Gui-Qi Zhu

Systematic review with network meta-analysis: the comparative effectiveness and safety of interventions in patients with overt hepatic encephalopathy

Interventional treatment for overt hepatic encephalopathy (OHE), includes non‐absorbable disaccharides, neomycin, rifaximin, L‐ornithine‐L‐aspartate and branched chain amino acids (BCAA). However, the optimum regimen remains inconclusive.

Systematic review with network meta-analysis: statins and risk of hepatocellular carcinoma

Objectives Usage of statins is suggested to decrease the incidence of HCC. When it comes to different statin subtypes, the chemopreventive action remains controversial. We aim to compare the usage of different statins and reduction of HCC risk. Methods We searched PubMed, Embase.com and Cochrane Library database up to August 10, 2015. Duplicated or overlapping reports were eliminated. We performed a traditional pair-wise meta-analysis and a Bayesian network meta-analysis to compare different treatments with a random-effects model. Results We reviewed five observational studies enrolling a total of 87127 patients who received at least two different treatment strategies including rosuvastatin, atorvastatin, simvastatin, pravastatin, fluvastatin, cerivastatin, and lovastatin or observation alone. Direct comparisons showed that usage of atorvastatin (OR 0.63, 95%CI 0.45-0.89) and fluvastatin (OR 0.58, 95%CI 0.40-0.85) could significantly cut the risk of liver cancer. The difference of indirect comparisons between the included regimens is not statistically significant. However, usage of all types of statins, such as fluvastatin (RR 0.55, 95%CI 0.26-1.11), atorvastatin (RR 0.59, 95%CI 0.30-1.16), simvastatin (RR 0.69, 95%CI 0.38-1.25), cerivastatin (RR 0.71, 95%CI 0.19-2.70), pravastatin (RR 0.72, 95%CI 0.37-1.45), lovastatin (RR 0.81, 95%CI 0.34-1.96) and rosuvastatin (RR 0.92, 95%CI 0.44-1.80), appeared to be superior to observation alone. Notably, fluvastatin was hierarchically the best when compared with the six other statins. Conclusions Our analyses indicate the superiority of usage of statins in reduction of liver cancer. Available evidence supports that fluvastatin is the most effective strategy for reducing HCC risk compared with other statin interventions.

Association between sex-specific serum uric acid and non-alcoholic fatty liver disease in Chinese adults: a large population-based study.

AbstractThe aim of this study was to examine the association between sex-specific serum uric acid (sUA) levels and NAFLD in a large population-based study.A total of 60,455 subjects from 2 separate medical centers were included. Sex-specific sUA quartiles (Q1–Q4) were defined: ⩽330, 331–380, 381–435, and ≥436 &mgr;mol/L for male; ⩽230, 231–270, 271–310, and ≥311 &mgr;mol/L for female. The odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs) for NAFLD were calculated across each quartile of sUA, using the Q1 as reference.After adjusting for known confounding variables in this study, the ORs for NAFLD in the cross-sectional population were 1.211 (95% CI 1.109–1.322), 1.519 (95% CI 1.395–1.654), 1.903 (95% CI 1.748–2.072) for Q2, Q3, and Q4, respectively. In the longitudinal population, compared with the reference group, those in Q2, Q3, and Q4 had HRs of 1.127 (95% CI 0.956–1.330), 1.380 (95% CI 1.157–1.644), 1.589 (95% CI 1.310–1.927) for NAFLD, respectively. Analysis for the sex-specific subgroup showed the adjusted ORs for Q4 versus Q1 were 2.898 (95% CI 2.36–3.588) in female and 1.887 (95% CI 1.718–2.072) in male in the cross-sectional population. In the longitudinal population, the HRs for the Q4 were 2.355 (95% CI 1.702–3.259) in female and 1.249 (95% CI 0.975–1.601) in male, compared with Q1.We report that a sex-specific sUA level is independently associated with NAFLD. The association between sUA and NAFLD was significantly greater in females than in males.

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.

Network Meta-Analysis of Randomized Controlled Trials: Efficacy and Safety of UDCA-Based Therapies in Primary Biliary Cirrhosis

AbstractMajor ursodeoxycholic acid (UDCA)-based therapies for primary biliary cirrhosis (PBC) include UDCA only, or combined with either methotrexate (MTX), corticosteroids (COT), colchicine (COC), or bezafibrate (BEF). As the optimum treatment regimen is unclear and warrants exploration, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse events (AE).PubMed, the Cochrane Library, and Scopus were searched for randomized controlled trials up to August 31, 2014. We estimated the hazard ratios (HRs) for MOLT and odds ratios (ORs) for AE. A sensitivity analysis based on the dose of UDCA was also executed.Thirty-one eligible articles were included. Compared with COT plus UDCA, UDCA (HR 0.38, 95% confidence interval [CI] 0.09–1.39), BEF plus UDCA (HR 0.29, 95% CI 0.02–4.83), COC plus UDCA (HR 0.39, 95% CI 0.07–2.25), MTX plus UDCA (HR 0.28, 95% CI 0.05–1.63), or OBS (HR 0.49, 95% CI 0.11–2.01) all provided an increased risk of MOLT. With respect to drug AE profile, although not differing appreciably, BEF plus UDCA was associated with more AEs compared with UDCA (OR 3.16, 95% CI 0.59–20.67), COT plus UDCA (OR 2.27, 95% CI 0.15–33.36), COC plus UDCA (OR 1.00, 95% CI 0.09–12.16), MTX plus UDCA (OR 2.03, 95% CI 0.23–17.82), or OBS (OR 3.00, 95% CI 0.53–20.75). The results of sensitivity analyses were highly consistent with previous analyses.COT plus UDCA was the optimal UDCA-based regimen for both MOLT and AEs. BEF plus UDCA was most likely to cause AEs, whereas monotherapy with UDCA and coadministriation of COT plus UDCA appeared to be associated with the fewest AEs for PBC treatment.

Serum uric acid: a new therapeutic target for nonalcoholic fatty liver disease

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a major, worldwide public health problem. NAFLD is recognized as a major cause of liver-related morbidity and mortality. However, physicians are currently limited by available treatment options. Recently, numerous studies have reported a correlation between serum uric acid (SUA) and NAFLD with numerous clinical and experimental studies demonstrating a significant correlation. This review will focus on the role of SUA in the development of NAFLD and its potential role as a new target for therapeutic intervention. Areas covered: This review discusses SUA as a significant independent factor in the development of NAFLD. Moreover, we introduce the causal relationship between SUA, metabolic syndrome, and NAFLD. We discuss two major theories of insulin resistance and inflammasomes as potential explanations of the mechanistic link between SUA and NAFLD. In addition, we review current and emerging therapeutic medications to control appropriate SUA levels. Expert opinion: There is an urgent need to develop novel, safe and effective therapies for the growing NAFLD epidemic. Reduction of SUA may be a promising potential treatment for patients with NAFLD. Clinical studies are required to determine the therapeutic effect of attenuation of hyperuricemia in humans with NAFLD.

Increased levels of systolic blood pressure within the normal range are associated with significantly elevated risks of nonalcoholic fatty liver disease.

AbstractA positive association between hypertension or high-normal blood pressure (BP) and risk of nonalcoholic fatty liver disease (NAFLD) is well-known; however, no data have been generated exploring the risk of NAFLD within the normal range of BP. We aimed to assess the association between normal systolic blood pressure (SBP) and risk of NAFLD.A total of 27,769 subjects from 2 separate medical centers were included. Subjects were divided into 4 groups (G1 to G4) by SBP levels: G1: 90–99 mmHg, G2: 100–109 mmHg, G3: 110–119 mmHg, and G4: 120–129 mmHg. The prevalence, hazard ratios (HRs) and 95% confidence intervals (CIs) for NAFLD were calculated across each group, using the G1 as reference.Higher SBP was observed in subjects with NAFLD than those without NAFLD. The prevalence of NAFLD in a cross-sectional population from G1 to G4 was 6.1%, 13.6%, 19.6%, and 25.8%, respectively. The HRs for NAFLD in the longitudinal population were 2.17 (95% CI 1.60–2.93), 3.87 (95% CI 2.89–5.16), 5.81 (95% CI 4.32–7.81) for G2, G3, and G4, respectively. After adjusting for known confounding variables, HRs of G2 to G4 were 1.44 (95% CI 1.06–1.96), 1.94 (95% CI 1.44–2.61), 2.38 (95% CI 1.75–3.23), respectively.This is the first study to demonstrate that increased levels of SBP within the normal range are associated with significantly elevated risks of NAFLD, independent of other confounding factors.

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.

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.

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.