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International Journal of Clinical and... 2015Chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide. Tenofovir monotherapy or tenofovir-based combination therapy have achieved...
Comparison of the efficacy of tenofovir monotherapy versus tenofovir-based combination therapy in adefovir-experienced chronic hepatitis B patients: a systematic review and meta-analysis.
BACKGROUND
Chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide. Tenofovir monotherapy or tenofovir-based combination therapy have achieved promising results in the treatment of chronic hepatitis B patients who failed adefovir therapy.
OBJECTIVE
The goal of this study was to assess the efficacy of tenofovir monotherapy compared with tenofovir-based combination therapy for treatment of adefovir-experienced chronic hepatitis B (CHB) patients.
METHODS
randomized and non-randomized control trials directly comparing tenofovir monotherapy and tenofovir-based combination therapy were searched in PUBMED, MEDLINE, EMBASE database up to April 30, 2015. The data were analyzed with Review Manager (v.5.3).
RESULTS
Seven articles (total of 478 patients) met entry criteria. The results found that the rates of undetectable hepatitis B virus DNA levels (64.7% vs. 68.5%, P = 0.58 for 24 weeks; 71.4% vs. 71.7%, P = 0.76 for 48 weeks; 71.6% vs. 73.0%, P = 0.92 for 96 weeks), alanine aminotransferase (ALT) normalization (72.6% vs. 69.2%, P = 0.46 for 48 weeks; 72.8% vs. 75.0%, P = 0.74 for 96 weeks) and hepatitis Be antigen loss (5.0% vs. 0, P = 0.43 for 48 weeks; 16.5% vs. 12.5%, P = 0.43 for 96 weeks) were not significantly different between the TDF alone and the TDF-based group. Moreover, the rate of adverse reactions was also not significantly different between the 2 groups (P = 0.06 for 96 weeks).
CONCLUSIONS
TDF monotherapy and TDF-based combination therapy are similarly effective and safe in adefovir-experienced CHB patients after 48 weeks and 96 weeks of antiviral therapy. Nevertheless, large scale randomized control trials should be carried out to elucidate the long-term outcome of TDF treatment.
PubMed: 26884924
DOI: No ID Found -
The Cochrane Database of Systematic... Jun 2019Hepatitis B virus (HBV) infection is a liver disease caused by hepatitis B virus, which may lead to serious complications such as cirrhosis and hepatocellular carcinoma.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatitis B virus (HBV) infection is a liver disease caused by hepatitis B virus, which may lead to serious complications such as cirrhosis and hepatocellular carcinoma. People with HBV infection may also have coinfections including HIV and other hepatitis viruses (hepatitis C or D), and coinfections may increase the risk of all-cause mortality. Chronic HBV infection increases morbidity, psychological stress, and it is an economic burden on people with chronic hepatitis B and their families. Radix Sophorae flavescentis, a herbal medicine, is administered mostly in combination with other drugs or herbs. It is believed that it decreases discomfort and prevents the replication of the virus in people with chronic hepatitis B. However, the benefits and harms of Radix Sophorae flavescentis on patient-centred outcomes are unknown, and its wide usage has never been established with rigorous review methodology.
OBJECTIVES
To assess the benefits and harms of Radix Sophorae flavescentis versus other drugs or herbs in people with chronic hepatitis B.
SEARCH METHODS
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and seven other databases to December 2018. We also searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp), ClinicalTrials.gov (www.clinicaltrials.gov/), and the Chinese Clinical Trial Registry for ongoing or unpublished trials to December 2018.
SELECTION CRITERIA
We included randomised clinical trials, irrespective of publication status, language, or blinding, comparing Radix Sophorae flavescentis versus other drugs or herbs for people with chronic hepatitis B. In addition to chronic hepatitis B, participants could also have had cirrhosis, hepatocellular carcinoma, or any other concomitant disease. We excluded polyherbal blends containing Radix Sophorae flavescentis. We allowed cointerventions when the cointerventions were administered equally to all intervention groups.
DATA COLLECTION AND ANALYSIS
Review authors in pairs individually retrieved data from published reports and after correspondence with investigators. Our primary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our secondary outcomes were hepatitis B-related mortality, hepatitis B-related morbidity, and adverse events considered 'not to be serious'. We presented the meta-analysed results as risk ratios (RR) with 95% confidence intervals (CI). We assessed the risk of bias using domains with predefined definitions. We conducted Trial Sequential Analyses to control the risks of random errors. We used GRADE methodology to evaluate our certainty in the evidence (i.e. "the extent of our confidence that the estimates of the effect are correct or are adequate to support a particular decision or recommendation").
MAIN RESULTS
We included 10 randomised clinical trials with 898 participants. We judged all trials at high risk of bias. The trials covered oral capsules, intravenous infusion, intramuscular injection, and acupoint (a specifically chosen site of acupuncture) injection of Radix Sophorae flavescentis with a follow-up period from 1 to 12 months. The drugs being used as a comparator were lamivudine, adefovir, interferon, tiopronin, thymosin, or other Chinese herbs. Two trials included children up to 14 years old. Participants in one trial had cirrhosis in chronic hepatitis B. None of the trials reported all-cause mortality, health-related quality of life, serious adverse events, hepatitis B-related mortality, or morbidity. We are uncertain as to whether Radix Sophorae flavescentis has a beneficial or harmful effect on adverse events considered 'not to be serious' (RR 0.86, 95% CI 0.42 to 1.75; I = 0%; 2 trials, 163 participants; very low-certainty evidence), as well as if it decreases or increases the proportion of participants with detectable HBV-DNA (RR 1.14, 95% CI 0.81 to 1.63; I = 92%; 8 trials, 719 participants; very low-certainty evidence). Radix Sophorae flavescentis showed a reduction in the proportion of participants with detectable hepatitis B virus e-antigen (HBeAg) (RR 0.86, 95% CI 0.75 to 0.98; I = 43%; 7 trials, 588 participants; very low-certainty evidence).Two of the 10 trials were not funded, and one received academic funding. The remaining seven trials provided no information on funding.The randomisation process in another 109 trials was insufficiently reported to ensure the inclusion of any of these studies in our review.
AUTHORS' CONCLUSIONS
The included trials lacked data on all-cause mortality, health-related quality of life, serious adverse events, hepatitis-B related mortality, and hepatitis-B related morbidity. The evidence on the effect of Radix Sophorae flavescentis on the proportion of participants with adverse events considered 'not to be serious' and on the proportion of participants with detectable HBV-DNA is still unclear. We advise caution regarding the results of Radix Sophorae flavescentis showing a reduction in the proportion of people with detectable HBeAg because the trials were at high risk of bias, because it is a non-validated surrogate outcome, and because of the very low certainty in the evidence. As we were unable to obtain information on a large number of studies regarding their trial design, we were deterred from including them in our review. Undisclosed funding may have influence on trial results and lead to poor design of the trial. In view of the wide usage of Radix Sophorae flavescentis, we need large, unbiased, high-quality placebo-controlled randomised trials assessing patient-centred outcomes.
Topics: Adolescent; Adult; Antiviral Agents; Child; DNA, Viral; Female; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Plants, Medicinal; Randomized Controlled Trials as Topic; Sophora
PubMed: 31232459
DOI: 10.1002/14651858.CD013106.pub2 -
Medicine Aug 2020The purpose of this study was to evaluate the efficacy of different nucleos(t)ide analogues in the prognosis of HBV-related hepatocellular carcinoma (HCC) patients after... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
The purpose of this study was to evaluate the efficacy of different nucleos(t)ide analogues in the prognosis of HBV-related hepatocellular carcinoma (HCC) patients after curative treatment by network meta-analysis.
METHODS
Literature retrieval was conducted in globally recognized databases, namely, PubMed, EMBASE, Cochrane Library databases, and Science Citation Index Expanded, to address relative studies investigating nucleot(s)ide analogues for HBV-related HCC patients after curative resection. Relative parametric data, including 1-, 3-, and 5-year overall survival rate and 1-, 3-, and 5-year recurrence-free survival rate were quantitatively pooled and estimated. The inconsistency factor, the cumulative ranking curve, and the publication bias were evaluated.
RESULTS
Fourteen observational studies of 2481 adults performed between 2000 and 2019 were eligible. In terms of overall survival, ADV (Adefovir dipivoxil) (Odds ratio (OR): 2.35, 95% confidence interval (CI): 1.17-4.73), Lamivudine (OR: 2.08, 95% CI: 1.78-5.58), and Entecavir (OR: 2.14, 95% CI: 1.59-2.88) were found to be more beneficial than control group while ADV has the highest probability of having the most efficacious treatment (SCURA values 66.3) for 5-year overall survival. In late recurrence-free survival, ADV (OR = 1.88, 95% CI: 1.77-4.60), Entecavir (OR = 1.96, 95% CI: 1.36-2.55), and Lamivudine (OR = 1.73, 95% CI: 1.06-2.82) all had better significant prognosis than patients without antiviral therapy postoperatively and patients with ADV as postoperative antiviral therapy has significantly recurrence-free survival benefit at 5-year follow-up compared to those undertaking Entecavir (OR = 1.96, 95% CI: 1.52-7.38) and Lamivudine (OR = 1.39, 95% CI: 1.09-3.01). Moreover, the application of ADV possessed the highest possibility of having the best clinical effects on 1- (surface under the cumulative ranking probabilities (SUCRA), 64.7), 3- (SUCRA, 64.7), and 5-year (SUCRA, 70.4) recurrence survival rate for HBV-related HCC patients.
CONCLUSIONS
Patients with postoperative nucleos(t)ide analogues antiviral therapy had better survival benefit than those without antiviral therapy for HBV-related HCC patients after curative treatment. Additionally, nucleotide analogues like ADV and Tenofovir disoproxil fumarate has better impact on early and late recurrence-free survival of patients after curative treatment than those undertaking nucleoside analogues.
Topics: Antiviral Agents; Carcinoma, Hepatocellular; Hepatitis B; Hepatitis B virus; Humans; Liver Neoplasms; Network Meta-Analysis
PubMed: 32871973
DOI: 10.1097/MD.0000000000020877 -
Journal of Gastroenterology May 2020Nucleos(t)ide analogues (NAs) are the main drug category used in chronic hepatitis B (CHB) treatment. Despite the fact that NAs have a favourable safety profile,...
Nucleos(t)ide analogues (NAs) are the main drug category used in chronic hepatitis B (CHB) treatment. Despite the fact that NAs have a favourable safety profile, undesired adverse events (AEs) may occur during the treatment of CHB. Given the eminent number of patients currently receiving NAs, even a small risk of any of these toxicities can represent a major medical issue. The main objective of this review was to analyse information available on AEs associated with the use of NAs in published studies. We choose the following MesH terms for this systematic review: chronic hepatitis B, side effects and treatment. All articles published from 1 January 1990 up to 19 February 2018 in MEDLINE of PubMed, EMBASE, the Cochrane Library and LILACS databases were searched. A total of 120 articles were selected for analysis, comprising 6419 patients treated with lamivudine (LAM), 5947 with entecavir (ETV), 3566 with tenofovir disoproxil fumarate (TDF), 3096 with telbivudine (LdT), 1178 with adefovir dipivoxil (ADV) and 876 with tenofovir alafenamide (TAF). The most common AEs in all NAs assessed were abdominal pain/discomfort, nasopharyngitis/upper respiratory tract infections, fatigue, and headache. TAF displays the highest density of AEs per patient treated among NAs (1.14 AE/treated patient). In conclusion, treatment of CHB with NAs is safe, with a low incidence of AEs. Despite the general understanding TAF being safer than TDF, the number of patients treated with TAF still is too small in comparison to other NAs to consolidate an accurate safety profile. PROSPERO Registration No. CRD42018086471.
Topics: Antiviral Agents; Hepatitis B, Chronic; Humans; Nucleosides; Nucleotides
PubMed: 32185517
DOI: 10.1007/s00535-020-01680-0 -
Infectious Diseases (London, England) Feb 2018Women of childbearing age who have developed chronic hepatitis B (CHB) infection, especially HBeAg-positive highly viraemic pregnant women, are largely responsible for...
BACKGROUND
Women of childbearing age who have developed chronic hepatitis B (CHB) infection, especially HBeAg-positive highly viraemic pregnant women, are largely responsible for the familial transmission of the infection. Therefore, choosing the most effective and safest antiviral medications to manage pregnant CHB patients is of crucial importance.
MATERIALS AND METHODS
The PubMed and Scopus databases were searched through September 2017, for all the journal articles possessing original results regarding treatment of CHB pregnant women with any nucleos(t)ide analogue (NA) therapies, including lamivudine (LAM), adefovir (ADV), entecavir (ETV), telbivudine (LdT), and tenofovir (TDF).
RESULTS
After the primary search, 882 studies were recognized, and updating the searching results, 41 journal articles with original data were investigated, involving 3874 newborn infants from mothers with CHB, and their mothers completed follow-up until the delivery. The most important basic data and results regarding the efficacy of drugs, the rate of vertical transmission, safety issues associated with pairs of mothers and infants, median levels of HBV DNA, breastfeeding data, and rate of rate of vaccination success were collected. Moreover, possible key conclusion, recommendations, and learned lessons were discussed. Among the evaluated NAs, all LAM was efficient and safe. LdT was found to be very effective but had some safety concerns. In contrast, TDF had the advantages of both effectiveness and safety.
CONCLUSION
According to data in the literature, initiation of TDF at the trimester of pregnancy in combination with immunoprophylaxis to prevent mother-to-child transmission (MTCT) of CHB infection is strongly recommended as well as successful immunization of CHB pregnant women by anti-HBV vaccines.
Topics: Antiviral Agents; Female; Hepatitis B Vaccines; Hepatitis B virus; Hepatitis B, Chronic; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Nucleosides; Nucleotides; Pregnancy; Pregnancy Complications, Infectious; Safety; Treatment Outcome; Vaccination; Viral Load
PubMed: 29020844
DOI: 10.1080/23744235.2017.1384957 -
Microbial Pathogenesis Feb 2020Recent available treatment guidelines are pointing up clearance or seroconversion of hepatitis B e-antigen (HBeAg) as a valuable endpoint in treating HBeAg-positive... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND AND AIMS
Recent available treatment guidelines are pointing up clearance or seroconversion of hepatitis B e-antigen (HBeAg) as a valuable endpoint in treating HBeAg-positive chronic hepatitis B (CHB) patients. To evaluate the effect of combination therapy [interferon (IFN) plus nucleos(t)ide analogues (NAs)] versus IFN monotherapy on HBeAg seroconversion or seroclearance in HBeAg-positive CHB patients.
METHODS
All available controlled clinical studies, published from Jan 2000 to Sep 2018, with CHB receiving IFN and NA combination therapy or IFN monotherapy were included. Risk ratio (RR) and their 95% confidence intervals (CIs) was estimated with a fixed-effects model when I <50% for the test for heterogeneity. Publication bias was measured using Egger's test.
RESULTS
Twelve studies were included. Our meta-analysis demonstrated that IFN and NA combination therapy had a superior HBeAg seroconversion rate or clearance rate compared with IFN monotherapy at the end of treatment (EOT). Sub-analysis showed IFN plus adefovir dipivoxi (ADV) therapy had a better HBeAg seroconversion or seroclearance rate at EOT or at the end of follow-up (EOF).
CONCLUSION
Compared with IFN monotherapy, the combined therapy had a higher e-antigen serological response at EOT, but failed to improve the sustained response at EOF. Only combination therapy with IFN and ADV is superior to IFN monotherapy at the EOT or EOF for HBeAg seroconversion or seroclearance in HBeAg-positive CHB patients. The effect of other combination therapies is not superior to IFN monotherapy.
Topics: Antibodies, Viral; Antiviral Agents; Drug Therapy, Combination; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Interferon-alpha; Lamivudine; Nucleosides; Randomized Controlled Trials as Topic; Seroconversion; Tenofovir; Treatment Outcome
PubMed: 31816402
DOI: 10.1016/j.micpath.2019.103912