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.
Objective
To explore the relationship between the level of serum ferritin (SF) and liver damage in patients with chronic hepatitis B (CHB).
Methods
The concentration of serum ferritin of 98 patients with CHB from July to October 2014 was measured, and then correlation analysis was performed to analyze the correlation between SF and such indexes as serum tumor marker α-fetoprotein, biochemical markers [alanine amino transferase (ALT), aspartate amino transferase (AST), total protein (TP), albumin and total bilirubin (TBIL)], and hepatitis B serum markers (hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B e antigen, hepatitis B e antibody, and hepatitis B core antigen). Serum hepatitis B virus DNA (HBV-DNA) viral load was also tested, and then the discrepancy of SF levels in the high and low viral load groups was analyzed.
Results
The average concentration of the abnormally elevated SF was (878.69±837.98) ng/mL. The SF mean difference between low-load HBV-DNA and high-load HBV-DNA was statistically significant (P < 0.05). Serum ferritin levels were independently and positively correlated with ALT, AST, and TBIL (P < 0.01) and inversely correlated with TP and albumin (P < 0.01).
Conclusion
The rise of SF is associated with liver damage, which can reflect the state of inflammation of patients with CHB.
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 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.
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.
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.
ObjectivesTo systematically review the risk factors of hepatocellular carcinoma (HCC) in patients with hepatic B surface antigen (HBsAg).MethodsScopus, EMbase, PubMed, and The Cochrane Library databases were systematically searched for relevant studies on HCC after HBsAg seroclearance from inception to October 31st, 2017. Two reviewers independently screened literature, extracted the data, and evaluated the risk of bias in the included studies. Meta-analysis was then conducted using R 3.5.3 software.ResultsA total of 28 studies involving 105 411 patients were included. Among 105 411 patients with chronic hepatitis B (CHB), 7 656 patients occurred spontaneously HBsAg seroclearance, while 1 248 patients had HBsAg seroclearance after interferon or nucleoside analogue therapy. The rate of HBsAg seroclearance was 6.77%. Meta-analysis showed that risk factors for HCC after serum HBsAg conversion included cirrhosis (OR=6.43, 95%CI 3.56 to 11.60, P<0.001), male (OR=2.72, 95%CI 1.66 to 4.46,P<0.001), and age ≥50 years at HBsAg seroclearance (OR=3.71, 95%CI 2.17 to 6.35,P<0.001).ConclusionsPatients with CHB after HBsAg seroclearance are still at risk of developing HCC. Therefore, periodic surveillance is recommended, especially for male patients, patients with cirrhosis, and patients who experience HBsAg seroclearance when over 50.
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.
ObjectiveTo systematically review the efficacy of lamivudine (LAM) plus adefovir (ADV) versus entecavir (ETV) monotherapy for LAM-resistant chronic hepatitis B patients.
MethodsWe electronically searched databases including PubMed, The Cochrane Library (Issue 12, 2013), CBM, CNKI, VIP, WanFang Data from their inception to December 2013, to collect randomized controlled trials (RCTs) or cohort studies of LAM+ADV versus ETV for LAM-resistant chronic hepatitis B. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.2 software.
ResultsA total of 13 RCTs and 5 cohort studies involving 1 336 patients were included. The results of meta-analyses of RCTs showed that:there were no significant differences between the LAM+ADV group and the ETV group in the negative rates of serum HBV-DNA (RR=1.00, 95%CI 0.91 to 1.10, P=0.94), HBeAg (RR=0.90, 95%CI 0.70 to 1.17, P=0.43), serum ALT recovery rate (RR=0.97, 95%CI 0.90 to 1.05, P=0.45) and serum HBeAg conversion rate (RR=0.71, 95%CI 0.40 to 1.24, P=0.22) at the 48th week. The results of meta-analyses of cohort studies showed that:there were no significant differences between the two groups in the negative rates of serum HBV-DNA (RR=1.37, 95% CI 0.91 to 2.06, P=0.13) and serum ALT recovery rate (RR=0.99, 95%CI 0.87 to 1.12, P=0.87), but the ETV group had higher serum HBeAg conversion rate (RR=0.24, 95% CI 0.07 to 0.79, P=0.02).
ConclusionCurrent evidence shows that the efficacy of LAM+ADV is similar to ETV at the 48th week for LAM-resistant chronic hepatitis B patients. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
