BACKGROUND: The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained viro...BACKGROUND: The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained virological response (SVR). Nevertheless, the majority of patients globally are unable to access these treatments because of cost and infrastructure constraints and, thus, remain untreated and uncured. DATA SOURCE: Relevant articles of peginterferon (PegIFN)-based treatments in HCV and sofosbuvir-based treatments, simeprevir, daclatasvir/asunaprevir, ritonavir-boosted paritaprevir/ombitasvir/dasabuvir, and grazoprevir/elbasvir, were searched in PubMed database, including general population and special population. RESULTS: PegIFN in combination with ribavirin remains an important and relevant option for some patients, achieving SVR rates of up to 79% in genotype 1 and 89% in genotype 2 or 3 infections, which increases for patients with favorable IL28B genotypes. Triple therapy of DAA plus PegIFN/ribavirin is effective in treating difficult-to-cure patients infected with HCV genotype 3 or with resistance-associated variants. Owing to its long history in HCV management, the efficacy, tolerability and long-term outcomes associated with PegIFN alfa-2a are well established and have been validated in large-scale studies and in clinical practice for many populations. Furthermore, emerging data show that IFN-induced SVR is associated with lower incidences of hepatocellular carcinoma compared with DAAs. On the contrary, novel DAAs have yet to be studied in special populations, and long-term outcomes, particularly tumor development and recurrence in patients with cirrhosis and/or hepatocellular carcinoma, and reactivation of HBV in dually infected patients, are still unclear. CONCLUSION: In this interferon-free era, PegIFN-based regimens remain a safe and effective option for selected HCV patients.展开更多
We report a case of pericarditis and chronic inflam- matory demyelinating polyneuropathy with biological signs of a lupus-like syndrome due to pegylated interferon alfa-2a therapy during treatment for chronic hepatiti...We report a case of pericarditis and chronic inflam- matory demyelinating polyneuropathy with biological signs of a lupus-like syndrome due to pegylated interferon alfa-2a therapy during treatment for chronic hepatitis C.The patient developed moderate weakness in the lower limbs and dyspnea.He was hospitalized for congestive heart failure.An electrocardiogram showed gradual ST-segment elevation in leads V1 through V6 without coronary artery disease.A transthoracic cardiac ultrasonographic study revealed moderate pericardial effusion with normal left ventricular function.Anti-DNA antibody and anti-ds DNA IgM were positive.Neu ro logical examination revealed a symmetrical predomina ntly sensory polyneuropathy with impairment of light touch and pin prick in globe and stoking-like distribution.Treatment with prednisolone improved the pericarditis and motor nerve disturbance and the treatment with intravenous immunoglobulin improved the sensory nerve disturbance.展开更多
AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, ...AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, who were treatment-naive, with a serum HBs Ag level < 100 IU/m L and an undetectable hepatitis B virus(HBV) DNA level(< 100 IU/m L). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBs Ag, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen(65.0%) of 20 treated patients achieved HBs Ag loss, 12 of whom achieved HBs Ag seroconversion. Mean HBs Ag level in treated patients decreased to 6.69 ± 13.04 IU/m L after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/m L. Serum HBV DNA level remained undetectable(< 100 IU/m L) in all treated patients during the study. HBs Ag level of the control group decreased from 25.72 ± 25.58 IU/m L at baseline to 17.11 ± 21.62 IU/m L at week 96(P = 0.108). In the control group, no patient experienced HBs Ag loss/seroconversion, and two(5.0%) developed HBV reactivation.CONCLUSION: IFN treatment results in HBs Ag loss and seroconversion in a considerable proportion of inactive HBs Ag carriers with low HBs Ag concentrations.展开更多
Background and Aims:The use of additional nucleos(t)ide analogues(NAs)without cross-resistance to previously used NAs as a rescue therapy is recommended by most international guidelines for chronic hepatitis B patient...Background and Aims:The use of additional nucleos(t)ide analogues(NAs)without cross-resistance to previously used NAs as a rescue therapy is recommended by most international guidelines for chronic hepatitis B patients with NAresistance.We aimed to investigate the efficacy and safety of combination therapy of peg-interferon(PegIFN)alfa-2a and NA in these patients,comparing to those who switch to an alternative NA therapy without cross-resistance.Methods:In this prospective,comparative and cohort study,data were collected from the patients'hospital records.Eligible patients were those with hepatitis B e antigen(HBeAg)positivity and resistance to one or more NAs.All patients were treated with alternative NA alone or in combination with PegIFN alfa-2a for 52 weeks or 72 weeks,respectively.HBeAg seroconversion was measured at the end of follow-up(EOF;more than 104 weeks after the end of treatment).Results:Sixty-three patients were recruited to the cohort study(NAtherapy group=31 patients;combination therapy group of NA and PegIFN alfa-2a=32 patients).At the EOF,significantly more patients in the combination therapy group(13/27,48.2%)achieved primary outcome of HBeAg seroconversion than those in the NA therapy group(4/32,12.5%)(p=0.003).Four patients(14.8%)in the combination therapy group achieved hepatitis B surface antigen(HBsAg)loss and HBsAg seroconversion,but none in the NA therapy group did(p=0.039).In the combination therapy group,16 patients(51.6%)achieved HBeAg seroconversion at the end of treatment,of which,11 patients(68.8%)maintained the response until EOF.Conclusions:Adding on PegIFN alfa-2a in combination with NA therapy might be an appropriate rescue treatment option for patients who have prior NA resistance.In addition,combination therapy induced sustained off-treatment biochemical responses in these patients.展开更多
AIM: To study the differential protein profile in serum of hepatitis B patients.METHODS: Serum samples were obtained from patients with chronic hepatitis B who were receiving peginterferon alfa-2b.The serum samples we...AIM: To study the differential protein profile in serum of hepatitis B patients.METHODS: Serum samples were obtained from patients with chronic hepatitis B who were receiving peginterferon alfa-2b.The serum samples were subjected to albumin depletion and analyzed by two-dimensional gel electrophoresis(2-DE).Differentially expressed protein spots were identified by electrospray ionizationquadrupole time-of-flight mass spectrometry.Alpha2-HS-glycoprotein,complement component C3c and CD5 antigen were further analyzed by an enzymelinked immunosorbent assay and immunonephelometry.RESULTS: Nineteen patients with HBeAg-positive chronic hepatitis B(CHB) were studied.These patients were followed for at least 1 year after treatment and were classified according to their treatment response: responders(n = 9) and non-responders(n = 10).2-DE and MS/MS analysis were performed to compare the serum proteins before initiating peginterferon alfa2b.From the quantitative analysis of the 2-D gel,7 proteins were detected between the two groups at different levels before treatment.Among these potential candidates,serum levels of alpha-2-HS-glycoprotein,complement component C3c and CD5 antigen-like precursor were further analyzed.In the validation phase,23 subjects,9 sustained responders and 14 nonresponders,were recruited.Interestingly,the levels of alpha-2-HS-glycoprotein and complement component C3c were elevated in the serum of the non-responders compared to the responders.CONCLUSION: Serum alpha-2-HS-glycoprotein and complement component C3c may be potential serum biomarkers in predicting the treatment response of peginterferon alfa-2b in patients with CHB prior to treatment.展开更多
AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open...AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin(800 mg/d for ≤ 65 kg; 1000 mg/d for > 65-85 kg; 1200 mg/d for > 85-105 kg; 1400 mg/d for > 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed.RESULTS: Eighty-two patients(35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response(RVR): while the figures were 74.1% for early virologic response(EVR) and 44.4% for sustained virologic response(SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events(SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication.CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.展开更多
文摘BACKGROUND: The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained virological response (SVR). Nevertheless, the majority of patients globally are unable to access these treatments because of cost and infrastructure constraints and, thus, remain untreated and uncured. DATA SOURCE: Relevant articles of peginterferon (PegIFN)-based treatments in HCV and sofosbuvir-based treatments, simeprevir, daclatasvir/asunaprevir, ritonavir-boosted paritaprevir/ombitasvir/dasabuvir, and grazoprevir/elbasvir, were searched in PubMed database, including general population and special population. RESULTS: PegIFN in combination with ribavirin remains an important and relevant option for some patients, achieving SVR rates of up to 79% in genotype 1 and 89% in genotype 2 or 3 infections, which increases for patients with favorable IL28B genotypes. Triple therapy of DAA plus PegIFN/ribavirin is effective in treating difficult-to-cure patients infected with HCV genotype 3 or with resistance-associated variants. Owing to its long history in HCV management, the efficacy, tolerability and long-term outcomes associated with PegIFN alfa-2a are well established and have been validated in large-scale studies and in clinical practice for many populations. Furthermore, emerging data show that IFN-induced SVR is associated with lower incidences of hepatocellular carcinoma compared with DAAs. On the contrary, novel DAAs have yet to be studied in special populations, and long-term outcomes, particularly tumor development and recurrence in patients with cirrhosis and/or hepatocellular carcinoma, and reactivation of HBV in dually infected patients, are still unclear. CONCLUSION: In this interferon-free era, PegIFN-based regimens remain a safe and effective option for selected HCV patients.
文摘We report a case of pericarditis and chronic inflam- matory demyelinating polyneuropathy with biological signs of a lupus-like syndrome due to pegylated interferon alfa-2a therapy during treatment for chronic hepatitis C.The patient developed moderate weakness in the lower limbs and dyspnea.He was hospitalized for congestive heart failure.An electrocardiogram showed gradual ST-segment elevation in leads V1 through V6 without coronary artery disease.A transthoracic cardiac ultrasonographic study revealed moderate pericardial effusion with normal left ventricular function.Anti-DNA antibody and anti-ds DNA IgM were positive.Neu ro logical examination revealed a symmetrical predomina ntly sensory polyneuropathy with impairment of light touch and pin prick in globe and stoking-like distribution.Treatment with prednisolone improved the pericarditis and motor nerve disturbance and the treatment with intravenous immunoglobulin improved the sensory nerve disturbance.
文摘AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, who were treatment-naive, with a serum HBs Ag level < 100 IU/m L and an undetectable hepatitis B virus(HBV) DNA level(< 100 IU/m L). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBs Ag, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen(65.0%) of 20 treated patients achieved HBs Ag loss, 12 of whom achieved HBs Ag seroconversion. Mean HBs Ag level in treated patients decreased to 6.69 ± 13.04 IU/m L after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/m L. Serum HBV DNA level remained undetectable(< 100 IU/m L) in all treated patients during the study. HBs Ag level of the control group decreased from 25.72 ± 25.58 IU/m L at baseline to 17.11 ± 21.62 IU/m L at week 96(P = 0.108). In the control group, no patient experienced HBs Ag loss/seroconversion, and two(5.0%) developed HBV reactivation.CONCLUSION: IFN treatment results in HBs Ag loss and seroconversion in a considerable proportion of inactive HBs Ag carriers with low HBs Ag concentrations.
基金The study was supported by the Third People's Hospital of Kunming City, Kunming, China
文摘Background and Aims:The use of additional nucleos(t)ide analogues(NAs)without cross-resistance to previously used NAs as a rescue therapy is recommended by most international guidelines for chronic hepatitis B patients with NAresistance.We aimed to investigate the efficacy and safety of combination therapy of peg-interferon(PegIFN)alfa-2a and NA in these patients,comparing to those who switch to an alternative NA therapy without cross-resistance.Methods:In this prospective,comparative and cohort study,data were collected from the patients'hospital records.Eligible patients were those with hepatitis B e antigen(HBeAg)positivity and resistance to one or more NAs.All patients were treated with alternative NA alone or in combination with PegIFN alfa-2a for 52 weeks or 72 weeks,respectively.HBeAg seroconversion was measured at the end of follow-up(EOF;more than 104 weeks after the end of treatment).Results:Sixty-three patients were recruited to the cohort study(NAtherapy group=31 patients;combination therapy group of NA and PegIFN alfa-2a=32 patients).At the EOF,significantly more patients in the combination therapy group(13/27,48.2%)achieved primary outcome of HBeAg seroconversion than those in the NA therapy group(4/32,12.5%)(p=0.003).Four patients(14.8%)in the combination therapy group achieved hepatitis B surface antigen(HBsAg)loss and HBsAg seroconversion,but none in the NA therapy group did(p=0.039).In the combination therapy group,16 patients(51.6%)achieved HBeAg seroconversion at the end of treatment,of which,11 patients(68.8%)maintained the response until EOF.Conclusions:Adding on PegIFN alfa-2a in combination with NA therapy might be an appropriate rescue treatment option for patients who have prior NA resistance.In addition,combination therapy induced sustained off-treatment biochemical responses in these patients.
基金Supported by The 90th Anniversary of Chulalongkorn University Fund(Ratchadaphiseksomphot Endowment Fund)The Thailand Research Fund,No.RMU5180051+2 种基金The Thailand Research Fund Senior Research Scholarship,No.RTA5380005The Higher Education Research Promotion and National Research University Project of Thailand,Office of the Higher Education Commission,No.HR1163AIntegrated Innovation Academic Center,Chulalongkorn University Centenary Academic Development Project,No.CU56-HR05,The Liver Research Unit,Chulalongkorn University
文摘AIM: To study the differential protein profile in serum of hepatitis B patients.METHODS: Serum samples were obtained from patients with chronic hepatitis B who were receiving peginterferon alfa-2b.The serum samples were subjected to albumin depletion and analyzed by two-dimensional gel electrophoresis(2-DE).Differentially expressed protein spots were identified by electrospray ionizationquadrupole time-of-flight mass spectrometry.Alpha2-HS-glycoprotein,complement component C3c and CD5 antigen were further analyzed by an enzymelinked immunosorbent assay and immunonephelometry.RESULTS: Nineteen patients with HBeAg-positive chronic hepatitis B(CHB) were studied.These patients were followed for at least 1 year after treatment and were classified according to their treatment response: responders(n = 9) and non-responders(n = 10).2-DE and MS/MS analysis were performed to compare the serum proteins before initiating peginterferon alfa2b.From the quantitative analysis of the 2-D gel,7 proteins were detected between the two groups at different levels before treatment.Among these potential candidates,serum levels of alpha-2-HS-glycoprotein,complement component C3c and CD5 antigen-like precursor were further analyzed.In the validation phase,23 subjects,9 sustained responders and 14 nonresponders,were recruited.Interestingly,the levels of alpha-2-HS-glycoprotein and complement component C3c were elevated in the serum of the non-responders compared to the responders.CONCLUSION: Serum alpha-2-HS-glycoprotein and complement component C3c may be potential serum biomarkers in predicting the treatment response of peginterferon alfa-2b in patients with CHB prior to treatment.
基金Supported by Virchow Biotech Private Limited,Hyderabad,India
文摘AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin(800 mg/d for ≤ 65 kg; 1000 mg/d for > 65-85 kg; 1200 mg/d for > 85-105 kg; 1400 mg/d for > 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed.RESULTS: Eighty-two patients(35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response(RVR): while the figures were 74.1% for early virologic response(EVR) and 44.4% for sustained virologic response(SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events(SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication.CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.
