Objective:To investigate the effects of nebulizedα-interferon on immune function in elderly patients with respiratory tract infection.Methods:A total of 120 elderly patients with respiratory tract infection admitted ...Objective:To investigate the effects of nebulizedα-interferon on immune function in elderly patients with respiratory tract infection.Methods:A total of 120 elderly patients with respiratory tract infection admitted to our hospital from June 2023 to June 2024 were selected and randomly divided into an observation group(n=60)and a control group(n=60)using the envelope method.The control group received conventional treatment,while the observation group received additional nebulizedα-interferon therapy based on conventional treatment.After the same treatment period,changes in immune function indicators(immunoglobulins IgG,IgA,IgM)were compared between the two groups.Patients were also followed up for 3 months to observe the frequency of respiratory tract infection recurrences.Results:After treatment,IgA and IgM levels decreased significantly,while IgG levels increased significantly in both groups.The improvement in each indicator was more pronounced in the observation group than in the control group(P<0.05).By the end of the follow-up period,all 120 patients had successfully completed the follow-up,and no patients were lost to follow-up.The frequency of respiratory tract infection recurrences was lower in the observation group than in the control group(P<0.05).Conclusion:Nebulizedα-interferon can improve immune function and reduce the frequency of recurrences in elderly patients with respiratory tract infection.展开更多
Objective To study the effect of γ-interferon （IFNγ）, tumor necrosis factor related apoptosis inducing ligand （TRAIL）, and cisplatin or etoposide induced apoptosis in human neuroblastoma cell line SH-SY5Y and it...Objective To study the effect of γ-interferon （IFNγ）, tumor necrosis factor related apoptosis inducing ligand （TRAIL）, and cisplatin or etoposide induced apoptosis in human neuroblastoma cell line SH-SY5Y and its possible molecular mechanisms. Methods The expressions of Caspase 8 mRNA and protein were detected with RT-PCR and Western blot analysis. The effects of IFNγ, TRAIL, IFNγ ＋ TRAIL, IFNγ ＋ Caspase 8 inhibitor ＋ TRAIL, IFNγ ＋ cisplatin ＋ TRAIL, and IFNγ ＋ etoposide ＋ TRAIL on the growth and apoptosis of SH-SY5Y cells were detected with the methods of MTT and flow cytometry. The relative Caspase 8 activity was measured with colorimetric assay. Results Caspase 8 was undetectable in SH-SY5Y cells but an increased expression of Caspase 8 mRNA and protein was found after treatment with IFNγ. SH-SY5Y ceils themselves were not sensitive to TRAIL, but those expressing Caspase 8 after treatment with IFNγ were. The killing effect of TRAIL on SH-SY5Y cells expressing Caspase 8 was depressed by Caspase 8 inhibitor. Cisplatin and etoposide could enhance the sensitivity of TRAIL on SH-SY5Y cells. The relative Caspase 8 activity of SH-SY5Y cells in IFNγ ＋ TRAIL group was significantly higher than those of control group, IFNγ group, TRAIL group, and inhibitor group （ P 〈 0. 01 ）. There was no significant difference among IFNγ ＋ TRAIL group, IFNγ ＋ cisplatin ＋ TRAIL group, and IFNγ ＋ etoposide ＋ TRAIL group. Conclusions IFNγ could sensitize SH-SY5Y cells to TRAIL-induced apoptosis and this may be realized by the up-regulation of Caspase 8. Cisplatin and etoposide could enhance the killing effect of TRAIL on SH-SY5Y cells.展开更多
Objective:To analyze the factors affecting the efficacy ofα-interferon in the treatment of chronic hepatitis B(CHB).Methods:A total of 100 patients with CHB treated in our hospital from June 2018 to June 2019 were se...Objective:To analyze the factors affecting the efficacy ofα-interferon in the treatment of chronic hepatitis B(CHB).Methods:A total of 100 patients with CHB treated in our hospital from June 2018 to June 2019 were selected.All patients were treated withα-interferon to evaluate the efficacy,and the factors affecting the effect ofα-interferon on CHB were analyzed.Results:After treatment,54 patients fully responded and 46 patients did not;the levels of white blood cells,HBV DNA,and HBsAg in the complete response group were lower than those in the incompletely response group,and the differences were statistically significant(P<0.05);Multivariate logistic regression analysis found that serum HBV DNA and HBsAg were independent factors affecting the efficacy ofα-interferon in the treatment of CHB(OR>1,P<0.05).Conclusion:Serum HBV DNA and HBsAg are risk factors that affect the efficacy ofα-interferon in the treatment of CHB.Monitoring the changes of serum HBV DNA and HBsAg levels has important clinical significance for predicting the efficacy.展开更多
BACKGROUND： Neuropeptide Y （NPY） may influence differentiation of Th cells immunological pathology of experimental allergic encephalomyelitis （EAE） is differentiation of Th cells It is assumed that the related to...BACKGROUND： Neuropeptide Y （NPY） may influence differentiation of Th cells immunological pathology of experimental allergic encephalomyelitis （EAE） is differentiation of Th cells It is assumed that the related to abnormal OBJECTIVE： To investigate the effect of NPY on white matter demyelination, the serum levels interleukin-4 （IL-4） and gamma-interferon （IFN-γ ）, as well as EAE pathogenesis in an EAE guinea pig model following NPY injection into the lateral cerebral ventricle. DESIGN, TIME AND SETTING： A randomized controlled animal study, which was performed in the Infection Immunity Animal Laboratory, Affiliated Hospital of Luzhou Medical College, China, from October 2005 to April 2006. MATERIALS： Thirty healthy female guinea pigs of 8-12 weeks of age, and 10 healthy female rats of three months of age were used. NPY was provided by Sigma Company, USA. NPY kit was provided by Beijing Huaying Biotechnology Institute, China. METHODS： Thirty guinea pigs were randomly divided into three groups： normal control group, EAE model group, and NPY intervention group （n =10 per group）. Normal control group and EAE model group： Saline （10μ L, once） was injected into the lateral cerebral ventricle. After one week, the same volume of Freund＇s adjuvant complete was either injected subcutaneously into two post-palms or EAE was modeled. NPY intervention group： EAE was modeled after one week and NPY was injected （10 μ L of 6 nmol NPY, once） into the lateral cerebral ventricle. Myelin basic protein （MBP） antigen made from rat spinal cord homogenate and Freund＇s adjuvant complete were injected subcutaneously into both post-palms （0.2 mL per palm） to establish the EAE model. MAIN OUTCOME MEASURES： White matter demyelination of the cerebrum, cerebellum, brain stem, and spinal cord were observed by light microscopy after HE staining. Levels of serum IFN-γ and IL-4 were detected by the double antibody sandwich ABC-ELISA technique. NPY content was detected by radioimmunoassay. RESULTS： Pathological alterations in the NPY intervention groups were reduced compared to those in the EAE model group, suggesting a reduction and remission of white matter demyelination with NPY treatment. When compared to the model group, the serum IL-4 level was increased in the NPY intervention group during the high-frequent EAE stage （P 〈 0.01）, but the serum IFN-γ level was decreased （P 〈 0.01）. Furthermore, the EAE latency was prolonged （P 〈 0.01）, the neurological scores were decreased in the high-frequent EAE stage （P 〈 0.01）, and the death rate was decreased （P 〈 0.05）. NPY content and the serum IL-4 level at the peak stage were positively correlated with those in the latent phase （r =0.863-0.900, P 〈 0.01）, but negatively correlated with neurological scores at the peak stage （r=- -0.068 to -0.863, P 〈 0.05-0.01）. The IFN-γ level at the peak stage was negatively correlated to that in the latent phase （r = -0.683-0.650, P 〈 0.05）, but positively correlated to neurological scores at the peak stage （r =0.975, 0.845, P 〈 0.05）. CONCLUSION： NPY injection into the lateral cerebral ventricle can promote the secretion of IL-4, inhibit the production of IFN-γ, relieve white matter demyelination, and inhibit EAE attack in an experimental model of EAE.展开更多
Objective: To study the effect of α-interferon + gemcitabine combined with infusion chemotherapy on the proliferation and infiltrative growth of advanced bladder cancer. Methods: Patients with advanced bladder cancer...Objective: To study the effect of α-interferon + gemcitabine combined with infusion chemotherapy on the proliferation and infiltrative growth of advanced bladder cancer. Methods: Patients with advanced bladder cancer who accepted bladder infusion chemotherapy in Wuhan Red Cross Hospital between March 2015 and August 2016 were selected and randomly divided into the IFN-α+GEM group and the GEM group who acceptedα-interferon + gemcitabine combined with infusion chemotherapy and single gemcitabine infusion chemotherapy respectively. The contents of bladder cancer markers, cancer cell apoptosis molecules and angiogenesis molecules in urine were detected before treatment and 3 months after treatment. Results: 3 months after treatment, NMP-22, BLCA-4, Apo-A1, HA, CYFRA21-1, ANG, NAC-1, VEGF and bFGF levels in urine of both groups of patients were significantly lower than those before treatment while PTEN, TRAIL, Bim, HSG and p16 levels were significantly higher than those before treatment, and NMP-22, BLCA-4, Apo-A1, HA, CYFRA21-1, ANG, NAC-1, VEGF and bFGF levels in urine of IFN-α+GEM group were significantly lower than those of GEM group while PTEN, TRAIL, Bim, HSG and p16 levels were significantly higher than those of GEM group. Conclusion: α-interferon + gemcitabine combined with infusion chemotherapy can be more effective than single gemcitabine infusion chemotherapy in killing cancer cells and inhibiting the proliferation and infiltrative growth of the cancer cells.展开更多
AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibr...AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-gamma groups, and 10.01 +/- 3.23 in fibrotic model group. The difference was statistically significant (P【0.01). Similar results were found in DMN-induced model. Pathological fibrosis scores were 6.30 +/- 0.48, 8.10 +/- 2.72 and 8.30 +/- 2.58, in high, medium and low doses IFN-gamma groups, and 12.60 +/- 3.57 in fibrotic model group. Hydroxyl proline contents were 2.72 +/- 0.58, 3.14 +/- 0.71 and 3.62 +/- 1.02, in the three IFN-gamma groups, and 12.79 +/- 1.54 in fibrotic model group. The difference was statistically significant (P【0.01).Serum hepatic fibrosis indices decreased significantly in the 47 patients after IFN-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 192.59 +/- 89.95 vs 156.98 +/- 49.22; C-I: 156.30 +/- 44.01 vs 139.14 +/- 34.47) and the differences between the four indices were significant (P 【0.05). Thirty-three patients received two liver biopsies, one before and one after IFN-gamma treatment. In thirty of 33 patients IFN-gamma had better effects according to semi-quantitative pathological scores (8.40 +/- 5.83 vs 5.30 +/- 4.05, P【0.05). CONCLUSION: All the three doses of IFN-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.展开更多
AIM To investigate the therapeutic potential of gamma interferon (IFN γ) gene modified human hepatocellular carcinoma (HCC) cells. METHODS The IFN γ gene was introduced retrovirally into four HCC cell lines. S...AIM To investigate the therapeutic potential of gamma interferon (IFN γ) gene modified human hepatocellular carcinoma (HCC) cells. METHODS The IFN γ gene was introduced retrovirally into four HCC cell lines. Secreted IFN γ activity was assessed using bioassay. The expression of MHC molecules was detected by FACS. Tumorigenicity was analysed by tumor formation in nude mice. RESULTS Four IFN γ gene transduced HCC cell lines secreted different amounts of IFN γ, as in the same case of five clones derived from one HCC cell line. Transduction with IFN γ caused significant increase in the expression of major histocompatibility complex (MHC) antigens on HCC cells. The expression of HLA class Ⅰ was increased by 2-3 times in terms of mean fluorescence intensities, while for class Ⅱ expression, the percentage of positive cells augmented from <10% to >50%. When equal amount of tumor cells were injected into nude mice, the tumorigenicity of some transduced cells decreased dramatically. CONCLUSION IFN γ gene transduction can convert weakly immunogenic HCC cells to activate antitumor immune response, and further pave the way for the future use of such gene modified tumor cells as a modality for the cancer immunotherapy.展开更多
Mild to moderate autoimmune thrombocytopenia(AITP) is a common finding in patients receiving interferonbased antiviral treatment, due to bone marrow suppression. Here we report the case of a patient with chronic genot...Mild to moderate autoimmune thrombocytopenia(AITP) is a common finding in patients receiving interferonbased antiviral treatment, due to bone marrow suppression. Here we report the case of a patient with chronic genotype 1b hepatitis C virus(HCV) infection treated with pegylated-interferon alpha-2a, ribavirin and telaprevir for 24 wk; the patient developed severe AITP three weeks after treatment withdrawal. We performed a systematic literature search in order to review all published cases of AITP related to HCV antiviral treatment. To our knowledge, this is the second case of AITP observed after antiviral treatment withdrawal. In most published cases AITP occurred during treatment; in fact, among 24 cases of AITP related to interferonbased antiviral treatment, only one occurred after discontinuation. Early diagnosis of AITP is a key factor in order to achieve an early interferon discontinuation; in the era of new direct antiviral agents those patients have to be considered for interferon-free treatment regimens. Prompt prescription of immuno-suppressant treatment(i.e., corticosteroids, immunoglobulin infusion and even rituximab for unresponsive cases) leads to favourable prognosis in most of cases. Physicians using interferonbased treatments should be aware that AITP can occur both during and after treatment, specially in the new era of interferon-free antiviral treatment. Finally, in the case of suspected AITP, presence of anti-platelet antibodies should be checked not only during treatment but alsoafter discontinuation.展开更多
AIM:To investigate the efficacy of short-term peginterferon(PEG-IFN)monotherapy for chronic hepatitis C patients who achieved an immediate virological response.METHODS:Defining an"immediate virological response(I...AIM:To investigate the efficacy of short-term peginterferon(PEG-IFN)monotherapy for chronic hepatitis C patients who achieved an immediate virological response.METHODS:Defining an"immediate virological response(IVR)"as the loss of serum hepatitis C virus(HCV) RNA 7 d after the first administration of PEG-IFNα,we conducted a 12-wk course of PEG-IFNα2a monotherapy without the addition of ribavirin for 38 patients who had low pretreatment HCV RNA load and exhibited IVR.The patients included 21 men and 17 women,whose ages ranged from 22 to 77 years(mean±SD:52.0±17.8 years).There were 4 patients with HCV genotype 1b,23 patients with genotype 2a and 4 patients with genotype 2b.HCV genotype was not determined for the remaining 7 patients.Patients were categorized into a sustained virological response(SVR)group,if serum HCV RNA remained negative for 24 wk after the end of treatment,or into a relapse group.RESULTS:Based on the intention-to-treat analysis,35 patients(92.1%)achieved SVR.One patient(2.6%)relapsed with serum HCV RNA 12 wk after the end of treatment.Two patients(5.3%)withdrew from the study during the 24-wk follow-up period.With regard to the HCV RNA genotype,the SVR rates were 100%(4/4) for genotype 1b,95.7%(22/23)for genotype 2a and 100%(4/4)for genotype 2b.The SVR rate in 7 patients,whose HCV RNA genotypes were not determined,was 71.4%(5/7).CONCLUSION:Short-term PEG-IFNα2a monotherapy is highly effective for chronic hepatitis C patients who have low pretreatment HCV RNA load and exhibit IVR.展开更多
AIM: To compare efficacy of telaprevir(TVR) and simeprevir(SMV) combined with pegylated interferon(PEG-IFN) and ribavirin(RBV) while treating chronic hepatitis C(CHC). METHODS: In all, 306 CHC patients were included i...AIM: To compare efficacy of telaprevir(TVR) and simeprevir(SMV) combined with pegylated interferon(PEG-IFN) and ribavirin(RBV) while treating chronic hepatitis C(CHC). METHODS: In all, 306 CHC patients were included in this study. There were 159 patients in the TVR combination therapy group and 147 patients in the SMV combination therapy group. To evaluate pretreatment factors contributing to sustained virological response at 12 wk(SVR12), univariate and multivariate analyses were performed in TVR and SMV groups. To adjust for patient background between TVR and SMV groups, propensity score matching was performed. Virological response during treatment and SVR12 were evaluated.RESULTS: Overall rates of SVR12 [undetectable serum hepatitis C virus(HCV) RNA levels] were 79.2% and 69.4% in TVR and SMV groups, respectively. Patients in the SMV group were older, had higher serum HCV RNA levels, lower hemoglobin, higher prevalence of unfavorable interleukin-28B(IL28B) genotype(rs8099917), and poorer response to previous PEG-IFN and RBV treatment. Propensity score matching was performed to adjust for backgrounds(n = 104) and demonstrated SVR12 rates of 74.0% and 73.1% in the TVR and SMV groups, respectively. In the TVR group, discontinuation rates were higher because of adverse events; however, breakthrough and nonresponse was more frequent in the in SMV group. Multivariate analysis revealed IL28 B genotype(rs8099917) as the only independent predictive factor of SVR12 in both groups.CONCLUSION: SVR12 rates were almost identical following propensity score matching.展开更多
AIM: To evaluate interferon-λ3(IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin(Peg-IFNα/RBV) therapy for genotype 2(G2) chronic hepatitis C.METHODS: Between January 2006 and June 2012,...AIM: To evaluate interferon-λ3(IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin(Peg-IFNα/RBV) therapy for genotype 2(G2) chronic hepatitis C.METHODS: Between January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis C virus(HCV) were treated with responseguided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response(RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype(TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HCV subgenotype 2a or 2b.RESULTS: Of the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response(SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate(96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5%(P < 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups(80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR(OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis according to HCV sub-genotype, no significant difference in the SVR rate was found between HCV sub-genotypes 2a and 2b.CONCLUSION: In response-guided Peg-IFNα/RBV combination therapy for chronically HCV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients.展开更多
AIM: To investigate if correction of hypovitaminosis D before initiation of Peg-interferon-alpha/ribavirin(Peg IFN/RBV) therapy could improve the efficacy of Peg IFN/RBV in previously null-responder patients with chro...AIM: To investigate if correction of hypovitaminosis D before initiation of Peg-interferon-alpha/ribavirin(Peg IFN/RBV) therapy could improve the efficacy of Peg IFN/RBV in previously null-responder patients with chronic genotype 1 or 4 hepatitis C virus(HCV) infection.METHODS:Genotype 1 or 4 HCV-infected patients with null response to previous Peg IFN/RBV treatment and with hypovitaminosis D(<30 ng/m L)prospectively received cholecalciferol 100000 IU per week for 4 wk[from week-4(W-4)to W0],followed by 100000 IUper month in combination with Peg IFN/RBV for 12 mo(from W0 to W48).The primary outcome was the rate of early virological response defined by an HCV RNA<12 IU/m L after 12 wk Peg IFN/RBV treatment.RESULTS:A total of 32 patients were included,19(59%)and 13(41%)patients were HCV genotype1 and 4,respectively.The median baseline vitamin D level was 15 ng/m L(range:7-28).In modified intention-to-treat analysis,29 patients who received at least one dose of Peg IFN/RBV were included in the analysis.All patients except one normalized their vitamin D serum levels.The rate of early virologic response was 0/29(0%).The rate of HCV RNA<12IU/m L after 24 wk of Peg IFN/RBV was 1/27(4%).The safety profile was favorable.CONCLUSION:Addition of vitamin D to Peg IFN/RBV does not improve the rate of early virologic response in previously null-responders with chronic genotype 1or 4 HCV infection.展开更多
AIM:To evaluate the effect of long-term treatment with leukocyte natural-interferon(ln-α-IFN)plus ribavirin(RBV).METHODS:Forty-six patients with hepatitis C virus(HCV)recurrence received 3 MU three times a week of ln...AIM:To evaluate the effect of long-term treatment with leukocyte natural-interferon(ln-α-IFN)plus ribavirin(RBV).METHODS:Forty-six patients with hepatitis C virus(HCV)recurrence received 3 MU three times a week of ln-α-IFN plus RBV for 1 mo;then,patients with good tolerability(n=30)were switched to daily IFN administration,while the remaining were treated with the same schedule.Patients have been treated for 12 mo after viral clearance while non-responders(NR)entered in the longterm treatment group.Liver biopsies were planned at baseline,1 year after sustained virological response(SVR)and at 36 mo after start of therapy in NR.MedCalc software package was used for statistical analysis.RESULTS:About 16.7%of genotype 1-4 and 70%of genotype 2-3 patients achieved SVR.Nine patients withdrew therapy because of non-tolerance or noncompliance.A significant improvement in serum biochemistry and histological activity was observed in all SVR patients and long-term treated;100%of patients with SVR achieved a histological response(fibrosis stabilization or improvement)with a significant reduction in mean staging value(from 2.1 to 1.0;P=0.0031);histological response was observed in 84%of long-term treated patients compared to 57%of drop-out.Six patients died during the entire study period(follow-up 40.6±7.7 mo);of them,5 presented with severe HCV recurrence on enrollment.Diabetes(OR=0.38,95%CI:0.08-0.59,P=0.01),leukopenia(OR=0.54,95%CI:0.03-0.57,P=0.03)and severe HCV recurrence(OR=0.51,95%CI:0.25-0.69,P=0.0003)were variables associated to survival.Long-term treatment was well tolerated;no patients developed rejection or autoimmune disease.CONCLUSION:Long-term treatment improves histology in SVR patients and slows disease progression also in NR,leading to a reduction in liver decompensation,graft failure and liver-related death.展开更多
Purpose: The optimal formulation of pegylated interferon a (PEG-IFa) as a part of combination therapy with ribavirin (RBV) is uncertain for patients infected with hepatitis C Genotypes 2 and 3. Methods: A multivariate...Purpose: The optimal formulation of pegylated interferon a (PEG-IFa) as a part of combination therapy with ribavirin (RBV) is uncertain for patients infected with hepatitis C Genotypes 2 and 3. Methods: A multivariate analysis of prospectively collected treatment data from two tertiary centres on 351 treatment na?ve HCV Genotype 2 or 3 patients who received PEG-IFa-2a or b plus ribavirin. Results: Univariate analyses demonstrate that PEG-IFa-2b based on regimens achieved a higher sustained virological response (SVR) than PEG-IFa-2a (77.9% versus 62.0%, P = 0.0012). On multivariate analyses, PEG-IFa-2b appeared superior to PEG-IFa-2a with an odds ratio (OR) and 95% confidence interval (CI95) for SVR of 2.19 (CI95 1.35-3.52, P = 0.0005). Genotype was a significant predictor of outcome in the multivariate model with 80% of Genotype 2 but only 67.7% of Genotype 3 subjects achieving SVR (OR 2.66 [CI95 1.35-5.92]). Increasing age was negatively associated with SVR (OR 0.97 [CI95 0.94-0.99]). Some of the differences in SVR are explained by higher relapse rates with PEG-IFa-2a (P = 0.009). Conclusions: PEG-IFa-2b and RBV achieve higher SVR rates than PEG-IFa-2a and RBV in Genotypes 2 and 3 chronic HCV infections. There is less relapse with PEG-IFa-2b. Genotype 2 infections are considerably easier to cure. SVR is higher in younger patients. These findings should influence a choice of PEG-IFa in the era of direct acting anti-viral drugs in therapy of Genotypes 2 and 3.展开更多
This is a case of 52 years old male patient with chronic obstructive pulmonary disease (COPD) who developed semi-invasive pulmonary aspergillosis while on pegylated-interferon alpha-2a and for chronic hepatitis C infe...This is a case of 52 years old male patient with chronic obstructive pulmonary disease (COPD) who developed semi-invasive pulmonary aspergillosis while on pegylated-interferon alpha-2a and for chronic hepatitis C infection. This complication is very rarely seen during interferon therapy for other any purposes. Pulmonary aspergillosis in particular group of chronic hepatitis C patients under immunosupressive therapy should also be in mind and interdisciplinary medical cooperation might be needed during the treatment for immune-suppressed patients. Pulmonary aspergillosis is also discussed from many aspects in the light of the literature.展开更多
干扰素-γ诱导蛋白16(interferon gamma-inducible protein 16,IFI16)是含pyrin和造血表达、干扰素诱导特性和核定位(hematopoietic expression,interferon-inducible nature,and nuclear localization,HIN)结构域的蛋白质(pyrin and HI...干扰素-γ诱导蛋白16(interferon gamma-inducible protein 16,IFI16)是含pyrin和造血表达、干扰素诱导特性和核定位(hematopoietic expression,interferon-inducible nature,and nuclear localization,HIN)结构域的蛋白质(pyrin and HIN domain-containing protein,PYHIN)家族的重要成员,其独特的分子结构使其能够识别细胞内的多种核酸分子。作为一种关键的免疫调节因子,IFI16可通过多种途径参与天然免疫信号转导,在宿主抗病毒防御中发挥重要作用。本文综述了IFI16的分子特征及其在天然免疫和病毒感染中的调控机制,为抗病毒感染的治疗靶点及药物开发提供理论依据。展开更多
文摘Objective:To investigate the effects of nebulizedα-interferon on immune function in elderly patients with respiratory tract infection.Methods:A total of 120 elderly patients with respiratory tract infection admitted to our hospital from June 2023 to June 2024 were selected and randomly divided into an observation group(n=60)and a control group(n=60)using the envelope method.The control group received conventional treatment,while the observation group received additional nebulizedα-interferon therapy based on conventional treatment.After the same treatment period,changes in immune function indicators(immunoglobulins IgG,IgA,IgM)were compared between the two groups.Patients were also followed up for 3 months to observe the frequency of respiratory tract infection recurrences.Results:After treatment,IgA and IgM levels decreased significantly,while IgG levels increased significantly in both groups.The improvement in each indicator was more pronounced in the observation group than in the control group(P<0.05).By the end of the follow-up period,all 120 patients had successfully completed the follow-up,and no patients were lost to follow-up.The frequency of respiratory tract infection recurrences was lower in the observation group than in the control group(P<0.05).Conclusion:Nebulizedα-interferon can improve immune function and reduce the frequency of recurrences in elderly patients with respiratory tract infection.
基金the National Natural Sciences Foundation of China(39470739)the Ministry of Public Health Research Foundation(20122167)the Doctor Startup-Natural Science Foundation of Li-aoning Province (20041047)
文摘Objective To study the effect of γ-interferon （IFNγ）, tumor necrosis factor related apoptosis inducing ligand （TRAIL）, and cisplatin or etoposide induced apoptosis in human neuroblastoma cell line SH-SY5Y and its possible molecular mechanisms. Methods The expressions of Caspase 8 mRNA and protein were detected with RT-PCR and Western blot analysis. The effects of IFNγ, TRAIL, IFNγ ＋ TRAIL, IFNγ ＋ Caspase 8 inhibitor ＋ TRAIL, IFNγ ＋ cisplatin ＋ TRAIL, and IFNγ ＋ etoposide ＋ TRAIL on the growth and apoptosis of SH-SY5Y cells were detected with the methods of MTT and flow cytometry. The relative Caspase 8 activity was measured with colorimetric assay. Results Caspase 8 was undetectable in SH-SY5Y cells but an increased expression of Caspase 8 mRNA and protein was found after treatment with IFNγ. SH-SY5Y ceils themselves were not sensitive to TRAIL, but those expressing Caspase 8 after treatment with IFNγ were. The killing effect of TRAIL on SH-SY5Y cells expressing Caspase 8 was depressed by Caspase 8 inhibitor. Cisplatin and etoposide could enhance the sensitivity of TRAIL on SH-SY5Y cells. The relative Caspase 8 activity of SH-SY5Y cells in IFNγ ＋ TRAIL group was significantly higher than those of control group, IFNγ group, TRAIL group, and inhibitor group （ P 〈 0. 01 ）. There was no significant difference among IFNγ ＋ TRAIL group, IFNγ ＋ cisplatin ＋ TRAIL group, and IFNγ ＋ etoposide ＋ TRAIL group. Conclusions IFNγ could sensitize SH-SY5Y cells to TRAIL-induced apoptosis and this may be realized by the up-regulation of Caspase 8. Cisplatin and etoposide could enhance the killing effect of TRAIL on SH-SY5Y cells.
文摘Objective:To analyze the factors affecting the efficacy ofα-interferon in the treatment of chronic hepatitis B(CHB).Methods:A total of 100 patients with CHB treated in our hospital from June 2018 to June 2019 were selected.All patients were treated withα-interferon to evaluate the efficacy,and the factors affecting the effect ofα-interferon on CHB were analyzed.Results:After treatment,54 patients fully responded and 46 patients did not;the levels of white blood cells,HBV DNA,and HBsAg in the complete response group were lower than those in the incompletely response group,and the differences were statistically significant(P<0.05);Multivariate logistic regression analysis found that serum HBV DNA and HBsAg were independent factors affecting the efficacy ofα-interferon in the treatment of CHB(OR>1,P<0.05).Conclusion:Serum HBV DNA and HBsAg are risk factors that affect the efficacy ofα-interferon in the treatment of CHB.Monitoring the changes of serum HBV DNA and HBsAg levels has important clinical significance for predicting the efficacy.
文摘BACKGROUND： Neuropeptide Y （NPY） may influence differentiation of Th cells immunological pathology of experimental allergic encephalomyelitis （EAE） is differentiation of Th cells It is assumed that the related to abnormal OBJECTIVE： To investigate the effect of NPY on white matter demyelination, the serum levels interleukin-4 （IL-4） and gamma-interferon （IFN-γ ）, as well as EAE pathogenesis in an EAE guinea pig model following NPY injection into the lateral cerebral ventricle. DESIGN, TIME AND SETTING： A randomized controlled animal study, which was performed in the Infection Immunity Animal Laboratory, Affiliated Hospital of Luzhou Medical College, China, from October 2005 to April 2006. MATERIALS： Thirty healthy female guinea pigs of 8-12 weeks of age, and 10 healthy female rats of three months of age were used. NPY was provided by Sigma Company, USA. NPY kit was provided by Beijing Huaying Biotechnology Institute, China. METHODS： Thirty guinea pigs were randomly divided into three groups： normal control group, EAE model group, and NPY intervention group （n =10 per group）. Normal control group and EAE model group： Saline （10μ L, once） was injected into the lateral cerebral ventricle. After one week, the same volume of Freund＇s adjuvant complete was either injected subcutaneously into two post-palms or EAE was modeled. NPY intervention group： EAE was modeled after one week and NPY was injected （10 μ L of 6 nmol NPY, once） into the lateral cerebral ventricle. Myelin basic protein （MBP） antigen made from rat spinal cord homogenate and Freund＇s adjuvant complete were injected subcutaneously into both post-palms （0.2 mL per palm） to establish the EAE model. MAIN OUTCOME MEASURES： White matter demyelination of the cerebrum, cerebellum, brain stem, and spinal cord were observed by light microscopy after HE staining. Levels of serum IFN-γ and IL-4 were detected by the double antibody sandwich ABC-ELISA technique. NPY content was detected by radioimmunoassay. RESULTS： Pathological alterations in the NPY intervention groups were reduced compared to those in the EAE model group, suggesting a reduction and remission of white matter demyelination with NPY treatment. When compared to the model group, the serum IL-4 level was increased in the NPY intervention group during the high-frequent EAE stage （P 〈 0.01）, but the serum IFN-γ level was decreased （P 〈 0.01）. Furthermore, the EAE latency was prolonged （P 〈 0.01）, the neurological scores were decreased in the high-frequent EAE stage （P 〈 0.01）, and the death rate was decreased （P 〈 0.05）. NPY content and the serum IL-4 level at the peak stage were positively correlated with those in the latent phase （r =0.863-0.900, P 〈 0.01）, but negatively correlated with neurological scores at the peak stage （r=- -0.068 to -0.863, P 〈 0.05-0.01）. The IFN-γ level at the peak stage was negatively correlated to that in the latent phase （r = -0.683-0.650, P 〈 0.05）, but positively correlated to neurological scores at the peak stage （r =0.975, 0.845, P 〈 0.05）. CONCLUSION： NPY injection into the lateral cerebral ventricle can promote the secretion of IL-4, inhibit the production of IFN-γ, relieve white matter demyelination, and inhibit EAE attack in an experimental model of EAE.
文摘Objective: To study the effect of α-interferon + gemcitabine combined with infusion chemotherapy on the proliferation and infiltrative growth of advanced bladder cancer. Methods: Patients with advanced bladder cancer who accepted bladder infusion chemotherapy in Wuhan Red Cross Hospital between March 2015 and August 2016 were selected and randomly divided into the IFN-α+GEM group and the GEM group who acceptedα-interferon + gemcitabine combined with infusion chemotherapy and single gemcitabine infusion chemotherapy respectively. The contents of bladder cancer markers, cancer cell apoptosis molecules and angiogenesis molecules in urine were detected before treatment and 3 months after treatment. Results: 3 months after treatment, NMP-22, BLCA-4, Apo-A1, HA, CYFRA21-1, ANG, NAC-1, VEGF and bFGF levels in urine of both groups of patients were significantly lower than those before treatment while PTEN, TRAIL, Bim, HSG and p16 levels were significantly higher than those before treatment, and NMP-22, BLCA-4, Apo-A1, HA, CYFRA21-1, ANG, NAC-1, VEGF and bFGF levels in urine of IFN-α+GEM group were significantly lower than those of GEM group while PTEN, TRAIL, Bim, HSG and p16 levels were significantly higher than those of GEM group. Conclusion: α-interferon + gemcitabine combined with infusion chemotherapy can be more effective than single gemcitabine infusion chemotherapy in killing cancer cells and inhibiting the proliferation and infiltrative growth of the cancer cells.
文摘AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-gamma groups, and 10.01 +/- 3.23 in fibrotic model group. The difference was statistically significant (P【0.01). Similar results were found in DMN-induced model. Pathological fibrosis scores were 6.30 +/- 0.48, 8.10 +/- 2.72 and 8.30 +/- 2.58, in high, medium and low doses IFN-gamma groups, and 12.60 +/- 3.57 in fibrotic model group. Hydroxyl proline contents were 2.72 +/- 0.58, 3.14 +/- 0.71 and 3.62 +/- 1.02, in the three IFN-gamma groups, and 12.79 +/- 1.54 in fibrotic model group. The difference was statistically significant (P【0.01).Serum hepatic fibrosis indices decreased significantly in the 47 patients after IFN-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 192.59 +/- 89.95 vs 156.98 +/- 49.22; C-I: 156.30 +/- 44.01 vs 139.14 +/- 34.47) and the differences between the four indices were significant (P 【0.05). Thirty-three patients received two liver biopsies, one before and one after IFN-gamma treatment. In thirty of 33 patients IFN-gamma had better effects according to semi-quantitative pathological scores (8.40 +/- 5.83 vs 5.30 +/- 4.05, P【0.05). CONCLUSION: All the three doses of IFN-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.
文摘AIM To investigate the therapeutic potential of gamma interferon (IFN γ) gene modified human hepatocellular carcinoma (HCC) cells. METHODS The IFN γ gene was introduced retrovirally into four HCC cell lines. Secreted IFN γ activity was assessed using bioassay. The expression of MHC molecules was detected by FACS. Tumorigenicity was analysed by tumor formation in nude mice. RESULTS Four IFN γ gene transduced HCC cell lines secreted different amounts of IFN γ, as in the same case of five clones derived from one HCC cell line. Transduction with IFN γ caused significant increase in the expression of major histocompatibility complex (MHC) antigens on HCC cells. The expression of HLA class Ⅰ was increased by 2-3 times in terms of mean fluorescence intensities, while for class Ⅱ expression, the percentage of positive cells augmented from <10% to >50%. When equal amount of tumor cells were injected into nude mice, the tumorigenicity of some transduced cells decreased dramatically. CONCLUSION IFN γ gene transduction can convert weakly immunogenic HCC cells to activate antitumor immune response, and further pave the way for the future use of such gene modified tumor cells as a modality for the cancer immunotherapy.
文摘Mild to moderate autoimmune thrombocytopenia(AITP) is a common finding in patients receiving interferonbased antiviral treatment, due to bone marrow suppression. Here we report the case of a patient with chronic genotype 1b hepatitis C virus(HCV) infection treated with pegylated-interferon alpha-2a, ribavirin and telaprevir for 24 wk; the patient developed severe AITP three weeks after treatment withdrawal. We performed a systematic literature search in order to review all published cases of AITP related to HCV antiviral treatment. To our knowledge, this is the second case of AITP observed after antiviral treatment withdrawal. In most published cases AITP occurred during treatment; in fact, among 24 cases of AITP related to interferonbased antiviral treatment, only one occurred after discontinuation. Early diagnosis of AITP is a key factor in order to achieve an early interferon discontinuation; in the era of new direct antiviral agents those patients have to be considered for interferon-free treatment regimens. Prompt prescription of immuno-suppressant treatment(i.e., corticosteroids, immunoglobulin infusion and even rituximab for unresponsive cases) leads to favourable prognosis in most of cases. Physicians using interferonbased treatments should be aware that AITP can occur both during and after treatment, specially in the new era of interferon-free antiviral treatment. Finally, in the case of suspected AITP, presence of anti-platelet antibodies should be checked not only during treatment but alsoafter discontinuation.
文摘AIM:To investigate the efficacy of short-term peginterferon(PEG-IFN)monotherapy for chronic hepatitis C patients who achieved an immediate virological response.METHODS:Defining an"immediate virological response(IVR)"as the loss of serum hepatitis C virus(HCV) RNA 7 d after the first administration of PEG-IFNα,we conducted a 12-wk course of PEG-IFNα2a monotherapy without the addition of ribavirin for 38 patients who had low pretreatment HCV RNA load and exhibited IVR.The patients included 21 men and 17 women,whose ages ranged from 22 to 77 years(mean±SD:52.0±17.8 years).There were 4 patients with HCV genotype 1b,23 patients with genotype 2a and 4 patients with genotype 2b.HCV genotype was not determined for the remaining 7 patients.Patients were categorized into a sustained virological response(SVR)group,if serum HCV RNA remained negative for 24 wk after the end of treatment,or into a relapse group.RESULTS:Based on the intention-to-treat analysis,35 patients(92.1%)achieved SVR.One patient(2.6%)relapsed with serum HCV RNA 12 wk after the end of treatment.Two patients(5.3%)withdrew from the study during the 24-wk follow-up period.With regard to the HCV RNA genotype,the SVR rates were 100%(4/4) for genotype 1b,95.7%(22/23)for genotype 2a and 100%(4/4)for genotype 2b.The SVR rate in 7 patients,whose HCV RNA genotypes were not determined,was 71.4%(5/7).CONCLUSION:Short-term PEG-IFNα2a monotherapy is highly effective for chronic hepatitis C patients who have low pretreatment HCV RNA load and exhibit IVR.
文摘AIM: To compare efficacy of telaprevir(TVR) and simeprevir(SMV) combined with pegylated interferon(PEG-IFN) and ribavirin(RBV) while treating chronic hepatitis C(CHC). METHODS: In all, 306 CHC patients were included in this study. There were 159 patients in the TVR combination therapy group and 147 patients in the SMV combination therapy group. To evaluate pretreatment factors contributing to sustained virological response at 12 wk(SVR12), univariate and multivariate analyses were performed in TVR and SMV groups. To adjust for patient background between TVR and SMV groups, propensity score matching was performed. Virological response during treatment and SVR12 were evaluated.RESULTS: Overall rates of SVR12 [undetectable serum hepatitis C virus(HCV) RNA levels] were 79.2% and 69.4% in TVR and SMV groups, respectively. Patients in the SMV group were older, had higher serum HCV RNA levels, lower hemoglobin, higher prevalence of unfavorable interleukin-28B(IL28B) genotype(rs8099917), and poorer response to previous PEG-IFN and RBV treatment. Propensity score matching was performed to adjust for backgrounds(n = 104) and demonstrated SVR12 rates of 74.0% and 73.1% in the TVR and SMV groups, respectively. In the TVR group, discontinuation rates were higher because of adverse events; however, breakthrough and nonresponse was more frequent in the in SMV group. Multivariate analysis revealed IL28 B genotype(rs8099917) as the only independent predictive factor of SVR12 in both groups.CONCLUSION: SVR12 rates were almost identical following propensity score matching.
文摘AIM: To evaluate interferon-λ3(IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin(Peg-IFNα/RBV) therapy for genotype 2(G2) chronic hepatitis C.METHODS: Between January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis C virus(HCV) were treated with responseguided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response(RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype(TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HCV subgenotype 2a or 2b.RESULTS: Of the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response(SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate(96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5%(P < 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups(80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR(OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis according to HCV sub-genotype, no significant difference in the SVR rate was found between HCV sub-genotypes 2a and 2b.CONCLUSION: In response-guided Peg-IFNα/RBV combination therapy for chronically HCV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients.
文摘AIM: To investigate if correction of hypovitaminosis D before initiation of Peg-interferon-alpha/ribavirin(Peg IFN/RBV) therapy could improve the efficacy of Peg IFN/RBV in previously null-responder patients with chronic genotype 1 or 4 hepatitis C virus(HCV) infection.METHODS:Genotype 1 or 4 HCV-infected patients with null response to previous Peg IFN/RBV treatment and with hypovitaminosis D(<30 ng/m L)prospectively received cholecalciferol 100000 IU per week for 4 wk[from week-4(W-4)to W0],followed by 100000 IUper month in combination with Peg IFN/RBV for 12 mo(from W0 to W48).The primary outcome was the rate of early virological response defined by an HCV RNA<12 IU/m L after 12 wk Peg IFN/RBV treatment.RESULTS:A total of 32 patients were included,19(59%)and 13(41%)patients were HCV genotype1 and 4,respectively.The median baseline vitamin D level was 15 ng/m L(range:7-28).In modified intention-to-treat analysis,29 patients who received at least one dose of Peg IFN/RBV were included in the analysis.All patients except one normalized their vitamin D serum levels.The rate of early virologic response was 0/29(0%).The rate of HCV RNA<12IU/m L after 24 wk of Peg IFN/RBV was 1/27(4%).The safety profile was favorable.CONCLUSION:Addition of vitamin D to Peg IFN/RBV does not improve the rate of early virologic response in previously null-responders with chronic genotype 1or 4 HCV infection.
文摘AIM:To evaluate the effect of long-term treatment with leukocyte natural-interferon(ln-α-IFN)plus ribavirin(RBV).METHODS:Forty-six patients with hepatitis C virus(HCV)recurrence received 3 MU three times a week of ln-α-IFN plus RBV for 1 mo;then,patients with good tolerability(n=30)were switched to daily IFN administration,while the remaining were treated with the same schedule.Patients have been treated for 12 mo after viral clearance while non-responders(NR)entered in the longterm treatment group.Liver biopsies were planned at baseline,1 year after sustained virological response(SVR)and at 36 mo after start of therapy in NR.MedCalc software package was used for statistical analysis.RESULTS:About 16.7%of genotype 1-4 and 70%of genotype 2-3 patients achieved SVR.Nine patients withdrew therapy because of non-tolerance or noncompliance.A significant improvement in serum biochemistry and histological activity was observed in all SVR patients and long-term treated;100%of patients with SVR achieved a histological response(fibrosis stabilization or improvement)with a significant reduction in mean staging value(from 2.1 to 1.0;P=0.0031);histological response was observed in 84%of long-term treated patients compared to 57%of drop-out.Six patients died during the entire study period(follow-up 40.6±7.7 mo);of them,5 presented with severe HCV recurrence on enrollment.Diabetes(OR=0.38,95%CI:0.08-0.59,P=0.01),leukopenia(OR=0.54,95%CI:0.03-0.57,P=0.03)and severe HCV recurrence(OR=0.51,95%CI:0.25-0.69,P=0.0003)were variables associated to survival.Long-term treatment was well tolerated;no patients developed rejection or autoimmune disease.CONCLUSION:Long-term treatment improves histology in SVR patients and slows disease progression also in NR,leading to a reduction in liver decompensation,graft failure and liver-related death.
文摘Purpose: The optimal formulation of pegylated interferon a (PEG-IFa) as a part of combination therapy with ribavirin (RBV) is uncertain for patients infected with hepatitis C Genotypes 2 and 3. Methods: A multivariate analysis of prospectively collected treatment data from two tertiary centres on 351 treatment na?ve HCV Genotype 2 or 3 patients who received PEG-IFa-2a or b plus ribavirin. Results: Univariate analyses demonstrate that PEG-IFa-2b based on regimens achieved a higher sustained virological response (SVR) than PEG-IFa-2a (77.9% versus 62.0%, P = 0.0012). On multivariate analyses, PEG-IFa-2b appeared superior to PEG-IFa-2a with an odds ratio (OR) and 95% confidence interval (CI95) for SVR of 2.19 (CI95 1.35-3.52, P = 0.0005). Genotype was a significant predictor of outcome in the multivariate model with 80% of Genotype 2 but only 67.7% of Genotype 3 subjects achieving SVR (OR 2.66 [CI95 1.35-5.92]). Increasing age was negatively associated with SVR (OR 0.97 [CI95 0.94-0.99]). Some of the differences in SVR are explained by higher relapse rates with PEG-IFa-2a (P = 0.009). Conclusions: PEG-IFa-2b and RBV achieve higher SVR rates than PEG-IFa-2a and RBV in Genotypes 2 and 3 chronic HCV infections. There is less relapse with PEG-IFa-2b. Genotype 2 infections are considerably easier to cure. SVR is higher in younger patients. These findings should influence a choice of PEG-IFa in the era of direct acting anti-viral drugs in therapy of Genotypes 2 and 3.
文摘This is a case of 52 years old male patient with chronic obstructive pulmonary disease (COPD) who developed semi-invasive pulmonary aspergillosis while on pegylated-interferon alpha-2a and for chronic hepatitis C infection. This complication is very rarely seen during interferon therapy for other any purposes. Pulmonary aspergillosis in particular group of chronic hepatitis C patients under immunosupressive therapy should also be in mind and interdisciplinary medical cooperation might be needed during the treatment for immune-suppressed patients. Pulmonary aspergillosis is also discussed from many aspects in the light of the literature.
文摘干扰素-γ诱导蛋白16(interferon gamma-inducible protein 16,IFI16)是含pyrin和造血表达、干扰素诱导特性和核定位(hematopoietic expression,interferon-inducible nature,and nuclear localization,HIN)结构域的蛋白质(pyrin and HIN domain-containing protein,PYHIN)家族的重要成员,其独特的分子结构使其能够识别细胞内的多种核酸分子。作为一种关键的免疫调节因子,IFI16可通过多种途径参与天然免疫信号转导,在宿主抗病毒防御中发挥重要作用。本文综述了IFI16的分子特征及其在天然免疫和病毒感染中的调控机制,为抗病毒感染的治疗靶点及药物开发提供理论依据。
