Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin / Efeito do polimorfismo do gene HFE sobre a resposta viral sustentada em portadores de hepatite crônica C com ferritina sérica elevada
Arq. gastroenterol
; 49(1): 9-13, Jan.-Mar. 2012. tab
Article
in English
| LILACS
| ID: lil-622555
Responsible library:
BR1.1
ABSTRACT
CONTEXT Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. OBJECTIVE:
To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin.METHODS:
A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2) and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week) and ribavirin (1.000 mg, daily) for 24 weeks.RESULTS:
Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis) and BclI (H63D mutation analysis) in 16 (37%) patients, all heterozygous (11 H63D, 2 C282Y and 3 both). Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41%) of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test).CONCLUSION:
Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.RESUMO
CONTEXTO:
Níveis séricos anormais de ferritina são encontrados em aproximadamente 20%-30% dos pacientes com hepatite crônica C e estão associadas a uma baixa taxa de resposta à terapia com interferon.OBJETIVO:
Avaliar a associação entre a presença de mutações do gene HFE e a taxa de resposta virológica sustentada ao interferon em pacientes portadores de hepatite crônica C com ferritina sérica elevada.MÉTODOS:
Um total de 44 pacientes, virgem de tratamento, infectado pelo vírus da hepatite C de genótipos não-1 (38 genótipo 3; 6 genótipo 2) e ferritina sérica acima de 500 ng/mL foi tratado com interferon (3 MU, três vezes por semana) e ribavirina (1000 mg/dia) por 24 semanas. Resposta virológica sustentada foi definida como HCV-RNA indetectável 24 semanas após o fim do tratamento. Foi utilizado técnica de reação em cadeia da polimerase em tempo-real com limite de detecção de 200 UI /mL.RESULTADOS:
Mutações do gene HFE foram detectadas por "restriction-enzyme digestion" com RsaI (análise de mutação C282Y) e BclI (análise de mutação H63D) em 16 pacientes (37%), todos heterozigotos (11 H63D, 2 C282Y e 3 ambos). Resposta virológica sustentada foi alcançada em 0 de 16 pacientes com mutações do gene HFE e 11 (41%) dos 27 pacientes sem mutações do gene HFE (P = 0,002; teste exato de Fisher).CONCLUSÃO:
A heterozigose para os genes H63D e/ou C282Y HFE está associada à redução significativa da taxa de resposta virológica sustentada ao tratamento com interferon e ribavirina em pacientes com hepatite crônica C, genótipo não-1 e com níveis séricos de ferritina acima de 500 ng/mL.
Full text:
Available
Collection:
International databases
Health context:
SDG3 - Health and Well-Being
Health problem:
Target 3.3: End transmission of communicable diseases
Database:
LILACS
Main subject:
Antiviral Agents
/
Ribavirin
/
Histocompatibility Antigens Class I
/
Interferons
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Hepatitis C, Chronic
/
Ferritins
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Membrane Proteins
Type of study:
Etiology study
/
Incidence study
/
Observational study
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Prevalence study
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Prognostic study
/
Qualitative research
/
Risk factors
Limits:
Adult
/
Female
/
Humans
/
Male
Language:
English
Journal:
Arq. gastroenterol
Journal subject:
Gastroenterology
Year:
2012
Document type:
Article
Affiliation country:
Brazil