Petta Salvatore, Cammà Calogero, Di Marco Vito, Alessi Nicola, Cabibi Daniela, Caldarella Rosalia, Licata Anna, Massenti Fatima, Tarantino Giuseppe, Marchesini Giulio, Craxì Antonio
Cattedra ed Unità Operativa di Gastroenterologia, University of Palermo, Palermo, Italy.
Am J Gastroenterol. 2008 May;103(5):1136-44. doi: 10.1111/j.1572-0241.2008.01813.x.
Metabolic factors may affect the course of chronic hepatitis C (CHC). Insulin resistance (IR) determines steatosis, but its direct role in affecting progression of hepatic fibrosis is less clear. We aimed to assess whether increasing degrees of IR, up to overt diabetes, are linked to steatosis and higher stages of fibrosis in patients with CHC resulting from genotype 1 HCV (G1-HCV).
Two hundred one consecutive patients with G1-HCV infection were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR, by the homeostasis model assessment (HOMA). Nondiabetic patients were defined as insulin resistant if HOMA-IR was >2.7. All biopsies were scored by one pathologist for staging and grading (Scheuer), and graded for steatosis.
Ninety-six patients were noninsulin resistant (group 1), 76 were insulin resistant without diabetes (group 2), and 29 were diabetic (group 3). At multivariate analysis, fibrosis of >/=3 was independently associated with high necroinflammatory activity (odds ratio [OR] 2.994, 95% confidence interval [CI] 1.422-6.098), low platelets (OR 0.994, 95% CI 0.981-0.999), low cholesterol (OR 0.987, 95% CI 0.976-0.998), high ferritin (OR 1.002, 95% CI 1.001-1.004), and a high prevalence of IR (OR 2.692, 95% CI 1.463-4.954). Diabetic patients were twice as likely to have severe fibrosis (60%) than those with IR but no diabetes (30%) (P= 0.006). The degree of steatosis and that of fibrosis were weakly associated with each other (P= 0.42).
In subjects with CHC resulting from G1-HCV, IR and overt diabetes are major determinants of advanced fibrosis, regardless of the degree of steatosis, mainly in the presence of severe necroinflammation.
代谢因素可能影响慢性丙型肝炎（CHC）的病程。胰岛素抵抗（IR）决定脂肪变性，但其在影响肝纤维化进展中的直接作用尚不清楚。我们旨在评估直至显性糖尿病的不同程度的IR是否与1型丙型肝炎病毒（G1-HCV）所致CHC患者的脂肪变性及更高阶段的纤维化相关。
对201例连续的G1-HCV感染患者进行肝活检以及人体测量和代谢指标检测，包括通过稳态模型评估（HOMA）检测IR。若HOMA-IR>2.7，则非糖尿病患者被定义为胰岛素抵抗。所有活检标本由一名病理学家进行分期和分级（Scheuer法），并对脂肪变性进行分级。
96例患者无胰岛素抵抗（第1组），76例患者有胰岛素抵抗但无糖尿病（第2组），29例患者患有糖尿病（第3组）。多因素分析显示，纤维化≥3级与高坏死性炎症活动独立相关（比值比[OR]2.994，95%置信区间[CI]1.422 - 6.098）、血小板减少（OR 0.994，95% CI 0.981 - 0.999）、胆固醇降低（OR 0.987，95% CI 0.976 - 0.998）、铁蛋白升高（OR 1.002，95% CI 1.001 - 1.004）以及IR的高患病率（OR 2.692，95% CI 1.463 - 4.954）相关。糖尿病患者发生严重纤维化的可能性是有胰岛素抵抗但无糖尿病患者的两倍（60%对30%）（P = 0.006）。脂肪变性程度与纤维化程度之间的相关性较弱（P = 0.42）。
在G1-HCV所致CHC患者中，IR和显性糖尿病是晚期纤维化的主要决定因素，与脂肪变性程度无关，主要存在于严重坏死性炎症的情况下。
