Wen-Yue Liu

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.

Traditional Chinese medicines benefit to nonalcoholic fatty liver disease: a systematic review and meta-analysis

Evidences from randomized controlled trials (RCTs) for the efficiency of traditional Chinese medicine (TCM) on the treatment of nonalcoholic fatty liver disease (NAFLD) are conflicting. Here we conducted a systematic review and meta-analysis of RCTs to evaluate the efficiency and safety of TCM in the treatment of NAFLD. Studies were searched on PubMed and China National Knowledge Infrastructure from January 1995 to June 2010. RCTs comparing either TCM formulations alone or in combination with placebo, ursodeoxycholic acid, insulin sensitizers, lipid-lowering drugs, or antioxidants were included. The category of most usually used herbs in the treatment of NAFLD was also calculated. Five thousand nine hundred and four patients from 62 RCTs were included for meta-analysis and 25,661 patients from 419 clinical studies were for TCM formulation analysis. Comparing with western medicines mentioned above, TCM had a better effect on the normalization of alanine aminotransferase and disappearance of radiological steatosis in the treatment of NAFLD. Furthermore, 246 kinds of Chinese herbs were included in our present study, with an average of 10 herbs (range 1–31) in each formulation. Hawthorn Fruit (321 times in 17,670 patients) was the most often used herb in the treatment of NAFLD. In conclusion, TCM is of modest benefit to the treatment of NAFLD.

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

The role of fibroblast growth factor 21 in the pathogenesis of liver disease: a novel predictor and therapeutic target

Introduction: Fibroblast growth factor 21 (FGF21) is one of the FGF family members that is produced mainly by tissues with high metabolic activity such as liver, pancreas, muscle and adipose tissue. The major function of FGF21 is to improve insulin sensitivity, ameliorate hepatic steatosis and enhance energy expenditure. Recently, several studies have reported a correlation between FGF21 and liver disease with numerous cross-sectional studies demonstrating significant correlation. This review will focus on the role of FGF21 in the pathogenesis of liver disease and its potential role as a biomarker and a new target for therapeutic intervention. Areas covered: This review discusses cross-sectional studies and underlying mechanisms of FGF21 as an endocrine hormone in several liver diseases. Two major theories of ‘endoplasmic reticulum stress’ and ‘FGF21 resistance’ in particular are explained. Moreover, early functional detection and pharmacological effect of FGF21 for liver disease are also described. Expert opinion: FGF21 can be a promising treatment in liver disease. However, still several problems are needed to be answered. The most important are whether different liver disease share common underlying mechanisms and the pharmacological effect in human with limited studies. Further studies are needed to explain the underlying mechanisms and develop potential therapeutic effect for human liver disease.

Preoperative platelet to lymphocyte ratio is a valuable prognostic biomarker in patients with colorectal cancer.

Objectives Recent studies suggest that an elevated preoperative platelet to lymphocyte ratio (PLR) may be considered a poor prognostic biomarker in patients with colorectal cancer (CRC). The aim of this study was to evaluate the prognostic impact of PLR in patients with CRC. Methods We enrolled 1314 patients who underwent surgery for CRC between 2005 and 2011. Preoperative PLR level was stratified into quintiles for Kaplan-Meier analysis and multivariable Cox proportional hazard regression models. Results Higher PLR quintiles were significantly associated with poorer overall survival (P = 0.002). Multivariate analysis showed that PLR was an independent risk factor for overall survival (OS) (P = 0.034). Patients in PLR quintile 5 had lower overall survival than in quintile 1 (hazard ratio (HR) = 1.701, 95% confidence interval (CI): 1.267–2.282, P < 0.001). Although patients in PLR quintile 5 had significantly lower disease-free survival (DFS) than in quintile 1 (HR = 1.522, 95% CI: 1.114–2.080, P = 0.008), this association was not significant after multivariable adjustment (P = 0.075). In the subgroup analysis, PLR remained an independent factor in terms of advanced tumor stage (III, IV), male sex, carcinoembryonic antigen (≤ 5 ng/ml), age (> 65 years) and body mass index (≤ 25) (P < 0.05 for all measurements). The results remained unchanged when the PLR was analyzed as a dichotomous variable by applying different cut-off values of 150, 185, 220. Conclusions Elevated preoperative PLR was independently associated with an increased risk of mortality in patients with CRC. The utility of PLR may help to improve prognostic predictors.

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.

Interleukin-28B rs12979860C/T and rs8099917T/G contribute to spontaneous clearance of hepatitis C virus in Caucasians.

Two single nucleotide polymorphisms rs12979860C/T and rs8099917T/G around interleukin-28B (IL28B) locus have been extensively investigated in their association with hepatitis C virus (HCV) spontaneous clearance. However, with the variable and even inconsistent results, it is necessary to conduct a meta-analysis. A literature search was conducted to seek articles about genetic variation of IL28B and spontaneous clearance of HCV. Odds ratio with 95% confidential interval were calculated to estimate their relationship. Furthermore, meta-regression analysis was performed to search for potential affective factors. A total of 8 studies including 2460 patients with chronic HCV infection and 1052 individuals with spontaneous HCV clearance met inclusion criteria, in which seven studies describing rs12979860 and three studies describing rs8099917. Analysis performed in Caucasian populations indicated that rs12979860CC and rs8099917TT contributed to HCV spontaneous clearance in both dominant model (CC vs. CT+TT, P<1×10(-4); TT vs. TG+GG, P<10(-4), respectively) and co-dominant model (CC vs. CT, P<1×10(-4), CC vs. TT, P<1×10(-4); TT vs. TG, P<10(-4), TT vs. GG, P=0.012, respectively). Meta-regression analysis suggested that male proportion (P=1×10(-5)) and mean age (P=1×10(-3)) might weaken the effect of rs12979860CC, but HCV genotype 1/4 (P=4×10(-4)) might contribute to it. IL28B rs12979860CC and rs8099917TT genotypes contribute to spontaneous HCV clearance in Caucasians.

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.

Secondary prophylaxis of variceal bleeding for cirrhotic patients: a multiple‐treatments meta‐analysis

To evaluate comprehensively the effects of 12 prophylaxis interventions for secondary prophylaxis of variceal bleeding using multiple‐treatments meta‐analysis.