Farci P, Alter H J, Wong D, Miller R H, Shih J W, Jett B, Purcell R H
Hepatitis Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
N Engl J Med. 1991 Jul 11;325(2):98-104. doi: 10.1056/NEJM199107113250205.
Although antibodies to the hepatitis C virus (HCV) are known to be associated with non-A, non-B hepatitis, little is known about the pattern of HCV replication, its relation to antibody levels, and the clinical course of non-A, non-B hepatitis.
We measured HCV RNA in serial serum samples from five patients with post-transfusion non-A, non-B hepatitis who were followed for 10 to 14 years after transfusion. We also studied four chimpanzees that were experimentally infected with serum from four of these patients. Serum HCV RNA was detected by a "nested" polymerase-chain-reaction (PCR) assay that used two sets of primers derived from the third (NS3) and fourth (NS4) non-structural gene regions of the HCV genome.
HCV sequences were detected by PCR in only two of the five patients and two of the four chimpanzees with the set of primers corresponding to the NS3 region, but in all five patients (and in all four chimpanzees) with the primers from the NS4 region. Serum HCV RNA was first detected within three weeks of transfusion in all five patients and within one week in three patients. The viremia lasted less than 4 months in the patient (and two chimpanzees) with acute, self-limited hepatitis, whereas it persisted for 10 to 14 years in the four patients (and for 1 and 3 years in two chimpanzees) with chronic non-A, non-B hepatitis. Antibodies to HCV were first detected at week 12 to 14; they disappeared after nine years in the patient with self-limited disease and became borderline after five years in one of the patients with chronic disease.
During the early phase of primary HCV infection, there is a period of several months of sero-negativity during which HCV RNA is the only diagnostic marker of infection. The disappearance of HCV RNA from serum appears to correlate with the resolution of non-A, non-B hepatitis, whereas viremia persists in patients whose disease progresses to chronic hepatitis. In contrast, antibody levels do not necessarily remain elevated in patients with chronic disease.
虽然已知丙型肝炎病毒（HCV）抗体与非甲非乙型肝炎相关，但对于HCV复制模式、其与抗体水平的关系以及非甲非乙型肝炎的临床病程了解甚少。
我们检测了5例输血后非甲非乙型肝炎患者系列血清样本中的HCV RNA，这些患者在输血后随访了10至14年。我们还研究了4只黑猩猩，它们被实验性感染了其中4例患者的血清。血清HCV RNA通过一种“巢式”聚合酶链反应（PCR）检测法进行检测，该方法使用了两组源自HCV基因组第三（NS3）和第四（NS4）非结构基因区域的引物。
使用对应于NS3区域的引物，仅在5例患者中的2例以及4只黑猩猩中的2只中通过PCR检测到HCV序列，但使用来自NS4区域的引物时，在所有5例患者（以及所有4只黑猩猩）中均检测到。所有5例患者在输血后3周内首次检测到血清HCV RNA，3例患者在1周内检测到。急性自限性肝炎患者（以及2只黑猩猩）的病毒血症持续时间不到4个月，而4例慢性非甲非乙型肝炎患者（以及2只黑猩猩中的1只和3只）的病毒血症持续了10至14年。HCV抗体在第12至14周首次检测到；在自限性疾病患者中，9年后抗体消失，在1例慢性病患者中，5年后抗体变为临界值。
在原发性HCV感染的早期阶段，有几个月的血清学阴性期，在此期间HCV RNA是感染的唯一诊断标志物。血清中HCV RNA的消失似乎与非甲非乙型肝炎的缓解相关，而病毒血症在疾病进展为慢性肝炎的患者中持续存在。相比之下，慢性病患者的抗体水平不一定持续升高。
