Assessing Cross-Sectional Association of Uremic Pruritus with Serum Heavy Metal Levels: A Single-Center Study.

(1) Background: Uremic pruritus (UP) is a common and taxing symptom in patients on maintenance hemodialysis (MHD). We have previously shown that blood lead levels (BLLs) and blood aluminum levels (BALs) were separately positively associated with UP in MHD patients. We also found that blood cadmium levels (BCLs) were positively associated with all-cause mortality and cardiovascular-related mortality in MHD patients. We wondered whether there is any correlation between BCLs and UP after adjusting for BLLs and BALs. (2) Methods: Patients enrolled in this study were all from three hemodialysis (HD) centers at Chang Gung Memorial Hospital, Lin-Kou Medical Center, including both the Taipei and Taoyuan branches. Correlations between UP and BLLs, BALs, BCLs, and other clinical data were analyzed. (3) Results: Eight hundred and fifty-three patients were recruited. Univariate logistic regressions showed that diabetes mellitus, hepatitis B virus infection, hepatitis C virus infection, HD duration, hemodiafiltration, dialysis clearance of urea, normalized protein catabolic rate, non-anuria, serum albumin levels, log (intact-parathyroid hormone levels), total serum cholesterol levels, serum low-density lipoprotein levels, log (blood aluminum levels), and log (blood lead levels) were associated with UP. Although log BCLs were not significantly associated with UP (p = 0.136) in univariate analysis, we still included log BCLs in multivariate logistic regression to verify their effect on UP given that our aim in this study was to verify associations between serum heavy metals and UP. Multivariate logistic regressions showed that log BLLs (OR: 27.556, 95% CI: 10.912-69.587, p < 0.001) and log BALs (OR: 5.485, 95% CI: 2.985-10.079, p < 0.001) were positively associated with UP. The other logistic regression, which stratified BLLs and BALs into high and low BLLs and BALs, respectively, showed that high BLLs or high BALs (low BLLs and low BALs as reference) (OR: 3.760, 95% CI: 2.554-5.535, p < 0.001) and high BLLs and high BALs combined (low BLLs and low BALs as reference) (OR: 10.838, 95% CI: 5.381-21.828, p < 0.001) were positively correlated with UP. (4) Conclusions: BLLs and BALs were positively correlated with UP. BCLs were not correlated with UP. Clinicians should pay more attention to the environmental sources of lead and aluminum to prevent UP.

Predicting Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Receiving Finite Periods of Antiviral Therapy.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most severe complications in chronic hepatitis B virus (HBV) infection. HCC can still develop in patients with chronic HBV (CHB) infection undergoing antiviral therapy. Several effective scoring systems for the prediction of HCC risk in CHB patients have been established. However, very few of them are designed for CHB patients receiving nucleos(t)ide analogues (NAs) therapy. Furthermore, none are available for HCC risk prediction in CHB patients receiving finite periods of antiviral therapy. METHODS: This study enrolled 790 consecutive treatment-naïve patients with CHB infection who had visited our liver clinics from 2008 to 2012 for pretreatment assessment before receiving antiviral therapies. The treatments were provided at finite periods according to the National Health Insurance Policy in Taiwan. The last follow-up date was 31 December 2021. We analyzed the virological and clinical factors in these 790 CHB patients receiving finite periods of NA treatments and identified the most significant risk factors for HCC to establish a novel predictive scoring system. By using stepwise selection in a multivariate Cox proportional hazards model, we divided the patients into three risk groups. RESULTS: Our predictive scoring system included five independent variables: genotype C (adjusted HR [aHR] = 2.23), NA-withdraw-related hepatitis relapse (aHR = 6.96), male (aHR = 4.19), liver cirrhosis (aHR = 11.14), and T1768A core promoter mutation (aHR = 3.21). This model revealed significant differences in HCC incidence among the three risk groups. The 5-year cumulative HCC risk significantly differed among the three risk groups (low risk: 1.33%, moderate risk: 4.99%, and high risk: 17.46%), with log-rank test p < 0.001. CONCLUSION: Our predictive scoring system is a promising tool for the prediction of HCC in CHB patients receiving finite NA treatments. Genotype C, NA-withdraw-related hepatitis relapse, male gender, liver cirrhosis, and the T1768A HBV core promoter mutation were significant independent risk factors.

An artificial intelligence algorithm for analyzing globus pallidus necrosis after carbon monoxide intoxication.

Globus pallidus necrosis (GPN) is one of typical neurological imaging features in patients with carbon monoxide (CO) poisoning. Current clinical guideline recommends neurological imaging examination for CO-intoxicated patients with conscious disturbance rather than routine screening, which may lead to undiagnosed GPN. We aimed to develop an artificial intelligence algorithm for predicting GPN in CO intoxication patients. We included CO intoxication patients with neurological images between 2000 and 2019 in Chang Gung Memorial Hospital. We collected 41 clinical and laboratory parameters on the first day of admission for algorithm development. We used fivefold cross validation and applied several machine learning algorithms. Random forest classifier (RFC) provided the best predictive performance in our cohort. Among the 261 patients with CO intoxication, 52 patients presented with GPN. The artificial intelligence algorithm using the RFC-based AI model achieved an accuracy = 79.2 ± 2.6%, sensitivity = 77.7%, precision score = 81.9 ± 3.4%, and F1 score = 73.2 ± 1.8%. The area under receiver operating characteristic was approximately 0.64. Top five weighted variables were Platelet count, carboxyhemoglobin, Glasgow Coma scale, creatinine, and hemoglobin. Our RFC-based algorithm is the first to predict GPN in patients with CO intoxication and provides fair predictive ability. Further studies are needed to validate our findings.

Patients with Non-Alcoholic Fatty Liver Disease and Alcohol Dehydrogenase 1B/Aldehyde Dehydrogenase 2 Mutant Gene Have Higher Values of Serum Alanine Transaminase.

Patients with non-alcoholic fatty liver disease (NAFLD) share similar pathophysiologies to those of patients with alcohol liver disease. Alcoholic metabolic enzyme-related genes (alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2)) may be associated with pathophysiology in NAFLD patients. In this study, the association between ADH1B/ALDH2 gene polymorphism and serum metabolic factors, body statures, and hepatic steatosis/fibrosis status was evaluated in patients with NAFLD. Using biochemistry data, abdominal ultrasonography, fibrosis evaluation (Kpa), and steatosis evaluation (CAP), ADH1B gene SNP rs1229984 and ALDH2 gene SNP rs671 polymorphism were analyzed in sixty-six patients from 1 January 2022 to 31 December 2022. The percentage of the mutant type (GA + AA) was 87.9% (58/66) in the ADH1B allele and 45.5% (30/66) in the ALDH2 allele. Patients with the mutant-type ADH1B/ALDH2 allele had higher values of alanine aminotransferase (ALT) than the wild type (ß = 0.273, p = 0.04). No association was observed between body mass index, serum metabolic factors (sugar and lipid profile), CAP, kPa, and ADH1B/ALDH2. A high proportion of the mutant-type ADH1B allele (87.9%) and ALDH2 allele (45.5%) was observed in patients with NAFLD. No association was observed between ADH1B/ALDH2 allele, BMI, and hepatic steatosis/fibrosis. Patients with the mutant-type ADH1B/ALDH2 allele had higher values of ALT than those with the wild type.

Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries.

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.

Waist-to-height ratio for the prediction of gallstone disease among different obesity indicators.

Background: Factors of metabolic syndrome such as obesity are well-known risk factors for gallstone disease (GSD). There are different indicators of obesity, including weight, body mass index, waist circumference, and waist-to-height ratio. The predictive ability of different obesity indicators for GSD remains unclear. Objective: To explore the most efficient predictor of GSD among the different anthropometric indicators of obesity. Methods: This population-based cross-sectional study included 2263 participants who completed a questionnaire detailing their demographics, medical history, and lifestyle between 2014 and 2017 in Taiwan. Blood samples were collected and physical examinations, including anthropometric measurements, were performed. Gallstone disease was ascertained using ultrasonography. Multivariate analyses were performed to identify independent risk factors for GSD. Results: The overall prevalence of GSD was 8.8%. According to the multivariate analysis, individuals with a waist-to-height ratio ≥0.5 (odds ratio|odds ratios (OR) = 1.65, 95% confidence interval (CI) = 1.10-2.48, p = 0.017) had an increased risk of GSD. Diabetes was the main risk factor for GSD in men (OR = 2.06, 95% CI = 1.17-3.65, p = 0.013). Among women, waist-to-height ratio >0.5 (OR = 1.76, 95% CI = 1.03-3.02, p = 0.040) and current hormone drug use (OR = 2.73, 95% CI = 1.09-6.84, p = 0.033) were significant risk factors for gallstones. Conclusion: GSD was independently associated with central obesity and exogenous hormone intake in women. Among the anthropometric indicators used to assess central obesity, waist-to-height ratio was the most accurate predictor of GSD.

A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma.

Sorafenib is currently a targeted agent widely used in the treatment of advanced hepatocellular carcinoma (aHCC). However, to date there is still a lack of a reliable marker capable of predicting sorafenib therapeutic responses. Here, we conducted a genome-wide association study (GWAS) to identify candidate single-nucleotide polymorphism outcome predictors in aHCC patients. A total of 74 real-world sorafenib-treated aHCC patients were enrolled for GWAS and outcome analysis. GWAS showed that rs1010816 (p = 2.2 × 10-7) was associated with sorafenib therapeutic response in aHCC patients. Kaplan-Meier analysis indicated that the "TT" genotype was significantly associated with a favorable therapeutic response but not significantly associated with overall survival (OS). Univariate followed by multivariate Cox proportional hazard analysis showed that ascites, main portal vein thrombosis, lower platelet count, lower total sorafenib doses, higher PALBI score in model A and higher ALBI grade in model B were significantly associated with a shorter OS. Subgroup analysis showed that only in alcoholic aHCC patients treated by sorafenib, rs1010816 "TT" genotype was significantly associated with longer OS (p = 0.021). Sorafenib had a favorable therapeutic outcome in alcoholic aHCC patients carrying rs1010816 "TT" genotype.

Serum Uric Acid but Not Ferritin Level Is Associated with Hepatic Fibrosis in Lean Subjects with Metabolic Dysfunction-Associated Fatty Liver Disease: A Community-Based Study.

Elevated serum ferritin and uric acid levels are common in patients with fatty liver disease. This study assessed the association between serum ferritin and uric acid levels and liver fibrosis in subjects with lean metabolic dysfunction-associated fatty liver disease (MAFLD). This cross-sectional study used data from a community screening examination for metabolic syndrome from December 2018 to September 2019 at Keelung Chang Gung Memorial Hospital. Subjects with lean MAFLD were defined as those with a body mass index (BMI) < 23 kg/m2 and hepatic steatosis according to the MAFLD criteria. A total of 182 lean subjects were included and were divided into lean MAFLD and lean healthy groups. Serum ferritin and uric acid concentrations were positively correlated with liver fibrosis, regardless of whether FIB-4, APRI, or NFS were used as references. Univariate logistic regression analysis showed that age and uric acid were associated with advanced liver fibrosis. After adjusting for potential confounders, only uric acid level was statistically significant in predicting the advanced liver fibrosis (OR = 6.907 (1.111−42.94), p = 0.038) in the lean MAFLD group. We found that an elevated serum uric acid level is an independent factor associated with advanced liver fibrosis in lean MAFLD subjects by noninvasive fibrosis scores.

Older Age and High α-Fetoprotein Predict Higher Risk of Hepatocellular Carcinoma in Chronic Hepatitis-B-Related Cirrhotic Patients Receiving Long-Term Nucleos(t)ide Analogue Therapy.

Background: Nucleos(t)ide analogues (NUCs) were proved to reduce hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients, but data were limited on their efficacy in cirrhotic CHB patients. Methods: A total of 447 cirrhotic CHB patients treated with tenofovir/entecavir were retrospectively analyzed and divided into HCC (n = 48) and non-HCC (n = 399) groups. The median follow-up period was 62.1 months. Results: A total of 48 patients (10.7%) developed HCC during surveillance. The annual incidence rate of HCC was 2.04 per 100 person-years. The cumulative incidence of HCC was 0.9%, 9.8%, and 22.1% at 1, 5, and 10 years, respectively. Significant predictors for HCC identified using a multiple Cox regression analysis were age ≥50 years (hazard ratio (HR): 2.34) and α-fetoprotein (AFP) ≥8 ng/mL (HR: 2.05). The incidence rate of HCC was 8.67-fold higher in patients with age ≥50 years and AFP ≥8 ng/mL (3.14 per 100 person-years) than those with age <50 years and AFP <8 ng/mL (0.36 per 100 person-years). Conclusions: Cirrhotic CHB patients with age <50 years and AFP <8 ng/mL had the lowest annual incidence of HCC. However, those with age ≥50 years or/and AFP ≥8 ng/mL had a significantly higher risk for HCC development and warrant a careful surveillance schedule.

Association of early changes of circulating cancer stem-like cells with survival among patients with metastatic breast cancer.

Background: This study aimed to investigate the role of circulating tumor cells (CTCs) and circulating cancer stem-like cells (cCSCs) before and after one cycle of chemotherapy and assessed the effects of early changes in CTCs and cCSCs on the outcomes of patients with metastatic breast cancer. Methods: Patients with stage IV invasive ductal carcinoma of the breast who received first-line chemotherapy between April 2014 and January 2016 were enrolled. CTCs and cCSCs were measured before the first cycle of chemotherapy (baseline) and on day 21, before the second cycle of chemotherapy commenced; a negative selection strategy and flow cytometry protocol were employed. Results: CTC and cCSC counts declined in 68.8 and 45.5% of patients, respectively. Declines in CTCs and cCSCs following the first chemotherapy cycle were associated with superior chemotherapy responses, longer progression-free survival (PFS), and longer overall survival (OS). An early decline in cCSCs remained an independent prognostic indicator for OS and PFS in multivariate analysis. Conclusions: A cCSC decline after one cycle of chemotherapy for metastatic breast cancer is predictive of a superior chemotherapy response and longer PFS and OS, implying that cCSC dynamic monitoring may be helpful in early prediction of treatment response and prognosis.

Prognosis Comparison Between Chronic Hepatitis B Patients Receiving a Finite Course of Tenofovir and Entecavir Treatment: A Nationwide Cohort Study in Taiwan.

PURPOSE: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are both recommended as first-line treatments for patients with chronic hepatitis B virus (CHB) infection according to international HBV treatment guidelines. However, recent studies reported conflicting results regarding the preferred antiviral in the prevention of hepatocellular carcinoma (HCC). This cohort study aimed to investigate this issue by using Taiwan's National Health Insurance Research Database, wherein a "finite" but not life-long treatment policy was applied. METHODS: From January 2008 to December 2013, a total of 12,388 consecutive adult patients with CHB who received a finite course of TDF treatment (n = 1250) or ETV treatment (n = 11,138) were analyzed through screening for study eligibility followed by the 1:4 propensity score matching method. FINDINGS: In the entire cohort, the annual incidence and survival between the ETV and TDF groups were not significantly different regarding HCC occurrence (2.05 vs 2.74 per 100 patient-years [PY]; P = 0.055; hazard ratio [HR], 0.975; log-rank, P = 0.966), cirrhosis-related complications (1.9 vs 2.4 per 100 PY; P = 0.149; HR, 0.869; log-rank, P = 0.388), or all-cause mortality (2.16 vs 1.6 per 100 PY; P = 0.119; HR, 0.831; log-rank, P = 0.342), respectively. Propensity score matching analyses yielded similar results regarding HCC occurrence, cirrhosis-related complications, and all-cause mortality. In addition, these findings were consistently reproduced in the subgroups of patients with chronic hepatitis and cirrhosis that developed before antiviral treatment. IMPLICATIONS: ETV and TDF did not significantly differ in prevention of HCC occurrence or reduction of cirrhosis-related complications and all-cause mortality in patients with CHB receiving a finite period of treatment.

Osteonecrosis of Femoral Head, An Overlooked Long-Term Complication after Paraquat Intoxication: A Retrospective Cohort Study.

With increasing numbers of patients surviving acute intoxication phase, long-term complication after paraquat intoxication is a topic worth exploring, such as osteonecrosis (ON) of femoral head. We reviewed 86 paraquat-intoxicated survivors between 2000 and 2012 in Chang Gung Memorial Hospital, a 3700-bed tertiary hospital in Taiwan. With all the patients underwent same detoxification protocol in the acute stage, 17.4% of paraquat poisoning survivors developed ON of femoral head requiring surgery during follow up. Most of ON episodes occurred within 2 to 4 years after paraquat intoxication and then plateau after 6 years. ON patients exhibited higher SOFA scores than non-ON patients (2.80 ± 2.14 vs. 1.76 ± 1.52, p = 0.028). Furthermore, AKIN scores are also higher in the ON patients than non-ON patients (0.87 ± 1.13 vs. 0.38 ± 0.74, p = 0.040). Multivariate logistic regression showed higher AKIN score and higher partial pressure of carbon dioxide in the blood 48 hours after admission significantly predicted ON of femoral head after paraquat intoxication (p = 0.002 and p = 0.006 respectively). Larger studies with longer follow-up durations are warranted to confirm our finding.

New Scoring Method to Predict Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C After Pegylated Interferon and Ribavirin Therapy.

Antiviral therapy for chronic hepatitis C (CHC) infection using pegylated interferon and ribavirin (PR) therapy can reduce the risk of hepatocellular carcinoma (HCC). Our study developed a new scoring method for predicting HCC risk after PR therapy. Between 2002 and 2016, 743 PR-treated patients with CHC were enrolled. Significant predictors for HCC were identified using multiple Cox regression analysis in study cohort: treatment age ≥60 years (hazard ratio [HR]: 2.04, 95% confidence interval [CI] = 1.3-3.7), pretreatment bilirubin ≥1.1 mg/dL (HR: 1.99, 95% CI = 1.08-3.67), α-fetoprotein ≥7.9 ng/mL (HR: 2.44, 95% CI = 1.16-5.32), no sustained virological response (SVR; HR: 1.91, 95% CI = 1.05-3.45), and baseline cirrhosis (HR: 4.45, 95% CI = 2.07-9.73). These predictors form the new HCC prediction scoring method with an area under the receiver operating characteristic curve of 0.884, sensitivity of 86.2%, and specificity of 74%. In patients with CHC and SVR, the cumulative incidence of HCC at 5 and 10 years was 16.7% and 30.4%, respectively, in patients with high risk scores and 1.2% and 4.2%, respectively, in patients with low risk scores (P < 0.001). Patients with SVR and high risk scores after viral eradication should remain under an intensive surveillance program for HCC. [Figure: see text].

Baseline circulating stem-like cells predict survival in patients with metastatic breast Cancer.

BACKGROUND: Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy. METHODS: Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM+Hoechst+CD45- cells and cCSCs as CD133+EpCAM+Hoechst+CD45- cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses. RESULTS: We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p < 0.001), overall survival (OS; median: 27.7 months vs. not reached, p < 0.001), and progression-free survival (PFS; median: 5.7 vs. 18.0 months, p < 0.001). Multivariate analysis revealed that along with other clinical variables, baseline cCSCs remained an independent prognostic factor for OS and PFS. CONCLUSIONS: Baseline cCSCs predict the treatment response as well as survival in patients with metastatic breast cancer undergoing first-line chemotherapy. Therefore, the measurement of cCSCs may assist in identifying early cancer treatment response and prognosis.

The Defective Allele of Aldehyde Dehydrogenase 2 Gene is Associated with Favorable Postoperative Prognosis in Hepatocellular Carcinoma.

Background: The Aldehyde dehydrogenase 2 (ALDH2) mutant genotypes contain an allele encoding defective ALDH2 with reduced efficacy of alcohol metabolism leading to accumulation of highly toxic and carcinogenic acetaldehyde. It can induce unpleasant "Asian flush syndrome" and associate with increased risk of cancers. However, to date, little is known about ALDH2 genotypes in relation to the postoperative prognosis of hepatocellular carcinoma (HCC). Methods: From 2002 to 2012, 419 HCC patients receiving surgical resection of HCC were enrolled for ALDH2-rs671 genotyping and outcome correlation. Results: Of the patients included, 202 were ALDH2-rs671 "GG" (wild type) and 217 were mutant (defective) "AA" + "GA" genotype. Kaplan-Meier analysis indicated that "GG" genotype significantly associated with shorter metastasis-free (P = 0.034) and overall (P = 0.005) survival, but not recurrence-free survival (P = 0.281). Univariate followed by multivariate Cox proportional hazard analysis showed that "GG" genotype was an independent clinical predictor for shorter time-to-distant metastasis (adjusted P = 0.019) and shorter overall survival (adjusted P = 0.001). Subgroup analysis showed that in patients with negative hepatitis B surface antigen, Edmonson's histology grade < 3, and aspartate transaminase > alanine transaminase, the ALDH2-rs671-GG genotype was associated with both shorter time-to-metastasis and shorter overall survival. Conclusions: HCC patients carrying a defective allele of ALDH2 had a favorable postoperative outcome.

Including Fibroblast Growth Factor-21 in Combined Biomarker Panels Improves Predictions of Liver Steatosis Severity in Children.

Background: Previous studies reported conflicting results regarding the association between fibroblast growth factor-21 (FGF-21) and non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the feasibility of combining FGF-21, obesity indices, and biochemical tests for predicting high-grade liver steatosis in children. Methods: A total of 203 children and adolescents aged 5-18 years were enrolled, and their anthropometric data, body composition, liver ultrasound score for NAFLD (range, 0-6), biochemical test results, and FGF-21, leptin, and adiponectin levels were analyzed. Children were categorized according to body mass index (BMI) and NAFLD scores. Univariate analysis and multivariate linear regression were used to identify independent predictors for the degree of liver steatosis. The accuracy of the models was also evaluated using a receiver-operating characteristic (ROC) curve. Results: FGF-21 levels were significantly higher in subjects with high-grade liver steatosis (P < 0.001). In obese and overweight children, regression analysis indicated that higher BMI and higher gamma-glutamyl transferase (γ-GT), triglycerides (TG), and FGF-21 levels were independent risk factors strongly correlated with NAFLD scores. FGF-21 combined with any of the above parameters showed a larger area under the ROC (AUROC, 0.861-0.873) than either parameter used alone. Overall, the best performance was obtained by combing FGF-21, γ-GT, and TG, with an AUROC of 0.871, specificity of 82.54%, and sensitivity of 83.78% for predicting high-grade liver steatosis. Conclusion: BMI, FGF-21, γ-GT, and TG levels were strongly correlated with liver steatosis severity. Including FGF-21 in the biomarker panels may improve the accuracy for identifying obese and overweight children with high-grade liver steatosis.

Blood lead level: an overlooked risk of carpal tunnel syndrome in hemodialysis patients.

Introduction: Carpal tunnel syndrome (CTS) is a severe complication observed in long-term maintenance hemodialysis (MHD) patients. The most common cause of CTS is dialysis-related ß2-microglobulin amyloidosis, which is associated with inflammation and oxidative stress in dialysis patients. Patients on MHD have higher blood lead levels (BLLs) than the general population. Lead (Pb) exposure in chronic dialysis patients has been noted to induce oxidative stress and inflammation. Therefore, lead-related inflammation and oxidative stress might contribute to CTS. Methods: The medical records of 866 MHD patients were reviewed. Two hundred and thirty-four patients with symptoms of CTS were surveyed by senior neurologists via physical examinations and nerve conduction studies. Patients in this study were stratified into groups with low-normal (<10 µg/dL), high-normal (10 to 20 µg/dL), and abnormal (>20 µg/dL) BLLs. The associations between CTS and BLLs and the clinical data were analyzed. Results: Multivariate logistic regression analyses showed that Log BLL (OR: 54.810, 95% CI: 13.622-220.54, p < .001), high-normal BLLs (OR: 4.839, 95% CI: 2.262-10.351, p < .001) with low-normal BLL as a reference, high BLLs (OR: 12.952, 95% CI: 5.391-31.119, p < .001) with low-normal BLL as a reference, and a BLL >12.3 µg/dL (OR: 6.827, 95% CI: 3.737-12.472, p < .001) were positively associated with CTS according to three different analyses. Discussion: In conclusion, blood lead levels were positively associated with CTS in patients on MHD. Dialysis patients should pay more attention to their environmental exposure to Pb. Avoidance of environmental Pb may reduce the incidence of CTS in MHD patients. Future studies will address the role of Pb in the pathophysiology of CTS in this patient population.

Uremic Pruritus is Associated with Two-Year Cardiovascular Mortality in Long Term Hemodialysis Patients.

BACKGROUND/AIMS: Uremic pruritus (UP) is an unpleasant complication in patients undergoing maintenance dialysis. Cardiovascular and infection related deaths are the major causes of mortality in patients undergoing dialysis. Studies on the correlation between cardiovascular or infection related mortality and UP are limited. METHODS: We analyze 866 maintenance hemodialysis (MHD) patients in our hemodialysis centers. Clinical parameters and 24-month cardiovascular and infection-related mortality are recorded. RESULTS: The associations between all-cause, cardiovascular and infection related mortality with clinical data including UP are analyzed. Multivariate Cox regression demonstrated that UP is a significantly predictor for 24-month cardiovascular mortality in the MHD patients (Hazard ratio: 3.164; 95% confidence interval, 1.743-5.744; p < 0.001). CONCLUSION: Uremic pruritus is one of the predictor of 24-month cardiovascular mortality in MHD patients.

Simple score to predict risk of hepatocellular carcinoma in chronic hepatitis C patients with advanced fibrosis after pegylated interferon and ribavirin therapy.

PURPOSE: Eradication of chronic hepatitis C virus (HCV) after interferon-based therapy and its association with the reduction of risk of hepatocellular carcinoma (HCC) in HCV-infected patients with advanced fibrosis is controversial. The study is aimed to develop a simple scoring model for HCC prediction among advanced fibrotic chronic hepatitis C (CHC) patients after pegylated interferon (pegIFN) and ribavirin (RBV) therapy. PATIENTS AND METHODS: We enrolled 271 biopsy-proven CHC patients with advanced fibrosis between 2003 and 2016, and divided them into non-HCC (n=211) and HCC (n=60) groups. The median observation duration was 6.0 years (range: 0.9-12.6 years). RESULTS: The HCC prevalence after pegIFN and RBV therapy in CHC patients with sustained virologic response (SVR) and without SVR was 14.7% and 32.2%, respectively. Multivariate Cox regression showed age ≥59.5 years old at initiation of therapy (HR: 2.542, 95% CI: 1.390-4.650, P=0.002), pretreatment total bilirubin ≥1.1 mg/dL (HR: 2.630, 95% CI: 1.420-4.871, P=0.002), pretreatment platelet counts <146.5 × 103/µL (HR: 2.751, 95% CI: 1.373-5.511, P=0.004), no achievement of SVR (HR: 2.331, 95% CI: 1.277-4.253, P=0.006), and no diabetes at treatment initiation (HR: 3.085, 95% CI: 1.283-7.418, P=0.012) were significant predictors of HCC development. The scoring model consisted of the five categorical predictors and had an optimal cutoff point of 2.5. The area under receiver operating characteristic (AUROC) of the scoring model was 0.774±0.035 (P<0.001). The sensitivity and specificity of the cutoff value to detect HCC were 81.3% and 57.5%. The 5-year and 10-year cumulative incidence of HCC was 4.9% and 10.0% in patients with simple score ≤2; and 25.9% and 44.6% in patients with simple score ≥3 (P<0.001). CONCLUSION: The simple clinical-guided score has high discriminatory power for HCC prediction in advanced fibrotic CHC patients after pegIFN and RBV therapy.

Association Between Environmental Particulate Matter and Carpal Tunnel Syndrome in Patients Undergoing Hemodialysis.

BACKGROUND/AIMS: The deposition of ß2-microglobulin induced by reactive inflammation causing carpal tunnel syndrome (CTS) is one of the complications of dialysis-related amyloidosis in maintenance hemodialysis (MHD) patients. Air pollution levels, especially particulate matter with an aerodynamic diameter of <2.5 mm (PM2.5), have significantly been associated with the elevation of systemic inflammatory markers. There is no previous research on possible associations between CTS and PM2.5. METHODS: This study enrolled 866 MHD patients treated at the outpatient HD centers. Senior neurologists diagnosed the presence of CTS. Air pollution levels were recorded by a network of 27 monitoring stations near or in the patients' living areas throughout Taiwan. The 12- and 24-month average concentrations of PM with an aerodynamic diameter of <10 and <2.5 mm (PM10 and PM2.5, respectively), sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone were included. RESULTS: Multivariate logistic regression analyses showed that HD duration, the normalized protein catabolic rate (nPCR), hypoalbuminemia (albumin < 4 g/dl), and the mean previous 12-month environmental PM2.5 were positively associated with CTS; HD duration, nPCR, hypoalbuminemia (albumin < 4 g/dl), and the mean previous 24-month environmental PM2.5 were positively associated with CTS; HD duration, hypoalbuminemia (albumin < 4 g/dl), and previous 12-month PM2.5 excess days were positively associated with CTS; and HD duration, nPCR, hypoalbuminemia (albumin < 4 g/dl), and previous 24-month PM2.5 excess days were positively associated with CTS. CONCLUSION: PM2.5 levels and PM2.5 excessing days were positively correlated with CTS.