慢性丙型肝炎抗病毒药物及其治疗方案研究进展

慢性丙型肝炎成为全球严重的公共卫生问题,近年来随着丙型肝炎的药物治疗不断发展,使丙型肝炎治愈成为可能。从丙型肝炎的流行现状,传统的标准治疗方案(聚乙二醇干扰素+利巴韦林)以及不同的口服小分子直接抗病毒药物(DAAs)的优势及副作用,总结了不同DAAs药物组合对于不同慢性丙型肝炎基因型治疗的利弊,并简要介绍了世界卫生组织对于丙型肝炎治疗的推荐意见。相信未来慢性丙型肝炎的药物治疗会不断飞跃,消灭丙型肝炎指日可待。     

慢性丙型肝炎治疗:更多的机遇,更多的挑战

自从聚乙二醇干扰素(PEG-IFN)α联合利巴韦林(RBV)应用于慢性丙型肝炎的治疗,并且基因2型或基因3型感染者可获得50%的持续病毒学应答(SVR)以来,PEG-IFN α联合RBV已经成为慢性丙型肝炎的标准治疗方案[1-2].     

聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎疗效观察

干扰素联合利巴韦林是我国<丙型肝炎防治指南>[1]推荐的治疗丙型肝炎的标准方案.我们对70例慢性丙型肝炎患者的感染途径、发现病情年限和治疗年限进行了调查,并给予聚乙二醇干扰素(PEG-IFN)α-2a联合利巴韦林治疗,现报道如下.     

慢性丙型肝炎的抗病毒治疗

198 9年首次报告丙型肝炎病毒 (ＨＣＶ)以来 ,慢性丙型肝炎的抗病毒治疗得到长足发展。大量的临床研究证实 :干扰素 (ＩＦＮ)治疗慢性丙型肝炎存在着应答和无应答两种状态。慢性丙型肝炎病程进展快 ,肝癌发生率高 ,抗病毒疗效不佳成为慢性丙型肝炎预后差的最主要原因。由于对慢性丙型肝炎的抗病毒治疗存在着不正确认识 ,造成一些医生进行慢性丙型肝炎抗病毒治疗时走入误区 ,影响抗病毒的疗效。本文将依据基础研究的结论阐述慢性丙型肝炎的抗病毒治疗。1　慢性丙型肝炎极差的预后要求抗病毒治疗通常致癌病毒将自己的基因插入宿主染色体中 ,引…     

干扰素治疗丙型肝炎的进展

丙型肝炎病毒(HCV)感染的临床过程和结局可能有很大的变化,大多数HCV病人会发生慢性肝病,约25％的慢性丙型肝炎(简称慢性丙肝)病人在3～20年内会发生肝硬化,出现晚期肝病的并发症,包括肝衰竭、门脉高压症和肝细胞癌。本文主要综述干扰素(IFN)治疗丙型肝炎的研究进展。 1.急性丙型肝炎的治疗 急性丙型肝炎(简称急性丙肝)的特点是70％以上会发展为慢性肝炎,在急性病变期间有效地治疗可以防止进展为慢性化。目前使用不同型和不同剂量的IFN治疗急性丙肝时,判断治疗反应的标准是检测HCV     

慢性丙型肝炎抗病毒治疗的新策略和新方法

随着聚合酶或蛋白酶抑制剂或治疗性疫苗联合PEG-IFN和RBV"三联"治疗的临床前和早期临床治疗阶段药物临床试验的结束,为未来慢性丙型肝炎的治疗提供了更加有效的治疗方法,同时在治疗策略方面的研究也取得了明显的进展。尽管聚乙二醇干扰素联合利巴韦林仍然是当前慢性丙型肝炎的标准治疗,但应答指导的个体化治疗使慢性丙型肝炎的治疗进入了一个新的时代,以PEG-IFN为基础联合特异性靶向抗病毒(STAT-C)的治疗将成为慢性丙型肝炎特别是难治型治疗的新方法。     

慢性丙型肝炎患者PBMC TBK1s表达

目的探讨蛋白激酶TBK1s在慢性丙型肝炎患者外周血单个核细胞（PBMC）的表达及其意义。方法采用实时荧光定量PCR法检测21例慢性丙型肝炎患者PBMC蛋白激酶TBK1、其剪接变体TBK1s和β-干扰素（IFN-β）水平。结果慢性丙型肝炎患者PBMC TBK1s水平显著性高于健康对照人群;经干扰素治疗的慢性丙型肝炎患者PBMC TBK1s表达与健康人比无显著性差异。结论 TBK1s水平与慢性丙型肝炎病毒感染相关,TBK1s可能在慢性HCV感染发病过程中发挥某种调空作用     

聚乙二醇化干扰素联合利巴韦林治疗慢性丙型肝炎疗效观察

丙型肝炎病毒（HCV）持续感染,可引起肝脏慢性炎症坏死和纤维化,如不积极治疗可进展至肝硬化和肝细胞癌（HCC）。聚乙二醇干扰素联合利巴韦林是目前慢性丙型肝炎（CHC）的标准治疗方案,本文对聚乙二醇干扰素联合利巴韦林治疗的58例慢性丙型肝炎患者疗效进行分析,现将结果报道如下。     

难治性丙型肝炎的治疗新进展

丙型肝炎病毒(HCV)感染后约50％-80％将发展为慢性肝炎,慢性丙型肝炎的患者一般多无症状,且平均40％的慢性丙型肝炎患者的ALT水平升高在2倍正常值以下而不能得到及时的诊断和治疗。对于慢性丙型肝炎的患者来说若不经过标准的抗病毒治疗,绝大多数的患者将发展为肝硬化甚至肝细胞癌。自1986年首次报道了干扰素(IFN)对慢性丙     

211例丙型肝炎患者10年随访观察

正慢性丙型肝炎是我们临床上常见的慢性肝病之一,易发生肝硬化甚至肝癌,预后较差,大量研究证实通过抗病毒治疗可以改善预后,我们通过对抗病毒治疗的211例慢性丙型肝炎患者采用回顾性调查与前瞻性研究相结合的方法定期随访,观察其预后,现总结报道如下。资料和方法一、临床资料211例慢性丙型肝炎均来自2004年1月至2015年12月我科住院及门诊治疗的患者,其诊断标准均符合2015年10月     

Daily or three times a week interferon alfa-2b in combination with ribavirin or interferon alone for the treatment of patients with chronic hepatitis C

BACKGROUND/AIMS: Data on hepatitis C virus (HCV) viral dynamics and on the effect of interferon in blocking virion production have suggested a rationale for daily administration of interferon in patients with chronic hepatitis C infection. We compared the efficacy and safety of daily interferon alfa-2b in combination with ribavirin with those of interferon alfa-2b three times a week alone or in combination with ribavirin. METHODS: We randomly assigned 321 patients with chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin for 48 weeks or daily interferon alfa-2b (3 million units per day for 12 weeks then 3 million units three times per week for 24 weeks) and ribavirin (36 week treatment). RESULTS: The rate of sustained virologic response (defined as an undetectable serum HCV-RNA level 72 weeks after initiation of treatment) was higher in patients who received combination therapy with three times weekly interferon (51.7%) or daily interferon (46.1%) than in patients who received interferon alone (25%) (P=0.0001 and P=0.002, respectively). Independent predictive factors for sustained virologic response were combination therapy, weight, genotype and viral load. In conclusion, in patients with chronic hepatitis C, combination therapy with induction treatment (daily interferon for 12 weeks) and shorter duration of treatment was not different from combination therapy for 48 weeks without induction treatment. CONCLUSIONS: Induction treatment with interferon for 12 weeks and combination therapy for a total duration of 36 weeks could therefore be cost effective.     

Influence of psychiatric diagnoses on interferon-alpha treatment for chronic hepatitis C in a veteran population

OBJECTIVE: The prevalence of psychiatric problems and substance abuse is high in the veteran population with hepatitis C. The purpose of this study was to retrospectively analyze the effect of preexisting psychiatric conditions in veteran patients undergoing treatment with interferon a-2b (IFN-alpha) with respect to adverse events, compliance, and treatment response. METHODS: Thirty-three veterans with chronic hepatitis C were treated with IFN-alpha (5 million units three times weekly) for 6 months, followed by a tapering dose for an additional 6 months. All patients fulfilled standard criteria for treatment eligibility. Psychiatric diagnoses, adverse events, and virological and biochemical responses to therapy were determined. RESULTS: Nineteen of 33 (58%) patients with hepatitis C had documented psychiatric conditions before starting IFN-alpha therapy. Of the patients with preexisting psychiatric diagnoses, 13/19 (68%) developed major adverse events requiring intervention or discontinuation of therapy. In contrast, 4/14 (29%) patients without psychiatric diagnoses developed major adverse events (p = 0.024) In the psychiatric group, 6/19 (32%) developed major neuropsychiatric side effects compared with 2/14 patients (14%) in the nonpsychiatric group (p = 0.25). Patients with and without psychiatric diagnoses had equivalent biochemical and virological responses to therapy. Overall, only 2/33 (6%) patients had a sustained virological response. CONCLUSIONS: Veterans with chronic hepatitis C and psychiatric diagnoses experienced a significantly greater number of major adverse events during treatment with IFN-alpha. Veteran patients with hepatitis C should be carefully screened for psychiatric conditions and may require more intensive monitoring during IFN-alpha therapy.     

Short-term interferon-alfa therapy for acute hepatitis C: a randomized controlled trial

Acute hepatitis C often progresses to chronic infection. We undertook a randomized controlled trial to determine whether short-term therapy with interferon (IFN) during acute hepatitis C is effective in preventing the development of chronic hepatitis. Thirty patients with acute hepatitis C were randomized into 1 of 2 treatment groups. IFN therapy was initiated 8 weeks after the onset of acute hepatitis in the early-intervention group and after 1 year of observation in the late-intervention group. Short-term therapy consisted of natural IFN-alfa (6 million units) administered on consecutive days for a period of 4 weeks. Any signs of recrudescence of disease were immediately followed by interval IFN therapy (3 times weekly for 20 weeks). In the early-intervention group, short-term therapy was associated with a sustained virological response in 13 of 15 patients (87%). Follow-up treatment was associated with a sustained virological response in both of the remaining 2 patients (100%). The sustained virological response rate was significantly higher in the early-intervention group (87%, 13 of 15 patients after short-term therapy alone, and 100%, 15 of 15 patients after short-term with or without follow-up therapy) than in the late-intervention group (40%, 6 of 15 patients after short-term therapy alone, and 53%, 8 of 15 patients after short-term therapy with or without follow-up therapy, P =.021 and P =.006, respectively). In conclusion, short-term (4 weeks) IFN treatment of patients with acute hepatitis C may be associated with satisfactory results, if initiated at an early stage of the disease.     

Treatment options of invasive fungal infections in adults

A panel of infectious disease specialists, clinical microbiologists and hospital epidemiologists of the five Swiss university hospitals reviewed the current literature on the treatment of invasive fungal infections in adults and formulated guidelines for the management of patients in Switzerland. For empirical therapy of Candida bloodstream infection, fluconazole is the drug of choice in non-neutropenic patients with no severe sepsis or septic shock or recent exposure to azoles. Amphotericin B deoxycholate or caspofungin would be the treatment option for patients with previous azole exposure. In neutropenic patients, empirical therapy with amphotericin B deoxycholate is considered first choice. In patients with severe sepsis and septic shock, caspofungin is the drug of first choice. For therapy of microbiologically-documented Candida infection, fluconazole is the drug of choice for infections due to C. albicans, C. tropicalis or C. parapsilosis. When infections are caused by C. glabrata or by C. krusei, caspofungin or amphotericin B deoxycholate are first line therapies. Treatment guidelines for invasive aspergillosis (IA) were stratified into primary therapy, salvage therapy and combination therapy in critically ill patients. Voriconazole is recommended for primary (ie upfront) therapy. Caspofungin, voriconazole (if not used for primary therapy) or liposomal amphotericin B are recommended for salvage therapy for refractory disease. Combination therapy with caspofungin plus voriconazole or liposomal amphotericin B should be considered in critically ill patients. Amphotericin B deoxycholate is recommended as initial therapy for the empirical therapy in patients with neutropenia and persistent fever with close monitoring of adverse events.     

Factors associated with failure of metronidazole in Clostridium difficile-associated disease

GOAL: To identify patients likely to fail metronidazole as initial treatment of C. difficile infection. BACKGROUND: For moderate to severe Clostridium difficile-associated diarrhea, metronidazole is the drug of choice for treatment. Oral vancomycin is given to patients who fail metronidazole or have intolerable side effects. STUDY: Retrospective review identified all patients treated for C. difficile-associated diarrhea during hospitalization from January 2000 to September 2001. C difficile was documented by a positive toxin assay or pseudomembranes on colonoscopy. Metronidazole failure was defined as persistent symptoms of C. difficile-associated diarrhea after 5 days of uninterrupted therapy. Response was defined as improvement in symptoms at day 5 of therapy including reduction of diarrhea to 相似文献   

3.0T 31P MR spectroscopy in assessment of response to antiviral therapy for chronic hepatitis C

AIM:To investigate the utility of phosphorus-31(31P)magnetic resonance spectroscopy(MRS)as a noninvasive test for assessment of response to interferon and ribavirin treatment in patients with different severities of hepatitis C virus infection.METHODS:Sixty chronic hepatitis C patients undergoing antiviral therapy with interferon and ribavirin underwent 31P MRS at 3.0T before treatment,6 mo after the start of treatment,and 1 year after the start of treatment.RESULTS:The phosphomonoester(PME)/phosphodiester(PDE)ratio at 6 mo after the start of antiviral therapy in the Child-Pugh B and C groups were significantly higher than those before therapy,but this was not seen in the Child-Pugh A group.In the antiviral therapy group,the PME/PDE ratios had decreased on follow-up MR spectroscopy.However,in the virological nonresponder group,the PME/PDE ratios on follow-up imaging were similar to the baseline values.CONCLUSION:31P MRS can be used to provide biochemical information on hepatic metabolic processes.This study indicates that the PME/PDE ratio can be used as an indicator of response to antiviral treatment in chronic hepatitis C patients.     

Evaluation of an intensified insulin treatment and teaching programme as routine management of Type 1 (insulin-dependent) diabetes

Summary It has been questioned whether aiming at near-normoglycaemia by intensified insulin treatment regimens is feasible and safe for the majority of patients with insulin-dependent diabetes. In this study, intensified insulin injection therapy (including blood glucose self-monitoring and multiple insulin injections) based upon a 5-day inpatient group teaching programme was evaluated in Type 1 (insulin-dependent) diabetes mellitus in the centralised health care system of Bucharest. One hundred patients (group A, initial HbA₁ 12.5%) were followed for 1 year on their standard therapy (individual teaching, no metabolic self-monitoring), and thereafter for 1 year on intensified therapy. Another 100 patients (group B, HbA₁ 12.3%) were followed for 2 years on intensified therapy. A third 100 patients (group C, HbA₁ 11.7%) were assigned to a basic 4-day inpatient group teaching programme with conventional insulin therapy (including self-monitoring of glucosuria and acetonuria) and followed for 1 year. Mean HbA₁ remained unchanged after standard treatment (group A: 12.8% at 12 months), but decreased during intensified therapy (group A: 10.1% at 24 months; group B: 9.3% at 12 months, 9.5% at 24 months; p<0.0001). In group C, no change was found compared to standard treatment (i.e. group A at 12 months). Incidence rates of ketoacidosis were 0.16 episodes per patient per year during standard treatment, 0.01 during intensified treatment (p<0.01) and 0.04 in group C (p<0.025). Hospitalisation rates were reduced by 60% during intensified therapy and by 40% in group C. Frequency of severe hypoglycaemia was not significantly different between the three treatment regimens. Thus, under the condition that insulin treatment is based upon a structured and comprehensive training of the patient, intensified insulin injection therapy performed as routine treatment of Type 1 diabetes significantly lowers HbA₁ levels without increasing the risk of severe hypoglycaemia.     

Response to pegylated interferon alpha-2b and ribavirin in children with chronic hepatitis C

GOALS: The purpose of this communication is to report our observations on the treatment of a diverse group of adolescent patients who were chronically infected with hepatitis C and received pegylated interferon and ribavirin. BACKGROUND: The currently accepted optimal therapy for adults with chronic hepatitis C is weekly injections of pegylated interferon and twice daily oral ribavirin. Information on interferon alone or in combination with ribavirin for chronic hepatitis C in children is limited. There is no published information on pegylated interferon and ribavirin in pediatric patients who previously failed interferon therapy. REPORT: Ten patients 11 to 18 years old received weekly pegylated interferon and twice daily ribavirin for hepatitis C. Treatment continued for 48 weeks, except for 1 patient with hepatitis C virus type 3a who was treated for 24 weeks and 1 patient who did not complete the course of treatment. The period of observation continued from November 2002 to December 2004. Within this group were 3 pediatric patients who had previously failed interferon therapy for hepatitis C. RESULTS: All but 1 patient had a viral response (no detectable virus) at some time during or after the treatment. Three patients achieved sustained viral response (no detectable virus 6 mo after the therapy). One patient who previously failed interferon therapy was among the sustained responders. CONCLUSIONS: In response to treatment with pegylated interferon and ribavirin, children and adolescents with chronic hepatitis C achieve results similar to those seen in adults. Previous antiviral therapy does not preclude positive response to pegylated interferon and ribavirin.     

Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C

Interferon-based regimens for the treatment of chronic hepatitis C have become increasingly effective and are able to eradicate virus in more than one half of cases. Early identification of patients who will not respond is desirable because treatment might be stopped, thereby avoiding the expense and inconvenience of unnecessary therapy. We examined the accuracy of different degrees of viral inhibition during the early weeks of treatment (early virologic response [EVR]) with pegylated interferon alfa-2b and ribavirin (PEG/R) in identifying patients who would not respond to therapy. The best definition of EVR was a reduction in hepatitis C virus (HCV) RNA by at least 2 logs after the first 12 weeks of treatment compared with baseline. Between 69% and 76% of patients achieved this threshold, depending on the treatment regimen, and sustained virologic response (SVR) occurred in 67% to 80% of these patients. Patients who did not reach EVR did not respond to further therapy. If treatment had been stopped in patients without EVR, drug costs would have been reduced by more than 20%. In conclusion, early confirmation of viral reduction following initiation of antiviral therapy for chronic hepatitis C is worthwhile. It provides a goal to motivate adherence during the first months of therapy and a milepost at which to reassess the need for continued treatment. Most patients who are able to complete the first 12 weeks of therapy achieve EVR and have a high probability of SVR. Patients who fail to achieve EVR will not clear virus even if an additional 9 months of therapy is received. Therapy can be confidently discontinued in those cases.     

Use of lactoferrin for Helicobacter pylori eradication. Preliminary results

BACKGROUND: One-week triple therapy is the most frequently recommended treatment of Helicobacter pylori infection. The associated eradication rate is satisfactory; nevertheless, it is advisable to look for more effective therapies. Our aim was to test the efficacy of a standard triple therapy plus bovine lactoferrin for the eradication of H. pylori infection. STUDY: This open, randomized, single-center study was designed to include 150 consecutive H. pylori-positive patients with dyspeptic symptoms and gastritis who received triple therapy with rabeprazole, clarithromycin, and tinidazole plus lactoferrin for 7 days (group A), rabeprazole, clarithromycin, and tinidazole for 7 days (group B), or rabeprazole, clarithromycin, and tinidazole for 10 days (group C). H. pylori status was assessed 8 weeks after the end of treatment by means of the 13C-urea breath test or H. pylori stool antigen test. RESULTS: The 7-day treatment including lactoferrin (group A) was successful in 100% (24/24) of the patients. The eradication rates in groups B and C were 76.9% (20/26 patients; 95% CI, 61%-93%) and 70.8% (17/24 patients; 95% CI, 53%-89%), respectively. A significant difference was found between group A and group B (P = 0.023) and group A and group C (P = 0.022). No differences were found between group B and group C (P = 1.00). CONCLUSION: These results suggest that lactoferrin could be a new, effective agent when added to antimicrobial therapy for the eradication of H. pylori. This treatment schedule could be proposed for larger trials of H. pylori eradication therapy, focusing on the excellent preliminary cure rate, good compliance to the treatment schedule, and relatively low price of lactoferrin for full treatment.