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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis
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Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis

机译：促纤维化趋化因子和病毒进化预测丙型肝炎迅速发展为肝硬化

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摘要

Chronic hepatitis C may follow a mild and stable disease course or progress rapidly to cirrhosis and liver-related death. The mechanisms underlying the different rates of disease progression are unknown. Using serial, prospectively collected samples from cases of transfusion-associated hepatitis C, we identified outcome-specific features that predict long-term disease severity. Slowly progressing disease correlated with an early alanine aminotransferase peak and antibody seroconversion, transient control of viremia, and significant induction of IFN-γ and MIP-1β all indicative of an effective, albeit insufficient, adaptive immune response. By contrast, rapidly progressive disease correlated with persistent and significant elevations of alanine aminotransferase and the profibrogenic chemokine MCP-1 (CCL-2), greater viral diversity and divergence, and a higher rate of synonymous substitution. This study suggests that the long-term course of chronic hepatitis C is determined early in infection and that disease severity is predicted by the evolutionary dynamics of hepatitis C virus and the level of MCP-1, a chemokine that appears critical to the induction of progressive fibrogenesis and, ultimately, the ominous complications of cirrhosis.
机译：慢性丙型肝炎可能遵循轻度和稳定的病程，或迅速发展为肝硬化和肝脏相关的死亡。疾病进展速度不同的机制尚不清楚。使用连续，前瞻性收集的与输血相关的丙型肝炎病例的样本，我们确定了可预测长期疾病严重程度的特定于结果的特征。进展缓慢的疾病与早期丙氨酸氨基转移酶峰和抗体血清转化，病毒血症的瞬时控制以及IFN-γ和MIP-1β的显着诱导有关，尽管有效但适应性免疫应答不足。相比之下，快速进展的疾病与丙氨酸转氨酶和促纤维化趋化因子MCP-1（CCL-2）持续且显着升高，病毒多样性和发散性较高以及同义替换率更高相关。这项研究表明，慢性丙型肝炎的长期病程是在感染的早期确定的，疾病的严重程度是由丙型肝炎病毒的进化动力学和MCP-1的水平预测的，该趋化因子对诱导进行性肝炎至关重要纤维化，并最终导致肝硬化的不祥并发症。

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  • 作者

    Patrizia Farci; Kurt Wollenberg; Giacomo Diaz; Ronald E. Engle; Maria Eliana Lai; Paul Klenerman; Robert H. Purcell; Oliver G. Pybus; Harvey J. Alter;

  • 作者单位

    Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda,MD 20892;

    Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;

    Department of Biomedical Sciences, University of Cagliari, 09123 Cagliari, Italy;

    Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;

    Department of Medical Sciences, University of Cagliari, 09042 Monserrato (Cagliari), Italy;

    Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kingdom;

    Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;

    Department of Zoology, University of Oxford, Oxford OX1 3PS, United Kingdom;

    Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    hepatitis C virus; slow progressors; rapid progressors; liver fibrosis;

    机译：丙型肝炎病毒;进展缓慢;快速进步者;肝纤维化;

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