Maylin Sarah, Martinot-Peignoux Michelle, Moucari Rami, Boyer Nathalie, Ripault Marie-Pierre, Cazals-Hatem Dominique, Giuily Nathalie, Castelnau Corinne, Cardoso Ana Carolina, Asselah Tarik, Féray Cyrille, Nicolas-Chanoine Marie Hélène, Bedossa Pierre, Marcellin Patrick
Université Paris VII, Hôpital Beaujon, Clichy, France.
Gastroenterology. 2008 Sep;135(3):821-9. doi: 10.1053/j.gastro.2008.05.044. Epub 2008 May 21.
BACKGROUND & AIMS: It is unclear whether hepatitis C virus (HCV) is eradicated in patients with chronic hepatitis C who achieved a sustained virologic response (SVR).
In this long-term follow-up study, including chronic hepatitis C patients who achieved SVR after interferon-based therapy, the presence of residual HCV RNA in serum, liver, and peripheral blood mononuclear cells (PBMCs) was assessed, using transcription-mediated amplification (sensitivity, <9.6 IU/mL). The benefit of SVR on liver fibrosis was evaluated using the METAVIR score.
A total of 344 patients were followed up for a median duration of 3.27 years (range, 0.50-18 y; interquartile range [IQR], 1.68-5.35 y). A total of 114 patients had a posttreatment liver tissue (median, 0.50 y; range, 0-14 y; IQR, 0-3.5 y) and a total of 156 had one PBMC (median, 3.0 y; range, 0.50-18 y; IQR, 1.25-5.50 y). Serum HCV RNA remained undetectable (1300 samples), indicating that none of the patients had a relapse. HCV RNA was detectable in 2 of 114 (1.7%) liver specimens, and in none of 156 PBMC specimens. Histologic analysis of 126 paired pretreatment and posttreatment liver biopsy specimens (median, 0.50 y; range, 0-14 y; IQR, 0-3.5 y) showed that fibrosis stage was improved in 56%, stable in 32%, deteriorated in 12%. Regression of cirrhosis was observed in 9 of 14 (64%) (95% confidence interval, 39-89) patients. No cirrhosis decompensation was observed, and 3 patients developed hepatocellular carcinoma.
In this large cohort of chronic hepatitis C patients, SVR was durable up to 18 years after treatment cessation, in addition to fibrosis stability/improvement (88%) and cirrhosis regression (64%). The presence of residual HCV RNA was observed only in liver tissue (1.7%). This result strongly suggests that SVR may be considered to show eradication of HCV infection.
目前尚不清楚在获得持续病毒学应答(SVR)的慢性丙型肝炎患者中丙型肝炎病毒(HCV)是否被清除。
在这项长期随访研究中,纳入接受基于干扰素治疗后获得SVR的慢性丙型肝炎患者,采用转录介导扩增法(灵敏度<9.6 IU/mL)评估血清、肝脏和外周血单个核细胞(PBMC)中残留HCV RNA的存在情况。使用METAVIR评分评估SVR对肝纤维化的益处。
共对344例患者进行了中位时长3.27年的随访(范围0.50 - 18年;四分位间距[IQR],1.68 - 5.35年)。共有114例患者有治疗后的肝组织样本(中位时长0.50年;范围0 - 14年;IQR,0 - 3.5年),156例患者有PBMC样本(中位时长3.0年;范围0.50 - 18年;IQR,1.25 - 5.50年)。血清HCV RNA仍未检测到(1300份样本),表明无患者复发。114份肝脏标本中有2份(1.7%)可检测到HCV RNA,156份PBMC标本中均未检测到。对126对治疗前和治疗后的肝脏活检标本(中位时长0.50年;范围0 - 14年;IQR,0 - 3.5年)进行组织学分析显示,纤维化阶段改善的占56%,稳定的占32%,恶化的占12%。14例患者中有9例(64%)(95%置信区间,39 - 89)观察到肝硬化消退。未观察到肝硬化失代偿,3例患者发生肝细胞癌。
在这一大型慢性丙型肝炎患者队列中,停止治疗后长达18年SVR仍然持久,此外肝纤维化稳定/改善(88%)且肝硬化消退(64%)。仅在肝组织中观察到残留HCV RNA(1.7%)。这一结果强烈提示可认为SVR表明HCV感染已被清除。