Chen Yi Mei Swee Lin G, Thompson Alexander J, Christensen Britt, Cunningham Georgina, McDonald Lucy, Bell Sally, Iser David, Nguyen Tin, Desmond Paul V
Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia.
Department of Medicine, University of Melbourne, Melbourne, Australia.
PLoS One. 2017 Oct 24;12(10):e0185609. doi: 10.1371/journal.pone.0185609. eCollection 2017.
BACKGROUND/AIMS: Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR) in people with chronic hepatitis C (CHC) infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart.
CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM) using transient elastography [FibroScan]) were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa) or advanced (METAVIR F3-4/ LSM >9.5 kPa). The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2) to advanced fibrosis at follow-up liver fibrosis assessment.
131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54-62) years with median estimated duration of infection 33-years (IQR 29-38). At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12-17). 109 (83%) participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002). The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343). However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F/U (p = 0.0001). SVR was independently associated with protection from liver fibrosis progression after adjustment for other variables including baseline ALT (p = 0.011), duration of HCV infection and mode of acquisition.
HCV eradication is associated with lower rates of liver fibrosis progression. The data support early treatment to prevent long-term liver complications of HCV infection.
背景/目的:缺乏验证慢性丙型肝炎(CHC)感染者持续病毒学应答(SVR)临床益处的长期随访研究。我们的目的是确定在一个大型、特征明确的CHC患者队列中肝纤维化进展的发生率和预测因素,这些患者相隔10年以上进行了配对肝纤维化评估。
确定2004年前接受过基线肝活检且10多年后进行了随访肝纤维化评估(活检或使用瞬时弹性成像[FibroScan]进行肝脏硬度测量[LSM])的CHC患者。对接受过基线肝活检但未进行随访纤维化评估的受试者进行LSM检查。纤维化分为轻度-中度(METAVIR F0-2/LSM结果≤9.5 kPa)或重度(METAVIR F3-4/LSM>9.5 kPa)。主要目标是评估SVR与至少10年肝纤维化进展率之间的关联,定义为从基线肝活检时的轻度-中度纤维化(METAVIR F0-2)进展到随访肝纤维化评估时的重度纤维化。
131名受试者纳入本分析:男性占69%,白种人占82%,基因1型丙型肝炎病毒(HCV)占60%,基因3型HCV占25%。随访纤维化分期时的中位年龄为57岁(四分位间距54-62岁),估计中位感染持续时间为33年(四分位间距29-38年)。随访时,86%的患者通过LSM进行肝纤维化评估,14%通过肝活检评估。纤维化评估之间的中位间隔时间为14年(四分位间距12-17年)。109名(83%)参与者接受了基于干扰素的抗病毒治疗。40%达到SVR。随访时,重度肝纤维化患者的比例显著增加:基线时为27%,随访时为46%(p=0.002)。达到SVR的受试者中重度纤维化的患病率没有变化,基线时为30%,随访时为25%(p=0.343)。然而,在持续病毒血症的受试者中,随访时重度纤维化更为常见:基线时为10%,随访时为31%(p=0.0001)。在对包括基线丙氨酸转氨酶(ALT)、HCV感染持续时间和感染获得方式等其他变量进行调整后,SVR与预防肝纤维化进展独立相关(p=0.011)。
根除HCV与较低的肝纤维化进展率相关。数据支持早期治疗以预防HCV感染的长期肝脏并发症。