Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study.
Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study.
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DOI：
10.1182/blood.v84.4.1020.bloodjournal8441020
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发表时间：
1994-08
期刊：
影响因子：
20.3
通讯作者：
M. Eyster;Michael;Fried;Adrian;Di Bisceglie;J. J. Goedert-J.
中科院分区：
文献类型：
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作者：
M. Eyster;Michael;Fried;Adrian;Di Bisceglie;J. J. Goedert-J.
我们之前观察到感染人类免疫缺陷病毒（HIV）的血友病患者肝功能衰竭的发生率增加。本研究的目的是定量 HIV 血清阳性 (HIV+) 和 HIV 血清阴性 (HIV-) 血友病患者在 HIV 血清转化前后的系列样本中的丙型肝炎病毒 (HCV) RNA 水平，并检查随时间推移 HCV RNA 水平与 CD4 细胞计数和肝功能障碍的关系。对出生日期 5 年内匹配的 17 名 HCV+/HIV+ 和 17 名 HCV+/HIV- 受试者的冷冻储存血清系列样本进行 HCV RNA 水平测量。在进入研究之前，所有人都是 HCV+。 HCV RNA 水平通过分支 DNA 增强标记扩增 (bDNA) 测定进行定量。对于小于截止值的样品，通过巢式聚合酶链式反应测量HCV RNA。将个体随时间的变化、临床组和预定时间窗口内的平均值与 Wilcoxon 秩和检验进行比较。 HIV 血清转化后的头 2 年期间，平均 HCV RNA 水平从 2.76（标准误差 [SE] 1.33）x 10(5) 增至 2.84 (SE 1.39) x 10(6) eq/mL (P = .006)。 HIV 血清转化前组的基线 HCV RNA 水平与仍处于 HIV 状态的患者的基线水平没有显着差异 (P = .79)。在整个研究期间，HIV 感染者中的 HCV RNA 水平增加了近三倍（平均 9.47 [SE 4.78] x 10(5) 至 2.81 [SE 1.13] x 10(6)/mL；P = .02）。在 HIV+ 患者中，HCV RNA 水平增加了 58 倍（平均 2.85 [SE 1.26] x 10(5) 至 1.66 [SE 0.57] x 10(7) eq/mL；P = .0001）。 HIV+ 受试者的 HCV RNA 水平增加速度是 HIV- 受试者的八倍（P = .009）。 5 名发生肝衰竭的受试者的 HCV RNA 水平比 12 名未发生肝衰竭的受试者高出两倍 (P = .43)。 HCV RNA 水平与 CD4 计数 (R = -.33, P = .01) 和血清天冬氨酸转氨酶 (AST) 水平 (R = .36, P = .007) 显着相关。我们得出的结论是，HIV+ 患者中的 HCV RNA 水平显着高于 HIV 多次输血血友病患者。 HCV 负荷随着时间的推移而增加，并因 HIV 而增强，并随着免疫缺陷的进展而进一步增加。 HCV RNA 水平与高 AST 水平直接相关。这些发现表明，HIV 引起的免疫缺陷可能会促进 HCV 复制增加。
We have previously observed an increased frequency of liver failure in human immunodeficiency virus (HIV)-infected hemophiliacs. The purpose of this study was to quantitate hepatitis C virus (HCV) RNA levels in serial samples from HIV-seropositive (HIV+) and HIV-seronegative (HIV-) hemophiliacs before and after HIV seroconversion, and to examine the relationship of HCV RNA levels to CD4 cell counts and to hepatic dysfunction over time. HCV RNA levels were measured on serial samples of serum stored frozen from 17 HCV+/HIV+ and 17 HCV+/HIV- subjects matched within 5 years of their birth dates. All were HCV+ before study entry. HCV RNA levels were quantitated by a branched DNA-enhanced label amplification (bDNA) assay. For samples less than the cut off, HCV RNA was measured by the nested polymerase chain reaction. Individual changes over time, clinical groups, and mean values within predetermined time windows were compared with Wilcoxon rank sum tests. Mean HCV RNA levels increased from 2.76 (standard error [SE] 1.33) x 10(5) to 2.84 (SE 1.39) x 10(6) eq/mL during the first 2 years after HIV seroconversion (P = .006). Baseline HCV RNA levels in the pre-HIV seroconversion group were not significantly different from the baseline levels in those who remained HIV (P = .79). Over the entire period of study, HCV RNA levels increased nearly threefold in those who remained HIV- (mean 9.47 [SE 4.78] x 10(5) to 2.81 [SE 1.13] x 10(6)/mL; P = .02). Among those who became HIV+, HCV RNA levels increased 58-fold (mean 2.85 [SE 1.26] x 10(5) to 1.66 [SE 0.57] x 10(7) eq/mL; P = .0001). The rate of increase in HCV RNA levels was eightfold faster for HIV+ subjects than for subjects who remained HIV- (P = .009). HCV RNA levels increased twofold higher in 5 subjects who developed liver failure compared with the 12 who did not (P = .43). HCV RNA levels correlated significantly with CD4 counts (R = -.33, P = .01) and serum aspartate aminotransferase levels (AST) (R = .36, P = .007). We conclude that HCV RNA levels are significantly higher in HIV+ than in HIV- multitransfused hemophiliacs. HCV load increases over time, is enhanced by HIV, and further increases as immune deficiency progresses. HCV RNA levels are directly associated with high AST levels. These findings suggest that HIV-induced immune deficiency may promote increased HCV replication.