Department of Oncology, Georgetown University, Washington, DC, United States of America.
Department of Biostatistics, Bioinformatics & Biomathematics, Georgetown University Medical Center, Washington, DC, United States of America.
PLoS One. 2021 Mar 11;16(3):e0247277. doi: 10.1371/journal.pone.0247277. eCollection 2021.
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.
HIV 合并感染与丙型肝炎（HCV）感染患者肝纤维化的快速进展有关。最近，为改善肝病的转归并确定合并感染患者的药物干预靶点，已开展了大量工作。在这项研究中，我们分析了妇女艾滋病研究机构（WIHS）1858 名参与者的临床数据，以确定与 APRI 和 FIB-4 等替代指标的肝纤维化进展相关的风险因素。我们评估了 661 名合并感染参与者中 887 个非同义单核苷酸变异（nsSNV）与肝纤维化风险改变的遗传相关性。所利用的变异产生了氨基酸取代，这些取代改变了 N 连接糖基化（NxS/T）序列或定位于与糖基化过程相关的基因。有 7 个变异与肝纤维化风险增加有关。最常见的变异是 ALPK2 rs3809973，与 HIV/HCV 合并感染患者的肝纤维化有关；与没有该变异的合并感染女性相比，罕见 C 等位基因纯合的个体显示出更高的 APRI（0.61，95%置信区间，0.334 至 0.875）和 FIB-4（0.74，95%置信区间，0.336 至 1.144）。虽然需要进一步验证，但 ALPK2 rs3809973 可能具有检测疾病进展风险增加的个体的潜力。
