Aspartate Aminotransferase/alanine Aminotransferase Research Articles

AST/ALT ratio as a significant predictor of the incidence risk of prostate cancer.

BackgroundTo investigate the effect of serum aspartate transaminase/alanine transaminase (AST/ALT) on the risk of prostate cancer.MethodsA total of 404 patients undergoing prostate biopsy from April 2016 to July 2019 were enrolled. One hundred and ninety‐four patients with prostatic cancer (PCa) were diagnosed by pathology. Two hundred and ten patients were diagnosed with benign prostatic hyperplasia (BPH). Multivariate logistic regression was used to analyze the effect of AST/ALT ratio and other factors on the incidence of PCa.ResultAST/ALT ratio was significantly higher in PCa than in BPH patients (OR 2.313, 95%CI 1.337‐4.003, P = .002). ROC curve indicated that the best cutoff was 1.155 in predicting the incidence risk of PCa. The age of PCa patients is higher than BPH patients (OR 1.054, 95%CI 1.027‐1.082, P < .001). We also found that platelets were lower in PCa than in BPH patients. Multivariate analysis showed that AST/ALT ratio could be used as an independent predictor to assess the incident risk of PCa(OR 1.043, 95%CI 1.014‐1.072, P = .003). However, AST/ALT ratio did not predict the incidence in high‐risk or low‐risk PCa.ConclusionAST/ALT ratio was an independent factor in predicting the incidence of PCa. When the level of AST/ALT ratio in serum raised, the incidence risk of PCa was significantly increased, which was helpful for the clinical diagnosis of PCa. We still needed a multicenter study to verify the role of AST/ALT ratio in the development of PCa.

Association between aminotransferase/alanine aminotransferase ratio and cardiovascular disease mortality in patients on peritoneal dialysis: a multi-center retrospective study

BackgroundElevated aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio is an independent risk factor for cardiovascular disease (CVD) among the general population. However, an association between AST/ALT ratio and CVD mortality in patients on peritoneal dialysis (PD) has received little attention.MethodsA total of 2224 incident PD patients from multi-centers were enrolled from November 1, 2005, to June 30, 2017, in this retrospective cohort study. The primary endpoint was CVD mortality. Eligible patients were divided into high and normal groups according to the AST/ALT ratio cut-off for CVD mortality with the receiver operating characteristic (ROC) curve. The associations between the AST/ALT ratio and CVD mortality were evaluated by the Cox regression model.ResultsOf eligible 1579 patients with a mean age of 49.3 ± 14.6 years, 55.4% of patients were male, 18.1% of patients had diabetes, and 64.2% of patients had hypertension. The prevalence of a high AST/ALT ratio was 76.6% in the cohort population. During a follow-up period with 4659.6 patient-years, 316 patients died, of which 193 (61.1%) deaths were caused by CVD episodes. The incidence of CVD mortality in the high group was significantly higher than that in the normal group (13.1% versus 9.2%, P = 0.024). Cumulative CVD mortality rates were significantly different between the two groups by Kaplan-Meier analysis [hazards ratio (HR) = 1.50, 95% confidence index (CI) 1.09–2.07, P = 0.014]. After adjusting for confounding factors, a higher AST/ALT ratio was independently associated with an increased risk of CVD mortality compared with their counterparts (HR = 1.43, 95%CI 1.08–2.41, P = 0.002).ConclusionsPD patients with high baseline AST/ALT ratio levels may be at a significant risk of CVD mortality.

Long-term outcome of islet transplantation on insulin-dependent diabetes mellitus: An observational cohort study.

Aims/IntroductionTo investigate the long‐term efficacy and safety of islet transplantation (ITx) compared with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII).Materials and MethodsAmong 619 patients diagnosed as insulin‐dependent diabetes mellitus or type 1 diabetes at Kyoto University, Kyoto, Japan, seven patients were selected as the ITx group and 26 age‐matched patients with no endogenous insulin secretion were selected as the MDI/CSII group. Hemoglobin A1c, aspartate aminotransferase/alanine aminotransferase (AST/ALT) and creatinine were assessed retrospectively at 1, 2, 5 and 10 years for both groups; serum C‐peptide immunoreactivity was assessed for the ITx group. Major clinical events were also assessed.ResultsHemoglobin A1c improvement in ITx was significant at 1 year (8.4% [7.8–9.9%] at baseline to 7.1% [6.3–7.4%] in ITx vs 8.2% [7.4–9.8%] at baseline to 8.1% [7.3–9.5%] in MDI/CSII, P < 0.01 between groups), and was maintained at 2 years (7.4% [6.3–8.2%] vs 8.4% [7.4–9.6%], P = 0.11). The increase of stimulated C‐peptide immunoreactivity was significant at 1 year (0.57 ng/mL [0.26–0.99 ng/mL], P < 0.05 from baseline) and 2 years (0.43 ng/mL [0.19–0.67 ng/mL], P < 0.05), although it became insignificant thereafter. There was no significant difference in AST/ALT or creatinine at 10 years, although a transient AST/ALT elevation was observed in ITx. In regard to clinical events, the occurrence of severe hypoglycemia was 14% vs 31% (relative risk 0.46, P = 0.64), that of infectious disease was 43% vs 12% (relative risk 3.71, P = 0.09) and digestive symptoms was 43% vs 7.7% (relative risk 5.57, P = 0.05) in ITx vs MDI/CSII, respectively. No patient died in either group.ConclusionsThe present findings showed that ITx was considered to contribute to the reduction of hypoglycemia and better glycemic control with tolerable, but attention‐requiring, risks over a period of 10 years compared with MDI/CSII.

The miRFIB-Score: A Serological miRNA-Based Scoring Algorithm for the Diagnosis of Significant Liver Fibrosis.

Background: The current diagnosis of early-stage liver fibrosis often relies on a serological or imaging-based evaluation of the stage of fibrosis, sometimes followed by an invasive liver biopsy procedure. Novel non-invasive experimental diagnostic tools are often based on markers of hepatocyte damage, or changes in liver stiffness and architecture, which are late-stage characteristics of fibrosis progression, making them unsuitable for the diagnosis of early-stage liver fibrosis. miRNAs control hepatic stellate cell (HSC) activation and are proposed as relevant diagnostic markers. Methods: We investigated the possibility of circulating miRNAs, which we found to be dysregulated upon HSC activation, to mark the presence of significant liver fibrosis (F ≥ 2) in patients with chronic alcohol abuse, chronic viral infection (HBV/HCV), and non-alcoholic fatty liver disease (NAFLD). Results: miRNA-profiling identified miRNA-451a, miRNA-142-5p, Let-7f-5p, and miRNA-378a-3p to be significantly dysregulated upon in vitro HSC activation, and to be highly enriched in their extracellular vesicles, suggesting their potential use as biomarkers. Analysis of the plasma of patients with significant liver fibrosis (F ≥ 2) and no or mild fibrosis (F = 0–1), using miRNA-122-5p and miRNA-29a-3p as positive control, found miRNA-451a, miRNA-142-5p, and Let-7f-5p, but not miRNA-378a-3p, able to distinguish between the two patient populations. Using logistic regression analysis, combining all five dysregulated circulating miRNAs, we created the miRFIB-score with a predictive value superior to the clinical scores Fibrosis-4 (Fib-4), aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and AST to platelet ratio index (APRI). The combination of the miRFIB-score with circulating PDGFRβ-levels further increased the predictive capacity for the diagnosis of significant liver fibrosis. Conclusions: The miRFIB- and miRFIBp-scores are accurate tools for the diagnosis of significant liver fibrosis in a heterogeneous patient population.

HEPATOPROTECTIVE EFFECT OF PERILLYL ALCOHOL (POH) ON HIGH-FAT DIET-LOW-DOSE STREPTOZOTOCIN-INDUCED TYPE 2 DIABETES IN EXPERIMENTAL RATS

Objective: The aim of the present study was to investigate the hepatoprotectivity effect of perillyl alcohol in high-fat diet (HFD)-low-dose streptozotocin (STZ)-induced diabetic rats.&#x0D; Methods: Diabetes was induced in male albino Wistar rats by 4 weeks diet manipulation followed by a low single intraperitoneal injection of STZ (35 mg/kg body weight). Perillyl alcohol was administered orally (50 mg/kg body weight and 100 mg/kg body weight) for 30 days. Glibenclamide was used as a standard drug and given orally 6 mg/kg body weight. At the end of treatment period, levels of alkaline phosphatase (ALP), aspartate transaminase (AST) alanine transaminase (ALT), and bilirubin and serum protein were measured in serum of experimental rats. Histopathological studies of liver were also done with microscope.&#x0D; Results: The levels of ALP, AST ALT, and bilirubin were increased significantly in HFD-STZ-induced diabetic rats. Perillyl alcohol-treated diabetic rats showed marked restoration in the activity of ALP, AST, ALT, and bilirubin when compared with diabetic control rats. Perillyl alcohol and glibenclamide drug-treated rats showed reversible tissue regeneration with prominent hepatocytes.&#x0D; Conclusion: The present results clearly indicate that the perillyl alcohol has a potent efficacy for hepatoprotective effect in HFD- low-dose STZ-induced diabetic rats.

A man with repeated cholangitis

A 67-year-old man, with a past medical history of remarkable left intrahepatic biliary stones and recurrent episodes of acute cholangitis, presented to our hospital with low-grade fever and epigastric dull aching followed by tea-colored urine for 1 week. Initial laboratory data were as follows: Hb 11.5 g/dL, WBC (white blood count) 17 700/mm3, CRP (C-Reactive Protein) 25.13 mg/dL, AST/ALT (aspartate transaminase/alanine transaminase) 39/45 IU/L, bilirubin (T/D) 7.5/4.6 mg/dL, alkaline phosphatase 596 IU/L, CEA (carcinoembryonic antigen) 1.92 ng/mL, AFP (Alpha-FetoProtein) 4.10 ng/mL, PSA (prostate specific antigen) 5.57 ng/mL, and CA 19-9 (Carbohydrate Antigen 19-9) 92.56 U/mL. Abdominal computed tomography demonstrated a new-onset mass lesion (10 cm in diameter) occupying the left lobe of liver. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the liver demonstrated a 10 cm liver mass with dilatation of adjacent IHDs (intrahepatic duct) in the left lobe (mainly in segment 4), indicating a malignant neoplasm (Figure 1). The preoperative diagnosis was ICC according to his clinical presentation and radiological images. He received an extended left hepatectomy after a thorough preoperative evaluation, including the ICG (Indocyanine green) test. The histopathological examination demonstrated intraductal papillary neoplasm of bile duct (IPNB) with low-grade dysplasia and marked chronic inflammation (Figure 2). His postoperative course was uneventful, and he was discharged 10 days after the operation. IPNB, formerly named biliary papillomatosis, is a rare biliary epithelial tumor with an exophytic nature exhibiting a papillary mass within the bile duct lumen and with a prominent intraductal growth pattern. It has been considered as a precursor lesion of invasive cholangiocarcinoma. The grade of intraepithelial neoplasia is defined as either low-intermediate, high, or invasive carcinoma according the World Health Organization's 2010 classification system.1 The clinical picture of IPNB consists of recurrent colicky abdominal pain and repeated episodes of acute cholangitis with fever and jaundice due to partial or intermittent biliary obstruction.2 Common radiological findings for IPNB are bile duct dilatation or intraductal masses, and liver solid tumors are rarely seen. It is difficult to distinguish IPNB from other inflammatory and neoplastic lesions based on radiological appearance alone, including DCE-MRI of liver.3 Patients with IPNB should be considered for treatment because of the high risk of recurrent cholangitis and malignant transformation. Resection is the treatment of choice when IPNB is localized according to preoperative imaging workup. The overall prognosis is better in patients with IPNB than ICC, and long-term survival is anticipated after curative resection.4 The author declares no conflict of interest.

High aspartate transaminase/alanine transaminase ratio predicts poor prognosis in patients with localized upper tract urothelial cancer: a propensity score-matched study in a large Chinese center.

Purpose: The aim of this study was to evaluate the prognostic value of the aspartate transaminase/alanine transaminase (AST/ALT) ratio in a large Chinese cohort surgically treated for localized upper tract urothelial carcinoma (UTUC) using propensity score matching (PSM) analysis.Methods: Data of 908 consecutive patients with localized UTUC who underwent radical nephroureterectomy (RNU) were retrospectively evaluated. The endpoints of prognosis were progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS) after RNU. We compared these endpoints according to the AST/ALT ratio before and after 1:1 PSM. The independent predictors for PFS, CSS and OS were also analyzed.Results: A high AST/ALT ratio was correlated with unfavorable factors, including elderly age, female gender, history of coronary disease, alcohol and tobacco consumption, lower body mass index, and larger tumor volume. Before PSM, the Kaplan–Meier curves showed significantly poorer survival outcomes in PFS, CSS, and OS (all P<0.001) for patients with high AST/ALT ratios. After PSM, the high AST/ALT ratio group also had significantly inferior survival outcomes in terms of PFS, OS and CSS (all P<0.001). Furthermore, multivariate analyses revealed that the AST/ALT ratio was an independent predictor for PFS, CSS and OS before PSM (PFS hazard ratio [HR] 1.454, P=0.001; CSS HR 2.577, P<0.001; OS HR 1.925, P<0.001) and after PSM (PFS HR 1.711, P<0.001; CSS HR 2.588, P<0.001; OS HR 1.957, P<0.001).Conclusion: The preoperative AST/ALT ratio can be a convenient and useful prognostic biomarker for patients with localized UTUC.

Comparison of laboratory indices of non-alcoholic fatty liver disease for the detection of incipient kidney dysfunction.

Non-alcoholic fatty liver disease (NAFLD) is closely linked to insulin resistance and related adverse health outcomes. We investigated the non-invasive index of NAFLD that has the best performance in estimating the renal manifestations of metabolic disturbances. This nation-wide, cross-sectional study included 11,836 subjects, using various non-invasive assessments comprising routinely measured clinical and laboratory variables. The subjects were native Koreans aged 20 years or older and had no diabetes, history of liver or kidney disease. All participants were divided into quintiles according to their fibrosis-4 (FIB-4) results. Participants in the highest quintile were more hypertensive and obese with greater glycemic exposure, poor lipid profiles, and impaired kidney function, than those in the other quintiles. Multiple logistic regression, adjusted for age, sex, smoking, systolic blood pressure, white blood cell, platelet, fasting plasma glucose, and triglyceride, demonstrated that FIB-4, the hepatic steatosis index, the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, Gholam’s model for non-alcoholic steatohepatitis, and the BARD score were independently associated with kidney dysfunction. ROC curve analysis revealed that FIB-4 (AUC = 0.6227, 95% CI [0.5929–0.6526], p = 0.0258) was the most precise in predicting kidney dysfunction. Our findings suggest that FIB-4 may be a favorable screening tool for the renal manifestation of hepatic metabolic disturbances.

Prevalence of Undetectable Vaccine-Induced Immunity Against Hepatitis B Virus in US Adults at High Risk for Infection.

In 2015, the Centers for Disease Control and Prevention reported a substantial increase in the number of acute hepatitis B virus (HBV) infections in the United States. Although national guidelines recommend vaccination of adults at high risk for HBV infection, the prevalence of undetectable immunity (i.e., susceptibility) in this population remains unknown. In this study, we analyzed a nationally representative sample using the National Health and Nutrition Examination Survey to evaluate the prevalence, trend, and predictors of undetectable vaccine-induced antibodies against HBV surface antigen (<10 mIU/mL) among high-risk adults from 2003-2014. Among adults at high risk for HBV infection, the prevalence of undetectable immunity decreased from 83.2% in 2003-2004 (95% confidence interval [CI]: 81.3-85.0) to 69.4% (about 64 million) in 2013-2014 (95% CI: 66.0-72.6). The prevalence decreased significantly in individuals with multiple sex partners or sexually transmitted disease and in pregnant women. However, there were no significant changes in men who have sex with men (MSMs), intravenous drug users (IDUs), hepatitis C virus (HCV)-infected and patients with diabetes, and those with elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT). Mexican Americans had the highest prevalence of undetectable immunity (77.6%, 95% CI: 72.6-81.9), followed by non-Hispanic whites (70.1%, 95% CI: 66.9-73.1). Older age, lower socioeconomic status, and having at least 1 high-risk factor were associated with a higher risk of undetectable immunity, whereas an increased risk among the foreign-born disappeared after multivariable adjustment. Conclusion: Approximately 64 million high-risk adults in the United States remain susceptible to HBV infection, especially MSMs, IDUs, diabetics, HCV patients, and populations with elevated AST/ALT. To eliminate HBV, efforts should be made to increase screening and vaccination in high-risk adults.

Pemetrexed/carboplatin plus gefitinib as a first-line treatment for EGFR-mutant advanced nonsmall cell lung cancer: a Bayesian network meta-analysis.

Background:First-line treatments for nonsmall cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations have been evaluated in various clinical trials. However, it remains unclear which is the optimal treatment.Methods:A Bayesian network meta-analysis was used to assess the efficacy and safety profile of gefitinib, erlotinib, afatinib, dacomitinib, osimertinib, erlotinib plus bevacizumab and pemetrexed/carboplatin, or pemetrexed alone plus gefitinib. Literature was sourced from electronic databases. Data regarding objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), treatment-related adverse events (TRAEs), treatment-related adverse event grades 3–5 (TRAE 3–5), specific TRAEs [diarrhea, rash, and elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT)] were extracted. The regimens were then ranked using the surface under the cumulative ranking curve (SUCRA).Results:A total of 19 studies involving 4607 EGFR-mutant NSCLC patients were analyzed. In regards to efficacy, pemetrexed/carboplatin (PC) plus gefitinib was superior in ORR and OS to chemotherapy and first-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). All the TKI-based regimens had equivalent DCR and PFS. Patients with the L858R mutation treated with PC plus gefitinib achieved a better outcome than most EGFR TKI-related groups (except osimertinib) in the PFS subgroup. In regards to safety, no statistical significance for TRAEs was observed among the eight treatments. In regards to SUCRA, PC plus gefitinib ranked first in terms of PFS, OS, and TRAE grades 3–5.Conclusions:Pemetrexed/carboplatin plus gefitinib is a promising treatment option for EGFR-mutant NSCLC patients in the first-line setting.

Predictive Value of a Noninvasive Serological Hepatic Fibrosis Scoring System in Cirrhosis Combined with Oesophageal Varices

Objective In recent years, the noninvasive serological scoring system has become a research hotspot in predicting hepatic fibrosis and has achieved good results. However, it has rarely been applied to the prediction of oesophageal varices. The aim of the study was to evaluate the predictive value of the four following scoring systems in cirrhosis combined with oesophageal varices: aspartate and platelet ratio index (APRI), aspartate aminotransferase-alanine aminotransferase ratio (AAR), FIB-4, and S index. Methods A total of 153 patients with cirrhosis were categorized into groups with or without oesophageal varices. In addition, cirrhosis patients with oesophageal varices were further divided into mild, moderate, and severe grades. The rank sum test was used to compare the significant differences of APRI, AAR, FIB-4, and S index between the two groups of cirrhosis patients with or without oesophageal varices. A ROC curve was generated to compare the area under the curve of the three groups and to obtain the corresponding optimal prediction value. Moreover, multivariate logistic regression analysis was employed to assess the predictive factors for cirrhosis combined with oesophageal varices. Results 44 patients had no oesophageal varices and 108 patients had oesophageal varices. Of the 108 patients with oesophageal varices, 43 were mild, 32 were moderate, and 33 were severe. The rank sum test indicated that the APRI, FIB-4, and S index were statistically significant between two groups (P < 0.05), while no significant difference was detected in terms of AAR between the two groups (P > 0.05). In addition, all four scoring systems were statistically significant between nonoesophageal varices group and severe oesophageal varices group (P < 0.05). In the ROC curve of oesophageal varices, the AUC values of APRI, FIB-4, and S index for predicting oesophageal varices were 0.681, 0642, and 0.673, respectively. However, in the ROC curve of severe oesophageal varices, the AUC values of APRI, AAR, FIB-4, and S index were 0.729, 0.648, 0.673, and 0.695, respectively. Multivariate logistic regression analysis indicated that APRI and FIB-4 were predictors of disease progression (P < 0.05). Conclusion AAR harboured a poor predictive value for oesophageal varices, APRI can be used as a reference index for the prediction of severe oesophageal varices, and the S index harboured potential value in predicting the degree of progression of cirrhosis.

Increased oxidative damage of RNA in liver injury caused by hepatitis B virus (HBV) infection

To evaluate the urinary levels of 8-oxo-7,8-dihydro-2′deoxyguanosine (8-oxo-dGsn) and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) in liver injury patients with hepatitis B virus (HBV) infection and to explore the relationship between urinary 8-oxo-dGsn or 8-oxo-Gsn and degree of liver damage. We enrolled 138 liver injury patients with HBV infection and 169 age- and sex-matched healthy controls in this study. A sensitive and accurate isotope-diluted liquid chromatograph mass spectrometer/mass spectrometer (LC-MS/MS) method was used to measure the urinary levels of 8-oxo-Gsn and 8-oxo-dGsn. Simultaneously, pathological analysis of liver biopsy tissues was carried out, and immunohistochemistry was carried out for 8-oxo-Guo, 8-oxo-dGuo and MTH1 protein in some liver injury tissues. We analysed the correlation between the degrees of inflammation and fibrosis and levels of 8-oxo-Gsn and 8-oxo-dGsn. We also analysed the levels of urinary 8-oxo-Gsn and 8-oxo-dGsn with clinical data of HBeAg, HBsAg, and HBV genotype and detected the levels of plasma aspartate aminotransferase, alanine aminotransferase (AST), platelet, alkaline phosphatase, prothrombin time (PT) and HBV DNA, and calculated the aspartate amino transferase-to–platelet ratio index (APRI) score. Nonparametric correlations were used to evaluate the correlation between 8-oxo-Gsn, 8-oxo-dGsn or APRI and various laboratory biochemical indicators. Results showed that the levels of urinary 8-oxo-Gsn and 8-oxo-dGsn in patients with liver injury were significantly higher than those of healthy controls (both p < .001). Urinary 8-oxo-Gsn was significantly associated with AST, APRI and PT (p = .013, p = .026 and p = .049). The receiver operating characteristic curves of 8-oxo-Gsn were 0.696 (0.632–0.759) and 0.731 (0.672–0.790) for inflammatory activity and fibrosis, respectively. Patients with higher levels of urinary 8-oxo-Gsn are more likely to have a high degree of fibrosis and urinary 8-oxo-Gsn may have a great potential in assessing liver fibrosis.

Performance of simple noninvasive scoring systems for the prediction of advanced fibrosis in patients with chronic hepatitis B.

The aim of the study was to analyze the diagnostic performance and clinical utility of simple noninvasive tests for the detection of advanced fibrosis in patients with chronic hepatitis B (CHB) infection seen at a tertiary referral center in Germany. We retrospectively analyzed 239 adult CHB patients with available liver biopsies. Patient demographics, hepatitis B markers, antiviral treatment, laboratory parameters, results from liver imaging, and histology were recorded. The sensitivity, specificity, and positive and negative predictive values were determined along with the area under receiver operating characteristic curves (AUROC) using published formulas and cut-off values for fibrosis index based on the four factors, aspartate aminotransferase-alanine aminotransferase ratio index (AAR), aspartate aminotransferase-to-platelet ratio index (APRI), and age-platelet index. The median documented duration of CHB infection was 31 months (range: 6-340 months); 86% of the patients were Caucasian and 71% were men. The AUROCs for the detection of advanced fibrosis were 0.75 [95% confidence interval (CI): 0.67-0.82], 0.72 (95% CI: 0.64-0.80), 0.48 (95% CI: 0.39-0.56), and 0.73 (95% CI: 0.66-0.81) for fibrosis index the four factors, APRI, AAR, and age-platelet index, respectively. Patients with advanced fibrosis on biopsy were misclassified as having mild fibrosis in 35% (APRI) to 82% (AAR) of cases. Because of their moderate test performance (AUROCs: 0.48-0.75) and their high misclassification rate, we could not confirm a reliable clinical utility for the analyzed noninvasive fibrosis scoring systems for the prediction of advanced fibrosis in mostly Caucasian CHB patients.

Quantification of EtG in hair, EtG and EtS in urine and PEth species in capillary dried blood spots to assess the alcohol consumption in driver’s licence regranting cases

BackgroundIn Belgium, the analysis of indirect biomarkers such as carbohydrate deficient transferrin (CDT%), gamma-glutamyltransferase (GGT), aspartate aminotransferase/alanine aminotransferase (AST/ALT) and mean corpuscular volume (MCV), is currently used to monitor the alcohol consumption in cases of fitness to drive assessment. We evaluated the use of direct ethanol markers for this purpose, exclusively determined in matrices obtained via non- or minimally invasive sampling. MethodsThree validated quantitative methods (ethylglucuronide (EtG) in hair and urine, ethylsulfate (EtS) in urine, and phosphatidylethanol species (PEth 16:0/18:1, PEth 18:1/18:1 and PEth 16:0/16:0) in capillary dried blood spots (C-DBS)) were used. Fifty volunteers, for whom fitness to drive had to be assessed and for whom a blood analysis for indirect biomarkers was requested, were included in the study. The sampling and analysis of hair, urine and C-DBS were added to the process currently used. ResultsHair EtG (24/50) and C-DBS PEths (29/50) are more sensitive than the currently used indirect biomarkers (13/50 for CDT%) to detect excessive and chronic alcohol consumption and allow to disprove an abstinence period. Urinary EtG and EtS are useful parameters to determine recent alcohol consumption. ConclusionThe combined use of the three strategies allows better inference about the evolution of the alcohol consumption prior to the sampling. Moreover, the exclusive use of non- or minimally invasive sampling (hair, urine and C-DBS) allows this to be performed directly during the fitness to drive assessment by regular staff members. This approach offers the potential to improve the Belgian driver’s licence regranting process.

Does Epoetin Beta Still Have a Place in Peginterferon Alpha-2a Plus Ribavirin Treatment Strategies for Chronic Hepatitis C?

To investigate the impact of epoetin beta (EPO) on sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients treated with peginterferon-ribavirin (RBV). Controlled, randomized, pragmatic multicenter study to assess 2 strategies, ie, the use (EPO group) or nonuse (control group) of EPO in terms of achieving SVR in treatment-naive, genotype non-2/non-3 HCV-infected patients receiving a 48-week treatment regimen of pegylated interferon α-2a (peg-IFN) plus RBV (randomization 2:1). The single-nucleotide polymorphisms of interferon lambda 3 (IFNL3) (rs12979860 and rs8099917), interferon lambda 4 (IFNL4) (ss469415590), and inosine triphosphatase (ITPA) (rs1127354 and rs7270101) were determined retrospectively. Two hundred twenty-seven patients were included in the study. In the global population (n = 227), the overall SVR rate was 52% (118/227). Nonresponse and relapse occurred in respectively 46/227 (20.3%) and 42/227 (18.5%) patients. In the intention-to-treat analysis, 55.5% of patients with anemia (n = 164) had a SVR, specifically 57.4% in the EPO group versus 52.4% in the control group, but the difference was not statistically significant. In the anemic population, independent factors associated with SVR were IFNL3 and IFNL4 polymorphisms, pretreatment HCV RNA level, iron level, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio. EPO has little impact on SVR in patients treated with peg-IFN+RBV and should be recommended only for patients with severe anemia.

Rhabdomyolysis in Ebola Virus Disease. Results of an Observational Study in a Treatment Center in Guinea.

The pathogenesis of Ebola virus disease (EVD) remains unclear. The sporadic nature of Ebola outbreaks and their occurrence in resource-limited settings have precluded the acquisition of extensive clinical and laboratory data. Rhabdomyolysis during EVD has been suggested to occur in previous studies showing increased aspartate aminotransferase-alanine aminotransferase ratios, but, to date, has not been confirmed with creatine kinase (CK) assays. We performed an observational study of 38 patients admitted to an Ebola treatment center from January to April 2015. CK values from patients with confirmed EVD were compared with those in patients without confirmed EVD. A panel of other analyses were also performed. In patients with EVD, characteristics were compared between survivors and nonsurvivors. High levels of CK were more frequent in patients with EVD than in those without (P = .002), and rhabdomyolysis was more frequent (59% vs 19%, respectively; P = .03). CK levels >5000 U/L were observed in 36% of patients with EVD. Also in patients with EVD, fatal outcome was significantly associated with higher creatinine and bilirubin levels, international normalized ratio, and viral load. Rhabdomyolysis is a frequent disorder in EVD and seems to be more common than in other viral infections. It may contribute to the renal failure observed in nonsurviving patients. More studies are needed to determine the impact of rhabdomyolysis on EVD outcome.

Clinical characteristics and outcome of hepatocellular carcinoma in alcohol related and cryptogenic cirrhosis: a prospective study

Non-alcoholic fatty liver disease (NAFLD) is becoming a leading cause of chronic liver disease. Hepatocellular carcinoma (HCC) is one of its complications. Although the pathophysiology is unclear, it is reasonable to expect that cryptogenic cirrhosis related HCC (cryptogenic HCC) behaves differently to other types of HCC. This study prospectively compared patients with cryptogenic HCC and those with HCC related to alcoholic cirrhosis. A total of 150 consecutive patients with HCC (89 cryptogenic HCC and 61 alcohol related HCC) referred to our unit over a 23-month period were studied. Their demographic data, liver function, tumor characteristics and outcomes were compared. Alcohol related HCC was seen only in males. Compared with cryptogenic HCC, alcohol related HCC had significantly higher aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio (1.7 vs 1.4, P=0.002), model for end-stage liver disease score (13 vs 11, P=0.018) and Child's score (7 vs 6, P=0.037). No significant difference was seen in platelet counts, serum sodium and AST to platelet ratio index. Single nodular tumors were more common in cryptogenic HCC, while diffuse type tumors and macroscopic vascular invasion were common in alcohol related HCC. In patients who could not be offered any treatment because of advanced tumors or poor liver function, alcohol related HCC had a significantly lower median survival (5.3 months) compared with cryptogenic HCC (9.3 months, P=0.034). Compared with cryptogenic HCC, alcohol related HCC had worse liver function and aggressive tumor morphology at presentation, and a higher proportion was untreatable. In patients who could not be treated, median survival was lower in patients with alcohol related HCC than in those with cryptogenic HCC.

Biomarkers in nonalcoholic fatty liver disease-the emperor has no clothes?

Fatty liver is present in over ten percentage of the world population and it is a growing public health problem. Nonalcoholic fatty liver disease (NAFLD) is not a single disease, but encompasses a spectrum of diseases of different etiologies. It is difficult to find highly specific and sensitive diagnostic biomarkers when a disease is very complex. Therefore, we should aim to find relevant prognostic markers rather than accurate diagnostic markers which will help to minimize the frequency of liver biopsies to evaluate disease progression. There are several biomarker panels commercially available, however, there is no clear evidence that more sophisticated panels are better compared to simple criteria such as, presence of diabetes over five years, metabolic syndrome, obesity, obstructive sleep apnea, aspartate transaminase/alanine transaminase (ALT) ratio > 0.8 or ferritin levels > 1.5 times normal in patients with over six month history of raised ALT and/or ultrasonological evidence of fat in the liver. Currently the biomarker panels are not a replacement for a liver biopsy. However the need and benefit of liver biopsy in NAFLD is questionable because there is no convincing evidence that biopsy and detailed staging of NAFLD improves the management of NAFLD and benefits the patient. After all there is no evidence based treatment for NAFLD other than management of lifestyle and components of "metabolic syndrome".

Preventive Effect of a Fraxinus Excelsior L Seeds/Fruits Extract on Hepatic Steatosis in Obese Type 2 Diabetic Mice

Background: Non-alcoholic fatty liver is recognized as one of harmful consequences of the metabolic syndrome and hepatocytes steatosis is well connected with loss of insulin sensitivity, impaired glucose tolerance and can lead to impaired fasting glucose and type2 diabetes mellitus. Fraxinus excelsior L. seed extract has been used as traditional folk medicine by Mediterranean population and Glucevia®, a natural extract of Fraxinus excelsior L. derived from seeds/fruits of the plant and standardized to 10% Nuzhenide and GI3, has been previously reported to regulate glucose homeostasis in healthy overweight people. Methods: The effect of seven-month administration of Glucevia® on liver parameters was investigated in a diabetic mouse strain (BKS ++Lepr db (db/db)). The severity of fatty change and grading of hepatic steatosis were determined by estimating the fat hepatocytes contain in animals fed with a control diet or with a control diet supplemented with 0.07 % (w/w) of the extract. Results: Glucevia® was shown to significantly reduce fatty liver in diabetics mice (-54%; p<0.05). A concomitant improvement in alkaline phosphatase (ALP) levels and in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio were observed between groups (p<0.05). A significant decrease in insulin plasma level (-22%; p<0.05) was measured in Glucevia® group leading to an improvement of HOMA-IR between groups (p<0.001) while no significant change of fasting blood glucose was observed between group. Conclusion: The results observed supports the potential hepatoprotective function of Glucevia®, which seems to prevent fatty liver formation in type 2 diabetes mice model.

The status of liver fibrosis evaluated by non-alcoholic fatty liver disease fibrosis score in hospitalized patients with type 2 diabetes mellitus

Objective To evaluate the severity of non-alcoholic fatty liver disease(NAFLD) and progressive liver fibrosis(stage＞2)in hospitalized patients with type 2 diabetes mellitus(T2DM) by using NAFLD fibrosis score (NFS).The risk factors associated with progressive fibrosis were also analyzed.Methods A total of 721 hospitalized patients with T2DM and uhrasound verified NAFLD were involved.The history information and laboratory examinations were collected,NFS was calculated.The low cutoff score (-1.455) of NFS was used to exclude,and high cutoff score (0.676) to further accurately diagnose progressive fibrosis.Results (1) A total of 721 subjects (male/female 371/350) were diagnosed as NAFLD by ultrasound.In those subjects,173 patients were with progressive fibrosis (24.0％),111 patients without progressive fibrosis (15.4％),and 437 patients (60.6％) with NFS ranged from-1.455 to 0.676.(2) Aging,raised body mass index,aspartate amino transferase/alanine aminotransferase (AST/ALT) ratio,lowered albumin,and platelet were risk factors for progressive fibrosis of NAFLD.In addition,NFS was positively correlated with duration of diabetes,waist circumference,SBP,glycated albumin (GA),and GA/HbA1c(all P＜0.01),and negatively with red blood cell count,hemoglobin,white blood cell count (WBC),total cholesterol (TC),triglyceride,apolipoprotein-B,ALT,γ-glutamyltranspeptidase (all P＜0.01),AST,low-density lipoprotein cholesterol (all P＜0.05).(3) Logistic stepwise regression analysis showed diabetes duration,waist circunference,and GA were positively correlated with progressive liver fibrosis(OR =1.182,1.076,1.074,all P＜0.01),and negatively with WBC and TC (OR =0.613,0.703,all P＜0.01).Conclusions The detection rate of progressive fibrosis in patients with NAFLD and T2DM was approximately 24.0％ by applying NFS.Only 15.4％ of those subjects could be excluded from progressive fibrosis.It suggests that we should be alert to the risk of liver fibrosis in patients with type 2 diabetes. Key words: Diabetes mellitus, type 2 ; Non-alcoholic fatty liver disease ; Fibrosis