The ideal endpoint of hepatitis B virus(HBV)antiviral therapy is HBsAg loss,a difficult goal to obtain,especially in HBeAg negative patients.Herein,we report the results obtained by the addition of peg-interferonα-2a...The ideal endpoint of hepatitis B virus(HBV)antiviral therapy is HBsAg loss,a difficult goal to obtain,especially in HBeAg negative patients.Herein,we report the results obtained by the addition of peg-interferonα-2a to a long-lasting nucleos(t)ide analogues therapy in a HBeAg negative,genotype D patient with steadily HBV-DNA negative/HBsAg positive values.In 2002,our Caucasian 44-year-old male patient received lamivudine and,4 years later,added adefovir because of a virological breakthrough.In 2011,considering his young age,liver stiffness(4.3 kPa)and HBsAg levels(3533IU/mL),we added Peg-interferonα-2a for six months(3in combination with nucleos(t)ide analogues followed by 3 mo of Peg-interferonα-2a monotherapy).A decrease of HBsAg levels was observed after 1 mo(1.21log)of Peg-interferon and 3 mo(1.88 log)after the discontinuation of all drugs.Later,a complete clearance of HBsAg was obtained with steadily undetectable HBVDNA serum levels(<9 IU/mL).HBsAg clearance by the addition of a short course of Peg-interferonα-2a represents an important result with clinical and pharmacoeconomic implications,considering that nucleos(t)ide analogues therapy in HBeAg negative chronic hepatitis B patients is considered a long-lasting/life-long treatment.展开更多
AIM： To evaluate the impact of therapeutic education on adherence to antiviral treatment and sustained virological response （SVR） in a real-life setting in genotype 2/3 hepatitis C, as there are few adherence data ...AIM： To evaluate the impact of therapeutic education on adherence to antiviral treatment and sustained virological response （SVR） in a real-life setting in genotype 2/3 hepatitis C, as there are few adherence data in genotype 2/3 infection, even from randomized trials. METHODS： This prospective survey included genotype 2/3 patients who received peg-interferon alfa-2b and ribavirin. There was no intervention. Adherence wasself-reported over the past 4 wk （peg-interferon） or 7 d （ribavirin）. Adherence to bitherapy was defined as adherence to the two drugs for ≥ 20 wk. SVR was defined as undetectable RNA ≥ 12 wk after the end of treatment. RESULTS： 370/674 patients received education during the first 3 mo of treatment. After 6 too, adherence to bitherapy was higher in educated patients （61% vs 47%, P = 0.01）. Adherence to peg-interferon was 78% vs 69% （P=0.06）. Adherence to ribavirin was 70% vs 56% （P = 0.006）. The SVR （77% vs 70%, P = 0.05） and relapse （10% vs 16%, P = 0.09） rates tended to be improved. After adjustment for baseline differences, education improved adherence [Odds ratio （OR） 1.58, P = 0.04] but not the SVR （OR 1.54, P = 0.06）. CONCLUSION： In genotype 2/3 patients, therapeutic education helped maintain real-life adherence to bitherapy.展开更多
AIM： To observe the efficacy of peg-interferon in the treatment of hepatitis delta virus （HDV） and to identify the factors that would be predictive of the sustained viral response （SVR）. METHODS： This prospectiv...AIM： To observe the efficacy of peg-interferon in the treatment of hepatitis delta virus （HDV） and to identify the factors that would be predictive of the sustained viral response （SVR）. METHODS： This prospective study was conducted in Medical Unit IV of the Liaquat University of Medi- cal and Health Sciences Hospital Jamshoro from June 2008 to September 2011. This study cohort included all patients of either sex who presented during this time with hepatitis B surface antigen positivity, hepa- titis B virus DNA 〉 20 000 IU/ml, serum glutamic py- ruvic transaminase （SGPT） 〉 2（upper limit of normal）, HDV-RNA positivity with fibrosis stage ≥ 2. Informed consent was obtained from each of these individuals. Patients were diagnosed with hepatitis D on the ba- sis of detectable viral antibodies and the presence of HDV-RNA in their serum. A liver biopsy was performed in all cases and fibrosis staging was performed in ac- cordance with the METAVIR scoring system. All eligible patients were administered peg-interferon at a weekly dosage of 1.5 μg/kg body weight for 48 wk. HDV-RNA was assayed at the end of this treatment period and again at 24 wk later. A biochemical response was de- termined by a normalization of SGPT at the end of the treatment or during follow up. The end of treatment response was defined by a HDV-RNA negative status. A sustained virological response was defined by unde- tectable serum HDV-RNA at six months after the end of treatment. RESULTS： Among the 277 patients enrolled in our present study, 238 completed a course of peg-interfer- on therapy of which 180 （75.6%） were male and 58 （24.4%） female. Biochemical responses were achieved in 122/238 （51.3%） patients. End of treatment re- sponses were achieved in 71/238 （29.8%） cases. A SVR was achieved in 70 of these patients （29.4%）. A strong association was found between the SVR and the end of treatment responses （P = 0.001）, biochemical responses （P = 0.001） and the degree of fibrosis （P = 0.002）. CONCLUSION： Peg-interferon therapy can induce re- mission in nearly one third of patients harboring HDV.展开更多
Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IF...Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IFN)alfa-2a.We assessed HBsAg loss with 48-and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.Methods:Hepatitis B e antigen(HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA<200 IU/mL with previous adefovir,lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48(n=153)or 96 weeks(n=150).The primary endpoint of this study was HBsAg loss at end of treatment.The ClinicalTrials.gov identifier is NCT01464281.Results:At the end of 48 and 96 weeks'treatment,14.4%(22/153)and 20.7%(31/150)of patients,respectively,who switched from NA to Peg-IFN alfa-2a cleared HBsAg.Rates were similar irrespective of prior NA or baseline HBeAg seroconversion.Among those who cleared HBsAg by the end of 48 and 96 weeks'treatment,77.8%(14/18)and 71.4%(20/28),respectively,sustained HBsAg loss for a further 48 weeks.Baseline HBsAg<1500 IU/mL and week 24 HBsAg<200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48-and 96-week treatment(51.4%and 58.7%,respectively).Importantly,extending treatment from 48 to 96 weeks enabled 48.3%(14/29)more patients to achieve HBsAg loss.Conclusions:Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a.HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks,although the differences in our study cohort were not statistically significant.Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.展开更多
Background:The efficacy of entecavir(ETV)add-on peg-interferon therapy compared with ETV monotherapy in treatment-naive hepatitis B virus(HBV)patients remains controversial.We investigated whether adding peg-interfero...Background:The efficacy of entecavir(ETV)add-on peg-interferon therapy compared with ETV monotherapy in treatment-naive hepatitis B virus(HBV)patients remains controversial.We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not.Methods:All patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital(China).Eligible HBV patients(n=144)were randomly divided(1:1)to receive either ETV monotherapy(n=70)or peg-interferon add-on therapy from week 26 to 52(«=74).Patients were followed-up for at least 2 years.Indexes including hepatitis B surface antigen(HBsAg)and hepatitis B e antigen(HBeAg)seroconversion rate,sustained virologic response,transient elastography value,and histological scores were evaluated every 3 months until the end of the study.The rate of patients with HBsAg loss was defined as the primary endpoint criteria.Results:At week 26,no patient achieved HBsAg seroconversion in either group.At week 52,one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group.The monotherapy group showed significantly better liver function recovery results than the combination therapy group.At week 78,one patient in the combination group had HBsAg seroconverted.At week 104,only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy.The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline.Both groups showed a favorable decrease in alpha-fetoprotein(monotherapy:4.5[2.8,7.1]vs.2.2[1.8,3.1]ng/mL,P<0.001;combination therapy:5.7[3.0,18.8]vs.3.2[2.0,4.3]ng/mL,P<0.001)and an improved result of liver biopsy examination scores.The combination group showed a better improvement in histology compared with the monotherapy group(mean transient elastography value 6.6[4.9,9.8]vs.7.8[5.4,11.1]kPa,P=0.028).But there was no significant difference in HBsAg conversion rate(1.8%[1/56]i^s.4.1%[3/73],P=0.809)and HBeAg conversion rate(12.5%[7/56]i/s.11.0%[8/73],P=0.787),as well as HBV-DNA,sustained virologic response(93.2%vs.98.5%,P=0.150)between the two groups.Conclusions:Both therapies supported liver function recovery and histology improvement.Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy.However,combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.Trial registration:ClinicalTrials.gov:NCT02849132;https://clinicaltrials.gov/ct2/show/NCT02849132.展开更多
AIM: To examine whether vitamin D improved viral response and predicted treatment outcome in patients with hepatitis C virus (HCV) genotype 2-3. METHODS: Fifty patients with chronic HCV genotype 2-3 were randomized co...AIM: To examine whether vitamin D improved viral response and predicted treatment outcome in patients with hepatitis C virus (HCV) genotype 2-3. METHODS: Fifty patients with chronic HCV genotype 2-3 were randomized consecutively into two groups: Treatment group [20 subjects, age 48 ± 14 years, body mass index (BMI) 30 ± 6, 65% male], who received 180 μg pegylated α-interferon-2a plus oral ribavirin 800 mg/d (Peg/RBV), together with oral vitamin D3 (Vitamidyne D drops; 2000 IU/d, 10 drops/d, normal serum level > 32 ng/mL) for 24 wk; and control group (30 subjects, age 45 ± 10 years, BMI 26 ± 3, 60% male), who received identical therapy without vitamin D. HCV RNA was assessed by reverse transcription polymerase chain reaction. Undetectable HCV RNA at 4, 12 and 24 wk after treatment was considered as rapid virological response, complete early virological response, and sustained virological response (SVR), respectively. Biomarkers of in? ammation were measured. RESULTS: The treatment group with vitamin D hadhigher BMI (30 ± 6 vs 26 ± 3, P < 0.02), and high viral load (> 400 000 IU/mL, 65% vs 40%, P < 0.01) than controls. Ninety-fi ve percent of treated patients were HCV RNA negative at week 4 and 12. At 24 wk after treatment (SVR), 19/20 (95%) treated patients and 23/30 (77%) controls were HCV RNA negative (P < 0.001). Baseline serum vitamin D levels were lower at baseline (20 ± 8 ng/mL) and increased after 12 wk vitamin D treatment, to a mean level of (34 ± 11 ng/ mL). Logistic regression analysis identifi ed vitamin D supplement [odds ratio (OR) 3.0, 95% CI 2.0-4.9, P < 0.001], serum vitamin D levels (< 15 or > 15 ng/mL, OR 2.2, P < 0.01), and BMI (< 30 or > 30, OR 2.6, P < 0.01) as independent predictors of viral response. Adverse events were mild and typical of Peg/RBV. CONCLUSION: Low vitamin D levels predicts negative treatment outcome, and adding vitamin D to conventional Peg/RBV therapy for patients with HCV genotype 2-3 signifi cantly improves viral response.展开更多
文摘The ideal endpoint of hepatitis B virus(HBV)antiviral therapy is HBsAg loss,a difficult goal to obtain,especially in HBeAg negative patients.Herein,we report the results obtained by the addition of peg-interferonα-2a to a long-lasting nucleos(t)ide analogues therapy in a HBeAg negative,genotype D patient with steadily HBV-DNA negative/HBsAg positive values.In 2002,our Caucasian 44-year-old male patient received lamivudine and,4 years later,added adefovir because of a virological breakthrough.In 2011,considering his young age,liver stiffness(4.3 kPa)and HBsAg levels(3533IU/mL),we added Peg-interferonα-2a for six months(3in combination with nucleos(t)ide analogues followed by 3 mo of Peg-interferonα-2a monotherapy).A decrease of HBsAg levels was observed after 1 mo(1.21log)of Peg-interferon and 3 mo(1.88 log)after the discontinuation of all drugs.Later,a complete clearance of HBsAg was obtained with steadily undetectable HBVDNA serum levels(<9 IU/mL).HBsAg clearance by the addition of a short course of Peg-interferonα-2a represents an important result with clinical and pharmacoeconomic implications,considering that nucleos(t)ide analogues therapy in HBeAg negative chronic hepatitis B patients is considered a long-lasting/life-long treatment.
文摘AIM： To evaluate the impact of therapeutic education on adherence to antiviral treatment and sustained virological response （SVR） in a real-life setting in genotype 2/3 hepatitis C, as there are few adherence data in genotype 2/3 infection, even from randomized trials. METHODS： This prospective survey included genotype 2/3 patients who received peg-interferon alfa-2b and ribavirin. There was no intervention. Adherence wasself-reported over the past 4 wk （peg-interferon） or 7 d （ribavirin）. Adherence to bitherapy was defined as adherence to the two drugs for ≥ 20 wk. SVR was defined as undetectable RNA ≥ 12 wk after the end of treatment. RESULTS： 370/674 patients received education during the first 3 mo of treatment. After 6 too, adherence to bitherapy was higher in educated patients （61% vs 47%, P = 0.01）. Adherence to peg-interferon was 78% vs 69% （P=0.06）. Adherence to ribavirin was 70% vs 56% （P = 0.006）. The SVR （77% vs 70%, P = 0.05） and relapse （10% vs 16%, P = 0.09） rates tended to be improved. After adjustment for baseline differences, education improved adherence [Odds ratio （OR） 1.58, P = 0.04] but not the SVR （OR 1.54, P = 0.06）. CONCLUSION： In genotype 2/3 patients, therapeutic education helped maintain real-life adherence to bitherapy.
基金Supported by Hepatitis Prevention and Control Program Sindh,Pakistan Chief Minister's initiative,a government organization provided peg-interferon treatment to patients for 48 wk free of cost
文摘AIM： To observe the efficacy of peg-interferon in the treatment of hepatitis delta virus （HDV） and to identify the factors that would be predictive of the sustained viral response （SVR）. METHODS： This prospective study was conducted in Medical Unit IV of the Liaquat University of Medi- cal and Health Sciences Hospital Jamshoro from June 2008 to September 2011. This study cohort included all patients of either sex who presented during this time with hepatitis B surface antigen positivity, hepa- titis B virus DNA 〉 20 000 IU/ml, serum glutamic py- ruvic transaminase （SGPT） 〉 2（upper limit of normal）, HDV-RNA positivity with fibrosis stage ≥ 2. Informed consent was obtained from each of these individuals. Patients were diagnosed with hepatitis D on the ba- sis of detectable viral antibodies and the presence of HDV-RNA in their serum. A liver biopsy was performed in all cases and fibrosis staging was performed in ac- cordance with the METAVIR scoring system. All eligible patients were administered peg-interferon at a weekly dosage of 1.5 μg/kg body weight for 48 wk. HDV-RNA was assayed at the end of this treatment period and again at 24 wk later. A biochemical response was de- termined by a normalization of SGPT at the end of the treatment or during follow up. The end of treatment response was defined by a HDV-RNA negative status. A sustained virological response was defined by unde- tectable serum HDV-RNA at six months after the end of treatment. RESULTS： Among the 277 patients enrolled in our present study, 238 completed a course of peg-interfer- on therapy of which 180 （75.6%） were male and 58 （24.4%） female. Biochemical responses were achieved in 122/238 （51.3%） patients. End of treatment re- sponses were achieved in 71/238 （29.8%） cases. A SVR was achieved in 70 of these patients （29.4%）. A strong association was found between the SVR and the end of treatment responses （P = 0.001）, biochemical responses （P = 0.001） and the degree of fibrosis （P = 0.002）. CONCLUSION： Peg-interferon therapy can induce re- mission in nearly one third of patients harboring HDV.
基金The authors would like to thank the patients and their families for their contribution to this studyThis study was supported by the National Science and Technology Major Project of China(2008ZX10002-006,2012ZX10002007001,2017ZX10202203-007,2017ZX10202203-008)+2 种基金the National Natural Science Foundation of China(81171561,30972584)This study was also supported in part by Shanghai Roche Pharmaceuticals LtdWriting assistance was provided by Stefanie Chuah,from Mudskipper Business Ltd,funded by F Hoffmann-La Roche
文摘Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IFN)alfa-2a.We assessed HBsAg loss with 48-and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.Methods:Hepatitis B e antigen(HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA<200 IU/mL with previous adefovir,lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48(n=153)or 96 weeks(n=150).The primary endpoint of this study was HBsAg loss at end of treatment.The ClinicalTrials.gov identifier is NCT01464281.Results:At the end of 48 and 96 weeks'treatment,14.4%(22/153)and 20.7%(31/150)of patients,respectively,who switched from NA to Peg-IFN alfa-2a cleared HBsAg.Rates were similar irrespective of prior NA or baseline HBeAg seroconversion.Among those who cleared HBsAg by the end of 48 and 96 weeks'treatment,77.8%(14/18)and 71.4%(20/28),respectively,sustained HBsAg loss for a further 48 weeks.Baseline HBsAg<1500 IU/mL and week 24 HBsAg<200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48-and 96-week treatment(51.4%and 58.7%,respectively).Importantly,extending treatment from 48 to 96 weeks enabled 48.3%(14/29)more patients to achieve HBsAg loss.Conclusions:Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a.HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks,although the differences in our study cohort were not statistically significant.Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.
基金This study was supported by grants from the Major Science and Technology Special Project of China Thirteenth Five-year Plan(No.2013ZX10002004,No.2017ZX10203202-003-007)supported by the Shanghai Science and Technology Development Fund(No.17411969500)the Shanghai Public Health Clinical Center Fund(No.XKJS-2019HBV-06,No.KYGW-2019-32).
文摘Background:The efficacy of entecavir(ETV)add-on peg-interferon therapy compared with ETV monotherapy in treatment-naive hepatitis B virus(HBV)patients remains controversial.We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not.Methods:All patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital(China).Eligible HBV patients(n=144)were randomly divided(1:1)to receive either ETV monotherapy(n=70)or peg-interferon add-on therapy from week 26 to 52(«=74).Patients were followed-up for at least 2 years.Indexes including hepatitis B surface antigen(HBsAg)and hepatitis B e antigen(HBeAg)seroconversion rate,sustained virologic response,transient elastography value,and histological scores were evaluated every 3 months until the end of the study.The rate of patients with HBsAg loss was defined as the primary endpoint criteria.Results:At week 26,no patient achieved HBsAg seroconversion in either group.At week 52,one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group.The monotherapy group showed significantly better liver function recovery results than the combination therapy group.At week 78,one patient in the combination group had HBsAg seroconverted.At week 104,only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy.The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline.Both groups showed a favorable decrease in alpha-fetoprotein(monotherapy:4.5[2.8,7.1]vs.2.2[1.8,3.1]ng/mL,P<0.001;combination therapy:5.7[3.0,18.8]vs.3.2[2.0,4.3]ng/mL,P<0.001)and an improved result of liver biopsy examination scores.The combination group showed a better improvement in histology compared with the monotherapy group(mean transient elastography value 6.6[4.9,9.8]vs.7.8[5.4,11.1]kPa,P=0.028).But there was no significant difference in HBsAg conversion rate(1.8%[1/56]i^s.4.1%[3/73],P=0.809)and HBeAg conversion rate(12.5%[7/56]i/s.11.0%[8/73],P=0.787),as well as HBV-DNA,sustained virologic response(93.2%vs.98.5%,P=0.150)between the two groups.Conclusions:Both therapies supported liver function recovery and histology improvement.Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy.However,combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.Trial registration:ClinicalTrials.gov:NCT02849132;https://clinicaltrials.gov/ct2/show/NCT02849132.
文摘AIM: To examine whether vitamin D improved viral response and predicted treatment outcome in patients with hepatitis C virus (HCV) genotype 2-3. METHODS: Fifty patients with chronic HCV genotype 2-3 were randomized consecutively into two groups: Treatment group [20 subjects, age 48 ± 14 years, body mass index (BMI) 30 ± 6, 65% male], who received 180 μg pegylated α-interferon-2a plus oral ribavirin 800 mg/d (Peg/RBV), together with oral vitamin D3 (Vitamidyne D drops; 2000 IU/d, 10 drops/d, normal serum level > 32 ng/mL) for 24 wk; and control group (30 subjects, age 45 ± 10 years, BMI 26 ± 3, 60% male), who received identical therapy without vitamin D. HCV RNA was assessed by reverse transcription polymerase chain reaction. Undetectable HCV RNA at 4, 12 and 24 wk after treatment was considered as rapid virological response, complete early virological response, and sustained virological response (SVR), respectively. Biomarkers of in? ammation were measured. RESULTS: The treatment group with vitamin D hadhigher BMI (30 ± 6 vs 26 ± 3, P < 0.02), and high viral load (> 400 000 IU/mL, 65% vs 40%, P < 0.01) than controls. Ninety-fi ve percent of treated patients were HCV RNA negative at week 4 and 12. At 24 wk after treatment (SVR), 19/20 (95%) treated patients and 23/30 (77%) controls were HCV RNA negative (P < 0.001). Baseline serum vitamin D levels were lower at baseline (20 ± 8 ng/mL) and increased after 12 wk vitamin D treatment, to a mean level of (34 ± 11 ng/ mL). Logistic regression analysis identifi ed vitamin D supplement [odds ratio (OR) 3.0, 95% CI 2.0-4.9, P < 0.001], serum vitamin D levels (< 15 or > 15 ng/mL, OR 2.2, P < 0.01), and BMI (< 30 or > 30, OR 2.6, P < 0.01) as independent predictors of viral response. Adverse events were mild and typical of Peg/RBV. CONCLUSION: Low vitamin D levels predicts negative treatment outcome, and adding vitamin D to conventional Peg/RBV therapy for patients with HCV genotype 2-3 signifi cantly improves viral response.
