Implementation of Microelimination Strategy in Eradication of Chronic Hepatitis C Infection in Patients with Hemophilia in the Northern region of Serbia: Is Eradication Possible?

BACKGROUND: Treating HCV in people with hemophilia prevents the development of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) and greatly increases the quality of life for people living with hemophilia. There are many obstacles in reaching the WHO goal of globally eradicating HCV by 2030, mainly its scale, complexity, and implementation. That is why many countries have implemented a micro-elimination strategy: a pragmatic elimination approach in populations with the most efficacy. The aim of this publication is to present the morbidity and mortality rates, the clinical course and treatment outcomes of chronic HCV infection in people with hemophilia (PwH), as well as to show an example of a successfully conducted HCV micro-elimination strategy among people with hemophilia in the Province of Vojvodina. METHODS: A retrospective, single-center study, performed using medical documentation of all registered PwH in the Clinical Center of Vojvodina from 1994. until 2020. It included 74 hemophilia patients, out of which 32 were patients with hemophilia and chronic HCV infection. RESULTS: The mean age of HCV-positive positive people with hemophilia (PwH) was 42.3 years, with the duration of infection of 30-35 years. Co-infection with HIV was observed in 6.25% of cases. Furthermore, 18.75% of patients had spontaneous HCV elimination, and 75% were treated with antiviral protocols. Cirrhosis developed in 21.87% with an incidence rate of 0.6 per 100 patient-years. After treatment with Pegylated IFN and ribavirin (RBV), 58.3% achieved SVR. Side effects of IFN-based therapy regimens were recorded in 20.8% of treated (PwH). In 37.5% PWH, DAA protocols were administered, and these patients achieved SVR. HCV- PwH have a statistically higher mortality rate than non-infected people with hemophilia. Among the HCV-positive PwH, hemophilia-related deaths were 6.25%, and HCV-related deaths were 9.37%. Currently, in the Registry of PwH in Vojvodina, there are no patients with active HCV infection. CONCLUSION: The micro-elimination strategy in the subpopulation of PwH was successfully implemented in Vojvodina by hematologists and infectious diseases specialists in close collaboration.

Angiogenesis and survival in patients with myelodysplastic syndrome.

Angiogenesis has been implicated in the pathogenesis and prognosis of myelodysplastic syndrome (MDS). In this study, we investigated the relationship between microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, common morphological and clinical factors, and survival in patients with MDS. We examined the MVD of paraffin-embedded bone marrow sections from 70 MDS patients and 31 controls. VEGF expression was determined in 50 patients and 20 controls. The median MVD in MDS patients was significantly higher than that in controls (p = 0.025), whereas there was no difference in VEGF expression between MDS patients and controls. In univariate analysis, increased MVD was associated with a shorter survival time (p = 0.023). However, in multivariate analysis, MVD was not an independent predictor of survival. The VEGF expression did not influence survival in univariate analysis. Survival was independently influenced by platelet count (p = 0.0073), cytogenetic risk category (p = 0.022), and transfusion dependence (p = 0.0073). Neither MVD nor VEGF expression were predictors for progression to acute myeloid leukemia in univariate analysis. Progression to acute myeloid leukemia was independently influenced only by the cytogenetic risk category (p = 0.022). This study confirmed increased MVD in MDS. It does not support an independent prognostic role of angiogenesis in MDS.

The hematopoietic cell transplantation comorbidity index is a predictor of early death and survival in adult acute myeloid leukemia patients.

The hematopoietic cell transplantation comorbidity index (HCT-CI) is predictive of early death and survival in elderly patients with acute myeloid leukemia (AML). The aim of this study was to determine the prognostic role of the HCT-CI for early death and survival in adult AML patients. In the single-center retrospective study, we analyzed the outcome of 233 adult AML patients. The results indicated that the HCT-CI score is an independent predictor of early death in entire cohort of adult patients with AML. In subgroup analysis, HCT-CI is an independent predictor for early death in elderly patients but not in patients younger than 60 years. A high HCT-CI score predicts shorter survival in adult patients with AML.

[Clinical and prognostic significance of CD34 expression in bone marrow biopsies in myelodysplastic syndrome].

INTRODUCTION: The expression of CD34 antigen is increased in a substantial portion of MDS patients, particularly in high risk patients, which was associated with unfavorable survival in some studies. The aim of this study was to determine the CD34 expression in bone marrow biopsies and its prognostic significance in MDS patients and to analyze it in the context of different clinical, laboratory and prognostic parameters. MATERIAL AND METHODS: The study was conducted in 53 MDS patients and 20 controls with normal bone marrow. The CD34 expression was determined by CD34 monoclonal antibody and labelled streptovidin biotin peroxidase method. The positivity was determined by counting the 500 cells and it was expressed as percentage. RESULTS: Among the 53 MDS patients there were 37 males and 16 females with average age of 62. The average CD34 expression in the MDS group was 1.37%, the range being 0-8.8%, and in the control group 0.78%, the range being 0-1.60%. The difference was statistically significant (p < 0.05). There was a statistically significant difference in the CD34 expression comparing RA and CMML group and high risk and low risk MDS (p < 0.02). The median survival in the patients with the CD34 expression with less than 2% was 22 months, while it was 6 months in the patients with the CD34 expression over 2% (p < 0.05). In a multivariate analysis the CD34 expression together with the karyotype and transfusion dependence had a statistical significance (p < 0.05). CONCLUSION: The CD34 expression in bone marrow biopsies is higher in the MDS patients comparing with the controls as well as in high risk comparing with low risk patients. The cutoff 2% seems to have a prognostic significance.

Syngeneic peripheral blood stem cell transplantation with immunosuppression for hepatitis-associated severe aplastic anemia.

Hepatitis-associated aplastic anemia occurs in up to 10% of all aplastic anemia cases. Syngeneic bone marrow transplantation is rare in patients with severe aplastic anemia and usually requires pre-transplant conditioning to provide engraftment. We report on a 29-year-old male patient with hepatitis-associated severe aplastic anemia who had a series of severe infectious conditions before transplantation, including tracheal inflammation. Life-threatening bleeding, which developed after bronchoscopy, was successfully treated with activated recombinant factor VII and platelet transfusions. Syngeneic peripheral blood stem cell transplantation using immunosuppressive treatment with antithymocyte globulin and cyclosporin A without high-dose pre-transplant conditioning was performed, followed by complete hematologic and hepatic recovery.

[Viral form of hemophagocytic syndrome with erythrodermal clinical picture--case report].

INTRODUCTION: Hemophagocytic syndrome is patophysiological entity with proliferation and over-activation of macrophages, with hemophagocytosis and production of proinflammatory cytokines. It arises as hereditary forms, or acquired, during viral, autoimmune or malignant diseases, and is usually a disorder with fulminant course and high incidence of lethal outcome. The precise mechanism is not resolved; it is a consequence of cytokine storm generated by over-activated T cells and macrophages, due to defects in T cellular cytototoxic function and inadequate down-regulation of immune response. CASE REPORT: A male patient, 26 years old, previously healthy, is presented. Generalized exfoliative dermatitis and lymphadenomegalia had lasted for half a year before admission to the hospital. Hemophagocytosis in lymph gland histology was diagnostic, with T cellular immunohistochemical profile CD3+, CD5-, CD8/-, CD43+/-, CD45RO+, bcl-2+, and numerous CD68+ histiocytes. Apart from elevated titer of Adenovirus serology, other laboratory findings and bone marrow histology were within normal limits. Two weeks of oral antibiotic and topical skin corticosteroid therapy were followed by a rapid improvement of clinical features. Residual skin lesions, linear petechia and flares of pale pink erythema used to recur for the next half a year. During the follow up, two years later there was no lymph gland enlargement, skin rash, or other signs. DISCUSSION: The diagnosis of virus-associated hemophagocytic syndrome with mild clinical course and seemingly spontaneous improvement was established, although it did not fulfill all proposed diagnostic criteria. It is possible that it increased the clinical awareness for these mild forms in immune-competent patients could account for the improved recognition of atypical cases with favorable outcome.