索磷布韦/维帕他韦联合或不联合利巴韦林治疗基因3型慢性丙型肝炎病毒感染者的疗效及安全性:一项真实世界研究

目的评估索磷布韦/维帕他韦(sofosbuvir/velpatasvir,SOF/VEL)联合或不联合利巴韦林(ribavirin,RBV)治疗基因3型慢性丙型肝炎病毒(hepatitis c virus,HCV)感染者的有效性及安全性。方法以2018年12月至2020年1月至成都市公共卫生临床医疗中心就诊的84例基因3型慢性HCV感染者为研究对象,其中慢性丙型肝炎56例,代偿期肝硬化17例,失代偿期肝硬化11例。根据患者病情予以SOF/VEL联合或不联合RBV抗病毒治疗12~24周,检测患者基线、治疗4周、治疗结束时以及治疗结束后12周肝功能[丙氨酸氨基转移酶(alanine transaminase,ALT)、天门冬氨酸氨基转移酶(aspartate transaminase,AST)、总胆红素(total bilirubin,TBil)、白蛋白(albumin,ALB)]、肾功能[尿素、肌酐(creatinine,Cr)]和血常规[白细胞(white blood cell,WBC)、血红蛋白(hemoglobin,HGB)和血小板(platelet,PLT)]等指标,检测基线和治疗结束后12周的肝硬度值。同时详细记录患者在治疗期间的不良事件。主要结局指标为治疗结束后12周的持续病毒学应答(sustained virological response,SVR)和治疗中不良事件的发生情况。结果共80例患者(95.2%)达到SVR12,其中慢性丙型肝炎、代偿期肝硬化及失代偿期肝硬化患者的SVR12分别为100%(56/56)、94.1%(16/17)和72.7%(8/11),差异有统计学意义(P=0.003)。慢性丙型肝炎组、代偿期肝硬化及失代偿期肝硬化患者治疗结束后12周肝硬度值均较基线显著降低[(6.7±0.7)kPa vs(7.4±1.1)kPa,(17.8±3.1)kPa vs(25.9±3.4)kPa,(23.0±4.5)kPa vs(31.0±4.9)kPa;P均<0.001]。3组患者治疗后ALT和AST均较基线显著降低(P均<0.05),尿素、Cr、WBC和PLT差异无统计学意义(P均>0.05)。代偿期肝硬化和失代偿期肝硬化患者治疗后ALB较基线显著升高,HGB较基线显著降低(P均<0.05)。84例患者总体不良事件发生率为13.1%(11/84),其中慢性丙型肝炎、代偿期肝硬化和失代偿期肝硬化患者不良事件发生率分别为8.9%(5/56)、11.8%(2/17)和36.4%(4/11),差异无统计学意义(P=0.055),常见的不良事件包括疲劳、头痛和贫血等,无严重不良事件发生,无因不良事件导致的治疗中止。结论应用SOF/VEL联合或不联合RBV方案治疗基因3型慢性HCV感染者具有较高的SVR12,不良事件发生率较低,疗效显著,安全性良好。     

直接抗病毒药物治疗慢性丙型肝炎肝硬化的回顾性分析

目的探讨直接抗病毒药物(direct-acting antiviral agent,DAA)治疗慢性丙型肝炎肝硬化患者实现持续病毒学应答(sustained virologic response,SVR)后的预后及转归。方法回顾性分析2014年1月至2017年6月于天津市第二人民医院临床诊断为慢性丙型肝炎肝硬化的95例患者,其中72例应用DAA获得SVR,23例未行抗病毒治疗,比较两组患者肝细胞癌发生率、病死率的差异。统计学分析采用独立样本t检验、曼-惠特尼U检验和χ²检验。结果在3~71个月的随访结束时,DAA治疗组丙氨酸转氨酶、天冬氨酸转氨酶、白蛋白、肝硬度测定值均较入组时改善[42(23,61)U/L比18(13,28)U/L,54(37,75)U/L比23(18,28)U/L,39(33,42)g/L比45(41,48)g/L,26(18,37)kPa比15(11,26)kPa,Z=-6.005、-7.008、-6.057、-3.162,均P<0.01],但DAA治疗组与未行抗病毒治疗组患者肝细胞癌发生率[12%(9/72)比17%(4/23)]、病死率[3%(2/72)比13%(3/23)]差异均无统计学意义(均P>0.05)。应用DAA治疗和未行抗病毒治疗的慢性丙型肝炎肝硬化患者进行肝细胞癌累积发生率分析,两组差异无统计学意义(P=0.609)。慢性丙型肝炎肝硬化发生肝细胞癌患者与未发生肝细胞癌患者年龄[(60.3±3.6)岁比(54.4±9.9)岁]差异有统计学意义(t=-3.948,P<0.01);代偿期肝硬化患者应用DAA治疗后,6例发生肝细胞癌的患者中4例患糖尿病,未发生肝细胞癌的患者糖尿病患病率为17%(7/42),发生肝细胞癌较未发生肝细胞癌者空腹血糖更高[(7.3±1.9)mmol/L比(5.9±1.1)mmol/L],差异均有统计学意义(χ²=7.430,t=-2.442,P=0.019、0.019)。结论DAA可以显著改善慢性丙型肝炎肝硬化患者的肝功能、肝纤维化,但未发现可以改善其近期肝细胞癌发生率、病死率;空腹血糖升高、糖尿病可能为代偿期慢性丙型肝炎肝硬化患者发生肝细胞癌的危险因素。     

索非布韦/达拉他韦加利巴韦林治疗丙型肝炎肝硬化的疗效及安全性

目的观察索非布韦/达拉他韦加利巴韦林治疗丙型肝炎肝硬化患者的疗效和安全性。方法纳入2016年5月至2017年5月就诊于昆明市第三人民医院肝病科的丙型肝炎肝硬化患者129例,给予索非布韦/达拉他韦加利巴韦林抗病毒治疗12周,治疗后随访12周,观察治疗结束12周后持续性病毒学应答(SVR12)、生化学应答、肝纤维化改善和治疗期间的不良反应。结果 129例患者HCV RNA基线水平为(5.91±1.33)lgIU/mL,治疗2周时为(1.67±1.24)lgIU/mL,治疗2周75.78%患者HCV RNA达到检测下限;治疗12周时93.44%患者HCV RNA检测不到。129例患者基线的FibroScan值为(17.57±9.86);治疗12周时的FibroScan值为(8.32±1.47)kPa(与基线相比,t=15.852,P=0.000);TBil、ALT、AST基线时分别为(24.07±18.12)μmol/L、(91.42±54.56)U/L和(81.06±40.45)U/L,治疗2周时TBil、ALT、AST均显著下降(t=2.408,P=0.017;t=11.054,P=0.000;t=12.227,P=0.000),生化学应答达100%。6例未取得SVR12的患者多因素回归分析显示,复治是独立预测因子。主要不良反应为乏力和头痛,无严重不良反应发生。结论丙型肝炎肝硬化患者索非布韦/达拉他韦加利巴韦林方案可获得较高的SVR12率和生化学应答率,肝纤维化改善明显,且具有良好的安全性。     

直接抗病毒药物治疗慢性丙型肝炎48周临床观察

背景慢性丙型肝炎(chronic hepatitis C,CHC)是全球公共卫生问题,随着直接抗病毒药(direct antiviral therapy,DAA)在中国的应用,DAA药物成为目前国内慢性丙型肝炎抗病毒一线方案,但目前真实世界DAA治疗后长期疗效数据尚少.目的观察慢性丙型肝炎患者接受直接抗病毒药物抗病毒治疗后48 wk病毒学应答及临床疗效.方法连续收集2018-04-01/2020-04-30在天津市第三中心医院接受DAA治疗的初治CHC患者,评估治疗基线、治疗结束、治疗后12 wk及48 wk的病毒学应答及肝肾功能、肝硬度、APRI及临床结局.结果共收集291例应用DAA治疗的CHC患者,纳入145例完成抗病毒治疗及随访的CHC患者进入本研究.其中肝硬化患者占28.3%,基因型1b、2a、3a、6a分别占78.0%、17.2%、2.8%、2.0%.DAA治疗结束、治疗后12 wk及48 wk获得持续病毒学应答(sustained virological response,SVR)比例分别为100%、97.9%和97.2%,其中基因型1b、2a、3a、6a的SVR48分别为97.3%、96%、100%、100%.治疗结束后48 wk与基线相比较,丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红素及白蛋白的复常率分别为93.2%、91.7%、73.3%及97.7%.治疗结束后48 wk肝硬度(liver stiffness measurement,LSM)及APRI与基线水平相比均明显下降(LSM 12.5 vs 10.2kpa P<0.01;APRI 0.34 vs 0.13 P<0.01),肝硬化组及非肝硬化组患者均有明显下降(P<0.05).48 wk随访期间,其中4例(2.8%)CHC患者进展为肝硬化,8例(5.6%)肝硬化患者进展为肝硬化失代偿,3例(2.1%)肝硬化患者发生新发肝细胞癌(hepatocellular carcinoma,HCC).结论本研究真实世界中慢性丙型肝炎患者应用DAA治疗后48 wk,总体病毒持续应答率较高,肝功能、肝硬度及APRI值均明显改善.2.1%患者出现新发HCC.     

丙型肝炎肝硬化患者抗病毒疗效的影响因素分析

目的探讨丙型肝炎肝硬化抗病毒治疗疗效影响因素.方法以干扰素(interferon,IFN) α为基础抗病毒治疗的丙型肝炎肝硬化患者作为研究对象,收集其流行病学资料、基线的相关化验指标、抗病毒治疗方案及经过.分析抗病毒治疗后获得的持续病毒学应答(sustained virological response,SVR)率及其影响因素.结果 28例经IFN α联合利巴韦林抗病毒治疗的丙型肝炎肝硬化患者入选,9例获得了SVR,占32.1%.SVR组和非持续病毒学应答(non-SVR,N-SVR)组基线性别比例、年龄、感染时限、HCV RNA、转氨酶、中性粒细胞绝对计数、HGB、PLT和Child-Pugh评分均无统计学差异(P > 0.05).应用聚乙二醇干扰素(pegylated interferon,Peg-IFN) α患者的SVR率高于普通IFN α(P =0.003),但去除中途脱落的患者后2组SVR率的差异无统计意义(P =0.308).依从性好的患者SVR率显著高于依从性差的患者(P =0.004).普通IFN α治疗的患者终止治疗的比例显著高于Peg-IFN α(P =0.009),Child-Pugh评分高的患者终止治疗的比例显著高于Child-Pugh评分低的患者(P=0.034).结论丙型肝炎肝硬化患者抗病毒治疗的SVR率较低,主要与其依从性差有关,而依从性与干扰素类型和肝硬化的严重程度有关.     

基因1型慢性丙型肝炎代偿期肝硬化患者抗病毒治疗后的长期随访研究

目的探讨基因1型慢性丙型肝炎代偿期肝硬化抗病毒治疗的长期疗效。方法采用平行对照回顾性队列研究,对基因1型慢性丙型肝炎代偿期肝硬化患者予聚乙二醇干扰素α-2a联合利巴韦林(PR)治疗,予以集落刺激因子对症治疗,5年长期随访并观察其转归。评估疗效、复发率,肝脏瞬时弹性超声成像检测肝脏硬度值(Stiffness值),比较持续病毒学应答(SVR)组和非持续病毒学应答(NSVR)组的临床事件(肝性脑病、腹水、消化道出血、肝癌或者死亡)发生。结果54例基因1型慢性丙型肝炎代偿期肝硬化患者接受了PR治疗,获得SVR的患者有35例。15例患者在第1次抗病毒治疗后获得SVR,9例、8例、2例、1例患者分别在第2、3、4、5次抗病毒治疗后获得SVR。仅有1例患者在获得SVR6周后出现复发。抗病毒治疗期间,患者的肝硬度值得到不同程度的改善,SVR组治疗后与基线值比较差异有统计学意义(P=0.0004)。结束治疗后的长期随访发现,SVR组患者的肝硬度值有进一步下降的趋势,并能保持在一个较低的水平。而NSVR组患者的肝硬度值没有改善。在平均为60个月的随访中,NSVR组新增3例肝癌患者,SVR组则无人发生。两组临床事件发生频率的差异有统计学意义[腹水:P=0.0168,RR=0.2353(95%CI 0.039~1.422),HCC:P=0.0391,RR=0.0000]。结论对于基因1型慢性丙肝代偿期肝硬化使用聚乙二醇干扰素α-2a联合利巴韦林能有效抑制病毒,应用集落刺激因子可提高患者治疗依从性。既往治疗失败患者,多次治疗及延长疗程能提高SVR率。获得SVR后的复发率低,能减少肝癌等临床事件的发生,缓解肝硬化进展。     

慢性HCV感染DAA应答特点和长期预后观察研究

目的 本研究旨在观察不同疾病进展阶段的HCV感染者直接抗病毒药物(direct-acting antiviral agents,DAA)治疗的应答特点和长期预后.方法 纳入2016年7月—2017年3月就诊于我中心的慢性HCV感染者127例,其中慢性丙型肝炎(chronic hepatitis C,CHC)患者85例,代偿期肝硬化(compensated-liver cirrhosis,CLC)患者32例,失代偿期肝硬化(decompensated-liver cirrhosis,DLC)患者10例.DAA治疗12或24周.比较3组患者HCV RNA转阴时间、停药后12周持续病毒学应答(sustained virologic response 12,SVR12)率以及停药后2年的转归情况.结果 所有CHC、CLC、DLC患者均完成DAA治疗.CHC、CLC和DLC患者的SVR12率分别为98.82％(84/85)、96.88％(31/32)和100％(10/10);CHC患者HCV RNA转阴时间明显早于CLC和DLC患者(P均<0.05).在2年随访期间,1例CLC患者发生病毒学复发,2例DLC患者分别出现肝功能恶化和肝细胞癌.结论 目前常用的DAA治疗方案对CHC、CLC和DLC的患者均有高效的抑制病毒复制的作用,并且SVR12率在96％～100％之间,有很高治愈率.对于肝硬化患者停药后仍须监测肝癌的发生或个别病例HCV复发等情况.     

肝硬化患者血钠水平与病情严重程度的关系探讨

目的探讨血钠水平与肝硬化患者病情严重程度的关系。方法调查代偿期和失代偿期肝硬化患者血钠水平及并发症情况,分别比较伴有血钠低于135 mmol/L(低钠血症)的代偿期和失代偿期肝硬化患者比例以及失代偿期肝硬化患者分别存在1种、2种及以上并发症时伴低钠血症的患者比例。结果 580例肝硬化患者包括代偿期肝硬化患者256例,失代偿期肝硬化患者324例;伴低钠血症的代偿期和失代偿期肝硬化患者比例分别为2.34%和16.36%,差异有统计学意义(χ2=30.74,P=0.000)。324例失代偿期肝硬化患者中,伴有1、2、3种并发症的病例分别为298、24、2例;在伴有1种、2种及以上并发症的患者中,伴低钠血症的患者比例分别是14.09%、42.31%,差异有统计学意义(χ2=13.91,P=0.000)。结论失代偿期肝硬化患者低钠血症更为常见,失代偿期肝硬化患者并发症数量越多,其病情越重,低钠血症越常见。低钠血症与肝硬化病情严重程度关系密切,在判断肝硬化患者的病情严重程度和预后时,应充分考虑低钠血症的影响和价值。     

肝功能基础对肝硬化及肝衰竭并发急性肾损伤转归及预后的影响

目的观察肝功能基础对肝硬化及肝衰竭并发急性肾损伤(AKI)转归及预后的影响,并分析相关的影响因素。方法回顾性分析2016年3月至2017年6月在海军军医大学长海医院感染科住院期间发生AKI的肝硬化(失代偿期)及肝衰竭患者157例的临床资料,随访短期预后。根据肝功能基础及AKI分期进行分层分析,明确肝功能基础对治疗、AKI转归和预后的影响。进一步通过Logistic回归分析AKI转归及预后的影响因素。结果 157例患者中,肝硬化(失代偿期)患者73例,肝衰竭患者84例,两组患者在发生AKI时的MELD评分(t=-13.05,P=0.000)、AKI分期(χ2=12.80,P=0.002)、AKI治疗应答情况(χ2=25.06,P=0.000)、AKI转归(χ2=26.01,P=0.000)以及预后(χ2=47.69,P=0.000)均差异有统计学意义。Logistic回归多因素分析显示,AKI分期(OR=0.079,P=0.000)及MELD评分(OR=1.073,P=0.002)是AKI转归的主要影响因素;而AKI转归(OR=22.753,P=0.000)及MELD评分(OR=0.823,P=0.000)是预后的主要影响因素。结论 2015年ICA更新的指南可提高诊断的敏感性,但需重点关注原发疾病和肝功能基础对治疗应答、AKI转归以及预后的影响;对肝衰竭的患者,密切观察下尽早诊断AKI并积极的干预,可能改善AKI转归及预后。     

直接抗病毒药物治疗慢性丙型肝炎的效果及对肝硬度、APRI的影响

目的探讨目前直接抗病毒药物(DAA)治疗方案下,慢性丙型肝炎患者真实世界病毒应答情况及对肝硬度值和天门冬氨酸/血小板比值指数(APRI)的影响。方法连续性纳入2018年4月1日-2018年11月30日在天津市第三中心医院接受DAA治疗的慢性丙型肝炎患者,应用无干扰素方案的DAA治疗12～24周,评估治疗结束后第12周病毒学应答情况,对比基线及治疗结束后12周肝硬度值和APRI的变化。计量资料两组间比较采用Wilcoxon秩和检验。结果共纳入212例慢性丙型肝炎患者,其中肝硬化患者占35. 4%,基因1b、2a、3a、6a型分别占75. 0%、18. 4%、4. 2%及2. 4%。174例患者完成了DAA治疗疗程及治疗后12周随访。在DAA治疗结束和治疗结束后12周获得持续病毒学应答(SVR)的比例分别为98. 3%及95. 4%。基因1b型、2a型、3a型及6a型患者的SVR12分别为96. 3%、93. 1%、80. 0%及100%。治疗结束后12周肝硬度值较基线[9. 8(6. 9～16. 3) kPa vs 11. 4(7. 7～19. 1) kPa,Z=-2. 5,P=0. 012]及APRI[0. 34(0. 25～0. 64) vs 0. 76(0. 56～2. 25),Z=-6. 6,P 0. 001]均明显下降。根据基线是否存在肝硬化进行分组,结果显示治疗结束12周非肝硬化组患者肝硬度值较基线显著降低[7. 6(6. 6～10. 7) k Pa vs 8. 8(7. 2～13. 0) kPa,Z=-2. 7,P=0. 007];而肝硬化组患者治疗前后肝硬度值无明显差异[17. 4(12. 7～22. 1) k Pa vs 19. 8(12. 8～24. 9) kPa,Z=-1. 4,P=0. 152]。肝硬化组和非肝硬化组患者APRI在治疗后12周较基线均明显下降[0. 73 (0. 52～1. 34) vs1. 37(0. 80～2. 11),Z=-3. 4,P 0. 001; 0. 29(0. 21～0. 36) vs 0. 54(0. 31～0. 95),Z=-6. 8,P 0. 001]。结论在该真实世界研究中,应用DAA治疗的慢性丙型肝炎患者总体病毒学应答率较高,治疗结束后12周肝硬度及APRI明显改善。     

Sofosbuvir plus velpatasvir treatment for hepatitis C virus in patients with decompensated cirrhosis: a Japanese real-world multicenter study

Background

Real-world data on the efficacy and safety of sofosbuvir plus velpatasvir (SOF/VEL) treatment for patients with hepatitis C virus (HCV)-related decompensated cirrhosis are limited in Japan.

Methods

A total of 190 patients with compensated (108) or decompensated (82) cirrhosis who initiated direct-acting antiviral (DAA) treatment between February 2019 and August 2019 were enrolled. Sustained virologic response (SVR) was defined as undetectable serum HCV-RNA at 12 weeks after the end of treatment (EOT).

Results

The SVR12 rates were 92.6% in patients with compensated cirrhosis and 90.2% in patients with decompensated cirrhosis (p = 0.564), and the treatment completion rates were 98.1% and 96.3%, respectively (p = 0.372). In patients with decompensated cirrhosis, 3 patients discontinued treatment and 2 patients died because of liver-related events. In patients with decompensated cirrhosis with SVR12, 50% of patients with Child–Pugh class B at baseline showed improvement to class A at SVR12, and 27% and 9% of patients with Child–Pugh class C at baseline showed improvement to class B and class A at SVR12, respectively. Patients who achieved SVR12 showed elevated serum albumin levels at the EOT, which were further elevated at SVR12, but no elevated serum albumin levels after the EOT were observed in patients with baseline serum albumin levels less than 2.8 g/dl.

Conclusions

Real-world efficacy of SOF/VEL treatment for patients with decompensated cirrhosis was similar to Japanese phase 3 study, although treatment discontinuation and death related to liver disease occurred. In patients with poor hepatic reserve, whether it improves continuously after viral clearance requires further evaluation.

     

Hepatitis C and End-stage Liver Disease

Cirrhosis secondary to infection with hepatitis C virus (HCV) is one of the leading causes of end-stage liver disease worldwide. The World Health Organization estimates that about 3% of the world population is chronically infected with HCV, with about 4 million infected individuals in the United States. Despite the declining US incidence of HCV, the complications of chronic HCV infection are rising rapidly. The cirrhosis can be classified as compensated or decompensated based on clinical complications. Compensated HCV-related cirrhosis can be treated safely per American Association for the Study of Liver Diseases guidelines. Treatment of decompensated HCV-related cirrhosis is challenging secondary to increased risk of complications and adverse effects during the course of antiviral therapy. The recommended treatment is the low, but accelerating dose regimen. HCV-related cirrhosis is associated with complications including ascites, variceal bleeding, renal insufficiency, hepatic encephalopathy, and hepatocellular carcinoma. Because of its poor prognosis, liver transplantation is the only definitive therapy for decompensated cirrhosis.     

Hepatitis C virus cures after direct acting antiviral-related drug-induced liver injury: Case report

The United States Food and Drug Administration recently warned that the direct acting antiviral(DAA) combination hepatitis C virus(HCV) treatment of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin(PODr + R) can cause severe liver injury in patients with advanced liver disease. Drug induced liver injury was observed in a small number of patients with decompensated cirrhosis treated with other DAAs, but has not been reported in patients with compensated cirrhosis. We report a case of a 74-year-old woman with chronic HCV and Child-Pugh class A cirrhosis(compensated cirrhosis) treated with PODr + R. The patient presented on day 14 of PODr + R therapy with jaundice and new-onset ascites. Her total bilirubin level increased to 23 mg/dL and international normalized ratio rose to 1.65, while aminotransferase levels remained relatively stable. Hepatitis C treatment was discontinued on day 24 and she gradually recovered. Follow-up testing showed that she achieved a sustained virologic response. In conclusion, hepatic decompensation developed within two weeks of starting treatment withPODr + R in a patient with Child-Pugh class A cirrhosis and was characterized by jaundice and ascites with stable aminotransferase levels. Careful monitoring is warranted in patients with HCV-related cirrhosis treated with PODr + R.     

Adjuvant ribavirin and longer direct‐acting antiviral treatment duration improve sustained virological response among hepatitis C patients at risk of treatment failure

The role of ribavirin (RBV) in the era of direct‐acting antivirals (DAA) is not clear, and DAA studies have been largely genotype‐ and regimen‐specific. Using data from the Chronic Hepatitis Cohort Study, we evaluated the role of RBV and increased DAA treatment duration among patients with chronic hepatitis C (HCV) in routine clinical care. We performed multivariable analysis of data from 4133 patients receiving any of the following: sofosbuvir (SOF); daclatasvir + SOF; grazoprevir + elbasvir; paritaprevir/ritonavir + ombitasvir; simeprevir + SOF; and SOF + ledipasvir; SOF + velpatasvir ± voxilaprevir; and glecaprevir + pibrentasvir—all with/ without RBV. Inverse probability treatment weighting was used to adjust for treatment selection bias. Sustained virological response (SVR) was defined by undetectable HCV RNA 12 weeks after end of therapy. The overall SVR rate was 95%. Mean treatment duration was 12 ± 4.5 weeks. The final model included treatment duration and diabetes, as well as the interaction of RBV with previous treatment status (treatment naïve, interferon treatment failure [TF] or previous DAA TF), cirrhosis status, and HCV genotype (GT). Each one‐month increment of treatment duration increased odds of SVR by 99% (aOR = 1.99). Diabetes, previous DAA TF, and decompensated cirrhosis significantly reduced odds of SVR. RBV significantly increased the likelihood of SVR among patients with decompensated cirrhosis (aOR = 5.05), previous DAA treatment failure (aOR = 5.43), and GT3 (aOR = 13.28). Among RBV‐free regimens, patients with GT3 were less likely to achieve SVR than those with GT1 or 2 (aOR 0.07). Diabetes, decompensated cirrhosis, and prior DAA TF independently reduced the likelihood of SVR. Longer treatment duration increased likelihood of SVR. Conclusion: RBV increased likelihood of SVR among patients with GT3, previous DAA TF, or decompensated cirrhosis.     

Improvement of Skeletal Muscle Mass after Ledipasvir and Sofosbuvir Treatment for Hepatitis C Virus in Decompensated Liver Cirrhosis

Hepatitis C virus (HCV) can be eliminated by direct-acting antivirals in patients with decompensated liver cirrhosis. Although viral clearance in decompensated liver cirrhosis leads to improvement of the liver function and quality of life, changes in the skeletal muscle mass after sustained virologic response (SVR) in patients with decompensated liver cirrhosis have not been reported. We present the first report of skeletal muscle mass improvement with the achievement of SVR for HCV in a 76-year-old woman with decompensated liver cirrhosis. After achieving SVR through ledipasvir/sofosbuvir treatment, the patient showed an improvement in her liver function and an increase in her skeletal muscle mass.     

Hepatitis C virus infection in Argentina: Burden of chronic disease

AIM: To estimate the progression of the hepatitis C virus (HCV) epidemic and measure the burden of HCV-related morbidity and mortality.METHODS: Age- and gender-defined cohorts were used to follow the viremic population in Argentina and estimate HCV incidence, prevalence, hepatic complications, and mortality. The relative impact of two scenarios on HCV-related outcomes was assessed: (1) increased sustained virologic response (SVR); and (2) increased SVR and treatment.RESULTS: Under scenario 1, SVR raised to 85%-95% in 2016. Compared to the base case scenario, there was a 0.3% reduction in prevalent cases and liver-related deaths by 2030. Given low treatment rates, cases of hepatocellular carcinoma and decompensated cirrhosis decreased < 1%, in contrast to the base case in 2030. Under scenario 2, the same increases in SVR were modeled, with gradual increases in the annual diagnosed and treated populations. This scenario decreased prevalent infections 45%, liver-related deaths 55%, liver cancer cases 60%, and decompensated cirrhosis 55%, as compared to the base case by 2030.CONCLUSION: In Argentina, cases of end stage liver disease and liver-related deaths due to HCV are still growing, while its prevalence is decreasing. Increasing in SVR rates is not enough, and increasing in the number of patients diagnosed and candidates for treatment is needed to reduce the HCV disease burden. Based on this scenario, strategies to increase diagnosis and treatment uptake must be developed to reduce HCV burden in Argentina.     

Real‐world impact following initiation of interferon‐free hepatitis C regimens on liver‐related outcomes and all‐cause mortality among patients with compensated cirrhosis

Few studies have investigated clinical outcomes among patients with cirrhosis who were treated with interferon (IFN)‐free direct‐acting antiviral (DAA). We aimed to quantify treatment impact on first decompensated cirrhosis hospital admission, first hepatocellular carcinoma (HCC) admission, liver‐related mortality and all‐cause mortality among a national cohort of cirrhotic patients. Through record linkage between Scotland's HCV Clinical Database and inpatient/day‐case hospitalization and deaths records, a study population comprising chronic HCV‐infected patients with compensated cirrhosis and initiated on IFN‐free DAA between 1 March 2013 and 31 March 2018 was analysed. Cox regression evaluated the association of each clinical outcome with time‐dependent treatment status (on treatment, responder, nonresponder or noncompliant), adjusting for patient factors including Child‐Pugh class. Among the study population (n = 1073) involving 1809 years of follow‐up, 75 (7.0%) died (39 from liver‐related causes), 47 progressed to decompensated cirrhosis, and 28 developed HCC. Compared with nonresponders, treatment response (96% among those attending their 12 weeks post‐treatment SVR test) was associated with a reduced relative risk of decompensated cirrhosis (hazard ratio [HR] = 0.14; 95% CI: 0.05‐0.39), HCC (HR = 0.17; 95% CI: 0.04‐0.79), liver‐related death (HR = 0.13; 95% CI: 0.05‐0.34) and all‐cause mortality (HR = 0.30; 95% CI: 0.12‐0.76). Compared with responders, noncompliant patients had an increased risk of liver‐related (HR = 6.73; 95% CI: 2.99‐15.1) and all‐cause (HR = 5.45; 95% CI: 3.07‐9.68) mortality. For HCV patients with cirrhosis, a treatment response was associated with a lower risk of severe liver complications and improved survival. Our findings suggest additional effort is warranted to address the higher mortality among the minority of cirrhotic patients who do not comply with DAA treatment or associated RNA testing.