Weigand Kilian, Peschel Georg, Grimm Jonathan, Müller Martina, Höring Marcus, Krautbauer Sabrina, Liebisch Gerhard, Buechler Christa
Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany.
Department of Gastroenterology, Gemeinschaftsklinikum Mittelrhein, 56073 Koblenz, Germany.
Biomedicines. 2022 Dec 6;10(12):3152. doi: 10.3390/biomedicines10123152.
: Infection with hepatitis C virus (HCV) lowers serum cholesterol levels, which rapidly recover during therapy with direct-acting antivirals (DAAs). Serum cholesterol is also reduced in patients with liver cirrhosis. Studies investigating serum cholesterol in patients with chronic liver diseases are generally based on enzymatic assays providing total cholesterol levels. Hence, these studies do not account for the individual cholesteryl ester (CE) species, which have different properties according to acyl chain length and desaturation. : Free cholesterol (FC) and 15 CE species were quantified by flow injection analysis high-resolution Fourier Transform mass spectrometry (FIA-FTMS) in the serum of 178 patients with chronic HCV before therapy and during treatment with DAAs. : Serum CEs were low in HCV patients with liver cirrhosis and, compared to patients without cirrhosis, proportions of CE 16:0 and 16:1 were higher whereas % CE 20:4 and 20:5 were reduced. FC levels were unchanged, and the CE/FC ratio was consequently low in cirrhosis. FC and CEs did not correlate with viral load. Four CE species were reduced in genotype 3 compared to genotype 1-infected patients. During DAA therapy, 9 of the 15 measured CE species, and the CE/FC ratio, increased. Relative to total CE levels, % CE 16:0 declined and % CE 18:3 was higher at therapy end. At this time, % CE 14:0, 16:0 and 16:1 were higher and % CE 20:4 and 22:6 were lower in the cirrhosis than the non-cirrhosis patients. Viral genotype associated changes of CEs disappeared at therapy end. : The serum CE composition differs between patients with and without liver cirrhosis, and changes through the efficient elimination of HCV. Overall, HCV infection and cirrhosis are associated with a higher proportion of CE species with a lower number of carbon atoms and double bonds, reflecting a less-favorable CE profile.
丙型肝炎病毒(HCV)感染会降低血清胆固醇水平,而在使用直接作用抗病毒药物(DAA)治疗期间血清胆固醇水平会迅速恢复。肝硬化患者的血清胆固醇也会降低。针对慢性肝病患者血清胆固醇的研究通常基于提供总胆固醇水平的酶法检测。因此,这些研究并未考虑到根据酰基链长度和去饱和度具有不同特性的各个胆固醇酯(CE)种类。通过流动注射分析高分辨率傅里叶变换质谱法(FIA-FTMS)对178例慢性HCV患者治疗前及使用DAA治疗期间的血清中的游离胆固醇(FC)和15种CE种类进行了定量分析。肝硬化的HCV患者血清CE水平较低,与无肝硬化患者相比,CE 16:0和16:1的比例较高,而CE 20:4和20:5的百分比降低。FC水平未发生变化,因此肝硬化患者的CE/FC比值较低。FC和CE与病毒载量无关。与基因型1感染患者相比,基因型3患者的4种CE种类减少。在DAA治疗期间,所检测的15种CE种类中的9种以及CE/FC比值升高。相对于总CE水平,治疗结束时CE 16:0的百分比下降,CE 18:3的百分比更高。此时,肝硬化患者的CE 14:0、16:0和16:1的百分比高于非肝硬化患者,而CE 20:4和22:6的百分比则较低。治疗结束时,病毒基因型相关的CE变化消失。有肝硬化和无肝硬化患者的血清CE组成不同,并且通过有效清除HCV会发生变化。总体而言,HCV感染和肝硬化与碳原子和双键数量较少的CE种类比例较高有关,这反映出CE谱不太理想。