Tian-Tian Zou

Systematic Review and Network Meta-Analysis of Randomized Controlled Trials: Comparative Effectiveness and Safety of Direct-Acting Antiviral Agents for Treatment-Naive Hepatitis C Genotype 1.

AbstractAll possible direct-acting antiviral agent (DAA) regimens for treatment-naive hepatitis C genotype 1 were evaluated by many randomized controlled trials (RCTs). However, the optimum regimen remains inconclusive. We aim to compare interventions in terms of sustained virological response at 12 (SVR12) and 24 (SVR24) weeks after the end of treatment and adverse effects (AEs) (fatigue, headache, nausea, insomnia).PubMed, Embase, and the Cochrane Library were searched for RCTs until July 31, 2015. We estimated odds ratios (ORs) between treatments on clinical outcomes.Twenty-two eligible RCTs were included. Compared with peginterferon-ribavirin (PR), daclatasvir plus PR (OR 8.90, P < 0.001), faldaprevir plus PR (OR 3.72, P < 0.001), simeprevir plus PR (OR 3.59, P < 0.001), sofosbuvir plus PR (OR 4.69, P < 0.001) yield a significant effect in improving SVR12. Consistently, simeprevir plus PR (OR 3.49, P < 0.001), sofosbuvir plus PR (OR 4.51, P < 0.001), daclatasvir plus PR (OR 4.77, P < 0.001) also improved the rates of SVR24 significantly compared with PR. With respect to AEs, compared with PR, ledipasvir plus sofosbuvir plus PR (OR 2.13, P < 0.001) confer a significant AE in nausea, whereas daclatasvir plus PR (OR 0.20, P < 0.001 and OR 0.18, P < 0.001, respectively) lowered the incidence of fatigue and nausea significantly when compared with ledipasvir plus sofosbuvir plus PR.Daclatasvir plus PR was the most effective in SVR12 and SVR24, but caused an increased AEs profile (headache and insomnia). Combined ledipasvir with sofosbuvir or combination of PR was associated with higher incidence of fatigue and nausea.

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.

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

ABSTRACT 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.

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

ABSTRACT 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.

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.

Sarcopenia Contributes to the Progression of Nonalcoholic Fatty Liver Disease- Related Fibrosis: A Meta-Analysis

Backgrounds and Aims: Previous studies have investigated that sarcopenia is associated with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis, and fibrosis in NAFLD. The study aims to investigate the risk for NAFLD, especially NAFLD-related significant fibrosis among subjects with sarcopenia. Methods: We searched electronic databases until 30, September 2017 and reviewed literature extensively. Effect estimates were pooled using random effect models regarding the risk for NAFLD and fixed effect models concerning the risk for significant fibrosis among sarcopenia patients. Sensitivity analysis was performed for the risk of NAFLD. Results: We identified 6 studies. Our results showed that subjects with sarcopenia exhibited an increased risk for NAFLD compared to those without sarcopenia (OR 1.29, 95% CI 1.12–1.49) with heterogeneity among the individual studies (I2 = 61%). And the risk for NAFLD-related significant fibrosis appeared to be more pronounced in sarcopenia patients (OR 1.57, 95% CI 1.29–1.90) with an I2 of 0%. Sensitivity analysis revealed that neither the direction nor the magnitude of the estimated pooled results for NAFLD was obviously affected. Furthermore, the pooled ORs were both close to initial analysis when omitting the study by Hong et al. [Hepatology 2014; 59: 1772–1778] (OR 1.24, 95% CI 1.11–1.39, I2 = 47%) or by Hashimoto et al. [Endocr J 2016; 63: 877–884] (OR 1.33, 95% CI 1.11–1.59, I2 = 67%), which were considered sources of heterogeneity. Conclusions: Our analysis demonstrated that sarcopenia served not only as a risk factor for the onset of NAFLD but also related to the progression of NAFLD-related significant fibrosis.

The LEPR K109R and Q223R might contribute to the risk of NAFLD: a meta-analysis.

BACKGROUND Leptin and insulin resistance have been pointed out to play a role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Increasing genes were shown to be associated with the risk of NAFLD. OBJECTIVE The study aimed to investigate the genetic association between two leptin receptor (LEPR) polymorphisms (Q223R and K109R) and the NAFLD risk. METHODS Studies were retrieved and included by using PubMed, Web of Science, the Cochrane Library databases, Chinese National Knowledge Infrastructure (CNKI) and EMBASE database. Genetic associations were assessed with pooled odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS Five case-control studies with 1711 NAFLD patients and 1732 healthy controls were included in this meta-analysis. The K109R was significantly associated with NAFLD in allelic model in Southeast Asian subgroup (p=0.01, OR=0.59, 95% CI [0.39- 0.90]), but not in Chinese subgroup (p=0.24, OR=1.10, 95% CI [0.94-1.29]). The Q223R was significantly associated with NAFLD in both allelic and recessive models (allelic model: p<0.001, OR=0.57, 95% CI [0.50-0.65]; recessive model: p=0.001, OR=0.67, 95% CI [0.52-0.85]). However, subgroup analysis showed that the significant association between Q223R and NAFLD in allelic model cannot be found in Southeast Asians subgroup (p=0.07, OR=0.67, 95% CI [0.52-0.85]). CONCLUSION LEPR K109R might be a susceptible factor for NAFLD in Southeast Asian population. And LEPR Q223R might be a susceptible factor for NAFLD in Chinese population.

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

ABSTRACT 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.

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.