Sezione di Gastroenterologia, DiBiMIS, University of Palermo, Palermo, Italy.
J Viral Hepat. 2012 Jul;19(7):465-72. doi: 10.1111/j.1365-2893.2011.01557.x. Epub 2011 Nov 28.
Methylenetetrahydrofolate reductase status, homocysteine and lipoproteins levels have been associated with severity of disease and both rapid and sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C (CHC). We aimed to assess the association of homocysteine and MTHFR status with serum cholesterol levels and their potential links to both histological findings and virological response, in patients with genotype 1 hepatitis C virus (HCV). A total of 119 consecutive patients were evaluated by biopsy and metabolic measurements. A total of 103 healthy blood donors were used as controls. Serum homocysteine and MTHFR C677T mutation were also evaluated. All patients underwent antiviral therapy with PEG-IFN alfa-2a plus ribavirin. HCV-RNA was assessed at baseline, week 4, week 12, at the end of therapy and after 6 months of follow-up. Mean serum values of homocysteine were higher in patients than in controls (15.8 ± 5.8 μg/L vs 12.5 ± 5.8 μg/L; P < 0.001), with a similar CC, CT and TT MTHFR distribution (23.6%, 48.7% and 27.7% in G1-CHC vs 34%, 48.5% and 17.5% in controls; P = 0.14). In genotype 1, HCV MTHFR TT homozygosis was independently linked to higher LDL (OR 1.016; CI 1.002-1.031; P = 0.03), but not to homocysteine. No association were found between homocysteine, MTHFR and histological features or both rapid virological response (RVR) and SVR. Low cholesterol (OR 0.988, 95%CI 0.975-0.999, P = 0.04) was independently linked to severe fibrosis, and high LDL was the only independent positive predictors of both RVR and SVR (OR 1.036; 95%CI 1.017-1.055; P < 0.001; and OR 1.016; 95%CI 1.001-1.031; P = 0.04 respectively). In patients with genotype 1 hepatitis C, showing higher homocysteine serum levels than controls, MTHFR C677T homozygosis, via modulating cholesterol levels, could interfere with liver fibrosis and response to antiviral therapy.
亚甲基四氢叶酸还原酶状态、同型半胱氨酸和脂蛋白水平与基因型 1 慢性丙型肝炎（CHC）患者的疾病严重程度以及快速和持续病毒学应答（SVR）有关。我们旨在评估同型半胱氨酸和 MTHFR 状态与血清胆固醇水平的相关性，以及它们与组织学发现和病毒学应答的潜在联系，在基因型 1 丙型肝炎病毒（HCV）患者中。总共评估了 119 名连续患者的活检和代谢测量结果。还使用了 103 名健康献血者作为对照。还评估了血清同型半胱氨酸和 MTHFR C677T 突变。所有患者均接受 PEG-IFN alfa-2a 联合利巴韦林的抗病毒治疗。HCV-RNA 在基线、第 4 周、第 12 周、治疗结束时和随访 6 个月时进行评估。与对照组相比，患者的血清同型半胱氨酸平均水平更高（15.8±5.8μg/L 比 12.5±5.8μg/L；P<0.001），MTHFR CC、CT 和 TT 分布相似（G1-CHC 中为 23.6%、48.7%和 27.7%，对照组中为 34%、48.5%和 17.5%；P=0.14）。在基因型 1 中，HCV MTHFR TT 纯合子与更高的 LDL 独立相关（OR 1.016；CI 1.002-1.031；P=0.03），但与同型半胱氨酸无关。同型半胱氨酸、MTHFR 与组织学特征或快速病毒学应答（RVR）和 SVR 之间均无相关性。低胆固醇（OR 0.988，95%CI 0.975-0.999，P=0.04）与严重纤维化独立相关，而高 LDL 是 RVR 和 SVR 的唯一独立阳性预测因子（OR 1.036；95%CI 1.017-1.055；P<0.001；OR 1.016；95%CI 1.001-1.031；P=0.04）。在基因型 1 丙型肝炎患者中，血清同型半胱氨酸水平高于对照组，MTHFR C677T 纯合子通过调节胆固醇水平，可能会干扰肝脏纤维化和抗病毒治疗的反应。
