Zapalenia tarczycy występujące w czasie leczenia interferonem przewlekłego zapalenia wątroby typu C

Thyroid function disorders affect between 5% and 15% of patients treated with IFNα and RBV for chronic hepatitis C. Women and patients with thyroid peroxidase antibodies (TPOAb) found before the treatment are at risk of developing the disorders (46.1% vs. 5.4%). The spectrum of IFNα-induced thyroiditis (IIT) includes two groups. Disorders with an autoimmune background are: presence of thyroid autoantibodies without clinical disease, Hashimoto’s disease and Graves’ disease. The second group comprises diseases caused by the direct toxic effect of IFNα on the thyroid gland, i.e. destructive thyroiditis and non-autoimmune hypothyroidism. Thyroid diseases are not an absolute contraindication for IFNα and RBV therapy. In patients diagnosed with thyroid dysfunction, before the antiviral therapy it is necessary to achieve euthyreosis. Thyroid function disorders may occur at any moment of the therapy. The earliest have been observed in the 4th week of treatment, and the latest 12 months after its termination. During the therapy, in order to diagnose IIT early, it is recommended to determine TSH level every 2–3 months depending on the presence of TPOAb before the treatment. The diagnosis and treatment of thyroid function disorders should be conducted in co-operation with an endocrinologist.Zaburzenia funkcji tarczycy dotyczą 5 do 15% leczonych IFNα i RBV z powodu przewlekłego zapalenia wątroby typu C. Zagrożone ich wystąpieniem są kobiety oraz chorzy, u których stwierdzono przed leczeniem obecność przeciwciał przeciwko tyreoperoksydazie (TPOAb) (46,1% v. 5,4%). Spektrum zapaleń tarczycy wywołanych przez IFNα (IIT) obejmuje dwie grupy. Do zaburzeń o podłożu autoimmunologicznym zalicza się: obecność przeciwciał przeciwtarczycowych bez objawów klinicznych choroby tarczycy, chorobę Hashimoto i chorobę Gravesa. Drugą grupę stanowią choroby spowodowane bezpośrednim toksycznym działaniem IFNα na tarczycę, tj. destrukcyjne zapalenie tarczycy, nieautoimmunologiczna niedoczynność tarczycy. Choroby tarczycy nie są bezwzględnym przeciwwskazaniem do leczenia IFNα i RBV. U chorych z rozpoznaną przed rozpoczęciem terapii przeciwwirusowej dysfunkcją tarczycy należy uzyskać eutyreozę. Zaburzenia funkcji tarczycy mogą się pojawić w każdym momencie terapii. Najwcześniej obserwowano ich rozwój w 4. tygodniu leczenia, najpóźniej 12 miesięcy po jego zakończeniu. W czasie terapii w celu szybkiego wykrycia IIT zaleca się oznaczanie TSH co 2 lub 3 miesiące, w zależności od obecności TPOAb przed leczeniem. Diagnostyka i leczenie zaburzeń funkcji tarczycy powinny być prowadzone przy współudziale lekarza endokrynologa

Ostra agranulocytoza w przebiegu leczenia przewlekłego zapalenia wątroby typu C powikłanego nadczynnością tarczycy. Opisy przypadków

Agranulocytosis is a life-threatening disorder characterised by a greatly decreased number of circulating neutrophils below 500/μL. This article presents two cases of agranulocytosis in patients treated with pegylated interferon and ribavirin due to chronic hepatitis C. Interferon induced hyperthyroidism, which required the use of a tyreostatic. Anti-thyroid drugs (ATD) used to treat hyperthyroidism can cause agranulocytosis. The synergistic reaction of ATD and interferon on bone marrow cannot be excluded.Agranulocytoza jest stanem bezpośredniego zagrożenia życia rozpoznawanym, gdy liczba granulocytów obojętnochłonnych jest niższa niż 500/μl. Przedstawiono dwa przypadki ostrej agranulocytozy, która wystąpiła u pacjentów leczonych pegylowanym interferonem i rybawiryną z powodu przewlekłego zapalenia wątroby typu C. Interferon spowodował nadczynność tarczycy wymagającą zastosowania tyreostatyku. Tyreostatyki stosowane w leczeniu nadczynności tarczycy mogą być przyczyną agranulocytozy. Nie można wykluczyć ich synergistycznego działania z interferonem na szpik kostny

Systemic inflammatory response syndrome and sepsis – epidemiology, differentiation, diagnostics in in clinical practice

Bacterial infection is an important factor causing morbidity and mortality in different populations. Every time exacerbation of infectious response (strength, time of symptom severity, time of progression) and whole cascade of inflammatory reaction is dependent on the efficiency of the organism’s homeostasis. In many situations, especially in case of patients with a decrease level of immune system efficiency, we observe very dynamic intensification of infection and inflammation symptoms. Every time the inflammatory response affect whole body functions and manifests itself in change of biochemical, hematological, and immunological parameters. Those changes are visible specially during systemic inflammatory response. SIRS (systematic inflammatory response syndrome) and sepsis with high levels of incidence and mortality from many years it is a the large diagnostic and therapeutic problem in clinical practice. Annual mortality caused by sepsis which reaches 30 and 50 deaths per 100 000 population, makes it classified as one of a top causes of death among patients under hospital care. Due to its dynamic nature of its course, it is necessary to thoroughly understand its course which may contribute to the search for more effective biochemical and hematological diagnostic markers which will allow to shorten the time of implementation of effective therapy and decrease mortality. The aim of this study was to present the specifity of a SIRS and sepsis and to show its progression, complications and available tools and methods of its diagnosis in clinical practice

HBV DNA suppression during entecavir treatment in previously treated children with chronic hepatitis B

The aim of this study was to assess HBV DNA suppression after 24 weeks of treatment with entecavir in previously treated children with CHB. Thirty children aged 5–17 years (25 males and 5 females) with CHB were treated with entecavir 0.5 or 1 mg daily. Twenty-two children were HBeAg-positive, eight were HBeAg-negative, and in eight HBV polymerase mutations were detected. After 24 weeks of treatment, mean and median HBV DNA levels and ALT activity were lower versus baseline, overall and in both subgroups. The overall median HBV DNA level decreased from 1.2 x 107 IU/mL to 3.3 x 102 IU/mL (p < 0.000004), in HBeAg-positive from 7.8x107 IU/mL to 6.3x103 IU/mL (p < 0.00004), and in HBeAg-negative from 2.5x104 IU/mL to 5.01x101 IU/mL (p < 0.03). The serum HBV DNA disappearance was observed in 7/8 (88%) HBeAg-negative and in 5/22 (23%) HBeAg-positive patients. The overall mean ALT activity decreased from 164+ 290 U/L to 34.1+ 18.9 U/L (p < 0.000007), in HBeAg-positive from 214+326 U/L to 38.59+19.2 U/L (p < 0.000074), and in HBeAg-negative from 27+14 U/L to 20+8 U/L (p < 0.03). Twenty-four weeks of treatment with entecavir results in suppression of HBV DNA in a substantial proportion of children previously treated ineffectively with CHB

Impact of IL-28B polymorphisms on pegylated interferon plus ribavirin treatment response in children and adolescents infected with HCV genotypes 1 and 4

IL-28B polymorphisms are predictors of response to therapy in adults infected with hepatitis C. We do not know whether they are markers of response to therapy in children and adolescents. The aim of this study was to determine whether single-nucleotide polymorphisms (SNPs) in the IL-28B gene could influence the probability of response to therapy compared with other known baseline prognostic factors and correlate with clinical findings in pediatric patients infected with hepatitis C virus (HCV) genotypes 1 or 4. We determined three SNPs of IL-28B (rs12979860, rs12980275, and rs8099917) in 82 patients with chronic HCV infection treated with pegylated interferon alpha and ribavirin (peg-IFNα/RBV). Treatment response and clinical data were analyzed. Overall, sustained virological response (SVR) was achieved by 45 % of patients infected with difficult-to-treat HCV genotypes 1 and 4. Except for IL-28B polymorphisms, there was no association of SVR with any other clinical data. IL-28B rs12979860 CC [odds ratio (OR), 6.81; p = 0.001] and rs8099917 TT (OR, 3.14; p = 0.013) genotypes were associated with higher SVR rates. IL-28B rs12980275 was not significantly associated with SVR ( p = 0.058). Only the distribution between CC and CT-TT genotypes of rs12979860 significantly differentiated patients achieving early virological response (EVR) (OR, 10.0; p = 0.011). Children with the rs12979860 CC genotype had significantly higher baseline viral load compared with CT-TT patients ( p = 0.010). In children and adolescents chronically infected with HCV genotypes 1 and 4, IL-28B rs12979860 and rs8099917 polymorphisms were the only predictors of response to peg-IFN/RBV

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin