Shiffman M L, Hofmann C M, Thompson E B, Ferreira-Gonzalez A, Contos M J, Koshy A, Luketic V A, Sanyal A J, Mills A S, Garrett C T
Hepatology Section, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
Hepatology. 1997 Sep;26(3):780-5. doi: 10.1002/hep.510260335.
The present study was conducted to evaluate the relationship between biochemical, virological, and histological response during the course of interferon therapy. Ninety consecutive patients with well-documented chronic hepatitis C virus (HCV) were treated with 5 MU of interferon alfa-2b three times weekly for 6 months. Liver biopsy was performed, and serum HCV RNA titer was measured before and at the completion of interferon treatment. Normalization of serum alanine transaminase (ALT) concentration (biochemical response) was observed in 50% of patients. In these patients, Knodell score declined significantly from 9.6 +/- 0.5 to 5.0 +/- 0.5 (P < .01), and 75% became HCV RNA negative. The remaining patients (50%) were biochemical nonresponders; mean Knodell score declined from 9.6 +/- 0.5 to 7.7 +/- 0.5 (P < .01), and 11% became HCV RNA negative. For both biochemical responders and nonresponders, the decline in Knodell score was confined to the components of hepatic inflammation (piecemeal necrosis + lobular + portal inflammation); no change in fibrosis was observed. Hepatic inflammation declined by 5 points or more in 69% of biochemical responders and 48% of biochemical nonresponders, and by at least 50% from pretreatment values in 74% and 38% of biochemical responders and biochemical nonresponders, respectively. For all patients (both biochemical responders and nonresponders) who remained viremic at the conclusion of interferon therapy, the reduction in hepatic inflammation was a linear function of the decline in HCV RNA titer. We conclude that more than one third of patients who had no biochemical response after 6 months of interferon therapy achieved a similar improvement in hepatic histology as was observed in patients with biochemical response. This improvement in hepatic histology appeared to correlate with a reduction in HCV RNA titer, especially in patients who remained viremic.
本研究旨在评估干扰素治疗过程中生化、病毒学和组织学反应之间的关系。连续90例有充分记录的慢性丙型肝炎病毒（HCV）患者接受每周3次、每次5 MU的干扰素α-2b治疗，疗程6个月。在干扰素治疗前及治疗结束时进行肝活检，并检测血清HCV RNA滴度。50%的患者血清丙氨酸转氨酶（ALT）浓度恢复正常（生化反应）。在这些患者中，Knodell评分从9.6±0.5显著降至5.0±0.5（P<0.01），75%的患者HCV RNA转为阴性。其余患者（50%）为生化无反应者；平均Knodell评分从9.6±0.5降至7.7±0.5（P<0.01），11%的患者HCV RNA转为阴性。对于生化反应者和无反应者，Knodell评分的下降均局限于肝炎症成分（界面性坏死+小叶+门管区炎症）；纤维化未见变化。69%的生化反应者和48%的生化无反应者肝炎症下降5分或更多，生化反应者和生化无反应者中分别有74%和38%的患者肝炎症较治疗前值至少下降50%。对于在干扰素治疗结束时仍有病毒血症的所有患者（生化反应者和无反应者），肝炎症的减轻是HCV RNA滴度下降的线性函数。我们得出结论，干扰素治疗6个月后无生化反应的患者中，超过三分之一在肝组织学方面取得了与生化反应患者相似的改善。肝组织学的这种改善似乎与HCV RNA滴度的降低相关，尤其是在仍有病毒血症的患者中。
