抗病毒治疗对不同类型HCV感染者外周血中CD4+CD25high调节性T细胞的影响

目的:探讨抗病毒治疗对不同类型HCV感染者外周血中CD4+ CD25high,调节性T细胞(Treg)频率及其功能的影响.方法:收集急性丙型肝炎患者26例、慢性丙型肝炎患者65例、肝硬化患者52例和健康对照者32例,分别抽取患者在治疗初期、治疗后和随访24周时的外周血,采用流式细胞术分析Treg细胞的表达频率,同时检测患者HCV-RNA和肝功能,ELISA法检测IFN-γ、IL-2和IL-10等细胞因子.结果:(1)急性丙型肝炎组患者治疗前、治疗后和随访后外周血标本中Treg细胞占CD4+T细胞的百分含量与健康对照组无明显差异(P＞0.05),但HCV-RNA和ALT均有较高的阴转率(80％以上).慢性丙型肝炎组患者(12.32±4.51)％和肝硬化组患者(18.17±4.16)％外周血中Treg细胞频率均明显高于健康对照组(4.69±2.16)％(P＜0.01),抗病毒治疗结束后[(7.66±4.03)％,(15.24±4.28)％]较治疗前均有明显下降(P＜0.05),其中慢性丙型肝炎组有66.2％的患者获得了SVR,肝硬化组亦有40.4％的患者获得了SVR,且获得SVR患者的Treg细胞频率明显低于本组未获得SVR患者(P＜0.05).(2)慢性丙型肝炎患者抗病毒治疗后,获得SVR患者外周血中随着Treg细胞频率的下降IFN-γ和IL-2明显升高,而IL-10则明显降低(P＜0.01);未获得SVR患者的IFN-γ和IL-2呈先升高后降低趋势,IL-10表达亦相反(P＜0.05).结论:Treg主要通过抑制HCV特异性Thl细胞反应来实现疾病的慢性化,通过抑制或去除Treg细胞来刺激HCV特异性免疫反应或许是治疗慢性HCV感染的一个新策略.     

老年丙型肝炎患者60例抗病毒疗效影响因素分析

目的 分析宿主因素、病毒因素、病毒应答模式以及干扰素(IFNα)种类和用药时间对老年丙型肝炎患者治疗结局的影响,寻找预测老年丙型肝炎患者持续病毒学应答(SVR)的相关因素.方法 回顾性分析2006年1月至2010年10月60例年龄≥60岁丙型肝炎患者的性别、年龄、体重指数(BMI)、HCV RNA定量及基因型、IFNα种类、病毒应答模式以及病毒阴转后用药时间等因素与SVR的关系.结果 SVR组与非SVR组性别、年龄和BMI无统计学差异;SVR组HCV RNA定量显著低于非SVR组(t=4.209,P=0.022),ALT或AST显著高于非SVR组(t=15.724,P=0.006;t=10.549,P=0.003);HCV RNA定量<1×105 IU/ml组SVR率显著高于HCV RNA定量≥1×105 IU/ml(χ2=6.801,P=0.009);基因1b型SVR率为56.8%,低于非1b型(60.9%);PEG IFNα-2a组SVR率为62.5%,普通IFNα-2a组SVR率为53.6%,两组比较无统计学差异(χ2=0.49,P=0.484);快速病毒学应答(RVR)患者95%获得SVR,早期病毒学应答(EVR)患者68.4%获得SVR;IFN治疗时间≥72周SVR率82.8%,复发率6.9%;HCV RNA定量阴转后用药≥40周患者复发率3.2%.结论 老年患者抗病毒治疗前低HCV RNA定量、ALT及AST≥2倍正常上限(ULN),HCV RNA非1b型患者可获得较高SVR.RVR比EVR患者SVR率高约30%,延长病毒阴转后用药时间可提高SVR.     

36例慢性丙型肝炎抗病毒副作用及对策

从1989年克隆HCV病毒以来[1],目前全球约有1．8亿人感染HCV,其中,20％-30％发生肝硬化和肝衰竭,2％-5％发生肝细胞癌（HCC）[2]。我国约有1000万HCV感染者,相关HCC年死亡率为23．5／10万人。丙肝病毒（HCV）是造成慢性肝炎、肝硬化及肝癌的重要原因之一。对丙型肝炎治疗的研究不断进展。目前丙型肝炎抗病毒治疗的标准方案是干扰素（IFN）联合利巴韦林（RBV）治疗。抗病毒治疗存在一定不良反应,影响疗效。本研究对36例进行抗病毒治疗的慢性丙型肝炎患者副作用进行了研究。     

肝移植术后丙肝复发抗病毒治疗的护理干预

<正>丙型肝炎病毒(HCV)感染相关终末期肝病进行肝移植的患者,移植术后HCV再感染的发生十分普遍。发生HCV再感染后有效的抗病毒治疗可阻止或延缓疾病的进展[1]。因此移植术后进行抗病毒治疗十分必要。为了帮助患者完成预定的抗病毒治疗疗程,本院对2005年1月以来     

一项新的关于对聚乙二醇干扰素和利巴韦林联合治疗持续应答的慢性丙型肝炎患者进展为肝癌的预测评分系统

感染丙型肝炎病毒(HCV)是慢性肝炎的重要原因,同时也是进展为肝癌的重要危险因素。目前,丙型肝炎患者使用聚乙二醇干扰素(peg-IFN)联合利巴韦林抗病毒治疗,30%～50%的患者可获得持续病毒应答(SVR)。有证据显示,抗病毒治疗能预防慢性丙型肝炎(CHC)患者进展为肝癌。然而,获得持续病毒学应答的患者中仍可能发展为肝     

抗HBV治疗与肝细胞肝癌术后生存率和肿瘤复发的关系

正肝细胞肝癌(HCC)是临床上常见的恶性肿瘤之一,慢性乙型肝炎病毒(HBV)感染是原发性肝细胞肝癌发生的主要危险因素。HBV导致HCC与多种机制有关,研究[1]证明高载量的病毒复制与肝癌的发生率呈正相关。研究[2-3]证明,合并乙肝病毒感染的HCC患者,肿瘤切除术后通过抗病毒治疗能显著减少HCC复发和延缓病情进展,明显提高生存率。为了防止肿瘤切除手术     

肝细胞癌与乙,丙型肝炎病毒感染关系的探讨

肝细胞癌(HCC)是许多国家常见的恶性肿瘤之一,中国、东南亚和非洲次撒哈拉是HCC高发区,每年男性新发病率为10～30/10万人,全世界HCC发病人数每年在25万～100万例,是男性第7位最常见的肿瘤.自从应用ELISA法检测乙肝标志物(HBVM)、抗一HCV和应用聚合酶链反应(PCR)技术检测HBV-DNA、HCV-RNA以来,乙型肝炎病毒(HBV)在HCC病因学的作用已得到肯定.近年来丙型肝炎病毒(HCV)与HCC的关系受到关注,已有许多研究报道,HCV感染是HCC发生的一项重要危险因素.对65例HCC患者进行HBVM、抗HCV和HBV-DNA、HCV-RNA检测,以探讨它们之间的关系.     

原发性肝细胞癌HBV、HCV感染状况的分析

为了探讨HCC与HBV、HCV感染的关系 ,了解HCC中HBV、HCV感染的构成 ,我们对 38例HCC及46例非肝癌癌症患者进行了HBV、HCV感染状况的研究。HCC及非肝癌癌症患者的HBV感染率分别为 78.95 %(30/38)、13.04 % (6/46 ) ,χ2 =36.90 ,P 2 =4.5 ,P <0.05。在原发性肝癌患者中A(“大三阳”)、B(“小三阳”)及C(HBsAg兼HBcAb双阳性 )这三种模式的检出率分别为 15.79% ,28.5 9% ,26.32 % ,但这三种模式在非肝癌癌症患者中均未出现 ,两组间有高度显著性差异。其中HBeAg均为阴性的检出率为 55.26%远高于HBeAg阳性者。HCC患者中 ,单纯乙肝感染者、单纯丙肝感染者、乙、丙肝混合感染者的构成分别为 41.18%、11.76%、47.06 %。以上结果提示 ,HCC的发生和HBV的感染有密切的关系 ;单纯HBV感染、HBV及HCV混合感染比单纯HCV感染者发生HCC的可能性大 ,但也并不说明单纯HCV感染者就没有发生HCC的危险性。     

聚乙二醇化干扰素联合利巴韦林治疗慢性丙型肝炎的疗效及影响因素分析

目的观察并分析聚乙二醇化干扰素(Peg IFNα-2α)联合利巴韦林治疗慢性丙型肝炎的疗效及其影响因素。方法回顾性分析2010年1月至2015年1月期间收治的256例慢性丙型肝炎患者的临床资料,均予Peg IFNα-2α(180μg/周或135μg/周)联合利巴韦林900~1 200 mg/d抗病毒治疗48~72周,随访24周。比较不同基因分型病毒性学应答率;比较不同丙氨酸氨基转移酶(ALT)水平与病毒学应答率的关系;观察慢性丙型肝炎患者病毒载量与疗效之间的关系。结果 256例患者中,获得快速病毒学应答率(RVR)166例(64.8%),早期病毒学应答率(EVR)243例(94.9%)和持续病毒学应答率(SVR)218例(85.2%);基因分型结果显示,157例基因1型(61.3%)与99例非1型(38.7%)感染者中SVR分别为83.4%和81.8%,两组比较差异无统计学意义(P0.05);按治疗前ALT水平分为高ALT水平组(ALT80 U/L)与低ALT水平组(ALT≤80 U/L),两组之间RVR、EVR及SVR无显著差异(P0.05);按HCV RNA基线水平,高病毒载量组(HCV RNA4×105IU/ml)RVR、ETVR和SVR均较低病毒载量组(HCV RNA≤4×105IU/ml)低,差异均有统计学意义(P0.05,P0.01);按是否获得SVR分为SVR组与非SVR组,非SVR组的年龄及病程明显高于SVR组,差异有统计学意义(P0.01)。结论 Peg IFNα-2α联合利巴韦林治疗慢性丙型肝炎能获得较高的EVR和SVR,年龄、病程及治疗前HCV RNA水平均是影响SVR的重要因素。     

乙肝肝硬化抗病毒治疗期间进展为原发性肝癌35例临床分析

【目的】探讨乙型肝炎肝硬化患者经抗病毒治疗后仍并发原发性肝癌(HCC)的原因。【方法】回顾性分析本院肝病科2012年6月至2015年6月收治的35例乙型肝炎肝硬化患者在抗病毒治疗期间并发原发性肝癌患者的临床资料、抗病毒治疗情况、相关疾病史等。【结果】35例患者中男性31例,女性4例；年龄大于40岁29例,小于40岁6例；7例有长期大量饮酒史,5例有长期吸烟史；6例合并有糖尿病,4例有 HCC 家族史(均为一级亲属)；乙型肝炎表面抗原(HBsAg)滴度在6000~9000 COI 所占比例最高,为57.13%；乙型肝炎 e 抗原 HBeAg 阳性8例,HBeAg 阴性27例；经规范抗病毒治疗后,23例乙型肝炎病毒载量(HBV-DNA)<20 IU/mL,11例20 IU/mL ﹤ HBV-DNA ﹤2.0×103 IU/mL,1例 HBV-DNA 为4.0×107 IU/mL。【结论】抗病毒治疗并不能完全消除乙型肝炎肝硬化患者并发 HCC 的风险,年龄大于40岁、男性、有肝癌家族史、长期饮酒、HBsAg 高滴度、HBV-DNA 阳性、糖尿病史等可能与 HCC 的发生相关。     

铁蛋白、甲胎蛋白和甲胎蛋白异质体检测对肝癌诊断及疗效评估的价值

[目的]探讨铁蛋白(FER)、甲胎蛋白(AFP)、甲胎蛋白异质体(AFP-L3)对肝癌诊断、疗效评估的价值.[方法]本院收治的肝癌患者80例作为肝癌组,选取同期收治的良性肝脏病患者80例作为良性肝病组.所有患者均于入院当日检测FER、AFP和AFP-L3水平,分析各指标对肝癌的诊断价值.肝癌患者均接受射频消融术治疗,于...     

Association between direct-acting antiviral agents in hepatitis C virus treatment and hepatocellular carcinoma occurrence and recurrence: The endless debate

Since direct-acting antiviral agents (DAAs) have been introduced into hepatitis C virus treatment, the sustained viral response (SVR) rate has significantly increased to more than 95%. Scientific evidence supports the idea that SVR after interferon therapy has beneficial effects related to cirrhosis progression, resulting in a reduction in the incidence of hepatocellular carcinoma (HCC). However, a significant debate exists related to DAA impact on HCC development. We reviewed the current literature highlighting the controversial data related to DAA association with de novo HCC occurrence or recurrence and possible pathophysiology of HCC related to DAAs. After a review of the published literature, we believe that the current evidence does not confirm or repudiate a higher rate of de novo HCC occurrence or recurrence related to DAA therapy. More trials are needed to determine if there is an association between HCC occurrence or recurrence and DAA or if it is related to preexisting liver cirrhosis.     

Long-term outcome after interferon therapy in elderly patients with chronic hepatitis C

OBJECTIVE: The purpose of this study was to elucidate the long-term outcome after interferon (IFN) therapy in chronic hepatitis C elderly patients. METHODS: We studied the incidence of hepatocellular carcinoma (HCC) and survival probability after the initiation of IFN therapy in 500 Japanese chronic hepatitis C patients >60 years. The mean age of initiation of IFN was 63 years and the mean follow-up period was 7.4 years. Cox proportional hazard regression analysis was used to evaluate the long-term outcome after initiation of IFN therapy. Sustained virological response (SVR) was defined as negative HCV-RNA by RT-nested PCR 6 months after the completion of long-term IFN therapy. Non-response (NR) was applied to patients who did not show SVR. Hepatic fibrosis was defined as the fibrosis score (score 0-4) according to Knodell et al. RESULTS: 140 patients (28%) had an SVR and 360 patients (72%) had an NR. 71 of 500 patients developed HCC during follow-up. The cumulative incidence of HCC was 9.6% at the 5th year, 17.4% at the 10th year, and 31.3% at the 15th year. HCC developed with significance when: (1) HCV was not cleared after IFN therapy (p < 0.0001), (2) sex was male (p < 0.0001), and (3) staging of liver fibrosis was >2 (p = 0.008). 53 of the patients died. The cumulative survival probability was 95.7% at the 5th year, 86.4% at the 10th year, and 78% at the 15th year. Patients achieved a long survival with significance when: (1) staging of liver fibrosis was 1 (p < 0.0001), (2) HCV was cleared after IFN therapy (p = 0.034), and (3) sex was female (p = 0.015). CONCLUSION: Chronic hepatitis C patients with clearance of HCV after IFN therapy had a significantly reduced risk of HCC appearance and achieved prolonged survival even if they are > or =60 years.     

HCV treatment with direct acting antivirals improves the insulin sensitivity

ABSTRACT

Background: There is strong link between hepatitis C virus (HCV) infection and the insulin resistance panel. Homeostatic model assessment (HOMA) β is an indirect measurement of insulin secretion from pancreatic β cells, while HOMA-S accounts for insulin sensitivity.

Aim: We examined the impact of HCV treatment with direct acting antivirals (DAAs) on HOMA-β and HOMA-S results.

Methods: HOMA-IR, HOMA-β, and HOMA-S were calculated before and 12 weeks after treatment in 511 treatment eligible patients with HCV. Five DAA treatment protocols were used. Values before and after treatment were compared.

Results: The mean age of patients was 50.63 years with a 3.2:1 male: female ratio. A total of 29.7% of patients were treatment experienced and 24.7% had diabetes. HCV sustained virological response (SVR) was achieved in 91% of patients. Unlike non-responders, SVR patients showed significantly decreased post-treatment HOMA-Β. Delta HOMA-Β was comparable between groups. HOMA-S increased significantly in patients with SVR compared to in non-responders, as did delta HOMA-S. HOMA-S and HOMA-β improved significantly under 5 and 2 DAA protocols, respectively. The treatment status did not affect the HOMA-β and S dynamics during treatment.

Conclusions: Insulin sensitivity improved markedly in patients who achieved HCV SVR.     

Successful treatment by glecaprevir/pibrentasvir followed by hepatoprotective therapy of acute chronic hepatitis exacerbation caused by daratumumab-based regimen for multiple myeloma: Case report and review of the literature

Hepatitis C virus (HCV) exacerbation is relatively rare as compared with hepatitis B virus reactivation in patients treated with immunosuppressive or anticancer drugs. We herein present the first reported case of acute exacerbation of chronic hepatitis in a patient with HCV persistent infection caused by combination treatment with daratumumab (DARA), bortezomib, and dexamethasone (DVd therapy). A 79-year-old woman diagnosed as having chronic HCV infection 11 years prior without successful viral elimination was referred to our hospital for the treatment of acute liver injury. Multiple myeloma (MM; IgG-κ type) was diagnosed two years before referral and subjected to several treatments. She had commenced DVd therapy four months prior to admission. Since her liver enzymes did not normalize with drug discontinuation and hepatoprotective therapy, we suspected HCV exacerbation and began direct-acting antiviral (DAA) treatment with glecaprevir/pibrentasvir (GLE/PIB). Soon afterwards, her liver enzymes normalized, and she achieved a sustained virological response after 8 weeks of treatment. Clinicians should bear in mind HCV exacerbation when encountering chronic HCV with acute liver injury under MM treatment including a DARA-based regimen. In such cases, DAA therapy is an option when other urgent treatments are needed.     

Interferon-free treatment choice according to baseline RASs leads to high SVR rates in HCV genotype 1 infected patients

Aim

Different combinations of direct antiviral agents (DAA) lead to high SVR rates in HCV genotype 1 infected patients. However, presence of baseline resistance-associated substitutions (RASs) represents a major risk factor for treatment failure. It is unknown whether choice of treatment based on RASs has the potential to decrease virologic failure rates.

Antiviral therapy for chronic hepatitis C in patients with inherited bleeding disorders: an international, multicenter cohort study

Summary. Background: Hepatitis C is a major co‐morbidity in patients with hemophilia. However, there is little information on the efficacy of antiviral therapy and long‐term follow‐up after treatment.Objectives: To assess the effect of interferon‐based (IFN‐based) therapy on hepatitis C virus (HCV) eradication, to identify determinants associated with treatment response, and to assess the occurrence of end‐stage liver disease (ESLD) after completing antiviral therapy.Patients and methods: In a multicenter cohort study, 295 treatment‐naïve hemophilia patients chronically infected with HCV were included. The effect of therapy was expressed as sustained virological response (SVR). Determinants associated with treatment response were expressed as odds ratios (ORs). Cumulative incidence of ESLD was assessed using a Kaplan–Meier survival table.Results: Among human immunodeficiency virus (HIV) negative patients (n = 235), SVR was 29% (29/101) for IFN monotherapy, 44% (32/72) for IFN with ribavirin, and 63% (39/62) for pegylated IFN (PegIFN) with ribavirin. In patients co‐infected with HIV (n = 60), IFN monotherapy, IFN with ribavirin, and PegIFN with ribavirin eradicated HCV in 7/35 (20%), 1/2 (50%), and 11/23 (48%), respectively. SVR increased with genotype 2 and 3 [OR 11.0, 95% CI: 5.8–20.5], and combination therapy (IFN and ribavirin OR 3.7, 95% CI: 1.7–8.4), PegIFN and ribavirin (OR 4.2, 95% CI: 1.8–9.5). Up to 15 years after antiviral treatment, none of the patients with a SVR relapsed and none developed ESLD. In contrast, among unsuccessfully treated patients the cumulative incidence of ESLD after 15 years was 13.0%.Conclusions: Successful antiviral therapy appears to have a durable effect and reduces the risk of ESLD considerably.     

Sustained virological response correlates with reduction in the incidence of glucose abnormalities in patients with chronic hepatitis C virus infection

OBJECTIVE: There is evidence to suggest that hepatitis C virus (HCV) infection is a high-risk condition for developing type 2 diabetes. However, there are no interventional studies that confirm that HCV infection causes diabetes. The main aim of this study was to compare the incidence of glucose abnormalities (diabetes plus impaired fasting glucose) between HCV-infected patients with or without sustained virological response (SVR) after antiviral therapy. RESEARCH DESIGN AND METHODS: Patients with normal fasting glucose (<100 mg/dl) with biopsy-proven chronic hepatitis C without cirrhosis and with at least 3 years of follow-up after finishing antiviral therapy were included in the study (n = 234). Patients received interferon alpha-2b (alone or with ribavirin) for 6 or 12 months according to genotype. Cumulative incidence of glucose abnormalities was evaluated by using the Kaplan-Meier method comparing subjects with and without a SVR to antiviral treatment. A multivariate Cox proportional hazards analysis was performed to explore the variables independently associated with the development of glucose abnormalities. RESULTS: During follow-up, 14 of 96 (14.6%) patients with SVR and 47 of 138 (34.1%) nonsustained responders developed glucose abnormalities (P = 0.001). Patients with SVR did not develop diabetes during follow-up, whereas nine cases of diabetes were detected in nonsustained responders (P = 0.007). After adjustment for the recognized predictors of type 2 diabetes, the hazard ratio for glucose abnormalities in patients with SVR was 0.48 (95% CI [0.24-0.98], P = 0.04). CONCLUSIONS: Our results provide evidence that eradication of HCV infection significantly reduces the incidence of glucose abnormalities in chronic hepatitis C patients. In addition, this study supports the concept that HCV infection causes type 2 diabetes.     

Current status of hepatitis C virus infection in Korea

Chronic liver disease, including liver cirrhosis and hepatocellular carcinoma (HCC), has been a major cause of mortality in Korea. The prevalence rates of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections in the general population of Korea are approximately 1 and 5%, respectively. The most common genotypes of HCV in Korea are 1b and 2a. The sustained virological response rates after antiviral therapies, including combined interferon-alpha and ribavirin, have been reported to be 38-59%. The annual incidence of HCC among HCV-related liver cirrhosis has been estimated at 5%, and approximately 12% of HCC is attributable to HCV and 68% to HBV in Korea. The mean age of patients with HCV-related HCC at the time of diagnosis was consistently 10 years older than that of patients with HBV-related HCC. Moreover, HCV-related HCC was accompanied by more advanced liver cirrhosis than HBV-related HCC. Coinfection with HBV seemed to increase the risk of developing HCC in chronic HCV infection. After the successful program of hepatitis B vaccination, HCV infection is now emerging as an important etiology of chronic liver disease in Korea, which warrants more detailed and large-scale studies.