High Liver Enzymes Research Articles

STUDY THE NUTRITIONAL AND THERAPEUTIC EFFECT OF FLAXSEED, SUNFLOWER AND PUMPKIN SEEDS ON THE LEVEL OF BLOOD LIPIDS AND WEIGHT GAIN ON RATS

This study was conducted to investigate the use of flaxseed, sunflower and pumpkin seeds to improve the level of serum lipid profile, high liver enzymes, renal function and antioxidant enzymes. Fifty four mature male albino rats weighing 150±10g were divided into two main groups; control negative group (6 rats) was fed on basal diet and the second main group (48 rats) which was fed on hyperlipidemic diet for four weeks to induce hyperlipidemia. Rats on the second main group supplements were divided into eight subgroups (each group consisted of 6 rats and fed on basal diet. Group were as a following: The first group was left as a control positive, the second group fed diet containing 5 % flaxseeds / kg in diet. The third group fed diet containing 5 % sunflower seeds / kg in diet. The fourth group fed diet containing 5 % pumpkin seeds kg in diet. The fifth group fed diet containing 5 % mix of pumpkin and sunflower seeds. The sixth group fed diet containing 5 % mix of pumpkin and flaxseeds. The seventh group fed diet containing 5 % mix of sunflower and flaxseeds. The eighth group fed diet containing 5 % mix of sunflower, flaxseeds and pumpkin. Feeding experiment lasted for 28 days. Serum total cholesterol, triglycerides, lipoprotein fractions (HDLc, LDLc and VLDLc), atherogenic index (AI), liver enzymes(ALT, AST, ALP),total protein, albumin, globulin, albumin/globulin (A/G) ratio, uric acid, urea, creatinine, antioxidant levels superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and malondialdehyde (MDA) were determined. Histopathological changes of heart was examined. The obtained results concluded that feeding with flaxseed (5%), sunflower (5%) and pumpkin seeds (5%) improved liver, kidney functions, lipid profile, antioxidant levels (SOD), (CAT), (GPX), (MDA), heart tissues changes. According to the results, flaxseed, sunflower and pumpkin seeds could be used to improve the health situation of obese rats along with weight loss.

Abnormal glucose metabolism in patients with Fontan circulation: Unique characteristics and associations with Fontan pathophysiology

Fontan patients exhibit a high prevalence of abnormal glucose metabolism (AGM). We aimed to characterize AGM and clarify its association with Fontan pathophysiology. We prospectively evaluated AGM with plasma glucose dynamics [mg/dL; fasting glucose (FPG), and maximum glucose increase (PG-spike)] during oral glucose tolerance test and hemoglobin A1c (HbA1c) in 276 consecutive Fontan patients (aged 19 ± 7 years). Of these, 176 patients had serial AGM assessments with a mean interval of 6.5 years. Initial analysis revealed a high prevalence of impaired glucose tolerance (38.4%) and diabetes mellitus (DM) (4.7%), and positive family history, high HbA1c, and high central venous pressure independently predicted presence of DM. HbA1c was independently determined by hypersplenism and presence of DM (P < .05). Serial assessments revealed an increased PG-spike and a decreased HbA1c (P < .001 for both). Prevalence of DM increased (6.3% to 10.3%), and positive family history, high liver enzymes, and AGM predicted new onset of DM (P < .05 for all). Twenty-one patients died during 7.1-year follow-up. FPG (P < .01) and PG-spike (P < .05) independently predicted all-cause mortality. Particularly, patients with FPG ≤ 74 and/or PG-spike ≥85 had a mortality rate 8.7 times higher than those without (P = .0129). AGM progressed even in young adult Fontan patients, and HbA1c showed limited predictive value for progression. Oral glucose tolerance test plays important roles in uncovering unique Fontan AGM as well as predicting all-cause mortality.

Long-term sexual impairment in relationship with metabolic health in testicular germ-cell tumor survivors.

e16060 Background: Treatment for germ-cell tumors (GCT) results in long-term sexual difficulties in GCT survivors, as we have shown previously. This study aimed to correlate the long-term sexual difficulties with serum parameters of metabolic functioning. Methods: GCT survivors (N = 155) from a national cancer center completed a Sexual Function Questionnaire that was modified from PROMIS Sexual Function and Satisfaction Questionnaire at a median 10 years of follow up (range 5-32). Twenty-nine (18%), 30 (19%) and 20 (13%) survivors have suffered from severe difficulty to achieve erection, maintain erection and achieve orgasm, respectively. Severe difficulty was characterized as a score of 0-2 (scale 0-5) in respective questions from the questionnaire. Sexual impairment was then correlated with parameters of metabolic functioning assessed from peripheral blood of all survivors drawn at the day of the clinical visit. Results: Survivors with difficulty to achieve erection had significantly higher levels of alanine-aminotransferase (ALT), aspartate-aminotransferase (AST) and lactate-dehydrogenase (all P &lt; 0.05). Impaired ability to achieve an orgasm also correlated with significantly higher levels of ALT, AST and LDH (all P &lt; 0.05). Survivors with difficulty to maintain erection had higher levels of LDH (P = 0.02) and AST (trend for P = 0.06), but not ALT ( P = 0.5) and their cholesterol levels were significantly higher ( P = 0.04). Furthermore, survivors with higher levels of glucose ( P = 0.04), thyroid stimulating hormone ( P = 0.04), but not of free-thyroxin ( P = 0.3) suffered from difficulty to achieve orgasm. Conclusions: Our prospective study shows that an impairment in sexual function resulting from curative treatment of GCTs may be related to metabolic health. Higher liver enzymes may be indicative of endothelial dysfunction and cardiovascular disorder. Long-term sexual impairment in GCT survivors should be a subject of further translational research to uncover the underlying molecular mechanisms.

Final Height and Endocrine Complications in Patients with β-Thalassemia Intermedia: Our Experience in Non-Transfused Versus Infrequently Transfused Patients and Correlations with Liver Iron Content.

Backgroundβ-thalassemia intermedia (TI) spans a wide spectrum of severity and carries higher morbidity than previously recognized, including extramedullary hematopoiesis, leg ulcers, gallstones, thrombosis, secondary heart failure, pulmonary hypertension, skeletal deformity, growth retardation and endocrine abnormalities, such as diabetes mellitus, hypothyroidism, osteoporosis, and hypogonadism.ObjectivesTo evaluate the final height and the endocrine complications encountered in young adult patients with TI followed at Hematology Section, Doha (Qatar) in relation to liver iron content in non-transfused versus infrequently transfused TI patients.Patients and MethodsThis retrospective cohort study was performed on 28 young adults with TI who were randomly selected from the Hematology Clinic of the Hematology Section, National Centre for Cancer Care and Research, Hamad Medical Corporation of Doha (Qatar).Eligibility criteria for this retrospective analysis included TI patients diagnosed by complete blood count, hemoglobin electrophoresis and young adult age ( ≥ 18 years).Group 1 included nine patients who did not receive any blood transfusion, and Group 2 included 19 patients who infrequently received blood transfusions.Data recorded from charts included demographic characteristics (gender, date of birth, ethnicity), disease and treatment characteristics (e.g., transfusion frequency, history of chelation therapy, and splenectomy), auxological and pubertal data [growth percentiles and pubertal stages, and body mass index (BMI)], laboratory data and target organ complications (including endocrinopathies and liver disease). Iron overload was assessed by direct (liver iron content; LIC) and indirect methods (SF), and bone mass index (BMA) by dual-energy X-ray absorptiometry (DXA).ResultsShort stature [Final Height (Ht) SDS < −2] occurred in 25% of patients with no difference between the two groups of patients. Insulin growth factor 1 (IGF-1) SDS was low in 35.7 % of patients with no statistical difference among the two groups. Impaired fasting blood glucose occurred in 17.8% of patients, diabetes mellitus in 25% and hypogonadotropic hypogonadism in 10.7% of them. Morning cortisol was low in one patient. No thyroid or hypo-parathyroid abnormalities were detected in any patient. Liver iron content (LIC) > 15 mg/g dry weight and SF > 2,000 ng/mL were detected in 75% of the patients. The values resulted significantly higher in the transfused group (Group 2). High liver enzyme level (ALT) was detected in 42.8 % of patients, and the values were significantly higher in the transfused group (Group 2). Total and fetal Hb was significantly higher in group 1 versus group 2. Osteopenia was diagnosed in 14.3% of patients. Females had significantly better final height SDS, higher IGF-1 SDS, lower LIC and fasting blood glucose level compared to males. Significant correlations were found between Ht-SDS and IGF-1 SDS; LIC and SF, level; ALT and LIC, SF levels. Total and fetal Hb did not correlate significantly with Ht-SDS or IGF-1 level.ConclusionsA significant number of TI patients have high LIC, short stature and endocrine disorders. Patients who require occasional transfusions have more liver iron overload and higher hepatic dysfunction. Females appear to attain a better final adult height and have higher IGF1-SDS versus males. Our data emphasize the need for long term surveillance for identification of organ-specific risk factors and early disease manifestations. We also recommend close monitoring of endocrine and other complications, according to the international guidelines.

SUN-130 A Not-So-Simple Work-Up of Diabetes: A Case of MODY 5

Introduction: Maturity-onset diabetes of the young 5 (MODY-5) is a rare type of inherited diabetes mellitus. It is an autosomal dominant disease, manifesting as a clinically heterogeneous disorder with a lack of autoantibodies. On the molecular level, MODY 5 is due to defects of hepatocyte nuclear factors 1B (HNF1B), which not only cause structural abnormalities, but also intrinsic organ dysfunction in the kidneys, liver, and pancreas as well. Case: This is a 33 year old female presented for diabetes type 2 management. Her past medical history originated at the age of 7, diagnosed with short ureters with reflux leading to frequent pyelonephritis, requiring reconstructive surgery. At 15, found to have high liver enzymes, which have had variable and persistent elevation; she had 4 liver biopsies, which were pathologically unremarkable and no cause found. At 27, diagnosed with type 2 DM based on her HbA1c being >7 and initiated on metformin. Recently was also diagnosed with PCOS after a first trimester missed abortion and subsequent infertility. Abdominal US subsequently revealed bilateral renal cysts. Family history was remarkable for type 1 diabetes in her father, type 2 diabetes in her sister and maternal uncle, and renal dysfunction in her niece. Physical exam was unremarkable, and BMI was 19.53 kg/m2. Laboratory workup revealed elevated liver enzymes (Alkaline Phosphatase: 445 U/l; Bilirubin: 1.7 mg/dl, ASL: 106 U/L, ALT 248 U/L). A1C was 5.3% at that time. Based off the presentation and exam, it was felt that her disease process did not fit the classic paradigm of type 2 diabetes mellitus, no obesity, no hypertension and no dyslipidemia. This prompted autoimmune diabetes screening which was negative. A MODY Sequencing Panel was then performed, which was positive for MODY type 5; she was found to be heterozygous in the HNF1B gene, c.544+1G>A variant. Given her diagnosis, an insulin regimen was initiated but due to allergic reaction, she was then converted to glipizide orally. She is now following with medical genetics. Conclusion: MODY is not commonly seen in the diabetes population, where prevalence accounts for 2 to 5 % of known diabetics. MODY-5 is a more uncommon subset in the population with MODY, manifesting as 5-10% of such cases. As such, many MODY patients are often misclassified has having either type 1 or type 2 diabetes. Given other organ dysfunctions affected by MODY-5, a lack of diagnosis of this condition can delay monitoring and treatment of the disease. As such, recognition of MODY should be increased, as is need for early screening for patients if the disease is suspected. Citation: Dubois-Laforgue, D,. et al. (2017). Diabetes, Associated Clinical Spectrum, Long-term Prognosis, and Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1B ( HNF1B ) Molecular Defects. Diabetes Care, 40(11), 1436-1443. doi:10.2337/dc16-2462. PMID: 28420700

A Dual Farnesoid X Receptor Agonist /Soluble Epoxide Hydrolase Inhibitor Prevents Non‐Alcoholic Steatohepatitis in Mice

Non‐alcoholic steatohepatitis (NASH) is becoming the most prevalent metabolic liver disorder and is a serious global health burden. Farnesoid X receptor (FXR) agonists are in late stage clinical development to counter the disease and promise therapeutic efficacy. However, the multi‐factorial nature of NASH pathogenesis and progression indicate the need for a therapeutic approach that will target multiple pathophysiological aspects of NASH. We have developed a dual FXR agonist/soluble epoxide hydrolase (sEH) inhibitor (FXRA/sEHI) and investigated its ability to prevent NASH in toxin‐ and diet‐induced mouse NASH models. Toxin‐induced NASH was achieved in male C57BL/6 mice by injecting 200 μg streptozotocin (STZ) solution two days after birth and feeding a high‐fat diet after 4 weeks of age. Diet‐induced NASH was carried out in adult (8–12 weeks old) male C57BL/6J mice fed a methionine‐choline deficient diet (MCD; D518810) and was compared to mice fed a composition‐matched methionine‐choline replete control diet (D518754) for 4 weeks. In toxin‐induced NASH model, mice were orally treated with vehicle or FXRA/sEHI (10 mg/kg, thrice daily) or an FXR agonist obeticholic acid (OCA, 10 mg/kg, once daily) for 4 weeks. The mice from diet‐induced NASH model treated with FXRA/sEHI (10 mg/kg/d) or vehicle given in drinking water for 4 weeks. At the end of the 4‐week treatment period, blood was collected for biochemical analysis, liver tissue was collected for mRNA expression and histopathological analysis. Mice of the toxin‐induced NASH model had higher liver enzyme, hyperlipidemia, liver fibrosis, and steatosis. FXRA/sEHI treatment reduced these parameters (by 20–50%, P&lt;0.05), while OCA displayed weak or no beneficial effect on NASH (P&gt;0.05). In diet‐induced NASH model, the mice exhibited 2‐fold higher hepatic fibrosis, 2–6‐fold higher hepatic mRNA expressions of inflammatory and fibrotic markers, and marked hepatic steatosis (P&lt;0.05). The dual modulator FXRA/sEHI robustly prevented hepatic steatosis, fibrosis, and inflammation (by 50–80%, P&lt;0.05) compared to vehicle. Our results demonstrate strong potential for dual FXRA/sEHI modulators as a novel therapeutic strategy in NASH and advocate multi‐targeted approaches in NASH treatment.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

649: Impact of hepatitis C virus infection on buprenorphine dose in pregnancy

Buprenorphine (BUP) is the preferred medication for opioid maintenance therapy in pregnancy and is primarily metabolized in the liver. Given that hepatitis C virus (HCV) infection is common in opiate dependent individuals, we sought to determine whether liver dysfunction related to HCV infection impacts the dose of BUP needed during pregnancy. A retrospective cohort study of 266 pregnancies with antenatal exposure to BUP from 2015-2018 at a single center. Individuals positive for HCV infection versus women negative for HCV infection were compared. For HCV prevalence, Kruskal-Wallis tests were performed with continuous variable and Chi-Square tests with categorical variables. Spearman correlation tests were used to assess the relationship between BUP dose and HCV status. In patients with antenatal exposure to BUP, the average age was 29 (18-42) years and 99% were Caucasian. HCV infection was present in 39% of the population. Patients with HCV infection required less dose increases throughout pregnancy (p=0.02). Among the HCV positive cohort, a positive correlation was seen between HCV viral load and the liver enzymes AST (0.30, p=0.003) and ALT (0.25, p=0.01). A negative correlation was noted among the HCV positive cohort for HCV viral load in relation to BUP dose during the second trimester (-0.27, p=0.01) and third trimester (-0.20, p=0.04). HCV infection was associated with less of an increase in BUP dose throughout pregnancy compared to mothers without HCV infection. Among HCV positive mothers, a higher HCV viral load was correlated with higher liver enzymes as well as lower BUP doses during the second and third trimester. These findings may be due to HCV related liver inflammation that potentially decreases liver clearance of BUP. Larger prospective studies as well as pharmacokinetic studies will be useful in further delineating this relationship.

Alterations of liver enzymes in T2DM: a case control study

Background: Liver plays an important role in regulation of blood glucose in fed state as well as in fasting. Diabetes mellitus can result as a consequence of liver disorder and vice versa. Objective of the present study is to compare the liver enzymes in type 2 diabetic patients as compared to non-diabetic patients.Methods: A case- control study was conducted in Clinical Biochemistry Laboratory, Adarsha Super speciality Hospital, Udupi from April 2018 to August 2018. The data of 174 diabetic patients and 118 healthy people as controls was collected. Fasting blood glucose, aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were estimated in the study subjects.Results: It was found that AST levels (47.55±4.69U/L) in diabetics extremely significantly high as compared to controls (33.51±2.33U/L). ALT levels were insignificantly high in diabetics compared to controls. ALP was significantly elevated (p=0.0002) in diabetics. Correlation study showed a weak positive correlation between AST, ALT and blood glucose. Odds ratio showed a higher risk of liver enzyme elevation in diabetics. Risk of elevation of AST was found to be 1.65 times high and ALT was 1.25 times high in diabetics compared to non-diabetics.Conclusions: Diabetics had high liver enzymes as compared to non-diabetics. An association was found between type 2 diabetes mellitus and liver enzymes. For better characterization of cause and effect, further studies need to be done on alterations in liver function tests along with the histopathological analysis of liver biopsy samples.

Hepatoprotective activity of Uncaria tomentosa extract against sub-chronic exposure to fipronil in male rats.

The effects of fipronil (FPN) on the liver of rats were studied. Rats (n = 6) were treated with 9.7mg/kg (1/10 of FPN LD50), and other rats (n = 6) received 120mg/kg of 10% Uncaria tomentosa extract, while a mixture of 9.7mg/kg FPN and 120mg/kg of 10% Uncaria tomentosa extract were administered orally to the rats (n = 6) daily for 6weeks. Body, hepatic weights, liver enzymes, and lipid profile were determined. Hepatic activities of MDA, TNO, TAC, TNF-α, and IL-6 in liver homogenate were measured. Immunohistochemistry of NF-kB and liver histopathology were performed. Fipronil-treated rats had a significant (P = 0.02) lower weight gain. Moreover, relative liver weight was significantly (P = 0.003) increased in FPN-treated rats. Rats administrated with FPN exhibited a significantly (P = 0.02) higher liver enzymes and promoted levels of MDA, TNO, TNF-α, and IL-6 (P < 0.0001) than that in the other groups. Immunostaining of NF-κB was increased (P < 0.0001) in FPN-treated rats. Interestingly, Uncaria tomentosa alone or with FPN decreased the liver immunostaining of NF-κB. In conclusion, FPN produced liver injury through lipid peroxidation and stimulation of NF-κB. However, Uncaria tomentosa combated the oxidative stress and liver damage induced by FPN via inhibition of NF-κB.

Retrospective analysis of incidence, clinical features, potential risk factors, and prognostic indicators for aspiration pneumonia in three brachycephalic dog breeds.

OBJECTIVE To investigate incidence, clinical features, potential risk factors, and prognostic indicators for aspiration pneumonia in Pugs, French Bulldogs, and Bulldogs. DESIGN Retrospective, observational study. ANIMALS 41 brachycephalic dogs with aspiration pneumonia. PROCEDURES Medical records of a veterinary referral hospital were retrospectively searched to identify Pugs, French Bulldogs, and Bulldogs treated for aspiration pneumonia between 2006 and 2015. Signalment, clinical data, and outcomes were recorded. Variables of interest were analyzed for statistical associations with outcome. Incidence of aspiration pneumonia for the population of interest was compared with that for all other dog breeds and for the general hospital population of dogs during the study. RESULTS 41 of 2,141 (1.91%) dogs of the selected brachycephalic breeds and 396 of 80,137 (0.49%) dogs overall had a diagnosis of aspiration pneumonia. Relative risk of the disease in the population of interest was 3.77 times that for all other breeds. Median age at disease onset was greater for Pugs (83 months) than for French Bulldogs (8 months) and Bulldogs (6 months). History of gastrointestinal signs was the most commonly observed preidentified risk factor (27/41 [66%]) in these breeds. Neurologic disease was significantly more common in Pugs than in French Bulldogs and Bulldogs. On univariate analysis, increased age, male sex, obtundation, hypoalbuminemia, azotemia, and high liver enzyme activities were associated with nonsurvival; on logistic regression, increased age was associated with nonsurvival. CONCLUSIONS AND CLINICAL RELEVANCE Age at onset and presence of other risk factors for aspiration pneumonia may vary among brachycephalic dog breeds. Prospective studies are needed to determine common risk factors and prognostic indicators for aspiration pneumonia in the larger population of brachycephalic dogs.

Serum and Urinary C-Reactive Protein Concentrations in Dogs with Leptospirosis

Background: Leptospirosis is a bacterial disease caused by pathogenic strains of Leptospira, which may affect human beings and a wide range of both domestic and wild animals. The disease in dogs is still a challenge for clinicians, since definitive diagnosis may be reached only few days after overt clinical signs. Besides that, dogs with leptospiruria have zoonotic risk, making development of rapid screening tests crucial for early diagnosis of disease. C-reactive protein is a positive acute phase protein, and in the dog a strong and fast response is expected after any tissue injury. The aim of this study was to evaluate serum and urinary C-reactive protein as potential early indicators of leptospirosis in dogs, and its association with clinical serum biochemistry, complete blood count (CBC) and clinical outcome. Materials, Methods & Results: A total of 62 dogs with risk factors and/or clinical signs of leptospirosis were prospectively obtained and included in this study. Definitive diagnosis was based on serology, using the microscopic agglutination test (MAT) against 13 serovars, and on a specific polymerase chain reaction (PCR) in blood or urine, using the primers sets G1/G2 and B64I/B64II, which amplify DNA of pathogenic leptospires. Clinical serum biochemistry included creatinine, urea, alanine aminotransferase, alkaline phosphatase, creatine kinase and albumin. C-reactive protein was performed in serum and urine using a semi-quantitative latex-agglutination test. A total of 49/62 (79%) dogs had a positive diagnosis of leptospirosis. From these, 12 (24.5%) had positive blood PCR, 17 (34.7%) positive urine PCR and 43 (87.7%) had positive serology. Concurrent positive serology and positive PCR (blood or urine) occurred in 19 (38.8%) dogs, whereas 24 (49%) dogs had positive serology only, and 6 (12.2%) dogs had positive PCR only. Dogs with negative results at serology and PCR were kept for analysis and participated as negative control group. Out of the 62 dogs, 25 (40.3%) had high liver enzymes, 18 (29%) had azotemia, 23 (37.1%) had leukocytosis, 37 (59.7%) had high creatine kinase levels and 37 (59.7%) had hypoalbuminemia. Twelve death cases (19.3%) occurred within 10 days after the sample collection. Positive serology was significantly associated with urinary C-reactive protein (P = 0.038). Only a weak association was found between serum C-reactive protein and blood PCR (area under curve= 0.68). There was no association between urinary C-reactive protein and urine PCR, urinary C-reactive protein and blood PCR, serum C-reactive protein and positive serology, or serum C-reactive protein and urine PCR. Increased liver enzymes (P = 0.04) and hypoalbuminemia (P = 0.002) were associated with high levels of serum C-reactive protein. There was no association between serum or urinary C-reactive protein and death. Discussion: In this study, it was hypothesized that increased blood C-RP may be expected in dogs having leptospiremia, whereas increased urinary C-RP may be expected in dogs having leptospiruria. However, the results showed that C-reactive protein was not useful to predict leptospiremia or leptospiruria in the naturally infected dogs of this study; and although association between urinary C-reactive protein and seropositivity was observed, it should not be used as a unique test for leptospirosis. In conclusion, although C-reactive protein may be used as part of a screening profile, it should not be considared as indicator alone of leptospirosis screening in dogs.

2448 The effect of allopurinol on pediatric patients undergoing maintenance chemotherapy for acute lymphoblastic leukemia or lymphoblastic lymphoma

OBJECTIVES/SPECIFIC AIMS: This study aims to assess the safety, feasibility, clinical benefits and pharmacodynamics of adding allopurinol to standard maintenance therapy that includes 6-mecaptopurine (6-MP) in pediatric patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma. Our goal is to investigate if allopurinol improves hepatotoxicity and GI toxicity, if it safely decreases acute neutrophil count (ANC), if it reduces the 6-MP dose required during chemotherapy, and if it works through our hypothesized mechanism by lowering the levels of the toxic metabolite, 6-methylmecaptopurine (6-MMP) and by raising the levels of the active metabolite, 6-thioguanine (6-TGN). METHODS/STUDY POPULATION: This is a single arm, nonblinded pilot study of patients under age 30 years who were being treated in the maintenance phase of therapy for ALL or lymphoblastic lymphoma, and had adverse effects such as high 6-MMP:6-TGN ratio, high ANC, and high liver enzymes. Patients enrolled were started with allopurinol in addition to ongoing oral chemotherapy. Data from beginning maintenance to end of chemotherapy was collected in the electronic medical record, EPIC for the 13 patients enrolled at Johns Hopkins, and data analysis was conducted using STATA and Excel. RESULTS/ANTICIPATED RESULTS: Initial data analysis reveals that the required dose of 6-MP after addition of allopurinol to the chemotherapy regimen was significantly lower compared with that before the addition of allopurinol in 11 out of the 12 patients assessed (p&lt;0.05). Among the 10 patients that were assessed for 6MMP:6TG ratio, all had lower average 6MMP:6TGN ratios after allopurinol compared to before allopurinol; the percentage of weeks that goal 6MMP:6TGN ratio (&lt;40) were maintained were statistically significant in 6 patients (p&lt;0.05) and close to significance in 2 other patients (p=0.057). The percentage of weeks that patients maintained alanine aminotransferase levels below 120 was significantly greater after addition of allopurinol compared to before the addition of allopurinol in 9 out of 13 patients assessed, suggesting that allopurinol may be associated with reduced hepatotoxicity. Further data analysis is ongoing to assess the percentage of weeks that patients maintained goal total bilirubin, direct bilirubin, and ANC, as well as average number of admissions for infections and average number of therapy holds after allopurinol addition compared to before allopurinol addition. DISCUSSION/SIGNIFICANCE OF IMPACT: Allopurinol is associated with reduction in required 6-MP dose, decrease in the percentage of weeks that patients have hepatotoxicity, and reduction in the ratio of toxic metabolite to active anti-leukemic metabolite in several patients. We hope that the results of this study can be used for further research and for guiding clinical practice since there are no established guidelines in pediatric oncology regarding addressing side effects of oral chemotherapy using 6-MP. If allopurinol indeed is safe and effective, adding it to the standard chemotherapy regimen can lead to better tolerance and compliance to oral maintenance chemotherapy, and hopefully improved outcomes for children with ALL and lymphoblastic leukemia.

Demographic Profile of Liver Injury Managed at a Tertiary Care Hospital in Central Nepal -A Retrospective Study

Background &amp; Objectives:The liver is one of the commonly injured solid organ following abdominal trauma. The aim of this study was to determine the outcome of liver injuries managed operatively or non-operatively and predict factors affecting morbidity and mortality.Materials &amp; Methods:This was a retrospective study of 40 liver injuries managed in the department of Surgical Gastroenterology at College of Medical Sciences over a period of 2 years. The liver injury was classified in accordance with the American Association for the Surgery of Trauma liver injury scoring scale. Patients were divided into two groups those managed operatively or non-operatively and were compared in terms of demographic profile and outcome.Results:Forty patients were analyzed. The mean age of the patients was 29.95years. Male predominance was seen with 72.5% of the cases. Road traffic accidents were the commonest mode of injury seen in 72.5% cases. The mean Revised Trauma Score (RTS) and Injury severity score (ISS) were 7.11and 22.58. The mean systolic BP, hospital stay and ICU stay were 93.80 mm of mercury, 11.55 days and 3.55 days respectively. Twenty six patients (65%) were initially managed non-operatively and 14 patients were managed operatively. Five patients had to be converted to operative management for hemodynamic instability. Mortality was 7.6% in patient undergoing non-operative management and 21.43% in patients managed operatively. Low systolic BP at presentation, low RTS score, high ISS score, high AST, ALT and prothrombin time were significantly associated with operative management and mortality.Conclusion:Patients with hemodynamic instability, low RTS score, high ISS score, high liver enzymes have high likelihood of operative management.

Hyperthyroidism induced reversible hepatotoxicity a case report and brief review

The patients presenting with high liver enzymes have multiple etiologies ranging from hepatotoxic viruses, drugs, and various toxins. While viral hepatitis continues to be the leading cause of elevated liver enzymes, other metabolic and endocrine disorders also lead to elevated liver enzymes in a given patient. There is a paucity of data regarding hyperthyroidism and the high liver enzymes. We present the clinical scenario in a young male who presented with jaundice without viral prodrome or offending drug intake. The patient had no high-risk behavior, and on evaluation, he had negative viral serologies. Autoimmune profile was negative as well. The physical examination was suggestive of irregular pulse and normal blood pressure. On further evaluation hyperthyroidism was unraveled. Following treatment with antithyroid medication, the liver enzymes in the index case settled, and he had full clinical recovery, explaining the cause and effect relationship. Report on this case and brief literature review is presented. A good clinical examination often is a lead to the cause of disease and in a Jaundiced patient, hyperthyroidism can be one of the causes of high liver enzymes which must be ruled out in a given setting.

Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound.

BackgroundFerric carboxymaltose (FCM) is a stable, non-dextran-based intravenous iron complex used to treat iron deficiency of various etiologies. As FCM is a nonbiological complex drug and cannot be fully characterized by physicochemical analyses, it is important to demonstrate in nonclinical models that FCM similars (FCMS) have similar biodistribution.Materials and methodsA total of 30 nonanemic rats were treated weekly with 40 mg iron/kg body weight intravenous FCM, FCMS, or isotonic saline (controls) for 4 weeks. Blood pressure, liver enzymes, and renal function were evaluated. In liver, heart, and kidney tissue, markers for oxidative stress (malondialdehyde to assess lipid peroxidation and antioxidant enzymes) and inflammation (TNFα and IL6) were measured. Iron deposits were localized.ResultsThe FCMS-treated group had significantly lower blood pressure, higher liver enzymes, increased proteinuria, and reduced creatinine clearance versus the FCM and control groups by day 29. Serum iron and transferrin saturation were significantly higher with FCMS versus FCM or controls. Iron deposition was altered in FCMS-treated animals, with decreased ferritin deposits and iron deposition outside the physiological storage compartments. Markers for lipid peroxidation and antioxidant-enzyme activity were significantly increased after FCMS administration versus FCM and controls, as were inflammatory markers.ConclusionResults from this blinded nonclinical study demonstrated significant differences between the originator FCM and this FCMS.

Diagnostics for Lassa Fever: Detecting Host Antibody Responses.

There are two types of viral diagnostics: (1) those that detect components of the pathogen (like viral RNA or proteins) and (2) those that detect host molecules that rise or fall as a consequence of pathogen infection (like anti-viral antibodies or virus-induced inflammatory cytokines). Quantitative PCR to detect Lassa RNA, and clinical chemistry to detect high liver enzymes (AST/ALT) are commonly used to diagnose Lassa fever. Here, we discuss the various types of diagnostics for Lassa fever and the urgent need for early diagnosis. We also describe a protocol for using the attenuated Lassa vaccine candidate, ML29 , as an antigen for detecting Lassa-specific antibodies. Since antibodies are developed late in the progression of Lassa fever disease, this is not an early diagnostic, but is more useful in surveillance of the population to determine the sero-prevalence of antibodies to Lassa virus (LASV ), and to define treatment options for people in close contact with a Lassa-infected person.

High Liver Enzyme Concentrations are Associated with Higher Glycemia, but not with Glycemic Variability, in Individuals without Diabetes Mellitus.

Elevated concentrations of liver enzymes have been associated with an increased risk of developing type 2 diabetes mellitus. However, it remains unclear to which specific aspects of diurnal glucose metabolism these associate most. We aimed to investigate the associations between liver enzyme concentrations and 24 h-glucose trajectories in individuals without diabetes mellitus from three independent cohorts. This cross-sectional study included 436 participants without diabetes mellitus from the Active and Healthy Aging Study, the Switchbox Study, and the Growing Old Together Study. Fasting blood samples were drawn to measure gamma-glutamyltransferase (GGT), alanine transaminase, and aspartate transaminase. Measures of glycemia (e.g., nocturnal and diurnal mean glucose levels) and glycemic variability (e.g., mean amplitude of glucose excursions) were derived from continuous glucose monitoring. Analyses were performed separately for the three cohorts; derived estimates were additionally meta-analyzed. After meta-analyses of the three cohorts, elevated liver enzyme concentrations, and specifically elevated GGT concentrations, were associated with higher glycemia. More specific, participants in the highest GGT tertile (GGT ≥37.9 U/L) had a 0.39 mmol/L (95% confidence interval: 0.23, 0.56) higher mean nocturnal glucose (3:00 to 6:00 a.m.) and a 0.23 mmol/L (0.10, 0.36) higher diurnal glucose (6:00 to 0:00 a.m.) than participants in the lowest GGT tertile (GGT <21.23 U/L). However, elevated liver enzyme concentrations were not associated with a higher glycemic variability. Though elevated liver enzyme concentrations did not associate with higher glycemic variability in participants without diabetes mellitus, specifically, elevated GGT concentrations associated with higher glycemia.

Low prevalence of non-alcoholic fatty liver disease in patients with type 1 diabetes is associated with decreased subclinical cardiovascular disease.

Non-alcoholic fatty liver disease (NAFLD) has been proposed as an independent cardiovascular risk factor. The present study evaluated the prevalence of NAFLD in a cohort of type 1 diabetic (T1D) patients and its potential relationship with subclinical cardiovascular disease (CVD). One hundred T1D patients (mean [±SD] age 39.4 ± 7.8 years, disease duration 21.7 ± 8.6 years) were included in the present cross-sectional study. All subjects underwent abdominal ultrasonography for detection of NAFLD, carotid ultrasonography to measure the carotid intima-media thickness (CIMT) and atheroma plaques, and cardiac tomography for evaluation of the coronary artery calcium score (CACS). Of the study cohort, 12% had NAFLD and 23% had a CACS >0. The T1D subjects with NAFLD had a greater CIMT than those without NAFLD (0.65 ± 0.17 vs 0.55 ± 0.14 mm; P = 0.029), but there were no significant differences between the two groups with regard to CACS, glycemic control, or the presence of carotid plaques. Patients with high liver enzyme concentrations (>20 U/L) had a higher CIMT (0.60 ± 0.16 vs 0.54 ± 0.13; P = 0.04) and there was a higher proportion of altered CACS (17 [73.9%] vs 6 [26.1%]; P = 0.001) and detection of carotid plaques (10 [76.9%] vs 3 [23.1%]; P = 0.014) in this group. A low prevalence of NAFLD was found in the T1D cohort that was associated globally with a low proportion of abnormal CVD imaging markers, although these imaging parameters were worse in subjects in whom NAFLD was detected.

Clinical characteristics and molecular epidemiology of hepatitis E in Shenzhen, China: a shift toward foodborne transmission of hepatitis E virus infection

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in China. Recently, a shift in molecular epidemiology from hepatitis E genotype 1 (HEV-1) to hepatitis E genotype 4 (HEV-4) has been observed in Northern China, marking a switch from human-to-human transmission to zoonosis. However, similar data from cities in Southern China are lacking. This observational study of human hepatitis E cases in Shenzhen, a metropolitan city in the Pearl River Delta region, aimed to describe the clinical features and molecular epidemiology of hepatitis E in Southern China. Over a 55-month period, we identified 20 patients with acute hepatitis E. Most were middle-aged men, and 50% of patients had concomitant liver disease, of whom 70% were identified to have non-alcoholic fatty liver disease; such patients had a trend toward higher liver enzymes. Quantitative real-time RT-PCR using archived serum samples showed that 12 patients had hepatitis E viremia at presentation. Sequencing of the RNA-dependent RNA polymerase gene was performed for five of these patients, and phylogenetic analysis revealed that these five HEV isolates belonged to subgenotype 4b and were clustered with swine HEV isolates from Southern China. Combined with other studies showing similar findings, this suggests that the molecular epidemiology of hepatitis E in China is evolving toward low-level endemicity driven by foodborne transmission from seafood or pork products. The importance of concomitant liver disease, in particular non-alcoholic fatty liver disease, as a risk factor for severe hepatitis E requires further study.Emerging Microbes & Infections (2017) 6, e115 doi:10.1038/emi.2017.107; published online 20 December 2017

Sclerosing Cholangitis with Ulcerative Colitis after Bariatric Surgery

Introduction: 48 years old Iraqi female presented in 2012 with 4 months upper abdominal pain with elevation of the liver enzymes and arthralgia, 1 year after sleeve gastrectomy for obesity with 25 kg weight loss. Labeled as auto immune hepatitis and was started on prednisolone 20 mg and azathioprine 100 mg, attended our center for second opinion. Her past history was impressive for gestational diabetes and ulcerative colitis diagnosed before 15 years and treated for 1 year with remission. Strong family history of diabetes including father, mother, brothers, and her uncle has ulcerative colitis. Investigations: Showed high liver enzymes, ALT 159, AST 286, ALP 455 and GGT 378, high eosinophil count. Imaging showed fatty liver with mild dilatation of the biliary system but CT scan, MRI, MRCP were not conclusive. ERCP showed features of sclerosing cholangitis with dominant stricture right hepatic duct, brushing and biopsy showed inflammatory changes. Colonoscopy showed pan colitis with ileal involvement, biopsy showed colitis with eosinophilic infiltration. She was treated with mesalazine, ursodiol, prednisolone and azathioprine. Regular follow over 4 years showed normal liver enzymes and last colonoscopy was reported as normal. Conclusion: A patient developed elevated liver enzymes after sleeve gastrectomy for obesity. Imaging and endoscopies showed typical sclerosing cholangitis with dominant right hepatic bile duct stricture, colonoscopy showed pan colitis with high eosinophilic infiltration. The problem was the evaluation of the dominant stricture and the exclusion of malignancy.