Neuroborreliosis is a form of Lyme Borreliosis (LB) that affects various structures of the centra... more Neuroborreliosis is a form of Lyme Borreliosis (LB) that affects various structures of the central and peripheral nervous system. Although most cases of LB can be cured with a course of antibiotics, some children can present prolonged symptoms, which may constitute post-treatment Lyme disease syndrome (PTLDS). The aim of our analysis was the long-term observation of children with NB and the determination of their risk of PTLDS. The clinical observation was supplemented by a laboratory study based on the assessment of the dynamics of anti-VlsE (variable major protein-like sequence, expressed) IgG antibodies in children with NB after antibiotic therapy. The prospective survey based on 40 children presented 1–2 forms of NB. The control group consisted of 36 patients with analogical symptoms for whom LB was excluded. Our long-term observation showed a low risk of developing long-term complications in children who received antibiotic therapy in accordance with the recommendations. The co...
Badania neuroelektrofizjologiczne umożliwiają nieinwazyjną ocenę czynności układu nerwowego, pełn... more Badania neuroelektrofizjologiczne umożliwiają nieinwazyjną ocenę czynności układu nerwowego, pełniąc tym samym istotną rolę w procesie diagnostycznym schorzeń neurologicznych. Elektroencefalografia jest najpowszechniej wykorzystywanym badaniem z tej grupy, mającym przede wszystkim zastosowanie w rozpoznawaniu chorób o charakterze napadowym. Niewątpliwymi zaletami metody są powtarzalność i możliwość porównywania w czasie, co w połączeniu z bezinwazyjnością rozszerza jej zastosowanie o monitorowanie przebiegu choroby. W pracy przedstawiamy opisy trojga pacjentów leczonych w Klinice z powodu zapalenia mózgu, u których wykorzystanie elektroencefalografii miało istotne znaczenie w potwierdzeniu wstępnego rozpoznania i umożliwiło włączenie adekwatnego, intensywnego leczenia.
BACKGROUND & AIMS Sofosbuvir-velpatasvir-voxilaprevir is a pangenotypic regimen for chronic h... more BACKGROUND & AIMS Sofosbuvir-velpatasvir-voxilaprevir is a pangenotypic regimen for chronic hepatitis C virus (HCV) infection. In the United States and Europe, sofosbuvir-velpatasvir-voxilaprevir once daily for 12 weeks is indicated for adults previously receiving an HCV NS5A inhibitor. In Europe, sofosbuvir-velpatasvir-voxilaprevir is also indicated in the absence of prior HCV direct-acting antiviral (DAA) therapy as an 8- or 12-week regimen. In an open-label study, we evaluated the safety, efficacy, and pharmacokinetics of sofosbuvir-velpatasvir-voxilaprevir in adolescents 12 to 17 years with chronic HCV of any genotype. METHODS In this Phase 2, multi-center study, sofosbuvir-velpatasvir-voxilaprevir 400/100/100 mg daily was administered to adolescents for 8 weeks if DAA-naïve or for 12 weeks for cirrhosis or prior DAA failure. The key efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Intensive pharmacokinetic sampling was done in 14 patients at week 2 or 4, and samples for population pharmacokinetics were collected in all patients. RESULTS All patients (n=21) were naïve to HCV DAAs, and none had cirrhosis. HCV genotype 3a infection was most common, occurring in 43% of patients. Overall, 100% of patients (21/21) reached SVR12. The most common adverse events were abdominal pain and headache (24% each) and nausea (19%); no adverse events led to discontinuation. The only serious adverse event, hypotension, was considered related to study drug and resolved the same day without interruption of treatment. Sofosbuvir-velpatasvir-voxilaprevir exposures were similar to those observed in adults. CONCLUSION The pangenotypic regimen of sofosbuvir-velpatasvir-voxilaprevir is highly efficacious and well-tolerated in treating chronic HCV infection in adolescents.
Pattern recognition receptors (PRRs) constitute a pivotal arm of innate immunity. Their distribut... more Pattern recognition receptors (PRRs) constitute a pivotal arm of innate immunity. Their distribution is widespread and not limited to cells of the immune system. Following our previous findings concerning the expression of Toll-like receptors (TLRs) 2, 3 and 4 in chronic viral hepatitis C of children, we wished to search for other PRRs, including other TLRs, NOD-like receptors (NLRs) and RIG-1-like helicase receptors (RLR) in infected hepatocytes. Liver biopsy fragments from ten children with chronic hepatitis B and C were used and two others in which hepatotropic virus infection was excluded. Frozen sections of liver samples were subjected to ABC immunohistochemistry (IHC) following incubation with a set of antibodies. Results of IHC findings were screened for correlation with clinical/laboratory data of patients. It was found that several PRRs could be shown in affected hepatocytes, but the incidence was higher in hepatitis C than in B. In hepatitis C, TLR1, 2, 4, NALP and RIG-1 h...
Pediatric inflammatory multisystem syndromes associated with Severe Acute Respiratory Syndrome Co... more Pediatric inflammatory multisystem syndromes associated with Severe Acute Respiratory Syndrome Coronavirus 2 are emerging in recent reports. We describe a patient with critical illness consistent with atypical Kawasaki disease with cardiac dysfunction and abdominal involvement presenting weeks after Severe Acute Respiratory Syndrome Coronavirus 2 infection. Our patient showed unique central nervous system involvement with small vessel vasculitis and profound hypocomplementemia, both not previously reported in case descriptions and may hint at possible disease mechanisms.
The aim of this study was to investigate the impact interferon type I based anti-viral therapy on... more The aim of this study was to investigate the impact interferon type I based anti-viral therapy on the immune system of chronically infected children with hepatitis C and B virus. Peripheral blood mononuclear cells were examined by three-color flow cytometry, using a panel of fluorochrome labeled monoclonal antibodies. It was found that the majority of white blood cell subsets were decreased in patients after termination of long-term anti-viral treatment. In particular, potentially cytotoxic, effector cell subsets, such as natural killer, natural killer T-lymphocytes and CD8 + CD28 - T cells were significantly decreased. Moreover, plasmacytoid dendritic cells were decreased, both in percentage and in absolute values. These data suggest that interferon-α based treatment, apart from its anti-viral effect, has also remarkable impact on patient's cell-mediated immunity.
Pediatric Gastroenterology, Hepatology & Nutrition, 2014
Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder in the absence of demo... more Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder in the absence of demonstrated stones. AAC is frequently associated with severe systemic inflammation. However, the exact etiology and pathogenesis of AAC still remain unclear. Acute infection with Epstein Barr virus (EBV) in childhood is usually aymptomatic, whereas it often presents as typical infectious mononucleosis symptoms such as fever, cervical lymphadenopathy, and hepatosplenomegaly. AAC may occur during the course of acute EBV infection, which is rarely encountered in the pediatric population. AAC complicating the course of a primary EBV infection is usually associated with a favorable outcome. Most of the patients recover without any surgical treatment. Therefore, the detection of EBV in AAC would be important for prediction of better prognosis. We describe the case of a 10-year-old child who presented with AAC during the course of primary EBV infection, the first in Korea, and review the relevant literature.
Background and Aim: Chronic hepatitis C (CHC) is still a significant clinical problem because of ... more Background and Aim: Chronic hepatitis C (CHC) is still a significant clinical problem because of not only a large proportion of infected individuals, but also unclear remote consequences of the disease. The aim of the study was to analyze the clinical course and the liver histology of CHC in children searching for potential influencing factors. Methods: Sixty-eight children were enrolled into the study (mean, 13.34 [SD, 3.27] years). Medical records and a current clinical status of children were analyzed considering clinical symptoms, liver function tests, and qualitative and quantitative hepatitis C virusYRNA assay with genotype and liver histology. Results: A parenteral route of infection concerned 98% of children; mean length of infection was 7.34 (SD, 4.03) years. Genotype 1a was found in 78% and 1b in 16.2% children. The history of malignancy was present in 74% of patients. The symptoms of liver cirrhosis with abnormal vein circulation were found in 2 children (3%). An increased alanine aminotransferase activity was detected in 62% of patients, whereas viral load less than 6 Â 10 5 IU/mL was found in 56 children (82%). Histological evaluation of biopsy specimens showed moderate inflammatory activity (G 2) and fibrosis (S 2 ; mean, 2.0). Progression of fibrosis was proportional to the age at infection. Conclusions: The clinical course of CHC is usually mild but may result in the liver cirrhosis during childhood. Transient or constant increased alanine aminotransferase activity is observed in majority of children. Inflammatory activity and fibrosis have moderate progression in children and are proportional to the age at infection.
Opiekun: dr hab. n. med. Iwona Mozer-Lisewska Zakażenia meningokokowe stanowią istotny problem ep... more Opiekun: dr hab. n. med. Iwona Mozer-Lisewska Zakażenia meningokokowe stanowią istotny problem epidemiologiczny, obarczony wysoką śmiertelnością. Cel pracy. Przedstawiono dziewięć przypadków chorobowych ilustrujących różnorodny obraz kliniczny i laboratoryjny zakażenia meningokokowego. Materiał i metody. Analizie poddano objawy kliniczne, wyniki badania przedmiotowego, biochemiczne i mikrobiologiczne wykładniki sepsy i inwazyjnej choroby meningokowej. Wyniki. Stwierdzono występowanie niecharakterystycznych objawów prodromalnych. Izolowana postać sepsy wystąpiła w pięciu przypadkach, w czterech rozpoznano inwazyjną chorobę meningokokową. Odnotowano występowanie istotnych zaburzeń koagulologicznych wskazujących na rozpoczynający się lub toczący proces wykrzepiania śródnaczyniowego. Dodatnie posiewy mikrobiologiczne pobranych materiałów uzyskano w siedmiu przypadkach. Wnioski. Zakażenie meningokokowe wykazuje dużą różnorodność przebiegu klinicznego. Stwierdzono korelację pomiędzy zaburzeniami koagulologicznymi a ciężkością choroby. Szybkie wdrożenie właściwego postępowania diagnostycznego i intensywnego leczenia nie gwarantuje sukcesu terapeutycznego. Słowa kluczowe: Neisseria meningitidis, sepsa, zespół wykrzepiania śródnaczyniowego (DIC), zespół Waterhouse-Friderichsena, zapalenie opon mózgowo-rdzeniowych Introduction. In spite of preventive measurements meningococcal infections are significant epidemiological problem with a burden of high mortality rate. Objective. Nine cases of meningococcal invasive disease (MID) were described to show varied clinical manifestations and laboratory findings. Patients and methods. Clinical symptoms were analysed including results of physical examination, clinical chemistry and microbiological features of sepsis and MID. Significant coagulation abnormalities were observed indicating initiating or existing process of disseminated intravascular coagulation. Positive culture results were obtained in 7 cases. Conclusions. Meningoccocal infections display varied clinical picture. Positive correlation between coagulation disorders and severity of disease was observed. Immediate implementation of proper diagnostic procedures and of early treatment does not guarantee therapeutic success.
Summary HIV epidemic started at the end of the twentieth century. The infection very quickly spre... more Summary HIV epidemic started at the end of the twentieth century. The infection very quickly spread to the whole world affecting over 33 million people globally. Women are considered half of the infected individuals mostly living in developing countries. In the countries where women's human rights are not respected, the risk of HIV-infection is much greater. First reports relating gender-related susceptibility to HIV-infection were published at the end of the twentieth century. The spread of the infection is associated with various biological and socio-economical factors. There is a strong need to reduce the burden of the epidemic among women. These include promotion and protection of women's human rights, increasing awareness among women and encouraging new preventative technologies. Mother-to-child transmission (MTCT) occurs when an HIV positive woman passes the virus to her baby during pregnancy, delivery, or breastfeeding. Estimated 2 million children living with HIV, which were in majority infected by their mothers. Significant proportion of these children will not live to adulthood. Despite existing antiviral treatment this way of prevention is unavailable in many regions. Although the world is effectively fighting with HIV epidemic, it is believed that more actions are required to restrict HIV transmission.
Lekarski I Akademii Medycznej im. K. Marcinkowskiego w Poznaniu Kierownik: prof. dr hab. med. Woj... more Lekarski I Akademii Medycznej im. K. Marcinkowskiego w Poznaniu Kierownik: prof. dr hab. med. Wojciech Służewski Wstęp. Wysoką mutagenność wirusa zapalenia wątroby typu C (HCV) oraz możliwość jego przetrwania w rezerwuarach pozawątrobowych, m.in. w mononuklearach krwi obwodowej (peripheral blood mononuclear cells-PBMCs) uważa się za jedne z głównych czynników utrudniających eliminację HCV z organizmu. Cel. Celem badania była analiza wpływu HCV RNA w PBMCs oraz aktywności aminotransferazy alaninowej (ALT) i wiremii HCV RNA w surowicy na uzyskanie trwałej odpowiedzi wirusologicznej (sustained virological response-SVR) u dzieci z przewlekłym wirusowym zapaleniem wątroby typu C (pwzw C) leczonych pegylowanym interferonem alfa i rybawiryną. Materiał i metody. Badaniem objęto 22 dzieci z rozpoznanym na podstawie ogólnie przyjętych kryteriów pwzw C leczonych pegylowanym interferonem alfa i rybawiryną. U dzieci poddano analizie przede wszystkim obecność HCV RNA w PBMCs oraz aktywność ALT i wiremię HCV RNA w surowicy. Wyniki. W zależności od uzyskanej w wyniku leczenia odpowiedzi wirusologicznej dzieci podzielono na grupę A (n = 15), która uzyskała SVR, i grupę B (n = 7), która nie wyeliminowała HCV RNA z surowicy. Wnioski. Na osiągnięcie SVR nie miała wpływu wyjściowa aktywność ALT czy wiremia HCV RNA. Obecność HCV RNA w PBMCs w momencie rozpoczęcia leczenia wydaje się nie mieć istotnego znaczenia dla osiągnięcia SVR. Ważna jest obserwacja pacjentów po leczeniu przeciwwirusowym z nieoznaczalnym HCV RNA w surowicy, ale obecnym zakażeniem w PBMCs. Leczenie przeciwwirusowe niejednoznacznie wpływa na zachowanie się wiremii HCV RNA w obrębie PBMCs. Słowa kluczowe: przewlekłe zapalenie wątroby typu C, interferon pegylowany, trwała odpowiedź wirusologiczna, mononukleary krwi obwodowej Introduction. The high mutagenic capacity of hepatitis C virus (HCV) and its ability to survive in extrahepatic reservoirs, i.e. peripheral blood mononuclear cells (PBMCs), are considered to be main causes of the difficulties in eliminating it. Aim. The aim of this study was to analyze the influence of HCV RNA in PBMCs, alanine aminotransferase (ALT) activity and HCV RNA viral load in serum on achieving of sustained virological response (SVR) in children with chronic hepatitis C (CHC) treated with pegylated interferon alpha and ribavirin. Patients and methods. Twenty-two children with CHC diagnosed according to current standard criteria were enrolled into the study. The children were treated with pegylated interferon alpha and ribavirin. The presence of HCV RNA in PBMCs, ALT activity and HCV RNA viral load in serum were analyzed in the study group. Results. On the basis of virological response to the treatment the children were divided in two groups: group A (n = 15) that achieved SVR, and group B (n = 7) that did not eliminate HCV RNA from serum. Conclusions. Baseline ALT activity and HCV RNA viral load did not influence achieving SVR. Careful observation of patients after antiviral treatment with negative HCV RNA in serum but positive results in PBMCs is essential. Antiviral treatment does not have an unequivocal effect on HVC RNA in PBMCs.
POSTERS to evaluate the diagnostic performance of serum YKL-40 and HA as noninvasive markers of l... more POSTERS to evaluate the diagnostic performance of serum YKL-40 and HA as noninvasive markers of liver fibrosis in KT patients with HCV chronic infection. Methods: This cross-sectional study included KT individuals with positive HCV-RNA, with biopsy-proven chronic hepatitis. Univariate analysis was used to identify variables associated with clinically significant fibrosis (F2, F3 or F4 METAVIR stages). The diagnostic values of the YKL-40 and HA were compared using receiver operating characteristic (ROC) curves. Results: 85 patients were included (60% males, mean age 44.9±9.4 years). The mean time since transplantation (TST) was 6.5±4.9 years and significant fibrosis was observed in 14 patients (17%). Patients with significant fibrosis, as compared to those with F0/F1 stages, were older (48.6±5.1 vs. 44.2±10.0 years, P = 0.020), showed a higher TST (10.1±5.4 vs. 5.7±4.5 years, P = 0.002) and higher prevalence of diabetes (85% vs. 28%, P < 0.001). Subjects with significant fibrosis also exhibited higher serum levels of YKL-40, although this difference did not reach statistical significance (292±163 ng/dL vs. 233±154 ng/dL, P = 0.198). Significantly higher median levels of HA were noted in subjects with METAVIR F2 (108 ng/dL vs. 37 ng/dL, P = 0.002). The AUROCs of YKL-40 and HA for predicting significant fibrosis were 0.615 and 0.765, respectively (P = 0.144). Based on ROC curves, two cutoffs were chosen for each marker. The diagnostic performances of the proposed cutoffs are summarized in the table below. If biopsy indication was restricted to patients with YKL-40 and HA levels in the intermediate range, 32% and 35% of liver biopsies could have been correctly avoided, respectively. Conclusions: YKL-40 and HA are promising markers of liver fibrosis in KT patients with chronic HCV infection.
Background and Aims: Renal toxicity of first generation protease inhibitors (IP) was not a safety... more Background and Aims: Renal toxicity of first generation protease inhibitors (IP) was not a safety signal in phase III clinical trials, until Mauss et al.’s report in Hepatology. Methods: We retrospectively analyzed 101 HCV patients receiving triple therapy with telaprevir (n = 36) or boceprevir (n = 26) or double therapy (n =39) and a close monitoring of eGFR (MDRD formula) during and after treatment (D0, W4, 8, 12, 16, 24, 36, 48, 60, 72). Changes in eGFR over time were assessed by a linear mixed effects model (LMEM) with search for possible explanatory covariates. Results: Patients treated with telaprevir, presented a significant decrease of eGFR with the same kinetics: initial decrease at W4, nadir at W8 (mean decrease 17.0±18.9ml/min/1.73m2) and in average normalization at W16. The W8eGFR was highly correlated with the D0eGFR (R = 0.49) and was significantly lower in patients with grade II anemia or more (p = 0.031). The LMEM showed that the slope of eGFR versus time was the same for all patients and eGFR nadir could be predicted. In multivariate analysis, eGFR during the first 8 weeks was associated with time, older age, male sex and cryoglobulinemia. Conclusions: The eGFR significantly varied in telaprevir group only. Our model showed that eGFR nadir mainly depended on initial eGFR. As telaprevir was shown to inhibit mostly the human renal drug transporter OCT2 which interacts with creatinin transport, the early decrease of eGFR observed could be a benign phenomenom. However, as true and unpredictable renal toxicity may occur at any time during therapy, we recommend a thorough follow-up of eGFR.
International Journal of Infectious Diseases, 2010
Background: Chronic hepatitis B (CHB) is still a significant clinical problem In the whole Word. ... more Background: Chronic hepatitis B (CHB) is still a significant clinical problem In the whole Word. It is estimated that 2 milliard people had contact with hepatitis B virus (HBV) and 400 millions suffer from CHB or its remote consequences. The study was aimed at remote analysis of the incidence of seroconversion in HBeAg/anti-HBe and HBsAg/anti-HBs after antiviral treatment and their relation to age at infection as well as evaluation of aminotransferase activity and chosen biochemical parameters. Methods: The study included 310 children (220 boys and 90 girls) with diagnosed CHB who underwent antiviral treatment with interferon-alpha (IFN-alpha) or lamivudine. 177 children were treated with IFN-alpha, 25 with lamivudine and 107 children were treated with lamivudine after prior lack of response to IFN-alpha treatment. Mean age at HBV infection diagnosis was 4.14 ± 3.23 years. Mean age At the beginning of observation was 6.93 ± 3.69 years. Mean length of follow-up was 7.11 ± 2.39 years. Results: In 222 children (71.6%) seroconversion in HBeAg/anti-HBe was present-on the average 6.69 ± 3.02 after the diagnosis and 2.19 ± 1.47 after the introduction of antiviral treatment. The group of children treated with IFN-alpha was introduced 3.72 ± 2.12 years and lamivudine 6.38 ± 3.71 years after the diagnosis of HBV infection. Reverse relation was found between the incidence of seroconversion and the age at diagnosis (r = −0,30; p < 0,001). ALT and AST activity at HBV diagnosis was compared in children with and without seroconversion. Children with HBeAg/anti-HBe seroconversion had higher aminotrasferase at the diagnosis of HBV infection in comparison with patients without seroconversion. Viral load in children with seroconversion revealed significant alterations in the following years of the follow-up period in children with seroconversion (p < 0.0089). Similar changes were not present in children without seroconversion. Conclusion: Age at infection seem to be a significant factor influencing the incidence of seroconversion. ALT and AST activity at the diagnosis is a good prognostic factor of HBeAg/anti-HBe and HBsAg/anti-HBs seroconversion.
International Journal of Infectious Diseases, 2010
e229 occult HBV infection isn't frequent in Iranian thalassemic patients who suffering from chron... more e229 occult HBV infection isn't frequent in Iranian thalassemic patients who suffering from chronic HCV infection.
The hepatitis C virus (HCV) is a globally prevalent human pathogen that causes persistent liver i... more The hepatitis C virus (HCV) is a globally prevalent human pathogen that causes persistent liver infections in most infected individuals. HCV is classified into seven phylogenetically distinct genotypes, which have different geographical distributions and levels of genetic diversity. Some of these genotypes are endemic and highly divergent, whereas others disseminate rapidly on an epidemic scale but display lower variability. HCV phylogeny has an important impact on disease epidemiology and clinical practice because the viral genotype may determine the pathogenesis and severity of the resultant chronic liver disease. In addition, there is a clear association between the HCV genotype and its susceptibility to antiviral treatment. Similarly to other RNA viruses, in a single host, HCV exists as a combination of related but genetically different variants. The whole formation is the actual target of selection exerted by a host organism and antiviral therapeutics. The genetic structure of the viral population is largely shaped by mutations that are constantly introduced during an error-prone replication. However, it appears that genetic recombination may also contribute to this process. This heterogeneous collection of variants has a significant ability to evolve towards the fitness optimum. Interestingly, negative selection, which restricts diversity, emerges as an essential force that drives HCV evolution. It is becoming clear that HCV evolves to become stably adapted to the host environment. In this article we review the HCV phylogeny and molecular evolution in the context of host-virus interactions.
Neuroborreliosis is a form of Lyme Borreliosis (LB) that affects various structures of the centra... more Neuroborreliosis is a form of Lyme Borreliosis (LB) that affects various structures of the central and peripheral nervous system. Although most cases of LB can be cured with a course of antibiotics, some children can present prolonged symptoms, which may constitute post-treatment Lyme disease syndrome (PTLDS). The aim of our analysis was the long-term observation of children with NB and the determination of their risk of PTLDS. The clinical observation was supplemented by a laboratory study based on the assessment of the dynamics of anti-VlsE (variable major protein-like sequence, expressed) IgG antibodies in children with NB after antibiotic therapy. The prospective survey based on 40 children presented 1–2 forms of NB. The control group consisted of 36 patients with analogical symptoms for whom LB was excluded. Our long-term observation showed a low risk of developing long-term complications in children who received antibiotic therapy in accordance with the recommendations. The co...
Badania neuroelektrofizjologiczne umożliwiają nieinwazyjną ocenę czynności układu nerwowego, pełn... more Badania neuroelektrofizjologiczne umożliwiają nieinwazyjną ocenę czynności układu nerwowego, pełniąc tym samym istotną rolę w procesie diagnostycznym schorzeń neurologicznych. Elektroencefalografia jest najpowszechniej wykorzystywanym badaniem z tej grupy, mającym przede wszystkim zastosowanie w rozpoznawaniu chorób o charakterze napadowym. Niewątpliwymi zaletami metody są powtarzalność i możliwość porównywania w czasie, co w połączeniu z bezinwazyjnością rozszerza jej zastosowanie o monitorowanie przebiegu choroby. W pracy przedstawiamy opisy trojga pacjentów leczonych w Klinice z powodu zapalenia mózgu, u których wykorzystanie elektroencefalografii miało istotne znaczenie w potwierdzeniu wstępnego rozpoznania i umożliwiło włączenie adekwatnego, intensywnego leczenia.
BACKGROUND & AIMS Sofosbuvir-velpatasvir-voxilaprevir is a pangenotypic regimen for chronic h... more BACKGROUND & AIMS Sofosbuvir-velpatasvir-voxilaprevir is a pangenotypic regimen for chronic hepatitis C virus (HCV) infection. In the United States and Europe, sofosbuvir-velpatasvir-voxilaprevir once daily for 12 weeks is indicated for adults previously receiving an HCV NS5A inhibitor. In Europe, sofosbuvir-velpatasvir-voxilaprevir is also indicated in the absence of prior HCV direct-acting antiviral (DAA) therapy as an 8- or 12-week regimen. In an open-label study, we evaluated the safety, efficacy, and pharmacokinetics of sofosbuvir-velpatasvir-voxilaprevir in adolescents 12 to 17 years with chronic HCV of any genotype. METHODS In this Phase 2, multi-center study, sofosbuvir-velpatasvir-voxilaprevir 400/100/100 mg daily was administered to adolescents for 8 weeks if DAA-naïve or for 12 weeks for cirrhosis or prior DAA failure. The key efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Intensive pharmacokinetic sampling was done in 14 patients at week 2 or 4, and samples for population pharmacokinetics were collected in all patients. RESULTS All patients (n=21) were naïve to HCV DAAs, and none had cirrhosis. HCV genotype 3a infection was most common, occurring in 43% of patients. Overall, 100% of patients (21/21) reached SVR12. The most common adverse events were abdominal pain and headache (24% each) and nausea (19%); no adverse events led to discontinuation. The only serious adverse event, hypotension, was considered related to study drug and resolved the same day without interruption of treatment. Sofosbuvir-velpatasvir-voxilaprevir exposures were similar to those observed in adults. CONCLUSION The pangenotypic regimen of sofosbuvir-velpatasvir-voxilaprevir is highly efficacious and well-tolerated in treating chronic HCV infection in adolescents.
Pattern recognition receptors (PRRs) constitute a pivotal arm of innate immunity. Their distribut... more Pattern recognition receptors (PRRs) constitute a pivotal arm of innate immunity. Their distribution is widespread and not limited to cells of the immune system. Following our previous findings concerning the expression of Toll-like receptors (TLRs) 2, 3 and 4 in chronic viral hepatitis C of children, we wished to search for other PRRs, including other TLRs, NOD-like receptors (NLRs) and RIG-1-like helicase receptors (RLR) in infected hepatocytes. Liver biopsy fragments from ten children with chronic hepatitis B and C were used and two others in which hepatotropic virus infection was excluded. Frozen sections of liver samples were subjected to ABC immunohistochemistry (IHC) following incubation with a set of antibodies. Results of IHC findings were screened for correlation with clinical/laboratory data of patients. It was found that several PRRs could be shown in affected hepatocytes, but the incidence was higher in hepatitis C than in B. In hepatitis C, TLR1, 2, 4, NALP and RIG-1 h...
Pediatric inflammatory multisystem syndromes associated with Severe Acute Respiratory Syndrome Co... more Pediatric inflammatory multisystem syndromes associated with Severe Acute Respiratory Syndrome Coronavirus 2 are emerging in recent reports. We describe a patient with critical illness consistent with atypical Kawasaki disease with cardiac dysfunction and abdominal involvement presenting weeks after Severe Acute Respiratory Syndrome Coronavirus 2 infection. Our patient showed unique central nervous system involvement with small vessel vasculitis and profound hypocomplementemia, both not previously reported in case descriptions and may hint at possible disease mechanisms.
The aim of this study was to investigate the impact interferon type I based anti-viral therapy on... more The aim of this study was to investigate the impact interferon type I based anti-viral therapy on the immune system of chronically infected children with hepatitis C and B virus. Peripheral blood mononuclear cells were examined by three-color flow cytometry, using a panel of fluorochrome labeled monoclonal antibodies. It was found that the majority of white blood cell subsets were decreased in patients after termination of long-term anti-viral treatment. In particular, potentially cytotoxic, effector cell subsets, such as natural killer, natural killer T-lymphocytes and CD8 + CD28 - T cells were significantly decreased. Moreover, plasmacytoid dendritic cells were decreased, both in percentage and in absolute values. These data suggest that interferon-α based treatment, apart from its anti-viral effect, has also remarkable impact on patient's cell-mediated immunity.
Pediatric Gastroenterology, Hepatology & Nutrition, 2014
Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder in the absence of demo... more Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder in the absence of demonstrated stones. AAC is frequently associated with severe systemic inflammation. However, the exact etiology and pathogenesis of AAC still remain unclear. Acute infection with Epstein Barr virus (EBV) in childhood is usually aymptomatic, whereas it often presents as typical infectious mononucleosis symptoms such as fever, cervical lymphadenopathy, and hepatosplenomegaly. AAC may occur during the course of acute EBV infection, which is rarely encountered in the pediatric population. AAC complicating the course of a primary EBV infection is usually associated with a favorable outcome. Most of the patients recover without any surgical treatment. Therefore, the detection of EBV in AAC would be important for prediction of better prognosis. We describe the case of a 10-year-old child who presented with AAC during the course of primary EBV infection, the first in Korea, and review the relevant literature.
Background and Aim: Chronic hepatitis C (CHC) is still a significant clinical problem because of ... more Background and Aim: Chronic hepatitis C (CHC) is still a significant clinical problem because of not only a large proportion of infected individuals, but also unclear remote consequences of the disease. The aim of the study was to analyze the clinical course and the liver histology of CHC in children searching for potential influencing factors. Methods: Sixty-eight children were enrolled into the study (mean, 13.34 [SD, 3.27] years). Medical records and a current clinical status of children were analyzed considering clinical symptoms, liver function tests, and qualitative and quantitative hepatitis C virusYRNA assay with genotype and liver histology. Results: A parenteral route of infection concerned 98% of children; mean length of infection was 7.34 (SD, 4.03) years. Genotype 1a was found in 78% and 1b in 16.2% children. The history of malignancy was present in 74% of patients. The symptoms of liver cirrhosis with abnormal vein circulation were found in 2 children (3%). An increased alanine aminotransferase activity was detected in 62% of patients, whereas viral load less than 6 Â 10 5 IU/mL was found in 56 children (82%). Histological evaluation of biopsy specimens showed moderate inflammatory activity (G 2) and fibrosis (S 2 ; mean, 2.0). Progression of fibrosis was proportional to the age at infection. Conclusions: The clinical course of CHC is usually mild but may result in the liver cirrhosis during childhood. Transient or constant increased alanine aminotransferase activity is observed in majority of children. Inflammatory activity and fibrosis have moderate progression in children and are proportional to the age at infection.
Opiekun: dr hab. n. med. Iwona Mozer-Lisewska Zakażenia meningokokowe stanowią istotny problem ep... more Opiekun: dr hab. n. med. Iwona Mozer-Lisewska Zakażenia meningokokowe stanowią istotny problem epidemiologiczny, obarczony wysoką śmiertelnością. Cel pracy. Przedstawiono dziewięć przypadków chorobowych ilustrujących różnorodny obraz kliniczny i laboratoryjny zakażenia meningokokowego. Materiał i metody. Analizie poddano objawy kliniczne, wyniki badania przedmiotowego, biochemiczne i mikrobiologiczne wykładniki sepsy i inwazyjnej choroby meningokowej. Wyniki. Stwierdzono występowanie niecharakterystycznych objawów prodromalnych. Izolowana postać sepsy wystąpiła w pięciu przypadkach, w czterech rozpoznano inwazyjną chorobę meningokokową. Odnotowano występowanie istotnych zaburzeń koagulologicznych wskazujących na rozpoczynający się lub toczący proces wykrzepiania śródnaczyniowego. Dodatnie posiewy mikrobiologiczne pobranych materiałów uzyskano w siedmiu przypadkach. Wnioski. Zakażenie meningokokowe wykazuje dużą różnorodność przebiegu klinicznego. Stwierdzono korelację pomiędzy zaburzeniami koagulologicznymi a ciężkością choroby. Szybkie wdrożenie właściwego postępowania diagnostycznego i intensywnego leczenia nie gwarantuje sukcesu terapeutycznego. Słowa kluczowe: Neisseria meningitidis, sepsa, zespół wykrzepiania śródnaczyniowego (DIC), zespół Waterhouse-Friderichsena, zapalenie opon mózgowo-rdzeniowych Introduction. In spite of preventive measurements meningococcal infections are significant epidemiological problem with a burden of high mortality rate. Objective. Nine cases of meningococcal invasive disease (MID) were described to show varied clinical manifestations and laboratory findings. Patients and methods. Clinical symptoms were analysed including results of physical examination, clinical chemistry and microbiological features of sepsis and MID. Significant coagulation abnormalities were observed indicating initiating or existing process of disseminated intravascular coagulation. Positive culture results were obtained in 7 cases. Conclusions. Meningoccocal infections display varied clinical picture. Positive correlation between coagulation disorders and severity of disease was observed. Immediate implementation of proper diagnostic procedures and of early treatment does not guarantee therapeutic success.
Summary HIV epidemic started at the end of the twentieth century. The infection very quickly spre... more Summary HIV epidemic started at the end of the twentieth century. The infection very quickly spread to the whole world affecting over 33 million people globally. Women are considered half of the infected individuals mostly living in developing countries. In the countries where women's human rights are not respected, the risk of HIV-infection is much greater. First reports relating gender-related susceptibility to HIV-infection were published at the end of the twentieth century. The spread of the infection is associated with various biological and socio-economical factors. There is a strong need to reduce the burden of the epidemic among women. These include promotion and protection of women's human rights, increasing awareness among women and encouraging new preventative technologies. Mother-to-child transmission (MTCT) occurs when an HIV positive woman passes the virus to her baby during pregnancy, delivery, or breastfeeding. Estimated 2 million children living with HIV, which were in majority infected by their mothers. Significant proportion of these children will not live to adulthood. Despite existing antiviral treatment this way of prevention is unavailable in many regions. Although the world is effectively fighting with HIV epidemic, it is believed that more actions are required to restrict HIV transmission.
Lekarski I Akademii Medycznej im. K. Marcinkowskiego w Poznaniu Kierownik: prof. dr hab. med. Woj... more Lekarski I Akademii Medycznej im. K. Marcinkowskiego w Poznaniu Kierownik: prof. dr hab. med. Wojciech Służewski Wstęp. Wysoką mutagenność wirusa zapalenia wątroby typu C (HCV) oraz możliwość jego przetrwania w rezerwuarach pozawątrobowych, m.in. w mononuklearach krwi obwodowej (peripheral blood mononuclear cells-PBMCs) uważa się za jedne z głównych czynników utrudniających eliminację HCV z organizmu. Cel. Celem badania była analiza wpływu HCV RNA w PBMCs oraz aktywności aminotransferazy alaninowej (ALT) i wiremii HCV RNA w surowicy na uzyskanie trwałej odpowiedzi wirusologicznej (sustained virological response-SVR) u dzieci z przewlekłym wirusowym zapaleniem wątroby typu C (pwzw C) leczonych pegylowanym interferonem alfa i rybawiryną. Materiał i metody. Badaniem objęto 22 dzieci z rozpoznanym na podstawie ogólnie przyjętych kryteriów pwzw C leczonych pegylowanym interferonem alfa i rybawiryną. U dzieci poddano analizie przede wszystkim obecność HCV RNA w PBMCs oraz aktywność ALT i wiremię HCV RNA w surowicy. Wyniki. W zależności od uzyskanej w wyniku leczenia odpowiedzi wirusologicznej dzieci podzielono na grupę A (n = 15), która uzyskała SVR, i grupę B (n = 7), która nie wyeliminowała HCV RNA z surowicy. Wnioski. Na osiągnięcie SVR nie miała wpływu wyjściowa aktywność ALT czy wiremia HCV RNA. Obecność HCV RNA w PBMCs w momencie rozpoczęcia leczenia wydaje się nie mieć istotnego znaczenia dla osiągnięcia SVR. Ważna jest obserwacja pacjentów po leczeniu przeciwwirusowym z nieoznaczalnym HCV RNA w surowicy, ale obecnym zakażeniem w PBMCs. Leczenie przeciwwirusowe niejednoznacznie wpływa na zachowanie się wiremii HCV RNA w obrębie PBMCs. Słowa kluczowe: przewlekłe zapalenie wątroby typu C, interferon pegylowany, trwała odpowiedź wirusologiczna, mononukleary krwi obwodowej Introduction. The high mutagenic capacity of hepatitis C virus (HCV) and its ability to survive in extrahepatic reservoirs, i.e. peripheral blood mononuclear cells (PBMCs), are considered to be main causes of the difficulties in eliminating it. Aim. The aim of this study was to analyze the influence of HCV RNA in PBMCs, alanine aminotransferase (ALT) activity and HCV RNA viral load in serum on achieving of sustained virological response (SVR) in children with chronic hepatitis C (CHC) treated with pegylated interferon alpha and ribavirin. Patients and methods. Twenty-two children with CHC diagnosed according to current standard criteria were enrolled into the study. The children were treated with pegylated interferon alpha and ribavirin. The presence of HCV RNA in PBMCs, ALT activity and HCV RNA viral load in serum were analyzed in the study group. Results. On the basis of virological response to the treatment the children were divided in two groups: group A (n = 15) that achieved SVR, and group B (n = 7) that did not eliminate HCV RNA from serum. Conclusions. Baseline ALT activity and HCV RNA viral load did not influence achieving SVR. Careful observation of patients after antiviral treatment with negative HCV RNA in serum but positive results in PBMCs is essential. Antiviral treatment does not have an unequivocal effect on HVC RNA in PBMCs.
POSTERS to evaluate the diagnostic performance of serum YKL-40 and HA as noninvasive markers of l... more POSTERS to evaluate the diagnostic performance of serum YKL-40 and HA as noninvasive markers of liver fibrosis in KT patients with HCV chronic infection. Methods: This cross-sectional study included KT individuals with positive HCV-RNA, with biopsy-proven chronic hepatitis. Univariate analysis was used to identify variables associated with clinically significant fibrosis (F2, F3 or F4 METAVIR stages). The diagnostic values of the YKL-40 and HA were compared using receiver operating characteristic (ROC) curves. Results: 85 patients were included (60% males, mean age 44.9±9.4 years). The mean time since transplantation (TST) was 6.5±4.9 years and significant fibrosis was observed in 14 patients (17%). Patients with significant fibrosis, as compared to those with F0/F1 stages, were older (48.6±5.1 vs. 44.2±10.0 years, P = 0.020), showed a higher TST (10.1±5.4 vs. 5.7±4.5 years, P = 0.002) and higher prevalence of diabetes (85% vs. 28%, P < 0.001). Subjects with significant fibrosis also exhibited higher serum levels of YKL-40, although this difference did not reach statistical significance (292±163 ng/dL vs. 233±154 ng/dL, P = 0.198). Significantly higher median levels of HA were noted in subjects with METAVIR F2 (108 ng/dL vs. 37 ng/dL, P = 0.002). The AUROCs of YKL-40 and HA for predicting significant fibrosis were 0.615 and 0.765, respectively (P = 0.144). Based on ROC curves, two cutoffs were chosen for each marker. The diagnostic performances of the proposed cutoffs are summarized in the table below. If biopsy indication was restricted to patients with YKL-40 and HA levels in the intermediate range, 32% and 35% of liver biopsies could have been correctly avoided, respectively. Conclusions: YKL-40 and HA are promising markers of liver fibrosis in KT patients with chronic HCV infection.
Background and Aims: Renal toxicity of first generation protease inhibitors (IP) was not a safety... more Background and Aims: Renal toxicity of first generation protease inhibitors (IP) was not a safety signal in phase III clinical trials, until Mauss et al.’s report in Hepatology. Methods: We retrospectively analyzed 101 HCV patients receiving triple therapy with telaprevir (n = 36) or boceprevir (n = 26) or double therapy (n =39) and a close monitoring of eGFR (MDRD formula) during and after treatment (D0, W4, 8, 12, 16, 24, 36, 48, 60, 72). Changes in eGFR over time were assessed by a linear mixed effects model (LMEM) with search for possible explanatory covariates. Results: Patients treated with telaprevir, presented a significant decrease of eGFR with the same kinetics: initial decrease at W4, nadir at W8 (mean decrease 17.0±18.9ml/min/1.73m2) and in average normalization at W16. The W8eGFR was highly correlated with the D0eGFR (R = 0.49) and was significantly lower in patients with grade II anemia or more (p = 0.031). The LMEM showed that the slope of eGFR versus time was the same for all patients and eGFR nadir could be predicted. In multivariate analysis, eGFR during the first 8 weeks was associated with time, older age, male sex and cryoglobulinemia. Conclusions: The eGFR significantly varied in telaprevir group only. Our model showed that eGFR nadir mainly depended on initial eGFR. As telaprevir was shown to inhibit mostly the human renal drug transporter OCT2 which interacts with creatinin transport, the early decrease of eGFR observed could be a benign phenomenom. However, as true and unpredictable renal toxicity may occur at any time during therapy, we recommend a thorough follow-up of eGFR.
International Journal of Infectious Diseases, 2010
Background: Chronic hepatitis B (CHB) is still a significant clinical problem In the whole Word. ... more Background: Chronic hepatitis B (CHB) is still a significant clinical problem In the whole Word. It is estimated that 2 milliard people had contact with hepatitis B virus (HBV) and 400 millions suffer from CHB or its remote consequences. The study was aimed at remote analysis of the incidence of seroconversion in HBeAg/anti-HBe and HBsAg/anti-HBs after antiviral treatment and their relation to age at infection as well as evaluation of aminotransferase activity and chosen biochemical parameters. Methods: The study included 310 children (220 boys and 90 girls) with diagnosed CHB who underwent antiviral treatment with interferon-alpha (IFN-alpha) or lamivudine. 177 children were treated with IFN-alpha, 25 with lamivudine and 107 children were treated with lamivudine after prior lack of response to IFN-alpha treatment. Mean age at HBV infection diagnosis was 4.14 ± 3.23 years. Mean age At the beginning of observation was 6.93 ± 3.69 years. Mean length of follow-up was 7.11 ± 2.39 years. Results: In 222 children (71.6%) seroconversion in HBeAg/anti-HBe was present-on the average 6.69 ± 3.02 after the diagnosis and 2.19 ± 1.47 after the introduction of antiviral treatment. The group of children treated with IFN-alpha was introduced 3.72 ± 2.12 years and lamivudine 6.38 ± 3.71 years after the diagnosis of HBV infection. Reverse relation was found between the incidence of seroconversion and the age at diagnosis (r = −0,30; p < 0,001). ALT and AST activity at HBV diagnosis was compared in children with and without seroconversion. Children with HBeAg/anti-HBe seroconversion had higher aminotrasferase at the diagnosis of HBV infection in comparison with patients without seroconversion. Viral load in children with seroconversion revealed significant alterations in the following years of the follow-up period in children with seroconversion (p < 0.0089). Similar changes were not present in children without seroconversion. Conclusion: Age at infection seem to be a significant factor influencing the incidence of seroconversion. ALT and AST activity at the diagnosis is a good prognostic factor of HBeAg/anti-HBe and HBsAg/anti-HBs seroconversion.
International Journal of Infectious Diseases, 2010
e229 occult HBV infection isn't frequent in Iranian thalassemic patients who suffering from chron... more e229 occult HBV infection isn't frequent in Iranian thalassemic patients who suffering from chronic HCV infection.
The hepatitis C virus (HCV) is a globally prevalent human pathogen that causes persistent liver i... more The hepatitis C virus (HCV) is a globally prevalent human pathogen that causes persistent liver infections in most infected individuals. HCV is classified into seven phylogenetically distinct genotypes, which have different geographical distributions and levels of genetic diversity. Some of these genotypes are endemic and highly divergent, whereas others disseminate rapidly on an epidemic scale but display lower variability. HCV phylogeny has an important impact on disease epidemiology and clinical practice because the viral genotype may determine the pathogenesis and severity of the resultant chronic liver disease. In addition, there is a clear association between the HCV genotype and its susceptibility to antiviral treatment. Similarly to other RNA viruses, in a single host, HCV exists as a combination of related but genetically different variants. The whole formation is the actual target of selection exerted by a host organism and antiviral therapeutics. The genetic structure of the viral population is largely shaped by mutations that are constantly introduced during an error-prone replication. However, it appears that genetic recombination may also contribute to this process. This heterogeneous collection of variants has a significant ability to evolve towards the fitness optimum. Interestingly, negative selection, which restricts diversity, emerges as an essential force that drives HCV evolution. It is becoming clear that HCV evolves to become stably adapted to the host environment. In this article we review the HCV phylogeny and molecular evolution in the context of host-virus interactions.
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