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Influence of quasispecies on virological responses and disease severity in patients with chronic hepatitis C

World Journal of Gastroenterology 2008年第5期14卷 701-708页

作者： Deepak Kumar Abdul Malik Mohammad Asim Anita Chakravarti Rakha H Das Premashis Kar Department of Medicine Department of Microbiology Maulana Azad Medical College New Delhi 110002 IndiaDeepak Comparative Genomics Unit Institute of Genomics and Integrative Biology Delhi University Campus Mall Road Delhi 110007 India Department of Microbiology Maulana Azad Medical College New Delhi 110002 IndiaDeepak Comparative Genomics Unit Institute of Genomics and Integrative Biology Delhi University Campus Mall Road Delhi 110007 India Department of Microbiology Maulana Azad Medical College New Delhi 110002 India

AIM:To elucidate the influence of quasispecies on virological response and disease severity in patients with chronic hepatitis C. METHODS:Forty seven patients with hepatitis C [32 with chronic active hepatitis (CAH), 9 with cirrhosis, and 6 with hepatocellular carcinoma (HCC)] were screened for the presence of quasispecies by single stranded conformational polymorphism (SSCP) analysis in the hypervariable region (HVR) and non-structural 5B (NS5B) viral genes of hepatitis C virus. The 41 patients excluding those with HCC were on therapy and followed up for a year with the determination of virological response and disease severity. Virus isolated from twenty three randomly selected patients (11 non-responders and 12 showing a sustained virological response) was sequenced for the assessment of mutations. RESULTS:The occurrence of quasispecies was proportionately higher in patients with HCC and cirrhosis than in those with CAH, revealing a significant correlation between the molecular evolution of quasispecies and the severity of disease in patients with hepatitis C. The occurrence of complex quasispecies has a significant association (P < 0.05) with the non-responders, and leads to persistence of infection. Significant differences (P < 0.05) in viral load (log10 IU/mL) were observed among patients infected with complex quasispecies (CQS), those infected with simple quasispecies (SQS) and those with no quasispecies (NQS), after 12 wk (CQS-5.2 ± 2.3, SQS-3.2 ± 1.9, NQS-2.8 ± 2.4) and 24 wk (CQS-3.9 ± 2.2, SQS-3.0 ± 2.2, NQS-2.1 ± 2.3) in the HVR region. However, a statistically significant difference (P < 0.05) was observed between the viral loads of patients infected with CQS and those infected with NQS in NS5B viral gene after 24 wk (CQS-3.9 ± 2.2, SQS-3.0 ± 2.2, and NQS-2.1 ± 2.3) and 48 wk (CQS-3.1 ± 2.7, SQS-2.3 ± 2.4, NQS-2.0 ± 2.3) of therapy. Disease severity was significantly associated with viral load during therapy. The strains isolated from non-responders sho

关键词： Hepatitis C virus single-strand conformational polymorphism Quasispecies Virological response Interferon therapy

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