JH：慢性丙型肝炎患者病毒学治愈后肝纤维化可缓慢消退

慢性丙型肝炎既是一种病毒性感染疾病，也是一种肝纤维化疾病。对于实现持续病毒学应答（SVR）且伴有肝纤维化患者，仍存在发生并发症的可能。由于无法反复对患者进行肝活检，因此，还没有相应的研究对慢性丙型肝炎治疗前后肝纤维化的动力学特征进行评估。Fibrotest已被确证是表征肝纤维化进展和消退的生物标志物，具有与肝活检相当的预测价值。

基于上述情况，来自法国巴黎肝脏中心的Thierry Poynard等人展开一项研究，旨在通过Fibrotest这一检测手段推测肝纤维化程度，并评估SVR对肝纤维化动力学的影响。该研究结果在线发表于2013年5月28日的《肝脏病学杂志》（Journal of Hepatology）杂志上。作者发现，对于慢性丙型肝炎患者，实现病毒学治愈与十年之后肝纤维化的缓慢消退、肝硬化发病率下降5%以及原发性肝癌发生率维持在5%相关。

这是一项前瞻性队列研究，主要终点是十年时间里肝纤维化的消退速度，定义为Fibrotest计算结果至少下降0.20，相当于一级METAVIR分期。该研究一共纳入930例患者，这些患者既重复多次进行过Fibrotest测试，也进行了瞬时弹性成像。

研究结果如下：第10年时，在基线水平为晚期肝纤维化的415例患者中，其中108例实现SVR的患者中有49%（95% CI，33-64%）肝纤维化程度有所消退，SVR组的这一比例比无应答患者组（n=219）高[23%（14-33%；P<0.001 vs SVR），且不低于未经治疗患者组（n=88）[45%（10-80%；P=0.39 vs SVR）]。在所有实现SVR的患者（n=171）中，其中的43例肝硬化患者中有24例肝硬化程度有所逆转，但在另外的128例患者中，出现15例新发的肝硬化患者，净减少率只有5.3%[（24-15）=9/171）；（2.4-9.8%）]。在SVR组，出现4例原发性肝癌[4.6%，（0-9.8）]，而无应答组有13例[5.6%，（1.5-9.8）；P=0.07]。

研究发现，对于慢性丙型肝炎患者，通过Fibrotest推测其肝纤维化程度后发现，病毒学治愈与十年之后肝纤维化的缓慢消退、肝硬化发病率下降5%以及原发性肝癌发生率维持在5%相关。

Slow regression of liver fibrosis presumed by repeated biomarkers after virological cure in patients with chronic hepatitis C.
BACKGROUND AND AIMS
Chronic hepatitis C is both a virologic and a fibrotic disease and complications can occur in patients with sustained virologic response (SVR) with residual fibrosis. Due to the limitations of repeated biopsies, no studies have assessed the dynamic of fibrosis before and after treatment. Using biopsy as reference, Fibrotest has been validated as a biomarker of fibrosis progression and regression, with similar prognostic values. The aim was to estimate the impact of SVR on the dynamic of fibrosis presumed by Fibrotest.
METHODS
In a prospective cohort, the main endpoint was the 10-year regression rate of fibrosis, defined as a minimum 0.20 decrease in Fibrotest, equivalent to one METAVIR stage.
RESULTS
A total of 933 patients with both repeated Fibrotest and transient elastography were included. At 10 years, among the 415 patients with baseline advanced fibrosis, 49%(95%CI 33-64%) of the 108 SVR had a regression, which was greater than in the 219 non-responders [23% (14-33%;P<0.001 vs SVR)] and not lower than in the 88 non-treated [45%(10-80%;P=0.39 vs SVR) ]. In all 171 SVR, cirrhosis regressed in 24/43 patients, but 15 new cirrhosis occurred out of 128 patients, that is only a net reduction of 5.3%[ (24-15)=9/171);(2.4-9.8%)]. Four cases of primary liver cancer occurred in SVR[4.6%(0-9.8) ], and 13 in non-responders [5.6%(1.5-9.8);P=0.07].
CONCLUSION
In patients with chronic hepatitis C, and as presumed by Fibrotest, virological cure was associated with slow regression of fibrosis 10 years later, a disappointing 5% decrease in cirrhosis cases, and a remaining 5% risk of primary liver cancer.