Małgorzata Inglot

Depression and neuroticism in patients with chronic hepatitis C: Correlation with peripheral blood mononuclear cells activation

BACKGROUND Hepatitis C virus (HCV) infection is commonly associated with cognitive dysfunction and depression, which could be related to direct brain infection. Viral sequences and proteins were found in brain macrophage/microglia cells and these cells were reported to be activated. Since blood leukocytes cross blood-brain barrier, activation state of peripheral blood mononuclear cells (PBMC) could reflect the state of brain immune cells. OBJECTIVE The aim of the study was to determine whether depression and neuroticism in chronic HCV infection correlates with the expression of key cytokines and chemokines in PBMC. DESIGN We studied 24 HCV-positive patients undergoing treatment with interferon and ribavirin. Patients were tested for depression using Beck Depression Inventory (BDI) and Montgomery Åsberg Depression Rating Scale (MADRS), while neuroticism was assessed by the Revised Eysenck Personality Inventory (N/EPO-R). Transcripts representing 28 various cytokines and chemokines were measured by real-time quantitative PCR in PBMC. RESULTS Prior to therapy BDI and MADRS positively correlated with viral load while neuroticism correlated with IL-3, IL-8 and M-CSF transcription levels. Six months after therapy there was positive correlation between depression and/or neuroticism scores and the levels of proinflammatory cytokines TNF-α and IL-12 transcripts, as well as IL-8, IL-10, IL-16, MCP-1, MCP-2, MIP-1-alpha, MIP-1-beta, and TGF-beta, and IFN-β transcripts. CONCLUSION Activation of PBMC, as measured by the level of cytokine and chemokine transcripts, correlates with depression and neuroticism scores. These findings suggest a pivotal role of immune cells activation in depression and possibly neurocognitive dysfunction among chronic hepatitis C patients.

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.

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.

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

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. 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. 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-β, 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-β. Pretreatment activation of the immune system, as reflected by cytokines transcripts upregulation, positively correlates with treatment outcome and closely reflects liver inflammatory activity.

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 HCV‑infected 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 HCV‑infected 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 HCV‑RNA 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 HCV‑infected patients.

Flaviviruses – new human pathogens

Rodzina Flaviviridae obejmuje wirusy przenoszone przez stawonogi, takie jak komary i kleszcze. Opisano już ponad 100 gatunków należących do rodziny Flaviviridae, z których większość jest patogenami zwierząt, choć nie można wykluczyć, że niektóre flawiwirusy zwierzęce staną się również przyczyną chorób u ludzi. Nazwa rodziny wywodzi się od wirusa żółtej gorączki – łaciński przedrostek flavus oznacza żółty. Zakażenia wywoływane przez Flaviviridae wciąż są ważnym problem zdrowia publicznego na świecie i istnieje obawa, że mogą rozprzestrzenić się również w rejonach nieendemicznych. Do istotnych z klinicznego punktu widzenia flawiwirusów zaliczane są m.in. wirusy: dengi, Zika, żółtej febry, kleszczowego zapalenia mózgu oraz wirus Zachodniego Nilu. Objawy kliniczne wywoływane przez te wirusy obejmują szeroki zakres – od bezobjawowych postaci zakażenia aż do śmiertelnych chorób. Wprawdzie charakterystyka tych wirusów jest dobrze zdefiniowana, są jednak nadal nieprzewidywalne pod względem: nasilenia wywoływanych objawów klinicznych oraz nietypowego ich przebiegu, nowych sposobów transmisji wirusów, zdolności do długotrwałego przetrwania w różnych warunkach klimatycznych, a także powstawania nowych gatunków. W artykule omówiono epidemiologię i symptomatologię istotnych klinicznie flawiwirusów, a także zwrócono uwagę na wpływ działalności człowieka na ich ewolucję i rozprzestrzenianie. Zmiany klimatyczne, urbanizacja i rozwój turystyki stworzyły możliwości rozprzestrzeniania się wirusów w nowych populacjach. Czynniki te sprawiają, iż rodzina Flaviviridae może stanowić potencjalne źródło nowych patogenów dla ludzi.

Assessment of dentists’ general attitude to wards HIV-infected patients

Introduction Patients are reluctant to admit they are HIV-positive during dental visit, because they fear refusal of treatment. In addition, dentists may be afraid about the risk of HIV infection during treatment of seropositive patients. It seems that knowledge about the risk of virus transmission after occupational exposure to potentially infectious material, is still unsatisfactory in many cases. This can lead to refusal of treatment of HIV-positive patient. Aim The aim of this study was to determine dentists’ general attitude to HIV infected patients and examine dentists’ knowledge about post-exposure procedures. Material and methods In study took part 374 dentists. The questionnaire survey results were statistically analyzed. Results Nearly 26% of dentists have been informed by patients about HIV infection. In this group, 9% of respondents admitted they refused to treat HIV-positive patients. Nearly 63% of dentists indicated that they are afraid of HIV transmission in the dental practice. About 46% of respondents said that HIV-positive patients should be treated in special clinic. Only 36% of dentists answered it is right that HIV-positive patients can decide whether they inform them about 1 Studenckie Koło Naukowe Chorób Zakaźnych, Chorób Wątroby i Nabytych Niedoborów Odpornościowych Uniwersytetu Medycznego we Wrocławiu 2 Katedra i Zakład Protetyki Stomatologicznej Uniwersytetu Medycznego we Wrocławiu 3 Katedra i Klinika Dermatologii, Wenerologii i Alergologii Uniwersytetu Medycznego we Wrocławiu 4 Katedra i Klinika Chorób Zakaźnych, Chorób Wątroby i Nabytych Niedoborów Odpornościowych Uniwersytetu Medycznego we Wrocławiu MARTYNA BIAŁA Studenckie Koło Naukowe Chorób Zakaźnych, Chorób Wątroby i Nabytych Niedoborów Odpornościowych, Uniwersytet Medyczny we Wrocławiu, ul. Koszarowa 5, 51-149 Wrocław, e-mail: biala.martyna@interia.pl Wpłynęło: 16.11.2015 Zaakceptowano: 28.12.2015 DOI: dx.doi.org/10.15374/FZ2015065 Artykuł jest dostępny na zasadzie dozwolonego użytku osobistego. Dalsze rozpowszechnianie (w tym umieszczanie w sieci) jest zabronione i stanowi poważne naruszenie przepisów prawa autorskiego oraz grozi sankcjami prawnymi. !

Impact of interaction between somatic illness and trait neuroticism on depressive symptoms

Background and Objectives: An interaction between neuroticism and burden of illness supports depressive symptoms even at subclinical level. We have assessed its effect in groups of patients with different kind of somatic illness. Methods: Depressive symptoms (SCAN 2.1) and a level of neuroticism (EPQ-R) were assessed in inpatients from 3 different hospital wards, namely the general internal, hematological and infectious wards, and in controls from the general population. Results: A total of 184 adult subjects were examined (45 with haematological malignancies, 46 treated for other, non-malignant internal diseases, 48 with HCV infection before treatment and 45 healthy persons as control). Differences in mean neuroticism scores were not statistically significant (ANOVA, F = 1.44, p = 0.23) whereas differences in mean depression scores were statistically significant (ANOVA, F = 6.34, p < 0.001). Results of ANCOVA for separate-slopes model analysis revealed a statistically significant level of interaction between groups and neuroticism in their influence on depression mean scores (F = 22.9, p < 0.001). The residual effect of the group variable was weak (F = 0.54, p = 0.21). Conclusions: The interaction is a significant factor related to depressive symptoms and can be used in estimating the extent of the psychological impact of a burden of illness.

Panuveitis as syphilis manifestation in HIV-1 infected patients

Summary Syphilis prevalence has been on the rise worldwide, including Poland, for the last 5 years, most often affecting young individuals who have unprotected intercourse. Currently most syphilitic patients, if diagnosed, are treated early and more advanced disease is rarely seen. We present a case of two individuals with AIDS and advanced syphilis with ocular in-volvement which was the reason to test for syphilis. It is worth reminding that syphilis and HIV share the same route of infection and in the light of recent epidemiological data it is wor-th considering if universal screening for syphilis is needed once again just like universal scre-ening for HIV has become the standard of care in many countries.

Chronic hepatitis C treatment in patients with HIV co-infection – results of the latest clinical trials

Summary Liver diseases, mainly viral hepatitis, recently have become the main cause of hospitalization and death in individuals with HIV infection. As HCV infection is predominant condition in this group of patients, treatment of hepatitis C is extremely important in halting hepatic injury. Large clinical trials (APRICOT, RIBAVIC, ACTG 5071) showed satisfactory efficacy and safety of therapy with pegylated interferon alpha and ribavirin. Other trials, searching ways to improve efficacy of chronic hepatitis C treatment in HIV co-infected individuals, are still running. Management possibilities include higher doses of ribavirin, prolonged course of treatment or higher doses of interferon in the early phase of therapy. The article summarizes current state of knowledge in the field of chronic hepatitis C treatment in HIV-infected individuals.