Interleukin 28B-related polymorphisms: A pathway for understanding hepatitis C virus infection?

AIM:To analyze the role of rs12979860 and rs8099917polymorphisms in hepatitis C virus(HCV)genotype 1infection of Brazilians.METHODS:A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C(CHC)who had completed a 48-wk regimen of pegylated-interferonα-2a or-2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and199 healthy blood donors(controls)from a single site between January 2010 and January 2012.Data on the patients’response to treatment was collected.Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin(IL)28B gene fragment encompassing the single nucleotide polymorphisms(SNPs)rs12979860(C/T)and rs8099917(T/G)was carried out for 79 of the CHC patients and 199 of the controls.Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients.RESULTS:SNP rs12979860 genotyping was successful in 99.5%of the controls and 97.2%of the CHC patients,whereas the SNP rs8099917 genotyping was successful in 95.5%of the controls and 100%of the CHC patients.The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups,with significantly higher genotype frequencies of CC and TT in the controls(P=0.037 and 0.046,respectively)and of TT and GG in the CHC patients(P=0.0009and 0.0001,respectively).Analysis of the CHC patients who achieved sustained virological response(SVR)to treatment(n=55)indicated that the rs12979860 C allele and CC genotype were predictors of SVR(P=0.02).No significant correlation was found between rs8099917 genotypes and treatment response,but carriers of the T allele showed significantly higher rates of SVR(P=0.02).Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917(P=0.07).CONCLUSION:The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCVinfected individuals may indicate a potential pro     

Factor VIII and IX deficiencies related to acquired inhibitors in a patient with chronic hepatitis C virus infection receiving treatment with pegylated interferon plus ribavirin

The development of clotting factor inhibitor autoantibodies is rarely observed, but can result in a potentially life-threatening haemorrhagic disorder. These acquired inhibitors are most frequently against factor VIII (FVIII), whilst the detection of inhibitors against other clotting factors is rarer. Inhibitors against FVIII and FIX are mostly observed in patients with classical hereditary haemophilia after receiving factor replacement therapy. We report a rare case of acquired FVIII and factor IX (FIX) inhibitors in a single, non-haemophilic patient with chronic hepatitis C virus (HCV) infection who was receiving antiviral treatment with pegylated interferon plus ribavirin. The FVIII and FIX activities were <1% and high titres of inhibitors autoantibodies were found in his serum samples. After achieving a sustained virological response, combined immunosuppression with oral corticosteroids (prednisone) and azathioprine was introduced, eradicating the inhibitory autoantibodies. The development of these inhibitors in association with antiviral therapy for chronic hepatitis C is poorly understood, and particular attention must be given to HCV-infected patients with worsening coagulopathy, particularly if coexistent with treatment related thrombocytopenia.     

Dried blood spot sampling as an alternative for the improvement of hepatitis B and C diagnosis in key populations

BACKGROUNDTo achieve the elimination of hepatitis B and C, there is an urgent need to develop alternative strategies to increase the access of diagnosis, particularly among key populations such as people living with human immunodeficiency virus (HIV), individuals with coagulopathies and chronic kidney disease (CKD) patients. AIMTo evaluate the use of dried blood spot (DBS) in the detection of hepatitis B virus (HBV) and hepatitis C virus (HCV) markers. METHODSA total of 430 individuals comprised of people living with HIV, coagulopathies and CKD provided paired serum and DBS samples. HBsAg, anti-HBc and anti-HCV were tested in those samples using a commercial electrochemiluminescence. Demographic and selected behavioral variables were evaluated to assess possible association with HBV and HCV positivity. RESULTSUsing DBS, HBsAg prevalence varied from 3.9% to 22.1%, anti-HBc rates varied from 25.5% to 45.6% and anti-HCV positivity ranged from 15.9% to 41.2% in key populations. Specificities of HBV and HCV tests using DBS varied from 88.9% to 100%. The HBsAg assay demonstrated the best performance in CKD and coagulopathy individuals and the anti-HCV test had a sensitivity and specificity of 100% in people living with HIV. Accuracy of HBV and HCV detection in DBS varied from 90.2% to 100%. In the CKD group, HBsAg positivity was associated with infrequent use of condoms, and anti-HBc positivity was associated with sharing nail cutters/razors/toothbrushes. Anti-HCV reactivity was positively associated with a history of transplantation and length of time using hemodialysis in both specimens. In people living with HIV, only the male gender was associated with anti-HBc positivity in serum and DBS.CONCLUSIONDBS with electrochemiluminescence are useful tools for the diagnosis and prevalence studies of hepatitis B and C among key populations and may increase the opportunity to foster prevention and treatment.     

Medical and related aspects of the Goiania accident: an overview

On 13 September 1987, a radiation accident occurred in the city of Goiania in Central Brazil. Approximately 250 people were exposed to a 137Cs source from an abandoned radiotherapy unit. At least 14 patients showed some degree of bone marrow depression, and eight developed the classical signs and symptoms of acute radiation syndrome (ARS). Twenty-eight people presented local radiation injuries ranging from first to third degree, and 104 individuals showed evidence of internal contamination. This paper describes the circumstances of the event, the first-aid measures taken, the criteria adopted for triage of the exposed population, and the radiation protection procedures used during the clinical management of the irradiated individuals.     

Clinical and hematological aspects of 137Cs: the Goiania radiation accident

Fifty persons involved in the 137Cs accident in Goiania showed symptoms of whole-body and local acute irradiation and also external or internal contamination mainly due to ingestion or absorption of 137Cs. Fourteen of the 50 developed severe bone marrow depression characterized by neutropenia and thrombocytopenia. Eight of these 14 received GM-CSF intravenously. None were submitted to bone marrow transplantation. Four of the 14 died due to hemorrhage and infection. For those with significant internal contamination evaluated by in-vitro and in-vivo assays, Prussian Blue was administered with doses ranging from 1.5 to 10 g d-1. Besides Prussian Blue, other measures were taken to increase decorporation of 137Cs, including administration of diuretics, water overload, and ergometric exercises. From 50 to 100 persons are being followed in a medical protocol.     

Novel biodosimetry methods applied to victims of the Goiania accident

Two biodosimetric methods under development at the Lawrence Livermore National Laboratory were applied to five persons accidentally exposed to a 137Cs source in Goiania, Brazil. The methods used were somatic "null" mutations at the glycophorin A locus detected as missing proteins on the surface of blood erythrocytes and chromosome translocations in blood lymphocytes detected using fluorescence in-situ hybridization. Biodosimetric results obtained approximately 1 y after the accident using these new and largely unvalidated methods are in general agreement with results obtained immediately after the accident using dicentric chromosome aberrations. Additional follow-up of Goiania accident victims will 1) help provide the information needed to validate these new methods for use in biodosimetry and 2) provide independent estimates of dose.