Research advances in direct-acting antiviral agents in the treatment of hepatitis C virus-related liver cirrhosis

You GuoQiong; Wang Li; Duan Meng; Zhu Peng

doi:10.3969/j.issn.1001-5256.2019.01.041

Volume 35 Issue 1

Jan. 2019

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Article Navigation > Journal of Clinical Hepatology > 2019 > 35(1): 187-190

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Research advances in direct-acting antiviral agents in the treatment of hepatitis C virus-related liver cirrhosis

DOI: 10.3969/j.issn.1001-5256.2019.01.041

Second Department of Hepatology, Chengdu Public Health Medical Center, Chengdu 610000, China

Research funding:

Published Date: 2019-01-20

Abstract

Abstract

Liver cirrhosis is common in clinical practice and is the common clinical outcome of various chronic liver diseases including chronic hepatitis C virus (HCV) infection.Before the development of direct-acting antiviral agents (DAAs) , anti-HCV therapy based on pegylated interferon (PEG-IFN.) and ribavirin (RBV) has a poor clinical effect due to the presence of liver cirrhosis, and decompensated liver cirrhosis itself is an absolute contraindication for PEG-IFN treatment.DAAs have gradually become the first-line drug for HCV infection, and many studies have shown that DAAs have good clinical effects and tolerability in the treatment of cirrhotic patients with HCV infection.On the one hand, DAAs have better clinical effect and safety than PEG-IFN/RBV in patients with compensated liver cirrhosis;on the other hand, patients with decompensated liver cirrhosis are tolerant to DAAs, and although they have a lower proportion of patients with sustained virologic response than normal patients, they can still benefit from DAAs from many aspects.This article reviews the latest research advances in DAAs in patients with HCV-related liver cirrhosis, in order to provide a reference for clinical diagnosis and treatment.
- hepacivirus,
- liver cirrhosis,
- antiviral agents,
- therapeutics,
- review

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肝硬化是各种慢性肝病发展的晚期阶段，我国肝硬化患者总人数约700万(或占总人口的0.5%)^[1]。全球每年因肝硬化并发症死亡人数超过100万，我国占11%^[2]。门静脉高压是肝硬化常见并发症之一，当肝静脉压力梯度(HVPG)＞12 mmHg时可发生食管静脉曲张破裂出血(esophageal varices bleeding, EVB)，当HVPG＞20 mmHg时提示预后不良^[3]。未经内镜治疗的EVB患者约60%可发生迟发性再出血，多在上次出血后1~2年发生^[4]。尽管内镜治疗联合NSBB对EVB的二级预防取得较为理想疗效，但一项随机对照研究^[5]观察结扎治疗联合纳洛多尔预防EVB再出的疗效，中位随访时间为21个月，再出血发生率仍为23%，静脉曲张闭塞后的复发率为26%，再出血死亡率为6.7%。另一项多中心随机对照研究^[6]中位随访时间为16个月，再出血发生率为14%，再出血死亡率为11.6%，1年内静脉曲张闭塞后的复发率达到54%。因此，如何进一步提高EVB二级预防的疗效，是临床亟需解决的问题。

EVB属于中医吐血或/和便血范畴，就其治疗思路，中医文献已有记载，如清代唐容川在《血证论》中提出治吐血四大原则：“止血、消瘀、宁血、补血”等。近年来，国内有报道^[7-9]采用止血功效中药联合内镜治疗EVB取得一定疗效。但目前已经明确，EVB的根本原因在于肝硬化引起的门静脉高压。因此，笔者团队提出EVB二级预防的基本思路为“急则治血，缓则治肝”，本研究初步观察了内镜下食管曲张静脉结扎术(endoscopic esophageal varix ligation, EVL)联合中医辨证论治在肝硬化食管胃静脉曲张破裂二级预防中的协同作用。

1. 资料与方法

1.1 研究对象

选取2015年4月—2021年2月上海中医药大学附属曙光医院肝硬化科行内镜下结扎治疗的EVB患者128例，排除16例恶性肿瘤，脱落4例，最终完成随访108例，其中西医组49例，中西医组59例。

1.2 诊断标准

西医诊断标准：(1)肝硬化诊断标准参考《肝硬化诊治指南》^[10]；(2)食管静脉曲张的分级标准参照《消化道静脉曲张及出血的内镜诊断和治疗规范试行方案》^[11]；(3)门静脉高压性胃病(portal hypertensive gastropathy，PHG)的分度：参考McCormack分类法^[12]，将内镜下PHG分为轻、重两度；(4)肝功能Child-Pugh分级参照《肝硬化诊治指南》^[10]。

中医辨证分型参考《肝纤维化中西医结合诊疗指南(2019年版)》^[13]和《肝硬化中西医结合诊疗共识》^[14]，肝硬化基本病机为“虚损生积”，基本治法为益气养阴，活血化瘀，软坚散结。基本处方为黄芪汤、一贯煎和下瘀血汤加减。基本方剂：生黄芪、生地黄、北沙参、麦冬、枸杞子、当归、地鳖虫、桃仁、制大黄、三七粉、鳖甲、黄连、甘草。

1.3 纳入标准

(1) 经实验室及影像学检查确诊为肝硬化，并经胃镜确诊为食管静脉曲张^[15]；(2)近1个月内有出血史；(3)全身情况可耐受。

1.4 排除标准

(1) 严重血液系统疾病和心、肺等重要器官严重不全；(2)肝癌或其他系统及组织恶性肿瘤；(3)严重出血倾向、重度黄疸、大量腹水；(4)严重全身感染或接受免疫制剂治疗；(5)静脉曲张直径粗大(直径＞1.0 cm)。

1.5 治疗方案

西医组：结扎+卡维地洛10 mg/d；中西医组：结扎+中医药治疗+卡维地洛10 mg/d。中医药治疗包括中药汤剂和或中成药制剂。中药汤剂是在肝硬化“虚损生积”中医基本病机理论指导下以黄芪汤或/和一贯煎合下瘀血汤为基础方进行辨证施治。中成药采用扶正化瘀片，1.6 g/次，3次/d，口服。中药汤剂及中成药的服用时间不少于总随访时长的2/3。

1.6 观察指标及方法

(1) 再出血发生率：早期再出血定义为出血控制后72 h~6 w内出现活动性出血；迟发性再出血定义为出血控制6 w后出现活动性出血。(2)病死率：指由于EVB导致的死亡。(3)PHG总有效率：参照PHG的疗效判定标准^[16]，显效定义为全胃黏膜充血水肿及樱桃红斑点、红斑消失；有效定义为胃黏膜病变范围明显缩小、仅部分区域黏膜出现淡红色斑点；无效定义为胃黏膜病变的范围及程度无明显变化。(4)食管静脉曲张消除效率：参照《消化道静脉曲张及出血的内镜诊断和治疗规范试行方案(2009年)》^[11]，消除包含根除和基本消失两种情况，根除是指完全看不到静脉曲张，消化道黏膜呈现其基本色泽；基本消失是指仍可见残留的细小血管。(5)食管静脉曲张复发率：静脉曲张完全消失后再次出现静脉曲张。

1.7 统计学方法

采用SPSS 25.0统计软件进行数据分析，所有统计检验均采用双侧检验，计量资料符合正态分布和方差齐者以x±s表示，两组间比较采用t检验；不符合正态分布以M(P₂₅~P₇₅)表示，采用Mann-Whitney U秩和检验；计数资料两组间对比采用χ²检验或Fisher确切概率法；采用Cox回归分析评估影响再出血的危险因素。P＜0.05为差异有统计学意义。

2. 结果

2.1 一般资料

两组患者性别、年龄、病程、Child评分、食管静脉曲张程度、PHG程度、基础疾病等差异均无统计学意义(P值均＞0.05) (表 1)。

表 1 两组基线资料比较

Table 1. Comparison of baselines between the two groups

项目	西医组(n=49)	中西医组(n=59)	统计值	P值
性别[例(%)]			χ²=0.02	0.889
男	25(51)	32(54)
女	24(49)	27(46)
年龄(岁)	61.00(50.0~68.0)	57.00(47.0~65.5)	Z=1664.5	0.177
病程(年)	4.00(1.00~8.00)	3.00(1.0~9.0)	Z=1479	0.838
肝硬化原因[例(%)]				0.882
AIH	1(2)	2(3)
PBC	6(12)	6(10)
丙型肝炎肝硬化	1(2)	1(2)
不明原因肝硬化	6(12)	11(19)
混合型肝硬化	6(12)	6(10)
酒精性肝硬化	6(12)	3(5)
血吸虫性肝硬化	3(6)	6(10)
乙型肝炎肝硬化	20(41)	23(39)
重叠综合征(AIH+PBC)	0(0)	1(2)
肝功能指标
TBil(μmol/L)	20.74(11.29~34.50)	20.40(8.80~31.35)	Z=1624.5	0.271
ALT(U/L)	31.00(21.00~39.00)	35.00(22.50~53.50)	Z=1172	0.092
AST(U/L)	38.00(30.00~45.00)	40.00(30.00~56.50)	Z=1248.5	0.224
Alb(g/L)	34.80(30.40~38.41)	35.60(32.15~38.65)	Z=1242.5	0.211
Child-Pugh分级[例(%)]				0.304
A级	18(37)	22(37)
B级	20(41)	30(51)
C级	11(22)	7(12)
食管静脉曲张程度[例(%)]				1.000
中度	5(10)	6(10)
重度	44(90)	53(90)
PHG[例(%)]			χ²=2.935	0.231
无	23(47)	19(32)
轻度	16(33)	28(47)
重度	10(20)	12(20)
高血压病[例(%)]			χ²=0.417	0.518
无	40(82)	44(75)
有	9(18)	15(25)
糖尿病[例(%)]			χ²=0.123	0.725
无	35(71)	45(76)
有	14(29)	14(24)
心脏病[例(%)]				1.000
无	48(98)	57(97)
有	1(2)	2(3)
饮酒史[例(%)]			χ²=0.101	0.750
无	36(73)	46(78)
有	13(27)	13(22)
吸烟史[例(%)]				1.000
无	41(84)	50(85)
有	8(16)	9(15)

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2.2 结扎联合中医药可显著降低再出血发生率

经结扎治疗后，两组患者在13~24个月时，西医组再出血6例(12%)，中西医组再出血1例(2%)，中西医组显著优于西医组(P＜0.05)(表 2)。

表 2 再出血的发生率

Table 2. Incidence of rebleeding

再出血时间	西医组 (n=49)	中西医组 (n=59)	P值
早期再出血[例(%)]
6周内	1(2)	1(2)	1.0
迟发性再出血[例(%)]
6周~6个月	3(6)	4(7)	1.0
7~12个月	2(4)	2(3)	1.0
13~24个月	6(12)	1(2)	0.045
25个月以后	0	1(2)	1.0

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2.3 结扎联合中医药可显著降低再出血的病死率

在随访期间，西医组因再出血死亡6例(12%)，中西医组因再出血死亡1例(2%)，中西医组显著低于西医组(P＜0.05)。

2.4 结扎联合中医药可显著提高PHG的改善率

所有患者中，合并PHG者西医组26例，中西医组40例，治疗后，西医组显效6例(23%)，有效14例(54%)，无效6例(23%)；中西医组显效21例(52%)，有效15例(38%)，无效4例(10%)。中西医组的疗效显著高于西医组(P＜0.05)。

2.5 结扎联合中医药对食管静脉曲张消除率的影响

内镜治疗后，西医组的食管静脉曲张消除18例(37%)，中西医组消除31例(53%)，但差异无统计学意义(P＞0.05)。

2.6 结扎联合中医药对静脉曲张复发率的影响

有静脉曲张史者西医组18例，中西医组31例，经内镜治疗，西医组的静脉曲张复发0例，中西医组静脉曲张复发5例(16%)，但差异无统计学意义(P＞0.05)。

2.7 食管胃静脉曲张再出血的风险因素分析

将患者组别、性别、年龄、基础疾病、治疗次数、食管静脉分级、PHG等因素纳入Cox回归分析中，发现基础疾病(主要包括糖尿病、高血压、心脏病)和肝功能Child-Pugh分级是影响再出血的显著危险因素(P值均＜0.05)(表 3)。

表 3 Cox回归分析

Table 3. Cox regression analysis

变量	B值	SE	Wald	Exp(B)	P值
组别	-0.037	0.554	0.004	0.964	0.947
性别	0.900	0.826	1.187	2.459	0.276
年龄	0.008	0.030	0.068	1.008	0.795
内镜治疗次数	-0.630	0.372	2.871	0.533	0.090
入组时食管静脉曲张分级	0.738	1.191	0.384	2.091	0.536
是否合并胃底静脉曲张	-1.198	0.898	1.779	0.302	0.182
是否合并PHG			0.367		0.832
轻度	0.184	0.738	0.062	1.202	0.803
重度	0.426	0.707	0.363	1.532	0.547
病程	0.093	0.081	1.343	1.098	0.247
基础疾病	1.546	0.655	5.572	4.693	0.018
饮酒史	0.892	0.847	1.109	2.440	0.292
吸烟史	0.977	0.805	1.475	2.657	0.225
肝硬化原因	0.674	0.700	0.926	1.962	0.336
肝功能Child-Pugh分级	1.550	0.539	8.260	4.713	0.004

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3. 讨论

EVB是肝硬化最严重、最凶险的并发症，在发生过急性EVB的患者中，1年内再出血的发生率为60%，病死率高达33%，因此，针对EVB的二级预防是降低EVB病死率的重要对策^[17]。近年来，随着内镜诊疗技术的进步，使得EVB的总体病死率从20世纪80年代的40%下降到目前的10%~15%^[18]。有研究建议对于肝硬化早期未出现门静脉高压症时多采用病因治疗^[19]，对于发生食管静脉曲张并且伴有红色征的患者，应接受非选择性β受体阻滞剂(NSBB)或者内镜下结扎治疗以预防首次出血^{[3, 20]}。我国对于肝硬化食管静脉曲张破裂出血的预防分为一级预防和二级预防，2019年专家共识^[15]建议：对于轻度代偿期的肝硬化患者的一级预防，可以通过中药以及他汀类药物进行抗纤维化治疗，以消除致病因素。对于中重度食管静脉曲张，且有明显出血倾向的患者，可进行一级预防，应首选EVL，联用NSBB则效果更佳，且并发症少。对于既往有EVB史的患者，建议EVL、ESI或者与NSBB联合使用。

中医认为肝硬化属于“积聚”、“胁痛”、“臌胀”等范畴，虽然导致肝硬化的原因各不相同，临床表现各异，但基本病机在于“虚损生积”。在肝硬化治疗方面，病因治疗是关键，抗纤维化治疗也是必须的，且在预防EVB方面，抗肝纤维化治疗被作为推荐疗法^[13]。刘平等^[21]开展的一项多中心、随机、双盲、对照试验，证实了扶正化瘀胶囊在降低纤维化分期、减轻肝组织炎症活动度、改善肝生化指标方面有着显著的疗效，且未发现有临床意义的不良反应。肖定洪等^[22]对181例肝硬化患者开展了一项随机、对照、双盲、多中心、前瞻性临床研究，结果显示扶正化瘀胶囊能降低轻度食管静脉曲张患者累积出血概率，与普萘洛尔联用则可降低中重度食管静脉曲张患者累积出血概率。

本研究中，中西医组早期再出血率与西医组早期再出血率均为2%，均低于国内报道^[23]的16.67%(中西医组)与46.67%(西医组)；中西医组的再出血率仅次于袁超等^[24]研究中的0，疗效较前研究报道大大提高。且本研究对内镜下结扎治疗后不同时间段的出血率进行统计分析，结果发现中西医组治疗后13~24个月的再出血率显著低于西医组(2% vs 12%)，治疗后中西医组因再出血死亡率显著低于西医组，且均低于刘浩雷等^[25]报道的13.3%, 也低于Meta分析^[26]所显示的14.76%，这表明中药可以降低肝硬化食管静脉曲张患者的再出血发生率及病死率。提示中医药可通过改善肝纤维化来降低再出血发生，但并非短期内可以见效，故内镜治疗后的患者建议坚持长期服用中药，可取得良好效果。

本研究还发现中西医组对PHG的改善率显著优于西医组。已有的研究^[27-29]表明，中药可以显著改善PHG，从而降低非EVB引起的上消化道出血。韦刚等^[30]研究显示，中西医结合治疗可以显著改善脾胃虚寒型PHG的临床症状、胃黏膜病变。但由于本研究中的中医辨证论治主要针对肝硬化，提示中医药缓解PHG的主要机制可能与改善硬化肝脏肝组织结构，进而降低门静脉压力有关。

此外，经Cox回归分析发现糖尿病、高血压、心脏病等基础疾病和肝功能Child-Pugh评分是影响再出血的显著危险因素，这与国内外文献^[31-32]报道的结果基本一致。

综上，两种治疗方式均可降低EVB再出血的发生发生率，但中西医组的远期(结扎后13~24个月)再出血发生率显著低于西医组，且可有效降低死亡率、提高PHG的改善率。另外，中西医组静脉曲张的消除率显示出一定优势。但由于本研究为观察性研究，随访时间跨度较大，样本量小，未来尚需开展多中心大样本、随机对照研究，进一步明确内镜治疗联合中医药对EVB的治疗作用；另外，本研究未将患者的临床症状、生活质量等评价指标纳入研究中，未来还需进一步提高数据的完整性，为该病中西医结合治疗方案的建立提供科学论据。

References(30)

References

[1]MOOSAVY SH, DAVOODIAN P, NAZARNEZHAD MA, et al.Epidemiology, transmission, diagnosis, and outcome of hepatitis Cvirus infection[J].Electr Physic, 2017, 9 (10) :5646-5656.

[2]Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association.The guideline of prevention and treatment for hepatitis C:A 2015 update[J].JClin Hepatol, 2015, 31 (12) :1961-1979. (in Chinese) 中华医学会肝病学分会, 中华医学会感染病学分会.丙型肝炎防治指南 (2015年更新版) [J].临床肝胆病杂志, 2015, 31 (12) :1961-1979.

[3]MOROZOV VA, LAGAYE S.Hepatitis C virus:Morphogenesis, infection and therapy[J].World J Hepatol, 2018, 10 (2) :186-212.

[4]European Association for the Study of the Liver.EASL recommendations on treatment of hepatitis C 2018[J].J Hepatol, 2018, 69 (2) :461-511.

[5]HUANG Y, LI MH, HOU M, et al.Peginterferon alfa-2a for the treatment of chronic hepatitis C in the era of direct-acting antivirals[J].Hepatobiliary Pancreat Dis Int, 2017, 16 (5) :470-479.

[6]SPENGLER U.Direct antiviral agents (DAAs) -A new age in the treatment of hepatitis C virus infection[J].Pharmacol T-her, 2018, 183:118-126.

[7]BROWN A, HEZODE C, ZUCKERMAN E, et al.Efficacy and safety of 12 weeks of elbasvir±grazoprevir±ribavirin in participants with hepatitis C virus genotype 2, 4, 5 or 6 infection:The C-SCAPE study[J].J Viral Hepat, 2018, 25 (5) :457-464.

[8]SPERL J, HORVATH G, HALOTA W, et al.Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin:A phase III randomized controlled trial[J].J Hepatol, 2016, 65 (6) :1112-1119.

[9]KWO P, GANE EJ, PENG CY, et al.Effectiveness of Elbasvir and Grazoprevir combination, with or without Ribavirin, for treatment-experienced patients with chronic hepatitis C infection[J].Gastroenterology, 2017, 152 (1) :164-175.e164.

[10]ASSELAH T, REESINK H, GERSTOFT J, et al.Efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 4 infection:A pooled analysis[J].Liver Int, 2018, 38 (9) :1583-1591.

[11]CORMAN S, ELBASHA EH, MICHALOPOULOS SN, et al.Costutility of Elbasvir/Grazoprevir in patients with chronic hepatitis Cgenotype 1 infection[J].Value Health, 2017, 20 (8) :1110-1120.

[12]MAUGHAN A, OGBUAGU O.Pegylated interferon alpha 2a for the treatment of hepatitis C virus infection[J].Expert Opin Drug Metab Toxicol, 2018, 14 (2) :219-227.

[13]JACOBSON IM, GORDON SC, KOWDLEY KV, et al.Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options[J].N Engl J Med, 2013, 368 (20) :1867-1877.

[14]LAWITZ E, MANGIA A, WYLES D, et al.Sofosbuvir for previously untreated chronic hepatitis C infection[J].N Engl JMed, 2013, 368 (20) :1878-1887.

[15]KUMADA H, SUZUKI Y, IKEDA K, et al.Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection[J].Hepatology, 2014, 59 (6) :2083-2091.

[16]ZEUZEM S, DUSHEIKO GM, SALUPERE R, et al.Sofosbuvir and ribavirin in HCV genotypes 2 and 3[J].N Engl J Med, 2014, 370 (21) :1993-2001.

[17]LAWITZ E, SULKOWSKI MS, GHALIB R, et al.Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients:The COSMOS randomised study[J].Lancet, 2014, 384 (9956) :1756-1765.

[18]ZHAO XT, NIE QH.Adverse effects, drug interactions, and safety of direct-acting antiviral agents in treatment of hepatitis C[J].J Clin Hepatol, 2017, 33 (6) :1067-1072. (in Chinese) 赵西太, 聂青和.直接抗病毒药物治疗丙型肝炎的毒副作用、药物相互作用及安全性[J].临床肝胆病杂志, 2017, 33 (6) :1067-1072.

[19]PREDA CM, POPESCU CP, BAICUS C, et al.Real-world efficacy and safety of ombitasvir, paritaprevir/r+dasabuvir+ribavirin in genotype 1b patients with hepatitis C virus cirrhosis[J].Liver Int, 2018, 38 (4) :602-610.

[20]FOSTER GR, AGARWAL K, CRAMP ME, et al.Elbasvir/grazoprevir and sofosbuvir for hepatitis C virus genotype 3 infection with compensated cirrhosis:A randomized trial[J].Hepatology, 2018, 67 (6) :2113-2126.

[21]JACOBSON IM, LAWITZ E, KWO PY, et al.Safety and efficacy of Elbasvir/Grazoprevir in patients with hepatitis C virus infection and compensated cirrhosis:An integrated analysis[J].Gastroenterology, 2017, 152 (6) :1372-1382.e1372.

[22]RAVAIOLI F, CONTI F, BRILLANTI S, et al.Hepatocellular carcinoma risk assessment by the measurement of liver stiffness variations in HCV cirrhotics treated with direct acting antivirals[J].Dig Liver Dis, 2018, 50 (6) :573-579.

[23]CALVARUSO V, CABIBBO G, CACCIOLA I, et al.Incidence of hepatocellular carcinoma in patients with HCV-associated cirrhosis treated with direct-acting antiviral agents[J].Gastroenterology, 2018, 155 (2) :411-421.e4.

[24]European Association for the Study of the Liver.EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis[J].J Hepatol, 2018, 69 (2) :406-460.

[25]BELLI LS, DUVOUX C, BERENGUER M, et al.ELITA consensus statements on the use of DAAs in liver transplant candidates and recipients[J].J Hepatol, 2017, 67 (3) :585-602.

[26]SORIANO V, BARREIRO P, de MENDOZA C, et al.Hepatic decompensation with sofosbuvir plus simeprevir in a patient with Child-Pugh B compensated cirrhosis[J].Antivir Ther, 2016, 21 (1) :91-92.

[27]LIONETTI R, CALVARUSO V, PICCOLO P, et al.Sofosbuvir plus daclatasvir with or without ribavirin is safe and effective for post-transplant hepatitis C recurrence and severe fibrosis and cirrhosis:A prospective study[J].Clin Transplant, 2018, 32 (2) :e13165.

[28]MANNS M, SAMUEL D, GANE EJ, et al.Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease:A multicentre, open-label, randomised, phase 2 trial[J].Lancet Infect Dis, 2016, 16 (6) :685-697.

[29]CHARLTON M, EVERSON GT, FLAMM SL, et al.Ledipasvir and Sofosbuvir plus Ribavirin for treatment of HCV infection in patients with advanced liver disease[J].Gastroenterology, 2015, 149 (3) :649-659.

[30]CHENG DY, LIU XM, OU MN, et al.Clinical efficacy of directacting antiviral agents in patients with HCV-related liver cirrhosis[J/CD].Chin J Exp Clin Infect Dis:Electronic Edition, 2017, 11 (6) :545-549. (in Chinese) 程丹颖, 刘晓民, 欧蔚妮, 等.直接抗病毒药物治疗丙型肝炎肝硬化的疗效观察[J/CD].中华实验和临床感染病杂志:电子版, 2017, 11 (6) :545-549.

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Research advances in direct-acting antiviral agents in the treatment of hepatitis C virus-related liver cirrhosis

DOI: 10.3969/j.issn.1001-5256.2019.01.041