 (OR = 0.25, p = 0.006) and CCR2-64I (OR = 0.59, p = 0.032) against HIV infection. Among KIR genes, 2DL3 was found to be a protective factor (OR = 0.30, p = 0.015). A similar effect was seen for 3DS1 but only in intravenous drug users (IDUs) (OR = 0.30, p = 0.019), not in sexually exposed people. 2DL5 was found to be a factor facilitating HIV infection (OR = 2.13, p = 0.013). A similar effect was observed for 2DL2 but only in females (OR = 2.15, p = 0.040), and 2DS1 in IDUs (OR = 3.03, p = 0.022). Our results suggest a beneficial role of KIR3DS1 and 2DL3 supporting resistance to HIV infection and a harmful effect of 2DS1, 2DL5, and 2DL2 genes promoting HIV acquisition.

The correlation between pretreatment cytokine expression patterns in peripheral blood mononuclear cells with chronic hepatitis C outcome.

BACKGROUD: Cytokine response against hepatitis C virus (HCV) is likely to determine the natural course of infection as well as the outcome of antiviral treatment. However, the role of particular cytokines remains unclear. The current study analyzed activation of cytokine response in chronic hepatitis C patients undergoing standard antiviral treatment. METHODS: Twenty-two patients were treated with pegylated interferon and ribavirin. Twenty-six different cytokine transcripts were measured quantitatively in peripheral blood mononuclear cells (PBMC) before and after therapy and correlated with therapy outcome as well as with clinical and liver histological data. RESULTS: We found that patients who achieved sustained virological response (SVR) showed higher pretreatment cytokine response when compared to subjects in whom therapy was unsuccessful. The differentially expressed factors included IL-8, IL-16, TNF-α, GM-CSF, MCP-2, TGF-ß, and IP-10. Serum ALT activity and/or histological grading also positively correlated with the expression of IL-1α, IL-4, IL-6, IL-10, IL-12, IL-15, GM-CSF, M-CSF, MCP-2 and TGF-ß. CONCLUSION: Pretreatment activation of the immune system, as reflected by cytokines transcripts upregulation, positively correlates with treatment outcome and closely reflects liver inflammatory activity.

Hepatitis C virus load and expression of a unique subset of cellular genes in circulating lymphoid cells differentiate non-responders from responders to pegylated interferon alpha-ribavirin treatment.

Based on investigations of liver biopsy material, certain cellular genes have been implicated as correlates of success or failure to interferon alpha-ribavirin (IFN/RBV) therapy against hepatitis C. The current study aimed at determining whether expression of host genes thought to be relevant to HCV replication in the liver would be correlated with HCV infection status in peripheral blood mononuclear cells (PBMCs) and also with patient responsiveness to IFN/RBV treatment. Therefore, PBMCs from patients with chronic hepatitis C responding (n = 35) or not (n = 49) to IFN/RBV and from healthy controls (n = 15) were evaluated for HCV RNA load and cellular gene expression. Non-responders had 3- to 10-fold higher basal levels of interleukin (IL)-8, IFN-stimulated gene 15 (ISG15), 2',5'-oligoadenylate synthetase (OAS), and Toll-like receptors (TLR)-4, -5, and -7 compared to responders. Non-responders with similar post-treatment follow-ups as responders persistently expressed 6- to 20-fold greater levels of IL-8, ISG15, and OAS after therapy. Higher expression of IFN-α, IFN-γ, and IFN-λ was found in PBMCs of individuals achieving sustained virological response, either before or after therapy. Pre-treatment HCV RNA loads in PBMCs of non-responders were significantly higher (P = 0.016) than those of responders. In conclusion, the data indicate that immune cells of responders and non-responders to IFN/RBV therapy exhibited significantly different virological and host gene expression profiles. Elevated baseline HCV loads and TLR-4, -5, and -7 levels, and persistently high levels of IL-8, ISG15, and OAS were correlated with IFN non-responsiveness. The results warrant further investigations on the utilization of PBMCs for predicting success or failure to IFN-based therapies.

Replication of hepatitis C virus in peripheral blood mononuclear cells in patients with chronic hepatitis C treated with pegylated interferon alpha and ribavirin.

INTRODUCTION: Hepatitis C virus (HCV) is a primarily hepatotropic virus, but hepatocytes are not the only localization of its replication. It is still unclear if extrahepatic HCV replication, measured as the detection of HCV RNA negative strand in peripheral blood mononuclear cells (PBMCs) before initiation of treatment, has an influence on therapy response. Detection of HCV RNA in extrahepatic sites for assessment of therapy efficacy is not routinely used in clinical practice. The aim of the study was to evaluate whether the replication of HCV in PBMCs affects the rate of sustained virological response (SVR). MATERIALS AND METHODS: The study group comprised 55 patients with chronic hepatitis C, originally treatment naive. They were treated with pegylated interferon (PEG-IFN) alpha 2a and ribavirin, with the standard dosing schedule. Parallel serum samples for HCV RNA and PBMC samples for HCV RNA negative strand were obtained at baseline, at the end of treatment and 24 weeks after finishing therapy. RESULTS: Undetectable HCV RNA in serum at the end of therapy was found in 48 patients (87.3%), while 33 patients (60.0%) achieved sustained virological response (SVR) (51% for HCV genotype 1 and 78% for genotype 3, respectively). Fifteen individuals (31.3%) were relapsers. Factors associated with significantly higher rate of SVR were young age, mild or no fibrosis and infection with HCV genotype 3. HCV RNA negative strand in PBMCs before treatment was found in 21.8% (12 out of 55 patients). HCV RNA negative strand was detected at baseline more frequently in patients who later achieved SVR. Relapse appeared significantly more often in patients with negative strand at the end of therapy: in 2 out of 15 individuals compared to 0 out of 33 patients (p=0.03). CONCLUSIONS: Presence of negative HCV RNA strand in PBMCs before treatment may be suggested as a potential marker of good treatment response. Detection of negative strand at the end of therapy is a predictor of relapse.

The Role of Plasminogen Activator Inhibitor 1 in Predicting Sepsis-Associated Liver Dysfunction: An Observational Study.

Sepsis-associated liver dysfunction (SALD) is associated with a poor prognosis and increased mortality in the intensive care unit. Bilirubin is one of the components of Sequential Organ Failure Assessment used in Sepsis-3 criteria. Hyperbilirubinemia is a late and non-specific symptom of liver dysfunction. This study aimed to identify plasma biomarkers that could be used for an early diagnosis of SALD. This prospective, observational study was conducted on a group of 79 patients with sepsis and septic shock treated in the ICU. Plasma biomarkers-prothrombin time, INR, antithrombin III, bilirubin, aspartate transaminase (AST), alanine transaminase, alkaline phosphatase, gamma glutamyl transferase, albumin, endothelin-1, hepcidin, plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex, and interferon-gamma inducible protein (10 kDa) were analysed. Plasma samples were obtained within 24 h after having developed sepsis/septic shock. Enrolled patients were followed for 14 days for developing SALD and 28 days for overall survival. A total of 24 patients (30.4%) developed SALD. PAI-1 with a cut-off value of 48.7 ng/mL was shown to be a predictor of SALD (AUC = 0.671, sensitivity 87.3%, and specificity 50.0%) and of 28-day survival in patients with sepsis/septic shock (p = 0.001). Measuring PAI-1 serum levels at the onset of sepsis and septic shock may be useful in predicting the development of SALD. This should be verified in multicenter prospective clinical trials.

An epidemiological and retrospective study in a cohort qualified for SARS-CoV-2 vaccination in the region of Lower Silesia, Poland.

BACKGROUND: Since the beginning of the coronavirus disease (COVID-19) pandemic, numerous infections have been observed with various symptoms and degrees of severity. Not all patients have had a confirmation of infection made using reverse transcription polymerase chain reaction (RT-PCR) or antigen tests. It has been observed that some people, including convalescents or those without knowledge of a past infection, perform serological tests to detect anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. OBJECTIVES: We aimed to evaluate the levels of anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies in a cohort of convalescents and in individuals not previously infected, who were willing to get vaccinated. We also aimed to assess several socio-clinical factors associated with participants' humoral responses. MATERIAL AND METHODS: We recruited 298 individuals from the region of Lower Silesia who were willing to get vaccinated for SARS-CoV-2. The participants were divided into 2 groups: convalescents (group I) and participants without a past infection (group II). Several seropositive individuals in group II were identified, and they were transferred to group I, resulting in a final distribution of 171 individuals in group I and 127 individuals in group II. For serological testing, the QuantiVac anti-SARS-CoV-2 (IgG) enzyme-linked immunosorbent assay (ELISA) was used. RESULTS: The results showed the presence of anti-SARS-CoV-2 IgG antibodies in participants from group I, with an average number of 190.3 IU/mL. Twenty-three participants (13.45%) did not have a detectable level of antibodies despite a previous SARS-CoV-2 infection. In 21 participants (12.28%), antibodies were detected despite no previous symptoms of infection (average level: 145.0 IU/mL). CONCLUSION: Older participants were more likely to experience a symptomatic SARS-CoV-2 infection, and the severity of the symptoms was related to higher antibody titers seen later after COVID-19. Numerous individuals from group II were unaware of past SARS-CoV-2 infections. In several participants, antibodies were not detected despite a previous infection.

HTR1A, TPH2, and 5-HTTLPR Polymorphisms and Their Impact on the Severity of Depressive Symptoms and on the Concentration of Tryptophan Catabolites during Hepatitis C Treatment with Pegylated Interferon-α2a and Oral Ribavirin (PEG-IFN-α2a/RBV).

BACKGROUND: Seeing that there are no data about associations between serotonin gene polymorphism and tryptophan catabolite concentration during PEG-IFN-α2a treatment, the aim of the current study is to examine (a) the associations between polymorphisms within the HTR1A, TPH2, and 5-HTT genes and the severity of depression symptoms and (b) the relationships among rs6295, rs4570625, and 5-HTTLPR rs25531polymorphisms and indoleamine 2,3-dioxygenase (IDO) activity, as well as kynurenine (KYN), tryptophan (TRP), kynurenic acid (KA), and anthranilic acid (AA) concentrations. MATERIALS AND METHODS: The study followed a prospective, longitudinal, single-center cohort design. The severity of the depressive symptoms of 101 adult patients with chronic HCV infections was measured during PEG-IFN-α2a/RBV treatment. We used the Montgomery-Åsberg Depression Rating Scale (MADRS) to assess the severity of depressive symptoms. The subjects were evaluated six times-at baseline and at weeks 2, 4, 8, 12, and 24. At all the time points, MADRS score, as well as KYN, TRP, KA, and AA concentrations, and IDO activity were measured. At baseline, rs6295, rs4570625, and 5-HTTLPR rs25531polymorphisms were assessed. RESULTS: Subjects with C/C genotypes of 5-HT1A and lower-expressing alleles (S/S, LG/LG, and S/LG) of 5-HTTLPR scored the highest total MADRS scores and recorded the highest increase in MADRS scores during treatment. We found associations between TRP concentrations and the TPH-2 and 5-HTTLPR rs25531 genotypes. CONCLUSIONS: Our findings provide new data that we believe can help better understand infection-induced depression as a distinct type of depression.

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.

How Humoral Response and Side Effects Depend on the Type of Vaccine and Past SARS-CoV-2 Infection.

Since the end of December 2020, it has been possible to vaccinate against COVID-19. Our aim was to evaluate and compare the effectiveness of the vaccines available at the time of the mass vaccination program in Poland and also to look into the most common adverse side effects. Patients' anti-SARS-CoV-2 antibodies levels were checked before vaccination and after the first and after the second/last dose by the anti-SARS-CoV-2 QuantiVac ELISA (IgG) (EUROIMMUN MedicinischeLabordiagnostica AG; Luebeck; Germany) test. Before each blood collection, all patients filled out a questionnaire regarding experienced side effects. We observed that 100% of patients responded to the vaccinations. After the first dose, convalescents had much higher levels of anti-SARS-CoV-2 antibodies than naive patients, although after the second dose, 61 out of 162 convalescents (37.7%) had lower results than before. The comparison of immunological responses in the convalescents group after the first dose and in the naive group after the second dose showed that convalescents had higher antibody titers, which may suggest the possibility of changing the vaccination schedule for convalescents. The highest antibody titers after both the first and second doses were observed after Moderna shots. Fever was identified as a significant factor regarding higher levels of antibodies after the first and second doses of the vaccine.

Prevalence of HBV genotypes in Central and Eastern Europe.

The importance of hepatitis B virus (HBV) genotypes for disease progression and response to interferon-alpha-based treatment is well established. While almost all patients in the Mediterranean area are infected with HBV genotype D, HBV genotype A is dominant in Northern Europe. However, the distribution of HBV genotypes is unknown for several Central and Eastern European countries. Data are described of 1313 HBsAg-positive patients recruited at 14 referral centers in eight countries. There were only very few cases of HBV genotype B, C, E, F, and H infection while HBV genotypes A and D were found in 42% and 48% of patients, respectively. Eight percent of patients had positive bands for more than one genotype using the hybridization assay. The frequency of genotype A was higher in Poland (77%) and the Czech Republic (67%) as compared to Hungary (47%), Lithuania (41%), Croatia (8%), and Germany (32%). In contrast, HBV genotype D was most frequent in Croatian, Romanian, and Russian patients with 80%, 67%, and 93% of cases, respectively. In conclusion, HBV genotype A versus D showed significantly different distribution patterns in Central and Eastern Europe which deserves consideration for national guidelines and treatment decisions.

[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.

Alterations in the metabolism of tryptophan in patients with chronic hepatitis C six months after pegylated interferon-α 2a treatment.

BACKGROUND: Risk of depression and suicide in patients on interferon remains also after the treatment, the pathogenesis of which is still unclear. We aimed to determine the influence of the PEG-IFN-α2a on tryptophan metabolism along the kynurenine pathway during treatment and up to 6 months after the end of treatment. METHODS: We evaluated 101 patients with chronic hepatitis C treated with PEG-IFN-α2a, and 40 controls, so as to determine the activation of indolamine 2,3-dioxygenase (IDO) and tryptophan (TRP) and their metabolites' concentrations/levels: kynurenine (KYN), kynurenic acid (KYNA) and anthranilic acid (AA). The subjects were evaluated before and after weeks 2, 4, 8, 12, 24, 48, as well as 6 months after the end of the treatment. RESULTS: In the group of patients treated 24 weeks, six months after the end of treatment IDO activity was significantly higher compared to baseline (69.5 vs 57.2 ß = 0.21 P = 0.000); TRP concentration was significantly lower compared to baseline (30.0 vs 35.6 ß=-0.21 P = 0.001); KYNA concentration was significantly higher compared to baseline (37.2 nmol/L vs 29.4 nmol/L ß = 0.22 P = 0.02), and AA concentration was significantly higher compered to baseline (51.0 nmol/L vs 38.4 nmol/L ß = 0.22 P = 0.05) In the group of patients treated 48 weeks six months, after the end of treatment both the IDO activity and KYNA concentration were significantly higher compared to baseline (respective values - IDO: 78.8 vs 56.2 ß = 0.14 P = 0.02; KYNA: 39.2 nmol/L vs 27.0 nmol/L ß = 0.26 P = 0.000). CONCLUSIONS: This is the first report of a prolonged activation of IDO six months after the end of PEG-IFN-α2a treatment. The clinical significance of the finding can be implicated in the pathophysiology of depressive episodes.

Transmission Networks of HCV Genotype 1a Enriched With Pre-existing Polymorphism Q80K Among HIV-Infected Patients With Acute Hepatitis C in Poland.

BACKGROUND: Hepatitis C virus (HCV) resistance-associated variants (RAVs) have been shown to adversely affect treatment response of direct-acting antivirals. Identifying pre-existing RAVs and transmission networks among HIV/HCV genotype 1 (G1)-infected patients from Poland will assist in shaping surveillance strategies for HCV. METHODS: NS3 and NS5A sequences were obtained from samples of 112 direct-acting antiviral-naive G1 patients (45 G1a and 67 G1b), of which 74 were chronically infected and 38 were diagnosed with acute hepatitis C (AHC). RAVs were identified using geno2pheno, and 98 concatenated NS3/NS5A alignments were constructed to identify transmission clusters using a maximum likelihood approach. RESULTS: G1a was notably more prevalent compared with G1b among men-having-sex-with-men (MSM) (60.0% vs. 31.3%, P = 0.004), AHC cases (46.7% vs. 25.4%, P = 0.019), and patients diagnosed with syphilis (52.2% vs. 24.5%, P = 0.009). The overall NS3/NS5A RAVs frequency was 14.3% with variants occurring more often in G1a compared with G1b (27.5% vs. 5.2%, P = 0.005), mostly for NS3 due to the high prevalence of polymorphism Q80K. NS5A RAVs were only found in 2.9% of sequences. Significant clustering was observed for 73.5% of the Polish sequences, however, more common in G1a MSM compared with G1b (50.0% vs. 25.9%, P = 0.02). The identified clusters contained sequences originating from up to 5 Polish cities, located within a mean distance of 370 km. CONCLUSIONS: Close clustering of Polish strains suggests the presence of compartmentalized epidemics of MSM that fuel the spread of G1a variants. Particularly patients with AHC form a national transmission network, including clusters enriched with the NS3 Q80K polymorphism.

[Chronic hepatitis C in patients with HIV/HCV coinfection with high CD4+ lymphocytes count]. / Obraz przewleklego zapalenia watroby typu C u pacjentów zakazonych HIV z wysoka liczba limfocytów CD4+.

AIM: analysis of data characterizing HCV infection in patients infected with HIV. MATERIAL AND METHODS: 37 persons (29 male and 8 female) aged 23-49 years (mediana 34), with HIV/HCV coinfection, treated (n=25) and untreated (n=12) with antiretroviral therapy. HAART was effective in treated patients; CD4+ count >350 cells/microl. Viral load of HIV and HCV, HCV genotypes, CD4/CD8, biochemical tests, histopathological examination were measured. Results were analyzed statistically. RESULTS: the majority of patients were former IVDUs (n=31.84%), 3 persons (8%)--MSM, 3 (8%)--route of infection unknown. Duration of HCV infection 1-10 years, mediana 5. All patients were in A1 or A2 stage of HIV infection. Among patients treated with HAART (n=25) mediana of CD4+ count before treatment was 263 (69-595) cells/micro, mediana of HIV viral load 75000 copies/ml (n=7); 2040-263414 copies/ml. 17 patients were currently treated with PI, 17 with NNRTI, and 2 patients with NRTI only. HCV genotype was determined in 32 patients: 3a--n=19 (59%), 1--n= 9 (28%) 4--n=4 (13%). HCV viral load: 2.4 x 10(5)-7.73 x 10(6) IU/ml, mediana 1.6 x 10(6). Levels of ALT: 21-358 IU/ml, mediana 102, AST: 20-195 IU/ml, mediana 62, GGTP--9-463 IU/ml, mediana 58. ALT level was significantly higher in HCV genotype 3a infection (p=0.0214). Fibrosis stage above 2 was revealed in 3 patients and in majority (62%) was below 2. None patient had liver cirrhosis. Fibrosis was significantly higher in patients with low CD4+ nadir (p=0.03). CONCLUSIONS: Progression of liver fibrosis is slow in patients coinfected with HIV/HCV with high CD4+ count. High percentage of HCV genotype 3 and mild fibrosis are good prognostic factors for effectiveness of HCV infection treatment in HIV infected persons.

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.

Lung cancer as an immune reconstitution disease in an HIV-1 positive man receiving HAART.

A case of small-cell lung cancer with prompt worsening of the clinical course was observed in a patient with significant immune restoration after receiving effective highly active antiretroviral therapy (HAART) for seven months. Rapid and enormous enlargement of metastatic liver was the main symptom. Chest x-ray showed an enlargement of the left hilus. The patient died 22 days after the onset of the fulminant disease. We suggest that the occurrence and aggressive course of the lung cancer resulted from the development of immune reconstitution syndrome.

Risk factors for chronic kidney disease do not influence the serum levels of asymmetric dimethylarginine in HIV-1-infected patients without significant renal disease.

INTRODUCTION Chronic kidney disease (CKD) is one of the consequences of human immunodeficiency virus-1 (HIV-1) infection. The disease increases the risk of progression to acquired immunodeficiency syndrome and death and complicates antiretroviral therapy. The prevalence of CKD in HIV-1-infected patients is difficult to estimate and depends on the diagnostic criteria for CKD. OBJECTIVES The aim of the study was to evaluate the usefulness of a single measurement of serum asymmetric dimethylarginine (ADMA) levels in the diagnosis of kidney damage in patients infected with HIV-1.  PATIENTS AND METHODS The study included 119 HIV-1-infected individuals (88 males [74%]), both on antiretroviral treatment and treatment-naive, with a negative history of kidney disease, and 31 healthy volunteers. We analyzed demographic characteristics as well as data on concomitant diseases, antiretroviral regimen, serum ADMA concentrations, parameters of renal function, CD4+ cell count, and HIV-1 viral load. RESULTS No significant impairment of renal function was observed. Mean serum ADMA levels in all HIV-1-infected patients, as well as in treatment-naive patients and treated patients, were significantly higher (P <0.0001; P = 0.0001; P <0.0001; respectively) compared with those in the control group. The difference between treatment-naive and treated HIV-1-infected patients was nonsignificant. ADMA levels were not correlated with the mean duration of antiretroviral therapy, antiretroviral drugs used, or other risk factors for CKD. CONCLUSIONS A single measurement of ADMA levels is not useful for the diagnosis of CKD in patients without significant renal pathology or as an indicator of kidney damage related to antiretroviral therapy. The significance of repeated measurements of ADMA levels in renal function assessment requires further research.