Objective To assess the efficacy and safety of Chinese medicinal herbs for asymptomatic hepatitis B virus(HBV) infection. Data Source The trials registers of the Cochrane Hepato-Biliary Group, the Cochrane Library and the Cochrane Complementary Medicine Field were searched in combination with MEDLINE, EMBASE, and handsearches of Chinese journals and conference proceedings. Data Selection Randomized clinical trials with 3 months follow-up comparing Chinese medicinal herbs versus placebo, no intervention, non-specific treatment, or interferon treatment for asymptomatic HBV carriers were included. No language and blinding limitations were applied. Data Extraction Data were extracted independently by two reviewers. The methodological quality of trials was assessed by the Jadad-scale plus allocation concealment. Results Three randomized clinical trials (307 patients) with low methodological quality following patients for three months or more after the end of treatment were included. Herbal compound Jianpi Wenshen recipe showed significant effects on clearance of HBV markers compared to interferon: relative risk 2.40 (95 % CI 1.01 to 5.72) for clearance of serum HBsAg, and 2.54 (1.13 to 5.70) for seroconversion of HBeAg to anti-HBe. Phyllanthus amarus and Astragalus membranaceus showed no significant antiviral effect compared with placebo. Analysis of pooling eight randomized clinical trials with less than three months follow-up did not show a significant benefit of Chinese medicinal herbs on viral markers. No serious adverse event was observed. Conclusions There is insufficient evidence for treatment of asymptomatic HBVcarriers using Chinese medicinal herbs due to the low quality of the trials. Further randomized, double blind, placebo-controlled trials are needed.
Objective To evaluate the efficacy and safety of genus Phyllanthus for chronic HBV infection. Design a systematic review of randomized clinical trials. Methods Randomized trials comparing genus Phyllanthus versus placebo, no intervention, general non-specific treatment, other herbal medicine, or interferon treatment for chronic HBV infection were identified by electronic and manual searches. Trials of Phyllanthus herb plus interferon versus interferon alone were also included. No blinding and language limitations were applied. The methodological quality of trials was assesses, by the Jadadscale plus allocation concealment. Results Twenty-two randomized trials (n=1 947) were identified. The methodological quality was high in five double blind trials and rest was low. The combined results showed that Phyllanthus species had positive effect on clearance of serum HBsAg (relative risk 5.64, 95%C1 1.85 to 17.21) compared with placebo or no intervention. There was no significant difference on clearance of serum HBsAg, HBeAg and HBV DNA between Phyllanthus and interferon. Phyllanthus species were better than non-specific treatment or other herbal medicines on clearance of serum HBeAg, HBeAg, HBV DNA, and liver enzyme normalization. Analyses showed a better effect of the Phyllanthus plus interferon combination on clearance of serum (1.56, 1.06 to 2.32) and HBV DNA (1.52, 1.05 to 2.21) than interferon alone. No serious adverse events were reported. Conclusions Based on the review Phyllanthus species may have positive effect on antiviral activity and liver biochemistry in chronic HBV infection. However, the evidence is not b due to the general low methodological quality and the variations of the herb. Further large trials are needed.
Background Hepatitis B is one of the major infectious diseases of mankind, and up to now, there is no effective way to handle it. Recent clinical trials have shown the potential advantages of Kurorinone an extract of Chinese herb, in treament of chronic HBV infection. Objectives Systermically review the safety and efficacy of Kurorinone in treatment of chronic HBV infection. Search strategy With the searching terms including Kurorinone, its products’ name, hepatitis B and chronic carrier status, the trials registers of the Cochrane Hepato- Biliary Group, the Cochrane Complementary Medicine Field, and the central database of the Cochrane Library as well as MEDILINE, EMBASE and Chinese Biomedical CD Database were searched from their date of inception onward. 20 Chinese medical journals and relevant academic conference proceedings have been searched by hand. The reference lists of identified documents were checked as the complementary search. Inclusion Criteria All RCTs that tested Kurorinone for chronic HBV infection were included in this review. Method of the review According the demand of Cochrane systematic review, selection of trial for inclusion, assessment of methodological quality, data extraction and data syntheses would be conducted for each included trial.
This study sought to investigate the in vivo antiviral effect of amantadine (AM) and biphenyl dimethyl dicarboxylate (DDB) on hepatitis B virus (HBV) in HBV replication mice. HBV replication-competent plasmid was transferred into male BALB/c mice by using hydrodynamics-based in vivo transfection procedure to develop HBV replication mouse model. The model mice were matched by body weigh, age and serum levels of hepatitis B e antigen (HBeAg) and were divided into four groups:AM group, DDB group, AM+DDB group and NS group, with the last one as control, and the mice of each group were administered corresponding agent orally twice a day, in a medication course lasting 3 d. On the third day, the mice were sacrificed 4-6 h after the last oral intake. HBV DNA replication intermediates in liver were analyzed by Southern blot hybridization. The serum hepatitis B surface antigen (HBsAg) and HBeAg were detected by enzyme linked immunosorbent assay (ELISA). Compared to the animals in the control group, HBV DNA replication intermediates in liver and HBsAg and HBeAg in serum from the AM and AM plus DDB group of mice decreased, and there was no difference between these two groups of mice. The levels of HBV DNA intermediate from liver and the serum HBsAg and HBeAg between the control and DDB group, however, were not obviously different. In conclusion, the inhibition effect of AM on HBV was detected, but treatment with DDB for 3 days did not influence the viral replication and expression of HBV in the HBV replication mice.
Objective Hepatitis B virus X (HBx) protein is involved in the initiation and progression of hepatocellular carcinoma (HCC) by regulating the host protein-coding genes. Herein, we want to explore whether HBx protein can alter the expression of microRNAs (miRNAs) to promote proliferation and transformation in malignant hepatocytesin vitro. Methods MiRNA microarray and quantitative reverse-transcription polymerase chain reactions (qRT-PCRs) were performed to identify miRNAs that were differentially regulated by HBx protein in HCC cells. Protein and mRNA expression analyses, cell cycle and apoptosis analyses, and luciferase reporter assays were performed to delineate the consequences of miR-16 family repression in HepG2 cells. Results HBx protein induced widespread deregulation of miRNAs in HepG2 cells, and the downregulation of the miR-16 family was reproducible in HepG2, SK-HEP-1, and Huh7 cells. CCND1, a target gene of the miR-16 family, was derepressed by HBx protein in HepG2 cells. C-myc mediated the HBx-induced repression of miR-15a/16 in HepG2 cells. Ectopically expressed miR-15a/16 suppressed the proliferation, clonogenicity, and anchorage-independent growth of HBx-expressing HepG2 cells by arresting them in the G1 phase and inducing apoptosis, whereas reduced expression of miR-16 accelerated the growth and cell-cycle progression of HepG2 cells. Conclusions HBx protein altered thein vitro expression of miRNAs in host malignant hepatocytes, particularly downregulating the miR-16 family. Repression of miR-15a/16 is c-myc mediated and is required for the HBx-induced transformation of HepG2 cellsin vitro. Therefore, miR-16 family may serve as a therapeutic target for hepatitis B virus (HBV)-associated HCC.
Objective To clarify incidence and risk factors of hepatitis B reactivation during short term (one month) in hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) patients receiving partial hepatectomy. Methods From January 2015 to December 2015, 214 consecutive patients with HBV-related HCC who underwent partial hepatectomy were retrospectively enrolled in this study. The risk factors affecting incidence of hepatitis B reactivation were analyzed. Results Hepatitis B reactivation happened in 7.0% (15/214) of patients within 1 month after partial hepatectomy. By univariate analysis, the preoperative HBV-DNA negativity and hepatitis B e antigen (HBeAg) positivity were significantly correlated with the occurrence of hepatitis B reactivation (P=0.023 and P=0.001, respectively). By multivariate analysis, the preoperative HBV-DNA negativity 〔OR=9.21, 95% CI (2.40, 35.45), P=0.001〕 and HBeAg positivity 〔OR=20.51, 95% CI (5.41, 77.73), P<0.001〕 were the independent risk factors for hepatitis B reactivation. Conclusions Hepatitis B reactivation is common after partial hepatectomy for HBV-related HCC during short term, especially in patients whose preoperative HBV-DNA negativity and HBeAg positivity. A close monitoring of HBV-DNA during short term after partial hepatectomy is necessary, once hepatitis B is reactivated, antiviral therapy should be given.
ObjectiveAntiviral treatments could benefit chronic hepatitis B (CHB) patients with the regression or improvement of liver fibrosis. However, the degree of dynamic change of liver fibrosis for patients who had not received antiviral treatment remained to be studied. The current study aimed to observe the long-term variation of liver stiffness measurement (LSM), virological and biochemical response on patients without standard antiviral therapy.MethodsA total of 220 patients who were diagnosed with chronic HBV infection, who had not reached the standard of antiviral therapy, and completed a follow-up date of over 2 years in the First Affiliated Hospital of Xi’an Jiaotong University from 2012 to 2018 were retrospectively enrolled. According to the changes of LSM in baseline and follow-up period, the patients were divided into regression group, non-progressive group, and progressive group. The virological and biochemical characteristics of each group were analyzed.ResultsAmong the 220 patients, 153 patients (69.5%) had no progress in LSM degree. Alanine aminotransferase (ALT), HBV DNA, and HBsAg in a few patients increased or slightly decreased, while the vast majority remained in a relatively stable state. 89.5% (137/153) of the non-progressive patients were in grade F0. In addition, 58 patients showed spontaneous improvement with a decreasing rate of 0.460 kPa per year. Patients with ALT of 1-2 ULN had a statistically significant decrease in LSM improvement compared to patients with normal ALT. 82.8% of the LSM-improving patients showed baseline LSM of F1-F3. Only 9 patients showed LSM deterioration, however, which could not be explained by virus replication or necroinflammatory activity. ConclusionsFor patients unsatisfying standard antiviral therapy, most patients with baseline LSM of F0 grade fail to progress, and patients with baseline LSM of F1-F3 show a decrease during follow-up, LSM progression occurs in 4.1% of patients.
ObjectiveTo summarize the research status of the relationship between hepatitis B virus X protein (HBx), hepatitis B virus (HBV) genotypes and hepatocellular carcinoma (HCC) at home and abroad, and to prospect its clinical significance.MethodThe literatures about HBx, HBV genotypes and HCC were reviewed.ResultsThere was a close relationship between HBx and the occurrence, development, migration and metastasis of HCC. There was a certain association between HBV genotypes and HCC, but the specific mechanism had not been clarified.ConclusionsHBx and HBV genotypes play an important role in the occurrence and development of HCC. With the further study of molecular mechanism, it will promote the diagnosis and treatment of hepatitis B, liver cirrhosis and liver cancer, and provide more individualized intervention for clinical workers.
Objective To investigate the prognostic value of serum gamma-glutamyltransferase-to-lymphocyte ratio (GLR) in patients with chronic hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) after radical resection. Methods The clinical data of HBV-HCC patients diagnosed and treated with radical hepatectomy in the Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital) from January 2012 to December 2022 were retrospectively collected and analyzed. Log-rank and multivariate Cox proportional hazard model were performed to analyze the risk factors affecting overall postoperative survival (OS) and relapse-free survival (RFS) of HBV-HCC patients, and receiver operating characteristic (ROC) curve was used to evaluate the predictive value of GLR for OS and RFS of HBV-HCC patients. Results A total of 196 eligible HBV-HCC patients underwent radical hepatectomy were included. The optimal cutoff value of GLR was 182.31 through ROC curve, and 144 cases were in low GLR group and 52 cases in high GLR group. Compared with the low GLR group, ratios of preoperative portal vein tumor thrombus, China liver cancer staging (CNLC) stage Ⅲ, preoperative AFP level ≥400 ng/mL and low tumor differentiation were higher in the high GLR group (χ2=10.071, P=0.002; χ2=32.552, P<0.001). Cox proportional hazard model showed that higher maximum tumor diameter (HR=1.099, P=0.009), GLR>182.31 (≤182.31 vs. >182.31, HR=0.211, P<0.001) and low tumor differentiation grade (high+moderate vs. low, HR=0.182, P<0.001) were risk factors for postoperative OS of HBV-HCC patients, and the area under curve (AUC) of these risk factor for predicting OS of HBV-HCC patients was 0.930 [95%CI (0.884, 0.977)]. Preoperative portal vein tumor thrombus (No vs. Yes, HR=0.404, P=0.002) and GLR>182.31 (≤182.31 vs. >182.31, HR=0.435, P=0.001) were risk factors for postoperative RFS of HBV-HCC patients, and the AUC of these risk factor for predicting RFS was 0.729 [95%CI (0.654, 0.805)]. Conclusion This study preliminarily indicates that GLR is associated with postoperative prognosis of HBV-HCC patients, and GLR combined with maximum tumor diameter and tumor differentiation degree has a certain value in predicting OS.