Xian-Feng Lin

Transient elastography: a meta-analysis of diagnostic accuracy in evaluation of portal hypertension in chronic liver disease

Transient elastography (TE), as a non‐invasive method, has been studied for evaluation of portal hypertension in patients with chronic liver diseases (CLD) with variable results. We studied the performance of TE for detection of significant portal hypertension, oesophageal varices and large oesophageal varices using meta‐analysis.

A model to predict 3-month mortality risk of acute-on-chronic hepatitis B liver failure using artificial neural network

Model for end‐stage liver disease (MELD) scoring was initiated using traditional statistical technique by assuming a linear relationship between clinical features, but most phenomena in a clinical situation are not linearly related. The aim of this study was to predict 3‐month mortality risk of acute‐on‐chronic hepatitis B liver failure (ACHBLF) on an individual patient level using an artificial neural network (ANN) system. The ANN model was built using data from 402 consecutive patients with ACHBLF. It was trained to predict 3‐month mortality by the data of 280 patients and validated by the remaining 122 patients. The area under the curve of receiver operating characteristic (AUROC) was calculated for ANN and MELD‐based scoring systems. The following variables age (P < 0.001), prothrombin activity (P < 0.001), serum sodium (P < 0.001), total bilirubin (P = 0.015), hepatitis B e antigen positivity rate (P < 0.001) and haemoglobin (P < 0.001) were significantly related to the prognosis of ACHBLF and were selected to build the ANN. The ANN performed significantly better than MELD‐based scoring systems both in the training cohort (AUROC = 0.869 vs 0.667, 0.591, 0.643, 0.571 and 0.577; P < 0.001, respectively) and in the validation cohort (AUROC = 0.765 vs 0.599, 0.563, 0.601, 0.521 and 0.540; P ≤ 0.006, respectively). Thus, the ANN model was shown to be more accurate in predicting 3‐month mortality of ACHBLF than MELD‐based scoring systems.

Upper limits of normal for serum alanine aminotransferase levels in Chinese Han population.

Background and Objectives Serum alanine aminotransferase (ALT) activity is the most common tool for the assessment of liver diseases. However, it is not clear whether the current normal ALT range really discriminate patients with or without liver diseases. The present study was to establish a new normal range of ALT and examine its ability to identify patients with hepatitis B or nonalcoholic fatty liver disease (NAFLD) in Chinese Han population. Methods 53037 adults were included in this study from January 1st 2008 to August 31st 2010. The 95th percentile of ALT in population with relative low risk factors for liver diseases was set as the new upper limits of normal ALT in gender-specific manner. Results The 95th percentile levels at low risk factors for liver diseases were achieved at 35 U/L for men and 23 U/L for women. The concordance statistics for detection were 0.873 (95%CI: 0.865–0.881) for HBV and 0.932 (95%CI: 0.927–0.937) for NAFLD in men while 0.857 (95%CI: 0.850–0.864) for HBV and 0.909 (95%CI: 0.903–0.915) for NAFLD in women. The median sensitivity of the current used ALT upper limit (40 U/L) was 6.6% for HBV and 29.7% for NAFLD and median specificity was 98.7% for men and 99.4% for women. Using our new-derived thresholds, the sensitivities ranged from 35.3% to 61.1% and the specificities were 94.8% for men and 94.6% for women. Conclusions Our results suggest that upper limits of ALT 35 U/L for men and 23 U/L for women in Chinese Han population. Re-consideration of normal limits of ALT should be recommended. Trial Registration ChiCTR.org ChiCTR-OCS-11001173

Interleukin-28B polymorphisms on the SVR in the treatment of naïve chronic hepatitis C with pegylated interferon-α plus ribavirin: a meta-analysis.

There are accurate but inconclusive data on the association between single nucleotide polymorphisms (SNPs) of interleukin (IL)-28B and sustained virological response (SVR) in chronic hepatitis C (CHC). This meta-analysis aimed to derive a more precise estimation of the effects of IL-28B SNPs locus (rs12979860 and rs8099917) on SVR in naïve CHC patients receiving pegylated interferon alpha (PEG-IFN-α) plus ribavirin. Literature search was conducted up to June, 2011, in PubMed, EMBASE and Cochrane Database of Systematic Reviews. A total of 36 studies involving 10912 cases with CHC receiving PEG-IFN-α plus ribavirin met the inclusion criteria. Analyses were stratified either by ethnicity or genotype of hepatitis C virus. In genotype 1/4 patients, rs12979860 CC was associated with high SVR in CHC patients (Caucasian: odds ratio (OR), 4.567; 95% confidence interval (CI), 3.826-5.452; Asian: OR, 4.033; 95%CI, 3.050-5.333; African American: OR, 4.297; 95%CI, 2.168-8.515; Hispanics: OR, 4.350; 95%CI, 2.817-6.717) but had no effect in genotype 2/3. In Caucasian (genotype 1/4: OR, 2.542; 95%CI, 2.108-3.065; genotype 2/3: OR, 1.363; 95%CI, 1.020-1.820) and Asian (genotype 1/4: OR, 5.214; 95%CI, 3.694-7.360; genotype 2/3: OR, 1.785; 95%CI, 1.095-2.910), rs8099917 TT was associated with high SVR in both genotype 1/4 and 2/3. Meta-regression showed that in Caucasians with CHC genotype 1/4, gender male might contribute to the effect of rs12979860 on SVR but advanced fibrosis might weaken this effect. Furthermore, in Asians with CHC genotype 1/4, high baseline viral load and advanced fibrosis might also undermine the effect of rs8099917 on SVR. This meta-analysis suggested that IL-28B rs12979860 CC and rs8099917 TT were associated with high SVR rate in CHC genotype 1/4. In CHC genotype 2/3, rs8099917 TT carriers also had higher SVR.

The tumour necrosis factor-α-238A allele increases the risk of chronic HBV infection in European populations

Summary.  Tumour necrosis factor‐α (TNF‐α) plays a pivotal role in viral clearance and host immune response to hepatitis B virus (HBV) infection, of which the production capacity in individuals is demonstrated to be influenced by a single nucleotide polymorphism within the promoter region of TNF‐α genes. However, there have been conflicting results reported in previous studies on TNF‐α‐238 and TNF‐α‐863 gene promoter polymorphisms in chronic HBV infection. To derive a more precise estimation of their relationship, we searched Pubmed (January, 1966–August, 2010) and China Biological Medicine Database (January, 1978–August, 2010) and carried out a meta‐analysis involving nineteen studies that included 5245 chronic HBV infection cases and 3181 controls describing G238A genotypes, and eleven studies totalling 3576 cases and 2044 controls describing C863A genotypes. The overall meta‐analysis did not suggest significant associations of TNF‐α‐238 and TNF‐α‐863 gene promoter polymorphisms with chronic HBV infection. However, in subgroup analysis by ethnicity, it indicated that TNF‐α‐238A allele carriers (GA + AA) in European populations had an increased risk of developing chronic HBV infection (OR = 2.22, 95% CI: 1.07–4.58, P = 0.032; OR = 4.46, 95% CI: 1.75–11.38, P = 0.002, respectively), when compared with spontaneous recovered and healthy populations, respectively. However, no significant associations were found in Asian populations in all genetic models. So, we draw the conclusion that the TNF‐α‐238A allele may increase the risk of chronic HBV infection in European populations.

Tumour necrosis factor-α-857T allele reduces the risk of hepatitis B virus infection in an Asian population.

Summary.  Tumour necrosis factor‐α (TNF‐α) plays a pivotal role in hepatitis B virus (HBV) clearance and host immune response determining the chronicity of HBV infection. However, studies of the association between TNF‐α‐857 polymorphism and chronic HBV infection have reported conflicting results. So a meta‐analysis was carried out to draw a more precise conclusion. Pubmed (January, 1966–March, 2011) and the China Biological Medicine Database (January, 1978–March, 2011) were searched using the keywords TNF‐α gene polymorphism in combination with HBV infection without language restriction. Fourteen studies including 4929 chronic HBV infection cases and 2702 controls describing the C857T genotype were included in the meta‐analysis. All fourteen studies focussed on an Asian population. The overall meta‐analysis suggested that TNF‐α‐857T allele reduced the risk of chronic HBV infection in the Asian population (OR = 0.82, 95% CI: 0.71–0.95, P = 0.008) when compared with a spontaneously recovered population. In the sensitivity analyses of the groups obeying Hardy–Weinberg equilibrium (HWE), without the largest study population and without the smallest study population, a similar association was revealed (OR = 0.81, 95% CI: 0.68–0.98, P = 0.043; OR = 0.77, 95% CI: 0.68–0.87, P = 0.0001; OR = 0.81, 95% CI: 0.70–0.95, P = 0.009, respectively). However, when compared with a healthy population, no significant association was found in the Asian population in all groups. So, we draw the conclusion that the TNF‐α‐857T allele reduces the risk of chronic HBV infection in this Asian population.

Decellularization technology in CNS tissue repair

Decellularization methodologies have been successfully used in a variety of tissue engineering and regenerative technologies and methods of decellularization have been developed for target tissues and organs of interest. The technology to promote regeneration and functional recovery in the CNS, including brain and spinal cord, has, however, made slow progress mainly because the intrinsic regenerative potential of the CNS is regarded as low. To date, currently available therapies have been unable to provide significant functional recovery and successful therapies, which could provide functional restoration to the injured brain and spinal cord are controversial. In this review, the authors provide a critical analysis, comparing the advantages and limitations of the major decellularization methods and considering the effects of these methods upon the biologic scaffold material. The authors also review studies that supplement decellularized grafts with exogenous factors, such as stem cells and growth factors, to both promote and enhance regeneration through decellularized allografts.

Risk stratification of spontaneous bacterial peritonitis in cirrhosis with ascites based on classification and regression tree analysis

Risk stratification for spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and ascites helps guide care. Existing prediction models, such as end-stage liver disease (MELD) score, are accurate but controversial in clinical practice. We developed and validated a practical user-friendly bedside tool for SBP risk stratification of patients with cirrhosis and ascites. Using classification and regression tree (CART) analysis, a model was developed for prediction of SBP in cirrhosis with ascites. The CART model was derived on data collected from 676 patients admitted from January 2007 to December 2009 retrospectively, and then was prospectively tested in another independent 198 inpatients between January 2010 and December 2010. The accuracy of CART model was evaluated using the area under the receiver operating characteristic curve. The performance of the model was further validated by comparing its predictive accuracy with that of the MELD score. Furthermore, the model was used to stratify SBP among patients with MELD scores under 15. CART analysis identified four variables for prediction of SBP: creatinine, total bilirubin, prothrombin time and white blood cell count, and three risk groups: low (2.0%), intermediate (27.5–33.3%) and high (60.6–86.4%) risk. The accuracy of CART model (0.881) exceeded that of MELD (0.791). Subjects in the intermediate risk and high risk groups had 22.21-fold (95% confident interval (CI), 9.98–49.45) and 173.50-fold (95% CI, 77.68–634.33) increased risk of SBP, respectively, comparing with the low risk group. Similar results were found when this risk stratification was applied to the validation cohort. Cirrhotic patients with ascites at low, intermediate, and high risk for SBP can be easily identified using CART model, which provides clinicians with a validated, practical bedside tool for SBP risk stratification.

Construction of the HBV S-ecdCD40L fusion gene and effects of HBV S-ecdCD40L modification on function of dendritic cells

Summary.  We examined the effect of dendritic cells engineered to express an HBV S antigen CD40L fusion gene (HBV S‐ecdCD40L). The DNA of HBV S gene and the cDNA of the extracellular domain of human CD40 ligand were linked by cloning. Peripheral blood mononuclear cells (PBMC) from healthy adults were incubated and induced into dendritic cells (DC) in presence of granulocyte/macrophage colony‐stimulating factor (GM‐CSF) and interleukin‐4(IL‐4). The DCs were transfected the novel construct, and the impact of the expressed clone assessed. We find that, compared with control groups, modification of DCs with HBV S‐ecdCD40L fusion gene resulted in the activation of DCs with upregulated expression of immunologically important cell surface molecules (CD80, CD86 and HLA‐DR) and proinflammatory cytokines (IL‐12). The DCs modified with HBV S‐ecdCD40L are able to stimulate enhanced allogeneic T‐cell proliferation in vitro. Thus, the fusion gene HBV S‐ecdCD40L can promote DC’s activation and enhance its function and may prove to be the foundation for a new type of hepatitis B vaccine.