Blocking and reversing hepatic fibrosis in patients with chronic hepatitis B treated by traditional Chinese medicine (tablets of biejia ruangan or RGT): study protocol for a randomized controlled trial
Abstract:BackgroundChronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC) and ultimately liver-related death. Although oral antiviral therapy for patients with CHB reduces the risk of such complications, once cirrhosis is established, the benefits of antiviral therapy are not robustly demonstrated. According to traditional Chinese medicine (TCM), some Chinese herbal medicines promote blood circulation and soften hard masses, and therefore they may block and reverse hepatic fibrosis. The aim… Show more
“…A number of clinical trials have been performed to assess the therapeutic efficacy and safety of CHM products. 1 13 14 On the other hand, a recent cohort study reported that adjunctive therapy with CHM may improve the survival of patients with liver cancer. 15 Although nucleoside analogue therapy is associated with reduced risk of HCC in patients with CHB virus infection and experience fewer side effects, in many cases the drug resistance and viral variation limit their efficacy as therapeutic agents for CHB.…”
ObjectivePatients with chronic hepatitis B (CHB) are reported to exhibit higher risk of subsequent hepatocellular carcinoma (HCC). However, it remains unclear if Chinese herbal medicine (CHM), an important category of traditional Chinese medicine (TCM), may lower HCC risk in this population. So this study aimed to investigate the effects of CHM on HCC risk among patients with CHB.MethodsThis cohort study used the Taiwanese National Health Insurance Research Database to identify 21 020 newly diagnosed patients with CHB from 1998 to 2007. Among them, 8640 received CHM products after CHB onset (CHM users), and the remaining 12 380 patients were designated as a control group (non-CHM users). All enrolees were followed until the end of 2012 to measure the incidence rate and HR of HCC.ResultsDuring 15 years of follow-up, 371 CHM users and 958 non-CHM users developed HCC, representing an incidence rate of 5.28% and 10.18% per 1000 person-years, respectively. CHM users had significantly lower HCC risk compared with non-CHM users (adjusted HR=0.63, 95% CI 0.56 to 0.72). The predominant effect was observed in those receiving CHM products for more than 180 days (adjusted HR=0.52). Some CHM products, such as Hedyotis diffusa, Scutellaria barbata, Rehmannia glutinosa, Isatis tinctoria, Yi Guan Jian, Xiao Chai Hu Tang, Wu Ling San and Gan Lu Yin, were significantly associated with lower risk of HCC.ConclusionsThe use of CHM was associated with a significantly reduced HCC risk in patients with CHB, which supports the integration of TCM with CHM into clinical practice to influence a favourable prognosis.
“…A number of clinical trials have been performed to assess the therapeutic efficacy and safety of CHM products. 1 13 14 On the other hand, a recent cohort study reported that adjunctive therapy with CHM may improve the survival of patients with liver cancer. 15 Although nucleoside analogue therapy is associated with reduced risk of HCC in patients with CHB virus infection and experience fewer side effects, in many cases the drug resistance and viral variation limit their efficacy as therapeutic agents for CHB.…”
ObjectivePatients with chronic hepatitis B (CHB) are reported to exhibit higher risk of subsequent hepatocellular carcinoma (HCC). However, it remains unclear if Chinese herbal medicine (CHM), an important category of traditional Chinese medicine (TCM), may lower HCC risk in this population. So this study aimed to investigate the effects of CHM on HCC risk among patients with CHB.MethodsThis cohort study used the Taiwanese National Health Insurance Research Database to identify 21 020 newly diagnosed patients with CHB from 1998 to 2007. Among them, 8640 received CHM products after CHB onset (CHM users), and the remaining 12 380 patients were designated as a control group (non-CHM users). All enrolees were followed until the end of 2012 to measure the incidence rate and HR of HCC.ResultsDuring 15 years of follow-up, 371 CHM users and 958 non-CHM users developed HCC, representing an incidence rate of 5.28% and 10.18% per 1000 person-years, respectively. CHM users had significantly lower HCC risk compared with non-CHM users (adjusted HR=0.63, 95% CI 0.56 to 0.72). The predominant effect was observed in those receiving CHM products for more than 180 days (adjusted HR=0.52). Some CHM products, such as Hedyotis diffusa, Scutellaria barbata, Rehmannia glutinosa, Isatis tinctoria, Yi Guan Jian, Xiao Chai Hu Tang, Wu Ling San and Gan Lu Yin, were significantly associated with lower risk of HCC.ConclusionsThe use of CHM was associated with a significantly reduced HCC risk in patients with CHB, which supports the integration of TCM with CHM into clinical practice to influence a favourable prognosis.
“…This was a multicenter prospective sub-study of our ongoing clinical trial of regression of HBV-related liver fibrosis in China (NCT01965418)[25]. The study meets the requirements of the Declaration of Helsinki, the protocol was approved by the ethics committee of each participating institution, and written informed consent was obtained from all patients.…”
BACKGROUND
Non-invasive evaluation for liver fibrosis is clinically important, especially in patients with undetectable hepatitis B virus (HBV) DNA treated with nucleoside analogs.
AIM
To clarify the monitoring power of hepatitis B core-related antigen (HBcrAg) for hepatic histologic changes in patients with chronic hepatitis B (CHB) treated with entecavir.
METHODS
This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression, respectively, in 403 CHB patients, including 374 with entecavir for 72 weeks (291 underwent paired liver biopsy) and 29 as controls.
RESULTS
Level of HBcrAg correlated negatively with liver fibrosis staging (
γ
= -0.357,
P
< 0.001) in hepatitis B e antigen (HBeAg)-positive patients, and positively with liver fibrosis staging in HBeAg-negative patients. Higher HBcrAg concentration was associated with younger age, HBeAg positive status, high HBV DNA loads, high level of hepatitis B surface antigen (HBsAg) and higher necroinflammation, but not with HBV genotype. Serum concentration of HBcrAg, basal core promoter/precore (BCP/PC) mutant, quantitation of HBsAg (qHBsAg) and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression. HBV DNA was undetectable in 88.37% of patients treated with entecavir at week 72, while their level of HBcrAg was still detectable. A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement. HBcrAg concentration > 6.33 log IU/mL at baseline and logarithmic reduction > 1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement, respectively.
CONCLUSION
HBcrAg level is associated with liver fibrosis progression. HBcrAg is an excellent monitor of hepatic histological changes, especially in CHB patients treated with nucleoside analogs.
“…Traditional Chinese medicine has been selected as an alternative treatment for liver fibrosis because of the low efficiency and unexpected side effects of the currently used therapeutic strategy [5]. Numerous herbal medicines are used for liver fibrosis therapy in clinical practice [6][7][8]. The Fuzheng Huayu formula is one of the most well-studied antifibrotic agents and has a good therapeutic effect on hepatitis B-induced cirrhosis [9,10].…”
On the basis of carbon tetrachloride (CCl4)induced liver fibrosis in rats, this study aims to investigate the dynamic changes in matrix metalloproteinase 1 (MMP1) and the tissue inhibitor of metalloproteinase 1 (TIMP1) in the antifibrotic process of Dahuang Zhechong Pill (DHZCP). A total of 50 male Sprague Dawley rats, aged 8 weeks, were randomly divided into 3 groups: the control group, the model group (the group treated with CCl4), and the treatment group (the group treated with CCl4 and DHZCP). Rats were sacrificed at Weeks 4 and 8. Liver tissues were separated for RNA sequencing and bioinformatics analysis. Real-time PCR, Western blot analysis, and histological staining were conducted to confirm the gene expression and pathological change in liver tissues. Compared with control group, rats in model group showed poor mental state and slow weight gain. The liver tissues of the rats in the model group exhibited a damaged hepatic lobule structure, fibrous connective tissue hyperplasia, and inflammatory cell infiltration among the hyperplastic tissues. DHZCP could significantly improve the appearance of rats and alleviate CCl4-induced fibrosis. Compared to model group, 798 differentially expressed mRNAs were found in the treatment group, of which 120 were up-regulated and 678 were down-regulated. Differentially expressed mRNAs between the CCl4-induced group and the DHZCP-treated group were mainly focused on the following KEGG pathways: focal adhesion, phagosome, tight junction, and ECM–receptor interactions. Relative to those in the control group, MMP1 was downregulated, whereas, TIMP1 and Col1A1 were upregulated in the CCl4-induced group at Weeks 4 and 8. DHZCP could reverse MMP1, TIMP1, and Col1A1 expression.DHZCP protects against liver injury and exerts an antifibrotic effect on liver fibrosis induced by CCl4 in rats. Its mechanism may be related to the upregulation of MMP1, downregulation of TIMP1, and promotion of collagen degradation.
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