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慢性丙型肝炎、肝硬化的磁共振波谱研究及应用波谱成像评估抗病毒治疗的疗效
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摘要
目的:
     探讨慢性丙型肝炎、丙型肝炎所致肝硬化的磁共振波谱代谢产物的变化及利用有价值的变化评估慢性丙型肝炎、丙型肝炎所致肝硬化抗病毒治疗的疗效。
     方法:
     1、有肝穿结果的丙型肝炎及丙型肝炎所致肝硬化患者45例(经入选标准及排除标准选择后),分别行3.0T磁共振1H-MRS及31P-MRS扫描。1H-MRS研究中将患者分为无脂肪肝组、轻度脂肪肝组、中度脂肪肝组及重度脂肪肝组。重建1H-MRS谱线获得水峰峰值、水峰峰下面积、脂峰峰值、脂峰峰下面积,根据以上数据,计算出水峰和脂峰的波峰值之比、波峰下面积之比。与病理比较,分析以上参数是否具有统计学意义。31P-MRS研究中将患者分为轻度肝炎组、中度肝炎组、肝硬化组,15例健康志愿者作为对照组,重建31P-MRS的波谱曲线,获得从左到右PE、PC、Pi、GPE、GPC、γ-ATP、α-ATP、β-ATP曲线,根据各自峰下面积计算峰下面积百分含量。与病理比较,分析以上参数是否具有统计学意义。
     2、将54慢性丙型肝炎、丙型肝炎所致肝硬化患者(经入选标准及排除标准选择后)在接受抗病毒治疗前、治疗6个月后分别进行1H-MRS及31P MRS成像。分别分析1H-MRS中水峰峰值、水峰峰下面积、脂峰峰值、脂峰峰下面积,水峰和脂峰的波峰值之比、波峰下面积之比的变化。及31P-MRS的代谢产物(PE+PC)/(GPE+GPC)变化。
     结果:
     1、45例有肝穿结果的患者中,1例1H-MRS未成功,44例成功病例中脂峰、脂峰峰下面积在无脂肪肝组与中度脂肪肝组之间、无脂肪肝组与重度脂肪肝组之间以及轻度脂肪肝组与中度脂肪肝组之间、轻度脂肪肝与重度脂肪肝组之间、中度脂肪肝与重度脂肪肝组比较差异均有统计学意义(P<0.05),无脂肪肝组与轻度脂肪肝组之间差异无统计学意义(P>0.05)。脂/水峰值比、脂/水峰下面积比各组间均具有统计学意义(P<0.05)。6例31P MRS未成功,39例成功病例中(PC+PE)%及(PC+PE)/(GPC+GPE)各组间均具有统计学意义(P<0.05),(PC+PE)/(GPC+GPE)差异具有显著统计学意义。
     2、54慢性丙型肝炎、丙型肝炎所致肝硬化患者在接受抗病毒治疗前、治疗6个月后脂质的峰值、脂质的峰下面积、脂/水峰值比和脂/水峰下面积比比较,对照组和治疗组治疗前无统计学意义(P>0.05),治疗后有统计学意义(P<0.05),对照组治疗前后无统计学意义(P>0.05),治疗组治疗前后有统计学意义(P<0.05)。(PC+PE)/(GPC+GPE)比值在治疗组抗病毒6月后较治疗前显著降低,具有统计学意义(P<0.05),在对照组没有明显变化。在抗病毒治疗应答组,(PC+PE)/(GPC+GPE)明显下降,病毒学无应答组,(PC+PE)/(GPC+GPE)比值类似于治疗前水平。
     结论:
     磁共振波谱可以用来提供肝细胞代谢水平的信息。1H-MRS可以定量评估脂肪沉积程度,31P-MRS可以准确反映丙型肝炎、丙型肝炎所致肝硬化肝纤维化的严重程度。应用1H-MRS及31P-MRS可以作为慢性丙型肝炎患者抗病毒治疗疗效及脂肪沉积程度的指标。
Objective:
     To investigate changes in magnetic resonance spectroscopy metabolites ofchronic hepatitis C and cirrhosis caused by hepatitis C. And to assess antiviraltreatment efficacy in chronic hepatitis C, cirrhosis of the liver caused by the hepatitisC using valuable changes.
     Method
     1.45cases of hepatitis C and cirrhosis of the liver caused by hepatitis C whohave liver biopsy results,26were male and19females, aged34-66years, mean44.2years old. All enrolled patients were naive to anti-viral treatments. Other inclusioncriteria were:(1) HCV RNA>500copies/mL;(2) absence of complications such asgastrointestinal bleeding, hepatic encephalopathy, and primary liver cancer; and (3)liver function defined as Child-Pugh grade A or B based on encephalopathy, andprothrombin time. Patients with hypersplenism were also enrolled. Exclusion criteriawere:(1) Infection infection with hepatitis A, B, D, or F virus, Epstein-Barr virus,cytomegalovirus, or human immunodeficiency virus; and (2) Presence presence ofalcoholic or drug-induced liver diseases, or severe heart, brain, or kidney disease.According to the2003branch of the Chinese Medical Association to develop liverfatty liver disease classification criteria for grading liver fat content[24],Hepaticsteatosis30%to50%of mild fatty liver;50%to75%for the moderate fatty liver;over75%of severe fatty liver. Fatty degeneration of the field of vision is less than30%of liver cells is not enough on fatty liver standard, known as hepatic steatosis, isno fatty liver. They were scored according to the Ishak system, The subdivisionof these patients into mild and moderate disease was based on the Ishak fibrosis (F)and necroinflammatory (NI) scoring system: mild hepatitis (F≤2andNI≤3),moderate hepatitis (3≤F<6and NI>4) and Cirrhosis(F=6).They wereperformed3.0T MRI1H-MRS and31P-MRS scans. Patients of1H-MRS study groupwill be divided into no fatty liver, mild fatty liver group, moderate and severe fattyliver fatty liver group. Reconstruction1H-MRS spectra obtained water peak, the area under water peak, fat peak, the area under fat peak. Based on the above data, ratio ofthe fat peak to the water peak and ratio of the area under fat peak to the area underwater peak were calculated. Compared with the pathological analysis whether theabove parameters are statistically significant. Patients will be divided into mildhepatitis, moderate hepatitis, cirrhosis, and15healthy volunteers as a control group in31P-MRS study. To reconstruct the curve of31P-MRS spectral, and obtain the curvefrom left to right PE, PC, Pi, GPE, GPC, γ-ATP, α-ATP, β-ATP. According to eacharea under the peak we can calculate the percentage of the area. Compared with thepathological analysis whether the above parameters are statistically significant.
     2. The54patients of chronic hepatitis C and cirrhosis caused by hepatitis C (afterinclusion criteria and exclusion criteria selection) before receiving antiretroviraltreatment and six months later after antiretroviral treatment, respectively perform1H-MRS and31P MRS scan. To analyze the changes of water peak, the area underwater peak, fat peak, the area under fat peak, ratio of the fat peak to the water peakand ratio of the area under fat peak to the area under water peak respectively in1H-MRS. And changes of metabolites (PE+PC)/(GPE+GPC) in31P-MRS.
     Result:
     1.45cases of patients who have liver biopsy results, and one case of1H-MRSwas not successful.44cases of successful cases, the difference between the differentlevels of pathology analysis of variance showed differences of fat peak, the area underfat peak, ratio of the fat peak to the water peak and ratio of the area under fat peak tothe area under water peak were statistically significant. With the increase of theseverity of fatty liver, each index value correspondingly increase (P <0.05). Pairwisecomparison results mean difference between groups of display, fat peak, the areaunder fat peak, ratio of the fat peak to the water peak and ratio of the area under fatpeak to the area under water peak were statistically significant in the non-fatty livergroup and moderate fatty liver group, no difference between group and severe fattyliver fatty liver group and a group with mild to moderate fatty liver fatty liver group,moderate and severe fatty liver fatty liver group(P<0.05), between non-fatty liver group and mild fatty liver group difference was not statistically significant (P>0.05).6cases were not successful in31P MRS,39cases of successful cases based on Isbakscoring system, Mild hepatitis,13cases (33.33%), moderate hepatitis,15cases(38.46%), cirrhosis,11cases (28.21%). With the increase of disease severity, PC+PE%increased significantly, GPC+GPE%reduction, PC+PE%between the groupswas statistically significant, The PC+PE/GPC+GPE increased this differencebetween the groups was statistically significance obviously. Among other metabolitesgroup (Pi%, γ-ATP%, α-ATP%, β-ATP%) was not statistically significant.
     2.54patients of chronic hepatitis C, cirrhosis of the liver caused by the hepatitisC comparing before receiving antiretroviral therapy with after6months treatment fatpeak, the area under fat peak, ratio of the fat peak to the water peak and ratio of thearea under fat peak to the area under water peak were statistically significant betweenthe control group and the treatment group.32patients sustained viral response toantiviral therapy.25cases in these patients ratio of the fat peak to the water peak andratio of the area under fat peak to the area under water peak were decline in follow-upmagnetic resonance spectroscopy after six months, P <0.05. Seven cases similar to theprevious after treatment.12cases of the virus non-responders11cases are similar tothe previous after treatment in ratio of the fat peak to the water peak and ratio of thearea under fat peak to the area under water peak. In the control group and thetreatment group before treatment PME/PDE was no significant difference, after sixmonths treatment, the difference was statistically significant. In the treatment group,PC+PE/GPC+GPE ratio was significantly reduced after antiretroviral therapycompared with prior, no significant change in the control group.32patients withsustained virological response to antiviral therapy,in these patients, PME/PDE ratiodecreased in25patients after antiretroviral therapy (78%),four cases had no change,while three cases increased slightly.12cases non-responders patients,1patient (8%)PME/PDE ratio decreased, two cases almost unchanged, nine cases increased slightly,p <0.05.
     Conclusion:
     MR spectroscopy is a noninvasive method,which can provide information onliver cell metabolism.1H-MRS can be quantitatively assess the extent of fatdeposition,31P-MRS can accurately reflect hepatitis C liver cell metabolism.Application of1H-MRS and31P-MRS in patients with chronic hepatitis C can beused as antiviral therapy and the indicator of the degree of fat deposition.
引文
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