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

Renal impairment in patients with chronic hepatitis C treated with first generation protease inhibitors

<div><p><b><i>Background</i></b>: The incidence, course and risk factors associated with renal impairment (RI) in patients treated with triple therapy (TT) with pegylated interferon, ribavirin and telaprevir/boceprevir (PR/TVR/BOC) vs. dual therapy (DT) with PR were analyzed in this study. The association between RI and the decline of hemoglobin (Hb) was also examined.</p><p><b><i>Methods</i></b>: Retrospective analysis included 110 patients with genotype 1b chronic HCV infection, aged 18 – 80 years, who underwent TT (48TVR/14BOC) or DT (48 patients). The estimated glomerular filtration rate (eGFR), serum creatinine concentration (SCr) and Hb were measured at baseline, at weeks 4, 12, 24, 48 of treatment, and post-treatment week 24.</p><p><b><i>Results</i></b>: RI occurred in 9/62 (14.5%) patients who underwent TT, eight of whom were treated with TVR, one with BOC, and none treated with DT. The risk factors associated with RI were the following: TT (p = 0.0078), usage of nephrotoxic drugs (p = 0.0288), and older age (p < 0.0001). RI was reversible. A drop of Hb was associated with RI, older age and TT.</p><p><b><i>Conclusions</i></b>: RI is not a rare but a reversible complication of TT. It is necessary to monitor SCr and eGFR, especially in patients with a potential risk factor of RI occurrence. The Hb drop is more severe in patients with RI than in those without it.</p></div

The Impact of IL28B Genotype and Liver Fibrosis on the Hepatic Expression of IP10, IFI27, ISG15, and MX1 and Their Association with Treatment Outcomes in Patients with Chronic Hepatitis C.

The strong impact of interleukin 28B (IL28B) polymorphisms on sustained virological response (SVR) after peginterferon and ribavirin treatment in patients with chronic hepatitis C (CHC) is well-known. We investigated IL28B variability and hepatic expression of IP10, IFI27, ISG15, and MX1 in CHC patients, the relation of each with their clinical characteristics, and how they associated with responses to combined therapy. Genotyping and gene expression analysis were conducted in a selected cohort of treatment-naïve patients who underwent interferon and ribavirin treatment. Differential expression of IP10, IFI27, ISG15, and MX1 genes was assessed from pretreatment liver biopsies using quantitative PCR. Histopathological evaluation of liver specimens was performed on the basis of the Scheuer's modified scale. We showed that hepatic IFI27, ISG15, and MX1 expression was lower in the IL28B CC 12979860 and TT rs8099917 groups than in the CT-TT rs12979860 and TG-GG rs8099917 groups (P < 0.001). We found no differences in IP10 expression between the IL28B genotypes (P > 0.05); in contrast, IP10 expression was significantly affected by the progression of fibrosis (P = 0.007). We showed that the rs12979860 CC genotype was associated with successful treatment when compared to the rs12979860 CT-TT genotype (P = 0.004). Additionally, the expression levels of IP10, IFI27 and ISG15, but not MX1, were significantly higher in non-SVR patients than in SVR patients. The effect of variation in IL28B on the results of IFN-based treatment may be associated with changes in IFI27 and ISG15, but not with IP10. Silencing of IP10 is positive and independent from IL28B prediction of SVR, which is strongly associated with liver fibrosis in CHC patients

Thromboprophylaxis in patients with Covid-19

Abstract For two years, the entire world has been grappling with the new challenge that is the Covid-19 pandemic. In December 2019 in China’s largest province, Wuhan, Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), was detected in a patient with severe respiratory failure. Shortly after, infections were detected in all regions of the world. So far, 265 million infections have been confirmed around the world, and 5.2 million of those infected have died due to Covid-19. Infection with SARS-CoV-2 is associated with an increased risk of cardiovascular complications, especially thromboembolic complications. Low-molecular-weight-heparin presents a basic form of prophylaxis against thromboembolic complications in individuals who are ill with COVID-19. Controversy still exists regarding the optimal dose of LMWH depending on disease severity, this problem requires further randomised trials

Venous Thromboembolic Disease in COVID-19, Pathophysiology, Therapy and Prophylaxis

For over two years, the world has been facing the epidemiological and health challenge of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Growing problems are also complications after the development of COVID-19 in the form of post and long- COVID syndromes, posing a challenge for the medical community, both for clinicians and the scientific world. SARS-CoV-2 infection is associated with an increased risk of cardiovascular complications, especially thromboembolic complications, which are associated with both thrombosis of small and very small vessels due to immunothrombosis, and the development of venous thromboembolism. Low molecular wight heparin (LMHW) are the basic agents used in the prevention and treatment of thromboembolic complications in COVID-19. There is still a great deal of controversy regarding both the prevention and treatment of thromboembolic complications, including the prophylaxis dose or the optimal duration of anticoagulant treatment in patients with an episode of venous thromboembolism

Association between IP10 expression and the progression of liver fibrosis.

<p>The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of expression levels. The <i>P</i> value was obtained by the Kruskal-Wallis test. F0, F1, F2, and F3 (fibrosis stages) are defined according to the modified Scheuer classification.</p

Impact of fibrosis stage and IL28B genotype on hepatic IP10 expression.

<p>Levels of IP10 expression were determined by rs12979860 (A) and rs8099917 (B) IL28B genotypes in patients, stratified by fibrosis F0-1 and F2-4 groups. Conversely, levels of IP10 expression were also determined according to the F0-1 and F2-4 fibrosis grouping in patients stratified by rs12979860 (C) and rs8099917 (D) IL28B genotypes. The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of gene expression levels. n = number of patients in each group.</p

Association between the hepatic expression of IP10, IFI27, ISG15, and MX1 with F0-1 and F2-4 fibrosis.

<p>The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of expression levels. Fibrosis stages are defined according to the modified Scheuer classification.</p