Objective\ To study the correlation between mutations in the NS5A region of hepatitis C virus genotype 1b and the efficacy of interferon alpha (IFN α) therapy. Methods\ Twenty patients with chronic HCV 1b infection, ...Objective\ To study the correlation between mutations in the NS5A region of hepatitis C virus genotype 1b and the efficacy of interferon alpha (IFN α) therapy. Methods\ Twenty patients with chronic HCV 1b infection, including 10 responders and 10 non responders to standard IFN α therapy, were investigated. HCV 1b NS5A 2209 2248 region was amplified by RT PCR and the second round product was directly sequenced before treatment. Results\ In IFN α response group, 4 out of 10 HCV isolates (40%) had mutations of amino acid in NS5A 2209 2248 region, which were all intermediate types; while in IFN α non response group, none of HCV isolates (0/10,0%) had mutations, which were all wild types (P<0.05). There was no mutant type isolates in these two groups. All patients (4/4,100%) infected with intermediate type and 6 out of 16 patients(37.5%) infected with wild type of HCV 1b were responsive to IFN α therapy (P<0.05). Conclusion\ The sequences in NS5A 2209 2248 region of Chinese HCV 1b isolates were relatively conservative. There may be a correlation between the efficacy of IFN α therapy and the mutations of amino acid in NS5A 2209 2248 region of Chinese HCV 1b isolates.展开更多
Conjunctival malignant melanoma (CMM) is a potentially lethal neoplasm with a high rate of recurrence. The modality of treatment includes a wide surgical excision, cryotherapy, topical mitomycin C and Interferon alpha...Conjunctival malignant melanoma (CMM) is a potentially lethal neoplasm with a high rate of recurrence. The modality of treatment includes a wide surgical excision, cryotherapy, topical mitomycin C and Interferon alpha 2b (INF α 2b). The aim of the study is to present the treatment of a case with CMM using topical Interferon alpha 2a. We present a 38-year-old female with diffuse bulbar dark pigmentation of the conjunctiva that arises from previously primary acquired melanosis (PAM). Biopsy resulted positive for CMM and further investigations were negative for any metastasis. Treatment with topical interferon alpha 2a was started immediately and after three months melanoma disappeared. One year after follow-up there was no sign of recurrence in regional lymph nodes or distant metastasis.展开更多
Objective To explore the predictive value of baseline HBsAg level and early response for HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A total o...Objective To explore the predictive value of baseline HBsAg level and early response for HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A total of 121 patients with HBeAg-positive chronic hepatitis B who achieved HBsAg loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators(HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during treatment. Results The median treatment time for HBsAg loss was 84 weeks(7-273 weeks), and 74.38%(90 cases) of the patients needed extended treatment(> 48 weeks). The correlation between baseline HBsAg levels and the treatment time of HBsAg loss was significant(B = 14.465, t = 2.342, P = 0.021). Baseline HBsAg levels together with the decline range of HBsAg at 24 weeks significantly correlated with the treatment time of HBsAg loss(B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005). Conclusion Baseline HBsAg levels and extended therapy are critical steps toward HBsAg loss. Baseline HBsAg levels together with early response determined the treatment time of HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.展开更多
AIM:To study predictive factors of thyroid dysfunction associated with interferon-alpha(IFNα) therapy in chronic hepatitis C(CHC) and to describe its long-term evolution in a large population without previous thyroid...AIM:To study predictive factors of thyroid dysfunction associated with interferon-alpha(IFNα) therapy in chronic hepatitis C(CHC) and to describe its long-term evolution in a large population without previous thyroid dysfunction.METHODS:We performed a follow-up of thyroid function and detection of thyroid antibodies in 301 patients treated for CHC with IFNα from 1999 to 2004.RESULTS:Thyroid disorder developed in 30/301(10%) patients with a mean delay of 6 ± 3.75 mo:13 patients had hyperthyroidism,11 had hypothyroidism,and 6 had biphasic evolution.During a mean follow-up of 41.59 ± 15.39 mo,9 patients with hyperthyroidism,3 with hypothyroidism,and 4 with biphasic evolution normalized thyroid function in 7.88 ± 5.46 mo.Recovery rate of dysthyroidism was not modified by treatment discontinuation,but was better for patients with negative thyroid antibodies before antiviral treatment(P = 0.02).Women had signif icantly more dysthyroidism(P = 0.05).Positive thyroid peroxidase and thyroglobulin antibodies were more frequent before antiviral treatment in patients who developed dysthyroidism(P < 0.0003 and P = 0.0003,respectively).In a multivariate model,low fibrosis was found to be a predictive factor of dysthyroidism(P = 0.039).CONCLUSION:In this monocentric population of CHC,dysthyroidism,especially hyperthyroidism,developed in 10% of patients.Low fibrosis was found to be a predictive factor of dysthyroidism.Thyroid disorder recovered in 16/30 patients(53%) and recovery was better in the non-autoimmune form.展开更多
Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B(CHB). The objective of the pr...Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B(CHB). The objective of the present study was to compare the efficacy and safety of pegylated interferon(Peg-IFN) alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone(1.5 μg/kg once weekly) or Peg-IFN alpha-2b plus adefovir(10 mg daily) for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30(36.7%) patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31(25.8%) in the monotherapy group(P=0.36). In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group(76.7% vs. 29.0%, P<0.001). Thyroid dysfunction was more frequent in the combination group than in the monotherapy group(P<0.05). In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.展开更多
AIM:To assess the long-term clinical benefit of sustained virological response(SVR)in patients with hepatitis C virus(HCV)cirrhosis treated by antiviral therapy using mostly ribavirin plus interferon either standard o...AIM:To assess the long-term clinical benefit of sustained virological response(SVR)in patients with hepatitis C virus(HCV)cirrhosis treated by antiviral therapy using mostly ribavirin plus interferon either standard or pegylated.METHODS:One hundred and thirteen patients with uncomplicated HCV biopsy-proven cirrhosis,treated by at least one course of antiviral treatment ≥ 3 mo and followed ≥ 30 mo were included.The occurrence of clinical events hepatocellular carcinoma(HCC),decompensation and death was compared in SVR and non SVR patients.RESULTS:Seventy eight patients received bitherapy and 63 had repeat treatments.SVR was achieved in 37 patients(33%).During a mean follow-up of 7.7 years,clinical events occurred more frequently in non SVR than in SVR patients,with a significant difference for HCC(24/76 vs 1/37,P = 0.01).No SVR patient died while 20/76 non-SVR did(P = 0.002),mainly in relation to HCC(45%).CONCLUSION:In patients with HCV-related cirrhosis,SVR is associated with a significant decrease in the incidence of HCC and mortality during a follow-up period of 7.7 years.This result is a strong argument to perform and repeat antiviral treatments in patients with compensated cirrhosis.展开更多
AIM: Mechanisms responsible for persistence of HCV infection and liver damage in chronic hepatitis C are not clear. Apoptosis is an important form of host immune response against viral infections. Anti-apoptotic prote...AIM: Mechanisms responsible for persistence of HCV infection and liver damage in chronic hepatitis C are not clear. Apoptosis is an important form of host immune response against viral infections. Anti-apoptotic proteinbcl-2 expression on liver tissue as well as the influence of interferon alpha 2b (IFNα2b) and ribavirin (RBV) were analyzed in patients with chronic hepatitis C. METHODS: In 30 patients with chronic hepatitis C (responders - R and non-responders - NR) treated with IFNα2b+RBV, protein bcl-2 was determined in hepatocytes and in liver associated lymphocytes before and after the treatment.RESULTS: The treatment diminished bcl-2 protein accumulation in liver cells in_patients with hepatitis C (P＜0.05). Before and after the therapy, we detected bcl-2 protein in R in 87±15% and 83±20% of hepatocytes andin 28± 18% and 26±10% of liver-associated lymphocytes, respectively. In NR, the values before treatment decreased from 94±32% to 88±21% of hepatocytes and 39±29% to 28±12% of lymphocytes with bcl-2 expression. There was no statistical correlation between bcl-2 expression on liver tissue with inflammatory activity, fibrosis and biochemical parameters before and after the treatment.CONCLUSION: IFNα2b+RBV treatment, by bcl-2 protein expression decrease, enables apoptosis of hepatocytes and associated liver lymphocytes, which in turn eliminate hepatitis C viruses.展开更多
Human interferon alpha-8(IFN-α8) is an important cytokine with multiple biological functions.A genetically engineered strain, E. coli XL1-Blue/pBm, was constructed by DNA recombination technology and characterized by...Human interferon alpha-8(IFN-α8) is an important cytokine with multiple biological functions.A genetically engineered strain, E. coli XL1-Blue/pBm, was constructed by DNA recombination technology and characterized by restriction analysis, DNA sequencing.展开更多
Background and Aims:Data are limited on the use of pegylated-interferon alpha-2a(peg-IFNα)in Chinese patients with chronic hepatitis B virus(HBV)infection(CHB).We evaluated the effectiveness and safety of peg-IFNαin...Background and Aims:Data are limited on the use of pegylated-interferon alpha-2a(peg-IFNα)in Chinese patients with chronic hepatitis B virus(HBV)infection(CHB).We evaluated the effectiveness and safety of peg-IFNαin Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice.Methods:In this prospective,multicenter,observational,non-interventional cohort study,patients were assessed for up to 1 year after peg-IFNαtreatment cessation.Treating physicians established the dosing and treatment duration according to Chinese clinical practice.Effectiveness of peg-IFNαtreatment was measured by the percentage of:patients with HBV DNA<2000 IU/mL and loss of hepatitis B surface antigen(commonly known as HBsAg);HBV DNA level at end of treatment(EOT),and 6 months and 1 year posttreatment;and time course change in quantitative HBV DNA and HBsAg.Results:At EOT,6 months posttreatment,and 1 year posttreatment,the percentage of patients with HBV DNA<2000 IU/mL was 90.0%,81.8%,and 82.2%,and that of patients with HBsAg loss was 6.5%,9.4%,and 9.5%,respectively.The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment.The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment.The incidence of adverse events was 52.0%.Conclusions:Peg-IFNαhas the potential to provide functional cure(HBsAg loss)for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China.展开更多
Objective: To compare the bone mass density in chronic hepatitis patients before and after interferon-a treatment.Methods: A total of 70 patients with chronic hepatitis C were treated with interferon-a and were evalua...Objective: To compare the bone mass density in chronic hepatitis patients before and after interferon-a treatment.Methods: A total of 70 patients with chronic hepatitis C were treated with interferon-a and were evaluated. The treatment dosage was three million IU three times a week for one year. All the patients underwent bone mass density detection at lumbar spine and femoral neck before and after the interferon-a treatment. All the necessary information such as age,sex, and laboratory test, history of occurrence of fractures, lifestyle, and menopause status was collected by interviewers face-to-face from participants at the research visit. Smoking was categorized by whether participants were nonsmokers or smokers. Menopause was designated if there had been complete cessation of menses for more than 12 months. All statistical analyses were performed by SPSS version 14(SPSS, Inc., Chicago, IL, USA).Results: Among 70 patients, 52% were male, 48% were female and the mean age was(57.0 ± 9.6) years(range: 24–79). Twenty-nine percent of the patients had a history of smoking. The mean body mass index was(24.4 ± 3.6) kg/m^2(range: 18.4–35.3). Of the70 cases, 21 had high fibrosis-4. The prevalence of overall fracture history was 2.9%(two patients).Conclusions: Chronic hepatitis C virus infection did increase the risk of development of metabolic bone disease in this cohort. Indeed, greater reduction of bone mass density occurs in advanced liver fibrosis. The bone loss in earlier stages of chronic hepatitis C infection is likely to result from increased bone reduction rather than decreased bone formation. Overall, these observations suggest an important role for chronic hepatitis C virus infection in increased bone turnover in osteodystrophy pathogenesis.展开更多
BACKGROUND: Much evidence demonstrates that the genotypes of hepatitis B virus (HBV) present differences in pathogenicity and outcomes owing to differences in genetic structure. This study aimed to investigate the inf...BACKGROUND: Much evidence demonstrates that the genotypes of hepatitis B virus (HBV) present differences in pathogenicity and outcomes owing to differences in genetic structure. This study aimed to investigate the influences of HBV genotypes on the anti-viral therapeutic efficacy of interferon-α (IFN-α) in chronic hepatitis B patients, and to determine the relationship between HBV genotypes and levels of viral replication or gene variations. METHODS: The chronic hepatitis B patients who were treated with IFN-α were selected randomly. Anti-viral therapeutic efficacy was monitored in these patients. The HBV genotypes were detected by PCR microplate hybridization ELISA. The levels of serum HBV-DNA were determined by fluorescence quantitative PCR. HBV gene variation at pre-C and basic core promoter (BCP) regions were assayed by gene chip technology. RESULTS: Genotypes B and C were predominant in 94 chronic hepatitis B patients. A, E and F genotypes were not found in these patients. The HBV-DNA levels of genotype C and mixed genotypes were significantly higher than those of genotype B. The response to IFN-α in patients with genotype B was markedly better than in those with genotypes C and D, and the complete response to IFN-α was only observed in genotype B. The response to IFN-α in patients with mixed genotypes was the least sensitive. The negative transition of HBeAg was correlated with variations in the HBV pre-C and BCP regions in patientswith partial or no response to IFN-α. The variation rates of HBV pre-C and BCP regions were clearly higher in genotype C than in genotype B. CONCLUSIONS: The results suggest that HBV genotype is correlated with the serum levels of HBV-DNA, HBV gene variations and therapeutic efficacy of IFN-α. The regular detection of HBV genotypes in the clinic will be of benefit for disease prognosis and planning of anti-viral therapeutic strategies.展开更多
Classical interferon-alpha has been shown to be correlated with the development of a variety of autoimmune disorders. A 38 year-old female patient developed simultaneously diabetic ketoacidosis and hyperthyroidism 5 m...Classical interferon-alpha has been shown to be correlated with the development of a variety of autoimmune disorders. A 38 year-old female patient developed simultaneously diabetic ketoacidosis and hyperthyroidism 5 mo following initiation of treatment with pegylated interferon-α and ribavirin for chronic hepatitis C. High titers of glutamic acid decarboxylase, antinuclear and thyroid (thyroid peroxidase and thyroglobulin) antibodies were detected. Antiviral treatment was withdrawn and the patient was treated with insulin for insulin-dependent diabetes mellitus and propranolol for hyperthyroidism. Twelve months after cessation of pegylated interferon-α therapy the patient was euthyroid without any medication but remained insulin-dependent.展开更多
BACKGROUND:Virological clearance,delayed progression to cirrhosis or liver cancer,and increased survival are the long-term goals of antiviral therapy in chronic hepatitis B patients.Identification of host factors corr...BACKGROUND:Virological clearance,delayed progression to cirrhosis or liver cancer,and increased survival are the long-term goals of antiviral therapy in chronic hepatitis B patients.Identification of host factors correlated with therapeutic response may contribute greatly to individual treatment.This study aimed at investigating whether T29C genotype polymorphism of estrogen receptor alpha(ESR1) is associated with the initial response to interferon-alpha(IFN-α)therapy in chronic hepatitis B patients.METHODS:The initial responses of 100 patients to IFN-α therapy were evaluated and compared by classifying them into three groups according to T29C genotype polymorphism of ESR1:T/T,T/C,and C/C genotype groups.Polymerase chain reaction-restriction fragment length polymorphism was used to analyze the genotype polymorphism in T29C.RESULTS:The frequency of initially combined response was markedly higher in both the T/T and T/C groups than in the C/C group(Z=10.326,P=0.006 and Z=26.247,P=0.000, respectively).In addition,the initial virological response was higher in the T/T and T/C groups than the C/C group(χ2=5.674, P=0.017 andχ2=4.980,P=0.026,respectively).In 78 initially HBeAg-positive patients,however,the frequency of initial e-antigen disappearance or seroconversion among the T/T,T/C, and C/C genotype groups was 34.15%,27.78%and 15.79%, respectively,which were not significantly different.CONCLUSION:The T29C genotype polymorphism of ESR1 is associated with the initial response to IFN-αin patients with chronic hepatitis B,and might be a significant marker for predicting the initial response to IFN-α,at least in this study population.展开更多
AIM: To investigate the safety and efficacy of long-term combination therapy with alpha interferon and lamivudine in non-responsive patients with anti-HBe-positive chronic hepatitis B.METHODS: 34 patients received com...AIM: To investigate the safety and efficacy of long-term combination therapy with alpha interferon and lamivudine in non-responsive patients with anti-HBe-positive chronic hepatitis B.METHODS: 34 patients received combination treatment (1 month lamivudine, 12 month lamivudine+interferon, 6month lamivudine), 24 received lamivudine (12 months),24 received interferon (12 months). Interferon was administered at 6 MU tiw and lamivudine at 100 mg orally once daily. Patients were followed up for 6 months after treatment.RESULTS: At the end of treatment, HBV DNA negativity rates were 88 % with lamivudine+interferon, 99 % with lamivudine and 55 % with interferon, (P=0.004, combination therapy vs. interferon, and P=0.001 lamivudine vs.interferon), and serum transaminase normalization rates were 84 %, 91% and 53 % (P=0.01 combination therapy vs. interferon, and P=0.012 lamivudine vs. interferon). Six months later, HBV DNA negativity rates were 44 % with lamivudine+interferon, 33 % with lamivudine and 25 % with interferon, and serum transaminase normalization rates were 61%, 42 % and 45 %, respectively, without statistical significance. No YMDD variants were observed with lamivudine+interferon (vs. 12 % with lamivudine). The combination therapy appeared to be safe. CONCLUSION: Although viral clearance and transaminase normalization are slower with long-term lamivudine+interferon than that with lamivudine alone, the combination regimen seems to provide more lasting benefits and to protect against the appearance of YMDD variants. Studies with other regimens regarding sequence and duration are needed.展开更多
Objective: To determine whether Interferon-alpha-2b(IFN-α2b) can modulate the autophagic response in hepatocellular carcinoma cells.Methods: Hepatocellular carcinoma cells were treated with IFN-α2b. Autophagy was as...Objective: To determine whether Interferon-alpha-2b(IFN-α2b) can modulate the autophagic response in hepatocellular carcinoma cells.Methods: Hepatocellular carcinoma cells were treated with IFN-α2b. Autophagy was assessed by acridine orange staining, GFP-LC3 dotted assay, transmission electron microscopy and immunoblotting.Results: Acridine orange staining showed that IFN-α2b triggered the accumulation of acidic vesicular and autolysosomes in HepG2 cells. The acridine orange HepG2 cell ratios were(4.3±1.0)%,(6.9±1.4)%, and(13.1±2.3)%, respectively, after treatment with 100, 1,000, and 10,000 IU/mL IFN-α2b for 48 h. A markedly punctate pattern was observed in HepG2 cells treated with 10,000 IU/mL IFN-α2b for 48 h, but only diffuse and weakly fluorescent GFP-LC3 puncta was observed in control cells. HepG2 cells treated with 10,000 IU/mL IFN-α2b for 48 h developed autophagosome-like characteristics, including single- or double-membrane vacuoles containing intact and degraded cellular debris. The Beclin1 and LC3-II protein expression was up-regulated by IFN-α2b treatment.Conclusion: Autophagy can be induced in a dose-dependent manner by treatment with IFN-α2b in HepG2 cells, and the Beclin1 signaling pathway was stimulated by IFN-α2b.展开更多
AIM: To investigate the effects of interferon-alpha (IFN-α) to restrain the growth and invasive potential of hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV) X protein. METHODS: The pcDNA3.1-HBx plas...AIM: To investigate the effects of interferon-alpha (IFN-α) to restrain the growth and invasive potential of hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV) X protein. METHODS: The pcDNA3.1-HBx plasmid was transfected into Chang cells by Lipofectamine in vitro, and Chang/HBx was co-cultured with IFN-α. Cell survival growth curve and clonogenicity assay were used to test the growth potential of Chang/pcDNA3.1, Chang/HBx and IFN-α-Chang/HBx in vitro. Growth assay in nude mice was used to detect the growth potential of Chang/ pcDNA3.1, Chang/HBx and IFN-α-Chang/HBx in vivo. Wound healing and transwell migration assays were used to detect the invasive ability of Chang/pcDNA3.1, Chang/HBx and IFN-α-Chang/HBx. RESULTS: Compared with CCL13 cells transfected with pcDNA3.1, CCL13 with stable expression of hepatitis B virus X protein showed the characteristics of malignant cells with high capability of growth and invasion by detecting their growth curves, colony forming efficiency, wound healing , transwell migration assays and growth assays in nude mice. Its capability of growth and invasion could be controlled by IFN-α. CONCLUSION: IFN-α can restrain the growth and invasive potential of HCC cells induced by HBx protein, which has provided an experimental basis for IFN-α therapy of HCC.展开更多
We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus (DM) after a 13-mo period of treatment with recombinant human interferon-alpha (IFN-α) 2b. The patien...We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus (DM) after a 13-mo period of treatment with recombinant human interferon-alpha (IFN-α) 2b. The patient presented with polydipsia, polyuria, hypergly-cemia, diabetic ketoacidosis, combined with C-peptide secretion defi ciency and positive islet cell autoantibody (ICAb). IFN-α 2b treatment was terminated and in-stead insulin treatment was initiated. Five months after cessation of the recombinant human IFN-α 2b therapy, the patient remained insulin-dependent. Her serum HBV DNA became negative and serum transaminase returned to the normal level after a 10-mo period of IFN therapy. Type 1 DM induced by IFN-α is relatively rare in patients with chronic hepatitis B. We should pay more attention to patients on IFN-α therapy to avoid destruction of pancreatic beta cells. This is the first case report from China.展开更多
AIM: To explore the prevalence of autoimmune gastritis in chronic hepatitis C virus (HCV) patients and the influence of α-intefferon (IFN) treatment on autoimmune gastritis.METHODS: We performed a prospective study o...AIM: To explore the prevalence of autoimmune gastritis in chronic hepatitis C virus (HCV) patients and the influence of α-intefferon (IFN) treatment on autoimmune gastritis.METHODS: We performed a prospective study on 189patients with positive anti-HCV and viral RNA enrolled in a 12-month IFN protocol. We evaluated: a) the baseline prevalence of autoimmune gastritis, b) the impact of IFN treatment on development of biochemical signs of autoimmune gastritis (at 3, 6 and 12 months), c) the evolution after IFN withdrawal (12 months) in terms of anti-gastric-parietal-cell antibodies (APCA), gastrin, anti-thyroid, and anti-non-organ-specific antibodies.RESULTS: APCA positivity and 3-fold gastrin levels were detected in 3 (1.6 %) and 9 (5 %) patients, respectively, at baseline, in 25 (13 %) and 31 (16 %) patients at the end of treatment (both P＜0.001, vs baseline), and in 7 (4 %) and 14 (7 %) patients 12 months after withdrawal (P=0.002and ,P=0.01 respectively, vs baseline; P=not significant vs end of treatment). The development of autoimmune gastritis was strictly associated with the presence of autoimmune thyroiditis (P =0.0001), no relationship was found with other markers of autoimmunity.CONCLUSION: In HCV patients, IFN frequently precipitates latent autoimmune gastritis, particularly in females. Following our 12-month protocol, the phenomenon generally regressed. Since APCA positivity and high gastrin levels are associated with the presence of antithyroid antibodies,development of autoimmune thyroiditis during IFN treatment may provide a surrogate preliminary indicator of possible autoimmune gastritis to limit the need for invasive examinations.展开更多
We investigated the possibility of producing chicken alpha interferon(ChIFN-α) in transgenic plants. The cDNA encoding ChIFN-α was introduced into lettuce(Lactuca sativa L.) plants by using an agro-infiltration tran...We investigated the possibility of producing chicken alpha interferon(ChIFN-α) in transgenic plants. The cDNA encoding ChIFN-α was introduced into lettuce(Lactuca sativa L.) plants by using an agro-infiltration transient expression system. The ChIFN-α gene was correctly transcribed and translated in the lettuce plants according to RT-PCR and ELISA assays. Re-combinant protein exhibited antiviral activity in vitro by inhibition of vesicular stomatitis virus(VSV) replication on chicken embryonic fibroblast(CEF). The results demonstrate that biologically active avian cytokine with potential pharmaceutical ap-plications could be expressed in transgenic lettuce plants and that it is possible to generate interferon protein in forage plants for preventing infectious diseases of poultry.展开更多
基金This project was supported by research fund from Department of Health and Department of Personal Jiangsu Province! 2 76EC960 6
文摘Objective\ To study the correlation between mutations in the NS5A region of hepatitis C virus genotype 1b and the efficacy of interferon alpha (IFN α) therapy. Methods\ Twenty patients with chronic HCV 1b infection, including 10 responders and 10 non responders to standard IFN α therapy, were investigated. HCV 1b NS5A 2209 2248 region was amplified by RT PCR and the second round product was directly sequenced before treatment. Results\ In IFN α response group, 4 out of 10 HCV isolates (40%) had mutations of amino acid in NS5A 2209 2248 region, which were all intermediate types; while in IFN α non response group, none of HCV isolates (0/10,0%) had mutations, which were all wild types (P<0.05). There was no mutant type isolates in these two groups. All patients (4/4,100%) infected with intermediate type and 6 out of 16 patients(37.5%) infected with wild type of HCV 1b were responsive to IFN α therapy (P<0.05). Conclusion\ The sequences in NS5A 2209 2248 region of Chinese HCV 1b isolates were relatively conservative. There may be a correlation between the efficacy of IFN α therapy and the mutations of amino acid in NS5A 2209 2248 region of Chinese HCV 1b isolates.
文摘Conjunctival malignant melanoma (CMM) is a potentially lethal neoplasm with a high rate of recurrence. The modality of treatment includes a wide surgical excision, cryotherapy, topical mitomycin C and Interferon alpha 2b (INF α 2b). The aim of the study is to present the treatment of a case with CMM using topical Interferon alpha 2a. We present a 38-year-old female with diffuse bulbar dark pigmentation of the conjunctiva that arises from previously primary acquired melanosis (PAM). Biopsy resulted positive for CMM and further investigations were negative for any metastasis. Treatment with topical interferon alpha 2a was started immediately and after three months melanoma disappeared. One year after follow-up there was no sign of recurrence in regional lymph nodes or distant metastasis.
基金supported by Beijing Science and Technology Commission(No.D121100003912001)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding,Support(No.ZY201402)
文摘Objective To explore the predictive value of baseline HBsAg level and early response for HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A total of 121 patients with HBeAg-positive chronic hepatitis B who achieved HBsAg loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators(HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during treatment. Results The median treatment time for HBsAg loss was 84 weeks(7-273 weeks), and 74.38%(90 cases) of the patients needed extended treatment(> 48 weeks). The correlation between baseline HBsAg levels and the treatment time of HBsAg loss was significant(B = 14.465, t = 2.342, P = 0.021). Baseline HBsAg levels together with the decline range of HBsAg at 24 weeks significantly correlated with the treatment time of HBsAg loss(B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005). Conclusion Baseline HBsAg levels and extended therapy are critical steps toward HBsAg loss. Baseline HBsAg levels together with early response determined the treatment time of HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.
文摘AIM:To study predictive factors of thyroid dysfunction associated with interferon-alpha(IFNα) therapy in chronic hepatitis C(CHC) and to describe its long-term evolution in a large population without previous thyroid dysfunction.METHODS:We performed a follow-up of thyroid function and detection of thyroid antibodies in 301 patients treated for CHC with IFNα from 1999 to 2004.RESULTS:Thyroid disorder developed in 30/301(10%) patients with a mean delay of 6 ± 3.75 mo:13 patients had hyperthyroidism,11 had hypothyroidism,and 6 had biphasic evolution.During a mean follow-up of 41.59 ± 15.39 mo,9 patients with hyperthyroidism,3 with hypothyroidism,and 4 with biphasic evolution normalized thyroid function in 7.88 ± 5.46 mo.Recovery rate of dysthyroidism was not modified by treatment discontinuation,but was better for patients with negative thyroid antibodies before antiviral treatment(P = 0.02).Women had signif icantly more dysthyroidism(P = 0.05).Positive thyroid peroxidase and thyroglobulin antibodies were more frequent before antiviral treatment in patients who developed dysthyroidism(P < 0.0003 and P = 0.0003,respectively).In a multivariate model,low fibrosis was found to be a predictive factor of dysthyroidism(P = 0.039).CONCLUSION:In this monocentric population of CHC,dysthyroidism,especially hyperthyroidism,developed in 10% of patients.Low fibrosis was found to be a predictive factor of dysthyroidism.Thyroid disorder recovered in 16/30 patients(53%) and recovery was better in the non-autoimmune form.
文摘Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B(CHB). The objective of the present study was to compare the efficacy and safety of pegylated interferon(Peg-IFN) alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone(1.5 μg/kg once weekly) or Peg-IFN alpha-2b plus adefovir(10 mg daily) for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30(36.7%) patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31(25.8%) in the monotherapy group(P=0.36). In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group(76.7% vs. 29.0%, P<0.001). Thyroid dysfunction was more frequent in the combination group than in the monotherapy group(P<0.05). In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.
文摘AIM:To assess the long-term clinical benefit of sustained virological response(SVR)in patients with hepatitis C virus(HCV)cirrhosis treated by antiviral therapy using mostly ribavirin plus interferon either standard or pegylated.METHODS:One hundred and thirteen patients with uncomplicated HCV biopsy-proven cirrhosis,treated by at least one course of antiviral treatment ≥ 3 mo and followed ≥ 30 mo were included.The occurrence of clinical events hepatocellular carcinoma(HCC),decompensation and death was compared in SVR and non SVR patients.RESULTS:Seventy eight patients received bitherapy and 63 had repeat treatments.SVR was achieved in 37 patients(33%).During a mean follow-up of 7.7 years,clinical events occurred more frequently in non SVR than in SVR patients,with a significant difference for HCC(24/76 vs 1/37,P = 0.01).No SVR patient died while 20/76 non-SVR did(P = 0.002),mainly in relation to HCC(45%).CONCLUSION:In patients with HCV-related cirrhosis,SVR is associated with a significant decrease in the incidence of HCC and mortality during a follow-up period of 7.7 years.This result is a strong argument to perform and repeat antiviral treatments in patients with compensated cirrhosis.
文摘AIM: Mechanisms responsible for persistence of HCV infection and liver damage in chronic hepatitis C are not clear. Apoptosis is an important form of host immune response against viral infections. Anti-apoptotic proteinbcl-2 expression on liver tissue as well as the influence of interferon alpha 2b (IFNα2b) and ribavirin (RBV) were analyzed in patients with chronic hepatitis C. METHODS: In 30 patients with chronic hepatitis C (responders - R and non-responders - NR) treated with IFNα2b+RBV, protein bcl-2 was determined in hepatocytes and in liver associated lymphocytes before and after the treatment.RESULTS: The treatment diminished bcl-2 protein accumulation in liver cells in_patients with hepatitis C (P＜0.05). Before and after the therapy, we detected bcl-2 protein in R in 87±15% and 83±20% of hepatocytes andin 28± 18% and 26±10% of liver-associated lymphocytes, respectively. In NR, the values before treatment decreased from 94±32% to 88±21% of hepatocytes and 39±29% to 28±12% of lymphocytes with bcl-2 expression. There was no statistical correlation between bcl-2 expression on liver tissue with inflammatory activity, fibrosis and biochemical parameters before and after the treatment.CONCLUSION: IFNα2b+RBV treatment, by bcl-2 protein expression decrease, enables apoptosis of hepatocytes and associated liver lymphocytes, which in turn eliminate hepatitis C viruses.
文摘Human interferon alpha-8(IFN-α8) is an important cytokine with multiple biological functions.A genetically engineered strain, E. coli XL1-Blue/pBm, was constructed by DNA recombination technology and characterized by restriction analysis, DNA sequencing.
基金The authors wish to thank all of the investigators and participating study sites,which are listed in Supplemental Table 1,as well as all the patients who participated in this studyThe authors also wish to thank Michelle Belanger,MD,of Edanz Medical Writing for providing medical writing assistance,which was funded by Shanghai Roche Pharmaceuticals Ltd.The study was funded by Shanghai Roche Pharmaceuticals Ltd
文摘Background and Aims:Data are limited on the use of pegylated-interferon alpha-2a(peg-IFNα)in Chinese patients with chronic hepatitis B virus(HBV)infection(CHB).We evaluated the effectiveness and safety of peg-IFNαin Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice.Methods:In this prospective,multicenter,observational,non-interventional cohort study,patients were assessed for up to 1 year after peg-IFNαtreatment cessation.Treating physicians established the dosing and treatment duration according to Chinese clinical practice.Effectiveness of peg-IFNαtreatment was measured by the percentage of:patients with HBV DNA<2000 IU/mL and loss of hepatitis B surface antigen(commonly known as HBsAg);HBV DNA level at end of treatment(EOT),and 6 months and 1 year posttreatment;and time course change in quantitative HBV DNA and HBsAg.Results:At EOT,6 months posttreatment,and 1 year posttreatment,the percentage of patients with HBV DNA<2000 IU/mL was 90.0%,81.8%,and 82.2%,and that of patients with HBsAg loss was 6.5%,9.4%,and 9.5%,respectively.The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment.The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment.The incidence of adverse events was 52.0%.Conclusions:Peg-IFNαhas the potential to provide functional cure(HBsAg loss)for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China.
基金Supported by Iran National Science Foundation(Grant No.91002993)
文摘Objective: To compare the bone mass density in chronic hepatitis patients before and after interferon-a treatment.Methods: A total of 70 patients with chronic hepatitis C were treated with interferon-a and were evaluated. The treatment dosage was three million IU three times a week for one year. All the patients underwent bone mass density detection at lumbar spine and femoral neck before and after the interferon-a treatment. All the necessary information such as age,sex, and laboratory test, history of occurrence of fractures, lifestyle, and menopause status was collected by interviewers face-to-face from participants at the research visit. Smoking was categorized by whether participants were nonsmokers or smokers. Menopause was designated if there had been complete cessation of menses for more than 12 months. All statistical analyses were performed by SPSS version 14(SPSS, Inc., Chicago, IL, USA).Results: Among 70 patients, 52% were male, 48% were female and the mean age was(57.0 ± 9.6) years(range: 24–79). Twenty-nine percent of the patients had a history of smoking. The mean body mass index was(24.4 ± 3.6) kg/m^2(range: 18.4–35.3). Of the70 cases, 21 had high fibrosis-4. The prevalence of overall fracture history was 2.9%(two patients).Conclusions: Chronic hepatitis C virus infection did increase the risk of development of metabolic bone disease in this cohort. Indeed, greater reduction of bone mass density occurs in advanced liver fibrosis. The bone loss in earlier stages of chronic hepatitis C infection is likely to result from increased bone reduction rather than decreased bone formation. Overall, these observations suggest an important role for chronic hepatitis C virus infection in increased bone turnover in osteodystrophy pathogenesis.
基金This study was supported by a grant from the Scientific and Technology Bureau of Hubei Province Foundation(No.2005AA301C26).
文摘BACKGROUND: Much evidence demonstrates that the genotypes of hepatitis B virus (HBV) present differences in pathogenicity and outcomes owing to differences in genetic structure. This study aimed to investigate the influences of HBV genotypes on the anti-viral therapeutic efficacy of interferon-α (IFN-α) in chronic hepatitis B patients, and to determine the relationship between HBV genotypes and levels of viral replication or gene variations. METHODS: The chronic hepatitis B patients who were treated with IFN-α were selected randomly. Anti-viral therapeutic efficacy was monitored in these patients. The HBV genotypes were detected by PCR microplate hybridization ELISA. The levels of serum HBV-DNA were determined by fluorescence quantitative PCR. HBV gene variation at pre-C and basic core promoter (BCP) regions were assayed by gene chip technology. RESULTS: Genotypes B and C were predominant in 94 chronic hepatitis B patients. A, E and F genotypes were not found in these patients. The HBV-DNA levels of genotype C and mixed genotypes were significantly higher than those of genotype B. The response to IFN-α in patients with genotype B was markedly better than in those with genotypes C and D, and the complete response to IFN-α was only observed in genotype B. The response to IFN-α in patients with mixed genotypes was the least sensitive. The negative transition of HBeAg was correlated with variations in the HBV pre-C and BCP regions in patientswith partial or no response to IFN-α. The variation rates of HBV pre-C and BCP regions were clearly higher in genotype C than in genotype B. CONCLUSIONS: The results suggest that HBV genotype is correlated with the serum levels of HBV-DNA, HBV gene variations and therapeutic efficacy of IFN-α. The regular detection of HBV genotypes in the clinic will be of benefit for disease prognosis and planning of anti-viral therapeutic strategies.
文摘Classical interferon-alpha has been shown to be correlated with the development of a variety of autoimmune disorders. A 38 year-old female patient developed simultaneously diabetic ketoacidosis and hyperthyroidism 5 mo following initiation of treatment with pegylated interferon-α and ribavirin for chronic hepatitis C. High titers of glutamic acid decarboxylase, antinuclear and thyroid (thyroid peroxidase and thyroglobulin) antibodies were detected. Antiviral treatment was withdrawn and the patient was treated with insulin for insulin-dependent diabetes mellitus and propranolol for hyperthyroidism. Twelve months after cessation of pegylated interferon-α therapy the patient was euthyroid without any medication but remained insulin-dependent.
基金supported by grants from the National Natural Science Foundation of China(No.30771907)the Foundation of Pre-973 Program Projects(No.2009CB526411)
文摘BACKGROUND:Virological clearance,delayed progression to cirrhosis or liver cancer,and increased survival are the long-term goals of antiviral therapy in chronic hepatitis B patients.Identification of host factors correlated with therapeutic response may contribute greatly to individual treatment.This study aimed at investigating whether T29C genotype polymorphism of estrogen receptor alpha(ESR1) is associated with the initial response to interferon-alpha(IFN-α)therapy in chronic hepatitis B patients.METHODS:The initial responses of 100 patients to IFN-α therapy were evaluated and compared by classifying them into three groups according to T29C genotype polymorphism of ESR1:T/T,T/C,and C/C genotype groups.Polymerase chain reaction-restriction fragment length polymorphism was used to analyze the genotype polymorphism in T29C.RESULTS:The frequency of initially combined response was markedly higher in both the T/T and T/C groups than in the C/C group(Z=10.326,P=0.006 and Z=26.247,P=0.000, respectively).In addition,the initial virological response was higher in the T/T and T/C groups than the C/C group(χ2=5.674, P=0.017 andχ2=4.980,P=0.026,respectively).In 78 initially HBeAg-positive patients,however,the frequency of initial e-antigen disappearance or seroconversion among the T/T,T/C, and C/C genotype groups was 34.15%,27.78%and 15.79%, respectively,which were not significantly different.CONCLUSION:The T29C genotype polymorphism of ESR1 is associated with the initial response to IFN-αin patients with chronic hepatitis B,and might be a significant marker for predicting the initial response to IFN-α,at least in this study population.
文摘AIM: To investigate the safety and efficacy of long-term combination therapy with alpha interferon and lamivudine in non-responsive patients with anti-HBe-positive chronic hepatitis B.METHODS: 34 patients received combination treatment (1 month lamivudine, 12 month lamivudine+interferon, 6month lamivudine), 24 received lamivudine (12 months),24 received interferon (12 months). Interferon was administered at 6 MU tiw and lamivudine at 100 mg orally once daily. Patients were followed up for 6 months after treatment.RESULTS: At the end of treatment, HBV DNA negativity rates were 88 % with lamivudine+interferon, 99 % with lamivudine and 55 % with interferon, (P=0.004, combination therapy vs. interferon, and P=0.001 lamivudine vs.interferon), and serum transaminase normalization rates were 84 %, 91% and 53 % (P=0.01 combination therapy vs. interferon, and P=0.012 lamivudine vs. interferon). Six months later, HBV DNA negativity rates were 44 % with lamivudine+interferon, 33 % with lamivudine and 25 % with interferon, and serum transaminase normalization rates were 61%, 42 % and 45 %, respectively, without statistical significance. No YMDD variants were observed with lamivudine+interferon (vs. 12 % with lamivudine). The combination therapy appeared to be safe. CONCLUSION: Although viral clearance and transaminase normalization are slower with long-term lamivudine+interferon than that with lamivudine alone, the combination regimen seems to provide more lasting benefits and to protect against the appearance of YMDD variants. Studies with other regimens regarding sequence and duration are needed.
基金supported by grants from the Scientific Support Project of Anhui Province Education Department of China (Grant No. KJ2012ZD08 and KJ2012Z162)the National Scientific and Technological Support Projects of China (Grant No. 81101273)the National Natural Science Foundation of China (Grant No. 30872253)
文摘Objective: To determine whether Interferon-alpha-2b(IFN-α2b) can modulate the autophagic response in hepatocellular carcinoma cells.Methods: Hepatocellular carcinoma cells were treated with IFN-α2b. Autophagy was assessed by acridine orange staining, GFP-LC3 dotted assay, transmission electron microscopy and immunoblotting.Results: Acridine orange staining showed that IFN-α2b triggered the accumulation of acidic vesicular and autolysosomes in HepG2 cells. The acridine orange HepG2 cell ratios were(4.3±1.0)%,(6.9±1.4)%, and(13.1±2.3)%, respectively, after treatment with 100, 1,000, and 10,000 IU/mL IFN-α2b for 48 h. A markedly punctate pattern was observed in HepG2 cells treated with 10,000 IU/mL IFN-α2b for 48 h, but only diffuse and weakly fluorescent GFP-LC3 puncta was observed in control cells. HepG2 cells treated with 10,000 IU/mL IFN-α2b for 48 h developed autophagosome-like characteristics, including single- or double-membrane vacuoles containing intact and degraded cellular debris. The Beclin1 and LC3-II protein expression was up-regulated by IFN-α2b treatment.Conclusion: Autophagy can be induced in a dose-dependent manner by treatment with IFN-α2b in HepG2 cells, and the Beclin1 signaling pathway was stimulated by IFN-α2b.
基金The grant from Natural Science Foundation of Guangxi Zhuang Autonomous Region, No. 0542068
文摘AIM: To investigate the effects of interferon-alpha (IFN-α) to restrain the growth and invasive potential of hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV) X protein. METHODS: The pcDNA3.1-HBx plasmid was transfected into Chang cells by Lipofectamine in vitro, and Chang/HBx was co-cultured with IFN-α. Cell survival growth curve and clonogenicity assay were used to test the growth potential of Chang/pcDNA3.1, Chang/HBx and IFN-α-Chang/HBx in vitro. Growth assay in nude mice was used to detect the growth potential of Chang/ pcDNA3.1, Chang/HBx and IFN-α-Chang/HBx in vivo. Wound healing and transwell migration assays were used to detect the invasive ability of Chang/pcDNA3.1, Chang/HBx and IFN-α-Chang/HBx. RESULTS: Compared with CCL13 cells transfected with pcDNA3.1, CCL13 with stable expression of hepatitis B virus X protein showed the characteristics of malignant cells with high capability of growth and invasion by detecting their growth curves, colony forming efficiency, wound healing , transwell migration assays and growth assays in nude mice. Its capability of growth and invasion could be controlled by IFN-α. CONCLUSION: IFN-α can restrain the growth and invasive potential of HCC cells induced by HBx protein, which has provided an experimental basis for IFN-α therapy of HCC.
文摘We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus (DM) after a 13-mo period of treatment with recombinant human interferon-alpha (IFN-α) 2b. The patient presented with polydipsia, polyuria, hypergly-cemia, diabetic ketoacidosis, combined with C-peptide secretion defi ciency and positive islet cell autoantibody (ICAb). IFN-α 2b treatment was terminated and in-stead insulin treatment was initiated. Five months after cessation of the recombinant human IFN-α 2b therapy, the patient remained insulin-dependent. Her serum HBV DNA became negative and serum transaminase returned to the normal level after a 10-mo period of IFN therapy. Type 1 DM induced by IFN-α is relatively rare in patients with chronic hepatitis B. We should pay more attention to patients on IFN-α therapy to avoid destruction of pancreatic beta cells. This is the first case report from China.
文摘AIM: To explore the prevalence of autoimmune gastritis in chronic hepatitis C virus (HCV) patients and the influence of α-intefferon (IFN) treatment on autoimmune gastritis.METHODS: We performed a prospective study on 189patients with positive anti-HCV and viral RNA enrolled in a 12-month IFN protocol. We evaluated: a) the baseline prevalence of autoimmune gastritis, b) the impact of IFN treatment on development of biochemical signs of autoimmune gastritis (at 3, 6 and 12 months), c) the evolution after IFN withdrawal (12 months) in terms of anti-gastric-parietal-cell antibodies (APCA), gastrin, anti-thyroid, and anti-non-organ-specific antibodies.RESULTS: APCA positivity and 3-fold gastrin levels were detected in 3 (1.6 %) and 9 (5 %) patients, respectively, at baseline, in 25 (13 %) and 31 (16 %) patients at the end of treatment (both P＜0.001, vs baseline), and in 7 (4 %) and 14 (7 %) patients 12 months after withdrawal (P=0.002and ,P=0.01 respectively, vs baseline; P=not significant vs end of treatment). The development of autoimmune gastritis was strictly associated with the presence of autoimmune thyroiditis (P =0.0001), no relationship was found with other markers of autoimmunity.CONCLUSION: In HCV patients, IFN frequently precipitates latent autoimmune gastritis, particularly in females. Following our 12-month protocol, the phenomenon generally regressed. Since APCA positivity and high gastrin levels are associated with the presence of antithyroid antibodies,development of autoimmune thyroiditis during IFN treatment may provide a surrogate preliminary indicator of possible autoimmune gastritis to limit the need for invasive examinations.
基金Project supported by the National Key Technology Research and Development Program of China (No. 2007BAD59B06)the Interna-tional Science and Technology Cooperation Program of China (No. 2007DFA31260)the Science Foundation for the Excellent Youth Scholars of Guizhou Province, China (No. 20030312)
文摘We investigated the possibility of producing chicken alpha interferon(ChIFN-α) in transgenic plants. The cDNA encoding ChIFN-α was introduced into lettuce(Lactuca sativa L.) plants by using an agro-infiltration transient expression system. The ChIFN-α gene was correctly transcribed and translated in the lettuce plants according to RT-PCR and ELISA assays. Re-combinant protein exhibited antiviral activity in vitro by inhibition of vesicular stomatitis virus(VSV) replication on chicken embryonic fibroblast(CEF). The results demonstrate that biologically active avian cytokine with potential pharmaceutical ap-plications could be expressed in transgenic lettuce plants and that it is possible to generate interferon protein in forage plants for preventing infectious diseases of poultry.
