Prediction of Effect of Interferon on Chronic Hepatitis C

Clinical, pathological, and virological analysisincluding hypervariable region-1 of hepatitis C virus(HCV) was performed to predict the effect of interferon(IFN) on 41 patients with chronic hepatitis type C. The low virus load, low frequency ofthe mutation in the hypervariable region-1 as the changeof amino acid and high level of serum aminotransferasemake one estimate the good effect of IFN on patients with HCV. Mutation in the hypervariableregion-1 of HCV measured by fast assay fluorescencesingle-stranded conformational polymorphism was morefrequent in nonresponders to IFN than responders. Themost frequently mutated position was amino acidnumber 406. This indicates that the specific mutationsite might affect the response of IFN.     

Treatment of Chronic Hepatitis C with Amantadine

Treatment of chronic hepatitis C infection withinterferon has been disappointing, with less than onethird of patients achieving a sustained response andmost experiencing significant side effects. For these reasons, an open-labeled prospectivepilot study was conducted to test the safety andefficacy of the antiviral drug, amantadine, in patientswith chronic hepatitis C infection who had previously failed therapy withinterferon-_b. Twenty-two patients withchronic hepatitis C were enrolled into the study andtreated with amantadine 100 mg orally twice daily forsix months. Control groups included the same cohort followed off therapy for 29-36months or during therapy with interferon. Serum alanineaminotransferase (ALT) values decreased in 64% (P =0.01) of patients with amantadine therapy compared to intervals without therapy or to interferontherapy. Twenty-seven percent of patients treated withamantadine had normalization of ALT values and loss ofHCV RNA after six months while 18% achieved a sustained response with loss of HCV RNA by PCRsix months after discontinuation of amantadine. Therapywith amantadine improved both biochemical andvirological markers in patients with hepatitis C who had previously not responded to treatment withinterferon.     

Viral and Host Factors in Determining Response of Relapsers with Chronic Hepatitis C to Retreatment with Interferon

In chronic hepatitis C the rate of relapse afteran end-of-treatment response to interferon may exceed50%. The usefulness of retreatment of relapsers withinterferon in obtaining a complete sustained response and the role of clinical, virological andimmunological features in determining long-term efficacyof retreatment are unclear. We aimed to assess theefficacy of interferon retreatment in obtaining acomplete sustained response, to evaluate whetherincreasing the dose may enhance responsiveness, and toidentify possible predictors of sustained response. Weenrolled 42 patients with biopsy-proven chronichepatitis C without cirrhosis who had previouslyresponded to a six-month course ofInterferon-_2b (total dose: group A, 22patients, 234 MU; group B, 20 patients, 468 MU) and thenrelapsed. All, except one, were HCV-RNA negative at the end of first cycle ofinterferon; most (31/42, 74%) were infected by HCV 1b.Subjects were randomly allocated to receive anothercycle of interferon either at the original dose (group A₁: 234 MU, 11 patients; groupB 468 MU, 10 patient) or twice the original dose (groupA₂: 468 MU, 11 patients; group B : 936 MU, 10patients). At the end of the second cycle of interferon,24 subjects (57%) had normal ALT and were HCV-RNAnegative, and 16 (39%) had normal ALT, but were HCV-RNApositive. A complete sustained response was obtained ineight patients (19%), at a similar rate in all treatment groups. Complete sustainedresponders were different from the other patients interms of age (35.9 ± 10.4 vs 44.1 ± 8.8,P = 0.027), rate of infection with non-1b HCV (6/8 vs5/34, P = 0.0005), serum HCV-RNA (74,016 vs 321,428median copies/ml, P = 0.037) and serum levels of90K/MAC-2 BP (5.76 ± 3.01 vs 10.25 ± 5.16units/ml, P = 0.02), an N-glycoprotein implicated incellular defense functions. Multivariate logistic analysisvalidated age and HCV genotype as independent predictorsof CSR. Among noncirrhotic relapsers who received atotal interferon dose 234 MU in the first cycle,retreatment usually induced end-of-treatment response. Acomplete sustained response was obtained in only one ofevery five subjects. Increasing the dose of interferonabove that of the first cycle did not enhance the rate of sustained response. In conclusionwe might assert that young subjects infected by non-1bHCV and with low levels of HCV-RNA and of 90K/MAC-2 BPare the best candidates for retreatment.     

Interferon-α 2b Therapy Is Efficacious in Asian-Americans with Chronic Hepatitis B Infection: A Prospective Controlled Trial

Chronic hepatitis B virus infection is endemicin Asian communities in the United States. The purposeof the current study was to compare the antiviralefficacy of interferon-_2b in a groupof adult Asian patients chronically infected withhepatitis B with active replication compared to acontrol group of Caucasian patients treated with thesame regimen. Patients with entry aminotransferase (ALT)levels greater than three times the upper limit ofnormal received interferon-_2b, 5million units, subcutaneously daily for 16 weeks.Patients with pretreatment ALT levels 1.5-3 times theupper limit of normal received prednisone for a total of sixweeks prior to interferon starting at 60 mg daily withreduction in dosage by 20 mg every two weeks with atwo-week period between finishing prednisone and starting interferon-_2b. Eight(62%) of the 13 Asians and six (60%) of the 10Caucasians cleared HBeAg and HBV DNA from serum (NS). Bythe end of one year of follow-up after therapy, four(67%) of six Caucasian responders but none of the Asianresponders had cleared hepatitis B surface antigen fromserum (P < 0.05). Loss of serum markers of activereplication appeared less durable in the Asian responders compared to the Caucasians withreappearance of serum HBeAg in two (25%) of eight of theformer but only one (17%) of the latter group. Threeother Asian patients subsequently redeveloped HBeAg in serum. It is concluded that adultAsian-Americans have an identical initial response rateto antiviral therapy withinterferon-_2b; however, the responsemay be less durable and does not usually lead to loss of HBsAg.     

绞股蓝总皂甙对小鼠产生IFN—r的影响

本文报道了绞股蓝总皂甙对正常和大黄脾虚模型小鼠IFN—r产生的影响。实验结果表明:ConA能诱导小鼠脾细胞产生IFN—γ;大黄脾虚模型小鼠IFN—γ水平比正常小鼠明显降低.绞股蓝总皂甙10～40mg/L以7/50～200mg/kg在体外、体内均可明显提高ConA诱导正常小鼠脾细胞产生的IFN—γ水平.其增加ConA诱导IFN—γ产生的最适浓度在体外为20mg/L,在体内为100mg/kg;绞股蓝总皂甙10～80mg/L以及50～100mg/kg在ConA协同下在体外、体内均能使大黄脾虚模型小鼠低下的IFN—γ水平明显提高,并使之恢复、甚至超过正常水平,其提高ConA诱导IFN一γ产生的最适浓度在体外、体内分别是20mg/L和50～100mg/kg.绞股蓝总皂甙能使大黄脾虚小鼠低下的IFN—γ水平恢复的实验结果进一步提示IFN—γ可能与机体的“正气”和“脾”的本质存在某种内在联系,IFN—γ可能是中医“脾气”的免疫学物质基础之一。     

Comparison of HCV RNA Levels by Branched DNA Probe Assay and by Competitive Polymerase Chain Reaction to Predict Effectiveness of Interferon Treatment for Patients with Chronic Hepatitis C Virus

To compare hepatitis C virus (HCV) RNA levelsdetermined by branched DNA probe assay and bycompetitive polymerase chain reaction (PCR) aspredictive markers of the response to interferon fortreatment of patients with chronic HCV infection, westudied data on 140 patients treated for six months withnatural interferon-alpha. Serum samples were tested forHCV RNA by PCR. HCV RNA was grouped into four genotypes by PCR with type-specific primers,and HCV RNA level was measured by branched DNA probeassay and by competitive PCR. HCV RNA was detected inall patients prior to initiation of the treatment. A complete response, sustained elimination ofHCV RNA, occurred in 51 patients (36.4%). With multiplelogistic regression analysis assessment, when usingcompetitive PCR, a low level of HCV RNA (P < 0.0001), younger age (P = 0.0054) and genotype 2a and 2b(P < 0.0158) were significant predictive markers fora complete response to interferon treatment. When usingbranched DNA probe assay, a low level of HCV RNA (P < 0.0001) and age (P = 0.0089) werepredictive markers, but genotype was not. The branchedDNA probe assay had a narrower linear range forquantitation of HCV RNA level than competitive PCR. In conclusion, HCV RNA level determined bybranched DNA probe assay proved to be useful forprediction of effects of interferon and it is costeffective as a marker of complete response to interferontreatment for patients with chronic HCVinfection.     

Early HCV RNA Values After Interferon Predict Response

The aim of this study is to determine inpatients infected with hepatitis C virus (HCV) whetherearly HCV RNA measurements at 48 hr following standarddoses of interferon- (IFN-) (3 million IU) would predict response during six months oftherapy. Twenty-three patients with HCV were treatedwith IFN- 3 million IU three times a week and HCVRNA levels were quantified by branched-chain (b-)DNA analysis at baseline and 24 and 48 hr followingIFN- and at one, three, and six months. Meanbaseline HCV RNA levels significantly declined from 6.0± 1.6 Meq/ml at baseline to 2.4 ± 0.7Meq/ml 24 hr after IFN-. However, HCV RNAvalues increased to 4.3 ± 1.1 Meq/ml by 48 hr.Mean HCV RNA values at one and six months were notsignificantly lower than 48-hr values. In six patientsin whom HCV RNA was negative by bDNA at 48 hr, threewere negative by polymerase chain reaction at sixmonths. Of the 17 patients who were positive by bDNA at48 hr, all were positive at one and three months; and in the nine of nine who continued therapy forsix months, there was no further decrease in HCV RNAlevels. In patients receiving standard doses ofIFN- (3 million IU), serum RNA values 48 hr after the first injection predict long-termresponse.     

γ—干扰素对肝癌细胞株Hep—G2 Fas,Bcl—2表达的影响

目的：观察γ－干扰素（γ－IFN）对肝癌细胞株Hep-G2细胞（Hep-G2)表达Fas,Bcl-2的影响。方法：应用γ-IFN预处理Hep-G2,用阿霉素诱导凋亡,MTT法分析细胞死亡率,电镜观察凋亡,免疫组织化学法研究γ-IFN作用于Hepp-G2细胞过程中Fas,Bcl-2的表达情况,结果： γ－IFN预处理的Hep-G2表达Fas增强,表达Bcl-2减弱（P＜0．05）,γ-IFN预处理后Hep-G2细胞对阿霉素的敏感性提高（P＜0．05）,结论：γ-IFN对肝癌细胞株Hep-G2Fas,Bcl-2表达有影响,并可提高肝癌细胞对阿霉素的敏感性。     

Endogenous Interferon-α Concentration and Outcome of Interferon Treatment in Patients with Chronic Hepatitis C

To verify its value with regard to the outcomeof therapy in chronic hepatitis C, seruminterferon- (IFN) was measured by ELISA in 70patients (43 male, 27 female) with chronic hepatitis C,treated with IFN 9 MU/week subcutaneously for up to oneyear. Serum IFN was detectable in 49/70 patients, 16 ofwhom had IFN values >125 pg/ml. Only 1/22 patientswho maintained a sustained response six months after the end of treatment had pretreatment serum IFN> 125 pg/ml, in comparison to 15/48 patients who didnot respond or who relapsed ( 6.1, P < 0.02). Atmultivariate analysis the predictive value of serum IFN was independent of age, sex, presence ofcirrhosis, infection by genotype 1b (improvement 7.1, P < 0.01). In patients with chronic hepatitis C,measurement of serum IFN at baseline might be useful for the selection of patients with higherprobability of long-term response.     

Tolerance and Antiviral Effects of High-Dose Interferon-α B/D in Patients with Chronic Hepatitis B

A novel recombinant interferon- B/Dhybrid was applied to assess tolerability, antiviraleffect, and biological activity in chronic hepatitis B.The study was designed as an open nonrandomized trial. Treatment comprised a two-week run-in phasewith 16 MU three times a week followed by 14 weeks with64 MU three times a week (or 48 MU if toxicity occurredwith 64 MU). Total follow-up was 36 weeks. Nineteen patients were included; three discontinuedtreatment during the run-in with 16 MU. Fourteen of 16patients had 14 weeks of treatment with 32 MU threetimes a week. Fourteen dose reductions were necessary in nine patients. The adverse experienceprofile was similar to other interferon-s.HBV-DNA decreased using all doses studied. HBV-DNAbecame undetectable in five patients, two of whom hadHBeAg seroconversion. No HBsAg seroconversion was observed. It isconcluded that interferon- B/D is well toleratedin high doses. The anti-viral effect starts at at least16 MU three times a week.