bicyclol and Hepatitis-B--Chronic

Chronic viral hepatitis B and C are diseases worldwide. At present, the number of effective and safe drugs for treatment of HBV and HCV is still limited. In order to develop novel anti-viral hepatitis drug, a number of analogues of the active component schizandrin C from Fructus Schiznadrae, a Chinese herb used in the therapy of viral hepatitis, were synthesized. Bicyclol, one of the analogues, was demonstrated to have actions of anti-hepatitis virus replication in duck hepatitis model and 2.2.15 cell line, anti-experimental liver injury induced by hepatotoxins such as CCl4, acetaminophen and ConA, and anti-liver fibrosis in rats and mice. The active mechanism of bicyclol might be anti-apoptosis of hepatocytes through multiple signaling pathways mainly inducing the expressions of hepatic heat shock proteins (HSP27 and HSP70), molecular chaperons. Clinical trial was performed by double blind, randomized and positive control or placebo method in multi-medical centers in China. Patients received bicyclol 25mg thrice daily for six months, then stopped treatment and followed up for 3 months. Oral administration of bicyclol normalized the elevated serum transaminases (ALT, AST) by approximately 50% in chronic viral hepatitis B and C, and also showed certain level of inhibiting HBV and HCV replication. No noticeable adverse reaction has been observed. In combination therapy of bicyclol with interferon alpha, lamivudine and adefovir dipivoxil in HBV or HCV, bicyclol may potentiate the anti-viral efficacy and reduce YMDD mutant and side effects. In 2004 China FDA issued license to manufacture bicyclol. Since then bicyclol has been widely used to treat chronic HBV and HCV in China.

Topics: Animals; Antiviral Agents; Biphenyl Compounds; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Molecular Structure

To evaluate the efficacy and safety of bicyclol for chronic hepatitis B.. The authors searched CBMDisk, CJFD (2000-2006), CJD-CD, PubMed (1966-2006) for randomized controlled trials (RCT) comparing bicyclol versus non-antiviral interventions, interferon alpha (IFN-a) and lamivudine for treatment of chronic hepatitis B. Two reviewers performed data extraction and quality assessment independently and discussed when there was different opinion. We analyzed the data with RevMan 4.2 software supplied by Cochrane Collabration.. Fourteen RCTs involving 1782 patients were included. ALT recovery rate of bicyclol group was 69.3 percent while that of the control group was 59.0 percent, the difference was statistical significant [RR 1.24, 95 percent CI (1.01, 1.52), P=0.04]. Loss of HBeAg in the bicyclol group (22.1 percent) was higher than that of the control group (13.5 percent) [RR 1.65, 95 percent CI (1.32, 2.06), P<0.00001]. No serious adverse events were reported.. Bicyclol might be beneficial to recovery of liver function and loss of serum HBV marker. However, more high quality clinical trials are needed for confirmation.

Topics: Antiviral Agents; Biphenyl Compounds; Hepatitis B virus; Hepatitis B, Chronic; Humans; Randomized Controlled Trials as Topic

Bicyclol is a novel synthetic 'anti-hepatitis' drug, used in China for chronic hepatitis B. Until now, systematic reviews of bicyclol therapy have not been performed.. To study the benefits and harms of bicyclol for patients with chronic hepatitis B.. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (July 2005), The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2005), MEDLINE (1950 to July 2005), EMBASE (1980 to July 2005), Science Citation Index Expanded (1945 to July 2005), The Chinese Biomedical Database (1994 to August 2005), VIP Chinese Science and Technique Journals Database (1994 to August 2005), and China National Infrastructure (CNKI)(1994 to August 2005). We also contacted manufacturers and researchers in the field.. Randomised clinical trials with bicyclol versus no intervention, placebo, or other interventions were included, irrespective of blinding, publication status, or language.. The primary outcome measures were mortality (total and liver-related) and liver-related morbidity (eg, cirrhosis and carcinoma). Secondary outcome measures were viral response and liver histology.. The search identified one randomised clinical trial comparing bicyclol with bifendate (biphenyldicarboxylate) for patients with hepatitis B. The follow-up was three months. There was no evidence that bicyclol was superior to bifendate for loss of HBeAg (RR 1.38, 95% CI 0.95 to 2.00), seroconversion of HBeAg to HBeAb (RR 1.44, 95% CI 0.90 to 2.29), loss of HBV DNA (RR 1.19, 95%CI 0.93 to 1.53), or number of patients with normalised alanine aminotransferase and aspartate aminotransferase activity (RR 0.88, 95% CI 0.70 to 1.11 and RR 0.97, 95% CI 0.79 to 1.20, respectively).. Only one randomised clinical trial has examined the potential benefit of bicyclol for patients with chronic hepatitis B. This small, short-term trial found no evidence to support or refute its use. Large, randomised double-blind clinical trials with long-term follow-up are needed to examine the possible benefits and harms associated with bicyclol. Bicyclol can only be recommended for use in randomised trials.

Topics: Biphenyl Compounds; Hepatitis B, Chronic; Humans

To investigate the clinical efficacy and safety of adefovir dipivoxil (ADV) in combination with bicyclol for the treatment of chronic hepatitis B (CHB) in seniors.. 96 senior patients with CHB were randomly divided into two groups, the treatment group and the control group. On the basis of routine liver protective treatment, patients in the treatment group received ADV (10 mg/d) and bicyclol tablets (25 mg, tid.) orally, and those in the control group were orally administrated ADV tablets (10 mg/d) only. The treatment course for both groups was 24 weeks. Serum ALT, AST, and alterations of virological parameters were observed before and after the treatment.. Before and at the end of the 24 weeks treatment, ALT level for the treatment group was (208.44 +/- 94.22) and (34.47 +/- 12.79) U/L, and those for the control group was (205.73 +/- 96.48) and (44.20 +/- 21.96) U/L, respectively (difference between groups P < 0.01). At the end of the 24 weeks treatment, ALT normalization rates for the treatment group and the control group were 76.6% and 54.5%, respectively, and AST normalization rates for them were 76.6% and 54.5%, respectively (both differences between groups P < 0.05); HBV DNA loads for the treatment group and the control group were decreased by (3.1 +/- 1.40) lgIU/ml and (2.98 +/- 1.17) lgIU/ ml, respectively (difference between groups P > 0.05). The incidence rates of adverse events between two groups were not statistically significant.. It suggested that the treatment of ADV in combination with bicyclol for senior patients with CHB is effective and safe.

Topics: Adenine; Aged; Aged, 80 and over; Antiviral Agents; Biphenyl Compounds; DNA, Viral; Female; Hepatitis B, Chronic; Humans; Liver; Male; Middle Aged; Organophosphonates

To analyze the efficacy of adefovir dipivoxil combined with bicyclol in treatment of HBeAg-positive chronic viral hepatitis B (CHB).. A total of 91 patients with CHB were randomized into experimental group and control group to be treated. The patients in experimental group (46 samples) received adefovir dipivoxil orally 10 mg daily and bicyclol orally 150 mg daily for 48 weeks and those in control group (45 samples) received adefovir dipivoxil orally 10 mg daily alone for 48 weeks. The serum aminotransferace (ALT/ AST), HBV-DNA, HBeAg/antiHBe were observed before and after treatment.. Compared with pretreatment, the serum aminotransferace were all decreased obviously in two groups, the experimental group is better (P < 0.05). HBVDNA negative conversion rate was significantly higher in experimental group than in the control group (47.8% vs. 31.1%, P < 0.05). There were nostatistically differrence between the two groups in the portion of HBeAg loss rate and HBeAg seroconversion rate. There were no obvious adverse reaction in the study.. Adefovir dipivoxil combined with bicyclol is efective in the treatment of chronic hepatitis B.

Topics: Adenine; Adolescent; Adult; Aged; Biphenyl Compounds; Drug Therapy, Combination; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged; Organophosphonates; Treatment Outcome; Young Adult

To investigate the relationship between the genetic polymorphisms of CYP3A5 and the clinical effectiveness of Bicyclol on patients with chronic hepatitis B to make individual medication possible.. 34 cases of chronic hepatitis B were treated by bicyclol tablets for 24 weeks. Liver function indexes (ALT and AST) were determined before and after treatment. Blood CYP3A5 genotyping of each patient was determined by the PCR-RFLP analysis.. All subjects were genotyped for the CYP3A5*3 gene and divided into different group. The groups comprised subjects with CYP3A5*3 carriers (n=18) and CYP3A5*1 carriers (n=16) which include CYP3A5*1/*1 (n=2) and CYP3A5*1/*3 (n=14). Compared with pre-treatment, the serum ALT and AST levels were decreased obviously in all patients. The mean percentage reduction of serum ALT and AST levels were significantly greater in subjects with CYP3A5*3 carriers (79.73% and 74.76%) than in those with CYP3A5*1 carriers (65.90% and 49.63%; P < 0.05) The recovery rates of ALT and AST were significantly highter in CYP3A5*3 carriers than those in CYP3A5*1 carriers (P < 0.05).. CYP3A5 genotype has an impact on the therapeutic effects of Bicyclol. The subjects with CYP3A5*3 carriers is more effective than the subjects with CYP3A5*1 carriers. CYP3A5 genotyping may be helpful in predicting therapeutic effects of Bicyclol especially in the terms of decreasing ALT and AST.

Topics: Adolescent; Adult; Alanine Transaminase; Biphenyl Compounds; Cytochrome P-450 CYP3A; Female; Genotype; Hepatitis B, Chronic; Humans; Liver; Male; Middle Aged; Polymorphism, Genetic

To analyze the efficacy and safety of bicyclol combined with thymosin in treatment of chronic viral hepatitis B (CHB).. A total of 135 patients with CHB were randomized into experimental group and control group. The patients in the experimental group received bicyclol orally 75 mg daily and thymosin 20 mg intramuscular injection once every 2 days for 24 weeks and those in control group received bicyclol orally 75 mg daily alone for 24 weeks. The levels of serum aminotransferase (ALT/AST), HBV-DNA, HBeAg /antiHBe were observed.. Compared with pre-treatment levels, the serum aminotransferase levels decreased significantly in both groups, but there were no statistically significant differences between them. HBeAg negative conversion rate was significantly higher in the experimental group than in the control group (35.3 percent vs.19.4 percent, P less than 0.05). HBV DNA negative conversion rate was significantly higher in the experimental group than in the control group (36.7 percent vs. 20.9 percent, P less than 0.05). No obvious adverse events which were probably related to the drugs were observed in this study.. The combination of bicyclol with thymosin had better effect in treatment of chronic hepatitis B ias compared with bicyvlol alone.

Topics: Adolescent; Adult; Biphenyl Compounds; Drug Therapy, Combination; Female; Hepatitis B, Chronic; Humans; Male; Middle Aged; Thymosin

To study histological changes of the livers in patients with chronic viral hepatitis B treated with bicyclol tablets.. Thirty one patients with chronic viral hepatitis B were divided into two groups and were treated with bicyclol orally at doses of 150 mg daily or 75 mg daily for 36 weeds. The histological changes of the livers were observed before and after the treatment.. Compared with pre-treatment findings, there were significant differences in histological activity index in each group (P < 0.01, P < 0.05), there were also significant differences between the two groups (P < 0.05). Decreased inflammatory reaction was also seen (P < 0.05).. Daily use of 150 mg and 75 mg bicyclol tablets are effective in improving liver histological changes in chronic hepatitis B patients. Bicyclol 150 mg daily was better.

Topics: Adult; Antiviral Agents; Biphenyl Compounds; DNA, Viral; Female; Hepatitis B Antibodies; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Liver; Male; Middle Aged; Tablets; Treatment Outcome; Young Adult

To evaluate treatment effectiveness and safety of bicyclo tablets in children with chronic hepatitis B or C.. A randomized controlled trial was conducted in 148 children with chronic hepatitis B or C for evaluating safety, tolerability, and efficacy of treatment with bicyclo tablets or Hugan tablets. Children in therapy group were treated with bicyclo tablets and control group treated with Hugan tablets.. (1) ALT and AST level decreased more prominently in therapy group than in control group (P<0.01). (2) Bicyclo was more effective than Hugan tablets (P<0.01). (3) Symptoms were ameliorated more prominently in bicyclo group than in control group (P<0.01). (4) Both groups had no significant adverse events.. Satisfactory therapeutic effect and safety were obtained with bicyclo tablets in children with chronic hepatitis B or C.

Topics: Adolescent; Biphenyl Compounds; Child; Child, Preschool; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Tablets; Treatment Outcome

Bicyclol, the most commonly-used liver hepatoprotective drug in China, is often selected to control disease progression in CHB patients who refuse anti-viral treatment. However, data on histological changes after bicyclol treatment in these patients are scarce. Therefore, this study has been conducted to find out whether bicyclol has good benefits of histological improvement in CHB patients who refuse anti-viral agents.. The demographic, clinical and pathological data were collected from CHB patients who received bicyclol from January 2010 to June 2016. Improvement in liver inflammation or fibrosis is defined as at least one-grade or one-stage decrease as measured by the Scheuer scoring system. Thirty patients treated with ETV for 48 weeks were chosen as a control group to compare the histological improvement between bicyclol and entecavir (ETV) after 48-week treatment.. A total of 123 patients with CHB treated with bicyclol were included in this study. Paired liver biopsies were performed in 70 patients. Inter-biopsy interval was 17.44 ± 8.90 months (12-60 months). As shown by facts, 41.4% patients achieved liver inflammation improvement, while only 10.0% patients showed liver inflammation progression after bicyclol treatment. In regarding to liver fibrosis, as shown by facts, 28.6% patients achieved fibrosis improvement. More importantly, It was found that the proportions of patients with liver inflammation and fibrosis improvement were both not significantly lower than those in ETV group (53.3% vs 63.3 and 36.7% vs 43.4%). Most of patients (82.4%) with elevated baseline ALT became normal after bicyclol treatment. More importantly, as shown by the multi-variate analysis, the treatment course of bicyclol was an independent factor for liver inflammation improvement. With the HBeAg status adjusted, ALT and HBV-DNA quantity, the odds ratio (95% confidence interval) of patients with ≥48-week treatment was 5.756 (1.893,17.500) when compared with patients via < 48-week treatment.. Bicyclol can improve liver inflammation and the ALT normalization rate of CHB patients, especially when the treatment course is prolonged. This has confirmed that bicyclol could control hepatitis activity, which might be a good choice for CHB patients who refuse anti-viral treatments.

Topics: Adult; Alanine Transaminase; Antiviral Agents; Biopsy; Biphenyl Compounds; Female; Hepatitis B, Chronic; Humans; Liver; Male; Middle Aged; Treatment Outcome

Bicyclol is a novel anti-hepatitis drug used for the treatment of chronic hepatitis B. Bicyclol is insoluble in water and poorly absorbed after oral administration. To date, formulation development studies to improve the in vitro dissolution profiles of bicyclol and the in vivo oral absorption characteristics have not been performed.. To overcome problems associated with the poor solubility and low oral bioavailability of bicyclol, a microemulsion system was prepared and evaluated in vitro and in vivo.. The solubility of bicyclol in various cosurfactants was determined. The optimized premicroemulsion concentrate consisted of transcutol, Tween 20, Cremophor RH 40, propylene glycol monocaprylate and bicyclol (ratio, 50:150:100:150:3). The in vitro solubility and dissolution profiles were determined, and the in vivo oral absorption pharmacokinetics were evaluated in rats (dose, equivalent to 25 mg/kg of bicyclol) in comparison with bicyclol suspended in 0.5% calcium-carboxymethylcellulose (Ca-CMC).. Of various cosurfactants tested, transcutol provided the most significantly increased solubility of bicyclol (>20 mg/ml). Bicyclol was rapidly dissolved from the premicroemulsion concentrate (approximately 80% within 10 min). Consistent with the improved in vitro profiles, the oral absorption of bicyclol was significantly increased for the premicroemulsion concentrate, i.e. AUC and C(max) were increased by 7.7- and 7.2-fold, respectively, over control values. These findings demonstrate that the microemulsion may be a useful drug delivery system to improve the oral bioavailability of bicyclol.

Topics: Absorption; Administration, Oral; Animals; Antiviral Agents; Biological Availability; Biphenyl Compounds; Chromatography, Liquid; Drug Carriers; Drug Compounding; Emulsions; Hepatitis B, Chronic; Male; Mass Spectrometry; Molecular Structure; Particle Size; Rats; Rats, Sprague-Dawley; Solubility; Tissue Distribution

To evaluate the effect of combination therapy with peginterferon alfa-2a (Pegasys) +/- nucleos(t)ide analogues (NUC) and bicyclol in chronic hepatitis B with high ALT levels at baseline and during early treatment.. CHB patients were treated with PEG-IFNalpha-2a for a minimum of 48 weeks. All patients were followed up for 26 weeks post-treatment. Patients with HBV DNA > or = 1 x 10(8) copies/ml were combined with NUC (adefovir or entecavir) treatment. Patients with ALT > 500 U/L at baseline or ALT > 300 U/L after first injection of PEG-IFNalpha-2a received bicyclol treatment for 1-2 months (treatment group). Patients with 2 x ULN < ALT < 300 U/L and ALT < 300 U/L during treatment were enrolled into PEG-IFNalpha-2a +/- NUC antiviral monotherapy (control group). Responses defined as HBV DNA < 1 x 10(3) copies/ml, normal serum ALT, and HBeAg/HBsAg loss and seroconversion were analyzed at 26 weeks post-treatment.. A total of 54 patients (44 HBeAg positive, 10 HBeAg negative) were divided into two groups according to combination of bicyclol: treatment group (n = 20)--those who received combinition therapy with PEG-IFNalpha-2a +/- NUC and bicyclol, and control group (n = 34)--those who were treated with PEG-IFNalpha-2a +/- NUC antiviral monotherapy. During the first month of treatment, ALT levels declined gradually in treatment group. At 26 weeks post-treatment, the rates of ALT normalization and HBV DNA below the limit of 1 x 10(3) copies/ml were similar in both groups. Six patients in treatment group achieved HBsAg seroconversion at 26 weeks post-treatment, whereas so did 4 patients of control group (30% vs. 11.8%, P = 0.044).. Bicyclol could significantly relief elevation of ALT induced by the IFN treatment.

Topics: Alanine Transaminase; Biphenyl Compounds; DNA, Viral; Drug Therapy, Combination; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Interferon-alpha; Polyethylene Glycols; Recombinant Proteins

To compare the efficacy of bicyclol tablets on patients infected with hepatitis B virus between genotype B and C.. 70 patients with chronic viral hepatitis B were selected. The patients divide into two groups: HBV genotypes B (26 cases) and HBV genotypes C (other 44 cases). All patients received bicyclol tablets orally 150 mg daily (50mg, tid, po) for 24 weeks. The efficacy were observed after 12 weeks and 24 weeks.. After treatment for 24 weeks, the serum aminotransferase were decreased obviously, and HBV DNA levels turn to be negative with 19.2 percent (genotype B group) and 15.9 percent (genotype C group), respectively. The difference was not statistically significant between HBV genotype B and C.. Bicyclol not only has hepatoprotective activity but also inhibited virus replication in patients infected with HBV. The difference of the response to bicyclol therapy between HBV genotypes B and C was not statistically significant.

Topics: Adolescent; Adult; Biphenyl Compounds; Female; Genotype; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged

To study the effect of bicyclol tablets on the levels of interleukin (IL)-4, IL-10 and interferon (IFN)-gamma in culture supernatants of peripheral blood mononuclear cells (PBMCs) from patients with chronic hepatitis B (CHB).. Whole blood samples were obtained from 30 patients with CHB before and at 1 and 3 months during bicyclol tablet therapy and also from 7 healthy donors for isolation of the PBMCs. The product of IL-4, IL-10 and IFN-gamma in the culture supernatant of PBMCs were determined by enzyme-linked immunosorbent assay (ELISA) after 72 h of cultivation.. At 3 months during the therapy, the level of IFN-gamma was increased significantly in the patients from 36.25+/-19.92 pg/ml to 53.19+/-7.28 pg/ml (P<0.05) and the level of IL-4 significantly decreased from 17.18+/-7.43 pg/ml to 9.74+/-7.75 pg/ml (P<0.01). The changes in the levels of IL-4 and IFN-gamma at 3 months during therapy were more obvious in patients with HBeAg positivity than in HBeAg-negative patients (8.74+/-6.12 pg/ml vs 20.51+/-9.16 pg/ml, 50.71+/-30.76 pg/ml vs 26.03+/-10.48 pg/ml, respectively, P<0.05).. Bicyclol tablets not only promote Th1 type cytokine-mediated immune responses but also down-regulates Th2 type cytokine-mediated immune responses.

Topics: Adolescent; Adult; Biphenyl Compounds; Female; Hepatitis B, Chronic; Humans; Interferon-gamma; Interleukin-10; Interleukin-4; Leukocytes, Mononuclear; Male; Middle Aged; Tablets