Prediction of a Competing Endogenous RNA Co-expression Network by Comprehensive Methods in Systemic Sclerosis-Related Interstitial Lung Disease.

Systemic sclerosis (SSc) is an immune-mediated connective tissue disease characterized by fibrosis of multi-organs, and SSc-related interstitial lung disease (SSc-ILD) is a leading cause of morbidity and mortality. To explore molecular biological mechanisms of SSc-ILD, we constructed a competing endogenous RNA (ceRNA) network for prediction. Expression profiling data were obtained from the Gene Expression Omnibus (GEO) database, and differential expressed mRNAs and miRNAs analysis was further conducted between normal lung tissue and SSc lung tissue. Also, the interactions of miRNA-lncRNA, miRNA-mRNA, and lncRNA-mRNA were predicted by online databases including starBase, LncBase, miRTarBase, and LncACTdb. The ceRNA network containing 11 lncRNAs, 7 miRNAs, and 20 mRNAs were constructed. Based on hub genes and miRNAs identified by weighted correlation network analysis (WGCNA) method, three core sub-networks-SNHG16, LIN01128, RP11-834C11.4(LINC02381)/hsa-let-7f-5p/IL6, LINC01128/has-miR-21-5p/PTX3, and LINC00665/hsa-miR-155-5p/PLS1-were obtained. Combined with previous studies and enrichment analyses, the lncRNA-mediated network affected LPS-induced inflammatory and immune processes, fibrosis development, and tumor microenvironment variations. The ceRNA network, especially three core sub-networks, may be served as early biomarkers and potential targets for SSc, which also provides further insights into the occurrence, progression, and accurate treatment of SSc at the molecular level.

Insulin-like growth factor binding protein 7 as a candidate biomarker for systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease clinically characterised by skin and internal organs fibrosis with high mortality. However, the pathogenesis of SSc is still controversial and the effect of the current treatment is far from satisfactory. We aimed to find out novel candidate genes related to the pathological process in SSc. METHODS: In this study, the weighted correlation network analysis (WGCNA) was conducted to identify the key module and hub genes most related to SSc in GSE58095, a microarray dataset from the Gene Expression Omnibus (GEO) database. Also, the key module was analysed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then we validated hub genes in other datasets (GSE32413, GSE125362, GSE45485, GSE76885, GSE95065). The serum of 37 patients with SSc and 25 healthy control subjects (HCs) were recruited and detected by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Five interested genes (IGFBP7, LRRC32, STMN2, C1QTNF5, CPXM1) were up-regulated in SSc microarray datasets from the GEO. And the level of serum IGFBP7, which encodes a secreted protein, was upregulated in SSc patients-also in dcSSc patients and SSc with ILD patients. CONCLUSIONS: Among the five interested genes, the IGFBP7 was a novel candidate gene for SSc and may be served as potential target and early biomarker for accurate treatment, which also provides further insights into the pathogenesis of SSc at the molecular level.

The m6A reader protein YTHDC2 is a potential biomarker and associated with immune infiltration in head and neck squamous cell carcinoma.

BACKGROUND: Increasing evidence has shown that N6-methyladenosine (m6A) RNA methylation regulators have important biological functions in human cancers. However, there are few studies on the value of m6A reader protein YTHDC2 in the diagnosis and tumor-infiltrating of head and neck squamous cell carcinoma (HNSCC). Therefore, it is important to understand the potential clinical value of YTHDC2 in the prognosis and immune infiltration of HNSCC. METHODS: In this study, gene expression profiles and the corresponding clinical information of 270 HNSCC patients were downloaded from the Gene Expression Omnibus (GEO) database. The gene co-expression network was established to verify whether YTHDC2 was related to the prognosis of HNSCC and verified again in the public database. The correlations between YTHDC2 and immune infiltration was investigated via Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). RESULTS: The results showed that YTHDC2 appeared in the blue module related to survival time and survival state and had a close correlation with the prognosis and immune infiltration level of HNSCC in public database. Patients with low expression of YTHDC2 had poor overall survival (OS) and recurrence-free survival (RFS) than those with high expression. In addition, the expression of YTHDC2 was positively correlated with the level of CD4+ T cell subpopulations infiltration in HNSCC. CONCLUSIONS: Through this study, we found that YTHDC2 is a tumor suppressor gene with high expression in normal tissues and low expression in tumor tissues. In addition, YTHDC2 is correlated with the immune infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells in HNSCC, which may become a potential marker for prognosis and immune infiltration of HNSCC.

Application of weighted gene co-expression network analysis to reveal key modules and hub genes in generalized aggressive periodontitis.

OBJECTIVE: The aim of this study was to construct a gene co-expression network to identify key modules and genes in people with generalized aggressive periodontitis. METHODS: We used database GSE79705 to construct a co-expression network by weighted gene co-expression network analysis (WGCNA). In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted. RESULTS: A total of 51 co-expression modules were conducted, darkseagreen1 and blue1 modules were the most significantly related to generalized aggressive periodontitis. Genes in the darkseagreen1 module enriched in affecting cellular response to tumor necrosis factor and vascular endothelial growth factor production, and the blue1 module enriched in the regulation of ion transport, proteinaceous extracellular matrix and neuropeptide binding. Besides, we found that 4 hub genes (SNRPG, MRPL22, MRPS18C and CEP290) played an important role in the occurrence of generalized aggressive periodontitis. CONCLUSION: Through this study, we identified two modules and four hub genes associated with generalized aggressive periodontitis. Besides, 4 hub genes (SNRPG, MRPL22, MRPS18C and CEP290) can be expected to trigger new therapeutic drug development for generalized aggressive periodontitis.

Identification and Validation of Key Genes Associated With Systemic Sclerosis-Related Pulmonary Hypertension.

Systemic sclerosis-associated with pulmonary arterial hypertension (SSc-PAH) is still a major cause of SSc related deaths. Early diagnosis and prompt treatment are crucial to reduce the mortality of patients with SSc-PAH. To screen the candidate biomarkers and potential therapeutic targets for SSc-PAH, we analyzed the data set (GSE33463 and GSE19617) for confirming key genes in peripheral blood mononuclear cells from SSc-PAH patients. A total of 105 SSc patients from gene expression omnibus (GEO) were included as discovery cohort (n = 69) and duplication cohort (n = 36) for screening hub genes by weighted gene co-expression network analysis (WGCNA). Furthermore, an independent validation cohort (n = 40), including healthy controls, SSc and SSc-PAH patients, was used for further validation by quantitative real-time polymerase chain reaction. The results showed that four key genes, including IFIT2, IFIT3, RSAD2, and PARP14, may serve as potential biomarkers in SSc-PAH. Also, they could be independent risk factors for SSc-PAH. In conclusion, the four key genes can be expected to become the potential therapeutic targets and early biomarkers for accurate therapy and diagnosis of SSc-PAH in the future, which also provides promising insights into the pathogenesis of SSc-PAH at the molecular level.

Increased serum calpain activity is associated with HMGB1 levels in systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) or scleroderma is an intractable autoimmune disorder that affects multiple organs. The objectives were to investigate clinical correlations of serum calpain activity and high mobility group box 1 (HMGB1) levels with immunological and clinical traits. METHODS: A total of 31 patients with SSc, 20 age- and gender-matched healthy control subjects (HC), and 10 patients with other connective tissue diseases (CTD) were recruited in the study. We measured serum calpain activity and HMGB1 levels and analyzed the datasets (GSE40839, GSE48149, GSE76808, GSE81292, GSE33463, and GSE58095) from Gene Expression Omnibus (GEO) database to explore the potential mechanism by which calpain exerts its function through bioinformatics methods. RESULTS: Serum calpain activity was significantly increased in patients with SSc compared with those in HC and in patients with CTD and was correlated with serum HMGB1 levels, modified Rodnan skin score, erythrocyte sedimentation rate, mean platelet volume, and plateletcrit. Notably, serum calpain activity and HMGB1 levels in SSc patients with interstitial lung disease (ILD) were significantly higher than those in SSc patients without ILD. Serum calpain activity and HMGB1 levels could be the independent risk factors for SSc-ILD and novel biomarkers in patients with SSc. CONCLUSION: This is the first study that reports increased serum calpain activity and the correlation between calpain and HMGB1 in patients with SSc or SSc-ILD. The serum calpain activity and HMGB1 levels may serve as measures of ILD in patients with SSc. Also, calpain and HMGB1 could be potential therapeutic targets for patients with SSc or SSc-ILD in the future.

Comparative efficacy and safety of immunosuppressive therapies for systemic sclerosis related interstitial lung disease: A Bayesian network analysis.

Objectives: Immunosuppressive therapies for the treatment of patients with systemic sclerosis (SSc) and SSc related interstitial lung diseases (SSc-ILD) include cyclophosphamide (CYC), mycophenolate mofetil (MMF), azathioprine (AZA) and methotrexate (MTX). The objectives were to compare and rank these therapies in term of forced vital capacity (FVC) % predicted, diffusing capacity of the lung for carbon monoxide (DLco) % predicted and adverse events (AEs).Methods: We present pooled estimates of mean difference (MD) and odds rates (ORs) with 95% confidence intervals (CIs) among different therapies. We also ranked these agents with surface under the cumulative ranking probability (SUCRA).Results: CYC plus AZA had the highest SUCRA probability (70%) on reducing risk of the deterioration of FVC compared with CYC, observation (OBS), MMF and AZA. While for the prevention of the deterioration of DLco, MMF showed the highest SUCRA probability (76%) compared with others. Moreover, AZA showed the lowest probability (32%) for AEs among active interventions.Conclusions: CYC plus AZA was the preferred immunosuppressive strategies compared to others on preventing the deterioration of FVC. MMF resulted with the highest probability as the best in preventing the deterioration of DLco. Monotherapy of AZA was less pulmonary function benefit but related less AEs.

MetS Risk Score: A Clear Scoring Model to Predict a 3-Year Risk for Metabolic Syndrome.

Although several risk factors for metabolic syndrome (MetS) have been reported, there are few clinical scores that predict its incidence. Therefore, we created and validated a risk score for prediction of 3-year risk for MetS. Three-year follow-up data of 4395 initially MetS-free subjects, enrolled for an annual physical examination from Wenzhou Medical Center were analyzed. Subjects at enrollment were randomly divided into the training and the validation cohort. Univariate and multivariate logistic regression models were employed for model development. The selected variables were assigned an integer or half-integer risk score proportional to the estimated coefficient from the logistic model. Risk scores were tested in a validation cohort. The predictive performance of the model was tested by computing the area under the receiver operating characteristic curve (AUROC). Four independent predictors were chosen to construct the MetS risk score, including BMI (HR=1.906, 95% CI: 1.040-1.155), FPG (HR=1.507, 95% CI: 1.305-1.741), DBP (HR=1.061, 95% CI: 1.002-1.031), HDL-C (HR=0.539, 95% CI: 0.303-0.959). The model was created as -1.5 to 4 points, which demonstrated a considerable discrimination both in the training cohort (AUROC=0.674) and validation cohort (AUROC=0.690). Comparison of the observed with the estimated incidence of MetS revealed satisfactory precision. We developed and validated the MetS risk score with 4 risk factors to predict 3-year risk of MetS, useful for assessing the individual risk for MetS in medical practice.

NAFL screening score: A basic score identifying ultrasound-diagnosed non-alcoholic fatty liver.

BACKGROUND: Several non-invasive diagnostic scores for non-alcoholic fatty liver (NAFL) have been developed, but the clinical application is limited because of their complexity. AIM: To develop and validate an easy-to-calculate scoring system to identify ultrasound-diagnosed NAFL. METHODS: 48,489 patients from 2 centers were included in this study. Multivariable logistic regression models were employed for model development. Ultrasonography was applied to diagnose NAFL. The selected variables were assigned an integer score proportional to the estimated coefficient from the logistic regression analysis, namely NAFL Screening Score (NSS). The ability of the NSS to identify NAFL was assessed by analyzing the area under the receiver operating characteristic curve (AUROC) and was tested in an independent validation cohort. Additionally, the performance of NSS was compared with existing models. RESULTS: NSS was developed as a basic score comprising of age, body mass index (BMI), triglyceride (TG), ALT/AST, fasting plasma glucose (FPG) and uric acid (UA) in both sexes. NSS showed a relatively good discriminative power (AUROC=0.825 for males, 0.861 for females in the validation cohort) in comparison with other models. The optimal cut-off point was 32 for males and 29 for females. CONCLUSION: We developed and validated NSS, an easy-to-use score sheet identify ultrasound-diagnosed NAFL. NSS may be clinically useful for initial diagnosing NAFL.

Development of a prognostic nomogram for cirrhotic patients with upper gastrointestinal bleeding.

BACKGROUND AND AIM: Upper gastrointestinal bleeding (UGIB) is a complication with a high mortality rate in critically ill patients presenting with cirrhosis. Today, there exist few accurate scoring models specifically designed for mortality risk assessment in critically ill cirrhotic patients with upper gastrointestinal bleeding (CICGIB). Our aim was to develop and evaluate a novel nomogram-based model specific for CICGIB. PATIENTS AND METHODS: Overall, 540 consecutive CICGIB patients were enrolled. On the basis of Cox regression analyses, the nomogram was constructed to estimate the probability of 30-day, 90-day, 270-day, and 1-year survival. An upper gastrointestinal bleeding-chronic liver failure-sequential organ failure assessment (UGIB-CLIF-SOFA) score was derived from the nomogram. Performance assessment and internal validation of the model were performed using Harrell's concordance index (C-index), calibration plot, and bootstrap sample procedures. UGIB-CLIF-SOFA was also compared with other prognostic models, such as CLIF-SOFA and model for end-stage liver disease, using C-indices. RESULTS: Eight independent factors derived from Cox analysis (including bilirubin, creatinine, international normalized ratio, sodium, albumin, mean artery pressure, vasopressin used, and hematocrit decrease>10%) were assembled into the nomogram and the UGIB-CLIF-SOFA score. The calibration plots showed optimal agreement between nomogram prediction and actual observation. The C-index of the nomogram using bootstrap (0.729; 95% confidence interval: 0.689-0.766) was higher than that of the other models for predicting survival of CICGIB. CONCLUSION: We have developed and internally validated a novel nomogram and an easy-to-use scoring system that accurately predicts the mortality probability of CICGIB on the basis of eight easy-to-obtain parameters. External validation is now warranted in future clinical studies.

Comparative efficacy of vasoconstrictor therapies for type 1 hepatorenal syndrome: a network meta-analysis.

INTRODUCTION: The outcome of a comparative efficacy and safety of vasoconstrictor therapies for treatment of patients with type 1 hepatorenal syndrome (HRS-1) remain inconclusive. Areas covered: We searched literature databases for randomized controlled trials (RCTs) until 31 January 2016, and included ten eligible RCTs. In conclusion, terlipressin was the most efficacious vasoconstrictor drug for HRS-1, but had a higher probability of causing AEs. Norepinephrine was an attractive alternative to terlipressin and associated with less AEs. Expert commentary: To date, most previous traditional meta-analyses included trials with a limited population and compared terlipressin alone or with albumin against no intervention or albumin. Since different HRS types have different diagnoses and show different responses to vasoconstrictors, it may be questionable to combine data from patients with type 1 and type 2 HRS, which has been reported for most previous meta-analyses. Thus, performing a high-quality network meta-analysis of the existing literature is a valuable way to interrogate published data and to draw conclusions which may inform on the best interventional strategy.

Stratified Platelet-to-lymphocyte Ratio: A Novel Target for Prognostic Prediction of Hepatocellular Carcinoma after Curative Liver Resection.

Background and Aims: Platelet-to-lymphocyte ratio (PLR) has been shown to predict prognosis of cancers. We aimed to evaluate the prognostic value of stratification of PLR in patients after curative liver resection (CLR) for hepatocellular carcinoma (HCC). Methods: A total of 1804 patients who underwent CLR for suspected HCC between January 2007 and January 2014 were screened for the study. All of the patients were categorized into equal tertiles according to the number of patients and the distribution of PLR. Prognostic significance was determined for overall survival (OS) and was assessed using Kaplan-Meier analysis. Univariate and multivariate Cox proportional hazard regression analyses were evaluated for association of all independent parameters with disease prognosis. Results: The optimal cut-off points of preoperative PLR were: (T1) 11.98-75.00, (T2) 75.00-113.33 and (T3) 113.33-567.50. There were obvious differences in each PLR tertile with mortality within 36 months of CLR (plog-rank < 0.001). Multivariable analysis suggested that the level of PLR (HR = 1.004, 95%CI: 1.001-1.008, p = 0.006), portal vein thrombosis (HR = 3.406, 95%CI: 1.185-9.794, p = 0.023), number of nodules (HR = 1.810, 95%CI: 1.345-2.437, p < 0.001), Child-Turcotte-Pugh score (HR = 1.741, 95%CI: 1.129-2.684, p = 0.012) and microvascular invasion (HR = 2.730, 95%CI: 1.777-4.196, p < 0.001) were significant predictors of mortality. Kaplan-Meier analysis of overall survival (OS) demonstrated that each PLR tertile showed a progressively worse OS and apparent separation (plog-rank = 0.016). The highest 5-year OS rate following CLR (58%) was revealed in tertile 1. In contrast, the lowest 5-year OS rate (30%) was revealed in tertile 3. Conclusion: Stratified preoperative PLR could strengthen the predictive power for OS in HCC patients with CLR.

Nucleos(t)ide analogues for preventing HBV reactivation in immunosuppressed patients with hematological malignancies: a network meta-analysis.

BACKGROUND: We aimed to evaluate the efficacy of five oral nucleos(t)ide analogues (NAs), including lamivudine, entecavir, adefovir, telbivudine and tenofovir, for the prevention of hepatitis B virus (HBV) reactivation and HBV-related complications in chronic hepatitis B virus (CHB) infected patients with hematological malignancies receiving chemotherapy or hematopoietic stem cell transplantation (HSCT) by network meta-analysis. METHODS: The search identified 28 articles involving 5 different prophylactic regimens covering 1478 participants. RESULTS: Among five prophylactic regimes, tenofovir (predicted probability, 90%), was the most effective intervention followed by entecavir (88%) in preventing HBV reactivation. There was no significant difference between tenofovir and entecavir for preventing HBV reactivation. With regards to other outcomes, tenofovir and telbivudine was not included to evaluate due to lack of relevant studies. Entecavir was the most effective intervention in reducing the risk of HBV related hepatitis (100%), HBV related death (61%) and all other causes of hepatitis (98%). CONCLUSION: Tenofovir and entecavir might be the most potent regimes in prevention of HBV reactivation for CHB infected patients with hematological malignancies undergoing chemotherapy or HSCT.

Serum alkaline phosphatase, a risk factor for non-alcoholic fatty liver, but only for women in their 30s and 40s: evidence from a large cohort study.

BACKGROUND: Several risk factors are able to predict non-alcoholic fatty liver (NAFL) development, but the predictive value of serum alkaline phosphatase (ALP) remains uncertain. Our aim is to investigate the association between serum ALP levels and NAFL. METHODS: 21,331 NAFL-free subjects were included. Sex-specific ALP quartiles (Q1 to Q4) were defined. With Q1 used as reference, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated across each quartile. RESULTS: After adjusting for confounding variables, values in Q2, Q3 and Q4 had HRs (95%CIs) of 1.16 (0.94-1.43), 1.38 (1.13-1.69), 1.51 (1.24-1.83) in females and 0.99 (0.90-1.09), 1.04 (0.95-1.14), 0.96 (0.87-1.05) in males, respectively. A subgroup analysis of age factors in females, from Q2 to Q4, adjusted HRs (95%CIs) were 1.31 (0.81-1.99), 1.86 (1.23-2.81), 2.44 (1.60-3.71) in their 30 s, 1.13 (0.83-1.54), 1.17 (0.85-1.62), 1.65 (1.22-2.25) in their 40 s, and 0.95 (0.51-1.78), 0.91 (0.52-1.62), 0.89 (0.53-1.52) in their 50 s. CONCLUSIONS: Higher serum ALP levels are considered a significant predictor for NAFL development in females aged 30 to 50.

The NAFL Risk Score: A simple scoring model to predict 4-y risk for non-alcoholic fatty liver.

BACKGROUND: Although several risk factors for non-alcoholic fatty liver (NAFL) have been reported, there are few clinical scores that predict its incidence in the long term. We developed and validate a scoring model for individual prediction of 4-y risk for NAFL. METHODS: Four-year follow-up data of 8226 initially NAFL-free subjects enrolled for an annual physical examination from Wenzhou Medical Center were analyzed. These subjects are randomly split into the training and the validation cohort. Univariate and multivariable logistic regression models were employed for model development. The selected variables were assigned an integer or half-integer risk score proportional to the estimated coefficient from the logistic model. Risk scores were tested in a validation cohort. We also compared the predictive performance of with that of the NAFLD Index by computing the area under the receiver operating characteristic curve (AUROC). RESULTS: The NAFL Risk Score was developed as 0 to 18 points comprising of BMI, TG×GGT, ALT/AST, LDL-C/HDL-C and UA in both sexes. Comparison of the observed with the estimated incidence of NAFL at both cohorts showed satisfactory precision. In addition, the NAFL Risk Score showed relatively good discriminative power (AUROC=0.739 for males, 0.823 for females) compared with the NAFLD Index (AUROC=0.661 for males, 0.729 for females) in these Chinese subjects. CONCLUSIONS: We developed and validated the NAFL Risk Score, a new scoring model to predict 4-y risk for NAFL. The NAFL Risk Score may be clinically simple and useful for assessing individual risk for NAFL.

Systematic Review with Network Meta-Analysis: Antidiabetic Medication and Risk of Hepatocellular Carcinoma.

Antidiabetic medication may modify the incidence of hepatocellular carcinoma (HCC). We aimed to compare the use of different antidiabetic strategies and the incidence of HCC. PubMed, Embase.com and Cochrane Library databases were searched up to 31 October 2015 and randomized controlled trials (RCTs), cohort studies or case-control studies were included for our analyses. A total of thirteen studies enrolling 481358 participants with 240678 HCC cases who received at least two different strategies were retrieved in this analysis. Direct comparisons showed that use of metformin (risk ratio [RR] 0.49, 95% CI 0.25-0.97) was associated with a significant risk reduction of HCC, while insulin (RR = 2.44, 95% CI 1.10- 5.56) may significantly increase the risk. Indirect evidence also suggested that insulin (RR = 2.37, 95% CI 1.21-4.75) was associated with a significantly increased risk of HCC. Additionally, metformin was effective in reducing the risk of HCC when compared with sulphonylurea (RR = 0.45, 95% CI 0.27-0.74) and insulin (RR = 0.28, 95% CI 0.17-0.47). Notably, metformin was hierarchically the best when compared with other antidiabetic therapies for the prevention of HCC. In summary, available evidence suggests that metformin was the most effective strategy to reduce HCC risk when compared with other antidiabetic interventions.

Comparative efficacy of oral nucleotide analogues for the prophylaxis of hepatitis B virus recurrence after liver transplantation: a network meta-analysis.

BACKGROUND: Prophylactic nucleos(t)ide anologues against hepatitis B virus (HBV) recurrence after liver transplantation (LT) include lamivudine, entecavir, tenofovir, adefovir. Since the most effective strategies for post-LT remain inconclusive, we aimed to compare 6 different treatment options (lamivudine, entecavir, tenofovir, adefovir, lamivudine plus adefovir, lamivudine plus tenofovir) in terms of HBV recurrence after LT using network meta-analysis. METHODS: The search identified seventeen studies involving 6 different prophylactic regimens covering 7274 patients. RESULTS: Compared with entecavir, lamivudine plus tenofovir (OR 2.00, 95%CI 0.02-183.29), lamivudine plus adefovir, (OR 2.83, 95%CI 0.18-33.57), tenofovir (OR 1.11, 95%CI 0.22-5.80), adefovir (OR 3.78, 95%CI 0.59-22.16), lamivudine (OR 4.62, 95%CI 1.75-11.39) were associated with an increased risk of HBV recurrence. CONCLUSION: Entecavir resulted with the highest probability (31%) as the best prophylactic option on reducing the risk of HBV recurrence. Entecavir is the preferred oral NAs treatment compared to other five different prophylactic regimens in the prevention of HBV recurrence after LT.

National incidence of autoimmune liver diseases and its relationship with the human development index.

OBJECTIVE: Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH) and immunoglobulin G4 related cholangitis represent the major autoimmune liver diseases (AILD). However, the relationship between AILD incidence and socioeconomic development levels is yet to be explored. RESULTS: A total of 43 studies were included. There was a positive but not significant correlation between the PBC incidence and HDI on a global level (r=0.348, P=0.082). However, in Europe, a significantly positive correlation existed between the PBC incidence and HDI (r=0.455, P=0.044). No statistical correlation between PSC incidence and HDI was observed (r=0.116, P=0.706). The incidence of AIH revealed a positive correlation with the national HDI both globally (r=0.638, P=0.014) and in Europe (r=0.644, P=0.045). Moreover, the PBC incidence demonstrated a positive correlation with the health index (r=0.422, P=0.036), but a negative correlation with the education index (r= -0.650, P<0.01). Moreover, the income index presented a positive correlation with both the PSC incidence (r=0.599, P=0.031) and the AIH incidence (r=0.649, P=0.012). METHODS: PubMed was searched to identify relevant epidemiological studies on AILD. The human development index (HDI) was applied as an indicator for socioeconomic development. HDI data were obtained and calculated based on the 2014 Human Development Report. Pearson coefficient and linear regression analysis were conducted to estimate the correlation between incidence and HDI. CONCLUSIONS: There is positive association between the national incidence of AILD and the socioeconomic status, as measured by HDI. In less-developed countries, the incidence of AILD, especially PBC and AIH, might be less common.

Systematic review with network meta-analysis: Comparative efficacy of oral nucleos(t)ide analogues for the prevention of chemotherapy-induced hepatitis B virus reactivation.

OBJECTIVES: Currently, no consensus exists regarding the optimal oral prophylactic regimens for hepatitis B surface antigen seropositive patients undergoing chemotherapy. We aimed to compare the efficacy of oral nucleos(t)ide analogues (NAs), including lamivudine, entecavir, adefovir, telbivudine and tenofovir, for the prevention of chemotherapy-induced hepatitis B virus (HBV) reactivation and its related morbidity and mortality in patients with chronic HBV (CHB) infection. RESULTS: Fifty-two eligible articles consisting of 3892 participants were included. For HBV reactivation, prophylactic treatment with NAs were all significantly superior to no prophylaxis, with odds ratio (OR) from 0.00 (95% confidence interval [CI] 0.00~0.04) for the most effective intervention (tenofovir) to 0.10 (95% CI 0.06~0.14) for the least effective intervention (lamivudine). For secondary outcomes, prophylaxis with NAs also significantly outperformed observation. The results suggested that entecavir reduced the risk of HBV related hepatitis (predicted probability, 83%), HBV related death (68%) and all causes of hepatitis (97%) most efficaciously. It ranked second in decreasing all causes of death (34%). MATERIALS AND METHODS: PubMed, Embase and Cochrane Library database were searched for controlled trials up to March 31, 2015. Primary outcome was the incidence of HBV reactivation. Secondary outcomes included the incidence of HBV-related hepatitis and death, all causes of hepatitis and death. Network meta-analysis combined direct and indirect evidence to estimate ORs for the clinical outcomes. A mean ranking and the probability of optimal therapeutic regime was obtained for each treatment based on clinical outcomes. CONCLUSIONS: Available evidence suggests that prophylatic therapy with tenofovir and entecavir may be the most potent interventions in prevention of HBV reactivation and HBV-related morbidity and mortality for CHB infection patients undergoing chemotherapy.