干扰素联合病毒唑治疗丙型肝炎疗效观察

将29例病人随机分为3组,于治疗结束时复查其ALT、HCV-RNA作疗效比较,结果表明干扰素联合病毒哇组ALT的复常率为75％,HCV-RNA阴转率为40％,干扰素治疗组ALT的复常率为54.54％,HCV-RNA阴转率为25％;病毒唑组ALT的复常率为50％,HCV-RNA阴转率为0,即联合组疗效优于其它2组。     

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     

口含干扰素治疗丙型肝炎16例

我们采用口含干扰素治疗丙型病毒性肝炎16例,临床疗效观察如下。 1 临床资料 所有病例均为1993年～1995年住院与门诊病人,男11例,女5例,年龄25～69岁,输血史者13例,输血浆2例,多次行光量子者1例,符合上海会议急性病毒性肝炎标准13例,慢性活动型肝炎3例,全部由HCV-RNA检查确诊。其中3例原有慢性活动型乙型肝炎。     

病毒唑联合重组干扰素治疗慢性丙型肝炎疗效观察

为探讨治疗慢性丙型肝炎较好的方法；本文采用病毒唑联合重组基因干扰素治疗３４例慢性丙型肝炎，并以单用ＩＦＮ－α２ｂ治疗的２８例为对照。结果；联合用药组的ＨＣＶ ＲＮＡ转阴率为５８．８２％，与对照组比差异显著；故认为，ＩＦＮ－α２ｂ联合病毒唑治疗慢性丙型肝炎比单用ＩＦＮ－α２ｂdisplay structure     

干扰素治疗慢性丙型肝炎的临床研究进展

近几年国际上广泛地开展了对丙型肝炎抗病毒治疗的研究。用基因工程干扰素进行的随机对照研究表明,该药治疗丙型肝炎有一定效果。 1 治疗对象的基本条件 ①ALT持续异常超过半年,且高于正常值上限的5倍。②有明显的临床症状,诊断为慢性肝炎。③有丙肝病毒(HCV)感染的血清学或流行病学证据。     

干扰素治疗丙型肝炎的现况与展望

自从１９８９年明确丙型肝炎病毒（ＨＣＶ）的分子结构以来，丙型肝炎（简称丙肝）的研究大大地推进。丙肝是当前西方国家中最重要的病毒性肝炎，人群中ＨＣＶ感染率为１％～２％，而在某些高危人群，如静脉药瘾者中高达６０％以上。据估计。美国至少有５００万慢性丙肝病人，成为治疗的棘手问题。慢性丙肝的危害性在于经过约２０年的发展，至少约２０％可演变为肝硬化，部分病人可发展为肝细胞肝癌。美国国立卫生研究院（ＮＩＨ）于１９９７年邀请欧美２５位专家就丙肝的病毒学、临床、诊断、预防和治疗进行讨论，并达成了一定的共识（编者…     

干扰素治疗丙型肝炎致出血1例

患者,男,50岁,干部。2年前因手术输血后检查发现PCR-HCV-RNA( ),诊断为慢性丙型肝炎。近4个月来用进口干扰素600万U～300万U肌注/每日,到300万U肌注/隔日,在院外治疗。因持续牙龈出血1天于1995年12月22日入院。体检:BP14/10kPa,HR80次/分,T36℃,R20次/分。腰部活动受限,腰椎下部压痛,四肢皮肤可见散在出血点紫癜,暗红色压之不褪色,以双前臂、双下腿为     

水剂和粉剂干扰素治疗慢性丙型肝炎的对照观察

目前慢性丙型肝炎（丙肝）的治疗以α干扰素为首选［１,２］,近年来推出了干扰素的一种新剂型———水剂干扰素（ＬｉｑｕｉｄＨＳＡＦｒｅｅＲｏｆｅｒｏｎＡ）,该剂型以合成的稳定剂取代了人血白蛋白,减少血源污染可能,应用方便,且可从瓶中分次抽取,便于剂量控制,减少浪费。为观察新剂型（水剂）与以往剂型（粉剂）的疗效,进行小样本的对比观察,现报告如下。材料和方法一、研究对象１９９７年１０月～１９９８年１２月上海第二医科大学瑞金医院传染科门诊的慢性丙肝患者１０例,女１例,男,９例;年龄１８～４４岁,采用配…     

Assessment of histological features and outcome of interferon therapy in chronic hepatitis C

The correlation between the histological features of liver biopsy specimens before interferon (IFN) treatment and the clinical effect of IFN administration on chronic hepatitis C was investigated. A study of the relation between several histological features that were graded in 60 liver biopsy specimens from chronic hepatitis C patients before IFN treatment disclosed that the grade of portal fibrosis was positively correlated with the grade of other inflammatory features, including piecemeal necrosis and portal and lobular inflammation. The degree of portal fibrosis adversely affected the rate of normalization of ALT levels in chronic hepatitis C during and after IFN treatment. We reexamined 36 liver biopsy specimens that showed a moderate degree of portal fibrosis, and found that the degree of piecemeal necrosis was inversely correlated with the extent of lymphoid follicle formation in the portal tracts. During IFN therapy, the group of chronic hepatitis C patients who showed marked piecemeal necrosis and less lymphoid follicle formation in the liver specimens had a poor response to IFN treatment, whereas another group that showed marked lymphoid follicle formation and little piece-meal necrosis in the liver specimens had a good response to IFN. These relationships gradually disappeared after the completion of IFN treatment.     

Pretreatment symptoms and dosing regimen predict side-effects of interferon therapy for hepatitis C

We analysed data from a multicentre interferon (IFN) treatment trial to evaluate symptoms in patients with chronic hepatitis C and to identify factors that might predict development of debilitating IFN side-effects. Two hundred and twenty-two patients (120 US, 102 French) received 3 or 5 million units (MU) of IFN-α three times weekly (t.i.w.) for 3 months. Those who had detectable hepatitis C virus (HCV) RNA, as detected by the branched DNA signal amplification (bDNA) assay, at 3 months were intensified to daily therapy, while patients who were bDNA negative continued t.i.w. dosing for the subsequent 3 months of treatment. Symptoms were assessed at baseline, and adverse effects were evaluated at 6 months of therapy. Prior to treatment, the most common symptom that interfered with daily functioning was fatigue, occurring in 25% of patients. The frequency of debilitating fatigue, myalgia, arthralgia, headache, the presence of dry eyes and dry mouth, and use of antidepressant medication increased significantly from baseline to 6 months of IFN therapy (all P  < 0.01). In multivariate analysis, the development of a debilitating side-effect at 6 months of treatment was associated with the presence of that symptom prior to therapy in all cases. Symptoms and adverse effects varied by gender and country. Compared with patients maintained on t.i.w. dosing, those who were dose intensified to daily IFN reported more debilitating fatigue, malaise, myalgia, arthralgia, fever, nausea, and headache, and the presence of dry mouth (all P  < 0.05). In conclusion, patient characteristics, including pretreatment symptoms, gender and nationality, as well as daily IFN dosing are associated with the development of debilitating adverse effects on IFN therapy.     

Treatment of hepatitis C with interferon and ribavirin

Hepatitis C is a worldwide problem that frequently results in end-stage liver disease and its complications. Treatment for hepatitis C virus (HCV) has been rather ineffective but several recent studies have clarified the role of interferon and ribavirin therapy. In line with therapeutic progress in HIV infection, hepatitis C is now entering the era of multidrug antiviral therapy. Ribavirin is an orally active synthetic guanosine analogue with theoretical antiviral and immunomodulatory actions. In this review we have evaluated the role of interferon and ribavirin in treatment-naive patients, relapsers and non-responders. In naive patients the combination results in improved end-of-treatment and sustained response rates, with an overall 41% sustained virological response rate in patients treated for 48 weeks. Therapeutic benefit also extends to the traditionally difficult to treat patients (genotype 1, high vital load and advanced fibrosis). The addition of ribavirin to interferon has also resulted in an increased toxicity profile, which has made therapy more difficult for both the patient and managing physician. However, the significant improvement in response rates for all patients makes combination therapy the most appropriate choice as the first-line therapy for suitable patients with chronic viral hepatitis C. Appropriate management with interferon and ribavirin includes assessing the patient's HCV genotype to determine the optimal duration of therapy, assessing therapeutic efficacy by measuring HCV-RNA at 24 weeks and monitoring for the additional ribavirin side-effects.     

Predicting interferon therapy efficacy from hepatitis C virus genotype and RNA titer

We classified 53 Japanese patients with chronic hepatitis C who were treated with natural interferon- into genotypes and also tested the amounts of hepatitis C virus (HCV) RNA. The rate of the long-term complete response group, whose alanine aminotransferase levels remained within the normal range during the six months after therapy, was significantly higher (P<0.01) in the type-III patients (4/5, 80.0%) than in type-II patients (4/43, 9.3%). For these long-term complete responders, the amounts of HCV RNA was less than 10⁷ copies/ml serum in type-II patients, whereas two type-III patients with relatively high amounts of HCV RNA responded completely. These results confirm that the genotype of HCV is an important factor for predicting the response to interferon therapy. The amounts of HCV RNA can also predict its efficacy in type-II patients.This work was supported by a Grant-in-Aid from the Ministry of Education, Science and Culture, Japan, and the Research Group of Intractable Hepatitis sponsored by the Ministry of Health and Welfare of Japan.     

A model to predict long-term sustained response to interferon therapy in chronic hepatitis C

Interferon therapy is used widely for chronic hepatitis C but only a minority of treated patients achieve a long-lasting sustained response. We have developed, by logistic regression, a mathematical model to estimate the probability of sustained response in an individual patient with chronic hepatitis C when treated with interferon-α (IFN-α). The model, which includes age, sex, disease duration, pretreatment serum γ-glutamyl-transpeptidase, alanine aminotransferase and virus genotype, was developed from a database of 307 patients and validated in a new set of 200 patients. It performed well as goodness-of-fit ( P = 0.71 and P = 0.15 in the development and test sample, respectively) and discrimination (area under receiver operating curve = 0.79 in the development and 0.78 in the test sample, respectively). This model may provide decision support in the treatment of chronic hepatitis C with IFN-α.     

Relationship between serum HCV markers and response to interferon therapy in chronic hepatitis C

Hepatitis C virus is the most frequent cause of chronic non-A, non-B hepatitis, and the antibodies to structural and nonstructural proteins encoded by viral genome have been suggested to be markers of ongoing HCV infection. We studied the behavior of these antibodies during interferon therapy in 18 patients with chronic hepatitis C and also during a follow-up period of at least four years. A significant decrease of anti-HCV titer was found only in patients who had shown positive response to therapy and all of them were anti-HCV negative at the end of follow-up. Analysis by recombinant immunoblotting assay showed that only anti-c100 were affected by interferon therapy, whereas anti-c22 and anti-c33 were not modified. Using polymerase chain reaction to detect small amounts of HCV genome in serum, we could confirm that the behavior of HCV-RNA during and after interferon therapy is similar to that of anti-HCV and the loss of anti-c100 seems to be closely related to HCV-RNA disappearance from serum. Our patients with chronic hepatitis C were found to be of type 1b and 2, according to the recent score of Simmonds, and the clearance of serum HCV-RNA during treatment and its sustained negative status are closely related to genotype 2 and to long-term positive response to interferon.     

Hepatic fas antigen expression before and after interferon therapy in patients with chronic hepatitis C

To assess the relationship between hepatitis C virus infection and Fas antigen expression on hepatocytes, we examined changes in hepatic Fas antigen expression in the presence or absence of active hepatitis C virus infection. Twenty patients with chronic hepatitis C infection were treated with interferon and underwent pre- and posttreatment liver biopsies. Patients were classified according to the absence (group A; n=9) or the presence (group B; n=11) of hepatitis C virus RNA (HCV-RNA) in the liver after interferon therapy. An immunohistochemical assay showed Fas antigen staining in hepatocytes membranes and cytoplasm with expression concentrated mainly in periportal areas. The percentage of Fas-positive cells in the liver before treatment was not different between group A (39.5 ± 19.1%) and group B (32.5 ± 15.6%). Hepatic Fas expression was reduced significantly after treatment (24.3 ± 10.6%) compared with the pretreatment values in group A (p < 0.05) but not in group B (25.9 ± 16.9%). There was no significant difference between the two groups in the degree of histologic improvement. These results suggest that hepatic Fas expression is associated with persistent infection of hepatitis C virus.     

Effects of combination therapy with interferon and ofloxacin on chronic type C hepatitis: A pilot study

Interferon is effective in only a limited number of patients with the 1b type of hepatitis C virus (HCV), indicating that a combination therapy with other antiviral drugs may be essential to obtain better results. In the present pilot study, the effects of a combination therapy with interferon (IFN) and an antibacterial drug, ofloxacin, were analysed. Ten patients with chronic type C hepatitis received the combination therapy (combination group). Six million units of natural IFN-α were administered daily for 3 weeks and then three times a week for 21 weeks. The combination therapy was initiated at the beginning of the eighth week of IFN treatment and 600 mg ofloxacin per day was administered for 12 weeks. As a control, changes in HCV-RNA were also analysed in patients who were treated with only IFN for the same period (IFN-alone group). In the combination group, serum transaminase levels and the titres of HCV decreased significantly with ofloxacin administration. Such changes were not observed in the IFN-alone group. The incidence of HCV-negativity at the end of ofloxacin administration of the combination group was significantly higher than in the IFN-alone group. The complete response rate was twice as high in the combination group as in the IFN-alone group. In two patients who did not respond well to the IFN-alone treatment, ofloxacin administration was commenced after the 24th week. Serum transaminase levels were normalized and HCV-RNA became negative in these two patients after the administration of ofloxacin. These results suggest that combination therapy with IFN and ofloxacin may be an effective treatment for chronic type C hepatitis.     

Effect of nucleoside analog‐interferon sequential therapy on patients with acute exacerbation of chronic hepatitis B

Aim: Nucleoside analog (NA)‐interferon (IFN) sequential therapy may enable the long‐term control of chronic hepatitis B (CHB) and the withdrawal of the nucleoside analog. We evaluated the efficacy of NA‐IFN sequential therapy for acute exacerbation of CHB. Methods: A total of 12 patients with acute exacerbation of CHB, nine of whom were positive for hepatitis B e antigen (HBeAg), were enrolled in this study. All the patients were treated with lamivudine 100 mg/day alone for 20 weeks, then with both IFN‐α 6 megaunits three times per week and lamivudine for 4 weeks, and lastly, with IFN‐α alone for 20 weeks. Patients whose serum alanine aminotransferase (ALT) level was normalized, whose serum hepatitis B virus (HBV) DNA level decreased to less than 5 log copies/mL, and HBeAg level was absent 24 weeks after the end of treatment were defined as having sustained virological response (SVR). The other patients were defined as having no response (NR). Results: Four out of nine (44.4%) HBeAg‐positive and all three HBeAg‐negative patients achieved SVR. The levels of serum alanine aminotransferase (ALT), HBV DNA and HBV core‐related antigen were similar between SVR and NR patients at baseline. Three of four patients (75.0%) whose serum HBeAg became negative at the end of treatment achieved SVR, while one of five (20.0%) whose serum HBeAg remained positive achieved SVR. Conclusion: NA‐IFN sequential therapy for patients with acute exacerbation of CHB enables the withdrawal of treatment and is particularly effective for patients whose serum HBeAg has become undetectable by the end of the IFN treatment.