Efficacy and safety of AnluoHuaxian pills on chronic hepatitis B with normal or minimally elevated alanine transaminase and early liver fibrosis: A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: The AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT<2ULN) and early liver fibrosis (F ≤ 2). AIM OF THE STUDY: We aimed to investigate whether monotherapy with AHP improves liver histology in these patients. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT<2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment. RESULTS: Per-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients. CONCLUSIONS: Treatment of CHB patients who had ALT<2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future.

Differences in MicroRNA Expression in Chronic Hepatitis B Patients with Early Liver Fibrosis Based on Traditional Chinese Medicine Syndromes.

The aim of this study was to determine if microRNA (miRNA) expression is different among chronic hepatitis B (CHB) patients with early liver fibrosis classified according to traditional Chinese medicine (TCM) syndromes. Eighteen CHB-fibrosis patients and 12 CHB patients without fibrosis were enrolled. The CHB-fibrosis group included 9 patients with the TCM syndrome of Ganyu Pixu Xueyu (GYPXXY), characterized by liver stagnation, spleen deficiency, and blood stasis, and 9 patients with the TCM syndrome of Qixu Xueyu (QXXY), characterized by deficiency of qi, blood, and blood stasis. Agilent miRNA microarray was performed first in liver specimens to determine whether miRNA expression is different in patients with these two TCM syndromes of CHB-fibrosis. Gene Ontology (GO) analysis and KEGG analysis were applied to determine the roles of the differentially expressed miRNAs. QRT-PCR was performed to validate the Agilent miRNA microarray results. Compared with GYPXXY patients, 6 differentially expressed miRNAs were upregulated (miR-144-5p, miR-18a-5p, miR-148b-3p, miR-654-3p, miR-139-3p, and miR-24-1-5p) and 1 was downregulated (miR-6834-3p) in QXXY patients. According to qRT-PCR data, miR-144-5p and miR-654-3p were confirmed as upregulated in CHB-liver fibrosis patients compared to CHB patients without fibrosis, whereas the other 4 miRNAs were not significantly different. More importantly, miR-654-3p was confirmed to be significantly upregulated in QXXY patients compared with values in GYPXXY patients, whereas no significant difference was found in miR-144-5p. Moreover, the pathways of central carbon metabolism in cancer and cell cycle related to miR-654-3p and the target genes of PTEN and ATM were found to be different between QXXY patients and GYPXXY patients. These results indicate that there are different miRNAs, pathways, and target genes between QXXY patients and GYPXXY patients. However, due to the limited sample, whether miR-654-3p and the target genes PTEN and ATM could be molecular markers to differentiate TCM syndromes could not be established.

Histological improvement in chronic hepatitis B patients treated with bicyclol: real world experience.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Protocol of a prospective study for the combination treatment of Shu-Gan-jian-Pi decoction and steroid standard therapy in autoimmune hepatitis patients.

BACKGROUND: Prednisone plus azathioprine is considered the mainstay of therapy in the current recommendations for autoimmune hepatitis (AIH). However, it does not provide good benefits for AIH patients because of its serious side effects. Therefore, more and more AIH patients prefer to seek for traditional Chinese medicine (TCM) to manage their symptoms and reduce the side effects of steroids in China. Shu-Gan-Jian-Pi Decoction is a popular used Chinese herbal formula in Guangdong province of China, which has demonstrated the effect of improving efficacy and reducing side effects of corticosteroids in AIH patients. The aim of this study is to evaluate the effects of Shu-Gan-Jian-Pi Decoction combined with steroid in AIH patients. So, this study aims to explore whether the combination treatment of Shu-Gan-Jian-Pi Decoction and steroid standard therapy could improve the clinical management of AIH. METHODS: A prospective non-randomized study on AIH will be conducted between October 2015 and June 2017 in Guangdong Provincial hospital of Chinese medicine. Eligible AIH patients will be classified as the case group (n = 66) and the control group (n = 66) based on the interventions. Patients taking Shu-Gan-Jian-Pi Decoction combined with prednisone and azathioprine will be in the case group and those taking prednisone and azathioprine will be in the control group. The whole study will last 48 weeks, including a 24-week observation period and a 24-week follow-up period. The primary outcome was complete response to therapy, defined as complete biochemical remission at the patient's last visit of observation period and the absence of predefined steroid-specific side effects throughout treatment. DISCUSSION: This trial will evaluate the efficacy and safety of Shu-Gan-Jian-Pi Decoction combined with prednisone and azathioprine on AIH patients. The achievement of this trial will provide evidence-based data for Shu-Gan-Jian-Pi Decoction, which could provide good benefits for AIH patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-OOC-15006155 . Registration date: 28 March 2015.

The Score Model Containing Chinese Medicine Syndrome Element of Blood Stasis Presented a Better Performance Compared to APRI and FIB-4 in Diagnosing Advanced Fibrosis in Patients with Chronic Hepatitis B.

This study aims to explore a useful noninvasive assessment containing TCM syndrome elements for liver fibrosis in CHB patients. The demographic, clinical, and pathological data were retrospectively collected from 709 CHB patients who had ALT less than 2 times the upper limit of normal from April 2009 to October 2012. Logistical regression and area under receiver-operator curve (AUROC) were used to determine the diagnostic performances of simple tests for advanced fibrosis (Scheuer stage, F ≥ 3). Results showed that the most common TCM syndrome element observed in this CHB population was dampness and Qi stagnation, followed by blood stasis, by heat, and less by Qi deficiency and Yin deficiency. The logistical regression analysis identified AST ≥ 35 IU/L, PLT ≤ 161 × 10(9)/L, and TCM syndrome element of blood stasis as the independent risk factors for advanced fibrosis. Therefore, a score model containing these three factors was established and tested. The score model containing blood stasis resulted in a higher AUC (AUC = 0.936) compared with APRI (AUC = 0.731) and FIB-4 (AUC = 0.709). The study suggested that the score model containing TCM syndrome element of blood stasis could be used as a useful diagnostic tool for advanced fibrosis in CHB patients and presented a better performance compared to APRI and FIB-4.

[Evaluation of Chai Shao Liu Jun Tang for the treatment of chronic hepatitis B].

OBJECTIVE: To evaluate the effect of Chai Shao Liu Jun Tang in combination with Lamivudine for the treatment chronic hepatitis B (CHB) patients. METHODS: 405 CHB patients in Guangdong Provincial Hospital were randomly divided into 2 groups, 220 in the treated group, and 185 in the control group. The control group was treated with Lamivudine for 18 months. The treated group was treated with Lamivudine in combination with Chai Shao Liu Jun Tang for 18months. At the 3rd, 6th, 9th, 12th and 18th month during the treatment, the clinical symptoms, ALT normalization rate, HBeAg seroconversion rate, the proportion of patients with undetectable serum HBV DNA, and YMDD mutation rate were observed. RESULTS: ALT normalization rates at the 3rd, 6th, 12th, 18th month of the treatment group (69.5%, 85.9%, 90.5%, 82.7%) were higher than those in the control group (50.3%, 65.4%, 78.4%, 69.7%; P < 0.01). HBeAg seroconversion rate, rate of HBV DNA undetectable, and YMDD mutation rate at he 12th and18th month are 77.7%, 57.7%, 25.5%, 6.8%; 86.8%, 74.1%, 33.2%, 8.6% in the treatment group, and 54.6%, 36.8%, 13.0%, 14.6%; 69.2%, 37.3%, 19.5%, 20.5% in the control group (P < 0.01, or P < 0.05). CONCLUSION: Compared to lamivudine alone, Cai Shao Liu Ju Tang in combination with lamivudine is more effective and induces less YMDD mutation rate in CHB patients.