Abstract Background: Evidence of direct-acting antiviral (DAA) treatment for refractory chronic hepatitis C (CHC) patients was limited. We aimed to evaluate the effectiveness and safety of Sofosbuvir/Velpatasvir (SOF/VEL) plus Ribavirin (RBV) in cirrhotic patients with hepatitis C virus genotype 3 (GT3) with or without HIV or HBV coinfection. Methods: From June 2019 to December 2022, CHC GT3 patients who received SOF/VEL plus RBV (dosage of RBV depended on weight) for 12 weeks were enrolled. Liver cirrhosis was diagnosed by clinical presentation . The primary endpoint was sustained virologic response at 12 weeks off-therapy (SVR12). Adverse events (AE)were assessed during treatment. Results:In total, 285 treatment-naive patients were recruited at the Kunming Third People’s Hospital. Mean age was 48.18±8.27 years-old and 74.04% (211/285) were male. All patients had GT3 HCV infection including 44 patients with GT3a and 241 patients with hepatitis C virus genotype 3b (GT3b) . Among these patients, 39 with HCV/HIV,10 with HBV/HCV, and 1 with HBV/HCV/HIV coinfection. All patients had liver cirrhosis, and 46.67% (133/285) of patients had compensated cirrhosis (CC), while 53.33% (152/285) of patients had decompensated cirrhosis (DCC). 98.95% (282/285) patients achieved SVR12 with SOF/VEL plus RBV treatment for 12 weeks, including 97.72% (43/44) in GT3a and 99.17% (239/241) in GT3b. According to the condition for 285 patients with liver cirrhosis, the SVR12 rate in the CC group was : 99.25% (132/133), the SVR12 rate in the DCC group was: 98.68% (150/152). After 12 weeks of treatment, the APRI score and FIB-4 score in CC group and DCC group were improved, and the improvement in the compensated cirrhosis group was better than that in decompensated cirrhosis group (PAPRI=0.001, PFIB-4=0.001). Mean ALT (from 74±27.23U/L to 39.31±12.22U/L, p<0.05) and AST (from 73.98±25.54U/L to 44.17±15.56U/L, p<0.05) also significantly declined after treatment.1 patient had serious AE of hemolysis but recovered after 2-3 days of interruption of RBV. Most AEs were consistent with clinical sequelae of advanced liver disease or known toxicities of RBV. Conclusion： SOF/VEL combined with RBV for cirrhotic GT3 hepatitis C patients all obtained high SVR12 (>95%), improved liver function during treatment, and for cirrhotic GT3 hepatitis C patients treatment with SOF/VEL combined with RBV is recommended as early as possible.

目的 观察初治的低病毒载量不确定期慢乙肝患者采用一线核苷(酸)类药物抗病毒治疗后的临床疗效及安全性.方法 纳入2019年1月至2022年4月期间在昆明市第三人民医院门诊就诊的96例初治低病毒载量不确定期慢性乙肝患者,根据使用药物不同将患者分为恩替卡韦组(ETV组)、富马酸替诺福韦酯组(TDF组)和富马酸丙酚替诺福韦组(TAF组).在持续用药的第12周、24周、48周观察3组的临床疗效及安全性差异.结果 经抗病毒治疗48周后,总共96.88％(93/96)患者HBV DNA获得完全病毒学应答(complete virologic response,CVR,定义为HBV DNA<100 IU/mL),3组的CVR率为:ETV组96.97％(32/33),TDF组96.97％(32/33),TAF组96.67％(29/30),组间差异无统计学意义(P=0.997).治疗48周时HBsAg水平较基线均有显著下降,但3组差异无统计学意义(P=0.348).TAF组较ETV组(P=0.013)、TDF组(P=0.047)显著提升eGFR水平,AFP水平较ETV组(P=0.008)和TDF组(P=0.007)显著下降.48周ALT复常率:TAF组(70％)和TDF组(45.45％),ETV组(60.61％)差异无统计学意义(P=0.135).治疗期间无严重不良事件发生.结论 治疗48周后3组CVR率均达96％以上,AFP水平下降及eGFR水平改善TAF组优于ETV组及TDF组,对ALT升高、低病毒载量慢乙肝不确定期患者行抗病毒治疗可使患者获益.

Objective:To evaluate the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without ribavirin in the treatment of patients diagnosed with chronic hepatitis C (CHC) and chronic kidney disease (CKD).Methods:From June 2018 to May 2022, a total of 75 patients with CHC and CKD, and treated with SOF/VEL±ribavirin at the Kunming Third People′s Hospital were enrolled in this study. The basic information of patients were collected. Assessments of renal function, liver function, virologic response rate and adverse events were conducted at baseline, four weeks and 12 weeks of treatment and 12 weeks after treatment withdrawal. Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used for statistical analysis.Results:Among the 75 patients, 51 cases(68.0%) were classified as CKD stage 2, 12 cases (16.0%) as CKD stage 3, four cases (5.3%) as CKD stage 4, eight cases (10.7%) as CKD stage 5. Additionally, 26 cases (34.7%) were classified as HCV type 3a, while 37 cases (49.3%) were classified as type 3b. Among the patients, 51 cases (68.0%) had cirrhosis, including 15(20.0%) compensated cirrhosis and 36(48.0%) decompensated cirrhosis. Twelve weeks after treatment withdrawal, there was a statistically significant improvement in the estimated glomerular filtration rate (eGFR) compared to baseline (81.76(60.94, 94.34) mL/(min·1.73 m 2) vs 70.99(52.86, 82.38) mL/(min·1.73 m 2), Z=8.12, P=0.040). From baseline to 12 weeks after treatment withdrawal, eGFR of patients with CKD stage 2 and stage 3 were both gradually increased, with statistical significance ( H=8.91 and 8.03, respectively, both P<0.05). For CKD stage 2 patients, eGFR increased from 78.82(70.98, 84.80) mL/(min·1.73 m 2) to 86.94 (75.91, 96.01) mL/(min·1.73 m 2), while CKD stage 3 patients had an increased from 51.24 (45.92, 53.37) mL/(min·1.73 m 2) to 64.58 (44.54, 74.34) mL/(min·1.73 m 2). Renal function was improved to CKD stage 1 in 21 patients (28.0%). Compared to baseline, CKD stage 2 patients exhibited a decrease of aspartate aminotransferase to platelet ratio index 12 weeks after treatment withdrawal, and alanine aminotransferase and aspartate aminotransferase levels were also significantly improved with statistical significance ( Z=8.03, 21.57 and 43.74, respectively, all P<0.05). The rate of sustained virological response (SVR)12 at 12 weeks after treatment withdrawal was 98.7%(74/75). Among these cases, 51 patients in CKD stage 2, 11 patients in CKD stage 3, 12 patients in CKD stage 4 and stage 5 reached SVR12. Adverse events occurred in 32 patients (42.7%), including 18 cases of mild hemolytic anemia, four cases of skin itching, three cases of rash, two cases of chest tightness, and five cases of fatigue. Conclusions:SOF/VEL with or without ribavirin for the treatment of patients with CHC and CKD has good effectiveness and safety. The renal function, liver function and liver fibrosis degree have been improved after antiviral treatment.

目的 探讨索磷布韦/维帕他韦±利巴韦林(sofosbuvir/velpatasvir±ribavirin,SOF/VEL±RBV)治疗基因 3 型丙型肝炎肝硬化患者的疗效和安全性.方法 回顾性纳入 2018 年 6 月至 2023 年 2 月就诊于昆明市第三人民医院诊断为基因 3 型(GT3)肝硬化患者,使用SOF/VEL+RBV治疗 12 周,如有RBV禁忌或者RBV不耐受,则采用SOF/VEL治疗 12 或 24 周.分析患者在治疗前、治疗 4 周、12 周及停药后 12 周的病毒学指标、肝肾功能指标和不良反应等.结果 最终纳入 319 例GT3 肝硬化患者,其中SOF/VEL+RBV组 308 例,SOF/VEL组 11 例.停药 12 周后,SOF/VEL+RBV组持续病毒学应答(SVR12)率达 98.37%(303/308),与基线相比,APRI评分和FIB-4 指数水平均下降(P<0.05),总胆红素、天冬氨酸转氨酶、丙氨酸转氨酶水平均下降,差异均有统计学意义(均P<0.05).SOF/VEL组SVR12 率为 72.73%(8/11).SOF/VEL+RBV组的不良反应为轻度溶血性贫血(15.26%)、乏力(8.12%)和皮疹(8.77%),SOF/VEL组为 1 例乏力(9.09%).结论 索磷布韦/维帕他韦联合利巴韦林方案在基因 3 型丙肝感染的代偿期肝硬化和失代偿期肝硬化患者中都能获得较高SVR12 率(98.37%),生化学指标和肝纤维化程度均较治疗前有所改善且安全性好.

目的 研究在高脂高糖饮食诱导建立的肥胖大鼠慢性肝损伤肝脏纤维化模型中,灯盏乙素(SCU)对其发病机制的影响,探讨SCU能否通过促进MMP2、MMP9,抑制TIMP-1的表达改善肝脏纤维化程度.方法 采用高脂高糖饮食诱导慢性肝损伤肝脏纤维化模型,SCU和姜黄素(CUR)灌胃治疗8周后,HE染色观察肝组织病理变化;Masson染色观察胶原纤维在肝脏中的沉积;Western blot和免疫组织化学染色观察肝脏组织TIMP-1、MMP2、MMP9的表达.结果 在肝脏组织中,模型组大鼠肝细胞形态不规则细胞水肿,并有大量脂肪空泡出现,汇管区有蓝色胶原纤维沉积,不同剂量的SCU和CUR干预后,脂肪空泡减少,肝细胞肿胀情况减少,纤维化程度得到改善.在大鼠肝细胞中,模型组MMP2、MMP9蛋白表达下调(P<0.01),不同剂量SCU和CUR干预后MMP2、MMP9蛋白表达上调(P<0.01);模型组TIMP-1蛋白表达上调(P<0.01),不同剂量SCU和CUR治疗后TIMP-1蛋白表达下调(P<0.01),没有很明显的剂量依赖性.结论 SCU可能通过促进MMP2、MMP9,抑制TIMP-1蛋白的表达,减少ECM的积累改善肥胖引起的肝脏纤维化.

目的 探讨灯盏乙素(SCU)抑制NOX(NOX2、NOX4)的表达,改善高脂高糖诱导的非酒精性脂肪性肝病(NAFLD)肝脏纤维化程度.方法 60只大鼠随机分为:正常组、模型组、SCU-25低剂量治疗组[25 mg/(kg·d)]、SCU-50 中剂量治疗组[50 mg/(kg·d)]SCU-100 高剂量治疗组[100 mg/(kg·d)]和姜黄素阳性药物治疗组[200mg/(kg·d)],每组10只.正常组给予普通饲料喂养24+8周,其余各组采用高脂高糖饲料喂养SD大鼠24周建立NAFLD动物模型后,给予不同浓度的SCU和姜黄素灌胃治疗8周.治疗完成后,称取大鼠的体重,麻醉状态下取大鼠血清和肝脏组织,称取肝脏的重量,计算肝脏指数;通过ELISA法检测血清和组织中ROS的含量;采用油红"0"染色检测肝脏组织脂质沉积,Masson染色检测肝脏组织的纤维化程度;Western blot和免疫组织化学法检测肝脏组织中NOX2、NOX4蛋白的表达.结果 模型组大鼠体重、肝重及肝脏指数增加(P＜0.01),不同剂量的SCU和姜黄素治疗后体重、肝重及肝脏指数降低,SCU-100高剂量治疗组和姜黄素阳性药物治疗组对体重和肝重降低的影响较为明显(P＜0.01).模型组血清和肝脏组织ROS含量增加(P＜0.01),不同剂量的SCU和姜黄素治疗后ROS含量降低(P＜0.05).在肝脏组织中,模型组出现大量的脂质沉积和组织的纤维化表现,不同剂量的SCU和姜黄素治疗后,脂质沉积减少,肝脏的纤维化程度改善.在肝脏组织细胞中,模型组的NOX2、NOX4蛋白表达上调(P＜0.05),不同剂量的SCU和姜黄素治疗后NOX2、NOX4的蛋白表达下调(P＜0.05),但剂量依赖不明显.结论 SCU可能通过抑制肝脏NOX2、NOX4蛋白的表达,降低ROS的产生,从而改善NAFLD的肝脏纤维化程度.

目的 观察索磷布韦维帕他韦联合利巴韦林(SOF/VEL+RBV)抗病毒治疗基因3(GT3)型初治慢性丙型肝炎患者的疗效和安全性.方法 选取就诊于昆明市第三人民医院肝病科的80例基因3型慢性丙型肝炎初治患者,观察组治疗方案为索磷布韦维帕他韦联合利巴韦林抗病毒治疗患者40例;对照组治疗方案为索磷布韦维帕他韦单药抗病毒治疗患者40例.观察治疗4周、12周、停药后随访12周持续病毒学应答、生化学指标变化、Fibroscan指标变化和治疗期间不良反应的情况.结果 采用观察组或对照组4周时SVR率分别为90.00％,70.00％、12周时SVR率分别为97.50％,80.00％、停药后随访12周时SVR率分别为97.50％,80.00％;在ALT、AST、GGT、ALB等血清生化指标在治疗4周、12周时,观察组比对照组下降更显著(P＜0.05),在停药后随访12周时,两组差异无统计学意义(P＞0.05);观察组比对照组在治疗12周时Fibroscan值显著下降(t=5.700,P=0.018),停药后随访12周时,两组的Fibroscan值无差异(t=0.012,P=0.912);治疗期间两组的不良反应主要为乏力、头痛和头晕.结论 对于基因3型初治慢性丙型肝炎患者,观察组比对照组抗病毒治疗可获得更高的SVR率和生化学应答率,肝纤维化明显改善且具有良好的安全性.

目的 观察索磷布韦维帕他韦治疗慢性丙型肝炎患者和HCV/HIV合并感染患者的临床疗效和安全性.方法 将2018年6月至2020年6月就诊于云南省昆明市第三人民医院的419例慢性丙型肝炎患者和56例HCV/HIV合并感染患者纳入到研究中.观察治疗4周、12周、治疗后随访12周持续病毒学应答(SVR12)、生化学应答、肝纤维化改善和治疗期间的不良反应.结果 停药12周后,单纯HCV患者的基因1(genotype,GT1)型的SVR12率为97.56％,GT2型的SVR12率为98.97％,3型的SVR12率为97.54％,6型的SVR12率为97.85％,P=0.870;对于HCV/HIV合并感染患者(除抗HIV治疗外给予索磷布韦维帕他韦抗HCV治疗)治疗12周后,GT1型患者的SVR12为85.71％,GT3型患者的SVR12为92.11％,GT6型患者的SVR12为90.91％,P=0.862;单纯HCV患者抗病毒治疗后的AST、ALT、ALB生化学指标明显好转,肾功能明显改善;单纯HCV患者的肝纤维化指标在治疗后,纤维化程度明显改善;不良反应发生的患者中GT3型出现腹泻、恶心、呕吐、乏力,其他基因型别的患者和HCV/HIV合并感染患者以乏力、头痛为主.结论 索磷布韦维帕他韦对于治疗初治慢性丙型肝炎患者、HCV/HIV合并感染患者的抗病毒治疗有效且有较高安全性.

目的 观察慢性乙型肝炎(CHB)患者使用富马酸丙酚替诺福韦(TAF)的临床疗效及肾脏安全性.方法 选取2018年1月至2020年2月期间在昆明市第三人民医院肝病门诊就诊的180例之前服用TDF抗病毒治疗48周至49周的慢性乙型肝炎患者为研究对象.根据用药的不同将其分为TAF治疗组和TDF治疗组.TAF治疗组患者将既往用TDF患者换用TAF治疗,TDF组患者采用继续用TDF进行治疗.持续用药48周后,对比两组患者的临床疗效和肾功能损伤发生情况.结果 在持续用药48周时的治疗疗效中,两组HBV-DNA抑制率差异有统计学意义(χ2=10.250,P=0.001),TAF组HBV-DNA抑制率优于TDF组;两组ALT复常率差异有统计学意义(χ2=6.871,P=0.009),TAF组ALT复常率优于TDF组,两组HBeAg血清学转化差异有统计学意义(χ2=3.881,P=0.049),TAF组HBeAg血清学转化优于TDF组;在安全性方面,两组尿 α1-微球蛋白异常差异有统计学意义(χ2=13.703,P=0.000),TAF组的尿 α1-微球蛋白异常率低于TDF组,血 β2微球蛋白检测两组之间差异无统计学意义(P≥0.05).结论 TAF治疗组临床疗效明显优于TDF治疗组且对肾脏安全性高于TDF,有较强的抗病毒效力、减少了肾功能损伤等副作用的发生率和降低患者肝硬化和肝癌的风险.