And/or Aspartate Aminotransferase Research Articles

Abstract MP25: Effect of Marine Omega-3 Fatty Acids on Risk of Incident Cardiovascular Disease Among Individuals With Non-Alcoholic Fatty Liver Disease: Secondary Analysis of a Randomized Clinical Trial

Background: Individuals with non-alcoholic fatty liver disease (NAFLD) are at increased risk for developing cardiovascular disease (CVD), often attributed to adverse metabolic derangements such as insulin resistance and elevated triglycerides. Marine omega-3 (n-3) fatty acids may partially ameliorate these metabolic consequences. Whether supplementation with n-3 fatty acids can reduce the risk of CVD in NAFLD remains unknown. Aims: To investigate the association between a NAFLD phenotype and incident CVD as well as assess whether randomization to n-3 fatty acids can modify this risk. Methods: Among 16,824 participants from the Vitamin D and Omega-3 Trial (VITAL; NCT01169259; a 2x2 factorial randomized trial of 1 g/d of EPA+DHA or 2000 IU/d of vitamin D 3 ) who provided baseline blood samples, we measured liver function tests. NAFLD was defined as baseline alanine aminotransferase (ALT)>40 U/L and/or aspartate aminotransferase (AST)>35 U/L, per guidance from the American Association for the Study of Liver Diseases. Incident CVD was a composite of myocardial infarction (MI), stroke, and CVD death. Multivariable-adjusted Cox models (adjusted for demographics, cardiovascular risk factors, and treatment assignment) were used to estimate hazard ratios (aHRs) and 95% confidence intervals (CI) for NAFLD with incident CVD. Effect of randomization to n-3 fatty acids was assessed among individuals with and without NAFLD. Results: We identified 2,495 participants with NAFLD at baseline, who tended to be younger, male, and non-White compared to individuals without NAFLD. After a median follow-up of 5.3 years, 522 CVD events were ascertained, with 101 occurring among those with NAFLD. Compared to individuals without NAFLD, those with NAFLD were at higher risk of developing CVD, aHR (95%CI): 1.48 (1.19, 1.84), P =0.0004. This association was predominantly driven by a higher incidence of total stroke, 1.53 (1.08, 2.17), P =0.02, compared with MI, 1.15 (0.81, 1.64), P =0.43. Randomization to n-3 fatty acids did not significantly reduce CVD incidence among individuals with, 1.13 (0.77, 1.68) or without NAFLD, 1.02 (0.85,1.24), P interaction =0.70. Conclusion: In a large primary prevention trial of older individuals, NAFLD was associated with a higher risk of CVD, particularly stroke. Randomization to n-3 fatty acids did not significantly reduce CVD outcomes in this high-risk population.

Concentrations of S100B and neurofilament light chain in blood as biomarkers for checkpoint inhibitor–induced CNS inflammation

Cancer treatment with immune checkpoint inhibition (ICI) can cause immune-related adverse events in the central nervous system (CNS irAE). There are no blood biomarkers to detect CNS irAE. We investigated if concentrations of S100-calcium-binding protein B (S100B) and neurofilament light chain (NfL) in blood can be used as biomarkers for CNS irAE and assessed the incidence of CNS irAE in a cohort of ICI-treated patients. In this single-centre, retrospective cohort study, we examined medical records and laboratory data of 197 consecutive patients treated with combined CTLA-4 and PD-1 inhibition (ipilimumab; ipi+nivolumab; nivo) for metastatic melanoma or renal cell carcinoma. CNS irAE was diagnosed using established criteria. Concentrations of S100B and NfL in blood were measured in patients with CNS irAE and in 84 patients without CNS irAE. Nine of 197 patients (4.6%) fulfilled criteria for CNS irAE. S100B and NfL in blood increased during CNS inflammation and normalized during immunosuppression. CNS irAE was detected with a sensitivity of 100% (S100B) and 79% (NfL) and a specificity of 89% (S100B) and 74% (NfL). Patients with CNS irAE had simultaneous increased concentration of C-reactive protein (CRP) (9/9) and alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) in blood (8/9). Analysis of S100B, NfL and CRP in blood facilitates the diagnosis of CNS irAE. CNS irAE may be more common than previously reported. There may be shared immune mechanisms between CNS and hepatitis irAE. Supported by funding from the Swedish Cancer Foundation, the ALF-agreement, and Jubileumsklinikens Cancerfond.

Minimal Risk of Drug-Induced Liver Injury With Molnupiravir and Ritonavir-Boosted Nirmatrelvir

Minimal Risk of Drug-Induced Liver Injury With Molnupiravir and Ritonavir-Boosted Nirmatrelvir

Prognostic factors for adult-onset Still disease: a retrospective analysis of 90 patients in China.

Adult-onset Still disease (AOSD) is a systemic auto-inflammatory disorder that can be divided into monocyclic, polycyclic and chronic arthritis subtypes based on the clinical course. Since the prognoses of the three patterns of AOSD are substantially different, it is important to identify clinical indices that can be used to differentiate them. To investigate the clinical features of the three patterns of AOSD in order to determine possible prognostic factors. Clinical records of inpatients admitted with a probable diagnosis of AOSD to the Second Xiangya Hospital of Central South University between 2009 and 2019 were retrospectively studied. Ninety patients were divided into a monocyclic group, a polycyclic group and a chronic arthritis group. The average age at onset was 39.01 ± 13.04 years, and female to male ratio was 3.3. Elevated white blood cell (WBC) count, even beyond 15 × 109/L, and increased serum level of interleukin-6 (IL-6) >5.3pg/mL (upper limit of normal value) were associated with the recurrence of AOSD, while the presence of rash and increased level of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) were more commonly seen in the monocyclic group. Our results indicate that gender, presence of rash, WBC count, serum level of IL-6, and ALT and/or AST are promising prognostic factors for AOSD. However, larger cohorts are needed to validate these factors due to the limitations of the retrospective study design and relatively small sample size.

Features of Changes in Blood Parameters of Some Laboratory Syndromes and their Constellations in Patients with Liver Cirrhosis with Disorders of Bone Mineral Density

Introduction. Investigation of changes in certain laboratory blood parameters, and verification with their help of laboratory syndromes, and detection of constellations of laboratory syndromes in patients with liver cirrhosis (LC), which is possible for clinicians of all levels of medical care, need to clarify their features, which would suspect or verify disorders of bone mineral density (DBMD). The aim of the study. Investigate the features of changes in blood parameters of some laboratory syndromes and their constellations in patients with liver cirrhosis with disorders of bone mineral density. Materials and methods. 90 patients (27 women (30.0 %) and 63 men (70.0 %) aged 18 to 66 years) with LC were stratified into several groups: experimental (EG) (patients with LC with DBMD) (72 patients (80.0 %))), from which two subgroups were formed - EG A (patients with LC with osteopenia) (46 patients (63.9 %))), and EG B (patients with LC with osteoporosis) (26 patients (36.1 %)))) and the comparison group (CG) (patients with LC without DBMD) (18 patients (20.0 %))). Among the laboratory syndromes and their blood parameters were studied such as: cytolysis (increased in plasma alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)), mesenchymal-inflammatory syndrome (increased thymol test (TT) and/or gamma-globulins), hepatocellular insufficiency (decreased fibrinogen, prothrombin index (PTI), total protein, or albumin), cholestasis (increased alkaline phosphatase (AP), gamma-glutamyltranspeptidase (GGTP), total bilirubin), porto-systemic shunting (decreased sodium and/or potassium, and/or increased creatinine) and dyslipidemia (increased serum cholesterol, B-lipoproteins, triglycerides, low-density lipoprotein (LDL), decreased high-density lipoprotein (HDL)). The study was performed in three stages, the first of which studied the features of laboratory syndromes and blood parameters that characterize them, the second - constellations of laboratory syndromes, and the third - the simultaneous manifestation of a number of different laboratory syndromes in patients with LC with DBMD, osteopenia and osteoporosis. Each stage involved three steps: the first was to study the frequency of laboratory syndromes and their laboratory blood parameters in patients with LC and determine their share in each of the study groups, the second was to identify significant differences in the frequency of cases, and the third was to identify a direct stochastic relationship between the studied trait and DBMD, including osteopenia and osteoporosis. Results. After performing all three stages and each of the planned steps, it was found that laboratory syndromes and their constellations are more common among patients with bone lesions. However, there are statistically significant differences in the frequency of cases between EG and CG in the case of a decrease in HDL and the simultaneous manifestation of five different laboratory syndromes; between EG A and CG - decrease in HDL and simultaneous manifestation of two and three different laboratory syndromes; between EG B and CG - increase in AP, decrease in HDL and simultaneous manifestation of five different laboratory syndromes; between EG A and EG B - cytolysis syndrome, increase in AST, gamma-globulins, AP, constellation of cytolysis syndrome with hepatocellular insufficiency syndrome or cholestasis syndrome and constellation of all three syndromes. Confirmed direct stochastic association was found: with all manifestations of DBMD - increase in TT, a decrease in HDL, and constellations of cytolysis, mesenchymal-inflammatory and dyslipidemic syndrome, which may be supplemented by hepatocellular insufficiency syndrome and/or cholestasis syndrome; with osteopenia - increase in TT, increase in blood cholesterol, decrease in HDL, and constellations containing dyslipidemia syndrome and supplemented by mesenchymal-inflammatory, and/or cytolysis and/or hepatocellular insufficiency and/or cholestasis syndromes, and simultaneously only two laboratory syndromes in a patient with LC; with osteoporosis - increase in blood AST, TT, gamma-globulins, AP, decrease in PTI, potassium, HDL, the presence of cytolysis, cholestasis syndromes, constellations of cytolysis syndrome with hepatocellular insufficiency syndrome and/or cholestasis syndrome, which are supplemented by mesenchymal-inflammatory and dyslipidemic syndrome, and the simultaneous manifestation only three or five different laboratory syndromes. Conclusions. Laboratory syndromes, blood parameters that characterize them, and constellations of laboratory syndromes have certain features in patients with cirrhosis of the liver with disorders of bone mineral density, as in most cases are more common in patients with bone lesions and have a confirmed stochastic relationship with disorders of mineral density bone tissue in general, and osteopenia and osteoporosis separately. Keywords: cirrhosis, bone mineral density, osteopenia, osteoporosis, cytolysis, mesenchymal-inflammatory, hepatocellular insufficiency, cholestasis, porto-systemic shunting, dyslipidemia, alanine aminotransferase, aspartate aminotransferase, thymol test, total protein, albumin, gamma-globulin, fibrinogen, prothrombin index, alkaline phosphatase, gamma-glutamyltranspeptidase, bilirubin, sodium, potassium, creatinine, cholesterol, B-lipoproteins, triglycerides, low-density lipoproteins, high-density lipoproteins.

Prevalence of elevated liver transaminases and their relationship with alcohol use in people living with HIV on anti-retroviral therapy in Uganda.

Isoniazid preventive therapy (IPT) reduces tuberculosis reactivation and mortality among persons living with HIV (PLWH), yet hepatotoxicity concerns exclude "regular and heavy alcohol drinkers" from IPT. We aimed to determine the prevalence of elevated liver transaminases among PLWH on antiretroviral therapy (ART) who engage in alcohol use. The Immune Suppression Syndrome Clinic of Mbarara, Uganda. We defined elevated liver transaminases as ≥1.25 times (X) the upper limit of normal (ULN) for alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST). We evaluated the associations of current alcohol use and other variables of interest (sex, body mass index, and ART regimen) with elevated transaminases at study screening, using multivariable logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence intervals (CI). Among 1301 participants (53% female, median age 39 years, 67.4% current alcohol use), 18.8% (95% CI: 16.8-21.1) had elevated transaminases pre-IPT, with few (1.1%) severe (≥5X the ULN). The proportion with any elevation among those currently using alcohol and those abstaining was 22.3% and 11.6%, respectively (p<0.01). In multivariable analyses, those currently using alcohol had higher odds of elevated transaminases compared to those abstaining (aOR 1.65, 95% CI 1.15-2.37) as did males compared to females (aOR 2.68, 95% CI 1.90-3.78). Pre-IPT elevated transaminases among PLWH receiving ART were common, similar to prior estimates, but severe elevations were rare. Current drinking and male sex were independently associated with elevated transaminases. Further research is needed to determine the implications of such transaminase elevations and alcohol use on providing IPT.

Lactate-dehydrogenase associated with mortality in hospitalized patients with COVID-19 in Mexico: a multi-centre retrospective cohort study

Introduction and ObjectivesAs of January 2021, over 88 million people have been infected with COVID-19. Almost two million people have died of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A high SOFA score and a D-Dimer >1 µg/mL identifies patients with high risk of mortality. High lactate dehydrogenase (LDH) levels on admission are associated with severity and mortality. Different degrees of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) abnormalities have been reported in these patients, its association with a mortality risk remains controversial. The aim of this study was to explore the correlation between LDH and in-hospital mortality in Mexican patients admitted with COVID-19. Materials & MethodsWe performed a retrospective multi-centre cohort study with 377 hospitalized patients with confirmed SARS-CoV-2 in three centres in Mexico City, Mexico, who were ≥18 years old and died or were discharged between April 1 and May 31, 2020. ResultsA total of 377 patients were evaluated, 298 (79.1%) patients were discharged, and 79 (20.9%) patients died during hospitalization. Non-survivors were older, with a median age of 46.7 ± 25.7 years old, most patients were male. An ALT > 61 U/l (OR 3.45, 95% CI 1.27−9.37; p = 0.015), C-reactive protein (CRP) > 231 mg/l (OR 4.71, 95% CI 2.35−9.46; p = 0.000), LDH > 561 U/l (OR 3.03, 95% CI 1.40−6.55; p = 0.005) were associated with higher odds for in-hospital death. ConclusionsOur results indicate that higher levels of LDH, CRP, and ALT are associated with higher in-hospital mortality risk in Mexican patients admitted with COVID-19.

Novel glucose-lowering drugs for non-alcoholic fatty liver disease.

BACKGROUNDThe efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) is unknown.AIMTo evaluate the efficacy of glucose-lowering drugs dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors in treating NAFLD and to perform a comparison between these treatments.METHODSElectronic databases were systematically searched. The inclusion criteria were: Randomized controlled trials comparing DPP-4 inhibitors, GLP-1 RAs, or SGLT2 inhibitors against placebo or other active glucose-lowering drugs in NAFLD patients, with outcomes of changes in liver enzyme [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] from baseline.RESULTSNineteen studies were finally included in this meta-analysis. Compared with placebo or other active glucose-lowering drug treatment, treatment with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors all led to a significant decrease in ALT change and AST change from baseline. The difference between the DPP-4 inhibitor and SGLT2 inhibitor groups in ALT change was significant in favor of DPP-4 inhibitor treatment (P < 0.05). The trends of reduction in magnetic resonance imaging proton density fat fraction and visceral fat area changes were also observed in all the novel glucose-lowering agent treatment groups.CONCLUSIONTreatment with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors resulted in improvements in serum ALT and AST levels and body fat composition, indicating a beneficial effect in improving liver injury and reducing liver fat in NAFLD patients.

Abstract P6-18-15: Ribociclib + endocrine therapy in hormone receptor-positive, HER2-negative advanced breast cancer: A pooled safety analysis

Abstract Background: In Phase III trials, ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) + various endocrine therapy (ET) partners has demonstrated significantly prolonged progression-free survival vs placebo (PBO) + ET in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC). Here we further evaluate the safety of RIB-based regimens of interest for the proposed indication (i.e. with a non-steroidal aromatase inhibitor [NSAI] or fulvestrant [FUL]) using pooled data from three Phase III trials (MONALEESA [ML]-2 [NCT01958021], -3 [NCT02422615], and -7 [NCT02278120]). Methods: Postmenopausal pts with HR+, HER2– ABC received RIB (600 mg/day; 3-weeks-on/1-week-off) or PBO + letrozole (LET; 2.5 mg/day; ML-2 [no prior ET for ABC]) or FUL (500 mg, Days 1 and 15 of Cycle 1, then Day 1 of every cycle thereafter; ML-3; no or ≤1 prior line of ET for ABC]). Premenopausal pts (ML-7; no prior ET and ≤1 chemotherapy for ABC]) received RIB or PBO + anastrozole (1 mg/day)/LET (2.5 mg/day) + goserelin (3.6 mg every 28 days). Adverse events (AEs) were characterized per Common Terminology Criteria for Adverse Events v4.03; safety analyses included time to first event, duration of event, and rate of associated RIB/PBO discontinuations. Results: Data for 1883 pts were pooled; 1065 pts received RIB + ET and 818 pts received PBO + ET (median exposure to study treatment: 17 and 13 months, respectively). Exposure-adjusted incidence rates for AEs of special interest were 561 and 131 per 100 pt-years in the RIB and PBO arms, respectively. The most common all-causality Grade 3/4 AEs (≥10% in any arm; RIB vs PBO) were neutropenia (59% vs 2%), leukopenia (18% vs 1%), and hypertension (13% vs 13%). A new Fridericia's corrected QT interval (QTcF) &amp;gt;480 ms occurred in (n/N) 52/1054 (5%) vs 11/814 (1%) pts in the RIB vs PBO arms; a new QTcF &amp;gt;500 ms occurred in 14/1054 (1%) vs 1/814 (&amp;lt;1%) pts. Median time to first event for Grade ≥2 neutropenia, elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), and QTc prolongation in the RIB arm was 2, 12, and 2 weeks, respectively; median duration of first Grade ≥2 event was 4, 4, and 2 weeks. In the RIB arm vs PBO arms, 7% vs 3% of pts discontinued study treatment due to AEs; common all-grade AEs leading to RIB/PBO discontinuation (≥2% in any arm) were elevated ALT (4% vs &amp;lt;1%) and elevated AST (2% vs 1%). Discontinuation due to QT prolongation occurred in 4 pts in the RIB arm and 2 in the PBO arm (both &amp;lt;1%). All-grade serious AEs occurred in 25% of pts in the RIB arm vs 15% of pts in the PBO arm. Conclusions: RIB in combination with various ET partners continues to demonstrate a predictable and manageable tolerability profile across a broad population of pts with HR+, HER2– ABC. Citation Format: Burris HA, Chan A, Im S-A, Chia S, Tripathy D, Esteva FJ, Campone M, Bardia A, Kong O, Bao W, Diaz-Padilla I, Rodriguez Lorenc K, Yardley DA. Ribociclib + endocrine therapy in hormone receptor-positive, HER2-negative advanced breast cancer: A pooled safety analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-15.

A Multicenter Study Into Causes of Severe Acute Liver Injury

The differential diagnosis of an increase in alanine aminotransferase (ALT) level and/or aspartate aminotransferase (AST) level of ≥1000 IU/L often is stated to include 3 main etiologies: ischemic hepatitis, acute viral hepatitis (typically hepatitis A and hepatitis B), and drug-induced (more specifically, acetaminophen/paracetamol) liver injury (DILI).1 Unfortunately, there are a paucity of studies examining the most common causes of acute liver injury (ALI) and those that have been published have been small,2 single-center,2 or examined less severe increases in ALT or AST levels.3,4 We conducted a multicenter study of all patients with an ALT and/or AST level ≥1000 IU/L. Our study had 3 main goals: (1) to determine the most common causes of an ALT and/or AST level ≥1000 IU/L, along with their relative frequencies; (2) todetermine differences in etiology based on hospital type (liver transplant center, community hospital, Veterans Affairs hospital); and (3) to confirm or disprove the differential heuristic that ischemic hepatitis, acute viral hepatitis, and acetaminophen toxicity are the most common etiologies.

Role of Elevated Aminotransferases in ICU Patients with Rhabdomyolysis

To evaluate whether patients with rhabdomyolysis and serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) higher than 1000 IU/L had higher mortality that patients with low aminotransferases. Retrospective analysis of intensive care unit patients with rhabdomyolysis [creatine kinase (CK) higher than 5000 IU/L]. Patients were classified in two groups: low aminotransferases group, when AST and ALT were equal or lower to 1000 IU/L, and elevated aminotransferases group, when AST or ALT was above 1000 IU/L. Forty-six out of 189 patients included in the analysis (24.3%) had elevated aminotransferases. The mortality of patients with rhabdomyolysis was 25.9 per cent, being higher in patients with elevated aminotransferases compared with patients with low aminotransferases (60.9% vs 14.7%; P < 0.001). Mortality stratified by quartiles of CK in patients with low aminotransferases was independent of the level of CK (P = 0.67). Logistic regression analysis showed that the independent variables associated with mortality were Simplified Acute Physiology Score II [1.11 (1.07-1.16) for each point of increase, P < 0.001], the international normalized ratio value [4.2 (1.6-10.7) for each point of increase, P = 0.003], and the need of renal replacement therapy [5.4 (1.7-17.2), P = 0.004]. Patients with rhabdomyolysis with elevated serum aminotransferases had higher mortality than patients with low serum aminotransferase levels.

The changes of the ratio of T helper 17 and regulatory T cells in the peripheral blood of patients with anti-tuberculosis drug-induced liver injury and its significance

Objective To observe the changes of the peripheral blood T helper (Th)17 cells/regulatory T cells (Treg) ratio in patients with anti-tuberculosis drug-induced liver injury, and to explore the relationship between Th17/Treg ratio and liver function. Methods Ninety inpatients with the diagnosis of secondary pulmonary tuberculosis (TB) from Affiliated Hospital of Zunyi Medical College from Feb. 2013 to Mar. 2015 were included in this study. All these patients had normal base line liver function. After 2 weeks of anti-TB chemotherapy, 21 patients with alanine transaminase (ALT) and/or aspartate aminotransferase (AST) ≥2×upper limit of normal (ULN) were defined as TB with liver injure group, the other 69 patients with ALT and/or AST<2×ULN were defined as TB with non-liver injured group. Before treatment and two weeks after anti-TB therapy, the peripheral blood Th17/Treg ratios and liver functions of all patients in both groups were detected in order to compare the changes of Th17/Treg ratios pre and post anti-TB chemotherapy and to explore the relationship between Th17/Treg ratio and ALT/AST levels. Student's t test was used for statistical analysis, and Pearson correlation analysis was used for correlation test. Results Before treatment, there was no statistical significance of Th17, Treg and Th17/Treg ratio between groups (P>0.05). The Th17 levels in TB with liver injured group ([2.522±0.388]/mL vs [2.075±0.369]/mL, t=3.633, P 0.05). The Th17 level and Th17/Treg ratio in TB with liver injured group were significantly higher than those in TB with non-liver injured group (t=2.203, P 0.05). Conclusion The changes of Th17/Treg ratio are related with anti-TB drug-induced liver injury in patients with secondary pulmonary tuberculosis. Key words: Tuberculosis, pulmonary; Drug-induced liver injury; Antitubercular; Th17/Treg

Hepatotoxic effects of mycotoxin combinations in mice

This study was performed to assess the individual and combined toxic effects of aflatoxin B1 (AFB1), zearalenone (ZEA) and deoxynivalenol (DON) within the liver of mice. A total of 56 4-week-old weanling female mice were divided into seven groups (n = 8). For 2 weeks, each group received an oral administration of either solvent (control), AFB1, ZEA, DON, AFB1 + ZEA, AFB1 + DON or ZEA + DON per day. The results showed that AFB1, ZEA and DON induced liver injury, indicated by elevated relative liver weight, activities of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), as well as decreased albumin (ALB) and/or total protein (TP) concentration in the serum. These mycotoxins also decreased hepatic total antioxidant capacity (T-AOC), and/or increased the concentration of malondialdehyde (MDA). Moreover, AFB1 + DON displayed synergistic effects, while AFB1 + ZEA displayed antagonistic effects on those parameters previously described. Furthermore, the apoptotic potential was demonstrated associated with an upregulation of the apoptotic genes Caspase-3 and Bax, along with a downregulation of the antiapoptotic gene Bcl-2 in liver. In conclusion, this study provides a better understanding of the toxic effects of AFB1, ZEA, DON, alone or in combinations on the liver of mice, which could contribute to the risk assessment of these mycotoxins in food and feed.

Prevalence and features of fatty liver detected by physical examination in Guangzhou

To investigate the prevalence of fatty liver discovered upon physical examination of Chinese patients and determine the associated clinical characteristics. A total of 3433 consecutive patients who received physical examinations at the Huangpu Division of the First Affiliated Hospital at Sun Yat-sen University in Guangzhou, China from June 2010 to December 2010 were retrospectively enrolled in the study. Results of biochemical tests, abdominal ultrasound, electrocardiography, and chest X-ray were collected. The diagnosis of fatty liver was made if a patient met any two of the three following ultrasonic criteria: (1) liver and kidney echo discrepancy and presence of an increased liver echogenicity (bright); (2) unclear intrahepatic duct structure; and (3) liver far field echo decay. The study population consisted of 2201 males and 1232 females, with a mean age of 37.4 ± 12.8 years. When all 3433 patients were considered, the overall prevalence of hyperlipidemia was 38.1%, of fatty liver was 26.0%, of increased alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels was 11.9%, of gallstone was 11.4%, of hyperglycemia was 7.3%, of hypertension was 7.1%, and of hyperuricemia was 6.2%. Of the 2605 patients who completed the abdominal ultrasonography exam, 677 (26.0%) were diagnosed with fatty liver and the prevalence was higher in males (32.5% vs females: 15.3%, P < 0.001). The overall prevalence of fatty liver increased with age, with the peak prevalence (39.5%) found in the 60 to 70-year-old age group. Among patients between the ages of 18 to 50-year-old, the prevalence of fatty liver was significantly higher in males (20.2% vs females: 8.7%, P < 0.001); the difference in prevalence between the two sexes in patients > 50-year-old did not reach statistical significance. Only 430 of the patients diagnosed with fatty liver had complete information; among those, increased ALT and/or AST levels were detected in only 30%, with all disturbances being mild or moderate. In these 430 patients, the overall prevalence of hypertriglyceridemia was 31.4%, of mixed type hyperlipidemia was 20.9%, of hypercholesterolemia was 12.3%, of hyperglycemia was 17.6%, of hypertension was 16.0%, of hyperuricemia was 15.3%, and of gallstone was 14.4%. Again, the prevalences of hypertriglyceridemia and hyperuricemia were higher in males (hypertriglyceridemia, 36.0% vs females: 12.0%, P < 0.05; hyperuricemia, 17.3% vs females: 7.2%, P < 0.05); in contrast, however, the prevalences of mixed type hyperlipidemia and hypercholesterolemia was higher in females (mixed type hyperlipidemia, 18.7% vs females: 30.1%, P < 0.05, hypercholesterolemia, 9.5% vs females: 24.1%, P < 0.05). Finally, comparison of the fatty liver group to the non-fatty liver group showed that prevalences of hyperlipidemia, hyperglycemia, hypertension, and hyperuricemia were higher in the former (all P < 0.01). A high prevalence of fatty liver is detected upon physical examination in Guangzhou, and the primary associated clinical findings are hyperlipidemia, hyperglycemia, hypertension, and hyperuricemia.

Early lactate clearance as a reliable predictor of initial poor graft function after orthotopic liver transplantation

Initial poor graft function (IPGF) following orthotopic liver transplantation is a major determinant of postoperative survival and morbidity. Lactate clearance is a good marker of liver function. In this study, we investigated the clinical utility of early lactate clearance as an early and accurate predictor for IPGF following liver transplantation. This was a prospective observational study of 222 patients referred to the surgical intensive care unit (SICU) after orthotopic liver transplantation. The IPGF group consisted of patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1500 IU/L within 72 hours after orthotopic liver transplantation. Early lactate clearance was defined as lactate at SICU presentation (hour 0) minus lactate at hour 6, divided by lactate at SICU presentation. The model for end-stage liver disease (MELD) score, Child-Pugh score and laboratory data including AST, ALT, total bilirubin (TB) and prothrombin time (PT) were recorded at SICU presentation and compared between the non-IPGF and IPGF groups. Receiver operating characteristic (ROC) curves were plotted to measure the performance of early lactate clearance, MELD score, Child-Pugh score, TB and PT. IPGF occurred in 45 of the 222 patients (20.3%). The early lactate clearance in the non-IPGF group was markedly higher than that in the IPGF group (43.2+/-13.8% vs 13.4+/-13.7% P<0.001). The optimum cut-off value for early lactate clearance predicting IPGF was 24.8% (sensitivity 95.5%, specificity 88.9%). The area under the curve of the ROC was 0.961, which was significantly superior to MELD score, Child-Pugh score, TB and PT. Patients with early lactate clearance ≤24.8% had a higher IPGF rate (OR=169) and a higher risk of in-hospital mortality (OR=3.625). Early lactate clearance can serve as a prompt and accurate bedside predictor of IPGF. Patients with early lactate clearance less than 24.8% are associated with a higher incidence of IPGF.

Risk of elevated liver enzymes associated with TNF inhibitor utilisation in patients with rheumatoid arthritis

ObjectiveLiver function test (LFT) elevations are reported with the use of tumour necrosis factor inhibitors (TNF-Is). The aim of this study was to compare LFT elevations in patients with rheumatoid...

A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity

We explored the role of the adiponutrin (PNPLA3) nonsynonymous-rs738409 single nucleotide polymorphism (SNP) in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) and whether this SNP contributes to the severity of histological disease. Two hundred sixty-six individuals were evaluated in a case-control association study, which included 172 patients with features of NAFLD and 94 control subjects. The rs738409 G allele was significantly associated with NAFLD (P < 0.001; OR 2.8 95%, CI 1.5-5.2), independent of age, sex, body mass index (BMI), and Homeostasis Model Assessment (HOMA) index. When we tested the hypothesis of a relation between the SNP and the histological spectrum of NAFLD, a significant association was observed [chi2 19.9, degree of freedom (df): 2, P < 5 x 10(-5), adjusted for HOMA and BMI]. The degree of liver steatosis, as evaluated by liver biopsy, was significantly associated with the rs738409 G allele. Patients with CC genotype showed a lower steatosis score (14.9% +/- 3.9) in comparison with the CG genotype (26.3% +/- 3.5) and GG genotype (33.3% +/- 4.0) (P < 0.005). The proportion of the total variation attributed to rs738409 genotypes was 5.3% (beta 0.23 +/- 0.07; P < 0.002). Our data suggest that the rs738409 G allele is associated not only with fat accumulation in the liver but also with liver injury, possibly triggered by lipotoxicity.

A prospective randomized study using N-acetyl-L-cysteine for early liver toxicity after allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (ASCT) and its conditioning with chemoradiotherapy often results in liver toxicity, the most severe form being veno-occlusive liver disease (VOD). N-acetyl-L-cysteine (NAC), an antioxidant glutathione precursor, may provide protection from liver toxicity. Patients with elevated bilirubin (>26 mmol/l) and/or elevated (ALT) (>1.4 microkat/l) and/or aspartate aminotransferase (AST) (>1.4 microkat/l) levels were randomized to treatment with NAC or no treatment. Among 522 transplanted patients, 160 were included in the trial. NAC was given, 100 mg/kg per day, as a 6-h i.v. infusion until normalization of bilirubin, ALT and AST values. Maximum bilirubin level was the same in patients randomized to NAC (n=72) or controls (n=88). Increase and recovery of ALT and AST were the same in patients randomized to NAC or controls. There were two patients in the NAC group who developed VOD, as compared to three of the controls. To conclude, NAC does not improve liver toxicity after ASCT.

Retrospective study of the hepatic safety profile of patients concomitantly treated with caspofungin and cyclosporin A

Mild, transient alanine aminotransferase (ALT) elevations were seen in Phase I studies of caspofungin and cyclosporin A (CsA). We conducted a retrospective chart review at four sites to characterize the hepatic safety in patients receiving > or =1 day of both drugs over a 20-month period. Investigators assessed reasons for discontinuing concomitant therapy and the presence/etiology of any hepatotoxicity. Forty patients receiving concomitant therapy for 1-290 days (median 17.5 days) were identified. Although common, liver enzyme abnormalities were frequently attributed to other comorbidities or medications. ALT and/or aspartate aminotransferase (AST) elevations occurred in 14 patients (35%). Five had AST elevations at least possibly related to caspofungin/CsA, but none were >3.6 times the normal upper limit. No ALT elevations were related to caspofungin/CsA. Two of 4 patients had discontinuation of therapy because of hepatotoxicity possibly related to caspofungin/CsA. No serious adverse events occurred because of caspofungin. These data do not suggest a significant risk of clinically relevant hepatotoxicity with concomitant caspofungin/CsA.

Combining carbohydrate-deficient transferrin and gamma-glutamyltransferase to increase diagnostic accuracy for problem drinking.

To examine methods for combining quantitative results for serum carbohydrate deficient transferrin (CDT), gamma-glutamyltransferase (GGT) and/or aspartate aminotransferase (AST), and refining these by inclusion of patient characteristics. Data from 1684 subjects, recruited from the general population, abstainer groups and alcohol treatment centres (participants in the five nations WHO/ISBRA study of biological markers of alcohol use), were used to develop clinical rules for combining results of GGT, AST and CDT. The algorithm derived by Sillanaukee and Olsson was tested, and compared with new algorithms derived by logistic regression and discriminant analysis. Diagnostic accuracy was assessed by area underneath the receiver operator characteristic curve. Effects of adding gender and clinical information to the algorithm were estimated. The predictive ability of combination rules derived from the two studies and by two different statistical techniques was remarkably consistent. For men, combining lnCDT and lnGGT provided the best accuracy for detecting daily consumption of 60 g ethanol or more in the past 30 days. For women, GGT alone provided the best accuracy for that consumption level. Clinical variables added significantly to the diagnostic accuracy of the models for both men and women, and conversely the test results modified the probability of problem drinking as assessed from clinical data alone. A graphic method was produced to help clinicians estimate probabilities for consumption of 60 g or more per day. Combining biochemical markers enhances detection of problem drinking in men but not in women. Information on clinical variables increases the ability to correctly detect problem drinking.