小剂量干扰素联合利巴韦林治疗丙型肝炎肝硬化的临床研究

目的探讨小剂量干扰素联合利巴韦林治疗丙型肝炎肝硬化的疗效、疗程及用药安全。方法将慢性丙型肝炎患者纳入治疗1组,给予干扰素a2b注射液500 wu联合利巴韦林抗病毒;肝硬化患者随机分为治疗2组(治疗48周)和治疗3组(治疗96周)给予小剂量干扰素a2b注射液(100~300 wu)联合利巴韦林抗病毒;观察各组的快速病毒学应答(RVR),早期病毒学应答(EVR),治疗结束时病毒学应答(ETVR),持续病毒学应答(SVR)及生化学指标的改变。结果肝硬化患者给予小剂量干扰素联合利巴韦林治疗后,生化各项指标、PTA及Child-Pugh评分均有所改善;治疗1组的ETVR、SVR均明显高于治疗2组(93.2%对68.5%、43.7%对24.1%),治疗3组的ETVR、SVR也明显高于治疗2组(92.9%对68.5%、54.8%对24.1%),差异具有统计学意义(P均0.05)。结论丙型肝炎肝硬化经小剂量干扰素联合利巴韦林抗病毒治疗后各生化指标及肝功能均有好转,用药疗程延长至96周可达到较高的SVR。     

受体IL-28B基因多态性对肝移植术后丙型肝炎复发抗病毒治疗及预后的影响

目的探讨受体白介素28B(interleukin-28B,IL-28B)基因多态性对肝移植术后丙型肝炎复发抗病毒治疗及预后的影响。方法对33例肝移植术后丙型肝炎复发患者进行干扰素联合利巴韦林抗病毒治疗,并通过肝组织进行受体IL-28B rs12979860位点的基因多态性检测,观察病毒学应答及预后情况。结果 33例患者获得治疗结束时病毒学应答(end of treatment virologic response,ETVR)24例(72.7%),其中获得持续性病毒学应答(sustained virologic response,SVR)12例(36.4%)。受体的基因型分布:CC型25例(75.8%)、非CC型8例(24.2%)。CC型与非CC型患者中ETVR率分别为84.0%、37.5%,SVR率分别为44.0%、12.5%,二者比较,CC型获得ETVR率较高(P0.05),SVR率差异无统计学意义(P0.05);CC型及非CC型患者中抗病毒治疗后移植肝硬化率分别为8.0%、50.0%,二者比较,CC型患者移植肝硬化率较低(P0.05)。结论受体IL-28B rs12979860位点CC基因型可能对移植术后丙型肝炎复发患者抗病毒治疗效果及预后存在有利影响。     

聚乙二醇干扰素联合利巴韦林治疗静脉药瘾致慢性丙型肝炎患者的疗效评价

目的评价静脉药瘾致慢性丙型肝炎患者接受聚乙二醇干扰素联合利巴韦林抗病毒的疗效及安全性。方法回顾性纳入静脉药瘾致慢性丙型肝炎患者51例,以病毒学应答、复发率为疗效评价指标,并分析可能影响此类患者获得持续病毒学应答(sustained virologic response,SVR)的因素。结果 (1)静脉药瘾致慢性丙型肝炎患者中位年龄32.5岁;男性占92.2%(47/51);HCV基因3型占52.9%(27/51)。(2)本组患者获得快速病毒学应答(rapid virologic response,RVR),早期病毒学应答(early virologic response,EVR),治疗结束病毒学应答(end-of-treatment virologic response,ETVR),SVR几率分别为66.7%、58.8%、60.8%、41.2%,复发率为32.3%。合并酒精性肝病患者获得SVR几率明显低于无酒精性肝病者(P=0.036)。(3)Logistic多因素分析显示静脉药瘾戒断时间每延长1个月,获得SVR几率增加1.365倍(P=0.004);获得ETVR的静脉药瘾致慢性丙型肝炎患者获得SVR的几率是未获得ETVR者的8.885倍(P=0.018)。结论静脉药瘾致慢性丙型肝炎患者以年轻男性多见,基因3型患者占50%以上;接受聚乙二醇干扰素联合利巴韦林抗病毒可获得相对较高的病毒学应答率,静脉药瘾戒断时间与ETVR是此类患者获得SVR的影响因素。     

肝移植术后丙型肝炎复发患者抗病毒治疗效果及其对肝纤维化的影响

目的通过对肝移植术后丙型肝炎复发患者进行抗病毒治疗,研究抗病毒治疗效果以及对肝纤维化进展的影响。方法对本院2005年6月至2012年12月收治的23例肝移植术后丙型肝炎复发患者进行干扰素联合利巴韦林抗病毒治疗,观察病毒学应答情况、不良反应以及治疗前后肝组织病理情况。计数资料以例数表示,不同抗病毒疗效组间肝纤维化情况比较采用等级资料秩和检验。结果 12例患者因不良反应终止治疗。23例患者共获得结束时病毒学应答(ETVR)18例,其中6例获得持续病毒学应答(SVR),12例出现反跳。19例患者完成前后肝组织病理检查,SVR组肝纤维化减轻3例、持平1例、进展0例;停药后反跳组肝纤维化减轻2例、持平3例、进展5例;无应答组肝纤维化减轻0例、持平1例、进展4例;3组间抗纤维化效果比较,差异有统计学意义(χ2=7.330,P=0.026)。结论肝移植术后丙型肝炎复发患者抗病毒治疗SVR率较低,有效的抗病毒治疗可延缓肝纤维化进展,取得SVR的患者肝纤维化改善效果最佳。     

12例丙型肝炎肝硬化患者脾切除术后抗病毒治疗的临床分析

目的 对部分符合外科脾切除术指征且有治疗意愿的失代偿期丙型肝炎肝硬化患者行脾切除术后给予小剂量干扰素联合利巴韦林抗病毒治疗,观察其疗效,并分析与疗效相关的可能影响因素. 方法 对部分符合外科脾切除术指征且有治疗意愿的失代偿期丙型肝炎肝硬化患者行脾切除术,术后给予个体化小剂量干扰素(普通干扰素3 ～ 5MU,隔日一次;或聚乙二醇干扰素50μg/周)联合利巴韦林0.6 ～ 0.9 g/d抗病毒治疗,基因1b型疗程≥72周,基因2a型≥36周.监测血常规、肝功能、凝血项、甲状腺功能、自身抗体等指标,处理不良反应;并监测HCV RNA水平,对病毒学应答进行评估.连续变量两组间比较采用t检验或秩和检验,计数资料采用x2检验.结果 12例患者均完成个体化治疗并随访6个月,其中3例患者因不能耐受聚乙二醇干扰素调整为普通干扰素,6例因溶血反应调整利巴韦林剂量.10例(83.3％)获得持续病毒学应答(SVR),1例无应答,1例复发.其中获得快速病毒学应答(RVR)者3例,占25.0％;获得完全早期病毒学应答(cEVR)者6例,占50.0％;24周获得应答的患者2例,占16.7％.RVR、cEVR对SVR率具有较好预测作用,获得RVR者SVR率为100％;获得cEVR者SVR率为83.3％;获得24周病毒学应答者SVR率为100％. 结论 对部分符合外科脾切除术指征且有治疗意愿的失代偿期丙型肝炎肝硬化患者可先行脾切除术,解决脾功能亢进,再行抗病毒治疗,以提高疗效;RVR、cEVR对SVR率具有较好预测作用;医师在抗病毒治疗早期与患者沟通、疗程中严密监测并给予患者足够的依从性教育和心理疏导是治疗得以维持的重要保证.     

慢性丙型肝炎合并甲型血友病患者抗病毒治疗的疗效及安全性观察

目的 探讨聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎合并甲型血友病的临床疗效和安全性.方法 将慢性丙型肝炎合并甲型血友病患者23例作为观察组,慢性丙型肝炎患者40例作为对照组.两组均给予聚乙二醇干扰素联合利巴韦林抗病毒治疗,观察病毒学应答、生化学应答及不良反应情况.结果 观察组患者快速病毒学应答(RVR)、早期病毒学应答(EvR)、治疗结束时病毒学应答(ETVR)、第12、24周时持续病毒学应答(SVR12、SVR24)分别为81.8％、86.4％、90.9％、81.8％、72.7％.对照组患者RVR、EVR、ETVR、SVR12、SVR24分别为81.1％、86.5％、91.9％、83.7％、78.4％,两组比较差异无统计学意义(P＞0.05).不良反应中,观察组乏力、食欲不振、精神症状发生率分别为43.5％、39.1％、39.1％,对照组为11.4％、15％、15.0％,观察组乏力、食欲不振、精神症状发生率高于对照组(P＜0.05).结论 慢性丙型肝炎合并血友病患者,在控制血友病的基础上,运用聚乙二醇干扰素联合利巴韦林治疗,多数患者可完成疗程,可获得较高的有效率.     

如何通过规范化的抗病毒治疗达到更高的治愈率

在近10年的临床试验和实践中,确立了持续病毒学应答(sustained viral response,SVR)为慢性丙型肝炎抗病毒治疗的目标.由于利巴韦林和聚乙二醇干扰素(Peg-IFN)的应用可显著提高抗病毒疗效,从而确立了利巴韦林和Peg-IFN在慢性丙型肝炎抗病毒治疗中的地位.诸多因素可以影响慢性丙型肝炎的抗病毒治疗效果,而抗病毒治疗中病毒的变化与SVR的获得有显著的预测性和相关性,为了使每一位患者有最大的几率获得SVR,既要遵循慢性丙型肝炎抗病毒治疗的标准化和规范化,又要正确理解和应用"应答指导治疗(response guide therapy,RGT)"的原则.     

干扰素联合利巴韦林治疗由一名献血员所致慢性丙型肝炎62例分析

目的 应用干扰素α-2b联合利巴韦林治疗由一名献血员所致62例慢性丙型肝炎(CHC)患者,评估其疗效.方法 62例输血后CHC患者给予干扰素α-2b联合利巴韦林治疗(标准干扰素3～5MU,隔日一次注射,口服利巴韦林0.6～ 1.0g/d),疗程48周,随访96周.以持续病毒应答(SVR)率、早期病毒学应答(EVR)率、治疗结束时病毒学应答(ETVR)率、停药后生物化学应笞率为考核指标,同时观察药物不良反应.计量资料用均数±标准差(x-±s)表示,计数资料用x2检验.结果 SVR率为83.9％ (52/62),EVR率为95.2％ (59/62),ETVR率为87.1％ (54/62),停药后生物化学应答率为100.0％.不同病毒载量(x 2=10.13,P＜0.05)和不同年龄(x 2=14.58,P＜0.01)患者SVR率差异明显.干扰素所致8例甲状腺功能轻度异常者经内分泌专科协助能坚持完成抗病毒治疗.结论 干扰素α-2b联合利巴韦林治疗CHC患者疗效显著,获得SVR的52例停药后随访96周均无复发,疗效与感染HCV时较年轻、感染时间较短、多数患者病毒载量较低、治疗依从性较好等因素有关,与性别无关.只要患者血清HCV RNA阳性,均应抗病毒治疗,以清除病毒、阻断和延缓病情进展.     

聚乙二醇干扰素α-2a 联合利巴韦林治疗基因1b 型慢性丙型肝炎临床观察

目的：观察聚乙二醇干扰素α-2a 联合利巴韦林治疗基因1b 型慢性丙型肝炎（CHC）的疗效及不良反应。方法40例基因1b 型 CHC 患者应用聚乙二醇干扰素α-2a 联合利巴韦林治疗,疗程48周,随访24周,观察病毒学应答情况及药物不良反应。结果获得快速病毒学应答（RVR）、完全早期病毒学应答（cEVR）、治疗结束时病毒学应答（ETVR）和持续病毒学应答（SVR）比例分别为65．0％、82．5％、90．0％、82．5％,获得 RVR 者均获得 SVR;合并脂肪肝者获得 SVR 的比例低于无脂肪肝者（P ＜0．05）;治疗过程中聚乙二醇干扰素α-2a 减量者8例,利巴韦林减量者6例。结论聚乙二醇干扰素α-2a 联合利巴韦林治疗基因1b 型 CHC 疗效良好;合并脂肪肝患者疗效低于无脂肪肝患者;治疗中不良反应普遍,但均能耐受。     

老年慢性丙型肝炎患者抗病毒治疗的疗效及安全性

目的探讨聚乙二醇干扰素α-2a联合利巴韦林治疗老年慢性丙型肝炎患者的临床疗效及安全性。方法回顾性分析慢性丙型肝炎患者共77例,年龄≥55岁患者36例为观察组,年龄<55岁患者41例为对照组。给予聚乙二醇干扰素α-2a联合利巴韦林抗病毒治疗,观察病毒学应答、生化学应答及不良反应情况。结果观察组患者快速病毒学应答(RVR)、早期病毒学应答(EVR)、治疗结束时病毒学应答(ETVR)、第12、24、48周时持续病毒学应答(SVR12、SVR24、SVR48)分别为80.6%、93.5%、96.7%、80.6%、80.6%、64%;对照组患者RVR、EVR、ETVR、SVR12、SVR24、SVR48分别为85%、92.5%、92.5%、90%、85%、87.5%,两组SVR48相比差异有统计学意义(P<0.05)。不良反应中,乏力发生率观察组为94.4%,对照组为73.2%,两组相比差异有统计学意义(P<0.05);精神症状发生率观察组为30.6%,对照组为12.2%,两组相比差异有统计学意义(P<0.05)。生化学应答及其他不良反应发生率无统计学差异(P>0.05)。结论老年慢性丙型肝炎患者,使用常规剂量的聚乙二醇干扰素及利巴韦林,在控制基础病基础上,只要能够积极预防,早期发现,及时治疗,多数患者能够坚持完成治疗,仍可获得较高的有效率和较好的耐受性。     

Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy

Patients with advanced hepatitis C virus (HCV) are at risk of death and are candidates for liver transplantation. After transplantation, HCV recurs and may rapidly progress to cirrhosis and graft loss. Treatment is needed to prevent progression of disease and minimize recurrence after liver transplantation. We evaluated the effectiveness, tolerability, and outcome of a low accelerating dose regimen (LADR) of antiviral therapy in the treatment of patients with advanced HCV. One hundred twenty-four patients (male/female ratio 81:43; age range 37-71 years; 70% genotype 1) were treated with LADR. Sixty-three percent had clinical complications of cirrhosis (ascites, spontaneous bacterial peritonitis, varices, variceal hemorrhage, encephalopathy). The mean Child-Turcotte-Pugh (CTP) score was 7.4 +/- 2.3, and the mean MELD score was 11.0 +/- 3.7. Fifty-six patients were CTP class A, 45 were class B, and 23 were class C. Forty-six percent were HCV RNA-negative at end of treatment, and 24% were HCV RNA-negative at last follow-up. Sustained virological response (SVR) was 13% in patients infected with genotype 1 HCV and 50% in patients infected with non-1 genotypes (P < .0001). Non-1 genotype, CTP class A (genotype 1 only), and ability to tolerate full dose and duration of treatment (P < .0001) were predictors of SVR. Twelve of 15 patients who were HCV RNA-negative before transplantation remained HCV RNA-negative 6 months or more after transplantation. In conclusion, in a sizeable proportion of patients with advanced HCV, LADR may render blood free of HCV RNA, stabilize clinical course, and prevent posttransplantation recurrence.     

肝移植后的丙型肝炎复发及对策

丙型肝炎(丙肝)肝移植后大部分会出现丙肝复发,疾病进展快于移植前,并有特殊的发病机制.影响复发的因素有HCV基因型、病毒载量、供者和受者人白细胞抗原匹配情况、复发时间、供者年龄以及免疫抑制剂的使用情况等.移植前干扰素抗病毒治疗以取得病毒阴转为目标,2/3的患者移植后HCV RNA阴性;移植后丙肝复发可用长效干扰素┼利巴韦林抗病毒,但持续病毒学应答仅30.2%.特异性靶向抗HCV治疗可能为肝移植后丙肝治疗带来希望.     

Pegylated interferon plus ribavirin combination therapy in postliver transplant recipients with recurrent hepatitis C virus infection

Posttransplant hepatitis C virus (HCV) recurrence is universal in chronic hepatitis C recipients. Antiviral therapy is suggested after liver transplant to halt disease progression. Pegylated interferon plus ribavirin therapy remains the standard of care in many areas where direct antiviral agents are poorly accessible. This study aimed to assess the treatment efficacy and safety of the regimen for Taiwanese patients with post-transplant HCV recurrence. Nine patients with HCV recurrence postliver transplantation were allocated. Patients received either pegylated interferon α-2a 180 μg/wk or pegylated interferon α-2b 1.5 mg/kg/wk plus ribavirin for 24–48 weeks. The primary endpoint was the achievement of sustained virological response (SVR), defined as undetectable HCV RNA throughout 6 months of follow-up after the end of treatment. The safety profiles were also documented. The rates of rapid virological response, early virological response, end-of-treatment virological response, and SVR were 33%, 63%, 75%, and 56% respectively. Of the four patients who failed antiviral treatment, the treatment responses were nonresponse (n = 1), loss of follow-up (n = 1), and relapse (n = 2). Three patients terminated therapy early due to severe adverse events, including severe anemia, intra-abdomen infection, and hepatocellular carcinoma recurrence. One of the three patients who terminated treatment early at Week 6 experienced rapid virological response followed by SVR. Pegylated interferon/ribavirin combination allowed a chance for cure with a fair SVR rate in Taiwanese chronic hepatitis C patients postliver transplantation. Early identification of side effects and careful monitoring during therapy might enhance the treatment efficacy.     

Liver Support With Albumin Dialysis Reduces Hepatitis C Virus Viremia and Facilitates Antiviral Treatment of Severe Hepatitis C Virus Recurrence After Liver Transplantation

Patients with severe hepatitis C virus (HCV) recurrence after liver transplantation (LT) present an ominous prognosis, rarely achieving sustained virological response (SVR). Dialysis procedures may transiently decrease the HCV viral load, but the effect of albumin dialysis is currently unknown. Here, we evaluated the impact of albumin dialysis using the Molecular Adsorbent Recirculating System (MARS) used as a co‐adjuvant antiviral treatment for severe HCV recurrence after LT. Thirteen patients (11 males, median age 48 years) with fibrosing cholestatic hepatitis or METAVIR fibrosis score ≥ F3 with severe portal hypertension underwent three consecutive MARS sessions. Antiviral therapy was initiated in 11 patients within 24 h after the MARS sessions. A contemporary cohort of seven patients who did not follow the MARS protocol is shown for comparison. MARS treatment resulted in consistent decreases of viral load from 7.59 log₁₀ IU/mL [6.15–8.90] to 6.79 log₁₀ IU/mL [5.18–7.84] (P = 0.003) as well as in decreases of serum bilirubin, gamma‐glutamyl transpeptidase, alanine aminotransferase and aspartate aminotransferase (all P < 0.05). The overall rate of SVR was 0% in the Control group and 54.6% in patients initiating antiviral therapy within 24 h after MARS. Survival at 1 and 3 years was, respectively, 93% and 70% in patients undergoing MARS, compared with 29% and 14% in the Control group (P = 0.001). No major adverse events related to MARS treatment were observed. In conclusion, the use of MARS may facilitate the achievement of SVR and improve the prognosis of patients with severe HCV‐recurrence after LT by reducing viral load and improving liver function prior to antiviral therapy.     

Monotherapy with peginterferon alpha-2b {12 kDa} for chronic hepatitis C infection in patients undergoing haemodialysis.

BACKGROUND: A combination of Peginterferon and Ribavirin is the standard treatment for patients with chronic hepatitis C viral infection (HCV). Ribavirin is contraindicated in patients with chronic renal failure (CRF). Conventional Interferon monotherapy is effective in around 30% of such patients. There is scanty data on the use of Peginterferon monotherapy in them. METHODS: We describe our preliminary experience of monotherapy with Peginterferon alpha- 2b {12 kDa} (Peg-IFN) for HCV patients undergoing haemodialysis for CRF. They were treated with Peg-IFN 1 microg/kg body weight subcutaneously once a week for 24 weeks. In all patients, clinical (age, sex, mode of acquiring HCV, pattern of haemodialysis) and virological (HCV RNA quantitative-PCR and genotype) profile was noted at baseline. Early virological response at 12 weeks (EVR), end-of-treatment virological response at 24 weeks (ETVR) and sustained virological response after 6 months of stopping treatment (SVR) were noted during the follow-up period. RESULTS: The clinical and virological characteristics of patients were as follows: Of a total number of 6 patients, 5 were male and 1 was female with an age range of 35 to 62 years. The duration of haemodialysis was from between 5 and 12 months before the start of treatment and its frequency lay between 1 and 3 times a week. The mode of acquiring HCV was blood transfusion (100%). All 6 cases suffered from chronic hepatitis. The genotype distribution was genotype 3 in 3 (50%), genotype 1 in 1 (16.7%) and genotype none of 6 in 2 (33.3%) patients. All the patients (100%) completed treatment. EVR was seen in all 6 patients (100%). ETVR was seen in 5 of 6 patients (83.3%). A follow-up period of more than 1 year was available in 4 patients. 3 of these 4 patients (75%) had SVR. A virological response was maintained in all 3 (100%) patients with SVR even after 6 months of renal transplantation. CONCLUSION: Peg-IFN monotherapy is safe and effective in patients with HCV who are on haemodialysis for CRF.     

Flexible and individualized treatment to achieve sustained viral response for recurrent hepatitis C in liver transplant recipients

Summary. Hepatitis C recurrence after liver transplantation is universal and is a major cause of long‐term graft failure. Improving the effectiveness of recurrent hepatitis C treatment is extremely important. We studied 35 anti‐hepatitis C virus (HCV)‐positive patients who underwent liver transplantation. Among the 35 patients, 25 patients had recurrent hepatitis C and received antiviral treatment. HCV RNA load after liver transplantation was increased by 3.68‐fold. The antiviral treatment regimen comprised pegylated‐interferon (180 μg) every 2 weeks and ribavirin at a dose of 200–400 mg every day. The treatment duration was flexible and individualized, and depended on viral response to treatment. The dosage of tacrolimus was decreased gradually to minimize immunocompromise. Median (interquartile) serum level of tacrolimus was 6.9 (6–8.9) ng/mL at initiation of treatment and 3.8 (3.6–5) ng/mL at the end of treatment. One patient (4.0%) was withdrawn from the study, and three patients (12%) died of infection during treatment. At end of treatment, 18 of 25 patients (72%) were negative for serum HCV RNA. After an additional 6 months following the end of treatment, 16 of the 25 patients (64%) had sustained viral response (SVR) and only two patients had HCV relapse. The 1‐year, 3‐year and 5‐year survival rates were 91.4%, 84.5% and 84.5% for all patients and 88.0%, 82.8% and 82.8% for the 25 patients who received antiviral therapy. In conclusion, recurrent HCV infection is an important issue in liver transplantation. The flexible regimen of antiviral therapy and individualized immunosuppressive agents that was applied in this study achieved a SVR rate of 64%.     

Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances

Management of hepatitis C (HCV) in liver transplantation (LT) population presents unique challenges. Suboptimal graft survival in HCV+ LT recipients is attributable to universal HCV recurrence following LT. Although eradication of HCV prior to LT is ideal for the prevention of HCV recurrence it is often limited by adverse events, particularly in patients with advanced cirrhosis. Antiviral therapy in LT candidates needs careful monitoring, and prophylaxis with HCV antibodies is ineffective. Early antiviral therapy after LT has been investigated, but no clear benefit has been demonstrated. Protocol liver biopsy is generally recommended in HCV+ LT recipients, and antiviral therapy can be considered in those with severe/progressive HCV recurrence. Sustained virological response (SVR) can be achieved in approximately 30% of LT recipients with pegylated interferon/ribavirin (PEG-IFN/RBV) with survival benefit, but adverse effects are common. Favorable patient characteristics for response to therapy include non-1 genotype, previously untreated, low baseline HCV-RNA, and donor IL28B genotype CC. Direct acting antiviral (DAA)-based triple therapy is associated with higher rates of SVR, but with similar or slightly higher rates of side effects, and immunosuppressive regimens need to be closely monitored and adjusted during the treatment period. Notably, the safety and efficacy of HCV treatment are very likely to improve with newer generation DAA. The benefit of immunosuppressive strategy on the natural history HCV recurrence has not been well elucidated. Based upon available evidence, cyclosporine A (CSA), mycophenolate mofetil (MMF), and sirolimus appear to have a neutral or small beneficial impact on HCV recurrence. Donor interleukin 28 B (IL28B) polymorphisms appear to impact the course and treatment outcomes in recurrent HCV. Retransplantation should be considered for patients with reasonable survival probability.     

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。     

Antiviral therapy of patients with decompensated cirrhosis to prevent recurrence of hepatitis C after liver transplantation

BACKGROUND/AIMS: After liver transplantation (LT) infection of the graft with the hepatitis C virus (HCV) is almost universal and chronic hepatitis and cirrhosis develop in a significant proportion of patients. One of the possible strategies to prevent HCV infection recurrence is to eradicate HCV before LT. METHODS: We evaluated the efficacy and safety of antiviral therapy to prevent HCV recurrence in 30 HCV-cirrhotic patients awaiting LT. At the time of inclusion 15 patients were Child-Pugh A and 15 Child-Pugh B/C. The infecting genotype was 1b in 25 patients. Treatment with interferon alpha-2b 3 MU/day and ribavirin 800 mg/day was initiated when the expected time for LT was less than 4 months and continued until LT. The median duration of treatment was 12 weeks. RESULTS: Nine patients (30%) achieved a virological response and 21 did not respond to therapy. In nine (43%) of the 21 non-responders viral load decreased > or =2 log10 during treatment. A viral load decrease > or = 2 log10 at week 4 of treatment was the strongest predictor of virological response. All nine virological responders have already undergone LT; six patients remain free of infection after a median follow-up of 46 weeks and HCV infection recurred in three patients after LT. In one of these patients HCV-RNA was still detectable in the explanted liver. Side effects were frequent and dose reduction was necessary in 19 (63%) of the 30 patients; no patient died while on therapy. CONCLUSIONS: Our data support the utilization of antiviral therapy in HCV-infected patients awaiting LT as one of the strategies to prevent hepatitis C recurrence after transplantation.