Malaguarnera Michele, Vacante Marco, Russo Cristina, Gargante Maria Pia, Giordano Maria, Bertino Gaetano, Neri Sergio, Malaguarnera Mariano, Galvano Fabio, Li Volti Giovanni
Department of Biochemistry, Medical Chemistry and Molecular Biology, University of Catania, Catania, Italy.
Hepat Mon. 2011 Feb;11(2):92-8.
Nonalcoholic fatty liver disease develops in patients with chronic hepatitis C. Interferon and ribavirin combination therapy is the standard treatment for chronic hepatitis C, but if present, NAFLD can reduce the virological response to anti-HCV therapies.
We determined whether the addition of rosuvastatin to interferon and ribavirin improves the sustained virological response (SVR) and reduces steatosis.
This study was a prospective, randomized, open-label trial. Between January 2004 and December 2007, 65 patients with chronic hepatitis (27 women and 38 men, mean age 48 years) aged 32-63 years (median 46 years) were consecutively enrolled. Patients were randomly assigned to receive leukocyte interferon alpha (3 MIU 3 times per week) plus ribavirin (1200 mg per day) for 12 months or interferon alpha and ribavirin at the same dosages plus rosuvastatin (5 mg per day). The primary endpoints were measurements in SVR, liver enzyme, cholesterol, triglyceride, CRP, glucose, and insulin levels; and Homa-IR, fibrosis, and steatosis scores.
After 12 months of treatment, we observed a significant improvement in SVR in 51% of patients who received interferon plus ribavirin plus rosuvastatin compared with 18% of relapsers (OR 1.52; 95% CI = 0.41-5.64; RR 1.13). There were 23 responders (69%) and 10 nonresponders (30%) (OR 1.38; 95% CI = 0.49-16.5; RR 1.11). When comparing interferon plus ribavirin group vs interferon plus ribavirin and rosuvastatin group after 12 months, we observed a significant difference in AST (85.70 vs.106.5.00 IU/ml) (OR 1.2; 95% CI= 0.29-4.94; RR 1.04; p<0.001), ALT (81.80 vs. 126.2 IU/ml) (OR 1.2; 95% CI = 0.29-4.94; RR 1.04; p < 0.001), LDL-cholesterol (0.01 vs. 0.60 mmol/l) (OR 14; 95% CI = 3.98-49.16; p RR 2.96; < 0.001), triglycerides (0.17 vs. 0.2 mmol/l) (OR 20; 95% CI = 4.94-80.89; RR 5.38; p < 0.05), and Viremia (1.8 vs. 2.48 UI/ml, p < 0.05). Mean fibrosis score decreased 0.10 vs. 0.50 (OR 4.5; 95% CI = 0.89-22.66; RR 1.5; p < 0.05), and mean steatosis score declined 0.30 vs. 0.50 (OR 11.2; CI = 2.88-43.53; RR 2.75; p < 0.001).
In HCV patients with NAFLD, the addition of rosuvastatin to interferon and ribavirin significantly reduces viremia, steatosis, and fibrosis without causing side effects.
非酒精性脂肪性肝病在慢性丙型肝炎患者中会出现。干扰素和利巴韦林联合疗法是慢性丙型肝炎的标准治疗方法，但如果存在非酒精性脂肪性肝病，可能会降低对抗丙型肝炎病毒疗法的病毒学应答。
我们确定在干扰素和利巴韦林中添加瑞舒伐他汀是否能改善持续病毒学应答（SVR）并减轻脂肪变性。
本研究是一项前瞻性、随机、开放标签试验。在2004年1月至2007年12月期间，连续纳入了65例年龄在32 - 63岁（中位数46岁）的慢性肝炎患者（27名女性和38名男性，平均年龄48岁）。患者被随机分配接受白细胞干扰素α（每周3次，每次3 MIU）加利巴韦林（每天1200 mg）治疗12个月，或接受相同剂量的干扰素α和利巴韦林加瑞舒伐他汀（每天5 mg）治疗。主要终点是SVR、肝酶、胆固醇、甘油三酯、CRP、葡萄糖和胰岛素水平的测量；以及Homa - IR、纤维化和脂肪变性评分。
治疗12个月后，我们观察到接受干扰素加利巴韦林加瑞舒伐他汀治疗的患者中，51%的患者SVR有显著改善，而复发者为18%（OR 1.52；95% CI = 0.41 - 5.64；RR 1.13）。有23例应答者（69%）和10例无应答者（30%）（OR 1.38；95% CI = 0.49 - 16.5；RR 1.11）。在比较12个月后干扰素加利巴韦林组与干扰素加利巴韦林和瑞舒伐他汀组时，我们观察到天冬氨酸转氨酶（AST）（85.70对106.5.00 IU/ml）（OR 1.2；95% CI = 0.29 - 4.94；RR 1.04；p < 0.001）、丙氨酸转氨酶（ALT）（81.80对126.2 IU/ml）（OR 1.2；95% CI = 0.29 - 4.94；RR 1.04；p < 0.001）、低密度脂蛋白胆固醇（0.01对0.60 mmol/l）（OR 14；95% CI = 3.98 - 49.16；p RR 2.96；< 0.001）、甘油三酯（0.17对0.2 mmol/l）（OR 20；95% CI = 4.94 - 80.89；RR 5.38；p < 0.05）和病毒血症（1.8对2.48 UI/ml，p < 0.05）有显著差异。平均纤维化评分从0.10降至0.50（OR 4.5；95% CI = 0.89 - 22.66；RR 1.5；p < 0.05），平均脂肪变性评分从0.30降至0.50（OR 11.2；CI = 2.88 - 43.53；RR 2.75；p < 0.001）。
在患有非酒精性脂肪性肝病的丙型肝炎病毒患者中，在干扰素和利巴韦林中添加瑞舒伐他汀可显著降低病毒血症、脂肪变性和纤维化，且无副作用。
