Clinical trial with traditional Chinese medicine intervention ''tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'' for chronic hepatitis B-associated liver failure

AIM:To study the clinical efficacy of traditional Chinese medicine(TCM)intervention"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")for treating liver failure due to chronic hepatitis B.METHODS:We designed the study as a randomized controlled clinical trial.Registration number of Chinese Clinical Trial Registry is Chi CTR-TRC-12002961.A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study.Participants were randomly assigned to the following three groups:(1)a modern medicine control group(MMC group,36patients);(2)a"tonifying qi and detoxification"("TQD")group(72 patients);and(3)a"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")group(36patients).Patients in the MMC group received general internal medicine treatment;patients in the"TQD"group were given a TCM formula"tonifying qi and detoxification"and general internal medicine treatment;patients in the"TTK"group were given a TCM formula of"TTK"and general internal medicine treatment.All participants were treated for 8 wk and then followed at 48 wk following their final treatment.The primaryefficacy end point was the patient fatality rate in each group.Measurements of various virological and biochemical indicators served as secondary endpoints.The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups.RESULTS:At the 48-wk post-treatment time point,the patient fatality rates in the MMC,"TQD",and"TTK"groups were 51.61%,35.38%,and 16.67%,respectively,and the differences between groups were statistically significant(P<0.05).However,there were no significant differences in the levels of hepatitis B virus DNA or prothrombin activity among the three groups(P>0.05).Patients in the"TTK"group had significantly higher levels of serum total bilirubin compared to MMC subjects(339.40μmol/L±270.09μmol/L vs 176.13μmol/L±185.70μmol/L,P=0.014).Serum albumin levels were significantly increased in both the"TQD"group and"TTK"group as compared with the MMC group(31.30 g/L±4.77g/L,30.72 g/L±2.89 g/L vs 28.57 g/L±4.56 g/L,P<0.05).There were no significant differences in levels of alanine transaminase among the three groups(P>0.05).Safety data showed that there was one case of stomachache in the"TQD"group and one case of gastrointestinal side effect in the"TTK"group.CONCLUSION:Treatment with"TTK"improved the survival rates of patients with liver failure due to chronic hepatitis B.Additionally,liver tissue was regenerated and liver function was restored.

Diwu Yanggan Modulates the Wnt/β-catenin Pathway and Inhibits Liver Carcinogenesis Signaling in 2-AAF/PH Model Rats

The activation of the Wnt/β-catenin signaling pathway in oval cells after liver injury is implicated in hepatocarcinogenesis.Diwu Yanggan capsule is a Chinese herbal medicine that has been used for treating liver disorder.The present study aimed to examine the mechanism by which Diwu Yanggan inhibits liver carcinogenesis,and the involvement of the Wnt/β-catenin signaling pathway.Diwu Yanggan capsule was administered to 2-acetaminofluorene/partial hepatectomy(2-AAF/PH)rats,a murine model of liver injury.The biomarkers of oval cells and key proteins in the Wnt/p-catenin signaling pathway were assessed on postoperative day 8,10,14,17,19 and 22.The results showed that treatment with Diwu Yanggan was associated with reduced expression of oval cell and stem cell biomarkers in the 2-AAF/PH animals.The expression pattern of key proteins in the Wnt/β-catenin pathway was altered in Diwu Yanggan-treated animals,indicating that the Diwu Yanggan treatment accelerated the activation of the Wnt/β-catenin pathway in the initial stage and contributed to its deactivation in the later stage.Histological findings indicated that hepatocyte proliferation was suppressed in Diwu Yanggan-treated animals,compared with untreated 2-AAF/PH animals.Taken together,Diwu Yanggan capsule may reduce the risk of hepatocarcinogenesis by modulating the Wnt/β-catenin signaling pathway.