HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. Recently, much work has been done to improve outcomes of liver disease and to identify targets for pharmacological intervention in coinfected patients. In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. Seven variants were associated with an increased likelihood of liver fibrosis. The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. Although warranting replication, ALPK2 rs3809973 may show utility to detect individuals at increased risk for liver disease progression.

中文翻译：

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ALPK2的基因组变异与HIV / HCV合并感染妇女的肝纤维化风险增加有关

HIV合并感染与丙型肝炎（HCV）感染中更快的肝纤维化进展有关。最近，已经进行了许多工作来改善肝病的预后并确定合并感染患者的药理干预目标。在这项研究中，我们分析了来自妇女机构间HIV研究（WIHS）的1858名参与者的临床数据，以表征与晚期肝纤维化的APRI和FIB-4替代指标变化相关的危险因素。我们评估了661个合并感染参与者的亚组中的887个非同义单核苷酸变异体（nsSNV）与肝纤维化风险变化的遗传关联。利用的变体产生了氨基酸取代，该氨基酸取代改变了N-连接的糖基化（NxS / T）后代或定位到与糖基化过程相关的基因上。七个变异与肝纤维化的可能性增加有关。最常见的变体ALPK2 rs3809973与HIV / HCV合并感染患者的肝纤维化相关；相对于那些没有变异的合并感染妇女，罕见的C等位基因纯合的个体显示出升高的APRI（0.61，95％CI，0.334至0.875）和FIB-4（0.74，95％CI，0.336至1.144）。尽管需要复制，但ALPK2 rs3809973可能显示出可用于检测肝病进展风险增加的个体。