ObjectiveTo evaluate the effect of autoantibody on the efficacy and safety of pegylated interferonα-2a (Peg-IFNα-2a) and ribavirin on chronic hepatitis C (HCV). MethodsWe enrolled 106 chronic HCV infected patients, who were divided into autoantibody-positive group and negative group based on the baseline autoantibody detection. The patients were treated for 48 weeks. The anti-viral response and adverse effects were observed. Data analyses were reported using the SPSS 20.0 statistical package. ResultsThe prevalence of any autoantibody in chronic hepatitis C patients amounted to 31.1%, and serum anti-nuclear antibody was positive in 24 patients. Difference in age, sex, serum alanine transaminase level, aspartate transaminase level, total bilirubin level, thyroid function and HCV RNA level between autoantibody-positive group and negative group was not significant (P > 0.05). The level of hemoglobin in autoantibody-positive group was significantly lower than the negative group (P=0.018). Of the 106 patients, 82 patients achieved sustained virological response (SVR), 56 achieved rapid virological response (RVR), 98 achieved ealy virological response (EVR) and 8 were non-responders. There were no significant differences between RVR, EVR and SVR in autoantibody-positive group and negative group (P > 0.05). The most common adverse effects in this study were fatigue, weight loss, hair loss and fever, and no significant differences in adverse effects were observed between the two groups (P > 0.05). ConclusionAutoantibody positivity may not affect the treatment response and is safe in chronic HCV infected patients with combination therapy of pegylated interferonα-2a plus ribavirin.
ObjectiveTo investigate the ultrasonic changes of liver during various immune periods with different number of CD4+ T lymphocytes in HIV/AIDS patients with chronic viral hepatitis. MethodsThe clinical data of 100 patients with chronic viral hepatitis diagnosed between January 2010 and December 2012 were selected. Among them, 50 simple chronic viral hepatitis patients were designated as the control group, and the other 50 HIV/AIDS patients with chronic viral hepatitis were regarded as the experimental group. Ultrasonographic observation was applied on patients of the experimental group according to different immune period based on the number of CD4+ T lymphocytes. Indexes observed included liver size, the edge of liver, capsule of liver and hepatic parenchymal echo. The cross-check analysis was employed between observed results and clinical laboratory results. ResultsAbnormal changes of the experimental group were shown on the ultrasound observation of liver in different CD4+ T lymphocyte count immune periods, including enlargement of the liver, slightly blunt liver margin, slightly thick capsule, dense and uniform, slightly rough and not so uniform, or rough and not uniform hepatic parenchymal echo. There was no significant difference in ultrasonic changes of liver between the two groups when the CD4+ T cell number was over 300/mm3. However, the difference was significant when the CD4+ T cell number was below 100/mm3. ConclusionLiver abnormalities become more obvious as CD4+ T cell count decreases in HIV/AIDS patients with chronic viral hepatitis. Comprehensive considerations of various liver ultrasound indicators are helpful in clinical evaluation of HIV/AIDS patients with chronic viral hepatitis.
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.
Objective To assess the efficacy of telbivudine in the treatment of chronic hepatitis B (CHB). Methods Randomized controlled trials (RCTs) of telbivudine therapy vs. lamivudine therapy in both Chinese and English were retrieved from seven electronic databases with a cut-off date in February 2010, including PubMed, EMbase, VIP, CBM, CNKI, and The Cochrane library. The meta-analyses and evaluation on methodology quality were performed for the included studies. Results Two RCTs as Grade-A study were included. The meta-analyses showed that telbivudine was superior to lamivudine in aspects of therapeutic response (RR=1.28, 95%CI 1.10 to 1.48, P=0.001), ALT normalization (RR=1.12, 95%CI 1.01 to 1.23, P=0.02), and PCR-negative HBV DNA or below the lower limit (RR=1.44, 95%CI 1.36 to 1.53, Plt;0.000 01), primary treatment failure (OR=0.28, 95%CI 0.18, to 0.43, Plt;0.000 01), viral breakthrough (OR=0.38, 95%CI 0.32 to 0.47, Plt;0.000 01) and viral resistance (OR=0.44, 95%CI 0.36 to 0.55, Plt;0.000 01). Conclusion Based on the current clinical evidence, telbivudine demonstrates superiority in comparison with lamivudine on all direct measures of antiviral efficacy for CHB. Because of the short follow-up duration and the small sample size of the included studies, it is expected to further discuss the long-term efficacy.
Objective To evaluate the effectiveness and safety of different doses of interferon alfa (INF-α) in the treatment of chronic hepatitis C (CHC). Methods Such databases as MEDLINE, EMbase, CENTRAL, CBM, CNKI, VIP and WanFang Data were searched to collect the randomized controlled trials (RCTs) on different doses of INF-α in the treatment of CHC published before August, 2012. According to the inclusion and exclusion criteria, two reviewers independently screened literature, extracted data and evaluated the quality of the included studies, and then meta-analysis was performed using RevMan 5.0 software. Results A total of 13 RCTs involving 1 442 patients were included. The results of meta-analysis on different doses of INF-α showed that, a) There was no significant difference in the complete response rate between the 3 MU dose group and the 1 MU dose group (RR=0.83, 95%CI 0.52 to 1.32, P=0.43), but there was significant difference in the sustained response rate between those 2 groups (RR=1.89, 95%CI 1.00 to 3.59, P=0.05); and b) No significant differences were found in the complete response rate among the 3 MU dose group, the 6 MU dose group, and the 1 MU dose group. Conclusion INF-α in dose of 3 MU, 3 times daily, is effective in treating CHC, but it would not rule out that higher dose takes more effective action. When INF-α is used to treat CHC, an individualized medication should be applied according to patients’ tolerance and economic status.
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 review the efficacy and safety of Heluo Shugan capsule in the treatment of hepatitis B fibrosis. MethodWe searched PubMed, The Cochrane Library (Issue 8, 2015), CBM, CNKI, VIP and WanFang Data from their inception to August 2015, to collect randomized controlled trials (RCTs) on Heluo Shugan capsule for hepatitis B fibrosis. 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. ResultsA total of 15 RCTs involving 1 840 patients were included. The results of meta-analysis showed that: (1) As for reduced level of serum hyaluronic acid (HA), Heluo Shugan capsule was superior to placebo (MD=82.31, 95%CI 37.44 to 127.19, P=0.000 3), but worse than Fuzheng Huayu capsule (MD=-137.45, 95% CI-196.29 to-78.62, P < 0.000 01), Fufang Biejia Ruangan tablet (MD=-51.19, 95% CI-67.58 to-34.81, P < 0.000 01) and Anti-fibrosis decoction (MD=-82.13, 95% CI-102.37 to-61.88, P < 0.000 01). (2) As for reduced level of serum laminin (LN), Heluo Shugan capsule was superior to placebo (MD=36.83, 95% CI 11.84 to 61.82, P=0.004), but worse than Fufang Biejia Ruangan tablet (MD=-36.00, 95% CI-64.29 to-7.71, P=0.01), Ganfujian capsule (MD=-22.14, 95% CI-37.28 to-7.00, P=0.004) and Anti-fibrosis decoction (MD=-38.64, 95% CI-75.00 to-2.29, P=0.04). (3) As for reduced level of serum procollagen type III peptide (PCIII), Heluo Shugan capsule was superior to placebo (MD=47.17, 95% CI 32.68 to 61.66, P < 0.000 01), but worse than Fuzheng Huayu capsule (MD=-4.80, 95% CI-9.08 to-0.51, P=0.03), Dahuang Zhechong pills (MD=-53.77, 95% CI-105.01 to-2.53, P=0.04), Ganfujian capsule (MD=-46.82, 95% CI-66.30 to-27.34, P < 0.000 01) and Anti-fibrosis decoction (MD=-28.68, 95% CI-55.59 to-1.77, P=0.04). (4) As for reduced level of serum type-IV-collagen (IV-C), Heluo Shugan capsule was superior to placebo (MD=72.77, 95% CI 47.65 to 97.89, P < 0.000 01), but worse than Fuzheng Huayu capsule (MD=-34.69, 95% CI-56.65 to-12.73, P=0.002), Dahuang Zhechong pills (MD=-21.26, 95%CI-38.79 to-3.73, P=0.02), Fufang Biejia Ruangan tablet (MD=-69.04, 95%CI-124.38 to-13.69, P=0.01), Ganfujian capsule (MD=-19.84, 95% CI-37.41 to-2.27, P=0.03) and Anti-fibrosis decoction (MD=-37.98, 95% CI-72.99 to-2.96, P=0.03). ConclusionCurrent evidence shows that, Heluo Shugan capsule was superior to placebo, but worse than Fufang Biejia Ruangan tablet, Fuzheng Huayu capsule, Dahuang Zhechong pills, Ganfujian capsule and Anti-fibrosis decoction in reducing the level of serum hepatic fibrosis. Due to the limited quantity and quality of included studies, more high-quality, large-scale RCTs are need to verify the above conclusion.
This study aims to clarify host factors of IFN treatment in the treatment of chronic hepatitis B (CHB) patients by screening the differentially expressed genes of IFN pathway CHB patients with different response to interferon (IFN) therapy. Three cases were randomly selected in IFN-responding CHB patients (Rs), non-responding CHB patients (NRs) and healthy participants, respectively. The human type I IFN response RT2 profiler PCR array was used to detect the expression levels of IFN-related genes in peripheral blood monocytes (PBMCs) from healthy participants and CHB patients before and after Peg-IFN-α 2a treatment. The results showed that more differentially expressed genes appeared in Rs group than NRs group after IFN treatment. Comparing with healthy participants, IFNG, IL7R, IRF1, and IRF8 were downregulated in both Rs and NRs group before IFN treatment; CXCL10, IFIT1, and IFITM1 were upregulated in the Rs; IL13RA1 and IFI35 were upregulated in the NRs, while IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1, and ADAR were downregulated. The expression of IL15, IFI35 and IFI44 was downregulated by 4.09 (t = 10.58, P < 0.001), 5.59 (t = 3.37, P = 0.028) and 10.83 (t = 2.8, P = 0.049) fold in the Rs group compared with the NRs group, respectively. In conclusion, IFN-response-related gene array is able to evaluate IFN treatment response by detecting IFN-related genes levels in PBMC. High expression of CXCL10, IFIT1 and IFITM1 before treatment may suggest satisfied IFN efficacy, while high expression of IL13RA1, IL15, IFI35 and IFI44 molecules and low expression of IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1 and ADAR molecules may be associated with poor IFN efficacy.
Objectives To determine the health benefit of elbasvir/grazoprevir versus peginterferon combing with ribavirin (PR regimen) for Chinese chronic hepatitis C patients with genotype 1b infection. Methods Markov cohort state-transition models were constructed to conduct cost utility analysis. Sensitivity analyses were performed based on base-case analysis. Results Elbasvir/grazoprevir was dominant versus PR, resulting in higher QALYs and lower costs for both noncirrhotic patients (13.867 5 QALYs, 82 090.82 RMB vs. 12.696 2 QALYs, 122 791.55 RMB) and cirrhotic patients (12.841 6 QALYs, 225 807.70 RMB vs. 8.892 4 QALYs, 326 545.01 RMB). Elbasvir/grazoprevir was economically dominant in nearly 100% among all patients within the range of threshold from 0 to 161 805 RMB/QALY. Conclusions Elbasvir/grazoprevir was dominant in treatment of genotype 1b chronic hepatitis C infection in China.
ObjectiveTo evaluate the clinical efficacy and safety of telbivudine (TEV) combined with adefovir dipivoxil (ADV) for chronic hepatitis B (CHB), so as to provide references for clinical practice and research. MethodsWe electronically searched databases including The Cochrane Library (Issue 7, 2013), PubMed, EMbase, Web of Science, CBM, CNKI, VIP, and WanFang Data from inception to August 21st, 2013, for the relevant randomized controlled trials (RCTs). Other sources were also retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the quality of included studies. Then, meta-analysis was performed using RevMan 5.1 software. ResultsA Total of 11 RCTs involving 1 010 patients were included. The trial group were given TEV combined with ADV, while the control group were given TEV alone or ADV alone. The results of metaanalysis showed that, the combined use was superior to TEV alone or ADV alone in improving HBV-DNA negative rates at 12-, 24-, 48-weeks, HBeAg negative rates at 12-, 24-, 48-weeks, and ALT recovery rates at 12-, 24-weeks (P < 0.05). The results of qualitative analysis showed that, the trial group had a lower drug resistance rate, and both were alike in the incidence of adverse reaction. ConclusionCompared with TEV alone or ADV alone, TEV combined with ADV could improve the clinical efficacy of treating CHB which is also fairly safe. Due to the limited quantity and quality of the included studies, the aforementioned conclusion still needs to be further verified by conducting more large-scale and high quality RCTs.