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.
Objective To evaluate the effectiveness and safety of treatment with Fuzheng Huayu capsule for liver fibrosis of chronic hepatitis B (CHB). Methods We searched MEDLINE, EMBASE, Cochrane Database of Controlled Trials (CCTR), CBMweb and CNKI up to March 2008. The references of retrieved literature were also hand searched. Randomized controlled trials (RCTs) which compared Fuzheng Huayu capsule with placebo or other drugs were collected. Data extraction and quality assessment were performed by two reviewers independently. The Cochrane Collaboration’ s software RevMan 4.2.10 was used for data analyses. Results Seven RCTs involving 590 cases of liver fibrosis of CHB were included. As for their methodological quality, one was graded A, one was graded B and the others were graded C. We carried out subgroup analyses based on treatment course and intervention measures. In terms of reducing haluronic acid, Fuzheng Huayu capsule was more effective than Huoluo Shugan capsule when the treatment course was 3 months (WMD=–61.75, 95%CI –105.20 to –18.30); significant differences were also noted between Fuzheng Huayu capsule and placebo (WMD=–187.72, 95%CI –244.23 to –31.21) or Huoluo Shugan capsule (WMD=–120.03, 95%CI –158.41 to –81.65) when the treatment course was 6 months. In terms of reducing IV-C, Fuzheng Huayu capsule was more effective than Gantaile when the treatment course was 6 months (WMD=–72.32, 95%CI –84.30 to –60.34). As for improving liver fibrosis at stage S, significant differences were observed between Fuzheng Huayu capsule and Gantaile (RR=2.33, 95%CI 1.37 to 3.96) or Huoluo Shugan capsule (RR=1.30, 95%CI 1.03 to 1.65). Except a very small number of gastrointestinal reactions, no significant adverse reactions were reported. Conclusion Fuzheng Huayu capsule is effective in reducing haluronic acid and improving liver fibrosis at stage S, especially when the treatment course is prolonged from 3 months to 6 months. No significant adverse reactions are reported. Because most of the included trials are of poor quality and small sample size, more high-quality RCTs are needed.
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 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.
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.
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.
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.
Objective To evaluate the effectiveness and safety of Gansu for chronic hepatitis B. Methods We searched The Cochrane Central Register of Controlled Trials (CCTR), PubMed, EMbase, CBM, CNKI, VIP, and Wanfang databases up to Dce. 2009. The methodological quality assessment and data extraction of the included studies were conducted by two reviewers independently according to the inclusion and exclusion criteria. Meta-analyses were performed for homogeneous studies using RevMan 4.2.10 software. Results A total of 14 studies involving 1 755 patients met the inclusion criteria. Of which, 12 studies did not report randomization method, and the other two studies reported inadequate methods of randomization. None of the studies enforced allocation concealment and performed blinding. We conducted subgroup analyses based on the outcome measures and interventions. The results of meta-analyses showed: (1) In terms of reducing ALT, Gansu + conventional therapy was superior to conventional therapy alone. (2) In terms of the HBsAg seroconversion rate, no significant difference was found between the two groups. (3) In terms of the HBeAg, no significant difference was found between the two groups at 3 months’ follow-up. (4) In terms of the HBV-DNA, Gansu + conventional therapy was superior to conventional therapy alone at 3 and 6 months’ follow-up, but theses differences were not found between Gansu + Lamivudine/ Adefovir and Lamivudine/ Adefovir alone. In terms of reducing the index of hepatic fibrosis, Gansu + conventional therapy was superior to conventional therapy alone. Conclusion Gansu might be effective in normalizing ALT levels, clearing HBV DNA, achieving virus seroconversion and improving hepatic fibrosis, without any serious adverse effects. However, because the overall effects cannot be pooled for analysis, more evidence is needed to support this finding.
Objective To investigate the current situation of randomized controlled trials or clinical controlled trial (RCT/CCT) on chronic hepatitis B and whether to offer reliable evidence for clinical practice in China. Methods RCT/CCT identified from six Chinese clinical journals were searched manually and assessed according to international standard of evidence-based medicine. Results 308 issues containing 212 therapeutic articles and 88 RCT/CCT on chronic hepatitis B were identified and analyzed. Conclusion the quantity and quality of RCT/CCT of chronic hepatitis B did not meet the need of clinical practice.
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.