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OBJECTIVE@#To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients.@*METHODS@#A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented.@*RESULTS@#The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns.@*CONCLUSION@#Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).
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Adult , Female , Humans , Male , Young Adult , Adenine , Therapeutic Uses , Antiviral Agents , Therapeutic Uses , Double-Blind Method , Drug Therapy, Combination , Drugs, Chinese Herbal , Therapeutic Uses , Hepatitis B e Antigens , Allergy and Immunology , Hepatitis B, Chronic , Drug Therapy , Allergy and Immunology , Medicine, Chinese Traditional , Organophosphonates , Therapeutic UsesABSTRACT
To evaluate the clinical curative effect of Compound Biejia Ruangan Tablets (CBRT) combined with Adefovir Dipivoxil in the treatment of chronic hepatitis B with liver fibrosis using Meta-analysis. Cochrane library, PubMed, CNKI, Wanfang databases, and VIP were retrieved comprehensively to collect randomized controlled trials (RCTs) of CBRT combined with Adefovir Dipivoxil in the treatment of chronic hepatitis B with hepatic fibrosis from their inception to October 2017. treatment group was treated with CBRT combined with Adefovir Dipivoxil, and the control group was treated with Adefovir Dipivoxil. All the data were analyzed using Revman 5.3. A total of 19 RCTs and 1 776 patients were included. Meta-analysis results showed that the serum indexes including HA, IV-C, LN, PCIII, ALT, AST, and TBIL of the treatment group, were significantly lower than those of control group. HA [SMD = -1.72, 95% CI (-2.26, -1.17), P = 0.000 01]; IV-C [SMD = -1.10, 95% CI (-1.66, -0.54), P = 0.000 10]; LN [SMD = -1.18, 95% CI (-1.64, -0.73), P = 0.000 01]; PCIII [SMD = -1.52, 95% CI (-1.97, -1.07), P = 0.000 01]; ALT [SMD =-0.48, 95% CI (-0.68, -0.28), P = 0.000 01]; AST [SMD = -1.19, 95% CI (-2.08, -0.29), P = 0.010 00]; TBIL [SMD = -0.98, 95%CI (-1.38, -0.58), P = 0.000 01]; There were no significant difference in serum HBV DNA, and HbeAg negative conversion rate treatment group compared with control group. HBV DNA [RR = 1.21, 95% CI (0.97, 1.50), P = 0.09]; HBeAg [RR = 1.05, 95% CI (0.82, 1.34), P = 0.70]; The total clinical effective treatment group was significantly better than control group. [RR = 1.25, 95% CI (1.15, 1.36), P = 0.000 01]. Compared with the single use of Adefovir Dipivoxil, the clinical curative effect of CBRT combined with Adefovir Dipivoxil in the treatment of chronic hepatitis B with liver fibrosis is better,which can significantly reduce the level of serum liver fiber markers and improve liver function in patients with biochemical indicators and the total clinical efficiency.
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In current study, adefovir dipivoxil (AD)-acetaminophen (AP) cocrystal (molar ratio, 1:1) was prepared by slow evaporation from acetonitrile, followed by physicochemical characterizations using differential scanning calorimetry, powder X-Ray diffraction and Fourier transform infrared spectroscopy. Molecular modeling showed that the phosphoester group of AD was connected with the amide group of AP through hydrogen bonds. In comparison to crystalline AD, the solubility and dissolution rate of AD from AD-AP cocrystal were significantly enhanced by 1.5-fold and 1.6-fold, respectively. In addition, based on the rat single-pass intestinal perfusion study, the permeabilities of AD in various intestinal sections (i.e., duodenum, jejunum, ileum and colon) were significantly improved (e.g., about 3-fold enhancement in duodenum) after cocrystallization with AP by inhibiting P-glyprotein mediated efflux of AD, which will benefit absorption in vivo and subsequent oral bioavailability of poorly permeable drug AD.
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Objective To compare the efficacy and safety of entecavir versus adefovir dipivoxil in the treatment of HBeAg positive chronic hepatitis B ( CHB) . Methods Ninety?six cases with HBeAg positive CHB were divided into ETV group and ADV group according to different medication. In addition to conventional treatment,ETV group received entecavir 0. 5 mg/d,ADV group received adefovir dipivoxil 10 mg/d. HBV DNA negative conversion rate,alanine aminotransferase ( ALT) recurrence rate and HBeAg negative conversion rate in 24 weeks,48 weeks and 96 weeks were compared as well as the adverse reactions and liver function in 96 weeks. Results HBV DNA negative conversion rates in ETV group were significantly higher than those in ADV group in 24 weeks,48 weeks and 96 weeks (24 weeks:64. 6％(31/48) vs. 41. 7％(20/48);48 weeks:83. 3％(40/48) vs. 52. 1％(25/48);96 weeks:97. 9％(47/48) vs. 62. 5％(30/48),χ2 =5. 06,10. 72,18. 96,P<0. 05) . ALT recurrence rates in ETV group were significantly higher than those in ADV group at 24 weeks,48 weeks ( 24weeks:77. 1％( 37/48 ) vs. 54. 2％( 26/48 );48weeks:85. 4％( 40/48 ) vs. 62. 5％( 30/48 ) ,χ2=5. 59,6. 54,P<0. 05). There was no significant difference in ALT complication rate at 96 week(χ2=0. 71,P>0. 05) . There was no significant difference in HBeAg negative conversion rate between the two groups through treatment(χ2=0. 07, 0. 22, 0. 44, P>0. 05 ) . After 96 weeks, ALT in both groups decreased significantly ( t =13. 56,11. 85,P<0. 05) ,while ALT in ETV group was significantly lower than that in ADV group ( ( 31. 8 ±8. 6) U/L vs. (38. 5±7. 5) U/L,t=4. 07,P<0. 05). AST in both groups decreased significantly(t=41. 27, 33. 68,P<0. 05),while AST in ETV group was significantly lower than that in ADV group ( (30. 3±6. 5) U/L vs.(37.6±7.1)U/L,t=5.25,P<0.05).TBIL in both groups decreased significantly(t=28.92,22.23,P<0. 05),while TBIL in ETV group was significantly lower than that in ADV group ( (13. 5±3. 3) μmol/L vs. (18. 7±3. 9) μmol/L,t=7. 05,P<0. 05). GGT in both groups decreased significantly (t=16. 99,13. 97,P<0.05),while GGT in ETV group was significantly lower than that in ADV group ( (35.6±10.4)U/L vs. (59. 7±12. 5)U/L,t=10. 27,P<0. 05). There was no significant difference in adverse reaction between the two groups (χ2=1. 96,P>0. 05) . Conclusion Entecavir has a higher rate of HBV DNA negative conversion rate, ALT recurrence rate and HBeAg negative conversion rate in the treatment of HBeAg positive CHB. It is an ideal antiviral drug.
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Objective@#To compare the effect of combined therapy using lamivudine (LAM) plus adefovir (ADV) versus telbivudine (LdT) plus adefovir corresponding to the renal function of CHB patients.@*Methods@#A total of 120 patients with chronic hepatitis B were enrolled. According to single daily dosing, they were divided into 4 groups: LdT + ADV group (n = 32), ADV+LdT group (n = 28), LAM + ADV group (n = 38) and ADV + LAM group (n = 22). Hepatorenal function, HBV serological markers, HBV DNA quantification, creatine kinase (CK) and other parameters were examined every 3 months. Serum alanine aminotransferase (ALT) normalization rate, undetectable HBV DNA rate, hepatitis B e antigen (HBeAg) seroconversion rate, level of serum creatinine (CR) and estimated glomerular filtration rate (eGFR) were analyzed at baseline time, and at weeks 24 and 52.Stastical data were analyzed by t- test and analysis of variance, count data using χ 2 test.@*Results@#There was no statistically significant difference between the four groups in terms of ALT normalization rate, HBeAg seroconversion rate, undetectable HBV DNA rate at 24 and 52 weeks. Compared with baseline, at 24 weeks of treatment, there was no significant change in serum creatinine and eGFR in the 4 groups, but after 52 weeks of treatment, serum creatinine decreased in LdT + ADV and ADV + LdT groups and eGFR increased (P < 0.05); Serum creatinine in ADV and ADV + LAM increased, and eGFR was decreased than before (P < 0.05). After treatment, there was no significant difference in renal function between the four groups at 24 weeks, but at week 52, eGFR increased and serum creatinine decreased in LdT + ADV group compared with LAM + ADV group (P < 0.05); ADV + LdT Compared with ADV + LAM group, eGFR increased and serum creatinine decreased (P < 0.05). At 52 weeks of treatment, 5 patients with mildly impaired renal function in the ADV + LdT group [n = 10, eGFR 60-90 ml·min-1 ·(1.73 m2)-1] returned to normal, and none of the ADV + LAM group (n = 9) returned to normal.@*Conclusion@#For patients with mild impaired renal function, adding LdT combined with ADV can improve renal function compared to that of LAM plus ADV.
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Objective To explore the effects of telbivudine (LdT) and entecavir (ETV) on renal function in chronic hepatitis B (CHB) patients with renal damage after adefovir dipivoxil (ADV) treatment. Methods The clinical data of 40 CHB patients with renal damage after ADV treatment from January 2015 to February 2016 were retrospectively analyzed. The patients were divided into 2 groups according to the substitution drugs. Twenty patients in ETV group received ETV replacement therapy, and 20 patients in LdT group received LdT replacement therapy. The serum alanine aminotransferase (ALT), serum creatinine, serum creatine kinase (SCK), urinary β2-microglobulin (Uβ2-MG), estimated glomerular filtration rate (eGFR), classification of renal function, improvement of renal function and positive rate of HBV-DNA were compared between 2 groups. Results There was no statistical difference in serum ALT between 2 group (P＞0.05). The serum creatinine, SCK, Uβ2-MG and eGFR levels after treatment in LdT group were significantly better than those in ETV group: (92.08 ± 9.35) μmol/L vs. (101.21 ± 10.31) μmol/L, (133.69 ± 31.29) U/L vs. (106.14 ± 26.19) U/L, (5 126.17 ± 415.79) μg/L vs. (6 381.92 ± 574.12) μg/L and (81.61 ± 20.52) ml/(min·1.73 m2) vs. (75.34 ± 19.67) ml/(min·1.73 m2), and there were statistical differences (P＜0.05). There was no statistical difference in the positive rate of HBV-DNA after treatment between 2 groups (P＞0.05). The abnormal rate of renal function classification after treatment in LdT group was significantly lower than that in ETV group: 0 vs. 20.0% (4/20), the improvement rate of renal function in ETV group was significantly higher than that in ETV group: 100.0% (20/20) vs. 80.0% (16/20), and there were statistical differences (P＜0.05). Conclusions The effect of LdT on renal function improvement in CHB patients with renal damage after ADV treatment is more obvious than that of ETV, which can significantly improve serum creatinine, SCK, Uβ2-MG and eGFR, and reduce the abnormal renal function.
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A 61-years male patients with chronic hepatitis B developed hypophosphatemic osteomalacia following long-term use of adefovir dipivoxil in our hospital.With "adefovir dipivoxil" and "osteomalacia" as the search terms,we searched Wanfang database and Chinese Biomedical bibliographic database since 2005,and retrieved 79 cases of adefovir dipivoxil-induced hypophosphatemic osteomalacia.Of the 80 cases,there were 63 males and 17 females with a mean age of (52 ± 11) years.The average duration of disease to first diagnosis made was 17 months,the average duration of adefovir dipivoxil administration to the onset of the disease was 62 months,and the average duration of hepatitis B was 11 years.The most common clinical manifestation was progressive bone pain in all parts of the body (80/80 cases);the most common laboratory finding was decreased serum phosphorus (80/80 cases),followed by abnormal urine tests (55/56 cases) including increased urinary phosphorus,urinary protein and positive urinary occult blood.The X-ray,CT and MRI showed different degrees of decreased bone density,osteoporosis,and bone fracture in severe patients (76/77 cases).It is suggested that clinicians should pay attention to the renal damage during the treatment of adefovir dipivoxil,and the renal function,electrolyte and bone density should be monitored regularly.
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Objective To investigate the clinical efficacy of entecavir and adefovir dipivoxil in the treatment of decompensated cirrhosis with hepatitis B virus. Methods 100 cases of decompensated cirrhosis of hepatitis B in our hospital (February 2015 to October 2016) were randomly divided into control group and experimental group, each with 50 cases. The control group was treated with adefovir dipivoxil, and the experimental group was treated with entecavir and adefovir dipivoxil. The clinical symptoms of the two groups were compared and analyzed. Results After treatment, the level of ALT in the experimental group was (46.20±3.21) U/L, and the level of AST was (52.40±3.90) U/L.The level of ALT in the control group was (70.43±10.90) U/L, and the level of AST was (70.33±9.19)U/L, and the two groups had statistical significance (P＜0.05). The negative rate of HBV-DNA in the experimental group was 76.0%, which was significantly higher than that in the control group (58.0%), and there was statistical difference (P＜0.05). The negative rate of HBeAg in the two groups was 22.0% and 24.0% respectively, and there was no significant difference. Conclusion Entecavir and adefovir dipivoxil in the treatment of hepatitis B liver cirrhosis patients clinical effect is ideal,can significantly improve the liver function, improve clinical symptoms, high safety, has clinical significance.
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Objective To investigate the clinical efficacy of entecavir and adefovir dipivoxil in the treatment of decompensated cirrhosis with hepatitis B virus. Methods 100 cases of decompensated cirrhosis of hepatitis B in our hospital (February 2015 to October 2016) were randomly divided into control group and experimental group, each with 50 cases. The control group was treated with adefovir dipivoxil, and the experimental group was treated with entecavir and adefovir dipivoxil. The clinical symptoms of the two groups were compared and analyzed. Results After treatment, the level of ALT in the experimental group was (46.20±3.21) U/L, and the level of AST was (52.40±3.90) U/L.The level of ALT in the control group was (70.43±10.90) U/L, and the level of AST was (70.33±9.19)U/L, and the two groups had statistical significance (P＜0.05). The negative rate of HBV-DNA in the experimental group was 76.0%, which was significantly higher than that in the control group (58.0%), and there was statistical difference (P＜0.05). The negative rate of HBeAg in the two groups was 22.0% and 24.0% respectively, and there was no significant difference. Conclusion Entecavir and adefovir dipivoxil in the treatment of hepatitis B liver cirrhosis patients clinical effect is ideal,can significantly improve the liver function, improve clinical symptoms, high safety, has clinical significance.
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Objective To compare the efficacy of lamivudine (LAM) plus adefovir dipivoxil (ADV) de novo combination therapy to optimization monotherapy for hepatitis B virus-related compensated cirrhosis,and analyze the prediction factors of early response of antivirus treatment.Methods A total of 158 cases of patients with hepatitis B virus-related compensated cirrhosis were selected and randomly assigned to combined group (n=81) and optimized group (n =77) according to randomized digital table.The patients in the combined group accepted LAM combined ADV.The patients in the optimized group were firstly treated with LAM or ADV,then they were given optimized therapy with ADV or LAM if they had poor response or virological breakthrough at week 24.The clinical efficaeies were compared between the two groups,and the prediction factors of early response were analyzed.Results At week 12,the decline level of HBV DNA in the combined group was higher than that in the optimized group (P＜ 0.05),but no statistically significant difference was found in the negative transformation rate of HBV DNA between the two groups (P＞ 0.418).At week 24,the decline level of HBV DNA,rate of undetectable HBV DNA and rate of complete response were higher than those in the optimized group,and rate of virological breakthrough was lower than that in the optimized group (P＜0.05).At week 48,the decline level and negative transformation rate of HBV DNA,negative transformation rate and seroconversion rate of HBeAg were higher than those in the optimized group,and serum levels of hyaluronic acid and a2-macroglobulin were lower than those in the optimized group (P＜0.05).There was no statistically significant difference in the recover rate of alanine aminotransferase (ALT),rate of complete response and rate of virological breakthrough between the two groups at week 48 (P＞0.05).Logistic regression analysis showed that the complete response at week 24 was correlated with HBV DNA load,expression of HBeAg,level of ALT and initial treatment (P＜0.05).Layered evaluation showed that the rate of early complete response in the combined group was significantly higher than that in the optimized group,regardless of HBV DNA load,expression of HBeAg,and level of ALT (P＜0.05).Conclusion LAM combined with ADV can reduce resistance and improve the rate of early complete response,which has stronger antiviral activity.In addition,it can improve the liver function and partially reverse cirrhosis.
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OBJECTIVE:To evaluate therapeutic efficacy of lamivudine(LAM)combined with adefovir dipivoxil(ADV) in the treatment of LAM-resistant chronic hepatitis B patients,and to study the relationship of therapeutic efficacy with hepatitis B virus(HBV)genotype. METHODS:A total of 101 LAM-resistant chronic hepatitis B patients selected during Dec. 2012 to Dec. 2014 were given LAM+ADV for 24 months at least. Regular outpatient visits or telephone follow-up were also performed. Polymerase chain reaction-reverse dot blot method was used to determine the HBV genotype. Chi-square test,Kaplan-Meier meth-od and Log-rank test were used to compare the virological response(HBV-DNA clearance rate)and biological response(ALT normalization rate and HBeAg seroconversion rate)among different genotypes at the 6th,12th,18th and 24th month of fol-low-up. RESULTS:The follow-up rate was 100%,without missed follow-up. Two genotypes were detected,including 34 pa-tients(33.7%)with genotype B and 67 patients(66.3%)with genotype C.At each time point mentioned above,the HBV-DNA clearance rates of 101 patients were 34.7%,55.4%,79.2% and 93.1%.At 6th month,HBV-DNA clearance rate and accumula-tive HBV-DNA clearance rate of genotype B were significantly higher than genotype C,with statistical significance(P<0.05). There was no statistical significance in HBV-DNA clearance rates or accumulative HBV-DNA clearance rates between different genotypes at other time points(P>0.05). At each time point mentioned above,ALT normalization rates of 101 patients were 40.6%,69.3%,82.2%,84.2%;there was no statistical significance in ALT normalization rates or accumulative ALT normaliza-tion rates between different genotypes(P>0.05). At each time point mentioned above,the HBeAg seroconversion rates of 101 patients were 10.9%,19.8%,24.8%,29.7%;there was no statistical significance in the HBeAg seroconversion rates or accu-mulative HBeAg seroconversion rates between different genotypes(P>0.05). CONCLUSIONS:LAM combined with ADV is ef-fective for LAM-resistant chronic hepatitis B patients. Moreover,the combination therapy can achieve earlier viological response in patients with genotype B than those with genotype C.
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To systemically review the efficacy and safety of Fuzheng Huayu Capsule (FHC) combined with Adefovir Dipivoxil in treatment of chronic hepatitis B with hepatic fibrosis. Wanfang, CNKI, VIP, CBM, PubMed, Cochrane and Embase were retrieved by computers to collect the RCTs of FHC combined with Adefovir Dipivoxil in treatment of chronic hepatitis B with hepatic fibrosis from their inception to March 2017. After two reviewers separately screened literature according to the inclusion and exclusion criteria, extracted data and assessed the quality of the included studies, data were analyzed with RevMan 5.3 sofware. Totally 14 RCTs were included with 1 400 patients involved. According to Meta-analysis, compared with Adefovir Dipivoxil alone, FHC combined with Adefovir Dipivoxil was more efficiently in reducing the liver fibrosis indexes HA [MD = -99.66, CI = -129.94 - -69.37], P < 0.000 01]; LN [MD = -40.99, CI = -58.56 - -23.41, P < 0.000 01]; PCIII [MD = -76.40, CI = -108.15 - -44.66, P < 0.000 01]; IV-C [MD = -55.24, CI = -79.19 - -31.29, P < 0.000 01], in improving the liver function ALT [MD = -21.05, CI = -22.58 - -19.52, P < 0.000 01]; AST [MD = -16.74, CI = -25.14 - -8.33, P < 0.000 1]; TBIL [MD = -10.38, CI = 14.17 - 6.59, P < 0.000 01]; ALB [MD = 4.35, CI = -3.48 - 5.23, P < 0.000 01], and improving the ultrasound imaging results. Also, no significant adverse reaction was reported. FHC combined with Adefovir Dipivoxil could significantly improve liver function, reduce liver fibrosis indexes, and had less adverse reactions, but more large sample, high quality clinical trial are required to verify the curative effect.
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Objective To analyze the efficacy and the predictive factors of adefovir dipivoxil (ADV) therapy in patients with chronic hepatitis B(CHB).Methods Fifty two CHB patients were recruited in this study.All patients were treated for 52 weeks.Liver function,blood cell amounts and HBV DNA levels were detected at time course.Results At time point of 4 weeks,the serum HBV DNA level in good response group were significantly less than poor response group (2.48 ± 0.45 log10 vs 4.72 ± 0.28 log10,P ＜ 0.05).The decreased log value of HBV DNA in good response group was significantly higher than poor response group (3.31 ± 0.36 vs 1.54 ± 0.44,P ＜0.05).At time point of 12 weeks,the decreased log value of HBV DNA and neutrophil percent in good response group were significantly higher than poor response group [3.31 ± 0.36 vs 1.54 ± 0.44,(58.38 ± 2.08) × 109/L vs (46.90 ± 3.01) × 109/L,P ＜ 0.05],the serum HBV DNA level and red blood cell level in good response group were significantly less than poor response group[0.80 ± 0.27 log10vs4.63 ±0.43 log10,(4.50±0.08) ×1012/L vs (6.01 ±0.13) × 1012/L,P ＜0.05].Conclusion The decreased log value of HBV DNA and red blood cell level of 12weeks are the independently predictive factors for adefovir dipivoxil (ADV) therapy in patients with chronic hepatitis B.
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OBJECTIVE:To prepare nanostructured lipid carrier of adefovir dipivoxil(ADV-NLC),and optimize the formula-tion. METHODS:Using stearic acid and glycerin monostearate as solid lipid,oleic acid as liquid lipid,Gemini surfactant and poly-sorbate 80 as emulsifier,sodium dodecyl sulfate (SDS) as stabilizer,solvent dispersion ultrasonic method was used to prepare ADV-NLC. And using particle size,polydispersity index,Zeta potential,encapsulation efficiency as indexes,single factor test was conducted to screen Gemini surfactant-polysorbate 80 ratio,emulsifier dosage(ratio of emulsifier to water phase),drug-lipid ratio, solid-liquid lipid ratio. RESULTS:The formula was as follow as 3% emulsifier (Gemini surfactant-polysorbate 80 ratio of 1:2), 4.5% drug-lipid ratio,solid-liquid lipid ratio of 6:5. The average particle size of the prepared ADV-NLC was(48.83±2.65)nm, polydispersity index<0.3,Zeta potential was(-28.7±1.8)mV,encapsulation efficiency was(77.65±0.03)%(n=3). CONCLU-SIONS:ADV-NLC is successfully prepared,and the formulation is reasonable and feasible.
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Objective: To analyze the clinical characteristics of hypophosphatemic osteomalacia induced by adefovir dipivoxil (ADV) in order to improve the understanding of the disease.Methods: A retrospective analysis was performed according to the medical records of 11 cases of ADV-induced hypophosphatemic osteomalacia.The medical history, laboratory indicators (ALT, AST, ALB, SCr, UA, blood glucose, blood pH, BE), bone metabolic markers (25OHD3, PTH, tP1NP, β-CTX, OC), urine indicators (urine pH, 24h urine Ca, 24h urine P, 24h urine Pro, urine Scr), DXA and skeleton ECT signs of the patients with hypophosphatemic osteomalacia induced by ADV were analyzed, and the symptoms, blood P, AKP level and urine routines were followed up after 1-month withdrawal and in July, 2016, respectively.Results: The mean ADV administration time of the 11 patients was (5.7±1.2) years, and the bone pain time was (2.2±0.6) years.The serum P was (0.45±0.99)mmol·L-1, 24h urine P was (17.9±4.8)mmol, AKP was (248±107)IU·L-1,the concentration threshold of renal phosphate was(0.31±0.10)mmol·L-1.After the one-month withdrawal of ADV, the bone pain in the patients were all relieved, and with the phosphorus supplement, the level of serum phosphorus was increased.In July of 2016, the average withdrawal time of ADV was (18.3±10.7) months, the serum phosphorus significantly increased and AKP significantly decreased when compared with that on the admission and 1 month after the ADV withdrawal (P<0.05), and the serum phosphorus of 2 patients returned to normal with the recovery rate of 20% (2/10).The regression analysis showed that the influencing factors on serum phosphorus on the admission were renal concentration threshold of phosphate and tP1NP (P<0.05);the influencing factor on serum phosphorus on the last follow-up was bone mineral density at the admission (P<0.05).Conclusion: Hypophosphatemic osteomalacia is a potential side effect of ADV, and ADV-induced renal injury is not completely reversible, which should be paid more attention in clinical work.
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Objective: To investigate the curative effect of low-frequency therapeutic instrument of hepatopathy combined with Reduning injection in clinical treatment for patients with scarlet fever and hepatitis injury. Methods: 94 patients with scarlet fever and hepatitis injury were divided into observation group (47 cases) and control group (47cases). Patients of control group received the therapy of Reduning injection combined with tablet of adefovir dipivoxil, while the patients of observation group received the therapy of therapeutic instrument of hepatopathy combined with the therapy of control group. The changes of curative effect, indicator of hepatic fibrosis and response rate between two groups were observed. Results: The total effective rate of the observation group (95.7%) was significantly higher than that of control group (70.2%) (x2=7.283, P<0.05). In observation group, the hepatic fibrosis hyaluronic acid, III type procollagen, IV type collagen and laminin of post-treatment were significant improvement than that of pre-treatment (t=3.42, t=2.83, t=2.74, t=2.52, P<0.05). While in control groups, only the laminin of post-treatment was significant improvement than that of pre-treatment (t=2.15, P<0.05). After treatment, CR, VR, BR and HBeAg of observation group were significant higher than that of control group (x2=5.235, x2=5.623, x2=4.993, x2=6.823, P<0.05). Conclusion: The combination of low-frequency treatment of hepatopathy and Reduning injuection for the treatment of patients with scarlet fever and hepatic injury has significant effect, and it can effectively enhance the conversion rate of HBeAg, and improve liver function of patients. Therefore, it is worthy to be further promoteed in the clinical application.
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Objective To evaluate urinary β2-microglobulin (β2-MG) and retinoid binging protein (RBP) in monitoring of early renal impairment in chronic hepatitis B (CHB) patients with long-term adefovir dipivoxil (ADV) treatment. Methods Three hundred and fifty five with CHB admitted in Shaoxing Municipal Hospital from June 2009 to June 2011 were enrolled in the study, among whom 180 cases study group) were treated with ADV monotherapy (n=100) or ADV + lamivudine (LAM) combination therapy (n=80); and 175 cases (control group) were treated with entecavir (ETV). Serum creatinine, urinary β2-MG, RBP and creatinine were measured and glomerular tration rate (eGFR) was estimated regularly during 5-year follow up. Kaplan-Meier method was used to calculate the cumulative incidence of changes in urinary β2-MG and RBP. Results Five-year follow-up results showed that in study group 2, 6, 10, 14 and 24 cases developed urinary β2-MG abnormality in year 1, 2, 3, 4 and 5 of treatment, respectively; and 2, 7, 11, 16 and 20 cases developed urinary RBP abnormality in year 1, 2, 3, 4 and 5 of treatment, respectively; eGFR decreased 20%-30% from baseline in 20 cases, 30%-50% in 13 cases and >50% in 2 cases. The decrease of eGFR ≥30% in 5 years was significantly correlated with urinary RBP and β2-GM abnormality. However, both serum creatinine and eGFR remained stable during the 5 years of follow-up in control group; only 2 cases developed urinary β2-MG abnormality and 3 cases developed urinary RBP abnormality. Conclusions Urinary RBP and β2-MG are sensitive biomarkers of early renal injury during long-term ADV treatment in CHB patients, and ADV should not be used as first-line treatment for CHB.
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Objective: To prepare and in vitro evaluate the self-microemulsifying drug delivery system (SMEDDS) of adefovir dipivoxil (ADV).Methods: The optimized formula was screened by solubility, compatibility, ternary phase diagram and orthogonal design with the self-emulsifying time and particle size of microemulsion as the indices.The property of self-emulsification and the dissolution in vitro of ADV-SMEDDS were also determined.Results: The optimized SMEDDS was composed of Cremophor EL35 (37.5%), Transcutol HP (37.5%) and PECEOL (25%), and the drug loading was 3%.The ADV-SMEDDS formed stable microemulsion after the dilution by 50-fold amount of water in 24 s, the average particle size was (26.30±0.46) nm, the zeta potential was (-8.96±0.57) mV, and the dissolution was more than 85% in 5 min.Conclusion: The optimized formula of ADV-SMEDDS has significantly enhanced solubility and dissolution of adefovir dipivoxil in vitro.
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Objective To evaluate the efficacy of telbivudine in HBeAg-positive chronic hepatitis B (CHB) patients by comparing the efficacy of initial telbivudine therapy in treatment-naive patients with sequential telbivudine therapy in patients with poor response to adefovir.Methods A total of 90 HBeAg-positive CHB patients were assigned to receive sequential telbivudine therapy following poor response to adefovir dipivoxil (n=45),or initial telbivudine therapy in antiviral treatment-naive patients (n=45).All patients were treated with telbivudine 600 mg daily for 104 weeks.The efficacy was evaluated in terms of liver function tests,serum HBV markers,HBV DNA and antiviral drug resistance.Results Telbivudine showed good overall efficacy after treatment for 104 weeks in terms of alanine aminotransferase normalization rate (91.1％),HBV DNA negative conversion rate (80.0％),HBeAg loss rate (57.8％),and HBeAg/HBeAb seroconversion rate (30.0％).The HBV DNA negative conversion rate in initial treatment group was significantly higher than that in sequential treatment group (P＜0.05).However,among the patients with early response,the efficacy did not show significant difference between groups (P＞0.05).The patients with early response showed significantly better efficacy than those without early response,in terms of higher HBV DNA negative conversion rate,higher HBeAg loss rate and HBeAg/ HBeAb seroconversion rate (P＜0.000 1 or P＜0.05),but lower virological breakthrough rate (P＜0.05).Conclusions Telbivudine has shown reliable efficacy in CHB patients.Initial telbivudine therapy is better than sequential therapy in CHB patients with poor response to adefovir.However,for patients with early response to telbivudine,no statistical difference is found between initial and sequential therapy in long-term treatment efficacy (104 weeks).The patients receiving sequential telbivudine therapy should be monitored closely for early antiviral response to optimize treatment.
ABSTRACT
Objective To evaluate the clinical efficacy of interferon(IFN) α-2b,adefovir dipivoxil (ADV),granulocyte-macrophage colony stimulating factor (GM-CSF) and hepatitis B vaccine in the treatment of patients with HBeAg-positive chronic hepatitis B (CHB).Methods Two hundredand forty HBeAg-positive CHB patients admitted in the First Affiliated Hospital,Zhejiang University School of Medicine during November 2013 and December 2015 were retrospectively reviewed.They were randomly assigned to four groups with 60 cases in each group,to receive IFNα-2b (group A),IFNα-2b + ADV (group B),IFNα-2b + ADV + GM-CSF (group C) or IFNoα-2b + ADV + GM-CSF + hepatitis B vaccine (group D) for treatment,respectively.All patients were treated for 48 wks and then followed up for 24 wks.The HBsAg serological response,HBeAg serological response,virological response,biochemical response,histological response and adverse effects were compared among 4 groups.Results After 48-wk treatment,the HBsAg negative conversion rate of group D was significantly higher than that of group A and B (x2 =8.634 and 8.634,both P ＜ 0.01);the seroconversion rate of HBsAg in group D was significantly higher than that in group A and group B (x2 =7.149 and 7.149,both P ＜0.01).The baseline drop rate of HBsAg in group C and D was higher than that in group A (t =4.194 and 4.508,both P ＜0.01).In 24-wk follow-up,HBsAg negative conversion rate was as same as that after 48-wk treatment;the seroconversion rate of HBsAg in group D was significantly higher than that in group A and B (x2 =8.634 and 8.634,both P ＜0.01).The baseline drop rate of HBsAg in group C and group D was higher than that in group A (t =4.546 and 4.969,both P ＜0.01).After 48-wk treatment,the HBeAg negative conversion rate in group D was significantly higher than that in group A (x2 =8.792,P ＜ 0.01);the HBeAg seroconversion rate of group C and D was higher than that of group A (x2 =7.064 and 10.159,P ＜0.01).In 24-wk follow-up,the HBeAg negative conversion rate in group C and D was higher than that in group A (x2 =10.159 and 13.713,P ＜0.01);the HBeAg negative conversion rate in group D was higher than that in group B (x2 =8.155,P ＜0.01);the seroconversion rate of HBeAg in group C and D was higher than that in group A (x2 =10.506 and 12.857,P ＜ 0.01).After 48-wk treatment,the negative rate of HBV DNA in group B,C and D was significantly higher than that in group A (x2 =12.452,17.062 and 20.670,all P ＜0.01).In the 24-wk follow-up,the negative rate of HBV DNA in group B,C and D was also significantly higher than that in group A (x2 =21.121,26.880 and 33.611,all P ＜ 0.01).After 48-wk treatment,the alanine aminotransferase (ALT) normalization rate of the group of C and D was significantly higher than that in group A (x2 =8.711 and 8.711,both P ＜0.01).In the 24-wk follow-up,the ALT normalization rate in group C and D was significantly higher than that in group A (x2 =8.076 and 9.624,P ＜0.01).After 48-wk treatment,the improvement rate of inflammation or fibrosis in the group of A,B and C was significantly higher than that in the group A (x2 =8.543,13.348 and 16.205,all P ＜ 0.01).There were no half-way withdrawal and no serious adverse reactions.The main adverse reactions were fever,headache and fatigue,and no significant difference of above reaction was observed among 4 groups (P ＞ 0.05).Conclusion The new anti-virus/immunoregulation therapy containing IFNα-2b + ADV + GM-CSF + hepatitis B vaccine has a better therapeutic effect for patients with HBeAg-positive CHB.