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 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.
ObjectiveTo systematically review the diagnostic value of FibroScan for the staging of liver fibrosis in chronic hepatitis B.
MethodsWe searched the PubMed, EMbase, Web of Knowledge, CBM, WanFang Data and CNKI databases for studies investigated the diagnostic value of FibroScan for hepatic fibrosis B from Jan. 1st, 2003 to Aug. 31st, 2013. Two reviewers independently screened literature according to the exclusion and inclusion criteria, extracted data and assessed methodological quality of included studies. Then, Stata 13.0 software was used to analyze the data.
ResultsA total of 15 studies involving 2 588 patients were included. The results of meta-analysis showed that:the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the AUC of SROC were 0.77 (95%CI 0.69 to 0.83), 0.84 (95%CI 0.70 to 0.87), 3.8 (95%CI 2.6 to 5.6), 0.29 (95%CI 0.22 to 0.38), 13 (95%CI 8 to 21), 0.82 (95%CI 0.82 to 0.88) for hepatic fibrosis; and were 0.81 (95%CI 0.73 to 0.87), 0.89 (95%CI 0.86 to 0.92), 7.5 (95%CI 5.3 to 10.3), 0.21 (95%CI 0.14 to 0.31), 36 (95%CI 20 to 65), 0.93 (95%CI 0.90 to 0.95) for early hepatic cirrhosis, respectively.
ConclusionThe current evidence suggests that FibroScan is of good accuracy in the diagnosis of early hepatic fibrosis but not for hepatic cirrhosis in patient with chronic hepatitis B.
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 evaluate the effectiveness and safety of kushenin for chronic hepatitis B. Methods We searched The Cochrane Hepato-Bil iary Group Controlled Trials Register (March, 2006), The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2006), MEDLINE (1966 to present), EMBASE (1966 to present), OVID (1965 to present), the Chinese Biomedical Database (CBM) (1978 to 2006) and CNKI. Qual ity assessment and data extraction were conducted by two reviewers independently, and disagreement, if any, was resolved by discussion. Meta-analyses were performed for homogeneous studies. Results A total of 56 studies involving 5156 patients met the inclusion criteria. These included 3 randomized controlled trials (RCTs), 7 quasi-RCTs, and 46 other studies that did not report randomization methods. None of the trials enforced allocation concealment and only one trial performed blinding.We conducted subgroup analyses based on the outcome measures and interventions. Compared with interferon,the HBeAg seroconversion rate at 12 months after treatment was lower in patients treated with kushenin (RR=0.72, 95%CI 0.58 to 0.90); compared with lamivudine, a lower HBV DNA seroconversion rate after 12 and 24 weeks of treatment was associated with kushenin (RR=0.48, 95%CI 0.33 to 0.70; RR=0.40, 95%CI 0.26 to 0.63). No significant differences were noted between the kushenin group and the control group for all the other outcome measures. Conclusion Kushenin might be effective in normal izing 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.
