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.
Objective To critically appraise and systematically reviewe the economic evaluations of all alternative interventions for hepatitis B in China. Methods We searched MEDLINE and the four largest Chinese electronic databases. The references of eligible studies were also screened. Economic evaluations of any type, which studied interventions for hepatitis B, were eligible for inclusion. A 25-item quality checklist modified from a BMJ checklist was used to appraise the quality of studies. The overall quality score was calculated against 100 points to indicate the risk of bias. Quality appraisal and data extraction were conducted by two independent reviewers. Results Nineteen full economic evaluations and two cost studies were included of which fourteen studies were scored 25-44 points, and seven scored 45-61 points. Most studies adequately documented effectiveness of interventions. However, the costs of interventions were not well reported in over 50% of studies. Many studies inadequately conducted data analysis, particular in sensitivity analysis and discounting. Ten studies compared lamivudine with interferon or conventional therapy for 1-year (or 6-month) effects, which indicated that lamivudine was generally cost-effective. Three evaluations studied 30-year outcomes of interferon compared with conventional therapy, which suggested that interferon usually saved additional costs and years of life. Another three studies compared interferon with less frequently used antiviral agents, however the comparative cost-effectiveness varied. Two cost studies showed the total costs and the percentage of medical costs increased rapidly in proportion to disease severity.Conclusions Of alternative interventions, lamivudine is cost effective for short-term effects. Interferon is superior to conventional therapy for long-term outcomes. However, the long-term economic outcomes cannot be justified by the current evidence. Quality of methods, particularly, that of costing and analytical methods, is a major limitation. There remains a b need to improve the quality of reporting. Careful considerations should be paid before applying the results to decision making.
目的 探討乙型肝炎病毒（HBV）表面抗原（HBsAg）陽性肝硬化患者血清中HBV前S1抗原(前S1抗原)、HBV e抗原（HBeAg）及HBV核酸定量檢測（HBV DNA）相關性。 方法 2008年7月－2011年5月對97例HBsAg陽性肝硬化住院患者和50份HBsAg陰性的健康體檢者血清進行前S1抗原、HBV血清標志物檢測及實時熒光定量PCR檢測HBV DNA結果進行分析。 結果 97份HBsAg陽性肝硬化患者血清中，前S1抗原、HBeAg及HBV DNA陽性率分別為53.6%（52/97）、22.7%（22/97）及61.8%（60/97）。22例HBeAg陽性血清中，前S1抗原陽性18例（81.8%）， HBV DNA陽性20例（90.9%)。75例HBeAg陰性血清中，前S1抗原陽性34例（45.3%），HBV DNA陽性40例（53.3%），兩者的前S1抗原與HBV DNA結果間都具有很好的相關性。HBV DNA含量與前S1抗原及HBeAg陽性結果顯示：HBsAg陽性的肝硬化患者血清中HBV DNA陰性率為38.1%（含量＜103 copies/mL），而陽性檢出率HBV DNA含量主要集中在103～105 copies/mL，占81.7%（49/60），HBV DNA含量＞105 copies/mL占18.3%（11/60）。 結論 HBsAg陽性的肝硬化患者血清中主要以HBV非HBeAg陽性血清學模式為主，HBV DNA陽性檢出率的含量主要集中在103～105 copies/mL。前S1抗原在HBeAg陽性血清中與其含有HBsAg病毒及HBeAg陽性患者具有很好的相關性，而在HBeAg陰性血清中存在著差異。Objective To study the correlation among Pre-S1 antigen, HBeAg and HBV DNA results in patients with HBsAg-positive liver cirrhosis. Methods We retrospectively analyzed the serum pre-S1-antigen, HBV serum markers and real-time quantitative PCR HBV DNA results in 97 patients with HBsAg-positive liver cirrhosis and 50 HBsAg-negative healthy volunteers in our hospital from July 2008 to May 2011. Results Among the 97 samples of HBsAg-positive liver cirrhosis patients’ serum, the positive rates of Pre-S1 antigen, HBeAg and HBV DNA were 53.6% (52/97), 22.7% (22/97) and 61.8% (60/97), respectively. In the 22 samples of HBeAg-positive serum, the number of positive pre-S1 antigen and HBV DNA was 18 (81.8%) and 20, respectively. In the 75 samples of negative HBeAg serum, the number of positive pre-S1 antigen and HBV DNA was 34 (45.3%) and 40 (53.3%) respectively. The pre-S1 antigen was correlated well with HBV DNA results in both the two groups. HBV DNA level, pre-S1 antigen and HBeAg-positive results showed that the serum HBV DNA negative rate of HBsAg-positive patients with cirrhosis was 38.1% (＜103 copies/mL), while the positive rate of HBV DNA level was mainly concentrated at 103~105 copies/mL, accounting for 81.7% (49/60), and HBV DNA level over 105 copies/mLaccounted for only 18.3% (11/60). Conclusions HBsAg-positive patients with cirrhosis mainly have a serum non-HBeAg-positive HBV serology pattern, and HBV DNA positive rate of the content is mainly concentrated at 103~105 copies/mL. There is a good correlation between pre-S1 antigen in HBeAg-positive serum and patients with HBsAg virus or positive HBeAg, while for Pre-S1 antigen in HBeAg-negative serum, it is quite different.
Objective To assess the efficacy of lamivudine in patients with HBeAg positive chronic hepatitis B.Methods MEDLINE, SCI, Current Content Connect, The Cochrane Library, and Chinese Biomedical Database were searched from the beginning to September 2005, and the references of eligible studies were manually screened. R.andomized controlled trials comparing lamivudine with non-antiviral interventions （ placebo, no treatment and standard care ） in patients with chronic hepatitis B were eligible for inclusion. Two investigators independently assessed the quality and extracted the data. Heterogeneity was examined by Chi-square test. Fixed and random effect meta-analysis were used to pool the data. Subgroup analyses were used in treatment course. Results Eleven R.CTs were included （ n = 1 237 ）. All reported the effect of lamivudine （100 mg/d） , and one of them included lamivudine （25 mg/d）. The treatment duration of 52 weeks and less than 26 weeks were reported in eight and three RCTs, respectively. Six RCTs adequately applied randomization, while other five RCTs were not reported in detail. Four RCTs adequately enforced allocation concealment, five RCTs enforced blinding bitterly. The others were not reported in detail. It was found by meta-analysis that, compared with the control, lamivudine （100 mg/d, 52 W） could significantly clear HBeAg [42.6% vs. 13% , RR 3.20, 95% CI （2.33, 4. 38）] and clearHBVDNA [71.78% vs. 20, 36%, RR3.42, 95%CI （2.80,4.19）], normalize ALT [65% vs. 34.9%, RR1.91, 95%CI （1.64,2.21）], achieve HBeAgseroconversion [16.1% vs. 7.29% , RR2.12, 95%CI （1.24,3.80） ] and histology response [57. 9% vs. 26.2%, RR 2. 17, 95% CI （ 1.67,2.81 ） ] ; Lanfivudine （100 mg/ d, 12 W） could effectively clear HBV DNA [ 50.7% vs 3.92% , RR 8.68, 95% CI （1.72,43.74 ） ] , but was not effective in loss of HBeAg, HBeAg seroconversion and normalization of ALT, Lamivudine （25 mg/d） could effectively clear HBV DNA [97.7% vs. 22.2% , RR 4.41, 95% CI （2.86,6.79） ] and improve histology response [59.3% vs. 30% , RR1.98, 95% CI （1.31,2.99 ） ], but was not effective in HBeAg seroconversion. Conclusions Lamivudine （100 mg/ d） is effective in clearing HBV DNA and HBeAg, normalizing ALT and achieving HBeAg seroconversion.
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.
ObjectiveTo systematically evaluate the association between human leukocyte antigen DQ (HLA-DQ) gene rs2856718A>G, rs9275572A>G polymorphisms and the risk of chronic hepatitis B. MethodsPubMed, EMbase, CBM, WanFang Data, CNKI and VIP databases were systematically searched from inception to April 2015 to collect case-control studies about HLA-DQ gene polymorphisms and the risk of chronic hepatitis B. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software, and Stata 12.0 software was used for sensitivity and publication bias analysis. ResultsA total of 6 papers involving 8 case-control studies were included, which involved 3 690 cases and 6 267 controls. The results of meta-analysis showed that:the rs2856718A>G polymorphism was associated with the decreased risk of chronic hepatitis B (AG+GG vs. AA:OR=0.63, 95%CI 0.51 to 0.78, P=0.000; GG vs. AG+AA:OR=0.69, 95%CI 0.61 to 0.79, P=0.000; GG vs. AA:OR=0.56, 95%CI 0.48 to 0.64, P=0.000; GA vs. AA:OR=0.64, 95%CI 0.47 to 0.88, P=0.006; G vs. A:OR=0.74, 95%CI 0.68 to 0.79, P=0.000). The rs9275572A>G polymorphism was not associated with the risk of chronic hepatitis B (AG+GG vs. AA:OR=1.11, 95%CI 0.55 to 2.23, P=0.770; GG vs. AG+AA:OR=1.10, 95%CI 0.84 to 1.45, P=0.500; GG vs. AA:OR=1.14, 95%CI 0.54 to 2.41, P=0.730; AG vs. AA:OR=1.06, 95%CI 0.56 to 2.02, P=0.860; G vs. A:OR=1.11, 95%CI 0.83 to 1.48, P=0.490). ConclusionHLA-DQ gene rs2856718 A>G polymorphism is significantly associated with decreased risk of chronic hepatitis B, but the rs9271319 A>G polymorphism is not associated with the risk of chronic hepatitis B.
Objective?To compare adefovir monotherapy with adefovir-thymosin alpha-1 combination therapy for chronic hepatitis B. Methods?We searched The Cochrane Library, MEDLINE, PubMed, the Chinese Biomedical Database (CBM), CNKI, Wanfang, and VIP databases up to February 2010 to identify randomized controlled trials (RCTs) comparing adefovir plus thymosin alpha-1 versus adefovir alone for chronic hepatitis B. We also scanned references of all included studies and pertinent reviews. The methodological quality assessment and data extraction were conducted by two reviewers independently according to the Cochrane Reviewer’s Handbook 5.0.2 . Meta-analyses were performed using RevMan 5.0 software. Results?Eleven trials involving 895 patients were included. The results of meta-analyses shoued: the HBeAg seroconversion rate of the combination therapy group was higher than that of the monotherapy group, both at the sixth month and the twelfth month (RR=1.77, 95%CI 1.38 to 2.27; RR=1.74, 95%CI 1.44 to 2.10); and there were also significant differences between the two groups for secondary outcomes including HBV-DNA negative, ALT normalization, etc.Conclusion?Adefovir-thymosin alpha-1 combination therapy might be more effective than adefovir monotherapy for chronic hepatitis B. Significant differences are even observed at the sixth month. However, the results should be interpreted with caution because of the low quality of the included studies. High-quality, large-scale RCTs are needed to further prove the results.
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.
目的 觀察阿德福韋酯聯合胸腺五肽治療乙型肝炎病毒e抗原（HBeAg）陽性慢性乙型肝炎2年的療效。 方法 2007年1月－2009年1月間178例慢性乙型肝炎患者隨機分為試驗組91例和對照組87例。試驗組給予胸腺五肽1 mg，隔日皮下注射，療程52周；同時阿德福韋酯10 mg/d口服104周。對照組給予阿德福韋酯10 mg/d，口服104周。治療26、52、104周及停藥52周時，分別檢測血清丙氨酸氨基轉移酶（ALT）、天冬氨酸氨基轉移酶（AST）、乙型肝炎病毒（HBV）DNA含量及HBV血清標志物。 結果 治療52周后，試驗組在ALT復常率、AST復常率、HBV DNA轉陰率、HBeAg轉陰率與HBeAg/HBeAb血清轉換率方面都比對照組高。停藥52周時，試驗組與對照組的ALT復常率、AST復常率、HBV DNA轉陰率、HBeAg轉陰率、HBeAg/HBeAb血清轉換率分別為74.73%與51.72%、75.82%與54.02%、25.27%與8.05%、26.37%與10.34%、18.68%與8.05%（χ2=10.652、9.313、9.421、7.574、4.313，P＜0.05）。 結論 阿德福韋酯聯合胸腺五肽治療HBeAg陽性慢性乙型肝炎比單獨使用阿德福韋酯抗病毒治療效果更好，有助于提高HBeAg/HBeAb血清轉換率，減少停藥后病毒學突破，并且使用安全。Objective To evaluate the efficacy of adefovir dipivoxil (ADV) combined with thymopentin on chronic hepatitis B patients with positive hepatitis B e antigen (HBeAg). Methods Between January 2007 and January 2009, 178 chronic hepatitis B patients with positive HBeAg were randomly divided into two groups: the treatment group (91 cases) and the control group (87 cases). All patients in two groups received 10 mg of ADV once a day for 104 weeks, while the patients in the treatment group received 1 mg of thymopentin for subcutaneous injection every other day for 52 weeks. The rates of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) normalization, serum hepatitis B virus (HBV) DNA clearance and HBeAg loss and anti- HBeAg seroconversion were evaluated at pretreatment, and 52, 104 and 156 weeks after treatment, respectively. Results After 52-week treatment, The rates of ALT and AST normalization, serum HBV DNA clearance and HBeAg loss and anti- HBeAg seroconversion in the treatment group were higher than those in the control group. In 52-week follow-up after 104 weeks treatment, the rates of ALT and AST normalization , serum HBV DNA clearance and HBeAg loss and anti- HBeAg seroconversion of two groups were 74.73% versus 51.72%, 75.82% versus 54.02%, 25.27% versus 8.05%, 26.37% versus 10.34%, 18.68% versus 8.05%, respectively (χ2 = 10.652, 9.313, 9.421, 7.574, 4.313; P＜0.05). Conclusions It is more effective for adefovir dipivoxil combined with thymopentin on HBeAg-positive patients with chronic hepatitis B than using adefovir alone. Combination treatment could improve the rates of HBeAg seroconversion and reduce the breakthrough of HBV after drug withdrawal. And it is safe.
Objective To evaluate the effectiveness and safety of foscarnet sodium in the treatment of chronic hepatitis B. Methods We searched MEDLINE, EMbase, The Cochrane Library and CNKI from 1978 to June 2006. Randomized controlled trials of foscarnet sodium versus other drugs or no drugs in the treatment of chronic hepatitis B were identified. The quality of the included trials was evaluated by two reviewers independently. Meta-analysis was done using The Cochrane Collaboration’s RevMan 4.2.7. Results Seven studies (337 patients) were included; one compared foscarnet sodium versus interferon, and the other six compared foscarnet sodium versus no drugs. All the included studies were graded in terms of the quality of randomization, allocation concealment and blinding. All 7 studies were graded as level C. The meta-analysis showed that: ① foscarnet sodium was not significantly different from interferon in clinical efficacy, liver function, negative-conversion rate of virological markers and side effects. ② compared with the no drugs group, the negative-conversion rate of virological markers was significantly higher for the foscarnet sodium group, HBeAg (RR 6.20, 95%CI 1.76 to 21.79) and HBV-DNA (RR 4.13, 95%CI 1.32 to 12.86); but there were no significant differences in clinical efficacy, liver function and side effects. Conclusions Available evidence shows that: in the treatment of chronic hepatitis B the effectiveness and safety of foscarnet sodium are not significantly different from interferon, but only one trial is included in this review, so the evidence is weak. Compared with no drugs, foscarnet sodium significantly improves the negative-conversion rate of virological markers, but the evidence is insufficient to show whether foscarnet sodium could improve clinical efficacy and liver function, as well as reduce side effects.