慢性丙型肝炎病人血糖血脂的变化及抗病毒治疗对其影响

发布时间：2018-07-27 18:55

【摘要】：背景及目的：慢性丙型肝炎（CHC）与糖脂代谢紊乱相关，但其引起血清血糖及血脂谱的变化趋势存在争议；干扰素联合利巴韦林抗HCV治疗后如何影响机体糖代谢及脂代谢，目前尚无定论。本文旨在探讨慢性丙型肝炎患者血糖、血脂的变化，以及普通干扰素联合利巴韦林抗病毒治疗对血脂、血糖及胰岛β细胞功能指标的影响。方法：本实验分为两部分，第一部分：从吉林大学第一医院肝胆胰内科2009年在吉林省某地流行病学调查中获得的样本中，筛选771例未经治疗的慢性丙型肝炎患者及679例健康对照人群。测定两组人群肝功、空腹血糖(FBG)、血清总胆固醇（TC）、甘油三酯（TG）。第二部分：从上述慢性丙型肝炎患者中筛选出183例接受规范普通干扰素（IFNα-2b）联合利巴韦林（RBV）治疗者。测定治疗前（0周）、治疗结束（48周）及治疗结束后24周（72周）时血清TC、TG、空腹胰岛素（FINS）、空腹C肽（FCP），并利用HOMA稳态模型计算各时间点胰岛素抵抗指数（HOMA-IR）、胰岛β细胞功能指数（HOMA-β）、胰岛素敏感性指数（ISI）。结果：第一部分：CHC组，血清TC水平显著低于健康组（4.82±1.10mmol/l vs5.29±1.16，P0.0001），，TG值亦较低（1.27±0.81mmol/l vs1.80±1.19mmol/l，P0.0001）。CHC组空腹血糖（FBG）明显高于健康组（5.77±2.23mmol/l vs5.37±1.43，P0.019）。Logistic回归分析可知，低总胆固醇（P0.0001，OR=0.714，95%CI：0.632，0.806），低甘油三酯（P0.0001，OR=0.629，95%CI：0.542，0.730），高龄（P0.0001，OR=1.123，95%CI：1.104，1.141）为CHC独立相关因素。第二部分：基线血清TC及TG在SVR组与非SVR组之间无差别（TC:P=0.111；TG：P=0.261）。SVR组患者血清TC在治疗结束时与基线相比较，显著下降（4.06±1.04vs4.51±0.95mmol/l，P0.0001），随访24周结束时，TC上升至4.45±0.89mmol/l，与基线水平持平。非SVR组，治疗过程，TC亦呈下降趋势，48周时明显低于基线水平（4.42±0.93mmol/l vs4.72±0.97mmol/l，P=0.010），但治疗结束后24周，TC值与48周时比较无差异，仍明显低于基线（4.39±0.78mmol/l vs4.72±0.97mmol/l，P=0.004）。 SVR组患者血清TG抗病毒治疗后由基线1.18±0.47mmol/l，升至1.61±1.07mmol/l（P0.0001)，随访24周结束时，持续处于较高水平，与基线相比显著差异（1.54±0.77mmol/l vs1.18±0.48mmol/l，P0.0001）。非SVR组，48周时TG较基线水平，亦明显升高（1.70±0.95mmol/l vs1.32±0.67mmol/l，P=0.03），而随访过程，TG下降，72周时较48周明显降低（1.42±0.87mmol/l vs1.70±0.95mmol/l，P=0.037），回复至基线水平（P=0.319）。 SVR组患者空腹胰岛素水平在治疗48周结束后，明显下降（7.88±4.15uU/ml vs8.30±3.80uU/ml，P=0.007），空腹C肽也呈现相同变化趋势（0.72±0.26nmol/l vs0.92±0.25nmol/l, P0.0001）。而非SVR组患者空腹胰岛素及空腹C肽在治疗前后均未出现明显变化。 SVR组患者，胰岛素抵抗（HOMA-IR）经抗病毒治疗后明显改善（1.62±0.94vs2.00±1.02，P0.0001），随访24周，SVR组胰岛素抵抗指数持续低于基线水平（1.86±1.20vs2.00±1.02，P=0.05）。同样的，胰岛素敏感性指数（ISI），治疗结束时较基线明显上升（-3.45±0.54vs-3.70±0.45，P0.0001），72周时，仍优于基线水平（P=0.05）。而非SVR组患者，HOMA-IR在治疗后亦出现下降，但与基线相比差异无显著性（2.16±1.42vs2.27±1.37，P=0.281），治疗结束后24周时，胰岛素抵抗即回复至基线水平，而ISI在治疗前后无变化。HOMA-β（β细胞功能），经治疗后，不论SVR与非SVR组，均出现明显升高（P0.0001），随访24周，较48时下降，但仍高于基线水平（SVR:P=0.01，NSVR:P=0.08）。 Logistic回归分析显示，高龄（P=0.004，OR=1.072，95%CI：1.023，1.123）、高病毒载量（P0.0001，OR=2.316，95%CI：1.596，3.362），基因型为1b型（P0.0001，OR=2.016，95%CI：1.116，3.122）为病毒学应答不佳的独立危险因素。结论： 1、慢性丙型肝炎患者血清总胆固醇、甘油三酯低于健康人群，血糖高于健康人群，在经抗病毒后有望恢复正常。 2、治疗前血清总胆固醇、甘油三酯与病毒学应答率无关。 3、血清总胆固醇经干扰素治疗呈现下降趋势，而甘油三酯水平上升。 4、有效抗病毒治疗可改善机体胰岛素抵抗、高胰岛素血症及胰岛β细胞功能。
[Abstract]:Background and purpose: chronic hepatitis C (CHC) is associated with glucose and lipid metabolism disorder, but the trend of blood glucose and blood lipid profiles in serum is controversial. The influence of interferon combined with ribavirin on glycometabolism and lipid metabolism after HCV treatment is not conclusive. The purpose of this study is to explore the blood glucose and blood lipid changes in chronic hepatitis C patients. And the effects of antiviral therapy combined with interferon and ribavirin on blood lipids, blood glucose and pancreatic beta cell function.
Methods: the experiment was divided into two parts. The first part: from the epidemiological survey of Jilin province in 2009, 771 cases of chronic hepatitis C and 679 healthy controls were selected from the hepatobiliary and pancreatic Department of No.1 Hospital of Jilin University. Two groups of human group liver function, fasting blood glucose (FBG), serum total cholesterol (TC) were measured. ), triglyceride (TG). Second: 183 patients were screened from the above chronic hepatitis C patients with normal interferon (IFN alpha -2b) combined with Leigh Bhave Lin (RBV). The serum TC, TG, FINS, FCP, and HOMA homeostasis were measured before treatment (0 weeks), treatment end (48 weeks) and 24 weeks (72 weeks) after the end of treatment. The insulin resistance index (HOMA-IR), islet beta cell function index (HOMA- beta) and insulin sensitivity index (ISI) at different time points were calculated by the model.
Results: the first part: in group CHC, the level of serum TC was significantly lower than that in the healthy group (4.82 + 1.10mmol/l vs5.29 + 1.16, P0.0001), and the TG value was also lower (1.27 + 0.81mmol/l vs1.80 + 1.19mmol/l, P0.0001).CHC group (FBG) was significantly higher than that of the healthy group (5.77 + 1.43. OR=0.714,95%CI:0.632,0.806), low triglyceride (P0.0001, OR=0.629,95%CI:0.542,0.730) and advanced age (P0.0001, OR=1.123,95%CI:1.104,1.141) were independent factors of CHC.
The second part: the baseline serum TC and TG were not different between the SVR group and the non SVR group (TC:P=0.111; TG:P=0.261).SVR group. The serum TC was significantly decreased (4.06 + 1.04vs4.51 + 0.95mmol/l, P0.0001) at the end of the treatment. At the end of the 24 weeks of follow-up, the TC increased to 4.45 + and was equal to the baseline level. TC also showed a downward trend, which was significantly lower than baseline (4.42 + 0.93mmol/l vs4.72 + 0.97mmol/l, P=0.010) at 48 weeks, but there was no difference between TC and 48 weeks at the end of the treatment, and still significantly lower than the baseline (4.39 + 0.78mmol/l vs4.72 + 0.97mmol/l, P=0.004).
The antiviral treatment of serum TG in group SVR was increased to 1.61 + 1.07mmol/l (P0.0001) after the baseline of 1.18 + 0.47mmol/l. At the end of the 24 week of follow-up, it continued to be at a higher level, compared with the baseline (1.54 + 0.77mmol/l vs1.18 + 0.48mmol/l, P0.0001). The non SVR group was also significantly higher than the baseline at 48 weeks (1.70 + 0.95mmol/l). L/l, P=0.03), and during the follow-up, TG decreased, and decreased significantly at 72 weeks compared with 48 weeks (1.42 + 0.87mmol/l vs1.70 + 0.95mmol/l, P=0.037), and returned to baseline (P=0.319).
The level of fasting insulin in group SVR was significantly decreased after 48 weeks of treatment (7.88 + 4.15uU/ml vs8.30 + 3.80uU/ml, P=0.007), and the same change trend was found in the fasting C peptide (0.72 + 0.26nmol/l vs0.92 + 0.25nmol/l, P0.0001), but there was no significant change in the fasting insulin and fasting C peptide in the non SVR group before and after treatment.
In group SVR, insulin resistance (HOMA-IR) improved significantly after antiviral therapy (1.62 + 0.94vs2.00 + 1.02, P0.0001), and followed up for 24 weeks. The insulin resistance index in SVR Group continued to be lower than the baseline (1.86 + 1.20vs2.00 + 1.02, P=0.05). Similarly, the insulin sensitivity index (ISI) and the baseline of treatment were significantly higher (-3.45 + 0.54vs-3.70 + 0.45). P0.0001) was still better than baseline (P=0.05) at 72 weeks. But in non SVR group, HOMA-IR was also decreased after treatment, but there was no significant difference compared with baseline (2.16 + 1.42vs2.27 + 1.37, P=0.281). At the end of the treatment, insulin resistance returned to the baseline level, and ISI had no change of.HOMA- beta (beta cell function) before and after treatment, and the treatment was treated before and after treatment. After treatment, both SVR and non SVR group increased significantly (P0.0001). After 24 weeks of follow-up, they decreased at 48, but still higher than baseline (SVR:P=0.01, NSVR:P=0.08).
Logistic regression analysis showed that the elderly (P=0.004, OR=1.072,95%CI:1.023,1.123), high viral load (P0.0001, OR=2.316,95%CI:1.596,3.362) and genotype 1b (P0.0001, OR=2.016,95%CI:1.116,3.122) were independent risk factors for virological response.
Conclusion:
1, serum total cholesterol and triglycerides in patients with chronic hepatitis C are lower than those in healthy people. Blood glucose is higher than healthy people, and is expected to return to normal after antiviral treatment.
2, serum total cholesterol and triglyceride were not correlated with virological response rate before treatment.
3, serum total cholesterol showed a downward trend after interferon treatment, while triglyceride level increased.
4, effective antiviral therapy can improve insulin resistance, hyperinsulinemia and islet beta cell function.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.63

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