Zeremski Marija, Dimova Rositsa B, Pillardy Jaroslaw, de Jong Ype P, Jacobson Ira M, Talal Andrew H
Division of Gastroenterology and Hepatology, Weill Cornell Medical College.
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine Department of Biostatistics, State University of New York, Buffalo.
J Infect Dis. 2016 Oct 15;214(8):1164-70. doi: 10.1093/infdis/jiw332. Epub 2016 Aug 2.
Fibrosis progression varies markedly in hepatitis C virus (HCV)-infected individuals. We investigated factors that influence fibrosis progression in chronic HCV infection.
HCV-infected patients who underwent at least 2 liver biopsies were included in this study. Associations between fibrosis progression and epidemiologic, virologic, and disease-associated factors were analyzed using logistic regression and multistate Markov modeling.
We analyzed 936 biopsy specimens obtained from 378 individuals. Mean age (±SD) at first biopsy was 48.3 ± 9.3 years, 59.3% of patients were male, 59.9% were white, and 86.7% were infected with HCV genotype 1. Fibrosis progression and cirrhosis occurred in 57.4% and 5.8%, respectively. Fibrosis progression between the first and last biopsies was associated with lower fibrosis in the first biopsy specimen (P < .001) and with the occurrence of at least 1 flare in the alanine aminotransferase (ALT) level (>200 U/L; P = .007). We found the highest fibrosis progression rate between stages 0 and 1 and the lowest between stages 2 and 3. Increased necroinflammation and higher ALT level were associated with faster progression. HCV genotype 3-infected patients were more likely to progress to cirrhosis (P < .001).
Fibrosis progression in HCV is not linear but varies according to stage, with the highest progression in patients with the lowest fibrosis severity. Patients who experience flares in the ALT level are also more likely to progress.
丙型肝炎病毒（HCV）感染个体的纤维化进展差异显著。我们研究了影响慢性HCV感染中纤维化进展的因素。
本研究纳入了接受至少2次肝活检的HCV感染患者。使用逻辑回归和多状态马尔可夫模型分析纤维化进展与流行病学、病毒学及疾病相关因素之间的关联。
我们分析了从378名个体获得的936份活检标本。首次活检时的平均年龄（±标准差）为48.3±9.3岁，59.3%的患者为男性，59.9%为白人，86.7%感染HCV 1型。纤维化进展和肝硬化的发生率分别为57.4%和5.8%。首次和末次活检之间的纤维化进展与首次活检标本中较低的纤维化程度相关（P<.001），并与丙氨酸氨基转移酶（ALT）水平至少出现1次升高（>200 U/L；P=.007）相关。我们发现0期和1期之间的纤维化进展率最高，2期和3期之间最低。坏死性炎症增加和ALT水平升高与进展加快相关。HCV 3型感染患者更易进展为肝硬化（P<.001）。
HCV的纤维化进展并非呈线性，而是根据阶段有所不同，纤维化严重程度最低的患者进展率最高。ALT水平出现波动的患者也更易进展。
