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Chronic HBV infection is an important phase in the natural history of HBV, but there are still controversies over the treatment of this stage. Traditional Chinese medicine has had unique advantages in the prevention and treatment of viral hepatitis since ancient times and plays an important role in prevention and treatment of viral hepatitis in China. Based on the pathological process of chronic HBV infection, the team of Department of Hepatology in Shenzhen Hospital of Traditional Chinese Medicine believes that the core pathogenesis of chronic HBV infection is "kidney deficiency and epidemic toxin lurking in liver blood" and established kidney-tonifying therapy for the treatment of chronic HBV infection. Under the support of the project of Prevention and Treatment of Major Infectious Diseases such as AIDS and Viral Hepatitis in The Eleventh Five Year Plan, The Twelfth Five Year Plan, and The Thirteenth Five Year Plan, the team has conducted studies on the regularity of syndromes and a series of clinical studies and investigated the clinical efficacy of kidney-tonifying therapy through multicenter, randomized, double-blind, placebo-controlled studies, thereby exploring the application and mechanism of traditional Chinese medicine treatment in patients with chronic HBV infection. However, there are still difficulties in the pathogenesis and treatment of chronic HBV infection, and with the inheritance, innovation, and modernization of traditional Chinese medicine, it is believed that traditional Chinese medicine can provide reliable regimens for the treatment of chronic HBV infection.
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Objective To study the effects of tonifying kidney therapy on pathology in chronic hepatitis B virus carriers.MethodsWith the multi-center, randomized, double-blinded and placebo-controlled methods, 600 cases of chronic hepatitis B virus carriers were divided intoBushen Qingtou group,Bushen Jianpi group and control group, 200 cases in each group, and were treated withBushen Qingtou prescription,Bushen Jianpi prescription and placebo prescription respectively for 52 weeks. The pathological changes of the liver biopsy were observed by liver biopsy examination before and after treatment. Inflammatory active degree and fibrosis were scored with Knodell HAI and Ishak.Results The number of decreasing more than 2 points on Knodell HAI inBushen Qingtou group,Bushen Jianpi group and control group was 21, 18, and 6 respectively (P0.05). The number of decreasing more than 1 points on Ishak in Bushen Qingtou group,Bushen Jianpi group, and control group was 13, 12, and 9 respectively (P>0.05); the number of increasing more than 1 points on Ishak inBushen Qingtou group,Bushen Jianpi group and control group was 8, 3, and 11 respectively, with statistical significance betweenBushen Jianpi group and controlled group (P0.05), which meantBushenJianpi prescription could prevent the deterioration of liver tissue fibrosis more significantly than placebo prescription did. ConclusionTonifying kidney therapy, includingBushen Qingtou prescription andBushen Jianpi prescription, can inhibit the inflammatory activity and slow down the fibrosis progression of the chronic HBV carriers.
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Objective To observe the changes of peripheral blood interleukin-2(IL-2) ,interleukin-4(IL-4) ,interleukin-10(IL-10) ,tumor necrosis factor-alpha(TNF-α) and interferon gamma (IFN-γ) in chronic hepatitis B(CHB) patients with positive e-anti-gen(HBeAg) treated by Bushenqingtou Decoction .Methods 60 cases of CHB with positive HBeAg were randomly divided into the treatment group and the control group ,30 cases in each group .The CHB treatment group received Bushenqingtou Decoction with the treatment course of 48 week ,while the CHB control group did not received the medication therapy .In the beginning and at 48 weeks of treatment ,the blood in the two CHB groups were collected for detecting HBV DNA ,IL-2 ,IL-4 ,IL-10 ,TNF-αand IFN-γ. Results Compared with before treatments ,the levels of IL-2 ,TNF-αand IFN-γafter treatments in the CHB treatment group were obviously increased ,while the levels of HBV DNA ,IL-4 and IL-10 were remarkably decreased (P0 .05) .Conclusion Bushenqingtou Decoction could inhibit the replication of HBV DNA in the CHB patients with positive HBeAg and improve the body immune func-tion .
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Objective To study the Sheng Mai San on the levels of cell factors induced by lipopolysaccharide in acute liver failure rats. Methods The models of chronic liver failure were constructed by injecting CCl4 in the abdomen of rats. The serum levels of lipopolysaccharide and cell factors were determined after treating with LPS and Sheng Mai San for 2 hours. Results The serum level of IL-6［(64.50±18.79)pg/ml vs (4.79±0.57)pg/ml］, ICAM-1［(25100.00±5258.85)pg/ml vs (4215.50±942.79)pg/ml］ and TNF-α［(17.55±2.39)pg/ml vs (10.92±5.02)pg/ml］ was increased by CCl4 (P＜0.05), but there is no effect on the serum level of LPS in rats ［(0.058±0.007)EU/ml vs (0.040±0.002)EU/ml,P＞0.05］. Sheng Mai San can significantly reduce the serum level of IL-6, ICAM-1 and TNF-α in rats with acute liver failure induced by CCl4 ［(17.20±3.12)pg/ml,(9490.00±2725.78)pg/ml,(3.00±1.00)pg/ml,P＜0.05］. After treating with LPS for 2 hours, the serum level of LPS, TNF-α, IL-6, ICAM-1 markedly increased ［(0.501±0.019)EU/ml,(19750.00±9655.17)pg/ml,(5615.00±490.50)pg/ml,(41000.00±589.88)pg/ml,P＜0.01］. Sheng Mai San could reduce the serum levels of LPS, TNF-α, IL-6, ICAM-1 and in rats with chronic liver failure (P＜0.01). Conclusions SD Rats in the state of chronic liver fail-ure, existing serious serum endotoxin, can induce the levels of cell factors by diversification inflammation reaction and. ShengMaiSan can regulating the levels of cell factors in rats with chronic liver failure.
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Objective To compare the clinical efficacy and safety of pegylated interferon α-2a (Peg IFN α-2a) or adefovir dipivoxil(ADV) monotherapy and their combination therapy in HBeAg positive chronic hepatitis B (CHB) patients. Methods An open randomized controlled multicenter clinical trial was performed. One hundred and twenty cases with CHB were divided into 3 groups: Peg IFN α-2a monotherapy (group A), ADV monotherapy (group B) and Peg IFN α-2a plus ADV combination therapy (group C). The virological response (VR), serological response (HBeAg, HBsAg clearance and seroconversion), biochemical response (BR) and sustained response (SR) were tested at week 24 and 48 of therapy and week 48 of follow-up after end of treatment (EOT) for'evaluation of therapeutic effects, safety and drug resistance. The efficacy was compared using X2 test. Results At week 48 of treatment, the VR (HBV DNA ≤500 copy/mL) rates were 36. 8%(14/38), 37. 5%(15/40) and 62. 9% (22/35), respectively in groups A, B and C; that in group C was higher than those in groups A and B (X2 = 4. 933, 4. 801, respectively; both P < 0. 05); HBeAg seroconversion rates in three groups were 44. 7% (17/38), 17. 5% (7/40) and 51. 4% (18/35), respectively. At week 48 of follow-up,SR rates in three groups were 34. 2%(13/38), 15. 0%(6/40) and 48. 6% (17/35), respectively; those in groups C and A were higher than that in group B (X2 = 9. 894,P<0. 01;X2 =3. 903, P<0. 05, respectively). Conclusions VRs at week 24 and 48 of Peg IFN α-2a plus ADV combination therapy are better than Peg IFN α-2a or ADV monotherapy. SRs at week 48 of follow-up after Peg IFN α-2a monotherapy and combination therapy are both better than ADV monotherapy.
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Objective To observe the effects of serum with drug Penthorum chinense Pursh extractum on transforming growth factor (TGF)-β1 and collagen I secretions of activated hepatic stellate cells. Methods Twenty male SD rats were divided into 2 groups, and were administered with 0.9% sodium chloride solution and Penthorum chinense Pursh extraetum via gastrogavage for 3 days respectively and then sacrificed. Serum samples of these rats were collected. HSC-T6 cells were divided into the normal group and the treatment group. The cells of the normal group were incubated in Dulbecco's modified eagle medium (DMEM)with sera of normal rats, while those of the treatment group were incubated in DMEM with sera from Penthorum chinense Pursh extractum treated rats. The HSC-T6 viability was observed by AlamarBlue assay, while the toxicity of Penthorum ehinense Pursh extractum was measured by 3-(4, 5-Dimethyhhiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The expression of collagen I and TGF-β1 mRNA were determined by real timepolymerase chain reaction (real time PCR). The protein expressions of collagen I and TGF-β1 were analyzed by Western blotting. The data were analyzed by single factor analysis of variance and pairwise comparison was done by q test. Results Different concentrations of sera from Penthorum chinense Pursh extractum treated rats could all inhibit HSC-T6 proliferation, especially when the sera concentration were 10% and the HSC-T6 cells were incubated for 24 h (P＜0.01 ). MTT assay indicated that sera from Penthorum chinense Pursh extractum treated rats showed no obvious toxicity to HSC-T6 compared with those from normal rats (P ＞0.05). After 24 h incubation, 10% sera from Penthorum chinense Pursh extractum treated rats could significantly down-regulate mRNA expression of TGF-β1 and collagen I compared with normal group (TGF-β1 2.790±0.174 vs 9. 827 ± 1.429, P＜0.01 ; collagen I 1.213 ± 0.099 vs 4.053 ± 1.005, P＜0.01 ). Mcanwhile, the protein expressions of TGF-β1 and collagen I were also obviously inhibited in drug treated group compared with normal group (P＜0.01). Conclusions Serum from Penthorum chinense Pursh extractum treated rats can significantly decrease TGF-β1 and collagen I secretions of activated hepatic stellate cells, which provides the experimental evidence for liver fibrosis treatment.
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Objective To investigate the value of detecting hepatitis B virus (HBV) YMDD variants by matrix-assisted laser de-sorption time of flight mass spectrometry (MALDI-TOF MS). Methods The assay is based on polymerase chain reaction (PCR) amplifica-tion and mass measurement of oligonucleotides containing sites of mutation of the YMDD motif. Result The MALDI-TOF MS-based genoty-ping assay was sufficiently sensitive to detect as few as 100 copies of HBV genome per milliliter of serum, and this method had superior spe-cificity for determining mixtures of wild-type and variant viruses. When sera of 40 patients were analyzed, the MALDI-TOF MS-based assay correctly identified known viral variants and additional viral quasi-species not detected by previous methods, as well as their'relative abun-dance. Conclusion The sensitivity, specificity and amenability to high-throughput analysis make MALDI-TOF MS-based assay suitable for mass screening of HBV infected patients who are receiving lamivudine.
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Objective To investigate the effects of "a determinant variants in chronic hepatitis B(CHB)patients on the expression of hepatitis B surface antigen(HBsAg) and anti-HBs antibodies (HBsAb). Methods Eight hundred sixty-six chronic hepatitis B patients were enrolled, which HBs Ag carriage was beyond a 6 month period.77 patients(8.9%)concomitantly carried both HBs Ag and anti-HBs antibodies,789 patients(91.1%)were only HBs Ag positive. Selection criteria for patients with both HBs Ag and anti-HBs were mainly focused on anti-HBs titers at least three times above the analytical threshold of the technique(10 U/L)on at least three consecutive visits.14 patients were selected from77 patients, who presented both markers(group Ⅰ),and 12 patients from another 789 patients who positive for HBs Ag only(group Ⅱ)were randomly selected as controls. The HBs Ag-encoding gene was amplified and cloned, and at least 15clones per patient were sequenced and analyzed. Results The number of residue changes within the S protein group Ⅰ was 2.7 times more frequently than that in group Ⅱ patients, and "a" determinant of the major hydrophilic region(MHR)occurred mostly. Ten patients (71%)from group Ⅰ and three patients(25%)from group Ⅱ presented at least two residue changes in the MHR. The most frequent changes in group Ⅰ patients were located at positions s145,s129,s126,s144, and s123 as described for immune escape variants. Conclusions In CHB patients, the coexistence of HBsAg and HBsAb is associated with an increase of "a" determinant variability, suggesting a selection of HBV immune escape mutants during chronic carriage. The consequences of this selection process play an important role in vaccine efficacy, diagnosis and clinical therapy.
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[Objective] To study the mechanism of Ruangan Granule (RG) in counteracting the experimental liver fibrosis and cirrhosis in SD rats. [Methods] As compared with colchicines, effect of RG in small and large dosages on serum transforming growth factor ? (TGF ?1 ), hydroxyproline (Hyp), collagen Ⅰ and Ⅲ , hepatic function and hepatic pathology were observed in rats. [ Results ] Both RG and colchicines could decrease serum levels of alanine aminotransferase (ALT) and alkaline phosphatase (AKP) and increase serum levels of total protein and albumin in rats with liver fibrosis induced by bovine serum albumin (P 0.05). Effect of large-dosage RG in improving hepatic pathology was better than that of colchicines. [Conclusion] RG has an inhibitory effect on the formation of liver fibrosis and cirrhosis. Its mechanism may be related to the improvement of hepatic function, decrease of serum TGF ft , collagen Ⅰ and Ⅲ and Hyp levels.