Background Hepatitis B virus infection is a serious health problem worldwide. Traditional Chinese medicinal herbs have been widely used to treat chronic liver diseases, and many controlled trials have been done to investigate their efficacy. Objectives To assess the efficacy and safety of traditional Chinese medicinal herbs for chronic hepatitis B infection. Search strategy Searches were applied to the following electronic databases: the CHBG Trials Register, the Cochrane Complementary Medicine Field Trials-Register, the Cochrane Library, MEDLINE, EMBASE and BIOSIS. Five Chinese journals and conference proceedings were handsearched. No language restriction was used. Selection criteria Randomized or quasi-randomized trials with at least three months follow-up. Thais of Chinese medicinal herbs (single or compound) compared with placebo, no intervention, general non-specific treatment or interferon treatment were included. Trials of Chinese medicinal herbs plus interferon versus interferon alone were also included. Trials could be double-blind, single-blind or not blinded. Data collection and analysis Data were extracted independently by two reviewers. The methodological quality of trials was evaluated using the Jadad-scale plus allocation concealment. Intention-to-treat analyses were performed. Main Resuits Nine randomized trials, including 936 patients, met the inclusion criteria. Methodological quality was considered adequate in only one trial. There was a significant funnel plot asymmetry (regression coefficient= 3.37, standard error 1.40, P=0.047). Ten different medicinal herbs were tested in the nine trials. Compared to non-specific treatment or placebo, Fuzheng Jiedu Tang (compound of herbs) showed significantly positive effects on clearance of serum HBsAg, HBeAg, and HBV DNA; Polyporus umbellatus, polysaccharide on serum HBeAg and HBV DNA; Phyllanthus amarus on serum HBeAg. Phyllanthus compound and kurorinone showed no significant effect on clearance of serum HBeAg and HBV DNA and on alanine aminotransferase normalization compared to interferon treatment. There were no significant effects of the other examined herbs. Reviewer’s conclusions Some Chinese medicinal herbs may work in chronic hepatitis B. However, the evidence too weak to recommend any single herb. Rigorously designed, randomized, double-blind, placebo-controlled trials are required.
ObjectiveTo systematically review the efficacy of peginterferon alpha (PEG-IFNα) initially combined with lamivudine (LAM) or adefovir (ADV) in treatment of HBeAg-positive chronic hepatitis B (CHB) patients.
MethodsWe electronically searched databases including The Cochrane Library (Issue 11, 2014), PubMed, CBM, CNKI, VIP, and WanFang Data from inception to December 2014, to collect randomized controlled trials (RCTs) about PEG-IFNα initially combined with LAM or ADV for HBeAg-positive CHB. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.2 software.
ResultsA total of 11 RCTs involving 2031 patients were included. The results of meta-analysis showed that: After 48 weeks of treatment, the HBsAg seroconversion rate of the PEG-IFNα plus ADV group was significantly higher than that of the PEG-IFNα monotherapy group (8.6% vs. 0%, OR=7.73, 95%CI 1.53 to 39.05, P=0.01) or the ADV monotherapy group (8.5% vs. 0%, OR=7.75, 95%CI 1.07 to 56.23, P=0.04); and the HBsAg seroclearance rate in the combination therapy group was significantly higher than that of the ADV monotherapy group (10.5% vs. 1.2%, OR=5.56, 95%CI to 2.14 to 14.47, P=0.0004). After 52 weeks of treatment, the HBsAg seroconversion rate of the PEG-IFNα plus LAM group was significantly higher than that of the PEG-IFNα monotherapy group (11.6% vs. 5.6%, OR=2.21, 95%CI 1.04 to 4.72, P=0.04). After 26 weeks of follow-up, no significant differences were found between the combination therapy group and the PEG-IFNα monotherapy group in HBsAg seroclearance rate and HBsAg seroconversion rate (all P values >0.05).
ConclusionCurrent evidence shows that, compared with PEG-IFNα, LAM, or ADV monotherapy, PEG-IFNα plus LAM or ADV could improve the HBsAg seroclearance or seroconversion rate after 48-52 weeks of treatment for HBeAg-positive CHB, but this effect is still limited. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
This study aims to clarify host factors of IFN treatment in the treatment of chronic hepatitis B (CHB) patients by screening the differentially expressed genes of IFN pathway CHB patients with different response to interferon (IFN) therapy. Three cases were randomly selected in IFN-responding CHB patients (Rs), non-responding CHB patients (NRs) and healthy participants, respectively. The human type I IFN response RT2 profiler PCR array was used to detect the expression levels of IFN-related genes in peripheral blood monocytes (PBMCs) from healthy participants and CHB patients before and after Peg-IFN-α 2a treatment. The results showed that more differentially expressed genes appeared in Rs group than NRs group after IFN treatment. Comparing with healthy participants, IFNG, IL7R, IRF1, and IRF8 were downregulated in both Rs and NRs group before IFN treatment; CXCL10, IFIT1, and IFITM1 were upregulated in the Rs; IL13RA1 and IFI35 were upregulated in the NRs, while IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1, and ADAR were downregulated. The expression of IL15, IFI35 and IFI44 was downregulated by 4.09 (t = 10.58, P < 0.001), 5.59 (t = 3.37, P = 0.028) and 10.83 (t = 2.8, P = 0.049) fold in the Rs group compared with the NRs group, respectively. In conclusion, IFN-response-related gene array is able to evaluate IFN treatment response by detecting IFN-related genes levels in PBMC. High expression of CXCL10, IFIT1 and IFITM1 before treatment may suggest satisfied IFN efficacy, while high expression of IL13RA1, IL15, IFI35 and IFI44 molecules and low expression of IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1 and ADAR molecules may be associated with poor IFN efficacy.
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.
ObjectiveTo investigate the clinical value of small-for-size left lobe liver auxiliary partial orthotopic liver transplantation (APOLT) in the treatment of decompensated cirrhosis. MethodThe preoperative and postoperative clinical data of 4 patients who received small-for-size left lobe liver APOLT in 2023 were retrospectively described and analyzed. ResultsOne patient suffered metabolic liver disease cirrhosis and the other three suffered hepatitis B cirrhosis, all of whom presented with decompensated cirrhosis. Preoperative evaluation showed that the graft-to-recipient weight ratio was less than 0.6%. All recipients underwent left hemihepatectomy. The grafts were derived from living donors in 3 cases, from donation after citizen death in 1 case. After APOLT treatment, 4 patients and grafts survived, 1 patient experienced transplantation rejection and recovered after modified anti-rejection therapy. Three patients with hepatitis B cirrhosis were treated with nucleoside analogues and hepatitis B immunoglobulin, the hepatitis B virus DNA was negative at the end of follow-up, one of three patients with hepatitis B cirrhosis showed negative results for hepatitis B virus in the graft biopsy at month one after surgery. ConclusionsFrom the summary results of these cases, small-for-size left lobe liver APOLT can be used to treat decompensated cirrhosis. The application and popularization of this treatment regimen is expected to expand the donor pool and benefit more decompensated cirrhosis patients with lower Model for End-stage Liver Disease score.
ObjectiveTo explore the combined application of neutrophil to lymphocyte ratio (NLR) and systemic immune inflammation index (SII) on the prognosis of hepatitis B-related hepatocellular carcinoma after resection.MethodsRetrospectively collected data of 180 patients with hepatitis B-related hepatocellular carcinoma who were hospitalized in the Department of Infectious Diseases and Hepatobiliary Surgery of the Affiliated Hospital of Southwest Medical University and received surgical treatment from January 2013 to December 2019, including general information, laboratory examination and abdominal CT or MRI results. NLR and SII values were measured at one week before operation, and their critical values of NLR and SII were determined by ROC curve analysis. Univariate and multivariate analysis were performed to determine the risk factors to predict the survival status of patients with hepatitis B-related hepatocellular carcinoma after hepatectomy.ResultsUnivariate analysis showed that AFP, platelets, TNM staging, portal vein tumor thrombus, tumor differentiation, NLR, SII, and NLR+SII combined score were significantly correlated with the prognosis of patients with hepatitis B-related hepatocellular carcinoma (P<0.05). Multivariate analysis showed that PLT [HR=1.791, 95%CI (1.124, 2.854), P=0.014], NLR [HR=4.289, 95%CI (2.571, 7.156), P<0.001], SII [HR=5.317, 95%CI (3.016, 9.374), P<0.001], and NLR+SII combined score [HR=7.901, 95%CI (4.124, 15.138), P<0.001] were independently correlated with the survival of patients with hepatitis B-related hepatocellular carcinoma.ConclusionsThe preoperative NLR+SII combined score can be used to evaluate the postoperative prognosis of patients with hepatitis B-related hepatocellular carcinoma. The higher the score, the lower the postoperative survival rate.
Objectives To conduct a meta-analysis to evaluate the efficacy and safety of thymosin-α1 for HBeAg-positive chronic hepatitis B. Methods We searched MEDLINE, Science Citation Index, Current Content Connect, Cochrane Controlled Trial Register and Chinese Biomedical Database (CBMdisc) to September 15, 2005, and screened the references of eligible trials by hand-searching. Randomized controlled trials (RCTs) comparing thymosin-α1 with non-antiviral interventions (placebo, no treatment and standard care) in patients with HBeAg positive chronic hepatitis B were eligible for inclusion. We conducted quality assessment and data extraction by two independent investigators with disagreement resolved by discussion. We used chi-square test and Galbraith plot to detect the heterogeneity, and used fixed (Mantel-Haenzel) and random effect model (DerSimonian-Laird) to pool the trials. When the results in two models differed, the results of random effect were reported. Subgroup analysis was performed to detect whether the duration affected the efficacy of thymosin. Results Four RCTs were included. It was found that the rate of loss of HBeAg was 38.8% in thymosin, significantly higher than that of 12.4% in control groups (RR 2.22, 95%CI 1.55 to 3.21, P=0.000). Loss of HBV-DNA was 36.9% in thymosin-α1, significantly higher than that of 13.8% in control groups (RR 2.18, 95%CI 1.50 to 3.17, P=0.000). Both short-duration (8-13 weeks) and regular duration (26-52 weeks) of thymosin-α1 achieved higher loss of HBeAg and HBV-DNA. The complete response rate was 32.3% in thymosin-α1, significantly higher than the control, 11.3% (RR 2.91, 95%CI 1.71 to 4.94, P=0.000). No statistical significance was found for HBeAg seroconversion and ALT normalization. No significant adverse drug reactions were found. Conclusions Thymosin-α1 might be efficacious in loss of HBeAg and HBV-DNA, and complete response for patients with HBeAg-positive chronic hepatitis B. Little evidence was available on HBeAg seroconversion, normalization of ALT, loss of HBsAg, and histological response. Further high-quality RCTs were needed for confirmation.
ObjectiveTo investigate differentially expressed genes (DEGs) and potential molecular mechanisms between hepatitis C-related hepatocellular carcinoma (HCV-HCC) and hepatitis B-related HCC (HBV-HCC). MethodsThe data of HCV-HCC and HBV-HCC gene expressions were downloaded and integrated from the public gene expression database, and the limma package was used to investigate the DEGs between the HCV-HCC and HBV-HCC samples. The gene set enrichment analysis (GSEA) was used to explore the differences in suppressed or activated gene sets between the HCV-HCC and HBV-HCC samples, and the MCODE was used to explore the key molecular modules, and then the potential biological processes and molecular pathways of the key molecular modules were analyzed. The effect of key genes on survival of the HCC patients was analyzed by the Kaplan-Meier-Plotter database.ResultsIn this study, 119 HBV-HCC samples and 163 HCV-HCC samples were obtained, and the 199 DEGs were screened out. Compared with HBV-HCC, the activated gene sets of HCV-HCC were mainly enriched in the gene sets of inflammation, complement, up-regulation of genes in response to interferon, up-regulation of genes in response to KRAS, genes regulated by the nuclear factor- κB-tumor necrosis factor pathway, and apoptosis. However, the cell cycle-related gene sets were obviously suppressed. Eight key molecular modules enriched by DEGs were found, which included 18 key genes (IFI27, DDX60, MX1, IRF9, OAS3, OAS1, RSAD2, GBP4, HERC6, ISG15, IFIT1, CMPK2, EPSTI1, IFI44, IFI44L, HERC5, IFITM1, CXCL10). GO analysis showed that the biological process was mainly concentrated in the body response related to virus infection, the molecular component was mainly in the host cells, and the molecular function was mainly enriched in the biological combination. KEGG analysis showed that the key genes were mainly involved in the molecular signaling pathway related to virus infection. The survival analysis showed that the 9 key genes (CXCL10, HERC6, DDX60, IFITM1, IFI27, GBP4, IFI44L, IFI44, MX1) were closely related to better prognosis of patients with HCC (HR<1, P<0.05). ConclusionsThere is an essential difference between HBV-HCC and HCV-HCC. Occurrence of HCV-HCC is mainly related to virus infection and immune response induced by the virus. Therefore, for HCV infection, active antiviral treatment is necessary for avoiding hepatitis turning into chronic viral infection and preventing or blocking HCV infection converting to HCC.
Objective To compare the combination of Xiao Chai Hu Tang and interferon versus the simple interferon for the management of chronic hepatitis B (CHB) in terms of clinical therapeutic effect and safety. Methods Such databases as PubMed, CBM disc, CNKI, VIP, Japana Centra Revuo Medicina were searched to include the randomized control trials (RCTs) of treating chronic hepatitis B by using Xiao Chai Hu Tang plus interferon as the treatment group and the interferon as the control group. The quality of the inclusive methodology was evaluated by two reviewers independently. RevMan5.0.24 software was employed for meta-analyses. Results Seven RCTs involving 668 patients were included and all of them were classified as Grade C methodologically. The results of meta-analyses demonstrated: compared with the simple interferon treatment, adding Xiao Chai Hu Tang to interferon was able to significantly increase the HBV-DNA negative conversion ratio (RR=1.44, 95%CI 1.18 to 1.76, P=0.000 4) and the HBeAg negative conversion ratio (RR=1.54, 95%CI 1.21 to 1.94, P=0.000 4); when the intervention duration was more than 12 weeks, the ALT normalization rate was improved significantly (24 weeks: RR=1.39, 95%CI 1.17 to 1.66, P=0.000 2; 12 weeks: RR=1.79, 95%CI 1.23 to 2.61, P=0.002) and the incidence of flu-like symptoms induced by interferon was significantly reduced (liver-protection treatment: RR=0.54, 95%CI 0.40 to 0.73, Plt;0.000 1; Non-liver-protection treatment: RR=0.75, 95%CI 0.59 to 0.95, P=0.02). The funnel plot was asymmetric, indicating publication bias. Conclusion Although Xiao Chai Hu Tang maybe has certain potential supplementary benefits to interferon for the management of CHB. The results of the above meta-analyses should be interpreted prudently because there exit disparities in domestic and international trails with the shortage of double blind or multi-centered clinical trials with high quality. The current evidence provides no way to compare the combination of Xiao Chai Hu Tang plus interferon with the simple interferon for the treatment of CHB and no accurate conclusion in terms of clinical therapeutic effects and safety.
ObjectiveTo investigate the psychological status of patients with chronic hepatitis B during the anti-virus treatment.
MethodThe questionnaires of 150 outpatients with chronic hepatitis B treated between May 2013 and May 2014 were collected. And the date was properly processed.
ResultsAll the patients were suffering from different degrees of worries, and the top 3 rates of worries were:the recurrence after stop using drugs (88.00%), the side effects of long-term medication (78.00%) and discrimination from people seeing the package of drugs (69.33%).
ConclusionsPatients with chronic hepatitis B are in different degrees of psychological hazard during the treatment of anti-virus; further nursing work in psychological counseling and health education are needed to eliminate the hidden trouble, as to enhance the curative effect.
