Objective To analyze the clinical characteristics of individuals with high hepatitis B virus (HBV) pregenomic RNA (pgRNA), and further explore the value of pgRNA in the management of patients with chronic hepatitis B. Methods From December 1st, 2020 to April 1st, 2022, chronic hepatitis B patients who had been treated with nucleotide analogues for a long time and followed up in the Hepatitis Clinic of the Center of Infectious Diseases, West China Hospital, Sichuan University were included, and the clinical characteristics of chronic hepatitis B patients with high pgRNA were analyzed and summarized. Results A total of 107 patients were included. Male patients accounted for 66.4%, with an average age of 44.02 years. There were no statistically significant differences in gender, age, aspartate transaminase, alanine transaminase, γ-glutamyl transferase, HBV surface antigen, proportion of patients with HBV e antigen ≥0.1 U/mL, HBV DNA, and alpha fetoprotein between the high and low pgRNA groups (P>0.05). The proportion of patients with HBV surface antigen<100 U/mL in the high pgRNA group was lower than that in the low pgRNA group (4.4% vs. 22.6%, P<0.05). Conclusion The proportion of chronic hepatitis B patients with high pgRNA whose HBV surface antigen≥100 U/mL is higher.
Objective To evaluate the effectiveness of combination therapy with lamivudine (LAM) and hepatitis B immunoglobulin (HBIG) versus LAM monotherapy in prevention of hepatitis B virus recurrence after liver transplantation. Methods Databases including MEDLINE (Ovid), PubMed, EMbase, Cochrane Central Register of Controlled Trials (CENTRAL), CBM, VIP, and CNKI were searched up to Dec. 2008. Clinical trials including randomized controlled, non-randomized concurrent-control and case-control studies about combination therapy with HBIG and LAM versus LAM monotherapy in prevention of hepatitis B virus recurrence after liver transplantation were screened. Trial selection and data extraction were conducted by two reviewers independently. Meta-analysis was performed using RevMan 5.0.18 software. Results Eleven non-randomized concurrent-control studies involving 1 421 patients (1 035 patients in combination therapy group, and 386 patients in LAM monotherapy group) were included. The results of meta-analyses showed: Compared with LAM monotherapy group, the risks of hepatitis B virus recurrence, YMDD mutation, and death associated with HBV recurrence were significantly reduced by 73% (RR=0.27, 95%CI 0.20 to 0.37, Plt;0.000 01), 72% (RR=0.28, 95%CI 0.15 to 0.53, P=0.000 01), and 79% (RR=0.21, 95%CI 0.09 to 0.49, P=0.000 3) respectively in combination therapy group after liver transplantation; overall survival rates of both recipients and grafts in combination therapy group were similar to LAM monotherapy group (RR=1.03, 95%CI 0.95 to 1.11, P=0.51; RR=1.04, 95%CI 0.97 to 1.12, P=0.26). Conclusion Current evidence indicates that compared with LAM monotherapy, combination therapy with LAM and HBIG could reduce the risks of hepatitis B virus recurrence, YMDD mutation, and death associated with HBV recurrence after liver transplantation.
Drugs may induce hepatitis B virus (HBV) reactivation (HBV-R). Here we have reviewed the definition and harm of HBV-R, the risk drugs and their underlying mechanism, the influence factors, as well as the early intervention measures. It is shown that multiple drugs, including chemotherapy drugs, immunotherapy drugs, directly acting antivirals, cell therapy, etc., can induce HBV-R by affecting host immunity or directly activating HBV transcription factors. HBV-R could cause severe liver damage, even interruption of treatment of original diseases, affecting the prognosis of patients. Through precisely identifying risk drugs, monitoring the influence factors, and prescribing preventive anti-HBV regimen if necessary, the incidence of HBV-R can be significantly reduced. It is also suggested that clinical physicians should not only pay attention to the early identification and intervention of HBV-R, but also further study the mechanism of HBV-R in depth, especially the underlying mechanism between host, HBV and risk factors. This will help to promote the discovery of more valuable markers for risk prediction and targets for early intervention, and to further reduce the risk of HBV-R and improve the prognosis of patients.
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 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 evaluate the efficacy and safety of antiviral drugs for hepatitis B with YMDD motif variant. Methods We electronically searched MEDLINE (1989-April, 2004), EMBASE (1989-April, 2004), CBMdisc (expand) (1989-April, 2004), and handsearched unpublished Chinese conference proceedings. Randomized and quasi-randomized trials in patients with chronic hepatitis B with YMDD motif variant correlative to lamivudine were collected. Two reviewers extracted the data and assessed the quality of literature independently. The data were then analyzed by RevMan 4.2 software. Results Five studies involving 6 trials and 284 patients were included. According to the results of meta-analysis, antiviral therapy with adefovir plus lamivudine showed significantly better effects on the clearance of serum HBV-DNA and HBeAg and normalization of ALT than that of lamivudine alone (RR 16.61, 95%CI 2.29 to 120.71; RR 6.66, 95%CI 1.23 to 35.88 and RR 6.26, 95%CI 2.29 to 17.12 respectively); also, oxymatrine plus thymothin showed obviously better effects on the clearance of serum HBV-DNA and HBeAg (RR 2.96, 95%CI 1.26 to 6.93 and RR 2.51, 95%CI 1.05 to 5.98 respectively).But adefovir alone showed no better effects on clearance of serum HBV-DNA and HBeAg than that of lamivudine alone (RR 11.00, 95%CI 0.65 to 186.02 and RR 7.00, 95%CI 0.39 to 126.92 respectively); interferon plus lamivudine showed no better effects on the clearance of serum HBV-DNA, HBeAg and the normalization of ALT (RR 3.50, 95%CI 0.90 to 13.58; RR 4.90, 95%CI 0.70 to 35.10 and RR 2.80, 95%CI 0.91 to 8.12 respectively). Chinese herbs plus lamivudine showed no better effects on the clearance of serum HBV-DNA (RR 1.16, 95%CI 0.89 to 1.51). There were no significant side effects in the groups, except flu like symptom in the interferon group, slight kidney impairment in the adefovir group, and aggravation of rare cases in lamivudine group. Conclusions Antiviral therapy with adefovir plus lamivudine, or oxymatrine plus thymothin, shows better effects than with lamivudine alone in terms of antiviral therapy and clinical outcome improvement. However, the evidence is too weak to draw a definite conclusion in this systematic review. Larger sample size and rigorously designed randomized, double blind, placebo control trials are required for future study.
ObjectiveTo explore the association between viral hepatitis and extrahepatic cholangiocarcinoma (ECC). MethodsDatabase of Medline, Embase, PubMed, CNKI, and Wanfang were searched for the articles which were related to the relationship between viral hepatitis and ECC. After the quality evaluation and the data extraction of the literatures, statistical software of RevMan 5.0 was used to perform Meta analysis. ResultsAccording to the inclusion criteria and exclusion criteria, 9 articles were enrolled, 8 articles of them were related to hepatitis B virus(HBV) and 6 articles of them were related to hepatitis C virus(HCV). Meta analysis results showed that the HBV infection may be the risk factor for ECC(OR=1.69, 95% CI:1.32-2.17, P<0.000 1). In the United States, HCV infection may be the risk factor for ECC(OR=5.53, 95% CI:2.21-13.82, P=0.000 3), but the relationship was not found in China(OR=0.82, 95% CI:0.44-1.52, P=0.520 0). ConclusionsThe present studies suggest that HBV infection may be a high risk factor for ECC. HCV in the United States can increase the incidence of ECC, but the situation can not be found in China.
ObjectiveTo explore the influence of paternal serum HBV-DNA load levels and pregnant women's HBsAb on vertical transmission of hepatitis B virus (HBV) from HBsAg positive fathers to infants in order to provide effective methods for paternal-fetal ventrical transmission of HBV prevention. MethodsUsing HBsAg and HBV-DNA as indicators to screen pregnant women and their husbands after gained consent, 121 families with HBVM negative or only HBsAb positive and HBV-DNA negative pregnant women, HBsAg positive husbands and their newborns were selected. In this case-control study, according to neonatal cord blood HBV-DNA detection, 23 newborns with cord blood HBV-DNA positive were selected as cases, 98 newborns as controls. ResultsThe positive rate of neonatal cord blood HBV-DNA was 19.0% (23/121); and there was dose-response relationship between paternal serum HBV-DNA load levels and neonatal cord blood HBV-DNA positive (trend χ2=60.108, P=0.000). The analysis of ROC curve showed that paternal serum HBV-DNA load level (106 copies/mL) is a better demarcation point to forecast the occurrence of vertical transmission of HBV from HBsAg positive fathers to infants, because there was a better sensitivity and specificity during forecast; and HBsAb negative pregnant women's were statistically significant (χ2=12.399, P=0.000). There was no significant difference at the positive rate of neonatal cord blood HBV-DNA between the case group and control group when paternal serum HBV-DNA load levels exceed 107 copies/mL (P > 0.05). ConclusionPaternal serum HBV-DNA load levels and HBsAb negative pregnant women are the risk factors of vertical transmission of HBV from HBsAg positive father to infants. Paternal serum HBV-DNA load level (106 copies/mL) is an appropriate index of the occurrence of vertical transmission.
ObjectiveTo investigate the correlation of spontaneous YMDD mutation in different hepatitis B virus (HBV) genotypes with HBV-related hepatocellular carcinoma (HCC). MethodFrom May 2010 to May 2012, 110 HBV-related hepatocellular cancer patients not treated by anti-virus drugs and 1 079 chronic HBV infectors (including asymptomatic HBV carriers, chronic hepatitis B patients, and HBV-related liver cirrhosis patients) were included in our study. HBV YMDD mutation was detected by fluorescence hybridization bioprobe polymerase chain reaction (PCR) and melting curve assay using Diagnosis Kit for HBV YMDD Mutation (Qiagen Biotechnology). Serum HBV genotype was detected by real time PCR using genotype specific TaqMan probe. According to data type, t-test, χ2-test and unconditional logistic regression were used for statistical analysis. ResultsIn the HCC group, genotype C virus, spontaneous YMDD mutation and genotype C virus with YMDD mutation were detected in 39 patients (35.5%), 16 patients (14.5%) and 14 patients (12.7%), respectively. In the chronic HBV infection group, HBV genotype C virus, spontaneous YMDD mutation and genotype C virus with YMDD mutation were detected in 153 patients (14.2%), 46 patients (4.3%) and 17 patients (1.6%), respectively. The difference between the two groups were statistically significant (χ2=33.368, P<0.001; χ2=21.353, P<0.001; χ2=48.889, P<0.001). Unconditional logistic regression analysis suggested that infection of genotype C virus and genotype C virus with spontaneous YMDD mutation might be important risk factors for the development of HCC[OR=2.943, 95%CI (1.778, 4.872), P<0.001; OR=5.989, 95%CI (2.394, 14.980), P<0.001]. ConclusionsInfection of genotype C virus with spontaneous YMDD mutation is tightly related with the occurrence of HCC and has important value for earlier warning of HCC.