Mauss Stefan, Buendgens Lukas, Christensen Stefan, Ingiliz Patrick, Berger Florian, Hüppe Dietrich, Simon Karl Georg, Lutz Thomas, Schewe Knud, Boesecke Christoph, Tacke Frank
Center for HIV and Hepato-Gastroenterology, Düsseldorf, Germany.
Department of Medicine III, University-Hospital Aachen, Aachen, Germany.
Z Gastroenterol. 2019 Feb;57(2):139-147. doi: 10.1055/a-0752-0514. Epub 2019 Feb 12.
Disease activity, but also demographics, lifestyle, and comorbidities, may influence alanine aminotransferase (ALT) levels in hepatitis C virus (HCV)-infected patients. Direct-acting antiviral agents (DAA) achieve virological cure in > 90 % of patients, regardless of HCV genotype and fibrosis stage. This allows assessing determinants for ALT levels before and after elimination of HCV.
Our prospective cohort included HCV- and HIV/HCV-infected patients treated with DAA at 9 German centers (GECCO cohort). We analyzed all consecutive patients with sustained virological response (SVR) at week 12 (SVR12) and/or 24. Normal ALT was defined as ≤ 35 U/L, regardless of sex.
At baseline, 1477 out of 1774 patients (83 %) had ALT > 35 U/L, and 297 (17 %) had ALT ≤ 35 U/L. Baseline ALT > 35 U/L was independently associated with male sex, higher body mass index (BMI), liver cirrhosis, and not being on opioid substitution. After SVR, > 80 % of patients normalized ALT, and even patients with low baseline ALT further reduced ALT levels. However, ALT remained > 35 U/L in 15 % (221/1477) after SVR12. By multivariate analysis, ALT > 35 U/L at SVR12 was associated with male sex, higher BMI, liver cirrhosis, baseline ALT, HCV genotype 2, and younger age. Obesity, cirrhosis, and ALT were also independent factors associated with ALT > 15 U/L at SVR12 in patients with normal ALT at baseline.
Male sex, advanced liver fibrosis, and obesity are main risk factors for the lack of ALT normalization and/or ALT decline after SVR, indicative of fatty liver disease as a relevant comorbidity in hepatitis C.
疾病活动度，以及人口统计学特征、生活方式和合并症，都可能影响丙型肝炎病毒（HCV）感染患者的丙氨酸氨基转移酶（ALT）水平。直接抗病毒药物（DAA）可使超过90%的患者实现病毒学治愈，无论HCV基因型和纤维化阶段如何。这使得我们能够评估HCV清除前后ALT水平的决定因素。
我们的前瞻性队列包括在9个德国中心接受DAA治疗的HCV感染患者和HIV/HCV合并感染患者（GECCO队列）。我们分析了所有在第12周（SVR12）和/或第24周获得持续病毒学应答（SVR）的连续患者。无论性别，正常ALT定义为≤35 U/L。
基线时，1774例患者中有1477例（83%）ALT>35 U/L，297例（17%）ALT≤35 U/L。基线ALT>35 U/L与男性、较高的体重指数（BMI）、肝硬化以及未接受阿片类药物替代治疗独立相关。实现SVR后，超过80%的患者ALT恢复正常，即使是基线ALT较低的患者也进一步降低了ALT水平。然而，在SVR12后，仍有15%（221/1477）的患者ALT>35 U/L。通过多变量分析，SVR12时ALT>35 U/L与男性、较高的BMI、肝硬化、基线ALT、HCV基因型2以及较年轻的年龄相关。肥胖、肝硬化和ALT也是基线时ALT正常的患者在SVR12时ALT>15 U/L的独立相关因素。
男性、晚期肝纤维化和肥胖是SVR后ALT未恢复正常和/或ALT未下降的主要危险因素，表明脂肪肝是丙型肝炎中一种相关的合并症。
