Division of Digestive Diseases and Nutrition, Department of Health and Human Services, National Institutes of Health, Bethesda, MD 20892-5450, USA.
Hepatology. 2010 Feb;51(2):585-94. doi: 10.1002/hep.23315.
Studies of the prognostic value of Ishak fibrosis stage are lacking. We used multi-year follow-up of the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial to determine whether individual Ishak fibrosis stages predicted clinical outcomes in patients with chronic hepatitis C. Baseline liver biopsy specimens from 1050 patients with compensated chronic hepatitis C who had failed combination peginterferon and ribavirin were reviewed by a panel of expert hepatopathologists. Fibrosis was staged with the Ishak scale (ranging from 0 = no fibrosis to 6 = cirrhosis). Biopsy fragmentation and length as well as number of portal tracts were recorded. We compared rates of prespecified clinical outcomes of hepatic decompensation and hepatocellular carcinoma across individual Ishak fibrosis stages. Of 1050 biopsy specimens, 25% were fragmented, 63% longer than 1.5 cm, 69% larger than 10 mm(2), and 75% had 10 or more portal tracts. Baseline laboratory markers of liver disease severity were worse and the frequency of esophageal varices higher with increasing Ishak stage (P < 0.0001). The 6-year cumulative incidence of first clinical outcome was 5.6% for stage 2, 16.1% for stage 3, 19.3% for stage 4, 37.8% for stage 5, and 49.3% for stage 6. Among nonfragmented biopsy specimens, the predictive ability of Ishak staging was enhanced; however, no association was observed between Ishak stage and outcomes for fragmented biopsy specimens because of high rates of outcomes for patients with noncirrhotic stages. Similar results were observed with liver transplantation or liver-related death as the outcome.
Ishak fibrosis stage predicts clinical outcomes, need for liver transplantation, and liver-related death in patients with chronic hepatitis C. Patients with fragmented biopsy specimens with low Ishak stage may be understaged histologically.
缺乏对 Ishak 纤维化分期的预后价值的研究。我们使用丙型肝炎抗病毒长期治疗肝硬化（HALT-C）试验的多年随访结果，来确定慢性丙型肝炎患者的个体 Ishak 纤维化分期是否可以预测临床结局。对 1050 例代偿性慢性丙型肝炎患者的基线肝活检标本进行了回顾性研究，这些患者曾联合使用聚乙二醇干扰素和利巴韦林治疗但失败。由一组专家病理学家采用 Ishak 评分系统（范围从 0 = 无纤维化到 6 = 肝硬化）对纤维化进行分期。记录了活检组织的碎片化和长度以及门脉管腔的数量。我们比较了各个 Ishak 纤维化分期的肝失代偿和肝细胞癌的特定临床结局的发生率。在 1050 份活检标本中，25%为碎片化，63%长度大于 1.5 厘米，69%面积大于 10 毫米 2 ，75%有 10 个或更多的门脉管腔。随着 Ishak 分期的增加，基线肝功能严重程度的实验室标志物恶化，食管静脉曲张的发生率更高（P < 0.0001）。第 6 年首次临床结局的累积发生率为 2 期 5.6%，3 期 16.1%，4 期 19.3%，5 期 37.8%，6 期 49.3%。在非碎片化活检标本中，Ishak 分期的预测能力得到了增强；然而，由于非肝硬化阶段患者的结局发生率较高，因此未观察到 Ishak 分期与活检标本结局之间的关联。对于肝移植或与肝脏相关的死亡作为结局，也观察到了类似的结果。
Ishak 纤维化分期可预测慢性丙型肝炎患者的临床结局、需要肝移植和与肝脏相关的死亡。具有低 Ishak 分期的碎片化活检标本的患者可能存在组织学分期不足。
