Zeuzem S, Lee J H, Franke A, Rüster B, Prümmer O, Herrmann G, Roth W K
Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt, Germany.
Hepatology. 1998 Apr;27(4):1149-56. doi: 10.1002/hep.510270433.
Although several virus- and host-related predictive factors for the response to interferon alfa (IFN-alpha) have been defined in patients with chronic hepatitis C, no pretreatment parameter can definitely predict the response to antiviral treatment. Assessment of the initial response by quantification of serum hepatitis C virus RNA before and 4 weeks after initiation of therapy may be a clinically applicable and reliable parameter to predict long-term response. Therefore, the aims of the present study were to test the predictive value of a decline in HCV RNA of at least 3 log in the first 4 weeks of treatment (deltaHCV RNA) in patients treated with 3 x 10(6) units of recombinant IFN-alpha2a (rIFN-alpha2a) three times per week subcutaneously and to compare deltaHCV RNA with other established predictive factors, such as HCV genotype and pretreatment viremia. Serum HCV RNA was measured by a validated quantitative reverse transcription-polymerase chain reaction (RT-PCR). Geno/subtyping of HCV was performed by direct sequencing of the nonstructural (NS) 5B region of PCR-amplified isolates and subsequent phylogenetic analysis. Stable HCV RNA levels (deltaHCV RNA < or = 1 log) within the first 4 weeks of IFN-alpha treatment were present in 42 of 70 patients. A decline in HCV RNA levels between 1 to 3 log and more than 3 log was observed in 9 (13%) and 19 patients (27%), respectively. In 21 of 70 patients (30%), HCV RNA was not detectable at the end of 12 months' treatment. Three of 26 patients (11%) with a pretreatment viremia of < or = 10(6) copies/mL (all HCV subtype 3a) and 6 of 44 patients (14%) with a pretreatment viremia of > 10(6) copies/mL (HCV subtypes 1b, 2a, 2c, 3a [two patients], and 4) achieved a virological sustained response to interferon-alpha2a treatment. All patients with a virological sustained response had an initial deltaHCV RNA of more than 3 log. In a stepwise discriminant-function analysis, the initial deltaHCV RNA was confirmed as the strongest predictor of virological sustained response (P < .0001). In conclusion, the data of the present study suggest that IFN-alpha treatment can be terminated after 4 weeks in patients with a decrease in HCV RNA levels of less than 3 log, when apparent HCV eradication is considered the therapeutic target. The predictive value of deltaHCV RNA clearly exceeds the significance of HCV genotype and pretreatment viremia as predictors of successful IFN-alpha treatment.
尽管在慢性丙型肝炎患者中已经确定了几种与病毒和宿主相关的、预测干扰素α（IFN-α）治疗反应的因素，但没有任何治疗前参数能够明确预测抗病毒治疗的反应。通过在治疗开始前和开始治疗4周后对血清丙型肝炎病毒RNA进行定量来评估初始反应，可能是一种临床适用且可靠的预测长期反应的参数。因此，本研究的目的是检测接受皮下注射3×10⁶单位重组IFN-α2a（rIFN-α2a）、每周3次治疗的患者在治疗的前4周内HCV RNA下降至少3个对数（ΔHCV RNA）的预测价值，并将ΔHCV RNA与其他已确立的预测因素（如HCV基因型和治疗前病毒血症）进行比较。血清HCV RNA通过经过验证的定量逆转录-聚合酶链反应（RT-PCR）进行检测。HCV的基因分型/亚型分析通过对PCR扩增分离株的非结构（NS）5B区域进行直接测序以及随后的系统发育分析来进行。在70例患者中，有42例在IFN-α治疗的前4周内HCV RNA水平稳定（ΔHCV RNA≤1个对数）。分别有9例（13%）和19例（27%）患者的HCV RNA水平下降在1至3个对数和超过3个对数之间。在70例患者中的21例（30%）在12个月治疗结束时HCV RNA检测不到。26例治疗前病毒血症≤10⁶拷贝/mL的患者中有3例（11%）（均为HCV 3a亚型）以及44例治疗前病毒血症>10⁶拷贝/mL的患者中有6例（14%）（HCV亚型为1b、2a、2c、3a[2例]和4）对干扰素α2a治疗获得了病毒学持续应答。所有获得病毒学持续应答的患者初始ΔHCV RNA均超过3个对数。在逐步判别函数分析中，初始ΔHCV RNA被确认为病毒学持续应答的最强预测因子（P<.0001）。总之，本研究数据表明，当将明显清除HCV视为治疗目标时，对于HCV RNA水平下降小于3个对数的患者，IFN-α治疗可在4周后终止。ΔHCV RNA的预测价值明显超过HCV基因型和治疗前病毒血症作为IFN-α治疗成功预测因子的意义。
