Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Sonographer School, Faculty of Health Science Technology, Chulabhorn Royal Academy, Bangkok, Thailand.
PLoS One. 2022 Jun 13;17(6):e0269641. doi: 10.1371/journal.pone.0269641. eCollection 2022.
Significant liver fibrosis regression occurs after hepatitis C virus (HCV) therapy. However, the impact of direct-acting antivirals (DAAs) on steatosis is less clear. This study was aimed at evaluating serial fibrosis and steatosis alterations in patients with HCV genotype 1, who achieved sustained virological response (SVR). We enrolled 55 HCV mono-infected and 28 HCV/HIV co-infected patients receiving elbasvir/grazoprevir from a clinical trial. Fibrosis and steatosis were assessed at baseline, follow-up week-24 (FUw24) and week-72 (FUw72) by magnetic resonance elastography (MRE) and proton density fat fraction (PDFF), respectively. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409, transmembrane six superfamily member 2 (TM6SF2) rs58542926 and membrane bound O-acyltransferase domain-containing 7 (MBOAT7) rs641738 polymorphisms were determined by allelic discrimination. Overall, mean MRE decreased significantly from baseline to FUw24 and FUw72. At FUw72, patients with baseline F2-F4 had higher rate of ≥30% MRE decline compared with individuals with baseline F0-F1 (30.2%vs.3.3%, P = 0.004). In multivariate analysis, significant fibrosis was associated with MRE reduction. The prevalence of steatosis (PDFF≥5.2%) at baseline was 21.7%. Compared to baseline, there were 17 (20.5%) patients with decreased PDFF values at FUw72 (<30%), while 23 (27.7%) patients had increased PDFF values (≥30%). Regarding the overall cohort, mean PDFF significantly increased from baseline to FUw72, and displayed positive correlation with body mass index (BMI) alteration. In multivariate analysis, the presence of diabetes, PNPLA3 CG+GG genotypes and increased BMI at FUw72 were significantly associated with progressive steatosis after SVR. Other genetic variants were not related to fibrosis and steatosis alteration. This study concluded that HCV eradication was associated with fibrosis improvement. However, progressive steatosis was observed in a proportion of patients, particularly among individuals with metabolic derangement and PNPLA3 variants. The combined clinical parameters and host genetic factors might allow a better individualized strategy in this sub-group of patients to alleviate progressive steatosis after HCV cure.
丙型肝炎病毒 (HCV) 治疗后会显著发生肝纤维化消退。然而，直接作用抗病毒药物 (DAA) 对脂肪变性的影响尚不清楚。本研究旨在评估接受格拉替雷/艾尔巴韦治疗的 HCV 基因 1 型患者的纤维化和脂肪变性的连续变化，这些患者达到持续病毒学应答 (SVR)。我们从临床试验中纳入了 55 名 HCV 单一感染和 28 名 HCV/HIV 合并感染患者，通过磁共振弹性成像 (MRE) 和质子密度脂肪分数 (PDFF) 分别在基线、随访 24 周 (FUw24) 和 72 周 (FUw72) 评估纤维化和脂肪变性。通过等位基因鉴别法测定 patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409、transmembrane six superfamily member 2 (TM6SF2) rs58542926 和 membrane bound O-acyltransferase domain-containing 7 (MBOAT7) rs641738 多态性。总体而言，MRE 平均值从基线到 FUw24 和 FUw72 显著下降。在 FUw72 时，基线 F2-F4 的患者与基线 F0-F1 的患者相比，MRE 下降≥30%的比例更高 (30.2%对 3.3%，P = 0.004)。多变量分析显示，显著纤维化与 MRE 降低相关。基线时脂肪变性 (PDFF≥5.2%) 的患病率为 21.7%。与基线相比，FUw72 时 17 名 (20.5%) 患者的 PDFF 值下降(<30%)，而 23 名 (27.7%) 患者的 PDFF 值升高(≥30%)。在总体队列中，PDFF 平均值从基线到 FUw72 显著增加，并且与体重指数 (BMI) 的变化呈正相关。多变量分析显示，SVR 后糖尿病、PNPLA3 CG+GG 基因型和 FUw72 时 BMI 增加与进行性脂肪变性显著相关。其他遗传变异与纤维化和脂肪变性变化无关。本研究得出结论，HCV 清除与纤维化改善相关。然而，在一部分患者中观察到进行性脂肪变性，特别是在存在代谢紊乱和 PNPLA3 变异的个体中。联合临床参数和宿主遗传因素可能允许在 HCV 治愈后对这组患者进行更好的个体化治疗策略，以减轻进行性脂肪变性。
