Hepatitis C virus in multiple episodes of acute hepatitis in polytransfused thalassaemic children

Lai, Maria Eliana; Mazzoleni, Anna Paola; Balestrieri, A; Argiolu, F; Virgilis, S De; Cao, Antonio; Purcell, Robert H.; Farci, Patrizia

doi:10.1016/s0140-6736(94)91224-6

Cited by 267 publications

(127 citation statements)

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“…These rates of viral clearance are consistent with other reports in nonhemophilic populations (1), although somewhat less than reported in children and young women infected through contaminated blood products (4,43). In the hemophilia cohort, repeatedly exposed to unsterilized blood products, it is possible that single episodes of spontaneous viral clearance were overshadowed by reinfection during subsequent exposures, as has been demonstrated in thalassemic patients who developed repeated episodes of acute hepatitis C following multiple exposures (44). Thus, the hemophilic subjects in the present study represent those with durable viral clearance suggesting a robust antiviral response, the nature of which is worthy of further investigation.…”

Section: Discussionsupporting

confidence: 90%

Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

et al. 2006

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Section: Discussionsupporting

confidence: 90%

Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

et al. 2006

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“…Although the profile of the adaptive immune response against HBV and HCV infections is similar, the antiviral immune response can provide protection against HBV 122 but not against HCV reinfection. 123,124 Moreover, although a vaccine based on the envelope protein of HBV, which induces envelope-specific antibody 122 and helper T-cell responses, [125][126][127] can elicit a sterilizing anti-HBV immunity, different HCV vaccine preparations able to prime similar profiles of T-and B-cell responses have so far failed to protect animals from HCV infection. 128,129 The different kinetics of HCV and HBV replication may represent one of the factors responsible for these differences.…”

Section: Final Remarksmentioning

confidence: 99%

Kinetics of the Immune Response During Hbv and Hcv Infection

2003

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The innate immune system has a role not only in protecting the host during the initial period of virus infection, but also in shaping the nature of the adaptive immune response. In this review, we follow the kinetics of the virologic and immunologic events occurring from the time of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We primarily discuss how the early events after infection might influence the development of the adaptive immune response in these 2 important viral infections and how new strategies for more efficient preventive and therapeutic vaccines can be derived from this knowledge. (HEPATOLOGY 2003; 38:4-13.)H epatitis B (HBV) and hepatitis C (HCV) viruses are the 2 major causes of chronic liver inflammation worldwide. 1,2 Despite distinct virologic features, both viruses are preferentially hepatotropic, not directly cytopathic, and elicit liver diseases that share several aspects of their natural history. HBV and HCV infections share also some important features of the adaptive immune response. Multispecific antiviral CD4 and CD8 responses with a T-helper type 1 profile of cytokine production are detectable in the blood of subjects with a self-limited infection. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] These responses are stronger than those found in patients with chronic infection. [17][18][19][20][21] Based on these observations, it has been proposed that the ability to mount an efficient cellular immune response is the main mechanism responsible for HBV and HCV control, whereas a defect in this response leads to chronicity. 2,22 However, the lack of suitable animal models to study the pathogenesis of HBV and HCV infections has so far hampered a definitive demonstration that associations between different infection outcomes and different vigor and breadth of T-cell responses have a causative effect. A recent report in HCV-infected chimpanzees, in which a clear association between T-cell response and virus clearance was not found, 23 added a further note of caution. Even so, it is difficult to argue against the importance of the cellular immune response in HBV and HCV control. In chimpanzees infected with HCV, expansion of a multispecific and sustained HCV-specific CD8 ϩ T-cell-mediated response was observed in 2 of 2 animals that cleared the virus, but not in the 4 animals that developed a chronic infection. 24 These results have been confirmed by recent reports showing that expansion of interferon ␥ (IFN-␥) ϩ , CD8 ϩ , and CD4 ϩ T cells precedes viral clearance in patients studied during the incubation phase of acute HCV infection in man 10 and in HCV-infected chimpanzees. 25 Similar findings have been reported in animal models of HBV infection 26 and in patients studied during the incubation phase of HBV infection, 27 in whom reduced early expansion of virusspecific T cells was associated with virus persistence. Moreover, the importance of virus-specific CD8 ϩ T cells in HBV control has been confirmed further by CD8 ϩ T-cell deletion experiments performed in HBV-i...

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“…Mixed cryoglobulinemia, purpura, provided us with a good model for studying these aspects, arthritis, proteinuria, decreased complement levels, because most of them were infected by HCV and have develrheumatoid factor and anti-GOR, smooth muscle anti-oped chronic hepatitis, 16,17 whereas the remaining were not, body (SMA), anti-nuclear antibody (ANA), and liver, kid-despite the same transfusion risk. Furthermore, the involveney microsome (LKM) autoantibodies were significantly ment of host dependent factors may be more easily explored more represented in HCV positive patients than in nega-in view of the genetic homogeneity of the Sardinian populative ones (P õ .05).…”

Section: Controls Three Hundred Fourteen Patients Became In-mentioning

confidence: 99%

Hla Class Ii Genes in Chronic Hepatitis C Virus–Infection and Associated Immunological Disorders

et al. 1996

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autoantibodies (anti-nuclear [ANA], 10 anti-smooth muscle To investigate the factors that may confer susceptibil- [SMA], 11 anti-GOR, 12 anti-liver, kidney microsomes [LKM] ity or protection to hepatitis C virus (HCV) infection and antibodies 13). Despite these observations, however, it reto HCV-associated immunological disorders, we demains to be established by controlled epidemiological studies signed two studies on 420 Sardinian transfusion-depenwhether these immunological abnormalities are more fredent thalassemia patients followed in our department in quent in patients with chronic HCV infection than in normal Cagliari since 1974. The first one was an epidemiological subjects. 14 While the HCV-associated immunological disorsurvey aimed to evaluate the prevalence of HCV infecders seem to be independent on HCV serotype, 15 a possible tion and HCV-associated immunological disorders. In relationship between HCV and host factors involved in the the second study, the distribution of different HLA class immune response, such as the antigens encoded by the HLA II genes was examined by DNA analysis in 116 HCV positive patients, 30 HCV negative patients, and 606 healthy class II region, has not been clearly established. controls. Three hundred fourteen patients became in-The large cohort of transfusion-dependent thalassemia pafected with HCV (74.7%) after 5.6 { 2.8 years of regular tients followed in our department from the first year of life transfusion program. Mixed cryoglobulinemia, purpura, provided us with a good model for studying these aspects, arthritis, proteinuria, decreased complement levels, because most of them were infected by HCV and have develrheumatoid factor and anti-GOR, smooth muscle anti-oped chronic hepatitis, 16,17 whereas the remaining were not, body (SMA), anti-nuclear antibody (ANA), and liver, kid-despite the same transfusion risk. Furthermore, the involveney microsome (LKM) autoantibodies were significantly ment of host dependent factors may be more easily explored more represented in HCV positive patients than in nega-in view of the genetic homogeneity of the Sardinian populative ones (P õ .05). A significant increase of HLA class tion. This is confirmed by the similar distribution of the vari-II DR2 subtype (DRB1*1601,DQB1*0502) was observed ous HLA class genes in all the districts of the Island 18,19 and in a group of 30 HCV negative patients who despite 10.3 the observation that 96% of 3,000 Sardinian b-thalassemics In light of these considerations we devised two complemenOur results represent clear evidence for a relationship tary studies. The first was an epidemiological survey to evalubetween HCV infection and immune extrahepatic abnor-ate the prevalence of clinical, biochemical, and immunologimalities. A gene(s) located in the human major histocom-cal HCV-associated abnormalities in a group of 420 patibility complex (MHC) region may play an important transfusion-dependent thalassemia patients. In the second role in conferring protection against HCV infection. one, after dividing...

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Hepatitis C virus in multiple episodes of acute hepatitis in polytransfused thalassaemic children

Cited by 267 publications

References 9 publications

Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

Kinetics of the Immune Response During Hbv and Hcv Infection

Hla Class Ii Genes in Chronic Hepatitis C Virus–Infection and Associated Immunological Disorders

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