Molecular Tools for Guiding Therapy in Patients With Staphylococcal Bone and Joint Infections: A Diagnostic Test Accuracy Meta-analysis.

Background: Timely detection of causative pathogens and their antimicrobial resistance are essential for guiding targeted therapies in bone and joint infections (BJI) patients. We performed a systematic review and meta-analysis to assess the diagnostic value of testing osteoarticular samples with the nucleic acid amplification tests (NAAT) for effective staphylococcal strain identification and the administration of appropriately targeted antimicrobial agents in BJI patients. Methods: Five databases, including PubMed, Embase, Scopus, Web of Science, and the Cochrane Library, were searched for related publications from inception to July 24, 2021. Studies comparing the diagnostic accuracy of NAAT to a microbiological culture reference standard of osteoarticular specimens were eligible. Pooled summary values of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of NAAT compared to the microbiological culture reference standard were calculated using bivariate random-effects meta-analyses. Results: From 906 citations, 11 studies were included. Eleven studies comprising 13 datasets (n = 1047) evaluated NAAT accuracy for methicillin-sensitive Staphylococcus aureus (MSSA) identification, while seven studies comprising nine datasets (n = 727) evaluated methicillin-resistant Staphylococcus aureus (MRSA) identification. Against the microbiological culture reference standard, the pooled summary estimates for detection of both MSSA [sensitivity: 0.89 (95% confidence interval [CI] 0.84-0.93), specificity: 0.99 (95% CI 0.97-0.99), PLR: 34.13 (95% CI 20.54-56.73), NLR: 0.19 (95% CI 0.12-0.3), and DOR: 283.37 (95% CI 129.49-620.1)] and MRSA [sensitivity: 0.81 (95% CI 0.67-0.91), specificity: 1.0 (95% CI 0.99-1.0), PLR: 62.1 (95% CI 24.5-157.6), NLR: 0.33 (95% CI 0.16-0.69), and DOR: 300.25 (95% CI 85.01-1060.5)] were comparable. Heterogeneity was moderate. GeneXpert was frequently used among NAA tests, and its diagnostic accuracy was in line with the overall pooled summary estimates. The heterogeneity in diagnostic efficacy (P >0.05) could not be explained by a meta-regression and subgroup analysis of the research design, sample condition, and patient selection technique. Conclusions: Our study suggested that NAAT can be applied as the preferred prescreening test for the timely diagnosis of staphylococcal strains associated with BJI in osteoarticular samples for successful antimicrobial therapy.

Clinical relevance of molecular testing methods in the diagnosis and guidance of therapy in patients with staphylococcal empyema: a systematic review and meta-analysis.

Background: Efficient detection tools for determining staphylococcal pleural infection are critical for its eradication. The objective of this meta-analysis was to assess the diagnostic utility of nucleic acid amplification tests (NAAT) in suspected empyema cases to identify staphylococcal strains and avoid unnecessary empiric methicillin-resistant Staphylococcus aureus (MRSA) therapy. Methods: From inception to July 24, 2021, relevant records were retrieved from PubMed, Embase, Scopus, Web of Science, and the Cochrane Library. The quality of studies was determined using the QUADAS-2 tool. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and hierarchical summary receiver operating characteristic (HSROC) curve for NAAT's diagnostic performance were evaluated using an HSROC model. Results: Eight studies comprising 424 samples evaluated NAAT accuracy for Staphylococcus aureus (SA) identification, while four studies comprising 317 samples evaluated methicillin-resistant Staphylococcus aureus (MRSA) identification. The pooled NAAT summary estimates for detection of both SA (sensitivity: 0.35 (95% CI 0.19-0.55), specificity: 0.95 (95% CI 0.92-0.97), PLR: 7.92 (95% CI 4.98-12.59), NLR: 0.44 (95% CI 0.14-1.46), and DOR: 24.0 (95% CI 6.59-87.61) ) and MRSA (sensitivity: 0.45 (95% CI 0.15-0.78), specificity: 0.93 (95% CI 0.89-0.95), PLR: 10.06 (95% CI 1.49-67.69), NLR: 0.69 (95% CI 0.41-1.15), and DOR: 27.18 (95% CI 2.97-248.6) ) were comparable. The I2 statistical scores for MRSA and SA identification sensitivity were 13.7% and 74.9%, respectively, indicating mild to substantial heterogeneity. PCR was frequently used among NAA tests, and its diagnostic accuracy coincided well with the overall summary estimates. A meta-regression and subgroup analysis of country, setting, study design, patient selection, and sample condition could not explain the heterogeneity (meta-regression P = 0.66, P = 0.46, P = 0.98, P = 0.68, and P = 0.79, respectively) in diagnostic effectiveness. Conclusions: Our study suggested that the diagnostic accuracy of NAA tests is currently inadequate to substitute culture as a principal screening test. NAAT could be used in conjunction with microbiological culture due to the advantage of faster results and in situations where culture tests are not doable.

Clinical Relevance of Xpert MRSA/SA in Guiding Therapeutic Decisions for Staphylococcal Infections: A Diagnostic Test Accuracy Analysis.

INTRODUCTION: Rapid identification of the causal organism and antibiotic resistance is crucial for guiding targeted therapy in patients with suspected staphylococcal infection. A meta-analysis was carried out to evaluate the diagnostic relevance of Xpert™ MRSA/SA (Xpert) from clinical samples of various origins for limiting the use of unnecessary empirical methicillin-resistant Staphylococcus aureus (MRSA) therapy. METHODS: Five databases, including the Cochrane Library, Scopus, PubMed, Web of Science, and Embase, were comprehensively inspected from inception to October 12, 2021. The pooled summary estimates were evaluated using a bivariate random-effects model. RESULTS: Our inclusion criteria were met by 49 publications containing 68 datasets out of 735 citations. A total of 21 studies (n = 4996) examined the accuracy of Xpert in detecting methicillin-sensitive S. aureus (MSSA), while 47 studies (n = 45,430) examined the accuracy of Xpert in detecting MRSA. As compared to MRSA, Xpert's diagnostic performance for MSSA detection was markedly higher [sensitivity: 0.97 (0.96-0.98), specificity: 0.97 (0.97-0.98), area under curve (AUC): 0.99 (0.99-1.0)]. Xpert's pooled sensitivity and specificity differed marginally across sample types, including screening of colonization, lower respiratory tract (LRT), osteoarticular, and bloodstream samples. Notably, the Xpert pooled specificity was consistently ≥ 92% against microbiological culture across all sample types. The diagnostic efficiency heterogeneity was not explained by a meta-regression and subgroup analysis of research design, sample conditions, and sampling methods (P > 0.05). CONCLUSION: Our findings suggest that Xpert could be used as the favoured screening test for the early detection of staphylococcal infection in a variety of sample types, with the goal of guiding therapeutic decisions.

The relationship between NTCP gene varieties and the progress of liver disease after HBV infection: an updated systematic review and meta-analysis.

BACKGROUND: The aim of this study was to analyze the relationship between sodium taurocholate cotransporting polypeptide (NTCP) gene varieties and hepatitis B virus (HBV) infection and the progress of HBV-related liver disease. METHODS: PubMed, EMBASE, Web of Science and Cochrane library were used to search eligible studies. STATA software was performed to combine results. Pooled odds ratios (OR) was used to assess the potential genetic relationships. RESULTS: A total of 18 eligible case-control studies with 24960 cases and 28342 controls were included in this meta-analysis. The A allele of rs2296651 polymorphism was found to be significantly linked to a protection of HBV infection in the whole combined analysis (P = 0.000). Meanwhile, this allele was significantly associated with a decreased risk of hepatocellular carcinoma (HCC) (A vs. G: OR = 0.668, 95% CI: 0.571-0.782, P = 0.000), and was significantly associated with HBV nature clearance (A vs. G: OR = 0.744, 95% CI: 0.585-0.946, P = 0.016; AA+GA vs. GG: OR = 0.775, 95% CI: 0.613-0.980, P = 0.033; GA vs. GG: OR = 0.748, 95% CI: 0.588-0.952, P = 0.018). However, rs4646287 genetic varieties had no statistical differences in all models with HBV infection or HBV-related disease progress, liver cirrhosis, acute-on-chronic liver failure and HCC, as well as rs7154439, rs4646285, rs4646296. CONCLUSIONS: Rs2296651 polymorphism (A allele) may protect from HBV infection and the progress of HBV-related disease (HBV-related HCC). Future research about other single nucleotide polymorphisms (SNPs) (rs4646287, rs7154439, rs4646285, rs4646296) of NTCP may be needed to clarify the relationship of NTCP gene varieties with HBV infection and HBV-related disease.

Antiviral Therapy for Chronic HBV Infection With Persistently Normal Alanine Aminotransferase: Controversy and Consensus.

ALT is one of the most sensitive biochemical indexes to reflect liver injury. It is generally believed that hepatitis B virus (HBV) infected patients with normal ALT levels are in either immune tolerance or low replication stage of the natural history of hepatitis B, and there is no or only mild inflammation in liver tissue, so antiviral therapy is not recommended. However, chronic HBV-infected patients with normal ALT levels are not always in a stable state. A considerable number of patients will develop active hepatitis or occult progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Therefore, whether antiviral therapy should be recommended for chronic HBV infection with normal ALT level has been a hot topic in clinical practice. In this paper, the definition of immune tolerance, the relationship between ALT and liver inflammation, and the benefits of antiviral therapy were reviewed, and we hope it will be helpful for clinicians to have a deeper understanding of whether antiviral therapy should be considered for chronic HBV infection with normal ALT.

Clinical Utility of Molecular Tests for Guiding Therapeutic Decisions in Bloodstream Staphylococcal Infections: A Meta-Analysis.

Background: Treatment of bloodstream staphylococcal infections (BSI) necessitates the prompt initiation of appropriate antimicrobial agents and the rapid de-escalation of excessive broad-spectrum coverage to reduce the risk of mortality. We, therefore, aimed to demonstrate the diagnostic accuracy of nucleic acid amplification tests (NAAT) for the identification of methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) in clinically suspected patients. Methods: Until November 23, 2020, databases including PubMed, Scopus, Embase, and Web of Science were scanned for eligible studies. A bivariate random-effects model was used for meta-analysis of the 33 included studies obtained from 1606 citations, and pooled summary estimates with 95% confidence intervals (CI) were generated. Results: Twenty-three studies (n = 8,547) assessed NAAT accuracy for MSSA detection, while three studies (n = 479) evaluated MRSA detection in adults. The pooled NAAT sensitivity and specificity for MRSA in adults was higher [sensitivity: 0.83 (95% CI 0.59-0.96), specificity: 0.99 (95% CI 0.98-1.0)] as compared to MSSA [sensitivity: 0.76 (95% CI 0.69-0.82), specificity: 0.98 (95% CI 0.98-0.99)]. Similarly, eight studies (n = 4,089) investigating MSSA in pediatric population reported higher NAAT accuracy [sensitivity: 0.89 (95% CI 0.76-0.96), specificity: 0.98 (95% CI 0.97-0.98)] compared to adults. Among NAA tests, SeptiFast (real-time PCR, commercial) was frequently applied, and its diagnostic accuracy corresponded well to the overall summary estimates. A meta-regression and subgroup analysis of study design, sample condition, and patient selection method could not explain the heterogeneity (P > 0.05) in the diagnostic efficiency. Conclusions: NAAT could be applied as the preferred initial tests for timely diagnosis and BSI management.

The effect of CYP2C19 gene polymorphism on the eradication rate of Helicobacter pylori by proton pump inhibitors-containing regimens in Asian populations: a meta-analysis.

Premise: The effects of proton pump inhibitors (PPI) depend on metabolic enzyme CYP2C19 that has different activity due to gene polymorphism. The purpose of this meta-analysis is to determine the potential effects of CYP2C19 polymorphism on the efficiency of PPI-based treatment. Materials & methods: The PubMed, EMBASE, Cochrane Library, etc. were searched for relevant articles published in English or Chinese from inception to 31 May 2020. Finally, 26 randomized controlled trials and 15 cohort studies met the inclusion criteria and used for the meta-analysis via STATA version 15. Results: Poor metabolizer (PM) genotype Helicobacter pylori eradication rates were highest for Asian individuals receiving triple or quadruple first-line therapy based on PPIs (p < 0.05). CYP2C19 polymorphism could influence H. pylori eradication rate only in Mainland China and Japan (p < 0.05). Conclusion: PM genotype facilitates the elimination of H. pylori in Asian populations. Rabeprazole-, esomeprazole- and pantoprazole-based eradication program was less affected by the CYP2C19 polymorphism.

Accuracy of Molecular Amplification Assays for Diagnosis of Staphylococcal Pneumonia: a Systematic Review and Meta-analysis.

Rapid and accurate identification of staphylococcal pneumonia is crucial for effective antimicrobial stewardship. We performed a meta-analysis to evaluate the diagnostic value of nucleic acid amplification tests (NAAT) from lower respiratory tract (LRT) samples from suspected pneumonia patients to avoid superfluous empirical methicillin-resistant Staphylococcus aureus (MRSA) treatment. PubMed, Scopus, Embase, Web of Science, and the Cochrane Library Database were searched from inception to 2 September 2020. Data analysis was carried out using a bivariate random-effects model to estimate pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Of 1,808 citations, 24 publications comprising 32 data sets met our inclusion criteria. Twenty-two studies (n = 4,630) assessed the accuracy of the NAAT for methicillin-sensitive S. aureus (MSSA) detection, while 10 studies (n = 2,996) demonstrated the accuracy of the NAAT for MRSA detection. The pooled NAAT sensitivity and specificity (with 95% confidence interval [CI]) for all MSSA detection were higher (sensitivity of 0.91 [95% CI, 0.89 to 0.94], specificity of 0.94 [95% CI, 0.94 to 0.95]) than those of MRSA (sensitivity of 0.75 [95% CI, 0.69 to 0.80], specificity of 0.88 [95% CI, 0.86 to 0.89]) in lower respiratory tract (LRT) samples. NAAT pooled sensitivities differed marginally among different LRT samples, including sputum, endotracheal aspirate (ETA), and bronchoalveolar lavage (BAL) fluid. Noticeably, NAAT pooled specificity against microbiological culture was consistently ≥88% across various types of LRT samples. A meta-regression and subgroup analysis of study design, sample condition, and patient selection method could not explain the heterogeneity (P > 0.05) in the diagnostic efficiency. This meta-analysis has demonstrated that the NAAT can be applied as the preferred initial test for timely diagnosis of staphylococcal pneumonia in LRT samples for successful antimicrobial therapy.

Association of IL-6, IL-10 and TGF-ß1 gene polymorphisms with brucellosis: A systematic review with meta-analysis.

BACKGROUND: Brucellosis is one of the major public health problems worldwide. Several current studies have provided data that polymorphisms in the interleukin-6 (IL-6), interleukin-10 (IL-10) and transforming growth factor beta1(TGF-ß1) gene were associated with the susceptibility to human brucellosis, but the results remain inconsistent. OBJECTIVES: The aim of present study was to investigate the relationship between IL-6 (-174 G/C), IL-10 (-1082 A/G, -819C/T) and TGF-ß1 (codon 10, codon 25) gene polymorphisms and brucellosis. METHODS: We performed a comprehensive search of the PubMed, EMBASE, Web of Science, OVID-EBMR, and the Cochrane Library up to Oct. 30, 2018. The search was designed using the following key words: "brucellosis" or" "brucella melitensis", "IL-10" or "interleukin10" or "interleukin-10", "IL-6" or "interleukin6" or "interleukin-6", "TGF-ß1" or "TGF-beta1" or "transforming growth factor ß1", "polymorphism" and "single nucleotide polymorphism (SNP)". Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of association between TGF-ß1, IL-10 and IL-6 polymorphisms and brucellosis risk. All the statistical analyses were conducted by Review manager 5.3 software. RESULTS: A total of 8 studies involving 1308 cases and 902 controls met the inclusion criteria for IL-6, IL-10, TGF-ß1 polymorphisms and brucellosis risk. There was a slightly trend of increasing risk of brucellosis in individuals with the G allele compared with individuals with the C allele (OR = 1.07, 95% CI: 0.85-1.33, P = 0.57) in IL-6 polymorphism. However, statistical analysis showed that these differences are not significant. Our results suggested TGF-ß1 (codon 25 G/C) GG genotype may be considered as a risk factor for brucellosis (OR = 1.67, 95% CI: 1.12-2.50, P = 0.01). Herein, we failed to find any significant association between IL-10 (-1082 A/G, -819C/T), TGF-ß1 (codon 10C/T) gene polymorphism and susceptibility to brucellosis in all gene models. CONCLUSION: IL-6 (-174 G/C), IL-10 (-1082 A/G, -819C/T), and TGF-ß1 (codon 10C/T) polymorphisms is not a risk factor for brucellosis infection. TGF-ß1 codon 25 GG genotype may be considered as a risk factor for brucellosis.

The efficacy of lamivudine prophylaxis against hepatitis B reactivation in breast cancer patients undergoing chemotherapy: a meta-analysis.

BACKGROUND/PURPOSE: Lamivudine has been recommended as prophylaxis for the reactivation of hepatitis B virus (HBV) infection in patients undergoing chemotherapy. However, information on breast cancer patients in particular has been lacking. The purpose of this meta-analysis was to assess the overall efficacy of lamivudine prophylaxis compared to untreated patients with hepatitis B S-antigen (HBsAg) seropositive breast cancer who had undergone chemotherapy. METHODS: Studies that compared the efficacy of treatment with lamivudine prophylaxis versus no prophylaxis in HBsAg seropositive breast cancer patients were identified through Medline, Cochrane, and Embase databases. RESULTS: Six studies involving 499 patients were analyzed. The rates of HBV reactivation in patients with lamivudine prophylaxis were significantly lower than those with no prophylaxis (risk ratio [RR] = 0.23, 95% confidence interval [CI]: 0.13-0.39, p < 0.00001). Patients given lamivudine prophylaxis had significant reductions in the rates of hepatitis attributable to HBV compared with those not given treatment (RR = 0.20, 95% CI: 0.08-0.47, p = 0.002). The rates of moderate and severe hepatitis in patients with lamivudine prophylaxis were significantly lower compared with those patients who had not received prophylaxis (RR = 0.25, 95% CI: 0.10-0.62, p < 0.003; RR = 0.25, 95% CI: 0.10-0.59, p = 0.002). Patients given lamivudine prophylaxis had significantly fewer disruptions of chemotherapy (RR = 0.36, 95% CI: 0.21-0.64, p = 0.0004). There was no significant heterogeneity in the comparisons. CONCLUSION: Lamivudine prophylaxis in HBsAg seropositive breast cancer patients undergoing chemotherapy is effective in reducing HBV reactivation and HBV-associated morbidity and mortality.

The association between CYP2E1 polymorphisms and hepatotoxicity due to anti-tuberculosis drugs: a meta-analysis.

BACKGROUND: Although there have been previous studies on the potential association between cytochrome P450 2E1 (CYP2E1) polymorphisms and the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH), the results have generally been controversial. METHODS: We searched Medline/PubMed, EMBASE, Web of Science, and the Cochrane Library using the following key words: cytochrome P450 2E1, CYP2E1, polymorphism, tuberculosis and TB. The strength of the association between the CYP2E1 PstI/RsaI and DraI polymorphism and ATDH risk as measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied. RESULTS: Compared with the wild genotype (c1/c1), the OR of ATDH was 1.41 (95% CI: 1.1-1.82, P=0.007) for the PstI/RsaI polymorphism, and 0.78 (95% CI: 0.51-1.18, P=0.23) for the DraI polymorphism. Compared with individuals with N-acetyltransferase 2 (NAT2) fast or intermediate acetylator genotype and c1/c1 genotype patients who were NAT2 slow acetylators and carried the high activity CYP2E1 c1/c1 genotype had higher risk for ATDH (OR=3.10, P<0.0001). CONCLUSION: The present meta-analysis indicates that the CYP2E1 c1/c1 genotype may be a risk factor for ATDH, and the concomitant presence of the slow acetylator NAT2 genotype may further increase this risk.

Measures to reduce mother-to-child transmission of Hepatitis B virus in China: a meta-analysis.

BACKGROUND: Mother-to-child transmission (MTCT) is the main mode of spread of hepatitis B virus (HBV) in China. We performed a meta-analysis to compare the effects of three measures for prevention of MTCT. METHODS: A meta-analysis was performed on randomized controlled trials and non-randomized studies comparing the index of MTCT among five groups of pregnant women: hepatitis B immunoglobulin (HBIG) administration, antiviral treatment, placebo, elective caesarean section, and vaginal delivery. RESULTS: Compared with the control group, the incidence of HBV intrauterine infection (RR = 0.42, 95 % CI 0.27-0.64, P < 0.0001) and the number of chronic hepatitis B (CHB) infants (RR = 0.44, 95 % CI 0.32-0.61, P < 0.00001) were lower in the HBIG administration group. In the antiviral treatment group, serum HBV DNA levels were lower (MD = -4.01, 95 % CI -5.07 to -2.94, P < 0.00001) at the time of delivery, and normalization of ALT levels was better (RR = 1.11, 95 % CI 1.06-1.17, P < 0.0001). Infant serum HBsAg positivity (RR = 0.45, 95 % CI 0.22-0.91, P = 0.03) and incidence of infant HBV transmission RR = 0.06, 95 % CI 0.01-0.24, P < 0.0001) were reduced in antiviral the treatment group. Infant serum anti-HBs positivity at birth (RR = 1.24, 95 % CI 0.89-1.74, P = 0.2) or at 6-7 months (RR = 0.98, 95 % CI 0.86-1.11, P = 0.73) was not significantly different between the caesarean section and vaginal delivery groups. The incidence of infant CHB infection may have been higher in the vaginal delivery group (RR = 2.20, 95 % CI 1.02-4.74, P = 0.04). CONCLUSIONS: Administration of HBIG or antiviral therapy to HBV carrier mothers during pregnancy is effective in reducing MTCT.

Efficacy of telbivudine on interruption of hepatitis B virus vertical transmission: a meta-analysis.

BACKGROUND AND OBJECTIVES: Hepatitis B virus (HBV) infection is one of the most common infections in the world. Vertical transmission is the main reason for the continued endemic infection rates, at least in Asia. This study aimed to investigate the efficacy of telbivudine on mother-to-child transmission (MTCT) interruption. METHODS: Studies up to April 2012 were collected by searching Pubmed, EMBASE, the Cochrane Library, EBM Review, WangFang Database and China National Knowledge Infrastructure. Serum hepatitis B surface antigen (HBsAg) and HBV DNA in newborns and infants, maternal HBV DNA negative conversion and alanine trans.aminase (ALT) normalization and adverse events were analyzed. RESULTS: Seven clinical trials involving 644 pregnant women were included in this meta-analysis. Telbivudine resulted in lower HBsAg and HBV DNA seroprevalence in newborns and infants. When maternal viral load prior to delivery was higher than 103copies/mL, HBsAg or HBV DNA positivity had no statistical difference. CONCLUSIONS: Telbivudine treatment has efficacy and safety on MTCT interruption during late pregnancy. In addition, we demonstrated benefit of telbivudine for mothers in terms of HBV DNA negative conversion and ALT normalization. Telbivudine treatment at the end of pregnancy should be considered in women with high viral load.

The influence of hepatitis B virus on antiviral treatment with interferon and ribavirin in Asian patients with hepatitis C virus/hepatitis B virus coinfection: a meta-analysis.

BACKGROUND: Clinical and laboratory studies have indicated that coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) can suppress one another, eliciting a dominant disease phenotype. To assess whether HBV can influence the antiviral effect of treatment on HCV, we performed a meta-analysis to comparatively analyze the response to interferon plus ribavirin treatment in patients with HBV/HCV coinfection and HCV mono-infection. METHODS: Published studies in the English-language medical literature that involved cohorts of HBV/HCV coinfection and HCV mono-infection were obtained by searching Medline, Cochrane and Embase databases. Studies that compared the efficacy of treatment with interferon plus ribavirin in HBV/HCV coinfection and HCV mono-infection were assessed. End-of-treatment virological response (ETVR), sustained virological response (SVR), HCV relapse rate, and alanine aminotransferase (ALT) normalization rate were compared between HBV/HCV coinfection and HCV mono-infection patients. RESULTS: Five trials involving 705 patients were analyzed. At the end of follow-up serum ALT normalization rates in patients with HCV mono-infection were significantly higher than in patients with HBV/HCV coinfection (odds ratio (OR) = 0.56, 95% confidence interval (CI): 0.40-0.80, P = 0.001). The ETVR and SVR achieved in HBV/HCV coinfection patients were comparable to those in HCV mono-infection patients (OR = 1.03, 95% CI: 0.37-2.82, P = 0.96 and OR = 0.87, 95% CI: 0.62-1.21, P = 0.38, respectively). The rate of relapse for HCV or HCV genotype 1 was not significantly different between HBV/HCV coinfection patients and HCV mono-infection patients (OR = 1.55, 95% CI: 0.98-2.47, P = 0.06; HCV genotype 1: OR = 2.4, 95% CI: 1.17-4.91, P = 0.19). CONCLUSIONS: Treatment with interferon and ribavirin achieves similar ETVR and SVR in HBV/HCV coinfection and HCV mono-infection. HBV/HCV coinfection patients had distinctively lower end of follow-up serum ALT normalization.

Association between serum platelet-derived growth factor BB and degree of liver damage, fibrosis and hepatitis B e antigen (HBeAg) status in CHB patients.

BACKGROUND/AIMS: The objective of this study was to determine the association of PDGF-BB with degree of liver damage, fibrosis and HBeAg status in CHB patients. METHODOLOGY: A total of 740 patients with previously untreated chronic hepatitis B were included in the study. We conducted the correlations analysis of se-rum PDGF-BB with the age, gender, medical history, se-rum HBV-DNA, liver function parameters and serum fibrosis markers (HA, PCIII, CIV, LN), analyzed the cor-relations of degree of liver damage with liver fibrosis markers and the serum levels of PDGF-BB and compared serum liver fibrosis markers and levels of PDGF- BB between HbeAg-negative and HbeAg-positive CHB patients. RESULTS: Liver function parameters and se-rum liver fibrosis markers were significantly correlated with serum PDGF-BB (p<0.01). Liver fibrosis markers and serum levels of PDGF-BB in CHB were positive correlated with degree of liver damage. Serum levels of PDGF-BB in HBeAg-negative CHB was significantly higher than that in the HBeAg-positive CHB (p<0.05). CONCLUSIONS: Serum levels of PDGF-BB can reflect degree of liver damage and degree of liver fibrosis in CHB.Serum levels of PDGF-BB in HBeAg-negative CHB were higher than the HBeAg-positive CHB.

Lamivudine plus adefovir combination therapy versus entecavir monotherapy for lamivudine-resistant chronic hepatitis B: a systematic review and meta-analysis.

BACKGROUND: Chronic hepatitis B virus (HBV) infection represents a serious global health problem and resistance to lamivudine (LAM) has become a serious clinical challenge. Previous rescue therapy for the treatment of chronic LAM-resistant hepatitis B infected patients included switching to entecavir (ETV) and adding adefovir (ADV) or tenofovir (TFV). At present, switching to ETV is not recommended for rescue therapy for LAM-resistant chronic hepatitis B (CHB). The aim of this report was to determine whether add-on ADV was a superior rescue strategy in the treatment of CHB patients with LAM resistance. METHODS: We searched Medline/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library. Relative risks (RRs) of virologic response, virologic breakthrough, normalization of serum alanine aminotransferase (ALT) levels and HBeAg seroconversion rates were studied. Factors predicting virologic response, standardized mean differences (SMD) in HBV DNA levels and safety were reviewed. RESULTS: Six eligible trials (451 patients in total) were included in the analysis. The rate of virologic breakthrough in the ETV group was higher than that in the LAM plus ADV group. There were no statistical differences in virologic response, ALT normalization and HBeAg seroconversion in either group 48 weeks post treatment. LAM plus ADV combination therapy produced faster and greater HBV DNA reduction rates 24 weeks post therapy compared to ETV monotherapy. HBV DNA baseline levels and the initial virologic response (IVR) were predictive of the virologic response. Additionally, combination therapy or monotherapy were both well tolerated. CONCLUSIONS: LAM plus ADV combination therapy was more effective and produced longer-lasting effects than switching to ETV monotherapy in treating CHB patients with LAM resistance. However, considering the practical benefits and limitations of ADV, individualized therapy will be needed in patients with prior history of LAM resistant infections.

Chronic hepatitis B serum promotes apoptotic damage in human renal tubular cells.

AIM: To investigate the effect of the serum of patients with chronic hepatitis B (CHB) on apoptosis of renal tubular epithelial cells in vitro and to study the role of hepatitis B virus (HBV) and transforming growth factor-beta (1) (TGF-beta (1)) in the pathogenesis of hepatitis B virus associated glomerulonephritis (HBV-GN). METHODS: The levels of serum TGF-beta(1) were measured by specific enzyme linked immunosorbent assay (ELISA) and HBV DNA was tested by polymerase chain reaction (PCR) in 44 patients with CHB ,and 20 healthy persons as the control. The normal human kidney proximal tubular cell (HK-2) was cultured together with the sera of healthy persons, CHB patients with HBV-DNA negative (20 cases) and HBV-DNA positive (24 cases) for up to 72 h. Apoptosis and Fas expression of the HK-2 were detected by flow cytometer. RESULTS: The apoptosis rate and Fas expression of HK-2 cells were significantly higher in HBV DNA positive serum group 19.01%+/-5.85% and 17.58%+/-8.35%, HBV DNA negative serum group 8.12%+/-2.80% and 6.96%+/-2.76% than those in control group 4.25%+/-0.65% and 2.33%+/-1.09%, respectively (P<0.01). The apoptosis rate and Fas expression of HK-2 in HBV DNA positive serum group was significantly higher than those in HBV DNA negative serum (P<0.01). Apoptosis rate of HK-2 cells in HBV DNA positive serum group was positively correlated with the level of HBV-DNA (r = 0.657). The level of serum TGF-beta (1) in CHB group was 163.05+/-91.35 microg/L, significantly higher as compared with 81.40+/-40.75 microg/L in the control group (P<0.01). CONCLUSION: The serum of patients with chronic hepatitis B promotes apoptotic damage in human renal tubular cells by triggering a pathway of Fas up-regulation. HBV and TGF-beta (1) may play important roles in the mechanism of hepatitis B virus associated glomerulonephritis.