Randomized controlled trial of steroid withdrawal followed by continuous and intermittent administration of natural α-interferon for chronic hepatitis B

Forty-two chronic hepatitis B patients positive for hepatitis B e antigen were randomly assigned to either intermittent or continuous administration of natural α-interferon after steroid withdrawal. The effects of the treatment were judged by their HBeAg/HBeAb serostatus and biochemical response. Temporary responses of HB e seronegative rates of these two protocols were 25.0% and 31.8%, and those of the HB e seroconversion rates were 15.0% and 13.6%, respectively. No significant difference was detected between the two treatment protocols. Biochemical response was seen in nine (40.9%) and eight (40.0%) cases out of 22 intermittent and 20 continuous cases, respectively. No significant difference was seen between the two groups. The patients' characteristics were examined for their relation to the sequelae of HB e antigen and biochemical responses. Younger age was a favorable condition for HB e antigen disappearance, although it was not statistically significant (P = 0.0791). The shorter interval between the cessation of steroid treatment and the beginning of interferon administration was a significantly favorable factor on biochemical response.     

Oxymatrine therapy for chronic hepatitis B： A randomized double-blind and placebo-controlled multi-center trial

AIM: To evaluate the efficacy and safety of capsule oxymatrine in the treatment of chronic hepatitis B. METHODS: A randomised double-blind and placebo-controlled multicenter trial was conducted. Injection of oxymatrine was used as positive-control drug. A total of 216 patients with chronic hepatitis B entered the study for 24 weeks, of them 108 received capsule oxymatrine, 36 received injection of oxymatrine, and 72 received placebo. After and before the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reaction were observed. RESULTS: Among the 216 patients, six were dropped off, and 11 inconsistent with the standard were excluded. Therefore, the efficacy and safety of oxymatrine in patients were analysed. In the capsule treated patients, 76.47% became normal in ALT level, 38.61% and 31.91% became negative both in HBV DNA and in HBeAg. In the injection treated patients, 83.33% became normal in ALT level, 43.33% and 39.29% became negative both in HBV DNA and in HBeAg. In the placebo treated patients, 40.00% became normal in ALT level, 7.46% and 6.45% became negative both in HBV DNA and in HBeAg. The rates of complete response and partial response were 24.51% and 57.84% in the capsule treated patients, and 33.33% and 50.00% in the injection treated patients, and 2.99% and 41.79% in the placebo treated patients, respectively. There was no significance between the two groups of patients, but both were significantly higher than the placebo. The adverse drug reaction rates of the capsule, injection and placebo were 7.77%, 6.67% and 8.82%, respectively. There was no statistically significant difference among them. CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.     

Randomized trial of peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin for chronic hepatitis C in Japanese patients

Background

Pegylated interferon (PegIFN) plus ribavirin is the standard therapy for patients with chronic hepatitis C genotype 1. Although several randomized clinical trials have compared PegIFNα-2a with PegIFNα-2b, these 2 regimens have not been directly compared in Asian patients. We, therefore, compared the safety and antiviral efficacy of these agents in Japanese patients.

Methods

A total of 201 PegIFN-na?ve, chronic hepatitis C patients were randomly assigned to once-weekly PegIFNα-2a (180?μg) or PegIFNα-2b (60–150?μg) plus ribavirin. We compared the sustained virological response (SVR) rates between the 2 regimens and analyzed their effects in relation to baseline characteristics, including single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene (rs8099917).

Results

PegIFNα-2a was associated with a higher SVR rate than PegIFNα-2b (65.3 vs. 51.0%, P?=?0.039). PegIFNα-2a and SNPs near IL28B independently predicted SVR (odds ratio 2.36; 95% confidence interval [CI] 1.19–15.50, and odds ratio 7.31; 95% CI 3.45–4.68, respectively) in logistic regression analysis. PegIFNα-2a was more effective than PegIFNα-2b (81.8 vs. 62.7%, P?=?0.014) in IL28B TT genotype patients, despite similarly low SVR rates in patients with TG or GG genotypes (36.4 vs. 35.9%). Patients weighing <60?kg, women, and patients aged >60?years had significantly higher SVR rates with PegIFNα-2a than with PegIFNα-2b (63.9, 61.3, and 67.3% vs. 43.8, 43.3,and 39.2%, respectively).

Conclusions

PegIFNα-2a plus ribavirin resulted in higher SVR rates than PegIFNα-2b plus ribavirin in Japanese patients. PegIFNα-2a-based treatment should therefore be the preferred choice for women, older or low-weight patients, and those with the IL28B TT genotype.     

Antioxidant therapy for chronic hepatitis C after failure of interferon： Results of phase Ⅱ randomized,double-blind placebo controlled clinical trial

AIM： TO assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus （HCV） infection.
METHODS： One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone, Primary end points were liver enzymes, HCV-RNA levels and histology.
RESULTS： Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo （P = 0.05）. Histology activity index （HAI） score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo （P = 0.21）. HCV-RNA levels decreased by l-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo （P = NS）. In part 11 of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.
CONCLUSION： Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.     

Ifosfamide, vindesine and recombinant α-interferon combination chemotherapy for metastatic renal cell carcinoma

Among 29 evaluable patients with progressive metastatic renal cell cancer treated by interferon2b in combination with vindesine and ifosfamide, we have observed an objective (complete and partial) response rate of 24.1% and an overall (complete and partial response and stable disease) response rate of 58.6%. The median duration of remission has not yet been reached, but the survival of responding patients is considerably longer than that of non-responders. Because we could not find any differences (sex, age, WHO performance status, prior therapy, site of metastatic disease) between responding and non-responding patients, we believe that the treatment might modify intrinsic characteristics of the tumour growth and/or host-tumour relationship in the long term. Although the toxicity recorded is high, the results are sufficiently positive to justify further investigation of this approach.Presented at the Satellite Symposium Ifosfamide in Tumor Therapy: Questions for the Nineties; 15th International Cancer Congress, Hamburg, August 16–22, 1990     

Randomized trial of albinterferon alfa-2b every 4 weeks for chronic hepatitis C virus genotype 2/3

Summary. Albinterferon alfa‐2b (albIFN) is a fusion protein of recombinant human albumin/recombinant interferon (IFN)‐α‐2b, with ～200‐h half‐life. Safety/efficacy of albIFN q4wk was evaluated in 391 treatment‐naive patients with chronic hepatitis C virus (HCV) genotype 2/3. Patients were randomized 3:4:4:4 to one of four open‐label treatment groups: pegylated IFN (Peg‐IFN)‐α‐2a 180 μg qwk or albIFN 900, 1200 or 1500 μg q4wk, plus oral ribavirin 800 mg/day, for 24 weeks. Primary efficacy endpoint was sustained virologic response (SVR; HCV RNA <20 IU/mL 24 weeks post‐treatment). SVR rates were as follows: 85%, 76%, 76% and 78% with Peg‐IFNα‐2a and albIFN 900, 1200 and 1500 μg, respectively (P = NS); corresponding rapid virologic response rates (HCV RNA <43 IU/mL at week 4) were as follows: 78%, 49% (P < 0.001), 60% (P = 0.01) and 71%. SVR rates were not influenced by interleukin 28B genotype, although rapid virologic response rates were greater with interleukin 28B CC (P = NS). Serious adverse event rates were as follows: 4%, 11%, 3% and 3% with Peg‐IFNα‐2a and albIFN 900, 1200 and 1500 μg, respectively. No increase in serious/severe respiratory events was noted with albIFN. Fewer absolute neutrophil count reductions <750/mm³ occurred with albIFN (P = 0.03), leading to fewer IFN dose reductions. Haemoglobin reductions <10 g/dL were less frequent with albIFN 900 and 1200 μg vs 1500 μg and Peg‐IFNα‐2a (P = 0.02), leading to fewer ribavirin dose reductions. albIFN administered q4wk produced fewer haematologic reductions than Peg‐IFNα‐2a, but had numerically lower SVR rates (P = NS) in patients with chronic HCV genotype 2/3.     

DA-9601 for erosive gastritis： Results of a double-blind placebo-controlled phase III clinical trial

AIM: To determine the efficacy and safety of DA-9601 on erosive gastritis versus cetraxate as a standard drug by gastrointestinal endoscopy. METHODS: Five hundred and twelve patients with erosive gastritis were divided into three groups. The groups received 180 mg or 360 mg of DA-9601, or 600 mg of cetraxate (Neuer) t.i.d. for 2 wk, respectively. Endoscopic observations were performed before and 2 wk after the treatment, and the cure and improvement rates were investigated. RESULTS: Of the 512 intention-to-treat (ITT) population, 457 patients comprised the per protocol (PP) analysis. Endoscopic cure rate was significantly higher in the DA-9601 group than in the cetraxate group in both the PP (56%, 58% vs 36%; DA-9601 180 mg, 360 mg and cetraxate, respectively) and ITT (52%, 51% vs 35%) populations. Two DA-9601 groups (180 and 360 mg) had significantly higher endoscopic improvement rates than the cetraxate group in both the PP (67%, 65% vs 46%) and ITT (63%, 58% vs 45%) populations. The percentage of symptom relief over the 2 wk was found not significantly different between groups. During the study, both DA-9601 and cetraxate produced no treatment-associated adverse events. CONCLUSION: From these results, it appears that DA-9601 has excellent efficacy on erosive gastritis. This study also confirms the safety profile of DA-9601.     

DA-9601 for erosive gastritis:Results of a double-blind placebo-controlled phase Ⅲ clinical trial

AIM:To determine the efficacy and safety of DA-9601 onerosive gastritis versus cetraxate as a standard drug bygastrointestinal endoscopy.METHODS:Five hundred and twelve patients with erosivegastritis were divided into three groups.The groupsreceived 180 mg or 360 mg of DA-9601,or 600 mg ofcetraxate (NeuerTM) t.i.d,for 2 wk,respectively.Endoscopicobservations were performed before and 2 wk after thetreatment,and the cure and improvement rates wereinvestigated.RESULTS:Of the 512 intention-to-treat (ITT) population,457 patients comprised the per protocol (PP) analysis.Endoscopic cure rate was significantly higher in the DA-9601 group than in the cetraxate group in both the PP(56%,58% vs36%,DA-9601 180 mg,360 mg and cetraxate,respectively) and ITT (52%,51% vs 35%) populations.Two DA-9601 groups (180 and 360 mg) had significantlyhigher endoscopic improvement rates than the cetraxategroup in both the PP (67%,65% vs46%) and ITT (63%,58% vs 45%) populations.The percentage of symptomrelief over the 2 wk was found not significantly differentbetween groups.During the study,both DA-9601 andcetraxate produced no treatment-associated adverse events.CONCLUSION:From these results,it appears that DA-9601 has excellent efficacy on erosive gastritis.This studyalso confirms the safety profile of DA-9601.     

A role for anabolic steroids in the rehabilitation of patients with COPD? A double-blind, placebo-controlled, randomized trial

STUDY OBJECTIVES: Skeletal muscle weakness commonly occurs in patients with COPD. Long-term use of systemic glucocorticosteroids further contributes to muscle weakness. Anabolic steroids could be an additional mode of intervention to improve outcome of pulmonary rehabilitation by increasing physiologic functioning, possibly mediated by increasing erythropoietic function. PATIENTS AND METHODS: We randomly assigned 63 male patients with COPD to receive on days 1, 15, 29, and 43 a deep IM injection of 50 mg of nandrolone decanoate (ND) [Deca-Durabolin; N.V. Organon; Oss, The Netherlands] in 1 mL of arachis oil, or 1 mL of arachis oil alone (placebo) in a double-blind design. All patients participated in a standardized pulmonary rehabilitation program. Outcome measures were body composition by deuterium and bromide dilution, respiratory and peripheral muscle function, incremental exercise testing, and health status by the St. George's Respiratory Questionnaire. RESULTS: Treatment with ND relative to placebo resulted in higher increases in fat-free mass (FFM; mean, 1.7 kg [SD, 2.5] vs 0.3 kg [SD, 1.9]; p = 0.015) owing to a rise in intracellular mass (mean, 1.8 kg [SD, 3.1] vs - 0.5 kg [SD, 3.1]; p = 0.002). Muscle function, exercise capacity, and health status improved in both groups to the same extent. Only after ND were increases in erythropoietic parameters seen (erythropoietin: mean, 2.08 U/L [SD, 5.56], p = 0.067; hemoglobin: mean, 0.29 mmol/L [SD, 0.73], p = 0.055). In the total group, the changes in maximal inspiratory mouth pressure (PImax) and peak workload were positively correlated with the change in hemoglobin (r = 0.30, p = 0.032, and r = 0.34, p = 0.016, respectively), whereas the change in isokinetic leg work was correlated with the change in erythropoietin (r = 0.38, p = 0.013). In the patients receiving maintenance treatment with low-dose oral glucocorticosteroids (31 of 63 patients; mean, 7.5 mg/24 h [SD, 2.4]), greater improvements in PImax (mean, 6.0 cm H(2)O [SD, 8.82] vs - 2.18 cm H(2)O [SD, 11.08], p = 0.046), and peak workload (mean, 20.47 W [SD, 19.82] vs 4.80 W [SD, 7.74], p = 0.023) were seen after 8 weeks of treatment with ND vs placebo. CONCLUSIONS: In conclusion, a short-term course of ND had an overall positive effect relative to placebo on FFM without expanding extracellular water in patients with COPD. In the total group, the improvements in muscle function and exercise capacity were associated with improvements in erythropoietic parameters. The use of low-dose oral glucocorticosteroids as maintenance medication significantly impaired the response to pulmonary rehabilitation with respect to respiratory muscle function and exercise capacity, which could be restored by ND treatment.     

Do synbiotics really enhance beneficial synbiotics effect on defecation symptoms in healthy adults?: Randomized,double-blind,placebo-controlled trial

Goals:We examined whether synbiotics enhance improvement by probiotics.Background:Probiotics, which are beneficial microbacteria, are a nutritional intervention for treatment of functional constipation or its tendency. Prebiotics, meanwhile, can promote the proliferation of probiotics in the gastrointestinal tract and enhance their beneficial effects. Synbiotics, a combination of probiotics and prebiotics, may be superior to probiotics in the treatment of defecation-related symptoms, but this requires elucidation.Study:This randomized, double-blind, placebo-controlled study enrolled 69 healthy adults with constipation tendency. Participants were allocated to either control, probiotics, or synbiotics groups and they recorded details of their defecations and their condition. The first 2 weeks were the observation period and the latter 2 weeks were the intervention period, in which participants took test foods. Probiotic foods included Bifidobacterium longum NT strain (10¹⁰ CFU/day), synbiotic foods included the NT strain (10¹⁰ CFU/day) and galactooligosaccharide (1 g/day). Placebo foods contained the vehicle only. Participants answered questionnaires (Patient Assessment on Constipation Symptoms [PAC-SYM], and one on dietary history) on the last day of each period.Results:Nine participants withdrew consent, and 2 of the remaining 60 had missing data. Age, body mass index, and sex were not significantly different between the 3 groups. Frequency of bowel movements in the fourth week, the primary endpoint, was not increased in the probiotics or synbiotics groups compared with the control group, and the frequency of bowel movements and days with defecation were not changed by probiotics or synbiotics during the intervention period. Probiotics and synbiotics did not improve stool conditions, although incomplete defecation was improved by probiotics but not by synbiotics compared with placebo. PAC-SYM indicated that stool condition and total scores were improved by probiotics but not by synbiotics during the intervention compared with placebo.Conclusion:The probiotic strain Bifidobacterium longum NT can improve constipation symptoms, especially stool condition, but it does not increase bowel movement frequency in healthy adults with constipation tendency. Synbiotics treatment seemed to diminish this improvement of constipation induced by probiotics. This study indicates the possibility of attenuation of beneficial effects from probiotics by the use of synbiotics, contrary to synbiotics theory.     

Treatment of postoperative ileus with choline citrate��results of a prospective, randomised, placebo-controlled, double-blind multicentre trial

Objectives

This was a prospective, randomised, placebo-controlled, double-blind multicentre trial to analyse the efficacy of choline citrate in patients with postoperative ileus (POI) after elective colorectal surgery.

Methods

From October 2005 until June 2008, 122 patients with POI were randomised to receive choline citrate or placebo. One hundred twenty patients were evaluable for tolerability and 107 patients were evaluable for efficacy. The treatment group, 47% (50/107), received 300.2?mg choline citrate intravenously, while the placebo group, 53% (57/107), received sodium chloride. Injections were performed every 12?h until defecation.

Results

Demographic data analysis did not show clinically differences between both groups. Operative procedures included 40% (43/107) hemicolectomy, 38% (41/107) sigmoid resection and 22% (23/107) other colorectal resections. Defecation occurred after an average of 91.8?±?26.6?h postoperatively in the treatment group, vs. 96.7?±?35.2?h in the placebo group (p?=?0.805). After laparoscopy, defecation occurred after 78.7?±?25.3?h, vs. 99.2?±?31.6?h after laparotomy (p?=?0.001). Serious adverse effects occurred in 2% (1/60) in the treatment group, vs. 3% (2/60) in the placebo group. None of the events have been assessed as related to the study medication.

Conclusion

An efficacy of choline citrate in the treatment of POI after elective colorectal surgery could not be verified. The problem of POI requiring drug treatment seems to be less frequent than suggested by the literature. With technical advances in surgery, especially laparoscopic and fast track surgery, the frequency of POI will further decrease in the future.     

Comparative trials of peginterferon α2a and peginterferon α2b for chronic hepatitis C

Standard of care for patients with chronic hepatitis C is pegylated interferon (pegIFN) combined with ribavirin (Rbv). It results in persistent viral eradication and prevents the progression of liver disease and the associated complications in about 50% of treated patients. Currently, two PegIFNs are available that differ significantly in terms of pharmacokinetic and pharmacodynamic profiles as a consequence of different pegylation chemistries. While the registration trials of the two therapeutic regimens demonstrated the superiority of each PegIFN vs the native IFN α2b, the superiority of one regimen over the other in terms of treatment efficacy remains unknown. Retrospective cohort studies and randomized prospective head-to-head trials have attempted to resolve the considerable controversy over this issue and support evidence-based treatment decisions.     

Randomized, double-blind, placebo-controlled study of peginterferon alfa-2a (40KD) plus ribavirin with or without amantadine in treatment-naïve patients with chronic hepatitis C genotype 1 infection

BACKGROUND/AIMS: Amantadine may augment virological response rates to interferon-based therapy in chronic hepatitis C patients. Using a novel design, amantadine was studied in na?ve genotype 1 patients treated in combination with peginterferon alfa-2a (40KD)/ribavirin. METHODS: Patients enrolled in this randomized, placebo-controlled multicenter trial were stratified by single-dose interferon sensitivity (stratum I, 24-h HCV-RNA decline >1.4-log10; II, 0.8-1.39-log10; III, <0.8-log10; a reliable means of identifying nonresponders to interferon/ribavirin) and fibrosis grade (F0/1/2 vs. F3/4) at baseline. All patients received peginterferon alfa-2a (40KD) 180 microg/week plus ribavirin 1000-1200 mg/day and were randomized to receive amantadine 100 mg twice daily (N = 114) or placebo (N = 95) for 48 weeks. RESULTS: Week-24 virological response rates in strata II and III, the primary outcome, were similar in patients treated with amantadine (63.7%) or placebo (65.7%), as were sustained virological response rates at week 72 (46.5 and 51.6%, respectively). Adverse event profiles were similar and amantadine did not improve health-related quality of life compared with placebo. Interferon sensitivity was the only significant predictor of treatment outcome. CONCLUSIONS: Adding amantadine to peginterferon alfa-2a (40KD)/ribavirin combination therapy does not augment virological response rates in genotype 1 patients. Virological response was almost exclusively determined by interferon sensitivity at baseline.     

Eficacy of six therapies for chronic hepatitis B

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Suggestion for new category of chronic hepatitis B

Since the fulminant hepatic failure(FHF)is de-fined initially by Trey and Davidson in the 1970s asthe occurrence of hepatic encephalopathy(HE)with-in 8 weeks of first symptoms of illness in a patientwithout previous liver disease,the nomenclatorial     

Potent hepatitis B surface antigen response to treatment of hepatitis-B-e-antigen-positive chronic hepatitis B with α-interferon plus a nucleos(t)ide analog

Background and Aim: Hepatitis B surface antigen (HBsAg) clearance is the closest cure outcome in hepatitis B. The goal of this study was to investigate clinical features in chronic hepatitis B patients achieving seroconversion of HBsAg after treatment with α‐interferon (IFN‐α) and a nucleos(t)ide analog. Methods: This retrospective study enrolled 38 chronic hepatitis B patients treated with IFN‐α plus a nucleos(t)ide analog who achieved HBsAg seroconversion during the period from June 2001 to May 2009. Clinical and laboratory data of the patients were collected before and after treatment every 3 months. All patients with HBsAg seroconversion in this study were followed up for at least 12 months post‐treatment. Results: A total of 38 out of 142 patients achieved HBsAg seroconversion after treatment with IFN‐α and a nucleos(t)tide analog for a prolonged period of time (medium 31 months). The median time to hepatitis B e antigen seroconversion and to HBsAg seroconversion was 19.5 months (range 3–60 months) and 25.5 months (range 9–63 months), respectively. Thirty‐six patients (95%) sustained HBsAg seroconversion during the post‐treatment follow up. Three different HBsAg response patterns were observed with classical model accounting for 57.9% (22/38 cases), simultaneous transition mode accounting for 23.7% (9/38 cases), and HBsAg prior transition model accounting for 18.4% (7/38 cases). Conclusions: Extended treatment with IFN‐α in combination with a nucleos(t)ide analog in patients with hepatitis‐B‐e‐antigen‐positive appears to be a promising approach for achieving a high rate of HBsAg clearance—the closest outcome to cure.