Sheng-Jie Wu

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.

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.

Establishment and Validation of ALPH-Q Score to Predict Mortality Risk in Patients With Acute-on-Chronic Hepatitis B Liver Failure: A Prospective Cohort Study

Abstract Currently, there are no robust models for predicting the outcome of acute-on-chronic hepatitis B liver failure (ACHBLF). We aimed to establish and validate a new prognostic scoring system, named ALPH-Q, that integrates electrocardiography parameters that may be used to predict short-term mortality of patients with ACHBLF. Two hundred fourteen patients were included in this study. The APLH-Q score was constructed by Cox proportional hazard regression analysis and was validated in an independent patient cohort. The area under the receiver-operating characteristic curve was used to compare the performance of different models, including APLH-Q, Child–Pugh score (CPS), model of end-stage liver disease (MELD), and a previously reported logistic regression model (LRM). The APLH-Q score was constructed with 5 independent risk factors, including age (HR = 1.034, 95% CI: 1.007–1.061), liver cirrhosis (HR = 2.753, 95% CI: 1.366–5.548), prothrombin time (HR = 1.031, 95% CI: 1.002–1.062), hepatic encephalopathy (HR = 2.703, 95% CI: 1.630–4.480), and QTc (HR = 1.008, 95% CI: 1.001–1.016). The performance of the ALPH-Q score was significantly better than that of MELD and CPS in both the training (0.896 vs 0.712, 0.896 vs 0.738, respectively, both P < 0.05) and validation cohorts (0.837 vs 0.689, 0.837 vs 0.585, respectively, both P < 0.05). Compared with LRM, APLH-Q also showed a better performance (0.896 vs 0.825, 0.837 vs 0.818, respectively). We have developed a novel APLH-Q score with greater performance than CPS, MELD, and LRM for predicting short-term mortality of patients with ACHBLF.

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.

Association between serum uric acid and bone health in general population: a large and multicentre study

Previous studies proposed that serum uric acid (UA), an endogenous antioxidant, could be a protective factor against bone loss. However, recently, a study with a population of US adults did not note the protective effects of serum UA. Therefore, the exact association between serum UA and bone health remains unclear. We performed a retrospective consecutive cohort study in a Chinese population to examine the association between serum UA and bone health. This cross-sectional study included 17,735 individuals who underwent lumbar spine bone mineral density (BMD) measurements as part of a health examination. In covariance analyses (multivariable-adjusted), a high serum UA level was associated with a high BMD, T-score, and Z-score. In binary logistic regression analyses (multivariable-adjusted), a high serum UA level was associated with low odds ratios (ORs) for at least osteopenia and osteoporosis in male (age ≥50 years) (OR = 0.72–0.60 and OR = 0.49–0.39, respectively) and postmenopausal female participants (OR = 0.61–0.51 and OR = 0.66–0.49, respectively). In conclusion, serum UA is associated with BMD, the T-score, and the Z-score, and has a strong protective effect against at least osteopenia and osteoporosis.

Increased levels of low-density lipoprotein cholesterol within the normal range as a risk factor for nonalcoholic fatty liver disease.

Objectives Dyslipidemia exists within the setting of NAFLD and the relationship of a normal level of low-density lipoprotein cholesterol (LDL-c) with NAFLD is largely unknown. This large population-based study aimed to investigate the association between LDL-c levels within the normal range and the incidence of NAFLD. Methods A total of 60527 subjects from 2 medical centers who had undergone liver ultrasonography were initially enrolled into this study. NAFLD was defined by ultrasonographic detection of steatosis in the absence of other liver disease. Subjects were divided into 4 groups (Q1 to Q4) by normal LDL-c quartiles : Q1: ≤ 2.00, Q2: 2.10-2.35, Q3: 2.36-2.68 and Q4: 2.69-3.12 mmol/L. The odds ratios (OR), hazard ratio (HR) and 95% confidence intervals (CIs) for NAFLD were calculated across each quartile of LDL-c, using the Q1 as reference. Results The prevalence rates of NAFLD in a cross-sectional population from Q1 to Q4 were 19.34%, 25.86%, 35.65% and 42.08%, respectively. The OR for NAFLD in the cross-sectional population were 1.31 (95% CI 1.14-1.54), 1.73 (95% CI 1.46-2.04), and 1.82 (95% CI 1.49-2.23), respectively, after adjusting for known confounding variables. The HR for NAFLD in the longitudinal population were 1.23 (95% CI 1.12-1.35), 1.57 (95% CI 1.44-1.72) and 2.02 (95% CI 1.86-2.21), compared with Q1. Subjects with higher LDL-c level within the normal range had an increased cumulative incidence rate of NAFLD. Conclusions Increased levels of LDL-c within the normal range may play a significant role in the prevalence and incidence of NAFLD, independent of other confounding factors.

Parabolic relationship between sex-specific serum high sensitive C reactive protein and non-alcoholic fatty liver disease in chinese adults: a large population-based study

Objectives To evaluate the association between sex-specific serum high sensitive C reactive protein (hsCRP) levels and NAFLD in a large population-based study. Results From Q1 to Q4, the incidence ratios were 21.1 (95% CI 17.5 24.7), 18.6 (95% CI 16.5 20.8), 24.8 (95% CI 22.4 27.2) and 31.1 (95% CI 28.5 33.6) in males and 6.2 (95% CI 4.4 8.0), 6.0 (95% CI 5.1 7.1), 11.4 (95% CI 9.2 13.7) and 19.5 (95% CI 16.1 22.9) in females. Compared with a 1.7-fold increase (Q4 vs Q2) in males, actuarial incidence increased 3.3-fold (Q4 vs Q2) in females. After adjusting for known confounding variables in this study, in the longitudinal population, compared with the reference group, those in Q1, Q3, and Q4 had HRs of 1.63 (95% CI 1.29-2.05), 1.11 (95% CI 0.93-1.31), 1.14 (95% CI 0.97-1.35) in male and 1.77 (95% CI 1.25-2.49), 1.22 (95% CI 0.93-1.59), 1.36 (95% CI 1.03-1.80) in female for NAFLD, respectively. Methods 8618 subjects from Wenzhou Medical Center of Wenzhou Peoples Hospital were included. Sex specific hsCRP quartiles (Q1 to Q4) were defined: 0-0.1, 0.2-0.4, 0.5-0.8 and 0.9-25.9 for male; 0-0.1, 0.2-0.6, 0.7-1.2 and1.3-28.4 for female. Applying Q2 as reference, Hazard ratios (HRs) and 95% confidence intervals (CIs) for NAFLD were calculated across each quartile of hsCRP. Conclusions We report that a sex-specific hsCRP level is independently associated with NAFLD. The association between hsCRP and NAFLD was significantly stronger in females than in males.

Nonalcoholic fatty liver disease contributes to subclinical atherosclerosis: A systematic review and meta‐analysis

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease. In our meta‐analysis, we aimed to assess the correlation of NAFLD and four surrogate markers of subclinical atherosclerosis. PubMed, Embase, and the Cochrane Library were searched up until April 2017. Original studies investigating the association between NAFLD and subclinical atherosclerosis were included. The outcome data were extracted and pooled for the effect estimate by using a random‐effects model. We used the Newcastle‐Ottawa Quality Assessment Scale to assess the quality of the included studies. Of the 434 initially retrieved studies, 26 studies involving a total of 85,395 participants (including 29,493 patients with NAFLD) were included in this meta‐analysis. The Newcastle‐Ottawa Quality Assessment Scale scores suggested the included studies were of high quality. The pooled effects estimate showed that subjects with NAFLD exhibited a significant independent association with subclinical atherosclerosis compared to the non‐NAFLD group (odds ratio, 1.60; 95% confidence interval, 1.45‐1.78). Subgroup analysis suggested that the presence of NAFLD yielded a remarkable higher risk of increased carotid artery intima‐media thickness/plaques, arterial stiffness, coronary artery calcification, and endothelial dysfunction with odds ratios (95% confidence interval) of 1.74 (1.47‐2.06), 1.56 (1.24‐1.96), 1.40 (1.22‐1.60), and 3.73 (0.99‐14.09), respectively. Conclusion: Our meta‐analysis revealed a close link between NAFLD and subclinical atherosclerosis in light of four different indices. Patients with NAFLD might benefit from screening and surveillance of early atherosclerosis, which would facilitate the prediction of potential cardiovascular disease burden, risk stratification, and appropriate intervention in the long term. (Hepatology Communications 2018;2:376‐392)

Quick chronic liver failure-sequential organ failure assessment: an easy-to-use scoring model for predicting mortality risk in critically ill cirrhosis patients.

Background and aim Critically ill cirrhosis patients have an increased risk of morbidity and mortality, even after admission to the ICU. Our objectives were to compare the predictive accuracy of model for end-stage liver disease (MELD), MELD-Na, UK model for end-stage liver disease, and chronic liver failure-sequential organ failure assessment (CLIF-SOFA) by the development and validation of an easy-to-use prognostic model [named quick CLIF-SOFA (qCLIF-SOFA)] for early risk prediction in critically ill patients with cirrhosis. Patients and methods Overall, 1460 patients were extracted from the MIMIC-III database and enrolled in this study at 30-day and 90-day follow-up. qCLIF-SOFA was developed in the established cohort (n=730) and a performance analysis was completed in the validation cohort (n=730) using area under the receiver operating characteristic curve. Results were compared with CLIF-SOFA. Results The performance of CLIF-SOFA was significantly better than that of MELD, MELD-Na, and UK model for end-stage liver disease for predicting both 30-day and 90-day mortality (all P<0.05). qCLIF-SOFA consisted of five independent factors (bilirubin, creatinine, international normalized ratio, mean arterial pressure, and vasopressin) associated with mortality. In the established cohort, CLIF-SOFA and qCLIF-SOFA predicted mortality with area under the receiver operating characteristic curve values of 0.768 versus 0.743 at 30-day, 0.747 versus 0.744 at 90-day, and 0.699 versus 0.706 at 1 year, respectively (all P>0.05). A similar result was observed in the validation cohort (0.735 vs. 0.734 at 30 days, 0.723 vs. 0.737 at 90 days, and 0.682 vs. 0.700 at 1 year, respectively, all P>0.05). Conclusion The utility of CLIF-SOFA was further shown to predict mortality for critically ill cirrhosis patients. The novel and simpler qCLIF-SOFA model showed comparable accuracy compared with existing CLIF-SOFA for prognostic prediction.

Acute circulatory failure–chronic liver failure–sequential organ failure assessment score: a novel scoring model for mortality risk prediction in critically ill cirrhotic patients with acute circulatory failure

Background and aim Acute circulatory failure (ACF) is associated with high mortality rates in critically ill cirrhotic patients. Only a few accurate scoring models exist specific to critically ill cirrhotic patients with acute circulatory failure (CICCF) for mortality risk assessment. The aim was to develop and evaluate a novel model specific to CICCF. Patients and methods This study collected and analyzed the data on CICCF from the Multiparameter Intelligent Monitoring in Intensive Care-III database. The acute circulatory failure–chronic liver failure–sequential organ failure assessment (ACF–CLIF–SOFA) score was derived by Cox’s proportional hazards regression. Performance analysis of ACF–CLIF–SOFA against CLIF–SOFA and model for end-stage liver disease systems was completed using area under the receiver operating characteristic curve. Results ACF–CLIF–SOFA identified six independent factors: mean arterial pressure [hazard ratio (HR)=0.984, 95% confidence interval (CI): 0.978–0.990, P<0.001], vasopressin (HR=1.548, 95% CI: 1.273–1.883, P<0.001), temperature (HR=0.764, 95% CI: 0.694–0.840, P<0.001), bilirubin (HR=1.031, 95% CI: 1.022–1.041, P<0.001), lactate (HR=1.113, 95% CI: 1.084–1.142, P<0.001), and urine output (HR=0.854, 95% CI: 0.767–0.951, P=0.004). ACF–CLIF–SOFA showed a better predictive performance than CLIF–SOFA and model for end-stage liver disease in terms of predicting mortality (0.769 vs. 0.729 vs. 0.713 at 30 days, 0.757 vs. 0.707 vs. 0.698 at 90 days, 0.733 vs. 0.685 vs. 0.691 at 1 year, respectively, all P<0.05). Conclusion ACF–CLIF–SOFA, as the first model specific to CICCF, enables a more accurate prediction at 30-day, 90-day, and 1-year follow-up periods than other existing scoring systems.