Long-term outcome of vertically acquired and post-transfusion hepatitis C infection in children

BACKGROUND AND AIM: To determine the natural history of perinatally acquired hepatitis C virus (HCV) infection, clinical and laboratory outcomes among 31 children with HCV infection were retrospectively reviewed. Fifteen children had acquired HCV by blood transfusion (BT) prior to 6 months of age and 16 had vertically acquired (VT) HCV. METHODS: Demographic data, clinical symptoms and signs, liver biochemistry, HCV antibody, HCV-RNA and liver histology were evaluated. RESULTS: Mean age at last visit was 13.0 years (range 9.0-16.8 years) in the BT group and 8.6 years (range 0.5-18.1 years) in the VT group. There were no abnormal clinical findings of chronic liver disease in either group. Estimated HCV-RNA clearance rate was 19%, with no significant difference between the groups. In HCV-RNA-negative children (n = 6), two lost anti-HCV antibody and two developed indeterminate anti-HCV antibody results, while all HCV-RNA-positive children (n = 25) remained both anti-HCV antibody positive and HCV-RNA positive throughout follow up. The alanine aminotransferase level was significantly higher in the VT group than in the BT group during the first 5 years of life. Liver biopsy, which was carried out in four children, revealed mild to moderate fibrosis and/or necroinflammatory activity, but no cirrhosis. CONCLUSIONS: Outcomes among children with HCV acquired in infancy demonstrate asymptomatic and slowly progressive disease, at least for the initial decade of infection. Mode of acquisition appears to have a limited impact on outcomes, with similar viral clearance and anti-HCV antibody seroreversion rates in vertical and transfusion acquired infection.     

Compensation of victims of nosocomial or post-transfusion hepatitis C virus infection

The purpose of this review is to inform physicians about the procedures for compensation of victims of nosocomial or post-transfusion hepatitis C virus infection. The different procedures are described in reference to the legislation and regulations. According to the law dated March 4, 2002 if Hepatitis C is contracted during care, in a private or public hospital, the hospital (and not the physician) is responsible for the damages resulting from the nosocomial infection, except if evidence of another cause is provided. For post-transfusion hepatitis C, the patient must show that a transfusion took place prior to the diagnosis of hepatitis C. The patient must also prove that there were no other sources of infection. The French Institute of Blood can sometimes not be held responsible by proving that none of the donors of the transfused blood were infected with the hepatitis C virus. This is a no fault system. Different examples of litigation show the important role of physicians, who must be aware of the main points of the procedures to better understand what is entailed by the medical certificates which the victim may request and also to provide him with any other steps to be taken to obtain compensation.     

聚合酶链反应技术对丙型肝炎病毒感染献血员的筛查

目的 对国内献血者丙型肝炎病毒“窗口期”感染的PCR筛查技术应用的调查。方法 卫生部临床检验中心组织全国12家血站，按统一标准采集上万份样品，分为两组，分别为A组（7173份）和B组（7477份），使用试剂按统一标准进行了本项调查研究，其中基因拷贝数≥10^3拷贝数/ml判为阳性。结果 A组中阳性样本数为21，百分比为0.29%，B组中未检测到阳性样本数。结论 血站有必要采用PCR技术筛查丙型肝炎病毒“窗口期”感染的献血者。但需规范采血术方法和评价适合血站筛查用的试剂。     

Pan-reactive platelet antibodies in post-transfusion purpura

BACKGROUND AND OBJECTIVES: The mechanism for the destruction of a patient's own platelets in post-transfusion purpura (PTP) is unknown. In order to test the hypothesis that the destruction of autologous platelets in PTP is related to the presence of platelet antibodies with pan-reactivity, we investigated sera from patients with PTP. MATERIALS AND METHODS: Sera from 12 patients with PTP were investigated for platelet antibodies by platelet-ELISA and monoclonal antibody-specific immobilization of platelet antigen assay. RESULTS: During the thrombocytopenic phase, antibodies of IgG and IgM classes with pan-specificity against platelet GPIIb-IIIa, GPIb-IX and GPIa-IIa were found together with HPA alloantibodies. After recovery, the pan-specific antibodies disappeared or the extent of reactivity diminished, whereas the IgG HPA alloantibodies persisted. CONCLUSION: These findings provide evidence that transient panreactive antibodies may be responsible for the autologous platelet destruction in PTP.     

TT viral infection through blood transfusion: retrospective investigation on patients in a prospective study of post-transfusion hepatitis

AIM To investigate the role of blood transfusion in TT viral infection (TTV).METHODS We retrospectively studied serum samples from 192 transfusion recipients who underwent cardiovascular surgery and blood transfusion between July 1991 and June 1992. All patients had a follow-up every other week for at least 6 months after transfusion. Eighty recipients recipents blood before screening donors for hepatitis C antibody (anti-HCV), and 112 recipients reveiver screened blood.Recipients with alanine aminotransferase level ＞ 2.5 times the upper normal limit were tested for serological markers for viral hepatitis A, B,C, G, Epstein-Barr virus and cytomegalovirus.TTV infection was defined by the positivity for serum TTV DNA using the polymerase chain reaction method. RESULTS Eleven and three patients, who reveiver anti-HCV unscreened and screened blood, respectively, had serum ALT levels ＞90 IU/L. Five patients (HCV and TTV: 1; HCV,HGV, and TTV: 1; TTV: 2; and CMV and TTV: 1 )were positive for TTV DNA, and four of them had sero-conversion of TTV DNA. CONCLUSION TTV can be transmitted via blood transfusion. Two recipients infected by TTV alone may be associated with the hepatitis.However, whether TTV was the causal agent remains unsettled, and further studies are necessary to define the role of TTV infection in chronic hepatitis.     

Selection of different 5' untranslated region hepatitis C virus variants during post-transfusion and post-transplantation infection

BACKGROUND: Hepatitis C virus (HCV) translation is initiated in a cap-independent manner by an internal ribosome entry site (IRES) located within the 5' untranslated region (5'UTR). Sequence changes in this region could affect translation efficiency and presumably viral replication. AIM: To determine translation efficiency of 5'UTR variants developing during post-transfusion hepatitis C in two immunocompetent subjects and in two immunosuppressed liver recipients with recurrent HCV. METHODS: Sequential samples were screened for 5'UTR changes by single-strand conformation polymorphism followed by cloning and sequencing whenever band pattern suggested sequence changes. 5'UTR variants were tested for IRES activity using a bicistronic dual luciferase expression plasmid transfected into HepG2 and Huh7 cell-lines. RESULTS: In the transfused patients, translation efficiency of 5'UTR variants from early post-transfusion samples was 5.1- to 13.7-fold higher than that of predominant variants found in late follow-up samples. Post-transplant variants in the other two patients had 2.6- to 5.9-fold higher translation efficiency than those present only in pretransplant samples. CONCLUSION: In the immunocompetent host there may be selection of low translation efficiency HCV variants over the course of infection. However, in immunosuppressed subjects the opposite seems to be true as low translation efficiency variants are superseded by high translation efficiency variants.     

High-dose IgG for post-transfusion purpura-revisited

Summary Therapy for post-transfusion purpura (PTP) is controversial. We have evaluated the effect of high-dose IgG (HDIgG) in 11 PTP cases investigated in our institution and summarized the clinical data of 8 additional cases reported in the literature. Two of these 19 cases had to be eliminated from the analysis (1 patient received a total dose of less than 30 g of IgG; 1 patient died 2 days after starting HDIgG therapy from congestive heart failure). Out of a total of 17 cases, 16 had good or excellent response reaching normal platelet values within few days; only one failure was observed. Five patients relapsed, but attained complete remission after a second course (dose) of IgG. Total doses per course ranged between 52 and 180 g of IgG. Five different IgG preparations were used and seemed similarly effective. No adverse reactions were observed. We conclude that HDIgG is the treatment of choice for PTP.     

Immunological abnormalities in acute post-transfusion hepatitis non-A non-B

A variety of immunological parameters has been serially examined in the blood of 12 patients with acute post-transfusion hepatitis non-A non-B (PTHNANB). Several alterations of these tests were transiently detected when comparing with healthy, extensively transfused subjects as well as with normal volunteers: 1. Low proportions of CD8+ T lymphocytes were observed at the disease onset, and these returned to normal after 1 month; 2. A diminution of the proliferative response of blood lymphocytes to mitogens was detected during the same period of time; 3. By the third month of disease, an enhanced spontaneous IgG secretion by cultured lymphocytes was found, and this observation was restricted to those patients who had not recovered. These alterations suggest that the immune system might be involved in the course of hepatitis C virus infection.     

C-reactive protein concentrations pre- and post-transfusion

In a prospective study, serum C-reactive protein (CRP) levels were analysed before and after 18 transfusional episodes, using a fluorescence polarization immunoassay. Only patients with a stable CRP value for two consecutive days before transfusion were assessed. Although small rises in CRP concentrations occurred following 55.6% of transfusions, there was no statistically significant difference between pre- and post-transfusion CRP values, and these increases also failed to reach clinical significance. An increase in CRP post-transfusion of greater than 100 mg/l occurred on only one occasion, and was more likely to be due to underlying infection.     

High-dose intravenous immunoglobulin for post-transfusion purpura

Five patients with post-transfusion purpura (four due to Zw(a), one presumably due to HLA antibodies) were treated with intravenous immunoglobulin (IgG) at doses of 0.4 g per kg body weight. IgG therapy was immediately effective as indicated by cessation of bleeding and rise of platelet counts in four out of five cases.     

Etiological spectrum of post-transfusion hepatitis.

Frequent occurrence of post-transfusion hepatitis continues despite screening for Australia antigen in blood before transfusion and elimination of commercial donor sources. The majority of these cases appears unrelated to hepatitis B virus. Preoperative, acute, and convalescent serra were screened for evidence of hepatitis B, hepatitis A, Epstein-Barr, and cytomegalovirus exposure in 34 cardiac surgery patients developing post-transfusion hepatitis postoperatively. Four patients showed evidence of hepatitis B infection and 3 patients developed significant antibody titer rises to cytomegalovirus. No patient showed evidence for acute hepatitis A infection postoperatively in response to blood transfusions. Epstein-Barr virus was also not responsible for any cases of post-transfusion hepatitis. Presently available laboratory methods failed to implicate hepatitis A, Epstein-Barr, or cytomegalo-virus in the majority of non-B post-transfusion hepatitis cases. This suggests that identification and characterization of additional hepatitis-producing agents will be required to define further the epidemiology of post-transfusion hepatitis and develop measures for its prevention.     

Antibody to hepatitis C virus in post-transfusion hepatitis.

OBJECTIVE: To evaluate the prevalence of antibodies to hepatitis C virus (anti-HCV), their relation to outcome, and the seroconversion rate in patients with post-transfusion non-A, non-B hepatitis. DESIGN: Retrospective analysis of prospectively collected serum specimens. SETTING: A referral-based university hospital. PATIENTS: Sixty-three consecutive patients who developed non-A, non-B post-transfusion hepatitis after open-heart surgery. All patients had follow-up with serial serum testing and clinical evaluation. The mean (+/- SD) duration of follow-up after hepatitis onset was 81 +/- 33 months (range, 13 to 132 months). Seventeen patients recovered after acute-phase illness, whereas 46 developed chronic disease which, in 30 cases, was confirmed histologically. MAIN RESULTS: Of 32 patients tested before transfusion, 1 (3.1%) had anti-HCV. Fifty-nine (93%) patients were anti-HCV positive during acute-phase hepatitis: Patients with "early" seroconversion (less than 15 days after hepatitis onset) did not differ from those with "late" seroconversion (greater than 60 days after onset) in epidemiologic, clinical, and biochemical features. The rate of anti-HCV positivity during acute-phase illness was not significantly different among patients who recovered (76%) compared with those who developed chronic disease (95%). At 6 to 12 months, patients whose disease resolved had lower antibody activity than those with progressive disease. Further, during long-term follow-up (1 to 9 years), 53% of patients whose disease resolved but only 6.9% of patients who had progressive disease became anti-HCV negative. CONCLUSIONS: Hepatitis C virus is the major cause of post-transfusion hepatitis in Italy. The time to anti-HCV seroconversion varies widely after hepatitis onset and is not significantly associated with acute-phase features or outcome of disease.     

Study of mechanisms of post-transfusion hypertension in thalassaemic patients

Post-transfusion hypertension, convulsion and cerebral haemorrhage is a serious complication that may occur in the thalassaemias. In this study we evaluated the effect of blood transfusion on blood pressure, plasma renin activity (PRA), blood viscosity, and urinary vanillylmandelic acid (VMA) and catecholamines in 11 beta-thalassaemia/haemoglobin E patients. The results showed that after each unit of blood transfusion the blood viscosity was increased and correlated with the increased in haematocrit level. At the same time the PRA level was significantly decreased and tended to return to the normal level in a few days after the transfusion. There was no alteration in the urinary VMA and catecholamine levels. During the study two patients developed hypertension and headache. Their PRA were still lower than the pre-transfusion levels and the blood pressure returned to the normal pre-transfusion levels within 30-90 minutes after the intravenous injection of furosemide.     

The emerging pattern of post-transfusion hepatitis.

The exclusion of commercial and hepatitis B surface antigen (HBs Ag)-positive donors, as measured by counterelectrophoresis, has markedly reduced the frequency of post-transfusion hepatitis (PTH). A further, significant reduction in type-B PTH can be achieved by prescreening donors for HBs Ag by solid-phase radioimmunoassay (RIA); When a voluntary donor population, pretreated by RIA, is used, approximately 90 per cent of residual hepatitis is serologically unrelated to either the type-A or type-B hepatitis viruses. Similarly, cytomegalovirus and the Epstein-Barr virus are not serologically implicated in "non-A, non-B" hepatitis. Additional human hepatitis virus(es) may exist.