Brouwer J T, Hansen B E, Niesters H G, Schalm S W
Department of Hepatogastroenterology, Erasmus University Hospital - Dijkzigt, Rotterdam, The Netherlands.
J Hepatol. 1999 Feb;30(2):192-8. doi: 10.1016/s0168-8278(99)80061-0.
BACKGROUND/AIMS: There is consensus that interferon for hepatitis C should be stopped if alanine aminotransferase (ALT) remains elevated after 12 weeks; however, this may lead to unjust treatment withdrawal in around 20% of potential sustained responders. No consensus exists for interferon-ribavirin combination therapy. The aim of this study was to assess the predictive value of an HCV RNA test at 4 weeks in comparison with ALT, both in interferon monotherapy and in interferon-ribavirin combination therapy.
Plasma HCV RNA was tested at 4 weeks in 149 naive patients undergoing 6 months and 187 undergoing up to 12 months of interferon monotherapy, and in 40 non-responders treated for 6 months with interferon-ribavirin combination therapy.
For 6 and up to 12 months of interferon monotherapy, the predictive value for non-response was 99% resp. 97% for a positive HCV RNA at week 4, versus 97% resp. 91% for an elevated ALT at week 12. Using a positive HCV RNA at week 4 as a stopping rule would lead to missing 5% resp. 12% of potential sustained responders, versus 10% resp. 28% for an elevated ALT at week 12. In interferon-ribavirin combination therapy, the predictive value for non-response was 100% for week 4 HCV RNA versus 95% for week 12 ALT, and 0% potential sustained responders were missed by a test for week 4 HCV RNA versus 20% for week 12 ALT. The overall sensitivity and specificity of a week 4 HCV RNA test was significantly better (area under ROC 0.85) as compared to testing ALT at week 4 (0.78, p<0.001), week 8 (0.76, p<0.001) or week 12 (0.78, p<0.001).
A positive HCV RNA test (> or =10(3) copies/ ml) at 4 weeks is highly predictive for non-response and leads to significantly less misidentification of potential sustained responders than ALT at week 4, 8 or 12, both in 6 or up to 12 months interferon monotherapy and in 6 months interferon-ribavirin combination therapy of chronic hepatitis C.
背景/目的：对于丙型肝炎患者，如果在12周后丙氨酸转氨酶（ALT）仍持续升高，则应停用干扰素，这一点已达成共识；然而，这可能会导致约20%的潜在持续应答者被不合理地终止治疗。对于干扰素 - 利巴韦林联合治疗，目前尚无共识。本研究的目的是评估在干扰素单药治疗和干扰素 - 利巴韦林联合治疗中，与ALT相比，4周时HCV RNA检测的预测价值。
对149例接受6个月干扰素单药治疗的初治患者、187例接受长达12个月干扰素单药治疗的患者以及40例接受6个月干扰素 - 利巴韦林联合治疗但无应答的患者，在4周时检测血浆HCV RNA。
对于6个月及长达12个月的干扰素单药治疗，4周时HCV RNA阳性对无应答的预测价值分别为99%和97%，而12周时ALT升高的预测价值分别为97%和91%。以4周时HCV RNA阳性作为停药标准，将导致5%和12%的潜在持续应答者被漏诊，而以12周时ALT升高作为停药标准，这一比例分别为10%和28%。在干扰素 - 利巴韦林联合治疗中，4周时HCV RNA对无应答的预测价值为100%，而12周时ALT的预测价值为95%；4周时HCV RNA检测未漏诊潜在持续应答者，而12周时ALT检测漏诊率为20%。与4周（0.78，p<0.001）、8周（0.76，p<0.001）或12周（0.78，p<0.001）时检测ALT相比，4周时HCV RNA检测的总体敏感性和特异性显著更好（ROC曲线下面积为0.85）。
在慢性丙型肝炎的6个月及长达12个月的干扰素单药治疗以及6个月的干扰素 - 利巴韦林联合治疗中，4周时HCV RNA检测阳性（≥10³拷贝/毫升）对无应答具有高度预测性，且与4周、8周或12周时检测ALT相比，显著减少了对潜在持续应答者的误判。
