中医辨证治疗难治性丙型肝炎疗效观察及中医证型与T淋巴细胞亚群关系的研究
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摘要
慢性丙型肝炎是一个严重危害人类健康的公共卫生问题。据WHO统计全球丙型肝炎病毒（HCV）感染率3%,约1.7亿人，每年新发丙肝3.5万例。根据2010年9月国家卫生部公布的最新流行病学调查结果显示，我国抗HCV阳性率为0.43％，大概全国HCV感染者达500多万。HCV自然感染史长，其慢性化率为50%～85%。肝硬化和肝癌是慢性丙型肝炎患者的主要死因，在感染的5～0年后30%～40%将发展为肝硬化，10～20年后5%～7%发展为肝癌。成为现今严重危害人民健康的传染病之一。尽管现代医学在慢性丙型肝炎的治疗上取得一些突破性进展，其三联疗法成为基因1b型等一些难治性丙肝的最新方案。但对于耐药、抗病毒无效者及在治疗中出现药物毒副作用、停药后复发、病毒学突破、部分应答、无效应答或无应答、基因1型或4型HCV感染、高病毒载量(HCV RNA≥1.5×106IU/mL)、合并其他病毒感染,或同时合并其他如糖尿病、甲状腺功能障碍、血友病、器官移植、肾脏疾病及血液透析等自身免疫功能障碍有关的疾病及肝硬化失代偿期等问题的存在，使得丙肝治疗依然是临床难题，即所谓的难治性慢性丙型肝炎。目前由HCV基因1型感染所致的慢性丙型肝炎在我国约占78%,高病毒载量的慢性丙型肝炎约占69%,所以可以说在我国大多数的慢性丙型肝炎属于难治性丙型肝炎。RHC形成复杂，因而其临床表现也多种多样。通过“十一五”对CHC中医症候辨证分型规范研究显示：正虚邪恋、肝郁脾虚、肝肾阴虚三型占所有证型的73%，故虚实夹杂的临床表现是CHC的主要特征，若不实行临床干预，任其进一步发展，必将形成肝硬化等难治性肝病，其预后不佳，对患者生命将形成极大的威胁，对治疗造成巨大的挑战。在RHC治疗方面，并无特别有效的方法。聚乙二醇化a干扰素(PEG-IFN-a)联合利巴韦林进行优化治疗或标准方案联合蛋白酶抑制剂对基因1型的治疗仍然是当前的首要选择。但是由于干扰素、利巴韦林及蛋白酶抑制剂具有难以适应的毒副作用，使RHC治疗更为困惑。因此，进一步探求难治性丙型肝炎免疫发病机制及寻找其治疗的有效方案是医学和临床的迫切需求，中医药以其独特优势，在防治慢性丙型病毒性肝炎方面积累了丰富的经验。从传统的辨证论治、专病专方专药、针灸、单药、民间验方，发展到现在的中西医结合治疗方案，都有中医药作出的贡献。多年的研究也证实，中医药在慢性丙型肝炎的防治中不仅可以缓解患者症状，减轻肝脏炎症，而且能抑制或抗病毒，逆转肝脏早期肝纤维化，减轻西药的毒副作用，延缓其慢性化，增强机体免疫，提高患者生活质量，以达到延长生存期，预防肝硬化、肝癌等终末期肝病，意义重大。
目的：本研究在“十一五”慢性丙型肝炎证候规律及中西医结合治疗方案研究的基础上，依托国家“十二五”难治性丙型肝炎的中医药治疗方案，以中药辨证方（益气解毒方、疏肝健脾方、补肾柔肝方）治疗难治性丙型肝炎，观察其临床疗效、转氨酶和HCV RNA转阴率及下降率（HCV RNA下降2log），并对其免疫功能与转氨酶、病毒载量以及中医证型与T淋巴细胞亚群、HCV RNA等相关性进行研究，运用计算机统计学软件进行数据处理和综合分析，以探讨中药辨证方对难治性丙型肝炎的临床疗效以及RHC的病毒载量、肝脏炎症、免疫调节机制与中医证型之间的相关性，以便进一步提高难治性丙型病毒性肝炎的临床治疗水平。
方法：实验分三个部分进行
第一部分：中医药辨证方治疗难治性丙型肝炎的疗效观察
将54例难治性丙型肝炎患者随机、对照分为试验组28例和对照组26例。试验组给予中药辨证方：益气解毒方、疏肝健脾方、补肾柔肝方治疗，对照组给予中药安慰剂治疗。治疗12，24，36，48周后观察并比较2组血HCV RNA阴转率和下降率、肝功能变化及2组中医症状积分变化。
第二部分：难治性丙型肝炎患者外周血T细胞亚群分析与病毒载量相关性研究
对153例难治性丙型肝炎感染者按基因1b、抗病毒治疗阴转后复发及肝硬化分成3组，分别采用流式细胞术和荧光定量PCR技术分别检测外周血中T淋巴细胞亚群(CD3+T、CD4+T、CD8+T、CD4+T/CD8+T)和HCV RNA载量。另选同期健康体检者150人外周血中T淋巴细胞亚群作为对照组。
第三部分：难治性丙型肝炎中医证型与T淋巴细胞亚群及HCV RNA载量等相关性研究
对153例RHC患者进行中医证型研究,用流式细胞仪检测其患者和150例正常健康对照者外周血T淋巴细胞亚群变化，荧光定量PCR检测患者RHCRNA含量、基因分型和肝功能检测，观察肝功能、血清RHC RNA载量及T淋巴细胞亚群指标与中医证型之间的关系。
结果：第一部分：中医药辨证方治疗难治性丙型肝炎的疗效观察
与对照组比较中药辨证方（益气解毒方、疏肝健脾方、补肾柔肝方）组能明显降低转氨酶水平、提高HCV RNA阴转率和下降率（P＜0.05)。第二部分：难治性丙型肝炎患者外周血T细胞亚群分析与病毒载量相关性研究
1与对照组相比RHC患者组CD3+T、CD4+T下降有统计学意义（p＜0.05），而CD8+T、CD4+T/CD8+T无统计学意义（p＞0.05）。
2高病毒载量患者组与对照组相比较CD3+T、CD4+T下降有统计学意义（P＜0.05），而CD8+T、CD4+T/CD8+T变化无显著差异（P＞0.05），低病毒载量患者组与对照组比较CD8+T下降有统计学意义（P＜0.05）。RHC高病毒载量患者组与低病毒载量患者T淋巴细胞亚群比较，差异无统计学意义（P＞0.05）。
3抗病毒治疗阴转后复发组与对照组比较CD3+T、CD4+T、CD8+T下降明显，差异有统计学意义（P＜0.05）。
4肝硬化组与对照组比较CD3+T、CD8+T下降明显，而CD4+T/CD8+T升高明显，差异有统计学意义（P＜0.05）。
5基因1b组与对照组相比较CD4+T、CD8+T下降明显，差异有统计学意义（P＜0.05）。
6治疗阴转复发组与肝硬化组无统计学意义，与基因1b型比较CD3+T、CD8+T下降明显，差异有统计学意义（P＜0.05）。
7肝硬化组与基因1b型组比较CD3+T、CD8+T下降明显、而CD4+T/CD8+T升高明显，差异有统计学意义（P＜0.05）。
第三部分：难治性丙型肝炎中医证型与T淋巴细胞亚群及HCV RNA载量等相关性研究
1难治性丙型肝炎常见的中医证型依次为正虚邪恋、肝郁脾虚、肝胆湿热、瘀血阻络、肝肾阴虚及脾肾阳虚等六型。
2ALT水平与中医证型的关系：即ALT从高到低在各证型中的排列顺序为：湿热中阻型、脾肾阳虚型、肝肾阴虚型、瘀血内阻型、肝郁脾虚型、正虚邪恋型，其湿热中阻型与其他证型相比较ALT明显升高，差异有统计学意义(P＜0.05)； AST水平与中医证型的关系：即AST从高到低在各证型中的排列顺序为：脾肾阳虚型、湿热中阻型、瘀血内阻型、肝肾阴虚型、肝郁脾虚型、正虚邪恋型，其中脾肾阳虚型与与其他类型相比较明显升高，差异有统计学意义(P＜0.05)；ALB与中医证型的关系为：脾肾阳虚型ALB与其他中医类型明显降低，差异有统计学意义(P＜0.05)。
3RHC RNA水平与中医证型有一定规律性，即湿热中阻型＞正虚邪恋型＞肝肾阴虚型＞瘀血内阻型＞肝郁脾虚型＞脾肾阳虚型；湿热中阻型与瘀血内阻型、脾肾阳虚型相比较，RHC RNA明显升高，差异有统计学意义(P＜0.05)。
4T淋巴细胞亚群指标(CD3+T、CD4+T、CD4+T/CD8+T)与中医辨证分型有一定相关性，与正常对照组相比较湿热中阻型CD8+T明显升高（P＜0.01），CD4+T/CD8+T明显下降（P＜0.05）；脾肾阳虚型和肝郁脾虚型与正常对照组相比较CD3+T、CD4+T明显下降（p＜0.01），CD8+T明显下降（P＜0.05）；正虚邪恋型、瘀血内阻型、肝肾阴虚型与正常对照组相比较(CD3+T、CD4+T、CD4+T/CD8+T)差异无统计学意义(P＞0.05)。
5在各证型相比较中脾肾阳虚型T淋巴细胞计数明显下降，与正虚邪恋型、湿热中阻型、瘀血内阻型、肝肾阴虚型差异有统计学意义（P＜0.05）；肝郁脾虚型T淋巴细胞计数明显下降，与湿热中阻型、肝肾阴虚型差异有统计学意义（P＜0.05）；肝胆湿热型T淋巴细胞计数明显升高，与瘀血内阻型、脾肾阳虚型比较差异有统计学意义（P＜0.05）；CD4+T/CD8+T明显下降，与瘀血内阻型比较差异有统计学意义（P＜0.05）。
结论：
1、中药辨证方能改善难治性丙型病毒性肝炎肝脏炎症，且具有一定的抗病毒作用。
2、长期慢性HCV感染会引起机体细胞免疫功能低下和免疫功能紊乱，可能是基因1b型、抗病毒治疗阴转后复发及肝硬化形成难治性的主要原因之一， RHC患者病毒载量高，病毒复制活跃，肝脏炎症亢进，免疫功能低下及免疫紊乱程度随HCV载量增高而逐渐加重。
3、RHC中医证型依次为正虚邪恋型、肝郁脾虚型、湿热中阻型、瘀血内阻型、肝肾阴虚型及脾肾阳虚型等六型;
4、RHC转氨酶、病毒载量及T淋巴细胞亚群与中医证型有一定相关性。
Chronic hepatitis c(HCV) is a public health problem whichcause serious damage to the human health. According to the WHO global HCV infection rate was3%, about170million people, thereare35000new hepatitis c patients every year. According to thelatest published by the state ministry of health in September，2010,the results of epidemiological investigation anti HCV positive ratewas0.43%in our country, probably the HCV infected more than5million.Nature of HCV infection history is long, a rate ofchronic at50%to85%. Liver cirrhosis and liver cancer is theleading cause of death among patients with chronic hepatitis c, theinfection of30%to40%will develop cirrhosis after5-10years,5%to7%after10-20years for the development of liver cancer. Oneof the most infectious diseases become the serious harm people'shealth. Although modern medicine in the treatment of chronichepatitis c made some breakthrough in the triple therapy as genotype1b，etc.some lastest scheme of refractory hepatitis c. But someunable to antiviral and virological breakthrough in the treatment,partial response, invalid response or no response, the side effectsof drugs, relapse after the drug was stopped, genotype1or4typeof HCV infection,a high viral load,merging other virus infection,orwith other such as diabetes, thyroid dysfunction Hemophilia organtransplant kidney disease and hemodialysis related diseases suchas autoimmune dysfunction,and the existence of the problems suchas cirrhosis of the liver decompensation period, makes thehepatitis c treatment is still a clinical problem, namely so-calledrefractory chronic hepatitis c. At present,caused by infection ofHCV genotype1chronic hepatitis c in China accounts for about78%,high viral load of chronic hepatitis c accounts for about69%,sothe vast majority of chronic hepatitis c in China belong to the
refractory hepatitisc.refractory hepatitis c be formed complex,Andso its clinical manifestations are diverse. Through the11thfive-year plan for CHC symptoms of TCM syndrome classification’study shows：zheng xu xie lian、liver depression and spleendeficiency、kidney Yin deficiency type three accounts for more than73%of all kind of this syndrome，So the factors of the clinicalmanifestations of intermingled deficiency and excess are the maincharacteristics of CHC， If people do not implement clinicalintervention, let it to further development,it will be formed theintractable liver disease such as cirrhosis，The poor prognosis，which would be a great threat to The life of the patients, and poseda great challenge to treat. There is no special effective methodin terms of RHC therapies. Polyethylene glycol (peg) a interferon(P E G a IF N a) plus ribavirin optimized treatment or standardsolutions combined with protease inhibitors for the treatment ofgenotype1is still the first choice. But because of interferon、ribavirin and protease inhibitors are difficult to adapt to the sideeffects of the refractory hepatitis c treatment more confused.Therefore, further to seek immune pathogenesis of refractoryhepatitis c and further to find effective scheme for the treatmentof refractory hepatitis c is the urgent need of medical and clinicaltraditional Chinese medicine for its unique advantages, in theprevention and treatment of chronic viral hepatitis c hasaccumulated rich experience. From the traditional treatment basedon syndrome differentiation, ZhuanBing specially designed medicine,acupuncture, medicine, folk prescription, development to combinetraditional Chinese and western medicine treatment, has thecontribution of Chinese medicine. Years of research also confirmed that the traditional Chinese medicine in the prevention andtreatment of chronic hepatitis c is liver enzyme and antiviraleffect, to turn the early suppression of liver fibrosis has beenrecognized, to reduce the rate of chronic, chemical medicine sideeffects to improve compliance, improve immunity, improvingsymptoms and quality of life, prolong the survival period, reducethe mortality and the incidence of major events is more obviousadvantages.
Purpose：This study on the basis of the "11th five-year plan" Thestudy of Chronic hepatitis c syndrome regularity and the treatmentprescription with the method of intergrated traditional andwestern medicine, relying on the national “12th five-year”refractory hepatitis c treatment of traditional Chinese medicine,in traditional Chinese medicine (TCM) syndrome (yiqi jiedu party,liver, spleen, kidney and liver) to treat refractory hepatitis c,and observe its clinical curative effect, transaminase and HCV RNAturn rate and falling rate drops2log (HCV RNA), and the immunefunction and transaminase, viral load and TCM syndrome type and Tlymphocyte subsets, HCV RNA and other correlation is studied, usingthe computer statistical software for data processing andcomprehensive analysis, to explore the clinical curative effect ofChinese medicine syndrome differentiation on refractory hepatitisc and RCHC viral load, liver inflammation, immune regulationmechanism and the correlation between TCM syndrome types, in orderto further improve the level of clinical treatment of refractorychronic viral hepatitis c.
Methods: the experiment divided into three parts
The first part: the syndrome differentiation of traditional Chinese medicine clinical observation on treatment of refractorychronic hepatitis c
54patients with refractory chronic hepatitis c were randomized,compared,28cases were divided into test group and control groupin26cases. Experimental group were given Chinese medicinesyndrome differentiation: yiqi jiedu, liver spleen, kidney andliver treatment, control group given a placebo treatment.,24,36,4812weeks after treatment to observe and compare the two groups ofblood HCV RNA Yin turn rate and falling rate, liver function andtwo groups of traditional Chinese medicine symptom integralchanges.
The second part: the peripheral blood T cell subsets in patientswith refractory chronic hepatitis c correlation research and viralload
153cases of intractable chronic HCV infection in1b gene,recurrence and liver cirrhosis after antiviral treatment Yin turninto three groups, respectively, by using flow cytometry andfluorescence quantitative PCR detection respectively in theperipheral blood T lymphocyte subsets (CD3+T，CD4+T，CD8+T，CD4+T/CD8+T) and HCV RNA loads. Alternate year healthy physicalexamination,150people in the peripheral blood T lymphocytesubgroup as control group.
The third part: refractory of TCM syndrome types of chronichepatitis c and T lymphocyte subgroup and HCV RNA loads such ascorrelation studies
TCM syndrome types was studied for the153patients, using flowcytometry to test which patients and150normal healthy controlsperipheral blood T lymphocyte subsets changes, fluorescence quantitative PCR detection RCHC RNA content, genotyping, andpatients with liver function test, to observe the liver function,serum RCHC RNA loads and T lymphocyte subgroup indicators and therelationship between the TCM syndrome type.
Results:
the first part: the syndrome differentiation of traditionalChinese medicine clinical observation on treatment of refractorychronic hepatitis c
Traditional Chinese medicine (TCM) syndrome compared with controlsparty (yiqi jiedu, liver, kidney and liver, spleen and party party)group can obviously reduce transaminase level, improve the HCV RNAYin turn rate and falling rate (P＜0.05) in the second part:peripheral blood T cell subsets in patients with refractory chronichepatitis c correlation research and viral load.
1RHC patients compared with the control group of CD3+T，CD4+Tdecline was statistically significant (P＜0.05), while CD8+T, CD4+T/CD8+T no statistical significance (P>0.05).
2A group of patients with high viral load compared with thecontrol group CD3+T, CD4+T decline was statistically significant (P<0.05), and CD8+T, CD4+T/CD8+T change there was no significantdifference (P>0.05), a group of patients with low viral load CD8+Tdecline was statistically significant compared with controls (P <0.05). RCHC group of patients with high viral load and low viralload in patients with T lymphocyte subsets, there was nostatistically significant difference (P>0.05).
3After antiviral treatment turn Yin relapse group and controlgroup comparison of CD3+T, CD4+T, CD8+T decreased significantly, thedifference was statistically significant (P <0.05).
4liver cirrhosis group and control group comparison of CD3+T,CD8+T decreased significantly, and CD4+T/CD8+T increasesignificantly， the difference was statistically significant (P <0.05).
5Gene1b group compared with control group, CD4+T, CD8+Tdecreased significantly, the difference was statisticallysignificant (P <0.05).
6Treatment Yin turn recurrence, no statistical significancebetween the groups with and cirrhosis of the liver, compared withgenotype1b CD3+T, CD8+T decreased significantly, the differencewas statistically significant (P <0.05).
7Cirrhosis group compared with genotype1b group of CD3+T,CD8+T decreased significantly, and CD4+T/CD8+T increasesignificantly，the difference was statistically significant (P <0.05).
The third part: refractory of TCM syndrome types of chronichepatitis c and T lymphocyte subgroup and HCV RNA loads such ascorrelation studies.
1Refractory common TCM syndrome types of chronic hepatitisc in the order is empty and, to change, liver and gallbladder dampand hot, blood stasis resistance winding, liver and kidney Yindeficiency and spleen kidney Yang deficiency and so on six type.
2ALT level and based on the relationship between TCM syndrometype：which is the ALT from high to low in sequence for each cardtype：humid heat to hinder type，spleen and kidney Yang deficiencytype，liver-kidney Yin deficiency type，blood stasis resistancetype， change the type is empty and type, including humid heat tohinder type compared with other syndrome types ALT increased significantly, the difference was statistically significant(P<0.05); AST level and based on the relationship between TCM syndrometypes: which is the AST from high to low in sequence for each cardtype：spleen kidney Yang deficiency type, humid heat to hinder type,blood stasis resistance type, liver-kidney Yin deficiency type,change the type is empty and type, the spleen and kidney Yangdeficiency type and compared with other types increasedsignificantly, the difference was statistically significant(P<0.05); Propagated and based on the relationship between TCMsyndrome types: spleen kidney Yang deficiency type A significantlylower with other types of traditional Chinese medicine, thedifference was statistically significant(P <0.05).
3RHC RNA levels and TCM syndrome types have a certain regularity,namely courage humid heat to hinder type> is empty and>liver-kidney Yin deficiency type> blood stasis resistance type>change the type> spleen kidney Yang deficiency type.The damp andhot resistance type and blood stasis resistance type compared thespleen kidney Yang deficiency type,RHC RNA increasedsignificantly,the difference was statistically significant(P<0.05).
4Index of T lymphocyte subsets (CD3+T, CD4+T, CD4+T/CD8+T) oftraditional Chinese medicine and have a certain correlation,compared with normal control group humid heat to hinder type CD8+T significantly increased (P<0.01), CD4+T/CD8+T decreasedobviously (P <0.05); Spleen and kidney Yang deficiency type andchange the type compared with normal control group T CD3+T, CD4+TT cells decreased obviously (P <0.01), and CD8+T significantlydecreased (P<0.05); Is virtual love evil, blood stasis resistance compared with the normal control group, liver and kidney Yindeficiency type (CD3+T, CD4+T, CD4+T/CD8+T) has no statisticalsignificance(P＞0.05).
5In each type of spleen kidney Yang deficiency syndromecompared T lymphocyte count declined obviously, and is empty andtype, humid heat to hinder type, blood stasis resistance type，liver and kidney Yin deficiency syndrome, type difference wasstatistically significant(P <0.05); Change the type of Tlymphocyte count drops obviously, and humid heat to hinder type,kidney Yin deficiency type difference was statisticallysignificant(P<0.05); Liver syndrome T lymphocyte count increasedsignificantly, compared with the blood stasis resistance type,spleen and kidney Yang deficiency type difference was statisticallysignificant(P <0.05)； CD4+T/CD8+T significantly decreased,compared with blood stasis type resistance difference wasstatistically significant(P <0.05).
Conclusion:
1Chinese medicine syndrome differentiation can improverefractory chronic viral hepatitis c liver inflammation, and hascertain antiviral effect.
2long-term chronic HCV infection can cause low organismcellular immunity function and immune dysfunction, may be thegenotype1b and antiviral treatment after turn Yin recurrence andliver cirrhosis formed one of the leading causes of refractory, RCHCpatients with high viral load, active viral replication, liverinflammation disease, weakened immune system and the immune levelof turbulence gradually aggravated with HCV higher loads.
3TCM syndrome type of RHC in turn is empty and type, change the type, liver and gallbladder damp and hot resistance type, bloodstasis resistance type, liver and kidney Yin deficiency type andspleen kidney Yang deficiency type and so on six type.
4RHC transaminase, viral load and T lymphocyte subsets andTCM syndrome types have certain relevance.
目的：本研究在“十一五”慢性丙型肝炎证候规律及中西医结合治疗方案研究的基础上，依托国家“十二五”难治性丙型肝炎的中医药治疗方案，以中药辨证方（益气解毒方、疏肝健脾方、补肾柔肝方）治疗难治性丙型肝炎，观察其临床疗效、转氨酶和HCV RNA转阴率及下降率（HCV RNA下降2log），并对其免疫功能与转氨酶、病毒载量以及中医证型与T淋巴细胞亚群、HCV RNA等相关性进行研究，运用计算机统计学软件进行数据处理和综合分析，以探讨中药辨证方对难治性丙型肝炎的临床疗效以及RHC的病毒载量、肝脏炎症、免疫调节机制与中医证型之间的相关性，以便进一步提高难治性丙型病毒性肝炎的临床治疗水平。
方法：实验分三个部分进行
第一部分：中医药辨证方治疗难治性丙型肝炎的疗效观察
将54例难治性丙型肝炎患者随机、对照分为试验组28例和对照组26例。试验组给予中药辨证方：益气解毒方、疏肝健脾方、补肾柔肝方治疗，对照组给予中药安慰剂治疗。治疗12，24，36，48周后观察并比较2组血HCV RNA阴转率和下降率、肝功能变化及2组中医症状积分变化。
第二部分：难治性丙型肝炎患者外周血T细胞亚群分析与病毒载量相关性研究
对153例难治性丙型肝炎感染者按基因1b、抗病毒治疗阴转后复发及肝硬化分成3组，分别采用流式细胞术和荧光定量PCR技术分别检测外周血中T淋巴细胞亚群(CD3+T、CD4+T、CD8+T、CD4+T/CD8+T)和HCV RNA载量。另选同期健康体检者150人外周血中T淋巴细胞亚群作为对照组。
第三部分：难治性丙型肝炎中医证型与T淋巴细胞亚群及HCV RNA载量等相关性研究
对153例RHC患者进行中医证型研究,用流式细胞仪检测其患者和150例正常健康对照者外周血T淋巴细胞亚群变化，荧光定量PCR检测患者RHCRNA含量、基因分型和肝功能检测，观察肝功能、血清RHC RNA载量及T淋巴细胞亚群指标与中医证型之间的关系。
结果：第一部分：中医药辨证方治疗难治性丙型肝炎的疗效观察
与对照组比较中药辨证方（益气解毒方、疏肝健脾方、补肾柔肝方）组能明显降低转氨酶水平、提高HCV RNA阴转率和下降率（P＜0.05)。第二部分：难治性丙型肝炎患者外周血T细胞亚群分析与病毒载量相关性研究
1与对照组相比RHC患者组CD3+T、CD4+T下降有统计学意义（p＜0.05），而CD8+T、CD4+T/CD8+T无统计学意义（p＞0.05）。
2高病毒载量患者组与对照组相比较CD3+T、CD4+T下降有统计学意义（P＜0.05），而CD8+T、CD4+T/CD8+T变化无显著差异（P＞0.05），低病毒载量患者组与对照组比较CD8+T下降有统计学意义（P＜0.05）。RHC高病毒载量患者组与低病毒载量患者T淋巴细胞亚群比较，差异无统计学意义（P＞0.05）。
3抗病毒治疗阴转后复发组与对照组比较CD3+T、CD4+T、CD8+T下降明显，差异有统计学意义（P＜0.05）。
4肝硬化组与对照组比较CD3+T、CD8+T下降明显，而CD4+T/CD8+T升高明显，差异有统计学意义（P＜0.05）。
5基因1b组与对照组相比较CD4+T、CD8+T下降明显，差异有统计学意义（P＜0.05）。
6治疗阴转复发组与肝硬化组无统计学意义，与基因1b型比较CD3+T、CD8+T下降明显，差异有统计学意义（P＜0.05）。
7肝硬化组与基因1b型组比较CD3+T、CD8+T下降明显、而CD4+T/CD8+T升高明显，差异有统计学意义（P＜0.05）。
第三部分：难治性丙型肝炎中医证型与T淋巴细胞亚群及HCV RNA载量等相关性研究
1难治性丙型肝炎常见的中医证型依次为正虚邪恋、肝郁脾虚、肝胆湿热、瘀血阻络、肝肾阴虚及脾肾阳虚等六型。
2ALT水平与中医证型的关系：即ALT从高到低在各证型中的排列顺序为：湿热中阻型、脾肾阳虚型、肝肾阴虚型、瘀血内阻型、肝郁脾虚型、正虚邪恋型，其湿热中阻型与其他证型相比较ALT明显升高，差异有统计学意义(P＜0.05)； AST水平与中医证型的关系：即AST从高到低在各证型中的排列顺序为：脾肾阳虚型、湿热中阻型、瘀血内阻型、肝肾阴虚型、肝郁脾虚型、正虚邪恋型，其中脾肾阳虚型与与其他类型相比较明显升高，差异有统计学意义(P＜0.05)；ALB与中医证型的关系为：脾肾阳虚型ALB与其他中医类型明显降低，差异有统计学意义(P＜0.05)。
3RHC RNA水平与中医证型有一定规律性，即湿热中阻型＞正虚邪恋型＞肝肾阴虚型＞瘀血内阻型＞肝郁脾虚型＞脾肾阳虚型；湿热中阻型与瘀血内阻型、脾肾阳虚型相比较，RHC RNA明显升高，差异有统计学意义(P＜0.05)。
4T淋巴细胞亚群指标(CD3+T、CD4+T、CD4+T/CD8+T)与中医辨证分型有一定相关性，与正常对照组相比较湿热中阻型CD8+T明显升高（P＜0.01），CD4+T/CD8+T明显下降（P＜0.05）；脾肾阳虚型和肝郁脾虚型与正常对照组相比较CD3+T、CD4+T明显下降（p＜0.01），CD8+T明显下降（P＜0.05）；正虚邪恋型、瘀血内阻型、肝肾阴虚型与正常对照组相比较(CD3+T、CD4+T、CD4+T/CD8+T)差异无统计学意义(P＞0.05)。
5在各证型相比较中脾肾阳虚型T淋巴细胞计数明显下降，与正虚邪恋型、湿热中阻型、瘀血内阻型、肝肾阴虚型差异有统计学意义（P＜0.05）；肝郁脾虚型T淋巴细胞计数明显下降，与湿热中阻型、肝肾阴虚型差异有统计学意义（P＜0.05）；肝胆湿热型T淋巴细胞计数明显升高，与瘀血内阻型、脾肾阳虚型比较差异有统计学意义（P＜0.05）；CD4+T/CD8+T明显下降，与瘀血内阻型比较差异有统计学意义（P＜0.05）。
结论：
1、中药辨证方能改善难治性丙型病毒性肝炎肝脏炎症，且具有一定的抗病毒作用。
2、长期慢性HCV感染会引起机体细胞免疫功能低下和免疫功能紊乱，可能是基因1b型、抗病毒治疗阴转后复发及肝硬化形成难治性的主要原因之一， RHC患者病毒载量高，病毒复制活跃，肝脏炎症亢进，免疫功能低下及免疫紊乱程度随HCV载量增高而逐渐加重。
3、RHC中医证型依次为正虚邪恋型、肝郁脾虚型、湿热中阻型、瘀血内阻型、肝肾阴虚型及脾肾阳虚型等六型;
4、RHC转氨酶、病毒载量及T淋巴细胞亚群与中医证型有一定相关性。
Chronic hepatitis c(HCV) is a public health problem whichcause serious damage to the human health. According to the WHO global HCV infection rate was3%, about170million people, thereare35000new hepatitis c patients every year. According to thelatest published by the state ministry of health in September，2010,the results of epidemiological investigation anti HCV positive ratewas0.43%in our country, probably the HCV infected more than5million.Nature of HCV infection history is long, a rate ofchronic at50%to85%. Liver cirrhosis and liver cancer is theleading cause of death among patients with chronic hepatitis c, theinfection of30%to40%will develop cirrhosis after5-10years,5%to7%after10-20years for the development of liver cancer. Oneof the most infectious diseases become the serious harm people'shealth. Although modern medicine in the treatment of chronichepatitis c made some breakthrough in the triple therapy as genotype1b，etc.some lastest scheme of refractory hepatitis c. But someunable to antiviral and virological breakthrough in the treatment,partial response, invalid response or no response, the side effectsof drugs, relapse after the drug was stopped, genotype1or4typeof HCV infection,a high viral load,merging other virus infection,orwith other such as diabetes, thyroid dysfunction Hemophilia organtransplant kidney disease and hemodialysis related diseases suchas autoimmune dysfunction,and the existence of the problems suchas cirrhosis of the liver decompensation period, makes thehepatitis c treatment is still a clinical problem, namely so-calledrefractory chronic hepatitis c. At present,caused by infection ofHCV genotype1chronic hepatitis c in China accounts for about78%,high viral load of chronic hepatitis c accounts for about69%,sothe vast majority of chronic hepatitis c in China belong to the
refractory hepatitisc.refractory hepatitis c be formed complex,Andso its clinical manifestations are diverse. Through the11thfive-year plan for CHC symptoms of TCM syndrome classification’study shows：zheng xu xie lian、liver depression and spleendeficiency、kidney Yin deficiency type three accounts for more than73%of all kind of this syndrome，So the factors of the clinicalmanifestations of intermingled deficiency and excess are the maincharacteristics of CHC， If people do not implement clinicalintervention, let it to further development,it will be formed theintractable liver disease such as cirrhosis，The poor prognosis，which would be a great threat to The life of the patients, and poseda great challenge to treat. There is no special effective methodin terms of RHC therapies. Polyethylene glycol (peg) a interferon(P E G a IF N a) plus ribavirin optimized treatment or standardsolutions combined with protease inhibitors for the treatment ofgenotype1is still the first choice. But because of interferon、ribavirin and protease inhibitors are difficult to adapt to the sideeffects of the refractory hepatitis c treatment more confused.Therefore, further to seek immune pathogenesis of refractoryhepatitis c and further to find effective scheme for the treatmentof refractory hepatitis c is the urgent need of medical and clinicaltraditional Chinese medicine for its unique advantages, in theprevention and treatment of chronic viral hepatitis c hasaccumulated rich experience. From the traditional treatment basedon syndrome differentiation, ZhuanBing specially designed medicine,acupuncture, medicine, folk prescription, development to combinetraditional Chinese and western medicine treatment, has thecontribution of Chinese medicine. Years of research also confirmed that the traditional Chinese medicine in the prevention andtreatment of chronic hepatitis c is liver enzyme and antiviraleffect, to turn the early suppression of liver fibrosis has beenrecognized, to reduce the rate of chronic, chemical medicine sideeffects to improve compliance, improve immunity, improvingsymptoms and quality of life, prolong the survival period, reducethe mortality and the incidence of major events is more obviousadvantages.
Purpose：This study on the basis of the "11th five-year plan" Thestudy of Chronic hepatitis c syndrome regularity and the treatmentprescription with the method of intergrated traditional andwestern medicine, relying on the national “12th five-year”refractory hepatitis c treatment of traditional Chinese medicine,in traditional Chinese medicine (TCM) syndrome (yiqi jiedu party,liver, spleen, kidney and liver) to treat refractory hepatitis c,and observe its clinical curative effect, transaminase and HCV RNAturn rate and falling rate drops2log (HCV RNA), and the immunefunction and transaminase, viral load and TCM syndrome type and Tlymphocyte subsets, HCV RNA and other correlation is studied, usingthe computer statistical software for data processing andcomprehensive analysis, to explore the clinical curative effect ofChinese medicine syndrome differentiation on refractory hepatitisc and RCHC viral load, liver inflammation, immune regulationmechanism and the correlation between TCM syndrome types, in orderto further improve the level of clinical treatment of refractorychronic viral hepatitis c.
Methods: the experiment divided into three parts
The first part: the syndrome differentiation of traditional Chinese medicine clinical observation on treatment of refractorychronic hepatitis c
54patients with refractory chronic hepatitis c were randomized,compared,28cases were divided into test group and control groupin26cases. Experimental group were given Chinese medicinesyndrome differentiation: yiqi jiedu, liver spleen, kidney andliver treatment, control group given a placebo treatment.,24,36,4812weeks after treatment to observe and compare the two groups ofblood HCV RNA Yin turn rate and falling rate, liver function andtwo groups of traditional Chinese medicine symptom integralchanges.
The second part: the peripheral blood T cell subsets in patientswith refractory chronic hepatitis c correlation research and viralload
153cases of intractable chronic HCV infection in1b gene,recurrence and liver cirrhosis after antiviral treatment Yin turninto three groups, respectively, by using flow cytometry andfluorescence quantitative PCR detection respectively in theperipheral blood T lymphocyte subsets (CD3+T，CD4+T，CD8+T，CD4+T/CD8+T) and HCV RNA loads. Alternate year healthy physicalexamination,150people in the peripheral blood T lymphocytesubgroup as control group.
The third part: refractory of TCM syndrome types of chronichepatitis c and T lymphocyte subgroup and HCV RNA loads such ascorrelation studies
TCM syndrome types was studied for the153patients, using flowcytometry to test which patients and150normal healthy controlsperipheral blood T lymphocyte subsets changes, fluorescence quantitative PCR detection RCHC RNA content, genotyping, andpatients with liver function test, to observe the liver function,serum RCHC RNA loads and T lymphocyte subgroup indicators and therelationship between the TCM syndrome type.
Results:
the first part: the syndrome differentiation of traditionalChinese medicine clinical observation on treatment of refractorychronic hepatitis c
Traditional Chinese medicine (TCM) syndrome compared with controlsparty (yiqi jiedu, liver, kidney and liver, spleen and party party)group can obviously reduce transaminase level, improve the HCV RNAYin turn rate and falling rate (P＜0.05) in the second part:peripheral blood T cell subsets in patients with refractory chronichepatitis c correlation research and viral load.
1RHC patients compared with the control group of CD3+T，CD4+Tdecline was statistically significant (P＜0.05), while CD8+T, CD4+T/CD8+T no statistical significance (P>0.05).
2A group of patients with high viral load compared with thecontrol group CD3+T, CD4+T decline was statistically significant (P<0.05), and CD8+T, CD4+T/CD8+T change there was no significantdifference (P>0.05), a group of patients with low viral load CD8+Tdecline was statistically significant compared with controls (P <0.05). RCHC group of patients with high viral load and low viralload in patients with T lymphocyte subsets, there was nostatistically significant difference (P>0.05).
3After antiviral treatment turn Yin relapse group and controlgroup comparison of CD3+T, CD4+T, CD8+T decreased significantly, thedifference was statistically significant (P <0.05).
4liver cirrhosis group and control group comparison of CD3+T,CD8+T decreased significantly, and CD4+T/CD8+T increasesignificantly， the difference was statistically significant (P <0.05).
5Gene1b group compared with control group, CD4+T, CD8+Tdecreased significantly, the difference was statisticallysignificant (P <0.05).
6Treatment Yin turn recurrence, no statistical significancebetween the groups with and cirrhosis of the liver, compared withgenotype1b CD3+T, CD8+T decreased significantly, the differencewas statistically significant (P <0.05).
7Cirrhosis group compared with genotype1b group of CD3+T,CD8+T decreased significantly, and CD4+T/CD8+T increasesignificantly，the difference was statistically significant (P <0.05).
The third part: refractory of TCM syndrome types of chronichepatitis c and T lymphocyte subgroup and HCV RNA loads such ascorrelation studies.
1Refractory common TCM syndrome types of chronic hepatitisc in the order is empty and, to change, liver and gallbladder dampand hot, blood stasis resistance winding, liver and kidney Yindeficiency and spleen kidney Yang deficiency and so on six type.
2ALT level and based on the relationship between TCM syndrometype：which is the ALT from high to low in sequence for each cardtype：humid heat to hinder type，spleen and kidney Yang deficiencytype，liver-kidney Yin deficiency type，blood stasis resistancetype， change the type is empty and type, including humid heat tohinder type compared with other syndrome types ALT increased significantly, the difference was statistically significant(P<0.05); AST level and based on the relationship between TCM syndrometypes: which is the AST from high to low in sequence for each cardtype：spleen kidney Yang deficiency type, humid heat to hinder type,blood stasis resistance type, liver-kidney Yin deficiency type,change the type is empty and type, the spleen and kidney Yangdeficiency type and compared with other types increasedsignificantly, the difference was statistically significant(P<0.05); Propagated and based on the relationship between TCMsyndrome types: spleen kidney Yang deficiency type A significantlylower with other types of traditional Chinese medicine, thedifference was statistically significant(P <0.05).
3RHC RNA levels and TCM syndrome types have a certain regularity,namely courage humid heat to hinder type> is empty and>liver-kidney Yin deficiency type> blood stasis resistance type>change the type> spleen kidney Yang deficiency type.The damp andhot resistance type and blood stasis resistance type compared thespleen kidney Yang deficiency type,RHC RNA increasedsignificantly,the difference was statistically significant(P<0.05).
4Index of T lymphocyte subsets (CD3+T, CD4+T, CD4+T/CD8+T) oftraditional Chinese medicine and have a certain correlation,compared with normal control group humid heat to hinder type CD8+T significantly increased (P<0.01), CD4+T/CD8+T decreasedobviously (P <0.05); Spleen and kidney Yang deficiency type andchange the type compared with normal control group T CD3+T, CD4+TT cells decreased obviously (P <0.01), and CD8+T significantlydecreased (P<0.05); Is virtual love evil, blood stasis resistance compared with the normal control group, liver and kidney Yindeficiency type (CD3+T, CD4+T, CD4+T/CD8+T) has no statisticalsignificance(P＞0.05).
5In each type of spleen kidney Yang deficiency syndromecompared T lymphocyte count declined obviously, and is empty andtype, humid heat to hinder type, blood stasis resistance type，liver and kidney Yin deficiency syndrome, type difference wasstatistically significant(P <0.05); Change the type of Tlymphocyte count drops obviously, and humid heat to hinder type,kidney Yin deficiency type difference was statisticallysignificant(P<0.05); Liver syndrome T lymphocyte count increasedsignificantly, compared with the blood stasis resistance type,spleen and kidney Yang deficiency type difference was statisticallysignificant(P <0.05)； CD4+T/CD8+T significantly decreased,compared with blood stasis type resistance difference wasstatistically significant(P <0.05).
Conclusion:
1Chinese medicine syndrome differentiation can improverefractory chronic viral hepatitis c liver inflammation, and hascertain antiviral effect.
2long-term chronic HCV infection can cause low organismcellular immunity function and immune dysfunction, may be thegenotype1b and antiviral treatment after turn Yin recurrence andliver cirrhosis formed one of the leading causes of refractory, RCHCpatients with high viral load, active viral replication, liverinflammation disease, weakened immune system and the immune levelof turbulence gradually aggravated with HCV higher loads.
3TCM syndrome type of RHC in turn is empty and type, change the type, liver and gallbladder damp and hot resistance type, bloodstasis resistance type, liver and kidney Yin deficiency type andspleen kidney Yang deficiency type and so on six type.
4RHC transaminase, viral load and T lymphocyte subsets andTCM syndrome types have certain relevance.
引文
[1]陈园生，李黎，崔富强，等.中国丙型肝炎血清流行病学研究[J］.中华流行病学杂志，2011，32(9):888-891．
[2] Sansonno D, Iacobelli AR, Cornacchiulo V, et al. Detection ofhepatitis C virus (HCV) proteins by immunofluorescence andHCV RNAgenomic sequences by non-isotopic in situ ybridizationin bone marrowand peripheral blood mononuclear cells ofchronically HCVinfected patients[J］. Clin Exp Immunol,1996,103(3):414-421．
[3] Irshad M，Ansari M A，Singh A，et al.HCV-genotypes: a reviewon their origin，global status，assay system，pathogenecityand response to treatment[J］.Hepatogastroenterology，2010，57(104):1529-1538．
[4] Ghany MG，Nelson DR，Strader DB，et al. An update on treatmentof genotype1chronic hepatitis C virus infection:2011practice guideline by the American Association for the Studyof Liver Diseases. Hepatology，2011，5（4）:1433-1444．
[5] Ghany MG，strager DB Thomas DL，etal.diagnosis，magement，and treatment of hepatitis： an update[J].Hepatology,2009,49(4)：1335-1374.
[6] Me Caug han GW,omata M, Am arapurkar D, et al. Asian PacificAssociation for the Study of the Liver consensus Statementson the diagnosis, management and treatment of hepatitis Cvirus in fection [J].J Gastroenterol Hepatol,2007,22(5):615一633.
[7] EuroPean Association for the Study of the Liver. EASL clinicalPractice guidelines: management of hepatitis C virus infection [J].J Hepatol,2011,55(2):245一264.
[8]马丽娜,陈新月,陈杰,等.聚乙二醇干扰素治疗慢性丙型肝炎临床疗效!影响因素及安全性分析(附89例临床分析)[J].中华实验和临床病毒学杂志,2006,20(2):42-45.
[9] Di Bisceglie AM, Thompson J, Smith一Wilkaitis N, et alCombination of interferon and ribavirin in chonic hepatitisC:retreatment o f nonresponders to interferon [J].Hepatology2001,33(3):704一707.
[10]中华人民共和国卫生部．今天是世界卫生大会倡议的第一个世界肝炎日[EB／OL]．[2012—03—25]．http：／／www．moh．gov．cn／pub—licfiles／business／htmlfiles／mohjbyfkzj／s3586／201007／48258．htm．
[11]陈旭，马玉梅．对我国《丙型肝炎防治指南》的解读[J］．中国实用乡村医生杂志，2007，14(2):49－51．
[12] Ford JA，Cheong-Lee C． The role of hepatology nurse in thedifficult-to-treat hepatitis C population[J］． Can JGastroenterol，2007，21(6):353－354.
[13]谢尧，李明慧．难治性丙型病毒性肝炎的治疗现状及发展趋势[J］．中华肝脏病杂志，2009，17(7):484－486．
[14]上海市中医药学会肝病分会专业委员会;国家“十一五”科技重大专项重大传染病中医药防治课题组[J].上海中医药杂志，2012,46(3):11-12．
[15] Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronichepatitis C: a randomized study of treatment duration andribavirin dose[J］. Ann Intern Med,2004,140(5):346-355.
[16] Manns MP, McHutchison JG, Gordon SC, et al. Peginterferonalfa-2b plus ribavirin compared with interferon alfa-2b plusribavirin for initial treatment of chronic hepatitis C: arandomised trial[J］.Lancet,2001,358(9296):958-965.
[17] McHutchison JG, Lawitz EJ, Shiffman ML, et al. Peginterferonalfa-2b or alfa-2a with ribavirin for treatment of hepatitisC infection[J］. N Engl J Med,2009,361(6):580-593.
[18] Ghany MG, Nelson DR, Strader DB, et al. An update on treatmentof genotype1chronic hepatitis C virus infection:2011practice guideline by the American Association for the Studyof Liver Diseases[J］. Hepatology,2011,55(4):1433-1444.
[19]梁喜爱，吴宗耀，李昱晓．抗慢性丙型病毒性肝炎药物研究进展[J］中医学报，2010，25(4):813－814．
[20]沈健，陈建杰，商斌仪．丙肝冲剂治疗难治性丙型肝炎研究[J］．现代中西医结合杂志，2013，22(18):1947-1949
[21] Ghany MG，Strader DB，Thomas DL，et al．Diagnosis，management，and treatment of hepatitis C: an update [J］．Hepatology．2009，49(4):1335－1374．
[22]窦晓光.难治性慢性丙型肝炎一我们面临的新挑战[J].中华肝脏病杂志,2009,17(7):486-487.
[23] You J，Zhuang L，Zhang YF，et al．Peripheral T－lymphocytesubpopulations in different clinical stages of chronic HBVinfection correlate with HBV load[J］． World J Gastroenterol，2009，15(27):3382－3393.
[24]沈书旭，刘英，关琪． HCV感染者外周血CD4+T细胞计数与病毒载量的相关性分析[J］．沈阳医学院学报，2009，11(4):213－214．
[25] U lsenh eim er A, Gerlach JT, Gruen er NH, et a.l Detectionof functionally altered hepat itis Cv iru s-specif ic CD4+T cells in acute and ch ron ic hepat itis C [J]. H epatology,2003,37:1189-1198.
[26] Rosen HR, M iner C, Sasak i AW, et a.l Frequ encies of HCVspecific effect or CD4+T cells by flow cytom etry: correlation w ith clin ical d isease s tages [J]. H epatology,2002,35:190-198.
[27] Kan tzanouM, Lu casM, Barnes E, et a.l V iral escape and T cellexhaust ion in h epatitisC virus in fection analysed us ingC lass I peptide tetram ers [J].Immuno lLett,2003,85:165-171.
[28]陈志刚，杨军，周婷，等．慢性丙型肝炎患者血清HCV RNA含量与IFN－γ及IL－4的变化关系[J］．临床检验杂志，2007，25(2):146．
[29]张武英，龙列明，冯冰，等．慢性丙型肝炎患者病毒载量与T细胞免疫功能关系分析[J］．广东医学，2010，31(21):2827－2828．
[30]高勇,贺永文,曾令兰,等.丙型肝炎病毒感染外周血单个核细胞对丙型肝炎的影响[J].同济医科大学学报,2000,20(5):450～452．
[31]沈书旭，吴玉海，关琪，等． CD4+CD25+调节性T细胞对HCV感染者疾病进程影响的研究[J］．沈阳医学院学报，2010，12(2):73－74．
[32]张缭云,赵和平,赵龙凤,等.丙型肝炎患者外周血T淋巴细胞亚群及sIL22R变化的研究[J].山西医科大学学报,2002，33(6):511-513.
[33]梁骑，焦艳梅，计云霞，等.慢性丙型肝炎患者DNT细胞及T细胞亚群的研究[J].首都医科大学学报,2012，33(2):214-217.
[34] Lechner F, W ong D K, Dunbar P R, et a.l Analysis of successfulimmune responses in persons infected with hepatitisCvirus[J]. J ExpMed,2000,191,1499-1512.
[35] Fe ld J J, H oofnag le J H. M echan ism o f action of in terferonand ribavirin in treatment of hepatitis C[J]. Nature,2005,436:967-972.
[36]周延美，周延英.肝硬化患者外周T淋巴细胞亚群变迁及免疫功能状态的分析[J].中国医药指南，2013,11（10）：635-636.
[37]王晶，慧吴标，黄玲，等.不同临床阶段乙型肝炎患者外周C D8+T淋巴细胞免疫记忆应答水平的比较[J].肝脏，2013,18（6）：369-373.
[38]林浩，谢玲珠，李秀芬.肝硬化患者CD4+T细胞的改变及意义[J].广东医学,2011，32（23）:3068-3070.
[39]田瑛，李太生．乙型肝炎病毒感染临床转归与宿主细胞免疫的相关性研究[J]．中华内科杂志，2007，46(12):1014－1017．
[40]曹振环，陈新月．慢性丙型病毒性肝炎患者体内T细胞亚群及细胞因子的变化[J］．中国病原生物学杂志，2008，3(11):855－857．
[41］Higuchi M，Tanaka E，Kiyosawa K． Epidemiology and clinicalaspects on hepatitis C[J］．Jpn J Infect Dis，2002，55(3):69－77．
[42］成军．丙型肝炎病毒基因变异及其临床意义[J］．中华肝脏病杂志，2006，14(1):54－55．
[43] Bengsch B，Thimme R，Blum HE． Role of host genetic factorsin the outcome of hepatitis C virus infection[J］．Viruses，2009，1(2):104－125．
[44]周友乾，尹凤鸣，冯经．慢性丙型肝炎抗病毒治疗后复发的影响因素分析[J］．临床肝胆病杂志，2012，28(8):609－611．
[45]王琰,朱新宇,王霞,等.太原地区丙型肝炎病毒基因分型及其临床意义[J].实用肝脏病杂志,2010,13(2):109-111.
[46]刘毓刚，王天然，李国良． HCV感染者外周血T淋巴细胞亚群的变化[J]．四川医学，2010，31(2):241-242．
[47]张琳,苗亮,韩峰.慢性丙型肝炎患者血清细胞因子水平的变化及意义[J].细胞与分子免疫学杂志，2011,27（3）:302-303．临床
[48] Masaki N, Fukushima S, Hayashi S. Lower th21/th22ratiobefore interferon therapy may favor long term virologicalresponses in patients with chronic hepatitis C[J]. Dig DisSci,2002,47(10):2163-2169．
[49]曹振环，陈新月．慢性丙型病毒性肝炎患者体内T细胞亚群及细胞因子的变化[J］．中国病原生物学杂志，2008，3(11):855－857．
[50]上海中医药大学附属曙光医院肝病科．全国第九届肝胆病学术会议论文集[D]，2000:17．
[51]车念聪，付修文，高连印，杜宇琼，王融冰，李秀惠．北京地区慢性丙型肝炎中医证候学研究及辨证分型的初步调查[J］．北京中医，2002，21(5):300－304．
[52]胡志军，丁辉，汪晓军．慢性丙型肝炎患者中医证型与ALT、AST、HCV-RNA之间的关系[J］．河南中医，2012，32(3):303－304．
[53] NGUYEN-KHAC E，CAPRON D，ASTELAIN S，et al. Personalized therapyfor chronic viral hepatitis C in the naive patient:How can weoptimize treatment duration as a function of viralgenotype[J].Eur J Intern Med，2007，18（7）:510-515.
[54] SCHINKEL J，KROES AC，WAGTMANS MJ，et al. Monitoring responseduring a randomised controlled trial of escalating interferondose for chronic hepatitis C infection:predictive value ofquantitative and qualitative HCV RNA assays[J]. J Clin Virol，2001，22（1）:61-71.
[55] TAKENOKUCHI M，YASUDA C，NAKAMACHI Y，et al. Comparativeevaluation of serum HCV RNA by Roche Monitor Assay.Versions1.0and2.0；as a predictive marker of subsequent responseto IFN therapy[J]. Rinsho Byori，2002，50（4）:392-397.
[56] FERN NDEZ I，CASTELLANO G，DOMINGO MJ，et al.Influence of viralgenotype and level of viremia on the severity of liver injuryand the response to interferon therapy in Spanish patientswith chronic C infection [J]. Scand J Gastroenterol，1997，32（1）:70-76.
[57] LEE SD，YU ML，CHENG PN，et al. Comparison of a6-month coursepeginterferon a-2b plus ribavirin and interferon a-2b plusribavirin in treating Chinese patients with chronic hepatitisC in Taiwan[J]. J Viral Hepatitis，2005，12，283-291.
[58]胡志军，丁辉，汪晓军．慢性丙型肝炎患者中医证型与ALT、AST、HCV-RNA之间的关系[J］．河南中医，2012，32(3):303－304．
[59]贾因棠,魏来,蒋栋等.干扰素刺激基因ISG20真核表达载体的构建及其抗丙型肝炎病毒复制作用的研究[J］.中国免疫学杂志.2006,22（11）:997-1001.
[60] Khakoo SI, T hio CL, Mar tin MP, et al. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection[J].Science,2004,305(5685):872-874.
[61] Li W, Krishn adas DK, Kumar R, etal. Priming and stimulationof hepatitis C virus-specific CD4+and CD8+T cells again stH CV antigens NS4, NS5a or NS5b from H CV-n aive individuals:implicat ions for prophylactic vaccine[J]. InternationalImmunology.2007,20(1):89-104.
[62] Jinushi M, T akehara T, T atsum i T, et al. Autocrine/paracrine IL-15that is required for type I IFN mediateddendritic cell expression of M HC class Irelated chain A andB is impair ed in hepatit is C virus infection [J]. J Immunol,2003,171(10):5423-5429.
[63]王全楚. T h1/T h2和T c1/T c2与慢性丙型肝炎[J].国外医学免疫学分册.2001,24(1):54-55.
[64]金波,王慧芬,王福生,等.慢性丙型肝炎患者型树突状细胞、淋巴细胞亚群的特点及临床意义[J].传染病信息.2008,21(2):115-118.
[65]杨江华,张永祥,苏川,等.慢性丙型肝炎患者CD4+CD25+调节性T细胞表达增加[J].世界华人消化杂志.2005,13(18):2201-2204.
[66]刘加顺，陈涛，刘丽丽，等.难治性丙型肝炎临床治疗的研究[J].当代医学.2013,19(31):130-131.
[67] Hézode C.Oral combination therapy:future hepatitis Cvirustreatment?[J].J Hepatology，2011，55(4):933-935.
[68] Gonzalez SA，Keeffe EB. Management of chronic hepatitis Ctreatment failures：role of consensus interferon[J].Biologics，2009，3：141-150.
[69] Sjogren MH，Sjogren R，Holtzmuller K，et al. Interferonalfacon-1and ribavirin versus interferon alpha-2b andribavirin in the treatment of chronic hepatitis C[J]. Dig DisSci，2005，50（4）：727-732.
[70] Leevy CB. Consensus interferon and ribavirin in patients withchronic hepatitis C who were nonresponders to pegylatedinterferonalfa-2b and ribavirin[J]. Dig Dis Sci，2008，53（7）：1961-1966.
[71] Bacon BR，Shiffman ML，Mendes F，et al. Retreating chronichepatitis C with daily interferon alfacon-1/ribavirin afternonresponse to pegylated interferon/ribavirin：DIRECTresults[J].Hepatology，2009，49（6）：1838-1846.
[72]周一鸣，曹建彪，范公忍.老年丙型肝炎肝硬化的中药治疗探讨[J］．实用老年医学，2013，27(6):477-479．
[73］陈文林，陆坚，李炜，等.慢性丙型肝炎中医证候量表分析[J］．山西中医学院学报，2010，11(1):33－35．
[74]金实.慢性丙型肝炎中医辨证分型与临床检测指标关系的探讨[J].中医杂志,1998;39(4):233-235．
[75] Kong L, Li S, Han X, et al. Inhibition of HCV RNA-dependentRNA polymerase activity by aqueous extract from FructusLigustri Lucidi [J]. Virus Res,2007,128:9-17.
[76]沈健，陈建杰，商斌仪．丙肝冲剂治疗难治性丙型肝炎研究[J］．现代中西医结合杂志，2013，22(18):1947-1949
[77]殷杰,曾皓明,薛博瑜,等.丙肝宁冲剂治疗慢性丙型肝炎的临床研究[J].南京中医药大学学报(自然科学版),2002,18(1):21-23.
[78]张绍辉,秦佳波,韩忠孝.三草参汤治疗丙型肝炎56例体会[J].黑龙江医药科学,2002,25(4):55.
[79]聂红明,陈建杰.慢性丙型肝炎的中西医治疗现状[J].传染病信息,2012,25(3):143-146.
[80]刘光伟，赵文霞，杨明波，等.健脾清化方联合干扰素及利巴韦林治疗慢性丙型肝炎35例[J］.中医研究，2008，11(11):31-32.
[1]中华人民共和国卫生部．今天是世界卫生大会倡议的第一个世界肝炎日[EB／OL]．[2012—03—25]．http：／／www．moh．gov．cn／pub—licfiles／business／htmlfiles／mohjbyfkzj／s3586／201007／48258．htm．
[2]牟怀德,陈霞,刘听,等.吸毒人群丙肝感染现状研究[J].现代预防学,2006,33(10):1752一1753.
[3] Lemon SM，McKeating JA，Pietschmann T，et al． Developmentof novel therapies for hepatitis C． Antiviral Res，2010，86(1):79-92．
[4] Pawlotsky JM. Treating hepatitis C in“difficult-to-treat”patients[J]. N Engl J Med，2004，351(5):422-423.
[5] Fried MW，Jensen DM，Rodriguez-Torres M，et al. Improved outcomesin patients with hepatitis C with difficult-to-treatcharacteristics: randomized study of higher doses ofpeginterferon alpha-2a and ribavirin [J]. Hepatology，2008，48(4):1033-1043.
[6] Alberti A. What are the comorbidities influencing themanagement of patients and the response to therapy in chronichepatitis C?[J]. Liver Int，2009，29(Suppl1):S15-S18.
[7] Fried MW，Jensen DM，Rodriguez-Torres M，et al. Improvedoutcomes in patients with hepatitis C with difficult-to-treatcharacteristics: randomized study of higher doses ofpeginterferonalph a-2a and ribavirin [J]. Hepatology，2008，48(4):1033-1043.
[8]窦晓光,丁洋.慢性丙型肝炎抗病毒治疗的新策略和新方法[J].中国实用内科杂志,2010,30(3):217-219.
[9] DiagoM, Hassanein T, Rodes J, et al. Op timized virologicresponse in hepatitis C virus genotype4withpeginterferon-alpha2a and ribavirin[J]. Ann InternMed,2004,6,140(1):72-73.
[10] Chevaliez S, Pawlotsky JM. Diagnosis and management of hronicviral hepatitis: antigens, antibodies and viral genomes [J].Best pract Res Clin Gastroenterol,2008,22(6):1031一1048.
[11] Ferenci P，Laferl H， Scherzer TM, et al. Peginterferon alfa-2a and ribavirin for24weeks in hepatitis C type1and4Patie nts with rapid virological response [J]. Gastroen-terology,2008，135(2):451一458.
[12] Moreno C, Deltenre P, Pawlotsky JM, et al. Shortenedtreatment duration in treatment-naive genotype1HCV patientswith rapid virological response: a meta一analysis [J].JHepatol,2010,52(l):25一31.
[13] Mangia A, Minerva N, Bacca D, et al.Individualizedtreatment duration for hepatitis C genotype1patients: a randomized controlled trial[J]. Hepatology,2008,47(l):43一50.
[14] Goedert JJ, EysterME, Lederman MM, et al. End stage liverdisease in persons with hemophilia and transfusion2-associated infections[J]. Blood,2002,100(5):1584-1589.
[15] SulkowskiMS. Viral hepatitis and H IV coinfection [J]. JHepatol,2008,48(2):353-367.
[16] Labarga P, Soriano V,VispoME, et al. Hepatotoxicity ofantiretroviral drugs is reduced after successful treatmentof chronic hepatitis C in H IV infected patients[J]. J InfectDis,2007,196(5):670-676.
[17] Soriano V, PuotiM, SulkowskiM, et al. Care of patientscoinfected with H IV and hepatitis C virus:2007updatedrecommendations from the HCV2H IV international panel [J]. AIDS,2007,21(9):1073-1089.
[18] Landau A, Batisse D, Van Huyen JP, et al. Efficacy and safetyof combination therapy with interferon2alpha2b and ribavirinfor chronic hepatitis C in H IV2infected patients [J]. A IDS,2000,14(7):839-844.
[19] Nasti G,Di Gennaro G, TavioM, et al. Chronic hepatitis C inH IV infection: feasibility and sustained efficacy of therapywith interfere on alfa22b and ribavirin[J]. A IDS,2001,15(14):1783-1787.
[20] Pascual-Pareja JF, Caminoa A, Larrauri C, et al. HAART isassociated with lower hepatic necroinflammatory activity inHIV-hepatitis C virus-coinfected patients with CD4cellcount of more than350cells/microl at the time of liverbiopsy[J]. AIDS,2009,23(8):971-975.
[21] Vogel M, Rockstroh J. The treatment of chronic hepatitis Cvirus infection in HIV co-infection[J]. Eur J Med Res,2009,14(12):507-515
[22] Liaw YF,Chen YC,Sheen IS,et al. Impact of acute hepatitisC virus superinfection in patient s wit h chronic hepatitisB virus infection[J]. Gast roenterology,2004,126(4):1024-1029.
[23] Marrone A, Zampino R, D’Onofrio M, et al. Combined interferonplus lamivudine treatment in young patients with dual HBV(HBeAg positive) and HCV chronic infection[J]. JHepatol,2004,41(6):1064-1065.
[24] GHANY MG， STRADER DB，THOMAS DL， et al. AASLD PRACTICE GUIDEL INES：diagnosis，management， and treatment of hepatitisC： an update[J]. Hepatology，2009，49（4）：1335-1374.
[25] zeuzem s, Diago M, Gane E, et al.peginterferon alfa2a (40kilod altons) and ribavirin in Patients with chroniehepatitis C an d normal am inotransferase levels [J]. Gastroenterology,2004,127(6):1724一1732.
[26] Reddy KR, Shiffman ML, Rodriguez－Torres M, et al. InductionPegylated interferon alfa－and high dose ribavirindo notincrease SVR in heavy patients with HCV genotype1and highviral loads [J]. Gastroenterology,2010,139(6):1972一1983
[27] Ghany MG, Nelson DR, Strader DB, et al. An update on treatmentof genotype1chronic hepatitis C virus infection：2011Practice Guideline by the A merican Association for the Studyof Liver Diseases [J].Hepatology2011,54(4):1433一1444.
[28] McCaughan GW，Omata M，Amarapurkar D，et al. Asian PacificAssociation for the Study of the Liver consensus statementson the diagnosis management and treatment of hepatitis C virusinfection[J]. J Gastroenterol Hepatol，2007，22(5):615-633.
[29] Ghany MG， Strader DB， Thomas DL， et al. Diagnosis,management,and treatment of hepatitis C: an update[J].Hepatology，2009，49(4):1335-1374.
[30]Heathcote EJ，Shiffman M，Cooksley WG，et al. Peginterferonalfa-2a in patients with chronic hepatitis C and cirrhosis[J].NEngl J Med，2000，343(23):1673-1680.
[31]胡忠金，周衍国，潘润洪．丙型肝炎肝硬化抗病毒治疗的临床疗效分析[J］．临床研究，2012，2(4):73－74．
[32] Ghany MG, Strader DB, Thomas DL, et al.Diagnosis,management,and treatment of hepatitis c: an update[J].Hepatology,2009,49(4):1335一1374.
[33] European Association for the Study of the Live r. EASL clinicalPractice guide lines: management of hepatitis C v irusinfection [J].J Hepatol,2011,55(2):245一264.
[34] MC Caughan GW,o mata M, Amarapurkar D, et al. Asian PacificAssociation for the Study of the Liver consensus sta tementson the diagnosis, management and treatment of hepaat itis Cvirus in fection[J].J Gastroenterol Hepatol,2007,22(5):615一633.
[35I acobellis A，Siciliano M，Perri F，et al. Peginterferon alfa-2band ribavirin in patients with hepatitis C virus anddecompensated cirrhosis: a controlled study [J]. J Hepatol，2007，46(2):206-212.
[36] Farnik H，Mihm U，Zeuzem S. Optimal therapy in genotype1patients[J]. Liver Int，2009，29(Suppl1):S23-S30.
[37] Poynard T，Colombo M，Bruix J，et al. Peginterferon alfa-2band ribavirin: effective in patients with hepatitis C whofailed interferon alfa/ribavirin therapy[J].Gastroenterology，2009，136(5):1618-1628.
[38] Jensen DM，Marcellin P，Freilich B，et al. Re-treatment ofpatients with chronic hepatitis C who do not respond topeginterferon-alpha2b: a randomized trial[J]. Ann InternMed，2009，150(8):528-540
[39] Jensen DM, Marcellin P，Freilich B, et al. Re一treatmentof patients with chronic hepatitis C who do not respond top eginterferon alpha2b:a randomized trial[J]. Ann InternM ed,2009,150(8):528一540.
[40] Ghany MG，Strader DB，Thomas DL，et al. Diagnosis, management,and treatment of hepatitis C: an update[J]. Hepatology，2009，49(4):1335-1374
[41] Muir AJ，Poordad FF，McHutchison JG，et o1．Retreatment withtelaprevir combination therapy in hepatitis C patients with well—characterized prior treatment response[J]．Hepatology，2011．54(5)：1538-1546
[42] Terrault NA. Hepatitis C therapy before and after livertransplantation[J]. Liver Transpl，2008，14(Suppl2):S58-S66.
[43] European Association for the Study of the Liver. EASL ClinicalPractice Guidelines: management of hepatitis C virusinfection[J]. J Hepatol,2011,55(2):245-264.
[44] Antúnez I，Aponte N，Fernández-Carbia A，et al. Steatosisas a predictive factor for treatment response in patients withchronic hepatitis C[J].P R Health Sci J，2004，23(2Suppl):S57-S60.
[45] Romano M, Vacante M, Cristaldi E, et al.Malaguarnera M.-carnitine treatment reduces steatosis in patients with chronic hepatitis C treated with alpha一interferon and ribavirin[J].Dig Dis Sci,2008,53(4):1114一1121.
[46] Romero-Gómez M，Diago M，Andrade RJ，et al. Metformin withpeginterferon alfa-2a and ribavirin in the treatment ofnaivegenotype1chronic hepatitis C patients with insulinresistance (TRIC-1): final results of a randomized anddoubleblinded trial [C/OL]//59th Annual Meeting of theAmerican Association for the Study of Liver Diseases (AASLD),San Francisco,CA,October31—November1,2008.[2009-06-10].
[47] Bressler BL，Guindi M，Tomlinson G，et al. High body mass indexis an independent risk factor for nonresponse to antiviraltreatment in chronic hepatitis C[J]. Hepatology，2003，38(3):639-644.
[48] Suzuki Y，Ikeda K，Suzuki F，Toyta J，Karino Y,Chayama K，et al.Dual oral therapy with daclatasvir and Daclatasvir andasunaprevir for patients with HCV genotype1b infection andlimited treatment opions.J Hepatol2013；58:655-662.
[49]马冠军，董少群．外邪“直中血络”初探[J］．河南中医，2010，30(5):435－436．
[50]王成宝，聂红明，李泓町．陈建杰教授治疗慢性丙型肝炎经验[J］．河南中医，2010，30(5):440－441．
[51]刁青蕊.薛博瑜教授治疗丙型肝炎临床经验[J].世界中西医结合杂志,2011,6(3):239-241.
[52]吴沛田．慢性丙型肝炎中医辨治应注意什么[J］．中医杂志，2008，49(1):88．
[53]吴乾生．大黄虫丸联合保肝治疗慢性丙型肝炎肝硬化疗效观察[J］．光明中医，2008，23(8):1129-1131．
[54]吴沛田．慢性丙型肝炎中医辨治应注意什么[J］．中医杂志，2008，49(1):88．
[55]车念聪.北京地区慢性丙型肝炎中医证候学研究及辨证分型的初步调查[J].北京中医,2002,2(1):300-304.
[56]李乾构.中西医对丙型肝炎的研究现状[J].中国中西医结合消化杂志,2002,10(2):120-1
[57]陈兰匆，昌文良．丙肝的中医治疗[J］．家庭中医药，2010，16(8):30-31．
[58]陈文林，陆坚，李炜，等.慢性丙型肝炎中医证候量表分析[J］．山西中医学院学报，2010，11(1):33-35．
[59]张永，高乘成，王伟芹，等.72例慢性丙型肝炎患者发病与中医证候分布规律调查[J］．山东中医杂志，2010，29(11):747－749．
[60]金实.慢性丙型肝炎中医辨证分型与临床检测指标关系的探讨[J].中医杂志,1998，39(4):233-235．
[61]车念聪,付修文，高连印，等.北京地区慢性丙型肝炎医证候学研究及辨证分型的初步调查[J],北京中医杂志，2002，21（5）：300-304.
[62]上海市中医药学会肝病分会专业委员会;国家“十一五”科技重大专项重大传染病中医药防治课题组.中国慢性丙型肝炎中医辨证分型规范研究[J].上海中医药杂志,2012,46(3):11-12.
[63]周珉.慢性丙型肝炎的辨治规律探讨[J].江苏中医，1998,(7):13-14.
[64]赵文霞.中医辨治慢性丙型肝炎38例[J].河南中医药学刊,1996,(3):52-54.
[65]苏进才.丙肝的中医论治[J].陕西中医学院学报,2003,26(1):24-25.
[66]葛香芹．辨证治疗肝郁脾虚型慢性丙型肝炎30例[J］．吉林中医药，2008，28(5):341－342．
[67]张雯，郑宜南，张云鹏．张云鹏治疗慢性丙型肝炎经验撷英[J］．上海中医药杂志，2011，45(4):1－2．
[68]景忠良,董靖,赵爱红.祛湿解毒活血汤为主治疗慢性丙型肝炎26例[J].实用中医内科杂志,2009(8):55-56.
[69]齐京,关幼波,温庆祥,等.复肝抑纤汤治疗慢性丙型肝炎肝纤维化36例临床观察[J].中国中医基础医学杂志,2003,9(11):42-44.
[70]安绪平,王晓岳,张顺宪.安络化纤丸治疗丙型肝炎肝硬化疗效观察[J].浙江临床医学,2010,12(5):507.
[71]徐建良,盛国光,李晓东,等.松栀丸治疗慢性丙型肝炎疗效观察
[J].湖北中医杂志,2007,29(2):12-13.
[72]谢国忠.二参双甲汤治疗丙型病毒性肝炎32例[J].陕西中医，2010，(5):526-527.
[73]李德华,李永光,李德宇.五苓丙肝散治疗丙型肝炎的临床研究[J].中医药信息杂志,2011,28(1):70-71.
[74］肖会泉，罗日永，吴婉芬．健脾活血方治疗慢性丙型肝炎32例疗效观察[J］．新中医，2005，1(37):46－47．
[75]李运东，陈建杰．苦参素注射液治疗慢性丙型肝炎38例临床观察[J］．山东中医药大学学报，2005，3(2):125－126．
[76]张富山．中西医结合治疗慢性丙型肝炎30例[J］．中医研究，2009，22(8):27－28．
[77]常占杰,李京涛.益气养肝方联合干扰素、利巴韦林治疗慢性丙型肝炎的疗效观察[J].中国肝脏病杂志（电子版）,2009，1（2）：24-26.
[78]伍玉南,孙克伟,彭建平,等.疏肝理脾片对干扰素联合利巴韦林治疗慢性丙型肝炎疗效的影响[J].中西医结合肝病杂志,2009，19(2):76-77.
[79]敬小华，祁培宏，张永霞，等.中药联合聚乙二醇干扰素α-2a治疗慢性丙型肝炎疗效观察[J].上海中医药杂志，2010，44(8):36-37.
[80]李镤主编.穴位注射疗法临床大全.北京:中国中医药出版社,1996.17.
[81]孔胜利，李志刚，孙立新．穴位注射联合苦参素综合治疗慢性丙型肝炎疗效观察[J］．中国误诊学杂志，2008，8(31):7586－7587．
[82]斯旭平．α-干扰素穴位注射治疗慢性丙型肝炎[J］．浙江中西医结合杂志，2002，12(2):121．
[83]小椋加枝．针灸治疗对丙型肝炎病毒量的影响:针刺手法与血中Th1、Th2细胞的关系[J］．全日本针灸学会杂志，2001，51(3):87．
[2] Sansonno D, Iacobelli AR, Cornacchiulo V, et al. Detection ofhepatitis C virus (HCV) proteins by immunofluorescence andHCV RNAgenomic sequences by non-isotopic in situ ybridizationin bone marrowand peripheral blood mononuclear cells ofchronically HCVinfected patients[J］. Clin Exp Immunol,1996,103(3):414-421．
[3] Irshad M，Ansari M A，Singh A，et al.HCV-genotypes: a reviewon their origin，global status，assay system，pathogenecityand response to treatment[J］.Hepatogastroenterology，2010，57(104):1529-1538．
[4] Ghany MG，Nelson DR，Strader DB，et al. An update on treatmentof genotype1chronic hepatitis C virus infection:2011practice guideline by the American Association for the Studyof Liver Diseases. Hepatology，2011，5（4）:1433-1444．
[5] Ghany MG，strager DB Thomas DL，etal.diagnosis，magement，and treatment of hepatitis： an update[J].Hepatology,2009,49(4)：1335-1374.
[6] Me Caug han GW,omata M, Am arapurkar D, et al. Asian PacificAssociation for the Study of the Liver consensus Statementson the diagnosis, management and treatment of hepatitis Cvirus in fection [J].J Gastroenterol Hepatol,2007,22(5):615一633.
[7] EuroPean Association for the Study of the Liver. EASL clinicalPractice guidelines: management of hepatitis C virus infection [J].J Hepatol,2011,55(2):245一264.
[8]马丽娜,陈新月,陈杰,等.聚乙二醇干扰素治疗慢性丙型肝炎临床疗效!影响因素及安全性分析(附89例临床分析)[J].中华实验和临床病毒学杂志,2006,20(2):42-45.
[9] Di Bisceglie AM, Thompson J, Smith一Wilkaitis N, et alCombination of interferon and ribavirin in chonic hepatitisC:retreatment o f nonresponders to interferon [J].Hepatology2001,33(3):704一707.
[10]中华人民共和国卫生部．今天是世界卫生大会倡议的第一个世界肝炎日[EB／OL]．[2012—03—25]．http：／／www．moh．gov．cn／pub—licfiles／business／htmlfiles／mohjbyfkzj／s3586／201007／48258．htm．
[11]陈旭，马玉梅．对我国《丙型肝炎防治指南》的解读[J］．中国实用乡村医生杂志，2007，14(2):49－51．
[12] Ford JA，Cheong-Lee C． The role of hepatology nurse in thedifficult-to-treat hepatitis C population[J］． Can JGastroenterol，2007，21(6):353－354.
[13]谢尧，李明慧．难治性丙型病毒性肝炎的治疗现状及发展趋势[J］．中华肝脏病杂志，2009，17(7):484－486．
[14]上海市中医药学会肝病分会专业委员会;国家“十一五”科技重大专项重大传染病中医药防治课题组[J].上海中医药杂志，2012,46(3):11-12．
[15] Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronichepatitis C: a randomized study of treatment duration andribavirin dose[J］. Ann Intern Med,2004,140(5):346-355.
[16] Manns MP, McHutchison JG, Gordon SC, et al. Peginterferonalfa-2b plus ribavirin compared with interferon alfa-2b plusribavirin for initial treatment of chronic hepatitis C: arandomised trial[J］.Lancet,2001,358(9296):958-965.
[17] McHutchison JG, Lawitz EJ, Shiffman ML, et al. Peginterferonalfa-2b or alfa-2a with ribavirin for treatment of hepatitisC infection[J］. N Engl J Med,2009,361(6):580-593.
[18] Ghany MG, Nelson DR, Strader DB, et al. An update on treatmentof genotype1chronic hepatitis C virus infection:2011practice guideline by the American Association for the Studyof Liver Diseases[J］. Hepatology,2011,55(4):1433-1444.
[19]梁喜爱，吴宗耀，李昱晓．抗慢性丙型病毒性肝炎药物研究进展[J］中医学报，2010，25(4):813－814．
[20]沈健，陈建杰，商斌仪．丙肝冲剂治疗难治性丙型肝炎研究[J］．现代中西医结合杂志，2013，22(18):1947-1949
[21] Ghany MG，Strader DB，Thomas DL，et al．Diagnosis，management，and treatment of hepatitis C: an update [J］．Hepatology．2009，49(4):1335－1374．
[22]窦晓光.难治性慢性丙型肝炎一我们面临的新挑战[J].中华肝脏病杂志,2009,17(7):486-487.
[23] You J，Zhuang L，Zhang YF，et al．Peripheral T－lymphocytesubpopulations in different clinical stages of chronic HBVinfection correlate with HBV load[J］． World J Gastroenterol，2009，15(27):3382－3393.
[24]沈书旭，刘英，关琪． HCV感染者外周血CD4+T细胞计数与病毒载量的相关性分析[J］．沈阳医学院学报，2009，11(4):213－214．
[25] U lsenh eim er A, Gerlach JT, Gruen er NH, et a.l Detectionof functionally altered hepat itis Cv iru s-specif ic CD4+T cells in acute and ch ron ic hepat itis C [J]. H epatology,2003,37:1189-1198.
[26] Rosen HR, M iner C, Sasak i AW, et a.l Frequ encies of HCVspecific effect or CD4+T cells by flow cytom etry: correlation w ith clin ical d isease s tages [J]. H epatology,2002,35:190-198.
[27] Kan tzanouM, Lu casM, Barnes E, et a.l V iral escape and T cellexhaust ion in h epatitisC virus in fection analysed us ingC lass I peptide tetram ers [J].Immuno lLett,2003,85:165-171.
[28]陈志刚，杨军，周婷，等．慢性丙型肝炎患者血清HCV RNA含量与IFN－γ及IL－4的变化关系[J］．临床检验杂志，2007，25(2):146．
[29]张武英，龙列明，冯冰，等．慢性丙型肝炎患者病毒载量与T细胞免疫功能关系分析[J］．广东医学，2010，31(21):2827－2828．
[30]高勇,贺永文,曾令兰,等.丙型肝炎病毒感染外周血单个核细胞对丙型肝炎的影响[J].同济医科大学学报,2000,20(5):450～452．
[31]沈书旭，吴玉海，关琪，等． CD4+CD25+调节性T细胞对HCV感染者疾病进程影响的研究[J］．沈阳医学院学报，2010，12(2):73－74．
[32]张缭云,赵和平,赵龙凤,等.丙型肝炎患者外周血T淋巴细胞亚群及sIL22R变化的研究[J].山西医科大学学报,2002，33(6):511-513.
[33]梁骑，焦艳梅，计云霞，等.慢性丙型肝炎患者DNT细胞及T细胞亚群的研究[J].首都医科大学学报,2012，33(2):214-217.
[34] Lechner F, W ong D K, Dunbar P R, et a.l Analysis of successfulimmune responses in persons infected with hepatitisCvirus[J]. J ExpMed,2000,191,1499-1512.
[35] Fe ld J J, H oofnag le J H. M echan ism o f action of in terferonand ribavirin in treatment of hepatitis C[J]. Nature,2005,436:967-972.
[36]周延美，周延英.肝硬化患者外周T淋巴细胞亚群变迁及免疫功能状态的分析[J].中国医药指南，2013,11（10）：635-636.
[37]王晶，慧吴标，黄玲，等.不同临床阶段乙型肝炎患者外周C D8+T淋巴细胞免疫记忆应答水平的比较[J].肝脏，2013,18（6）：369-373.
[38]林浩，谢玲珠，李秀芬.肝硬化患者CD4+T细胞的改变及意义[J].广东医学,2011，32（23）:3068-3070.
[39]田瑛，李太生．乙型肝炎病毒感染临床转归与宿主细胞免疫的相关性研究[J]．中华内科杂志，2007，46(12):1014－1017．
[40]曹振环，陈新月．慢性丙型病毒性肝炎患者体内T细胞亚群及细胞因子的变化[J］．中国病原生物学杂志，2008，3(11):855－857．
[41］Higuchi M，Tanaka E，Kiyosawa K． Epidemiology and clinicalaspects on hepatitis C[J］．Jpn J Infect Dis，2002，55(3):69－77．
[42］成军．丙型肝炎病毒基因变异及其临床意义[J］．中华肝脏病杂志，2006，14(1):54－55．
[43] Bengsch B，Thimme R，Blum HE． Role of host genetic factorsin the outcome of hepatitis C virus infection[J］．Viruses，2009，1(2):104－125．
[44]周友乾，尹凤鸣，冯经．慢性丙型肝炎抗病毒治疗后复发的影响因素分析[J］．临床肝胆病杂志，2012，28(8):609－611．
[45]王琰,朱新宇,王霞,等.太原地区丙型肝炎病毒基因分型及其临床意义[J].实用肝脏病杂志,2010,13(2):109-111.
[46]刘毓刚，王天然，李国良． HCV感染者外周血T淋巴细胞亚群的变化[J]．四川医学，2010，31(2):241-242．
[47]张琳,苗亮,韩峰.慢性丙型肝炎患者血清细胞因子水平的变化及意义[J].细胞与分子免疫学杂志，2011,27（3）:302-303．临床
[48] Masaki N, Fukushima S, Hayashi S. Lower th21/th22ratiobefore interferon therapy may favor long term virologicalresponses in patients with chronic hepatitis C[J]. Dig DisSci,2002,47(10):2163-2169．
[49]曹振环，陈新月．慢性丙型病毒性肝炎患者体内T细胞亚群及细胞因子的变化[J］．中国病原生物学杂志，2008，3(11):855－857．
[50]上海中医药大学附属曙光医院肝病科．全国第九届肝胆病学术会议论文集[D]，2000:17．
[51]车念聪，付修文，高连印，杜宇琼，王融冰，李秀惠．北京地区慢性丙型肝炎中医证候学研究及辨证分型的初步调查[J］．北京中医，2002，21(5):300－304．
[52]胡志军，丁辉，汪晓军．慢性丙型肝炎患者中医证型与ALT、AST、HCV-RNA之间的关系[J］．河南中医，2012，32(3):303－304．
[53] NGUYEN-KHAC E，CAPRON D，ASTELAIN S，et al. Personalized therapyfor chronic viral hepatitis C in the naive patient:How can weoptimize treatment duration as a function of viralgenotype[J].Eur J Intern Med，2007，18（7）:510-515.
[54] SCHINKEL J，KROES AC，WAGTMANS MJ，et al. Monitoring responseduring a randomised controlled trial of escalating interferondose for chronic hepatitis C infection:predictive value ofquantitative and qualitative HCV RNA assays[J]. J Clin Virol，2001，22（1）:61-71.
[55] TAKENOKUCHI M，YASUDA C，NAKAMACHI Y，et al. Comparativeevaluation of serum HCV RNA by Roche Monitor Assay.Versions1.0and2.0；as a predictive marker of subsequent responseto IFN therapy[J]. Rinsho Byori，2002，50（4）:392-397.
[56] FERN NDEZ I，CASTELLANO G，DOMINGO MJ，et al.Influence of viralgenotype and level of viremia on the severity of liver injuryand the response to interferon therapy in Spanish patientswith chronic C infection [J]. Scand J Gastroenterol，1997，32（1）:70-76.
[57] LEE SD，YU ML，CHENG PN，et al. Comparison of a6-month coursepeginterferon a-2b plus ribavirin and interferon a-2b plusribavirin in treating Chinese patients with chronic hepatitisC in Taiwan[J]. J Viral Hepatitis，2005，12，283-291.
[58]胡志军，丁辉，汪晓军．慢性丙型肝炎患者中医证型与ALT、AST、HCV-RNA之间的关系[J］．河南中医，2012，32(3):303－304．
[59]贾因棠,魏来,蒋栋等.干扰素刺激基因ISG20真核表达载体的构建及其抗丙型肝炎病毒复制作用的研究[J］.中国免疫学杂志.2006,22（11）:997-1001.
[60] Khakoo SI, T hio CL, Mar tin MP, et al. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection[J].Science,2004,305(5685):872-874.
[61] Li W, Krishn adas DK, Kumar R, etal. Priming and stimulationof hepatitis C virus-specific CD4+and CD8+T cells again stH CV antigens NS4, NS5a or NS5b from H CV-n aive individuals:implicat ions for prophylactic vaccine[J]. InternationalImmunology.2007,20(1):89-104.
[62] Jinushi M, T akehara T, T atsum i T, et al. Autocrine/paracrine IL-15that is required for type I IFN mediateddendritic cell expression of M HC class Irelated chain A andB is impair ed in hepatit is C virus infection [J]. J Immunol,2003,171(10):5423-5429.
[63]王全楚. T h1/T h2和T c1/T c2与慢性丙型肝炎[J].国外医学免疫学分册.2001,24(1):54-55.
[64]金波,王慧芬,王福生,等.慢性丙型肝炎患者型树突状细胞、淋巴细胞亚群的特点及临床意义[J].传染病信息.2008,21(2):115-118.
[65]杨江华,张永祥,苏川,等.慢性丙型肝炎患者CD4+CD25+调节性T细胞表达增加[J].世界华人消化杂志.2005,13(18):2201-2204.
[66]刘加顺，陈涛，刘丽丽，等.难治性丙型肝炎临床治疗的研究[J].当代医学.2013,19(31):130-131.
[67] Hézode C.Oral combination therapy:future hepatitis Cvirustreatment?[J].J Hepatology，2011，55(4):933-935.
[68] Gonzalez SA，Keeffe EB. Management of chronic hepatitis Ctreatment failures：role of consensus interferon[J].Biologics，2009，3：141-150.
[69] Sjogren MH，Sjogren R，Holtzmuller K，et al. Interferonalfacon-1and ribavirin versus interferon alpha-2b andribavirin in the treatment of chronic hepatitis C[J]. Dig DisSci，2005，50（4）：727-732.
[70] Leevy CB. Consensus interferon and ribavirin in patients withchronic hepatitis C who were nonresponders to pegylatedinterferonalfa-2b and ribavirin[J]. Dig Dis Sci，2008，53（7）：1961-1966.
[71] Bacon BR，Shiffman ML，Mendes F，et al. Retreating chronichepatitis C with daily interferon alfacon-1/ribavirin afternonresponse to pegylated interferon/ribavirin：DIRECTresults[J].Hepatology，2009，49（6）：1838-1846.
[72]周一鸣，曹建彪，范公忍.老年丙型肝炎肝硬化的中药治疗探讨[J］．实用老年医学，2013，27(6):477-479．
[73］陈文林，陆坚，李炜，等.慢性丙型肝炎中医证候量表分析[J］．山西中医学院学报，2010，11(1):33－35．
[74]金实.慢性丙型肝炎中医辨证分型与临床检测指标关系的探讨[J].中医杂志,1998;39(4):233-235．
[75] Kong L, Li S, Han X, et al. Inhibition of HCV RNA-dependentRNA polymerase activity by aqueous extract from FructusLigustri Lucidi [J]. Virus Res,2007,128:9-17.
[76]沈健，陈建杰，商斌仪．丙肝冲剂治疗难治性丙型肝炎研究[J］．现代中西医结合杂志，2013，22(18):1947-1949
[77]殷杰,曾皓明,薛博瑜,等.丙肝宁冲剂治疗慢性丙型肝炎的临床研究[J].南京中医药大学学报(自然科学版),2002,18(1):21-23.
[78]张绍辉,秦佳波,韩忠孝.三草参汤治疗丙型肝炎56例体会[J].黑龙江医药科学,2002,25(4):55.
[79]聂红明,陈建杰.慢性丙型肝炎的中西医治疗现状[J].传染病信息,2012,25(3):143-146.
[80]刘光伟，赵文霞，杨明波，等.健脾清化方联合干扰素及利巴韦林治疗慢性丙型肝炎35例[J］.中医研究，2008，11(11):31-32.
[1]中华人民共和国卫生部．今天是世界卫生大会倡议的第一个世界肝炎日[EB／OL]．[2012—03—25]．http：／／www．moh．gov．cn／pub—licfiles／business／htmlfiles／mohjbyfkzj／s3586／201007／48258．htm．
[2]牟怀德,陈霞,刘听,等.吸毒人群丙肝感染现状研究[J].现代预防学,2006,33(10):1752一1753.
[3] Lemon SM，McKeating JA，Pietschmann T，et al． Developmentof novel therapies for hepatitis C． Antiviral Res，2010，86(1):79-92．
[4] Pawlotsky JM. Treating hepatitis C in“difficult-to-treat”patients[J]. N Engl J Med，2004，351(5):422-423.
[5] Fried MW，Jensen DM，Rodriguez-Torres M，et al. Improved outcomesin patients with hepatitis C with difficult-to-treatcharacteristics: randomized study of higher doses ofpeginterferon alpha-2a and ribavirin [J]. Hepatology，2008，48(4):1033-1043.
[6] Alberti A. What are the comorbidities influencing themanagement of patients and the response to therapy in chronichepatitis C?[J]. Liver Int，2009，29(Suppl1):S15-S18.
[7] Fried MW，Jensen DM，Rodriguez-Torres M，et al. Improvedoutcomes in patients with hepatitis C with difficult-to-treatcharacteristics: randomized study of higher doses ofpeginterferonalph a-2a and ribavirin [J]. Hepatology，2008，48(4):1033-1043.
[8]窦晓光,丁洋.慢性丙型肝炎抗病毒治疗的新策略和新方法[J].中国实用内科杂志,2010,30(3):217-219.
[9] DiagoM, Hassanein T, Rodes J, et al. Op timized virologicresponse in hepatitis C virus genotype4withpeginterferon-alpha2a and ribavirin[J]. Ann InternMed,2004,6,140(1):72-73.
[10] Chevaliez S, Pawlotsky JM. Diagnosis and management of hronicviral hepatitis: antigens, antibodies and viral genomes [J].Best pract Res Clin Gastroenterol,2008,22(6):1031一1048.
[11] Ferenci P，Laferl H， Scherzer TM, et al. Peginterferon alfa-2a and ribavirin for24weeks in hepatitis C type1and4Patie nts with rapid virological response [J]. Gastroen-terology,2008，135(2):451一458.
[12] Moreno C, Deltenre P, Pawlotsky JM, et al. Shortenedtreatment duration in treatment-naive genotype1HCV patientswith rapid virological response: a meta一analysis [J].JHepatol,2010,52(l):25一31.
[13] Mangia A, Minerva N, Bacca D, et al.Individualizedtreatment duration for hepatitis C genotype1patients: a randomized controlled trial[J]. Hepatology,2008,47(l):43一50.
[14] Goedert JJ, EysterME, Lederman MM, et al. End stage liverdisease in persons with hemophilia and transfusion2-associated infections[J]. Blood,2002,100(5):1584-1589.
[15] SulkowskiMS. Viral hepatitis and H IV coinfection [J]. JHepatol,2008,48(2):353-367.
[16] Labarga P, Soriano V,VispoME, et al. Hepatotoxicity ofantiretroviral drugs is reduced after successful treatmentof chronic hepatitis C in H IV infected patients[J]. J InfectDis,2007,196(5):670-676.
[17] Soriano V, PuotiM, SulkowskiM, et al. Care of patientscoinfected with H IV and hepatitis C virus:2007updatedrecommendations from the HCV2H IV international panel [J]. AIDS,2007,21(9):1073-1089.
[18] Landau A, Batisse D, Van Huyen JP, et al. Efficacy and safetyof combination therapy with interferon2alpha2b and ribavirinfor chronic hepatitis C in H IV2infected patients [J]. A IDS,2000,14(7):839-844.
[19] Nasti G,Di Gennaro G, TavioM, et al. Chronic hepatitis C inH IV infection: feasibility and sustained efficacy of therapywith interfere on alfa22b and ribavirin[J]. A IDS,2001,15(14):1783-1787.
[20] Pascual-Pareja JF, Caminoa A, Larrauri C, et al. HAART isassociated with lower hepatic necroinflammatory activity inHIV-hepatitis C virus-coinfected patients with CD4cellcount of more than350cells/microl at the time of liverbiopsy[J]. AIDS,2009,23(8):971-975.
[21] Vogel M, Rockstroh J. The treatment of chronic hepatitis Cvirus infection in HIV co-infection[J]. Eur J Med Res,2009,14(12):507-515
[22] Liaw YF,Chen YC,Sheen IS,et al. Impact of acute hepatitisC virus superinfection in patient s wit h chronic hepatitisB virus infection[J]. Gast roenterology,2004,126(4):1024-1029.
[23] Marrone A, Zampino R, D’Onofrio M, et al. Combined interferonplus lamivudine treatment in young patients with dual HBV(HBeAg positive) and HCV chronic infection[J]. JHepatol,2004,41(6):1064-1065.
[24] GHANY MG， STRADER DB，THOMAS DL， et al. AASLD PRACTICE GUIDEL INES：diagnosis，management， and treatment of hepatitisC： an update[J]. Hepatology，2009，49（4）：1335-1374.
[25] zeuzem s, Diago M, Gane E, et al.peginterferon alfa2a (40kilod altons) and ribavirin in Patients with chroniehepatitis C an d normal am inotransferase levels [J]. Gastroenterology,2004,127(6):1724一1732.
[26] Reddy KR, Shiffman ML, Rodriguez－Torres M, et al. InductionPegylated interferon alfa－and high dose ribavirindo notincrease SVR in heavy patients with HCV genotype1and highviral loads [J]. Gastroenterology,2010,139(6):1972一1983
[27] Ghany MG, Nelson DR, Strader DB, et al. An update on treatmentof genotype1chronic hepatitis C virus infection：2011Practice Guideline by the A merican Association for the Studyof Liver Diseases [J].Hepatology2011,54(4):1433一1444.
[28] McCaughan GW，Omata M，Amarapurkar D，et al. Asian PacificAssociation for the Study of the Liver consensus statementson the diagnosis management and treatment of hepatitis C virusinfection[J]. J Gastroenterol Hepatol，2007，22(5):615-633.
[29] Ghany MG， Strader DB， Thomas DL， et al. Diagnosis,management,and treatment of hepatitis C: an update[J].Hepatology，2009，49(4):1335-1374.
[30]Heathcote EJ，Shiffman M，Cooksley WG，et al. Peginterferonalfa-2a in patients with chronic hepatitis C and cirrhosis[J].NEngl J Med，2000，343(23):1673-1680.
[31]胡忠金，周衍国，潘润洪．丙型肝炎肝硬化抗病毒治疗的临床疗效分析[J］．临床研究，2012，2(4):73－74．
[32] Ghany MG, Strader DB, Thomas DL, et al.Diagnosis,management,and treatment of hepatitis c: an update[J].Hepatology,2009,49(4):1335一1374.
[33] European Association for the Study of the Live r. EASL clinicalPractice guide lines: management of hepatitis C v irusinfection [J].J Hepatol,2011,55(2):245一264.
[34] MC Caughan GW,o mata M, Amarapurkar D, et al. Asian PacificAssociation for the Study of the Liver consensus sta tementson the diagnosis, management and treatment of hepaat itis Cvirus in fection[J].J Gastroenterol Hepatol,2007,22(5):615一633.
[35I acobellis A，Siciliano M，Perri F，et al. Peginterferon alfa-2band ribavirin in patients with hepatitis C virus anddecompensated cirrhosis: a controlled study [J]. J Hepatol，2007，46(2):206-212.
[36] Farnik H，Mihm U，Zeuzem S. Optimal therapy in genotype1patients[J]. Liver Int，2009，29(Suppl1):S23-S30.
[37] Poynard T，Colombo M，Bruix J，et al. Peginterferon alfa-2band ribavirin: effective in patients with hepatitis C whofailed interferon alfa/ribavirin therapy[J].Gastroenterology，2009，136(5):1618-1628.
[38] Jensen DM，Marcellin P，Freilich B，et al. Re-treatment ofpatients with chronic hepatitis C who do not respond topeginterferon-alpha2b: a randomized trial[J]. Ann InternMed，2009，150(8):528-540
[39] Jensen DM, Marcellin P，Freilich B, et al. Re一treatmentof patients with chronic hepatitis C who do not respond top eginterferon alpha2b:a randomized trial[J]. Ann InternM ed,2009,150(8):528一540.
[40] Ghany MG，Strader DB，Thomas DL，et al. Diagnosis, management,and treatment of hepatitis C: an update[J]. Hepatology，2009，49(4):1335-1374
[41] Muir AJ，Poordad FF，McHutchison JG，et o1．Retreatment withtelaprevir combination therapy in hepatitis C patients with well—characterized prior treatment response[J]．Hepatology，2011．54(5)：1538-1546
[42] Terrault NA. Hepatitis C therapy before and after livertransplantation[J]. Liver Transpl，2008，14(Suppl2):S58-S66.
[43] European Association for the Study of the Liver. EASL ClinicalPractice Guidelines: management of hepatitis C virusinfection[J]. J Hepatol,2011,55(2):245-264.
[44] Antúnez I，Aponte N，Fernández-Carbia A，et al. Steatosisas a predictive factor for treatment response in patients withchronic hepatitis C[J].P R Health Sci J，2004，23(2Suppl):S57-S60.
[45] Romano M, Vacante M, Cristaldi E, et al.Malaguarnera M.-carnitine treatment reduces steatosis in patients with chronic hepatitis C treated with alpha一interferon and ribavirin[J].Dig Dis Sci,2008,53(4):1114一1121.
[46] Romero-Gómez M，Diago M，Andrade RJ，et al. Metformin withpeginterferon alfa-2a and ribavirin in the treatment ofnaivegenotype1chronic hepatitis C patients with insulinresistance (TRIC-1): final results of a randomized anddoubleblinded trial [C/OL]//59th Annual Meeting of theAmerican Association for the Study of Liver Diseases (AASLD),San Francisco,CA,October31—November1,2008.[2009-06-10].
[47] Bressler BL，Guindi M，Tomlinson G，et al. High body mass indexis an independent risk factor for nonresponse to antiviraltreatment in chronic hepatitis C[J]. Hepatology，2003，38(3):639-644.
[48] Suzuki Y，Ikeda K，Suzuki F，Toyta J，Karino Y,Chayama K，et al.Dual oral therapy with daclatasvir and Daclatasvir andasunaprevir for patients with HCV genotype1b infection andlimited treatment opions.J Hepatol2013；58:655-662.
[49]马冠军，董少群．外邪“直中血络”初探[J］．河南中医，2010，30(5):435－436．
[50]王成宝，聂红明，李泓町．陈建杰教授治疗慢性丙型肝炎经验[J］．河南中医，2010，30(5):440－441．
[51]刁青蕊.薛博瑜教授治疗丙型肝炎临床经验[J].世界中西医结合杂志,2011,6(3):239-241.
[52]吴沛田．慢性丙型肝炎中医辨治应注意什么[J］．中医杂志，2008，49(1):88．
[53]吴乾生．大黄虫丸联合保肝治疗慢性丙型肝炎肝硬化疗效观察[J］．光明中医，2008，23(8):1129-1131．
[54]吴沛田．慢性丙型肝炎中医辨治应注意什么[J］．中医杂志，2008，49(1):88．
[55]车念聪.北京地区慢性丙型肝炎中医证候学研究及辨证分型的初步调查[J].北京中医,2002,2(1):300-304.
[56]李乾构.中西医对丙型肝炎的研究现状[J].中国中西医结合消化杂志,2002,10(2):120-1
[57]陈兰匆，昌文良．丙肝的中医治疗[J］．家庭中医药，2010，16(8):30-31．
[58]陈文林，陆坚，李炜，等.慢性丙型肝炎中医证候量表分析[J］．山西中医学院学报，2010，11(1):33-35．
[59]张永，高乘成，王伟芹，等.72例慢性丙型肝炎患者发病与中医证候分布规律调查[J］．山东中医杂志，2010，29(11):747－749．
[60]金实.慢性丙型肝炎中医辨证分型与临床检测指标关系的探讨[J].中医杂志,1998，39(4):233-235．
[61]车念聪,付修文，高连印，等.北京地区慢性丙型肝炎医证候学研究及辨证分型的初步调查[J],北京中医杂志，2002，21（5）：300-304.
[62]上海市中医药学会肝病分会专业委员会;国家“十一五”科技重大专项重大传染病中医药防治课题组.中国慢性丙型肝炎中医辨证分型规范研究[J].上海中医药杂志,2012,46(3):11-12.
[63]周珉.慢性丙型肝炎的辨治规律探讨[J].江苏中医，1998,(7):13-14.
[64]赵文霞.中医辨治慢性丙型肝炎38例[J].河南中医药学刊,1996,(3):52-54.
[65]苏进才.丙肝的中医论治[J].陕西中医学院学报,2003,26(1):24-25.
[66]葛香芹．辨证治疗肝郁脾虚型慢性丙型肝炎30例[J］．吉林中医药，2008，28(5):341－342．
[67]张雯，郑宜南，张云鹏．张云鹏治疗慢性丙型肝炎经验撷英[J］．上海中医药杂志，2011，45(4):1－2．
[68]景忠良,董靖,赵爱红.祛湿解毒活血汤为主治疗慢性丙型肝炎26例[J].实用中医内科杂志,2009(8):55-56.
[69]齐京,关幼波,温庆祥,等.复肝抑纤汤治疗慢性丙型肝炎肝纤维化36例临床观察[J].中国中医基础医学杂志,2003,9(11):42-44.
[70]安绪平,王晓岳,张顺宪.安络化纤丸治疗丙型肝炎肝硬化疗效观察[J].浙江临床医学,2010,12(5):507.
[71]徐建良,盛国光,李晓东,等.松栀丸治疗慢性丙型肝炎疗效观察
[J].湖北中医杂志,2007,29(2):12-13.
[72]谢国忠.二参双甲汤治疗丙型病毒性肝炎32例[J].陕西中医，2010，(5):526-527.
[73]李德华,李永光,李德宇.五苓丙肝散治疗丙型肝炎的临床研究[J].中医药信息杂志,2011,28(1):70-71.
[74］肖会泉，罗日永，吴婉芬．健脾活血方治疗慢性丙型肝炎32例疗效观察[J］．新中医，2005，1(37):46－47．
[75]李运东，陈建杰．苦参素注射液治疗慢性丙型肝炎38例临床观察[J］．山东中医药大学学报，2005，3(2):125－126．
[76]张富山．中西医结合治疗慢性丙型肝炎30例[J］．中医研究，2009，22(8):27－28．
[77]常占杰,李京涛.益气养肝方联合干扰素、利巴韦林治疗慢性丙型肝炎的疗效观察[J].中国肝脏病杂志（电子版）,2009，1（2）：24-26.
[78]伍玉南,孙克伟,彭建平,等.疏肝理脾片对干扰素联合利巴韦林治疗慢性丙型肝炎疗效的影响[J].中西医结合肝病杂志,2009，19(2):76-77.
[79]敬小华，祁培宏，张永霞，等.中药联合聚乙二醇干扰素α-2a治疗慢性丙型肝炎疗效观察[J].上海中医药杂志，2010，44(8):36-37.
[80]李镤主编.穴位注射疗法临床大全.北京:中国中医药出版社,1996.17.
[81]孔胜利，李志刚，孙立新．穴位注射联合苦参素综合治疗慢性丙型肝炎疗效观察[J］．中国误诊学杂志，2008，8(31):7586－7587．
[82]斯旭平．α-干扰素穴位注射治疗慢性丙型肝炎[J］．浙江中西医结合杂志，2002，12(2):121．
[83]小椋加枝．针灸治疗对丙型肝炎病毒量的影响:针刺手法与血中Th1、Th2细胞的关系[J］．全日本针灸学会杂志，2001，51(3):87．