Magrin S, Craxi A, Fabiano C, Marino L, Fiorentino G, Lo Iacono O, Volpes R, Di Marco V, Almasio P, Vaccaro A, Urdea M S, Wilber J C, Bonura C, Gianguzza F, Capursi V, Filiberti S, Stuyver L, Pagliaro L
Istituto di Medicina Generale e Pneumologia, University of Palermo, Italy.
J Hepatol. 1996 Nov;25(5):583-90. doi: 10.1016/s0168-8278(96)80224-8.
BACKGROUND/AIMS: To investigate host- and virus-related factors predictive of early and sustained alanine aminotransferase normalization after interferon therapy for HCV-related chronic liver disease, in an area where genotype 1 is highly prevalent.
We studied 100 patients with HCV-RNA positive chronic liver disease (73 chronic hepatitis and 27 cirrhosis) undergoing alpha-interferon treatment. Thirty-four patients had an early response but relapsed, 15 patients remained into sustained response for at least 12 months after therapy, and 51 patients did not respond. Serum HCV-RNA levels were assessed by bDNA (Chiron), and genotype by LiPA (Innogenetics) and by sequencing of the 5' non-coding region.
Mean pre-treatment HCV-RNA level (x 10(3) genome equivalents/ml +/- SD) was lower in sustained responders (3854 +/- 7142) than in relapsers (9587 +/- 10163) or in non-responders (5709 +/- 6618). HCV subtype 1b was highly prevalent (82%), while types 1a, 2a, 3 and 4 were rare (about 5% each). However, the prevalence of 1b was much lower (31%) under 40 years of age. The prevalence of subtype 1b among sustained responders (74%) was similar to that observed among relapsers (82%) or non-responders (84%), but some nucleotide substitutions in the putative RNA loop of the 5' non-coding region were seen only among relapsers or non-responders. Multiple logistic regression model showed that early response to interferon was predicted by absence of cirrhosis and a pre-treatment HCV-RNA level below 350. Sustained response to interferon was predicted by pre-treatment HCV-RNA level below 350 and a low fibrosis score.
Among patients with hepatitis C from an area where subtype 1b is highly prevalent, absence of cirrhosis and low pre-treatment serum HCV-RNA level are the most important predictors of response to IFN. Some nucleotide substitutions found in the 5' non-coding region of subtype 1b are associated with non-response or relapse.
背景/目的:在1型基因型高度流行的地区,研究丙型肝炎病毒(HCV)相关慢性肝病患者接受干扰素治疗后,预测丙氨酸氨基转移酶早期和持续恢复正常的宿主及病毒相关因素。
我们研究了100例HCV-RNA阳性慢性肝病患者(73例慢性肝炎和27例肝硬化)接受α干扰素治疗的情况。34例患者有早期应答但复发,15例患者治疗后持续应答至少12个月,51例患者无应答。血清HCV-RNA水平采用分支DNA法(Chiron公司)评估,基因型采用线性探针分析(LiPA,Innogenetics公司)及5'非编码区测序法检测。
持续应答者治疗前平均HCV-RNA水平(×10³基因组当量/ml±标准差)(3854±7142)低于复发者(9587±10163)或无应答者(5709±6618)。HCV 1b亚型高度流行(82%),而1a、2a、3和4型少见(各约5%)。然而,40岁以下人群中1b型的流行率低得多(31%)。持续应答者中1b亚型的流行率(74%)与复发者(82%)或无应答者(84%)相似,但仅在复发者或无应答者中观察到5'非编码区假定RNA环中的一些核苷酸替换。多因素logistic回归模型显示,无肝硬化及治疗前HCV-RNA水平低于350可预测对干扰素的早期应答。治疗前HCV-RNA水平低于350及低纤维化评分可预测对干扰素的持续应答。
在1b亚型高度流行地区的丙型肝炎患者中,无肝硬化及治疗前血清HCV-RNA水平低是对干扰素应答的最重要预测因素。在1b亚型5'非编码区发现的一些核苷酸替换与无应答或复发相关。