Concise review: Interferon-free treatment of hepatitis C virus-associated cirrhosis and liver graft infection

Chronic hepatitis C is a major reason for development of cirrhosis and hepatocellular carcinoma and a leading cause for liver transplantation. The development of direct-acting antiviral agents lead to(pegylated) interferon-alfa free antiviral therapy regimens with a remarkable increase in sustained virologic response(SVR) rates and opened therapeutic options for patients with advanced cirrhosis and liver graft recipients. This concise review gives an overview about most current prospective trials and cohort analyses for treatment of patients with liver cirrhosis and liver graft recipients. In patients with compensated cirrhosis Child-Pugh-Turcotte(CTP) class A, all approved agents are safe and SVR rates do not significantly differ from patients without cirrhosis in general. In patients with decompensated cirrhosis CTP class B or C, daclastasvir, ledipasvir, velpatasvir, and sofosbuvir are approved, and SVR rates higher than 90% can be achieved. Especially for patients with a model of end stage liver disease score higher than 15 and therefore eligible for liver transplantation, data is scarce. Reported SVR rates in patients with cirrhosis CTP class C are lower compared to patients with a less severe liver disease. In liver transplant recipients with a maximum of CTP class A, SVR rates are comparable to patients without LT. Patients with decompensated graft cirrhosis should be treated on an individual basis.

Factors influencing the failure of interferon-free therapy for chronic hepatitis C:Data from the Polish EpiTer-2 cohort study

BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have analyzed the factors causing therapy failure in some patients.AIM To analyze factors influencing the failure of direct antiviral drugs in the large,multicenter EpiTer-2 cohort in a real-world setting.METHODS The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020.Data collected from the online EpiTer-2 database included the following:hepatitis C virus(HCV)genotype,stage of fibrosis,hematology and liver function parameters,Child-Turcotte-Pugh and Model for End-stage Liver Disease scores,prior antiviral therapy,concomitant diseases,and drugs used in relation to hepatitis B virus(HBV)and/or human immunodeficiency virus(HIV)coinfections.Adverse events observed during the treatment and follow-up period were reported.Both standard and machine learning methods were used for statistical analysis.RESULTS During analysis,12614 patients with chronic hepatitis C were registered,of which 11938(mean age:52 years)had available sustained virologic response(SVR)data[11629(97%)achieved SVR and 309(3%)did not].Most patients(78.1%)were infected with HCV genotype 1b.Liver cirrhosis was diagnosed in 2974 patients,while advanced fibrosis(F3)was diagnosed in 1717 patients.We included patients with features of hepatic failure at baseline[ascites in 142(1.2%)and encephalopathy in 68(0.6%)patients].The most important host factors negatively influencing treatment efficacy were liver cirrhosis,clinical and laboratory features of liver failure,history of hepatocellular carcinoma,and higher body mass index.Among viral factors,genotype 3 and viral load also exerted an influence on treatment efficacy.Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex,which was not confirmed by the multivariate analysis using the machine learning algorithm(random forest).Coinfection with HBV(including patients with on-treatment reactivation of HBV infection)or HIV,extrahepatic manifestations,and renal failure did not significantly affect the treatment efficacy.CONCLUSION In patients with advanced liver disease,individualized therapy(testing for resistance-associated variants and response-guided treatment)should be considered to maximize the chance of achieving SVR.

Antiviral therapies for chronic hepatitis C virus infection with cirrhosis

Patients who are infected with hepatitis C virus(HCV) and also have advanced fibrosis or cirrhosis have beenrecognized as "difficult-to-treat" patients during an era when peginterferon and ribavirin combination therapy is the standard of care. Recent guidelines have clearly stated that treatment should be prioritized in this population to prevent complications such as decompensation and hepatocellular carcinoma. Recent advances in the treatment of chronic hepatitis C have been achieved through the development of direct-acting antiviral agents(DAAs). Boceprevir and telaprevir are first-generation DAAs that inhibit the HCV NS3/4A protease. Boceprevir or telaprevir, in combination with peginterferon and ribavirin, improved the sustained virological response rates compared with peginterferon and ribavirin alone and were tolerated in patients with HCV genotype 1 infection without cirrhosis or compensated cirrhosis. However, the efficacy is lower especially in prior non-responders with or without cirrhosis. Furthermore, a high incidence of adverse events was observed in patients with advanced liver disease, including cirrhosis, in real-life settings. Current guidelines in the United States and in some European countries no longer recommend these regimens for the treatment of HCV. Next-generation DAAs include second-generation HCV NS3/4A protease inhibitors, HCV NS5 A inhibitors and HCV NS5 B inhibitors, which have a high efficacy and a lower toxicity. These drugs are used in interferon-free or in interferon-based regimens with or without ribavirin in combination with different classes of DAAs. Interferon-based regimens, such as simeprevir in combination with peginterferon and ribavirin, are well tolerated and are highly effective especially in treatmentnave patients and in patients who received treatment but who relapsed. The efficacy is less pronounced in nullresponders and in patients with cirrhosis. Interferonfree regimens in combination with ribavirin and/or two or more DAAs could be used for treatment-nave, treatment-experienced and even for interferon-ineligible or interferon-intolerant patients. Some clinical trials have demonstrated promising results, and have shown that the efficacy and safety were not different between patients with and without cirrhosis. There are also promising regimens for genotypes other than genotype 1. Interferonis contraindicated in patients with decompensated cirrhosis, and further studies are needed to establish the optimal treatment regimen for this population. In the future, interferon-free and ribavirin-free regimens with high efficacy and improved safety are expected for HCVinfected patients with advanced liver diseases.

大剂量干扰素治疗是黑素瘤术后辅助治疗的首选方案(附450例观察)

目的:回顾分析黑素瘤患者术后辅助治疗的临床资料,评价不同的术后辅助治疗方案对患者无病生存(disease-free survival,DFS)的影响。方法:收集2006年1月至2009年7月我科就诊的450例Ⅰ至Ⅲ期恶性黑素瘤患者(来自全国28个省市,男239、女211例,年龄12～85岁,中位年龄51岁)的临床资料。所有患者均接受手术治疗,术后辅助治疗包括大剂量干扰素治疗(2 200万IU静注,每周5次,共4周;900万IU皮下注射,每周3次,共11个月)、化疗(方案以达卡巴嗪或替莫唑胺为主,也有联合顺铂、紫杉醇、长春新碱等药物的方案)、化疗联合放疗和单纯放疗(原发灶或淋巴结引流区域放疗,剂量40～60 Gy)等4个方案。结果:450例Ⅰ至Ⅲ期恶性黑素瘤患者,分别行原发病灶的局部切除、扩大切除或扩大切除联合区域淋巴结切除。术后184例患者未接受任何治疗、84例患者接受了化疗、25例患者接受了联合放化疗、2例患者接受了单纯放疗,该4组患者的中位DFS分别为13个月、20个月、29个月、23个月;而155例接受了大剂量干扰素治疗患者的中位DFS尚未达到。化疗的不良反应主要为消化道不良反应、骨髓抑制、肝功能损伤等;干扰素治疗的不良反应主要有白细胞降低、发热、乏力、转氨酶升高、厌食,其中白细胞降低以及转氨酶升高达3或4级不良反应的发生率分别为15%和10%;经对症处理后,患者的不良反应均恢复正常。结论:Ⅰ至Ⅲ期恶性黑素瘤患者的手术切除方式以及术后辅助治疗的方案对于患者的DFS极为重要,术后接受大剂量干扰素治疗延长恶性黑素瘤患者DFS的效果最好,且安全性较好。

Direct-acting antiviral agents against hepatitis C virus and lipid metabolism

Hepatitis C virus (HCV) infection induces steatosis and is accompanied by multiple metabolic alterations including hyperuricemia, reversible hypocholesterolemia and insulin resistance. Total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels are increased by peginterferon and ribavirin combination therapy when a sustained virologic response (SVR) is achieved in patients with HCV. Steatosis is significantly more common in patients with HCV genotype 3 but interferon-free regimens are not always effective for treating HCV genotype 3 infections. HCV infection increases fatty acid synthase levels, resulting in the accumulation of fatty acids in hepatocytes. Of note, low-density lipoprotein receptor, scavenger receptor class B type I and Niemann-Pick C1-like 1 proteins are candidate receptors that may be involved in HCV. They are also required for the uptake of cholesterol from the external environment of hepatocytes. Among HCV-infected patients with or without human immunodeficiency virus infection, changes in serum lipid profiles are observed during interferon-free treatment and after the achievement of an SVR. It is evident that HCV affects cholesterol metabolism during interferon-free regimens. Although higher SVR rates were achieved with interferon-free treatment of HCV, special attention must also be paid to unexpected adverse events based on host metabolic changes including hyperlipidemia.

Management of hepatitis C infection before and after liver transplantation

Chronic hepatitis C(CHC) is the most common indication for liver transplantation(LT). Aggressive treatment of hepatitis C virus(HCV) infection before cirrhosis development or decompensation may reduce LT need and risk of HCV recurrence post-LT. Factors associated with increased HCV risk or severity of recurrence include older age, immunosuppression, HCV genotype 1 and high viral load at LT. HCV recurrence post-LT leads to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Currently, interferon(IFN)-based regimens can be used in dualagent regimens with ribavirin, in triple-agent antiviral strategies with direct-acting antivirals(e.g., protease inhibitors telaprevir or boceprevir), or before transplant in compensated patients to reduce HCV viral load to prevent or reduce the risk of post-LT recurrence and complications; they cannot be used in patients with decompensated cirrhosis. IFN-based regimens are used in less than half of HCV-infected patients waiting for LT due to extremely low efficacy and poor tolerability. However, antiviral therapy is indicated after LT in patients with histologically confirmed CHC despite tolerability issues. Improvements in side effect management have increased survival in patients achieving therapeutic targets. HCV treatment pre- and post-LT results in significant health care costs especially when lack of efficacy leads to disease worsening, although studies have shown sofosbuvir treatment before LT vs conventional post-LT dual antiviral is cost effective. The suboptimal efficacy and tolerability of IFN-based therapies, plus the significant economic burden, means the need for effective and well tolerated IFN-free antiHCV therapy for pre- and post-LT remains high.

New treatment strategies for hepatitis c infection

Hepatitis C infection can lead to cirrhosis and hepatocellular carcinoma and it is an important cause of mortality and morbidity. Achieving a sustained virological response has been the major aim for decades. Interferon treatment was the primarily developed therapy against the infection. Addition of the guanosine analog ribavirin to stop viral RNA synthesis increased the response rates as well as the adverse effects of the treatment. The increasing demands for alternative regimens led to the development of direct-acting antivirals(DAAs). The approval of sofosbuvir and simeprevir signaled a new era of antiviral treatment for hepatitis C infection. Although the majority of studies have been performed with DAAs in combination with interferon and resulted in a decrease in treatment duration and increase in response rates, the response rates achieved with interferon-free regimens provided hope for patients ineligible for therapy with interferon. Most DAA studies are in phase Ⅱ leading to phase Ⅲ. In the near future more DAAs are expected to be approved. The main disadvantage of the therapy remains the cost of the drugs. Here, we focus on new treatment strategies for hepatitis C infection as well as agents targeting hepatitis C virus replication that are in clinical development.

Ⅲ期恶性黑色素瘤的综合治疗及临床病理参数对DFS的影响

目的：评价不同术后辅助治疗方案及临床病理参数对Ⅲ期恶性黑色素瘤患者无病生存（DFS）的影响.方法：收集2006年1月至2012年1月新疆医科大学附属肿瘤医院收治的130例Ⅲ期恶性黑色素瘤患者的临床资料,患者均接受规范的手术治疗,分为3组：（1）氮烯咪胺组：42例为（2006-2009年）,患者接受氮烯咪胺（400 mg,d1-4,4～6个周期;）（2）干扰素组：63例（2009-2012年）,患者接受大剂量干扰素治疗（α-2b干扰素,2 200万U静脉输注,每周5次,共4周,900万U皮下注射,每周3次,共11个月）;（3）未治疗组（25例）：因经济等问题术后未接受任何治疗.结果：随访时间为4～76个月,中位随访时间31个月.氮烯咪胺组、干扰素组、未治疗组患者DFS分别为（31.0±2.5）月、（24.0±1.8）月、（15.1±1.3）月.3组比较,差异有统计学意义（P＜0.05）.接受辅助治疗者DFS较未接受辅助治疗者长;大剂量干扰素治疗延长DFS最为显著（P＜0.05）.年龄、病理类型、原发灶厚度、有无溃疡等因素均不影响DFS（P＞0.05）.结论：Ⅲ期黑色素瘤患者,常见临床病理参数对DFS无影响,治疗应以规范综合治疗为主,大剂量干扰素治疗可延长恶性黑素瘤患者DFS,效果及安全性较好,值得推广.

Hepatitis C virus genotypes in Myanmar

Myanmar is adjacent to India, Bangladesh, Thailand, Laos and China. In Myanmar, the prevalence of hepatitis C virus(HCV) infection is 2%, and HCV infection accounts for 25% of hepatocellular carcinoma. In this study, we reviewed the prevalence of HCV genotypes in Myanmar. HCV genotypes 1, 3 and 6 were observed in volunteer blood donors in and around the Myanmar city of Yangon. Although there are several reports of HCV genotype 6 and its variants in Myanmar, the distribution of the HCV genotypes has not been well documented in areas other than Yangon. Previous studies showed that treatment with peginterferon and a weight-based dose of ribavirin for 24 or 48 wk could lead to an 80%-100% sustained virological response(SVR) rates in Myanmar. Current interferon-free treatments could lead to higher SVR rates(90%-95%) in patients infected with almost all HCV genotypes other than HCV genotype 3. In an era of heavy reliance on direct-acting antivirals against HCV, there is an increasing need to measure HCV genotypes, and this need will also increase specifically in Myanmar. Current available information of HCV genotypes were mostly from Yangon and other countries than Myanmar. The prevalence of HCV genotypes in Myanmar should be determined.

Hepatitis C virus NS5A region mutation in chronic hepatitis C genotype 1 patients who are non-responders to two or more treatments and its relationship with response to a new treatment

To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. METHODSSequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed via direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), n = 49; IFN-α + ribavirin (RBV), n = 75; pegylated (peg) IFN-α + RBV, n = 47; first-generation direct-acting antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR). RESULTSFor both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR (SVR vs NVR; PKRBD: 5.82 ± 3 vs 4.86 ± 2 mutations, P = 0.045; ISDR: 2.65 ± 2 vs 1.51 ± 1.7 mutations, P = 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD, P = 0.02; ISDR, P = 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (P = 0.001). CONCLUSIONThe obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL.

干扰素联合无乳糖奶粉治疗轮状病毒肠炎的临床疗效分析

目的:观察干扰素联合无乳糖奶粉治疗轮状病毒肠炎的疗效。方法:将轮状病毒肠炎患儿180例随机分为对照组87例和观察组93例。对照组给予常规基础治疗,观察组在此基础上给予干扰素联合无乳糖奶粉治疗,观察临床疗效。结果:治疗后观察组症状评分明显低于对照组,观察组总有效率95.7%,高于对照组的88.3%。结论:干扰素α-1b联合无乳糖奶粉辅助治疗轮状病毒肠炎能够有效减轻腹泻症状。

重组人干扰素α1b联合无乳糖饮食对小儿轮状病毒感染性肠炎肠黏膜损伤及心肌酶谱的影响

目的 观察临床应用重组人干扰素α1b联合无乳糖饮食对小儿轮状病毒(RV)感染性肠炎肠黏膜损伤及心肌酶谱的影响。方法 采用前瞻性研究方法,选取2015年10月至2018年2月四川大学华西医院资阳医院收治的轮状病毒感染性肠炎患儿86例,采用随机平行分组法随机分为对照组和观察组,每组各43例。对照组患儿给予重组人工干扰素α1b治疗,观察组患儿给予重组人工干扰素α1b+无乳糖饮食治疗。对比分析两组患儿治疗后临床疗效、心肌酶谱检测指标及血清中晚期糖基化终末产物(AGEs)、内毒素(EXT)以及二胺氧化酶(DAO)水平变化。结果 观察组患儿治疗总有效率明显高于对照组(95. 3%vs. 85. 7%)(P <0. 05);治疗前,两组患儿心肌酶谱检测指标水平比较,差异无统计学意义(P> 0. 05);治疗后,观察组患儿天门冬氨酸氨基转移酶(AST)(33. 43±3. 62 U/L vs. 39. 61±5. 63 U/L)、α-羟丁酸脱氢酶(α-HBDH)(130. 27±32. 46 U/L vs. 167. 07±31. 35 U/L)、乳酸脱氢酶(LDH)(210. 43±19. 91U/L vs. 232. 53±20. 64 U/L)、肌酸激酶同工酶(CK-MB)(15. 74±2. 46 U/L vs. 21. 13±3. 00 U/L)以及肌酸激酶(CK)(110. 51±12. 24 U/L vs. 156. 82±16. 51 U/L)水平,差异具有统计学意义(P <0. 05)。治疗前,两组患儿血清中晚期糖基化终末产物(AGEs)、内毒素(EXT)、二胺氧化酶(DAO)水平比较,差异无统计学意义(P> 0. 05);治疗后,观察组患儿AGEs(165. 43±21. 52 ng/L vs. 243. 64±35. 23 ng/L)、EXT(0. 37±0. 06 EU/ml vs. 0. 77±0. 15 EU/ml)、DAO(0. 62±0. 21 U/L vs. 1. 33±0. 65 U/L)水平明显低于对照组,差异具有统计学意义(P <0. 05)。结论 临床应用重组人干扰素α1b联合无乳糖饮食对小儿RV感染性肠炎进行治疗能对心肌起到明显保护作用,有效改善肠黏膜损伤状态,提高治疗效果。

慢性丙型肝炎合并肝硬化的抗病毒方案

经过目前标准的治疗方案治疗后,慢性丙型肝炎(丙肝)合并肝硬化的患者疗效不佳。随着治疗丙肝新药越来越多,许多新的治疗慢性丙肝合并肝硬化的抗病毒方案出现了。由于第一代蛋白酶抑制药博赛匹韦、特拉匹韦的不良反应较大,因此用于丙肝合并肝硬化患者的治疗需要谨慎。其他治疗丙肝的新药辛姆匹韦、索非布韦、来第帕韦对于丙肝合并代偿性硬肝化患者有疗效,但是有合并症患者的病毒应答(SVR)低于没有合并症的患者。因此,今后需要优化这些药物组合的治疗方案,以此缩小持续性的病毒应答的差距。

干扰素刺激基因15抗病毒免疫研究进展

干扰素刺激基因15(ISG15)蛋白是由干扰素或病原体刺激产生的泛素样蛋白。ISG15能够通过酶促级联反应与靶蛋白共价结合形成ISGylation,称为ISG化。ISG15在干扰素诱导的抗病毒免疫应答过程中发挥重要作用。研究发现,ISG15对多种病毒均具有抗病毒活性。此外,ISG15在细胞自噬、宿主损伤、DNA修复、蛋白翻译等过程中也具有重要作用。论文通过对近年来国内外学者在ISG15类泛素修饰系统、抗病毒免疫分子机制以及ISG15单体生物学功能等方面取得的研究进展进行综述,以期为ISG15抗病毒免疫研究和抗病毒药物的研制提供参考。

胃炎方对脾胃湿热型慢性萎缩性胃炎的疗效及对患者IFN-β、自由基的影响

目的:观察胃炎方对脾胃湿热型慢性萎缩性胃炎患者的疗效及干扰素-β(IFN-β)、自由基的变化。方法:选取我院(2013年1月~2018年11月)收治的脾胃湿热型慢性萎缩性胃炎患者114例,根据治疗方法不同分为2组。对照组给予常规西药对症治疗,观察组在对照组基础上给予胃炎方治疗,分析2组患者治疗后的临床疗效。结果:2组治疗前中医症状积分组间比较,差异不具有统计学意义(P>0.05)。观察组治疗后胃痞胀痛(1.01±0.22)分、口苦口臭(0.91±0.27)分、恶心或呕吐(0.82±0.21)分、胃脘灼热(0.93±0.22)分、大便黏滞或稀溏(0.63±0.23)分低于对照组(P<0.05)。2组治疗前IFN-β、白细胞介素-23(IL-23)、胃泌素-17(G-17)、自由基水平组间比较,差异不具有统计学意义(P>0.05)。观察组治疗后G-17、超氧化物歧化酶(SOD)水平高于对照组,IFN-β、IL-23、丙二醛(MDA)水平低于对照组(P<0.05)。观察组总有效率为91.23%,对照组为73.68%,观察组患者总有效率高于对照组(P<0.05)。结论:胃炎方治疗脾胃湿热型慢性萎缩性胃炎可改善氧化应激状态,减轻炎症状态,促进G-17的分泌,提高疗效。

α干扰素联合无乳糖奶粉治疗婴儿轮状病毒肠炎的临床疗效分析

目的:探讨干扰素α1b联合无乳糖奶粉治疗婴儿轮状病毒肠炎的疗效。方法:收治婴儿轮状病毒肠炎患儿108例,随机分为常规组和干扰素组。干扰素组予干扰素α1b肌注联合无乳糖奶粉喂养,常规组予普通婴儿配方奶粉喂养。结果:干扰素组腹泻治愈率80.7%,好转率15.3%;常规组治愈率44.6%,好转率44.6%。结论:干扰素α1b联合无乳糖奶粉治疗婴儿轮状病毒肠炎疗效显著,可以缩短病程,提高治愈率,减少住院天数及减少滥用抗生素。

注射用重组人干扰素α2b联合无乳糖奶粉治疗小儿秋季腹泻的疗效观察

目的探讨注射用重组人干扰素α2b联合无乳糖奶粉治疗小儿秋季腹泻的疗效。方法将60例年龄4～18个月,病程在1周内,以母乳或普通配方奶喂养为主的秋季腹泻患儿随机分为A、B、C组:(1)A组给予补液及对症治疗;(2)B组在A组治疗的基础上联合应用注射用重组人干扰素α2b治疗;(3)C组在B组治疗的基础上联合无乳糖奶粉治疗。A、B组继续母乳或普通配方奶喂养,C组改用无乳糖奶粉喂养。观察三组的疗效、退热和止泻时间。结果三组的总体疗效比较差异有统计学意义(P<0.01),但止泻和退热时间B、C组均短于A组(P<0.01);而C组止泻时间又短于B组(P<0.01)。结论注射用重组人干扰素α2b联合无乳糖奶粉治疗婴幼儿腹泻可缩短腹泻病程,疗效好且安全。

Direct-acting Antiviral Agents for the Treatment of Chronic Hepatitis C Virus Infection

Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma (HCC) in the US and Japan.Therefore,eradication of HCV may reduce the occurrence of HCC in HCV-infected individuals.In 2011,the use of firstgeneration HCV NS3/4A protease inhibitors such as telaprevir and boceprevir was initiated for clinical treatment of HCV.Administration of telaprevir and boceprevir plus peginterferon and ribavirin increased rates of sustained virological response (SVR) in HCV genotype 1-infected patients.However,this treatment regimen also led to severe adverse events.Second-generation direct-acting antiviral agents (DAAs) for HCV,such as simeprevir plus peg-interferon and ribavirin also resulted in higher SVR rates,with similar adverse events to other peg-interferon and ribavirin treatments.Higher SVR rates in HCV genotype 1-and 2-infected patients were achieved with 12-16 weeks of sofosbuvir plus other class DAAs with/without ribavirin and 12 weeks of sofosbuvir plus ribavirin,respectively,For "difficult-to-treat"HCV-infected patients,more therapeutic options are needed.Further studies examining the efficacy and adverse effects of such therapies will be required for the development of additional treatments.

Antiviral therapy for ＂difficult-to-treat＂ hepatitis C virus-infected patients

Objective To review the updated research on direct antiviral agents （DAAs）-including regimens for hepatitis C virus （HCV）,and focus on ＂difficult-to-treat＂ HCV-infected patients.Data sources The literature concerning DAAs and hepatitis C cited in this review was collected from PubMed and Google Scholar databases published in English up to July 2013.Study selection Data from published articles regarding HCV and DAAs in clinical trials and in clinical use were identified and reviewed.Results It was recognized that some ＂difficult-to-treat＂ patients would still exist,even though stronger treatments using such as DAAs,including telaprevir and boceprevir,which lead to higher sustained virological response rates,are available.Such patients include those with advanced fibrosis/cirrhosis,elderly persons,children,HCV-human immunodeficiency virus co-infected patients,HCV-infected recipients,and so on.Conclusions Certain ＂difficult-to-treat＂ patients would still exist,even though stronger treatment is available.Although evidence from clinical trials is still lacking,interferon-sparing regimens could have stronger effects for eradicating HCV in such cases.

慢性丙型肝炎抗病毒治疗进展

近年慢性丙型肝炎抗病毒治疗的标准治疗方案优化和直接抗病毒药物研发均取得突破性进展。本文综述近年国内外相关研究进展以及新药研发趋势。