拉米夫定联合干扰素-α2b治疗慢性乙型肝炎68例

抗病毒治疗是慢性乙型肝炎治疗的关键，临床大量资料表明单一抗病毒治疗疗效不理想。联合用药已成为慢性乙型肝炎治疗的新出路。本院应用拉米夫定联合干扰素-α2b治疗慢性乙型肝炎68例。达到协同抗病毒作用。     

拉米夫定联合干扰素延长疗程对e抗原阳性慢性乙型肝炎患者表面抗原转换的作用

慢性乙型肝炎(CHB)的治疗,目前有两类抗病毒药物--核营(酸)类似物单用存在耐药问题、单药干扰素(IFN)的疗效有限.本研究回顾性探讨拉米夫定(LAM)联合IFN治疗CHB的疗效,分析其可能的作用机制.     

拉米夫定联合干扰素延长疗程对e抗原阳性慢性乙型肝炎患者表面抗原转换的作用

慢性乙型肝炎(CHB)的治疗,目前有两类抗病毒药物--核营(酸)类似物单用存在耐药问题、单药干扰素(IFN)的疗效有限.本研究回顾性探讨拉米夫定(LAM)联合IFN治疗CHB的疗效,分析其可能的作用机制.     

拉米夫定联合干扰素延长疗程对e抗原阳性慢性乙型肝炎患者表面抗原转换的作用

慢性乙型肝炎(CHB)的治疗,目前有两类抗病毒药物--核营(酸)类似物单用存在耐药问题、单药干扰素(IFN)的疗效有限.本研究回顾性探讨拉米夫定(LAM)联合IFN治疗CHB的疗效,分析其可能的作用机制.     

拉米夫定联合干扰素延长疗程对e抗原阳性慢性乙型肝炎患者表面抗原转换的作用

慢性乙型肝炎(CHB)的治疗,目前有两类抗病毒药物--核营(酸)类似物单用存在耐药问题、单药干扰素(IFN)的疗效有限.本研究回顾性探讨拉米夫定(LAM)联合IFN治疗CHB的疗效,分析其可能的作用机制.     

拉米夫定联合干扰素延长疗程对e抗原阳性慢性乙型肝炎患者表面抗原转换的作用

慢性乙型肝炎(CHB)的治疗,目前有两类抗病毒药物--核营(酸)类似物单用存在耐药问题、单药干扰素(IFN)的疗效有限.本研究回顾性探讨拉米夫定(LAM)联合IFN治疗CHB的疗效,分析其可能的作用机制.     

拉米夫定联合干扰素延长疗程对e抗原阳性慢性乙型肝炎患者表面抗原转换的作用

慢性乙型肝炎(CHB)的治疗,目前有两类抗病毒药物--核营(酸)类似物单用存在耐药问题、单药干扰素(IFN)的疗效有限.本研究回顾性探讨拉米夫定(LAM)联合IFN治疗CHB的疗效,分析其可能的作用机制.     

拉米夫定联合干扰素延长疗程对e抗原阳性慢性乙型肝炎患者表面抗原转换的作用

慢性乙型肝炎(CHB)的治疗,目前有两类抗病毒药物--核营(酸)类似物单用存在耐药问题、单药干扰素(IFN)的疗效有限.本研究回顾性探讨拉米夫定(LAM)联合IFN治疗CHB的疗效,分析其可能的作用机制.     

拉米夫定联合干扰素延长疗程对e抗原阳性慢性乙型肝炎患者表面抗原转换的作用

慢性乙型肝炎(CHB)的治疗,目前有两类抗病毒药物--核营(酸)类似物单用存在耐药问题、单药干扰素(IFN)的疗效有限.本研究回顾性探讨拉米夫定(LAM)联合IFN治疗CHB的疗效,分析其可能的作用机制.     

拉米夫定联合干扰素延长疗程对e抗原阳性慢性乙型肝炎患者表面抗原转换的作用

慢性乙型肝炎(CHB)的治疗,目前有两类抗病毒药物--核营(酸)类似物单用存在耐药问题、单药干扰素(IFN)的疗效有限.本研究回顾性探讨拉米夫定(LAM)联合IFN治疗CHB的疗效,分析其可能的作用机制.     

Combination of "low-dose" ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected non-responders and relapsers after interferon alfa-2a monotherapy

AIM: To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a low dose of ribavirin for relapsers and non-responders to alpha interferon monotherapy. METHODS: Thirty four chronic hepatitis C virus-infected non responders to interferon alfa-2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa-2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10mg/kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy. RESULTS: Seven (20.6%) of 34 non responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%) non responders, the combined therapy was stopped after three months because of non response. Ten of the 27 non responders completed the 12 month treatment course. At a mean follow up of 28 months (16-37 months) after the treatment, 4/10 (15%) previous non responders still remained complete responders. All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22 months (9-36 months) after treatment, 6/13 (46%) the previous relapsers were still sustained complete responders. CONCLUSION: Our treatment schedule of the combined therapy for 6 months of interferon Alfa-2a with a low dose of ribavirin (10mg/kg/day) followed by 6 months of interferon Alfa-2a monotherapy is able to induce a sustained complete response rate in 15% of non responders and 46% of relapsers with chronic hepatitis C virus related liver diseases comparable to those obtained with the standard doses of ribavirin 1000-1200 mg/day. Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be performed.     

干扰素治疗慢性乙型肝炎时e抗原血清学转换的相关因素

目的探讨HBeAg阳性慢性乙型肝炎在聚乙二醇干扰素α-2a（PEG-IFN α-2a）治疗过程中HBeAg血清学转换和病毒学应答的相关因素，HBeAg血清学转换与HBV DNA应答的相关性。方法患者采用PEG-IFNα-2a每次180μg，皮下注射，每周1次，共治疗48周，治疗结束后随访24周。用Abbott公司生产的第三代HBV血清学检测试剂和AXSYM自动酶标检测仪检测血清HBeAg、抗-HBe，实时荧光定量PCR检测HBVDNA载量，分析不同治疗阶段和随访结束的病毒学应答率（HBV DNA〈1．0×10^5拷贝／ml），HBeAg血清转换率及变化规律和影响病毒学应答和HBeAg血清转换的因素。结果治疗12周和随访结束时HBeAg血清转换组和非转换组的ALT水平比较，差异有统计学意义。病毒学应答无论在治疗期还是随访结束时，应答组与非应答组之间的ALT水平差异均有统计学意义。HBeAg血清学转换与非转换组之间的HBV DNA载量之间在治疗12周、治疗结束和随访结束时，差异无统计学意义。治疗期间病毒学应答与非应答组的HBV DNA载量之间的差异有统计学意义，但持续病毒学应答与HBV DNA载量无显著相关性。治疗12、24周和48周获得病毒学应答组的HBeAg血清转换率分别为43．8％、21．4％和18．9％。治疗12、24周和48周时病毒学应答组，在随访结束时的HBeAg的血清转换率分别为42．9％、33．3％和27．6％。多因素分析显示，治疗72周的HBeAg血清转换与治疗结束时的HBV DNA阴转显著相关（OR=2．15，95．0％CI=1．744-2．664，P〈0．01）。结论治疗12周和持续HBeAg血清学转换以及病毒学应答均与ALT基线水平相关，HBeAg血清学转换与基础HBV DNA载量无关，但与治疗过程中病毒学应答相关。     

Cardiovascular manifestations associated with interferon alfa-2A]

Interferon-alpha is currently prescribed for many viral and neoplastic diseases; however, its side effects are poorly known. In this study, cardiovascular manifestations were specifically evaluated in 138 patients given interferon-alpha 2a for various dermatological diseases between 1987 and 1990. These patients were subjected to an indepth cardiovascular examination before the initiation of therapy and were monitored regularly throughout the treatment period. Six cardiac manifestations (4.3%) were observed, among which one unreported complete atrioventricular block. These side effects occurred at low doses (3-12 x 10(6) IU) in patients whose mean age was 63 years; 5 of the 6 patients had had previous cardiovascular incidents. These events seem to be independent of the cumulated dose. These findings draw attention to the cardiovascular side effects of interferon-alpha and advise prudence in high-risk patients.     

Psychiatric side effects of pegylated interferon alfa-2b as compared to conventional interferon alfa-2b in patients with chronic hepatitis C

AIM: To assess systematically the spectrum and extent of depressive symptoms comparing patient groups receiving peginterferon or conventional interferon. METHODS: Ninety-eight patients with chronic hepatitis C and interferon-based therapy (+ribavirin) were consecutively enrolled in a longitudinal study. Patients were treated with conventional interferon alfa-2b (48/98 patients; 5 MIU interferon alfa-2b thrice weekly) or peginterferon alfa-2b (50/98 patients; 80-150 μg peginterferon alfa-2b) in combination with weight-adapted ribavirin (800-1 200 mg/d). Repeated psychometric testing was performed before, three times during and once after antiviral therapy: Depression was evaluated by the Hospital Anxiety and Depression Scale (HADS), anger/hostility by the Symptom Checklist-90 Items Revised (SCL-90-R). RESULTS: Therapy with pegylated interferon alfa-2b produces comparable scores for depression (ANOVA: P = 0.875) as compared to conventional interferon. Maximums of depression scores were even higher and cases of clinically relevant depression were frequent during therapy with peginterferon. Scores for anger/hostility were comparable for both therapy subgroups. CONCLUSION: Our findings suggest that the extent and frequency of depressive symptoms in total are not reduced by peginterferon. Monitoring and management of neuropsychiatric toxicity especially depression have to be considered as much as in antiviral therapy with unmodified interferon.     

A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C

This international, randomized, active-controlled, parallel-group, double-blind dose-finding study compared peginterferon alfa-2b (PegIntron) to interferon alfa-2b for the initial treatment of compensated chronic hepatitis C. We randomly assigned 1,219 subjects to receive either the standard three-times-weekly (TIW) interferon alfa-2b dose (3 MIU) or the once-weekly (QW) peginterferon alfa-2b (0.5, 1.0, or 1.5 microg/kg). Subjects were treated for 48 weeks and then followed for an additional 24 weeks. All 3 peginterferon alfa-2b doses significantly (P < or =.042) improved virologic response rates (loss of detectable serum HCV RNA) after treatment and after follow-up, as compared with interferon alfa-2b. Unlike the end-of-treatment virologic response, the sustained virologic response rate was not dose-related above 1.0 microg/kg peginterferon alfa-2b because of a higher relapse rate among patients treated with 1.5 microg/kg peginterferon alfa-2b, particularly among patients infected with genotype 1. All 3 peginterferon alfa-2b doses decreased liver inflammation to a greater extent than did interferon alfa-2b, particularly in subjects with sustained responses. No new adverse events were reported, and the majority of adverse events and changes in laboratory values were mild or moderate. In conclusion, peginterferon alfa-2b maintained (0.5 microg/kg) or surpassed (1.0, 1.5 microg/kg) the clinical efficacy of interferon alfa-2b while preserving its safety profile. The higher rate of virologic response during treatment with 1.5 microg/kg peginterferon alfa-2b in patients infected with genotype 1 and high viral levels warrants further evaluation.     

Effect of ribavirin in genotype 1 patients with hepatitis C responding to pegylated interferon alfa-2a plus ribavirin

BACKGROUND & AIMS: Pegylated interferon alfa-ribavirin combination is the standard treatment for chronic hepatitis C, but the mechanisms by which ribavirin enhances the rate of sustained hepatitis C virus (HCV) eradication remain unknown. We aimed to investigate the role of ribavirin in HCV clearance during therapy and to evaluate the consequences of ribavirin discontinuation in patients infected with genotype 1 hepatitis C who cleared HCV RNA at week 24. METHODS: A total of 516 patients were treated with pegylated interferon alfa-2a, 180 microg/wk, plus ribavirin, 800 mg/day. Seventy percent were RNA negative at week 24. They were randomized to continue with the combination or receive pegylated interferon alone. RESULTS: Responders at week 24 who stopped ribavirin had a significantly higher rate of breakthroughs during, and relapses after, therapy (sustained virologic response, 52.8% vs 68.2%; P = .004), but their side-effect profile and quality of life tended to improve. Multiple logistic regression analysis in the pegylated interferon alfa monotherapy group allowed identification of responders at week 24 who could stop ribavirin without losing their chance of a sustained virologic response, based on baseline viral load and age. Forty-eight weeks of ribavirin may not be needed when HCV RNA is undetectable at week 2. CONCLUSIONS: We made 3 conclusions from this study. First, ribavirin primarily acts by sustaining the virologic response to pegylated interferon alfa; second, ribavirin must be administered for the full treatment duration in most genotype 1-infected patients who respond; third, baseline parameters may help identify patients who could discontinue ribavirin or reduce the dose without losing their chance of success.     

干扰素-α2b治疗非母婴传播HBeAg阳性慢性乙型肝炎患者疗效分析

目的 探讨非母婴传播HBeAg阳性慢性乙型肝炎（CHB)患者应用干扰素α2b抗病毒治疗的疗效。方法 选择2013年我院收治的非母婴传播的HBeAg阳性CHB患者13例,以同期母婴传播的HBeAg阳性CHB患者19例作为对照,应用国产干扰素α2b抗病毒治疗48周。采用化学发光免疫分析法测定血清HBV标志物,采用罗氏ABI 7500实时定量PCR系统检测血清HBV DNA定量。结果 在治疗24周和48周,两组完全应答率分别为15.4%、30.8%和15.8%、26.3% （P>0.05);在治疗48周,非母婴传播组血清HBsAg定量低于1500 IU/ml的发生率46.2%,显著高于母婴传播组的22.2% （P=0.045);在疗程结束后24周,非母婴传播组发生完全应答率为38.5%,显著高于母婴传播组的5.3% （P=0.029)。结论 非母婴传播HBeAg阳性CHB患者应用干扰素α2b抗病毒治疗可获得更高的持续应答率。     

Acute pancreatitis attributed to the use of interferon alfa-2b

Two patients experienced episodes of acute pancreatitis shortly after starting treatment with interferon alfa-2b (IFN-alpha) for a chronic hepatitis C infection. The first patient was a 40-year-old man who developed acute pancreatitis after 15 weeks of treatment with 3 MU IFN-alpha subcutaneously (SC) 3 times weekly and 1200 mg ribavirin. After disappearance of symptoms and normalization of laboratory values, oral intake of solid foods and IFN-alpha therapy were restarted. Within hours, a relapse of acute pancreatitis occurred. A rechallenge with IFN-alpha 4 days later was followed by a prompt increase in serum lipase level, and IFN-alpha therapy was discontinued. The second patient was a 38-year-old man who developed acute pancreatitis 2 hours after SC administration of 5 MU IFN-alpha. Ultrasound endoscopy showed sludge in the gallbladder. The patient was rechallenged 5 weeks later with 3 MU IFN-alpha SC. Although serum amylase and lipase levels increased after readministration of IFN-alpha, treatment was continued. The patient was readmitted 2 weeks later with severe abdominal pain, and IFN-alpha administration was discontinued. Considering the temporal relationship between the start of IFN-alpha treatment and development of acute pancreatitis, the absence of other clear etiologic factors for acute pancreatitis, disappearance of symptoms after discontinuation of IFN-alpha, and positive reactions to rechallenge, IFN-alpha is the most probable cause for development of acute pancreatitis in these patients.