High Serum Lipopolysaccharide-Binding Protein Level in Chronic Hepatitis C Viral Infection Is Reduced by Anti-Viral Treatments

Background
Lipopolysaccharide-binding protein (LBP) has been reported to associate with metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease. Since chronic hepatitis C virus (HCV) infection is associated with metabolic derangements, the relationship between LBP and HCV deserves additional studies. This study aimed to determine the serum LBP level in subjects with or without HCV infection and investigate the change of its level after anti-viral treatments with or without interferon.
Methods and Findings
We recruited 120 non-HCV subjects, 42 and 17 HCV-infected subjects respectively treated with peginterferon α-2a/ribavirin and direct-acting antiviral drugs. Basic information, clinical data, serum LBP level and abdominal ultrasonography were collected. All the subjects provided written informed consent before being enrolled approved by the Research Ethics Committee of the National Taiwan University Hospital. Serum LBP level was significantly higher in HCV-infected subjects than non-HCV subjects (31.0 ± 8.8 versus 20.0 ± 6.4 μg/mL; p-value < 0.001). After multivariate analyses, LBP at baseline was independently associated with body mass index, hemoglobin A1c, alanine aminotransferase (ALT) and HCV infection. Moreover, the baseline LBP was only significantly positively associated with ALT and inversely with fatty liver in HCV-infected subjects. The LBP level significantly decreased at sustained virologic response (27.4 ± 6.6 versus 34.6 ± 7.3 μg/mL, p-value < 0.001; 15.9 ± 4.4 versus 22.2 ± 5.7 μg/mL, p-value = 0.001), regardless of interferon-based or -free therapy.
Conclusions
LBP, an endotoxemia associated protein might be used as an inflammatory biomarker of both infectious and non-infectious origins in HCV-infected subjects.

研究背景
脂多糖结合蛋白（Lipopolysaccharide-binding protein, LBP）既往被证实与肥胖、糖尿病、非酒精性脂肪性肝病等代谢性疾病存在关联。鉴于慢性丙型肝炎病毒（Hepatitis C Virus, HCV）感染常伴随代谢紊乱，LBP与HCV感染之间的关联仍需进一步研究。本研究旨在明确HCV感染者与非感染者的血清LBP水平，并探讨接受或未接受干扰素抗病毒治疗后其水平的变化。

研究对象与方法及研究结果
本研究共招募120名非HCV感染者，以及分别接受聚乙二醇干扰素α-2a/利巴韦林（peginterferon α-2a/ribavirin）和直接抗病毒药物（direct-acting antiviral drugs）治疗的42名与17名HCV感染者。研究人员收集了受试者的基本信息、临床数据、血清LBP水平及腹部超声检查结果。所有受试者在入组前均签署了书面知情同意书，本研究方案已获台湾大学医院研究伦理委员会批准。
结果显示，HCV感染者的血清LBP水平显著高于非感染者（31.0±8.8 对比 20.0±6.4 μg/mL；p值<0.001）。经多因素分析，基线LBP水平与体质量指数、糖化血红蛋白（hemoglobin A1c, HbA1c）、丙氨酸氨基转移酶（alanine aminotransferase, ALT）及HCV感染独立相关。此外，在HCV感染者亚组中，基线LBP水平仅与ALT呈显著正相关，与脂肪肝病呈负相关。无论接受基于干扰素还是无干扰素的抗病毒治疗，受试者在获得持续病毒学应答（sustained virologic response, SVR）时，血清LBP水平均显著下降（分别为27.4±6.6 对比 34.6±7.3 μg/mL，p值<0.001；15.9±4.4 对比 22.2±5.7 μg/mL，p值=0.001）。

研究结论
脂多糖结合蛋白（LBP）作为一种与内毒素血症相关的蛋白，可作为HCV感染者感染性与非感染性来源炎症的生物标志物。