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.
ObjectiveTo analyze the influencing factors for hepatitis B virus (HBV) infection screening in lymphoma patients prior to chemotherapy with a focus on HBV reactivation after chemotherapy. MethodsThe HBV infection screening data of 449 patients with lymphoma treated by chemotherapy between June 2010 and July 2012 were analyzed retrospectively. ResultsAmong the 449 patients, 387 (86.2%) were screened for HBV before initiation of chemotherapy, and patients with elevated aminotransferase levels were more likely to receive pre-chemotherapy HBV testing (OR=2.509, P=0.040). HBV reactivation was observed in 16.1% (9/56) of the HBsAg-positive patients after chemotherapy, and it was more likely to occur in patients with the use of rituximab (29.2% vs. 6.3%; P=0.030). Prophylactic antiviral therapy can significantly reduce the incidence of chemotherapy-induced HBV reactivation (12.0% vs. 50.0%; P=0.046). Two cases of reactivation occurred in patients who were HBsAg negative and hepatitis B core antibody positive. ConclusionHBV reactivation, especially for people with the use of rituximab, is a common complication in patients with HBV infection. HBV infection testing should be considered for lymphoma patients who were planned for chemotherapy. Prophylactic antiviral therapy can greatly decrease the incidence of HBV reactivation.
The infection of Hepatitis B virus (HBV) can result in severe consequences, including chronic hepatitis, liver fibrosis, cirrhosis, and even liver cancer. Effective antiviral treatment has the potential to slow down the progression of the disease. HBV serum biomarkers play a crucial role in the dynamic management of chronic hepatitis B (CHB) patients. However, the conventional hepatitis B virus markers, such as hepatitis B serologic testing and HBV DNA, are insufficient to meet the clinical requirements. This review provided a comprehensive overview of the current research on the quantification of HBsAg and anti-HBc, HBV RNA and HBV core-associated antigen, which summarized the crucial role these markers play in the administration of antiviral medications, predicting the efficacy of treatment and anticipating the likelihood of virologic rebound following drug cessation, as well as assessing disease progression in CHB patients.
ObjectiveTo study the value of hepatitis B virus surface antigen (HBsAg) in the evaluation of antiviral efficacy and its influencing factors under a complex population background resulting from various nationalities in Xinjiang. MethodsWe retrospectively analyzed patients with chronic hepatitis B (CHB) admitted and administrated with nucleot(s)ide analogues (NAs) for the first time in Traditional Chinese Medical Hospital of Xinjiang Uygur Autonomous Region from January 2012 to August 2013. The biological, virological, and serological responses were analyzed as well as the possible factors related to HBsAg levels and its reduction levels. ResultsThere were 63 CHB patients enrolled. After 48 weeks' treatment, all patients achieved biological response, and 59 of them achieved complete virological response in spite of 4 patients with partial response. In all the 30 hepatitis B virus e antigen (HBeAg) positive patients, 5 achieved HBeAg seroconversion. After correlation and regression analysis, it turned out that the history (P=0.033) and HBeAg levels at week 48 (P<0.001) were independent impact factors for HBsAg level at week 48. And the reduction degree of HBsAg at week 48 was influenced by HBsAg at week 48. In 21 patients counting to week 72 maintaining biological response, 18 achieved complete virological response. Unfortunately, all 8 HBeAg positive patients encountered no HBeAg loss or seroconversion. After correlation and regression analysis, it turned out that HBsAg level at week 72 was influenced by HBsAg at week 48 (r=0.700, P<0.001). And the decline degree of HBsAg at week 72 was related to baseline HBsAg level. ConclusionSatisfactory efficacy can be achieved via NAs treatment in CHB patients. But when HBsAg is used separately as an indicator for therapeutic efficacy, we should be aware that intrahepatic covalently closed circular DNA (cccDNA) is not only the impact factor of HBsAg variation, the history, the variations of HBeAg and HBsAg itself during the treatment should also be considered.
ObjectiveTo systematically review the efficacy of different nucleosides (acids) in preventing hepatitis B virus reactivation after chemotherapy in cancer patients. MethodsThe Cochrane Library, PubMed, EMbase, Web of Science, CNKI, WanFang Data, and VIP databases were electronically searched to collect randomized controlled trials (RCTs) of different nucleosides (acids) to prevent HBV reactivation after chemotherapy in cancer patients from inception to June 7th, 2021. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Network meta-analysis was then performed by using Stata 16.0 software. ResultsA total of 43 RCTs involving 3 269 patients were included. There were 7 interventions, namely entecavir (ETV), lamivudine (LAM), adefovir dipivoxil (ADV), telbivudine (LdT), tenofovir dipivoxil (TDF), lamivudine combined with entecavir (LAM+ETV), and lamivudine combined with adefovir dipivoxil (LAM+ADV). The results of network meta-analysis showed that the efficacy of reducing the reactivation rate of ETV, LAM, ADV, LdT, TDF, LAM+ETV, LAM+ADV were superior than the control group. The ETV, LAM and ADV were not as effective as LAM+ETV. The leading drug combinations were LAM+ETV (94.8%), LdT (81.5%) and LA+ADV (58.0%). ConclusionsCurrent evidence shows that LAM+ETV, LdT, and LA+ADV are more effective in preventing hepatitis B virus reactivation after chemotherapy in cancer patients. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusions.
ObjectiveTo explore the single locus mutation that related to hepatitis B virus (HBV) co-infection by means of genome-wide association study (GWAS) in Chinese Han patients with pulmonary tuberculosis (TB).MethodsA total of 946 patients with pulmonary TB enrolled between March 2013 and March 2018 were genotyped by Illumina Human Omni Express gene chip. After quality control, 389 972 single nucleotide polymorphisms (SNPs) of 703 patients with single TB infection and 53 patients with TB-HBV co-infection were included in the follow-up association analysis.ResultsThe SNP with the strongest statistical correlation signal was rs118122819 (P=2.923×10−12, odds ratio=7.933) located on chromosome 8p23.1. Other potential susceptibility genes included CDH4 (rs73309833), MARCH1 (rs3797020), and DNER (rs13393112), etc. In addition, a strong linkage imbalance between rs118122819 and rs4840365 (D’=0.88, r2=0.76) was found, while rs4840365 was located in the MFHAS1 gene region.ConclusionsThis study provides evidence for the presence of susceptibility gene locus for HBV co-infection in pulmonary TB patients, and provides important clues for the mechanism research, disease prevention, and treatment of co-infection. But these associations must be replicated and validated in larger studies.
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.
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.
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.
ObjectiveTo investigate the efficacy of lamivudine combined with low-dose hepatitis B immune globulin to prevent HBV reinfection after liver transplantation. MethodsThe clinical data of 76 cases of HBV-related liver disease after liver transplantation using lamivudine combined with low-dose hepatitis B immune globulin to prevent HBV re-infection were retrospectively analyzed, and the HBV re-infection risk factors were analyzed. ResultsSeventy-six patients' HBsAg became negative after liver transplantation, HBV re-infect in 9 cases.The re-infection rate was 9.2% (7/76) and 11.8% (9/76), respectively, in 1-year and 2-year after liver transplantation. ConclusionsLamivudine combined with low-dose hepatitis B immune globulin after liver transplantation can be effective preventing re-infection with HBV.HBeAg positive and HBV-DNA positive before liver transplantation is risk factors of HBV re-infection.