血清铁蛋白水平与慢性丙型肝炎的一种独特表型相关，这种表型对聚乙二醇干扰素-α和利巴韦林治疗反应不佳。

Serum ferritin levels are associated with a distinct phenotype of chronic hepatitis C poorly responding to pegylated interferon-alpha and ribavirin therapy.

机构信息

Division of Gastroenterology and Hepatology, University Hospital Lausanne, Lausanne, Switzerland.

出版信息

Hepatology. 2012 Apr;55(4):1038-47. doi: 10.1002/hep.24787. Epub 2012 Feb 9.

DOI:10.1002/hep.24787

PMID:22095909

Abstract

UNLABELLED

Elevated serum ferritin levels may reflect a systemic inflammatory state as well as increased iron storage, both of which may contribute to an unfavorable outcome of chronic hepatitis C (CHC). We therefore performed a comprehensive analysis of the role of serum ferritin and its genetic determinants in the pathogenesis and treatment of CHC. To this end, serum ferritin levels at baseline of therapy with pegylated interferon-alpha and ribavirin or before biopsy were correlated with clinical and histological features of chronic hepatitis C virus (HCV) infection, including necroinflammatory activity (N = 970), fibrosis (N = 980), steatosis (N = 886), and response to treatment (N = 876). The association between high serum ferritin levels (> median) and the endpoints was assessed by logistic regression. Moreover, a candidate gene as well as a genome-wide association study of serum ferritin were performed. We found that serum ferritin ≥ the sex-specific median was one of the strongest pretreatment predictors of treatment failure (univariate P < 0.0001, odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.34-0.60). This association remained highly significant in a multivariate analysis (P = 0.0002, OR = 0.35, 95% CI = 0.20-0.61), with an OR comparable to that of interleukin (IL)28B genotype. When patients with the unfavorable IL28B genotypes were stratified according to high versus low ferritin levels, SVR rates differed by > 30% in both HCV genotype 1- and genotype 3-infected patients (P < 0.001). Serum ferritin levels were also independently associated with severe liver fibrosis (P < 0.0001, OR = 2.67, 95% CI = 1.68-4.25) and steatosis (P = 0.002, OR = 2.29, 95% CI = 1.35-3.91), but not with necroinflammatory activity (P = 0.3). Genetic variations had only a limited impact on serum ferritin levels.

CONCLUSION

In patients with CHC, elevated serum ferritin levels are independently associated with advanced liver fibrosis, hepatic steatosis, and poor response to interferon-alpha-based therapy.

摘要

未标注

血清铁蛋白水平升高可能反映全身炎症状态以及铁储存增加，这两者都可能导致慢性丙型肝炎（CHC）的不良结局。因此，我们对血清铁蛋白及其遗传决定因素在 CHC 的发病机制和治疗中的作用进行了全面分析。为此，我们在接受聚乙二醇干扰素-α和利巴韦林治疗或肝活检前，将基线时的血清铁蛋白水平与慢性丙型肝炎病毒（HCV）感染的临床和组织学特征（包括坏死性炎症活动[N=970]、纤维化[N=980]、脂肪变性[N=886]和治疗反应[N=876]）进行了相关性分析。通过逻辑回归评估高血清铁蛋白水平（>中位数）与终点之间的关联。此外，还进行了候选基因和全基因组关联研究。我们发现，血清铁蛋白水平≥性别特异性中位数是治疗失败的最强预处理预测因子之一（单变量 P<0.0001，比值比[OR]=0.45，95%置信区间[CI]=0.34-0.60）。在多变量分析中，该关联仍然具有高度显著性（P=0.0002，OR=0.35，95%CI=0.20-0.61），与白细胞介素（IL）28B 基因型的比值相当。当根据高血清铁蛋白水平与低血清铁蛋白水平对 IL28B 基因型不利的患者进行分层时，在 HCV 基因型 1 感染和 3 感染患者中，SVR 率差异>30%（P<0.001）。血清铁蛋白水平还与严重的肝纤维化（P<0.0001，OR=2.67，95%CI=1.68-4.25）和脂肪变性（P=0.002，OR=2.29，95%CI=1.35-3.91）独立相关，但与坏死性炎症活动（P=0.3）无关。遗传变异对血清铁蛋白水平的影响有限。