Biochemical Liver Function Tests Research Articles

Abstract PO2-15-03: Platelet-to-lymphocyte ratio in patients with metastatic breast cancer treated with eribulin

Abstract Eribulin is widely used to treat metastatic breast cancer (BC). Higher neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) are associated with higher mortality in several cancer types. However, the association between BC prognosis and peripheral immune status remains controversial. We quantified the relative effects of NLR and PLR on survival in patients with recurrent/stage IV BC and evaluated their clinical prognostic value. This retrospective study included 156 patients with recurrent/stage IV BC who received eribulin monotherapy at Saitama Medical University International Medical Center. We examined clinicopathological features (peripheral blood findings and biochemical liver and kidney function test results) and conducted univariate and multivariate analyses of the overall survival (OS). The 156 eribulin-treated patients had a median follow-up duration of 18.3 months. Before eribulin treatment, patients with absolute lymphocyte counts (ALC) >1500/uL, NLRs < 3.0, and PLRs < 150 had significantly longer OS than those with lower ALCs, and higher NLR and PLRs (median OS, 25.5 vs. 15.5 months; p< 0.01; 20.3 vs. 13.6 months, P< 0.01; and 29.2 vs. 14.8 months; P< 0.001, respectively). Patients with anemia (hemoglobin < 10 g/dL) or liver dysfunction (albumin-bilirubin grade 2/3) had significantly shorter OS than those without (P< 0.001, respectively). Multivariate analysis revealed low albumin-bilirubin grade (P< 0.001), high hemoglobin (P< 0.01), and low PLR (P< 0.05) as independent factors of longer OS after eribulin administration. Low PLR, anemia, and liver dysfunction might be factors associated with prolonged OS in patients with recurrent/stage IV BC on eribulin therapy, which could be clinically useful, as their evaluation requires neither new equipment nor invasive testing. Citation Format: Hiroko Shimada, Kazuo Matsuura, Shunsuke Kohyama, Aya Asano, Masahiro Ohara, Hiroshi Ishiguro, Akihiko Osaki, Toshiaki Saeki. Platelet-to-lymphocyte ratio in patients with metastatic breast cancer treated with eribulin [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-15-03.

Resveratrol Administration Ameliorates Hepatotoxicity in Mercuric Chloride-‎Induced Liver Injury in Rats

Mercuric chloride (HgCl2) pollution and poisoning has been a worldwide health ‎concern for decades, especially after the industrial revolutions. The aim of this study ‎was to investigate the role of resveratrol in reversing the deleterious effects of ‎HgCl2 exposure to resume the normal functions of hepatocyte. To achieve the study, ‎mature Sprague Dawley rats were assigned to five groups. Negative control group ‎‎(C) kept without any treatment; vehicle-treated group (D) received dimethyl ‎sulfoxide (DMSO); resveratrol-treated group (R), received 100 mg/kg of resveratrol; ‎HgCl2-intoxicated group (HD), received i.p. injection of HgCl2 at a dose of 1 mg/kg ‎for 30 consecutive days along to oral gavage of DMSO; and finally HgCl2-‎intoxicated group treated with resveratrol (HR) as same treatment strategy of R-‎group. At the endpoint of the experiment, blood samples were collected for ‎biochemical liver function tests along with serum concentrations of ‎malondialdehyde (MDA), glutathione (GSH), body weight, as well as ‎histopathological investigation was done too. Study results revealed a significant ‎‎(P<0.05) elevation in serum AST, ALP, GGT, and MDA in HD group in comparison ‎with HR group. However, resveratrol treatment has led to a significant (P<0.05) ‎increase in serum levels of GSH in HR group in comparison with the HD group. ‎Histopathological sections showed vacuolar degeneration in HD hepatocytes while ‎resveratrol treatment protected the hepatocytes against the chemical injury. ‎Altogether, It is concluded that resveratrol administration has the ability to increase ‎the resistance of liver against the HgCl2-induced hepatotoxicity via increase the ‎antioxidant yields such as GSH resulted in reduction of hepatocellular texture ‎damage.

The standardized extract of Centella asiatica L. Urb attenuates the convulsant effect induced by lithium/pilocarpine without affecting biochemical and haematological parameters in rats

BackgroundStatus epilepticus (SE) is a type of epileptic activity characterized by a failure of the inhibitory mechanisms that limit seizures, which are mainly regulated by the GABAergic system. This imbalance increases glutamatergic neurotransmission and consequently produces epileptic activity. It is also associated with oxidative stress due to an imbalance between reactive oxygen species (ROS) and antioxidant defences. Unfortunately, long-term treatment with anti-epileptic drugs (AEDs) may produce hepatotoxicity, nephrotoxicity, and haematological alterations. In this way, some secondary metabolites of plants have been used to ameliorate the deterioration of nervous system disorders through their antioxidant properties, in addition to their anticonvulsant effects. An example is Centella asiatica, a plant noted to have a reputed neuroprotective effect related to its antioxidant activity. However, similar to conventional drugs, natural molecules may produce side effects when consumed in high doses, which could occur with Centella asiatica. Therefore, we aimed to evaluate the effect of a standardized extract of Centella asiatica L. Urb with tested anticonvulsant activity on biochemical and haematological parameters in rats subjected to lithium/pilocarpine-induced seizures.MethodsTwenty-eight adult male Wistar rats were randomly divided into four groups (n = 7 each): vehicle (purified water), Centella asiatica (200 and 400 mg/kg), and carbamazepine (CBZ) (300 mg/kg) as a pharmacological control of anticonvulsant activity. Treatments were administered orally every 24 h for 35 consecutive days. On Day 36, SE was induced using the lithium/pilocarpine model (3 mEq/kg, i.p. and 30 mg/kg s.c., respectively), and the behavioural and biochemical effects were evaluated.ResultsCentella asiatica 400 mg/kg increased the latency to the first generalized seizure and SE onset and significantly reduced the time to the first generalized seizure compared to values in the vehicle group. Biochemical parameters, i.e., haematic cytometry, blood chemistry, and liver function tests, showed no significant differences among the different treatments.ConclusionThe dose of Centella asiatica that produces anticonvulsant activity in the lithium/pilocarpine model devoid of hepatotoxicity, nephrotoxicity, and alterations in haematological parameters suggests that the standardized extract of this plant could be of utility in the development of new safe therapies for the treatment of convulsions associated with epilepsy.

Portal Hypertensive Gastropathy and its Association among the Patients with Decompensated Chronic Liver Disease

Background: Although portal hypertension remains the crucial factor for the development of PHG, other factors should be considered in the development and progression of this condition like hepatic function, oesophageal varices, type of hepatitis virus and hypersplenism as evidenced by haematological variables (Anemia, leucopenia and thrombocytopenia). Aim & Objectives: To study the frequency of portal hypertensive gastropathy and its correlation with haematological and biochemical parameters and other endoscopic findings. Materials and methods: A prospective, hospital based, time bound study of 100 patients, admitted with decompensated chronic liver disease (diagnosed based on the evidence of sonography criteria) in a tertiary care center. Patients aged > 18 years and above admitted in SDM medical college and hospital were considered, demographic data, physical examination was done, basic investigations, hematological, biochemical (renal function test and liver function test) , coagulation profile, serology were evaluated. Upper gastrointestinal endoscopy procedure was done and data was collected in a pre designed performa. Results: The frequency of PHG in our study was 64%.Presence of PHG had significant association with SBP, DBP, haemoglobin, TLC. We also found significant association between PHG and grade 1 and 3 of esophageal varices, gastric varices and erosive gastritis. Conclusion: The frequency of PHG was 64% in the studied group and the presence of PHG correlates with presence of esophageal varices, erosive gastritis and gastric varices suggesting a common pathophysiology.

Study of thyroid hormones effect on biochemical parameters of liver function in Iraqi patients

This study was aimed to study the effect of thyroid hormones on some biochemical tests of liver function in Iraqi male patients and to study the relationship between them. A controlled study included 135 samples from patients and controls, group B, 45 patients with a liver disorder, and group C: 45 patients with a thyroid disorder, and group A: 45 healthy people (as the controls group). The study concluded that there were significant statistically significant differences for patients with liver disease, as well as for patients who suffer from abnormalities in the functions of the thyroid gland. For triiodothyronine (T3) and thyroxine (T4), there was clear importance and a slight impact for patients with liver disease. Because of the defect in the liver enzymes, this led to an increase in the TSB percentage, which increased significantly. Alkaline and Albumin levels indicate statistical significance within the results of our study. Serum protein levels had no significant changes in our study.

The Effects of Active Video Game Exercise Based on Self-Determination Theory on Physical Fitness and Cognitive Function in Older Adults.

Background: Aging and physical inactivity are associated with declines in physical fitness and cognitive function. Active video games have proven to be beneficial for the physical health of older adults, but the exact effect of active video games on physical fitness and cognitive function was still unclear. Based on self-determination theory (SDT), which is a widely used theory of healthy behavior change, this study aimed to explore the effects of an active video game intervention on fitness and cognitive function in older adults. Methods: A total of 38 participants (mean age = 65.68 ± 3.78 years, 24 female) were randomly assigned to either an intervention group (active video game training) or a control group (no additional intervention). The participants in the intervention group trained for a total of 36 sessions (3 times per week for 50–55 min each) for 12 weeks. The control group continued with their normal daily living. The pre- and posttest measurements included: IPAQ-C score and physical fitness (BMI, body fat percent, blood pressure, reaction time, sit and reach, vital capacity, grip strength, static balance, blood biochemical tests for liver function, kidney function, blood lipids, glucose and insulin levels) and cognitive functions (processing speed, spatial ability, working memory, language ability, associative memory). Result: The intervention group showed a significantly smaller decrease in total average physical activity relative to the control group. BMI, vital capacity, systolic blood pressure, diastolic blood pressure, and spatial cognition significantly improved after training in the intervention group (BMI: F = 9.814, p = 0.004, d = −0.93, vital capacity: F = 4.708, p = 0.038, d = 0.67, systolic blood pressure: F = 5.28, p = 0.028, d = −0.68, diastolic blood pressure: F = 6.418, p = 0.016, d = −0.86, spatial cognition: F = 8.261, p = 0.007, d = 0.72). Three measures of static balance (closed eyes) also showed improvements after training (total length of swing: F = 3.728, d = −0.62, total velocity of swing: F = 3.740, d = −0.62, total area of swing: F = 2.920, d = −0.70). No significant training effects were evident in the results from the blood biochemical tests. Conclusion: This study indicates a positive influence of active video game training on physical fitness and cognitive function. The use of SDT-based active video game exercise as a feasible, safe, and effective training method for improving community older adults’ healthy, promoting group cohesion, and increasing motivation to exercise.

Demystifying post-hepatectomy enzyme kinetics for the surgical learner: an analysis of 989 major hepatectomies

PurposeFew resources exist for surgical learners in interpreting trends in biochemical markers following major hepatic resections.MethodsAdult patients who underwent major hepatectomy between 2010 and 2020 were included from twelve international centers. Patients were classified as healthy donor, benign disease, non-alcoholic fatty liver disease, prior chemotherapy, or cirrhosis. Median values of total bilirubin and INR were plotted against time and compared across groups using the Kruskal–Wallis test.ResultsAcross groups (n = 989), median total bilirubin and INR were observed to peak on postoperative day (POD) 1. While the healthy donor group (n = 156) had the highest median total bilirubin on POD1 (2.4, IQR: 1.7–3.3), they had the fastest rate of recovery such that by POD5, values were lower than those of the NAFLD (n = 26), chemotherapy (n = 92), and cirrhosis (n = 668) groups. Donor patients also had the highest POD1 INR (median 1.5, IQR: 1.4–1.7), while patients with NAFLD had the highest POD5 INR levels (1.2, IQR: 1.1, 1.4). The lowest POD1 total bilirubin and INR levels were observed in the cirrhosis group (1.5, 1.3, respectively). Statistically significant differences in total bilirubin and INR were observed across groups at all timepoints (p < 0.05).ConclusionsWe observed the healthy donor patients to have the highest postoperative enzyme peaks, but most rapid rate of return to normal. This illustration of the postoperative kinetics of biochemical liver function tests may serve as a useful reference for clinical learners monitoring patients in the first week following major hepatectomy.

Demystifying Post-hepatectomy Enzyme Kinetics for the Surgical Learner: An Analysis of 989 Major Hepatectomies

Introduction: Few resources exist for surgical learners in interpreting trends in biochemical markers following major hepatic resections. Methods: Adult patients who underwent major hepatectomy between 2010-2020 were included from twelve international centers. Patients were classified as healthy donor, benign disease, non-alcoholic fatty liver disease, prior chemotherapy, or cirrhosis. Median values of total bilirubin and INR were plotted against time and compared across groups using the Kruskal-Wallis test. Results: Across groups (n=989), median total bilirubin and INR were observed to peak on postoperative day (POD) 1. While the healthy donor group (n=156) had the highest median total bilirubin on POD1 (2.4, IQR: 1.7-3.3), they had the fastest rate of recovery such that by POD5, values were lower than those of the NAFLD (n=26), chemotherapy (n=92), and cirrhosis (n=668) groups. Donor patients also had the highest POD1 INR (median 1.5, IQR: 1.4-1.7), while patients with NAFLD had the highest POD5 INR levels (1.2, IQR 1.1, 1.4). The lowest POD1 total bilirubin and INR levels were observed in the cirrhosis group (1.5, 1.3 respectively). Statistically significant differences in total bilirubin and INR were observed across groups at all time points (p<0.05). Conclusions: We observed the healthy donor patients to have the highest postoperative enzyme peaks, but most rapid rate of return to normal. This illustration of the postoperative kinetics of biochemical liver function tests may serve as a useful reference for clinical learners monitoring patients in the first week following major hepatectomy.

Smoking and fatty liver disease in rural therapeutic area residents

Aim: Evaluate the relationship of Smoking with fatty liver disease (FLD) of various etiologies.Materials and Methods: Out of1568 residents of the rural therapeutic area agreed to participate in the study of 1123 residents of the rural medical area with negative markers of hepatitis B and / or C. The survey included the collection of anamnesis for smoking and alcohol consumption. An objective, laboratory (complete blood count, biochemical liver function tests) and instrumental examination, including ultrasound examination of the abdominal organs, were carried out.Results: Non-alcoholic fatty liver disease (NAFLD) was detected in 247 (22.0%) people, alcoholic liver disease (ALD) — in 276 (24.6%) (p&gt;0.05). 542 people smoked of the surveyed. Among patients with NAFLD, Smoking was 20.2%, their Smoking experience was 35.1±11.5 years, and the Smoking index was 24.5±10.9. Among patients with ALP, Smoking is higher-93.1% (p&lt;0.05), Smoking experience is less — 29.5±9.8 years (p&lt;0.05), as is the Smoking index of 21.8±7.7 (p&lt;0.05). Among smokers, 56.8% had FLD, 83.8% of them were of alcoholic etiology, and 16.2% were non — alcoholic (p&lt;0.05). Among non-smokers, compared with smokers, FLD was detected less frequently — in 37.2% of people (p&lt;0.05), of which alcohol etiology — in 8.8% (p&lt;0.05), non — alcoholic-in 91.2% (p&lt;0.05).Conclusion: In the rural therapeutic area, 93.1% of ALD sufferers smoke, and 20.2% of NAFLD patients smoke (p&lt;0.05). In patients with NAFLD, the duration of smoking was longer (35.1 ± 11.5) than in patients with ALD — 29.5 ± 9.8 years (p &lt;0.05); the smoking index was 24.5 ± 10.9 and 21.8 ± 7.7 pack-years (p&lt;0.05), respectively. In smokers, FLD was more common (56.8%) than in non-smokers (37.2%) (p&lt;0.05). FLD in smokers was of alcoholic etiology more often (83.8%) than non-alcoholic (16.2%) (p&lt;0.05), in non-smokers non-alcoholic etiology prevailed (91.2%) (p&lt;0.05).

Toxicological assessment of Opuntia dillenii (Ker Gawl.) Haw. cladode methanol extract, fractions and its alpha pyrones: Opuntiol and opuntioside

Ethnopharmacological relevanceThe edible plant Opuntia dillenii (Ker Gawl.) Haw. commonly known as Nagphana, belongs to the Cactaceae family. It is traditionally used to treat various ailments including inflammation, gastric ulcers, diabetes, hepatitis, asthma, whooping cough and intestinal spasm. Aim of the studyDespite its traditional use in various countries, detailed toxicological studies of O. dillenii cladode are few. Thus in the current study, toxicity of O. dillenii cladode derived methanol extract, fractions and its α-pyrones: opuntiol and opuntioside have been addressed. MethodsThe test agents were assessed using both in vitro and in vivo toxicity assays. MTT on human embryonic kidney cell line (HEK-293), tryphan blue exclusion in rat neutrophils, Cytokinesis-B block micronucleus (CBMN) in human lymphocytes and genomic DNA fragmentation using agarose gel electrophoresis were performed. In acute toxicity test, mice orally received extract (5 g/kg) for 7 days followed by measurements of relative organ weight, biochemical (blood profile, liver and kidney function test) and histological studies (liver and kidney) were carried out. Rat bone marrow micronucleus genotoxicity assay was also conducted. ResultsO. dillenii derived test agents were non-cytotoxic and had no effect on the integrity of DNA. Methanol extract (5 g/kg) orally administered in mice did not cause any significant change in relative organ weights, biochemical parameters and liver and kidney histology as compared to vehicle control. In parallel, extract did not stimulate micronuclei formation in rat bone marrow polychromatic erythrocytes. ConclusionThese results led to conclude that edible O. dillenii extract is non-toxic via the oral route and appears to be non-cyto-, hepato-, nephro- or genotoxic, thereby supporting its safe traditional use against various ailments. Therefore, opuntiol and opuntioside may serve as lead compounds in designing new drug(s) derived from edible plants.

Elevated mean platelet volume in oral lichen planus and increased blood urea nitrogen level in its red-form: an observational study

BackgroundThis retrospective observational study aims to assess platelet count, mean platelet volume (MPV), blood biochemical tests for liver and kidney function in Chinese oral lichen planus (OLP) patients.MethodsEighty pathologically confirmed OLP patients and 51 healthy controls were enrolled. Data on full blood count and biochemical tests were obtained from the electronic medical record system of the hospital.ResultsMPV was elevated in OLP patients compared to controls (10.68 ± 0.97 fL versus 10.33 ± 0.89 fL, P = 0.042) while platelet count showed no difference between them. Red-form OLP group had increased blood urea nitrogen (BUN, 5.24 ± 1.15 mmol/L versus 4.69 ± 0.98 mmol/L, P = 0.036) than white-form OLP group. By contrast, there were no differences between those two groups in the other variables including MPV, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine. In terms of C-reactive protein (CRP), 92.5% of the OLP patients had a value of less than 3.48 mg/L. Besides, 75% of the OLP patients were overweight with body mass index (BMI) more than 25 kg/m2.ConclusionsThese findings indicate MPV might play roles in inflammation in OLP. The red-form OLP might be associated with damage or reduction of kidney function.

The Relationship Between Osteoarthritis and Sarcopenia in Geriatric Diabetic Patients

Objectives:Osteoarthritis is a common disease affecting the quality of life in the elderly population. Osteoarthritis is a painful condition commonly encountered in patients aged 65 years and older and it may cause muscle weakness. Sarcopenia is a condition that has an increasing prevalence in the elderly population. The present study evaluated the relationship between sarcopenia and osteoarthritis.Methods:The study included 100 patients aged 65 years and older who were diagnosed with diabetes mellitus. The patients were divided into two groups as Group 1 and Group 2. Group 1 was composed of 50 patients with diabetes and osteoarthritis and Group 2 was composed of 50 patients with diabetes but without osteoarthritis. A detailed medical history was obtained from all patients and all patients underwent physical examination. The get-up and go test was performed, handgrip strength was measured with a hand dynamometer, bioimpedance analysis was performed, and mid-upper arm circumference, calf circumference and waist circumference were measured, and laboratory tests including complete blood count, biochemical nutritional parameters, liver and kidney function tests, and erythrocyte sedimentation rate were ordered. The Kellgren and Lawrence grading system was used to evaluate the severity of osteoarthritis and the skeletal muscle mass index was used to evaluate the muscle mass. These parameters were compared between the two groups.Results:Of the study participants, 1% had severe sarcopenia, 22% had moderate sarcopenia, and 77% did not have sarcopenia. Albumin (p=0.013), magnesium (p=0.038), total protein (0.004), erythrocyte sedimentation rate (p=0.047), hemoglobin level (p=0.018), muscle strength (p=0.046), height (p=0.033), and muscle mass (p<0.05) were significantly different in patients with osteoarthritis compared to patients without osteoarthritis. Patients with osteoarthritis achieved poorer results on the get-up and go test (p=0.014), and mid-upper arm circumference (p=0.028), and calf circumference (p=0.016) were lower in this group. There was a negative moderate correlation between the muscle mass and the Kellgren and Lawrence grade (p<0.05, r: −0.405), whereas there was a positive moderate correlation between sarcopenia index and the Kellgren and Lawrence grade (p<0.05, r: 0.320) in patients with osteoarthritis.Conclusion:The present study is the first to evaluate the relationship between sarcopenia and osteoarthritis in geriatric diabetic patients. The present study found a significant relationship between osteoarthritis and sarcopenia in geriatric patients with type II diabetes mellitus. The authors suggest that pain associated with osteoarthritis results in immobility, decrease in functional performance, and thus development of sarcopenia.

P0331ASSESSMENT OF DELIVERY OF NICE APPROVED USE OF TOLVAPTAN (JINARC) IN ADULTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE IN A UK RENAL CENTRE

Abstract Background and Aims Until recently, the management of ADPKD has largely been limited to lifestyle changes (smoking cessation, salt avoidance and diet with weight loss) and tight blood pressure control, in addition to kidney pain management and prompt treatment of complications such as infections. The approval of Tolvaptan, a highly selective vasopressin V2 receptor antagonist, by NICE, following the pivotal TEMPO 3:4 trial provides clinicians with an opportunity to modify the progression of ADPKD and preserve kidney function. Tolvaptan works by slowing cyst growth patients with ADPKD (and therefore potentially reducing kidney pain, urinary tract infections and haematuria). During the TEMPO 3:4 trial, a reversible elevation (&amp;gt; 3X upper limit) of liver enzymes was observed in 4.4% patients taking tolvaptan vs 1% on placebo. The onset of liver injury was between 3 – 14 months of initiation of tolvaptan; therefore, monthly blood tests are required to mitigate the potential injury associated with the increase in liver enzymes. The main side effects are polyuria and thirst. The aims for the audit were Method We carried out a prospective questionnaire-based study on all patients who were on tolvaptan therapy. All patients received a comprehensive explanation of the merits and side-effects of Tolvaptan with written literature and a copy of their initial assessment consultation prior to commencement of therapy. In addition, we reviewed patients’ clinic attendances, relevant biochemical results and liver function test as per licence agreement tolvaptan therapy. This was approved by the Hull University Teaching Hospitals (HUTH) NHS Trust Audit department with a signed Clinical Governance Form 1. Results In total, 27 patients, consisting of 18 males and 9 females [mean age 44.5yrs] and all Caucasian on tolvaptan therapy were evaluated. The median duration of treatment was 10months. Two patients [7.4%] dropped out of treatment: one patient opted out of treatment due to the polyuria interfering with his job requirements and the other had relocated to another country; giving HUTH a retention rate of 92.6%. 55.5% of patients responded to not having missed a dose of drug at any time at any time despite a significant number experiencing side-affects (Figure1). Some purposely missed medication due to a social event. Although 100% of patients did respond to experiencing side effects of tolvaptan, 74% of patients said it did not interfere with their quality of life. 88.8% of patients were on the full dose of 90mg in the morning and 30mg after 8 hours. The Tolvaptan clinic in HUTH is run as a pharmacist led with consultant oversight. Currently no issues have arisen but the patients’ view of a pharmacist led-clinic is currently being studied. Conclusion This study demonstrates that despite a number of expected side-affects; with good patient education and follow-up, few patients stopped therapy and most patients remain compliant to tolvaptan therapy. Currently a pharmacist led, consultant backed tolvaptan clinic has not adversely affected this success.

Correlation of Type, Quantity, and Duration of Alcohol Consumption With Biochemical Markers and Liver Function Tests.

To study the correlation of type, quantity, and duration of alcohol consumption with biochemical markers and liver function tests. The study included 103 patients with a history of alcohol use presenting to the psychiatry department of a hospital in India from March 1, 2017, to February 28, 2018. A self-administered structured questionnaire was used to assess demographics and clinical characteristics. Biochemical markers and laboratory tests included hemoglobin, total leukocyte count, mean corpuscular volume, liver function, and lipid profile. Liver ultrasonography was also conducted. Patients completed the Alcohol Use Disorders Identification Test to assess excessive alcohol use. Of the patients, 17.5% had a hemoglobin level < 12 g/dL. The mean total leukocyte count was 7.292 per cu mm, and a significant (P = .05) correlation was observed with duration of alcohol consumption; 26% had a mean corpuscular volume > 100 fL. One-third (33%) of the patients had total bilirubin values > 1 mg/dL. The majority (81.6%) had a γ-glutamyl transferase level > 47 U/L, and 19.4% had a serum glutamic-oxaloacetic transaminase/pyruvic transaminase ratio > 2. Liver size was increased in 71% of the patients. There was a significant correlation (P = .05) between type and quantity of alcohol and liver function tests, signifying poor quality of alcohol (ie, many patients drank "local spirit" alcohol, which is liquor made in the countryside of the Indian subcontinent) and that higher alcohol consumption caused more damage to the liver. The positive correlation between duration and lipid derangement signifies that longer duration of alcohol consumption leads to more lipid profile abnormalities, which in turn causes liver injury. Early detection of liver injury with these investigations, keeping in mind the quantity, type, and duration of alcohol consumption, will help in primary and secondary prevention of alcohol-induced disorders.

Nonalcoholic Fatty Liver Disease Associated With Bladder Cancer

Nonalcoholic fatty liver disease (NAFLD) is regarded as a feature of metabolic syndrome in the liver. Metabolic syndrome is associated with a higher risk of bladder cancer. However, the association between NAFLD and bladder cancer is unclear. We aimed to investigate the association between NAFLD and bladder cancer. The records of all patients (n=251) diagnosed with the bladder cancer in our hospital between 2009 and 2013 were reviewed. We also randomly collected the records of adults without cancer (n=266) as the control group. Clinical characteristics, biochemical tests for liver and metabolic function and abdominal computed tomography were assessed. The incidence of NAFLD was 12.0% in the bladder cancer group and 4.9% in the control group. By multiple logistic regression analysis, NAFLD (P=0.007; odds ratio [OR]: 2.61; 95% confidence interval [CI]: 1.30-5.22), male sex (P < 0.001; OR: 2.34; 95% CI: 1.61-3.41) and use of lipid lowering drugs (P=0.001; OR: 0.43; 95% CI: 0.26-0.72) showed significant associations with bladder cancer. In bladder cancer patients, the median survival time was significantly longer in patients without NAFLD than in these with NAFLD (40 months versus 21.5 months, P=0.022). NAFLD was positively associated with bladder cancer and was a poor prognostic factor of bladder cancer. Further studies are needed to confirm whether NAFLD is a factor for the development of bladder cancer.

Evaluation of the biochemical, haematological and histopathological parameters of female Wistar rats fed with aqueous and ethanol extracts of Aspilia africana leaves.

Introduction: Aspilia africana is a plant commonly used to stop bleeding, heal wound, and manage various stomach complaints. This study aimed at evaluating the impact of aqueous and ethanol leaf extracts of A. africana on biochemical (liver function tests, renal function tests, and lipid profile), histopathological (kidney and liver) and haematological parameters of the female Wistar rats. Methods: To study acute toxicity, the median lethal dose (LD50) was determined by oral administration of different doses of the extract to 8 groups of 3 rats each and the animals were observed for 24 hours for signs of toxicity. To evaluate the toxicological effect of the extract, 3 groups of 5 animals each received 0.5 mL normal saline (control), 250 or 500 mg/kg of the extracts for 2 consecutive weeks. Results: Data revealed the LD50 of the extract to be &gt;5000 mg/kg.bw. There was no significant variation in organosomatic indices of the animals fed with aqueous and ethanol extracts of A. africana leaves. In comparison with the control, there were significant increases (p&lt;0.05) in serum liver and kidney biomarkers, high density lipoprotein, and white blood cells while some red cells indices, platelets, some lipid profile levels reduced significantly (p&lt;0.05). A marked alteration in hepatic and renal architectures was also observed. Conclusion: The result of this study shows that the A. africana leaf may not be safe as medicine despite the outcome of LD50 acute toxicity studies. For it to be integrated in folk medicine, we recommend its use at minimal doses.

INTESTINAL FAILURE ASSOCIATED LIVER DISEASE IN ADULT PATIENTS: A ONE-YEAR PROSPECTIVE STUDY

Intestinal Failure Associated Liver Disease (IFALD) results from liver injury due to factors related to intestinal failure (IF) and/or to home parenteral nutrition (HPN), and no other evident cause. The epidemiology of IFALD depends on the criteria used for the diagnosis. The aim of the study was to assess the prevalence and the incidence of IFALD in the first 12 months of HPN in adult patients. 18 adult patients (13 Females; age 46±16 years; short bowel syndrome, 72%) who started HPN between Jan 2016 and December 2017 (T0) were enrolled in the study: 13 completed the 12-month follow-up (T12), 5 are ongoing. Biochemical liver function tests were collected at T0, 6-months (T6) and T12; liver ultrasound (US) was performed at T0 and T12. IFALD-criteria diagnosis: IFALD-Cholestasis: two of ɣglutamyltransferase, alkaline phosphatase and conjugated bilirubin ≥1.5 upper normal level for ≥ 6 months; IFALD-Steatosis: echogenicity at US; IFALD-Fibrosis: FIB-4 index. Statistic: descriptive analysis. Prevalence at T0, T6, T12, respectively: Cholestasis, 50%, 22%, 15%; Steatosis, 69%, 71%, 71%; Fibrosis, 16%, 27%, 0%. Incidence between T0 at T12: Cholestasis, 0%; Steatosis, 50%; Fibrosis, 0%. Our results indicate that IFALD can be present at the beginning of HPN, IFALD-cholestasis and IFALD-fibrosis may disappear during the first period of HPN, whereas IFALD-steatosis remains. This would suggest that at starting HPN, liver may be affected by the metabolic alterations of the acute IF, that subside when turning in chronic IF.

Mesenchymal stem cells suppress hepatic fibrosis accompanied by expanded intrahepatic natural killer cells in rat fibrosis model.

Natural killer (NK) cells have antifibrotic effects. We have evaluated the influence of rat bone marrow-mesenchymal stem cell (BM-MSC) treatment on liver histology, biochemical liver function tests, systemic immunoregulatory state and NK cell distribution in liver and peripheral blood in rat model of common bile duct (CBD) ligation and compared the results with the control group. Rats were divided into three groups: (1) CBD ligated (CBDL) rats received phosphate-buffered saline (CBDL + PBS group) or (2) MSC (CBDL + MSC group) and sham-operated rats received MSC (healthy + MSC group). We found significantly decreased fibrosis scores with BM-MSC treatment in CBDL rats compared to the control (CBDL + PBS) group while no fibrosis developed in sham operated (healthy + MSC) group. BM-MSC treatment has decreased the inflammation as reflected by the significantly decreased T cell proliferation and inflammatory cytokine concentrations from splenocyte culture and liver tissue itself compared to CBDL + PBS. NK cells both in parenchyme and portal areas decreased significantly in liver and blood in CBDL + PBS compared to healthy + MSC while they were found to be increased in CBDL + MSC compared to CBDL + PBS rats. In conclusion, BM-MSCs may suppress hepatic fibrosis accompanied by expanded intrahepatic NK cells in CBDL rats. Thus, our animal study shows that MSC treatment holds great promise for treatment of patients with end-stage liver diseases through a possible mechanism by adopting the NK cell population and new studies investigating the role of NK cells and clinical fibrosis are warranted.Trial registration number: Marmara University Animal Care and Use Committee approval code: 73.2013.mar.

Biomarker and Genomic Risk Factors for Liver Function Test Abnormality in Hazardous Drinkers.

Alcohol dependence and long-term excessive alcohol use may cause liver damage, but only some patients develop cirrhosis. Similarly, high alcohol intake without evident liver disease often but not always produces abnormal enzymatic liver function tests (LFTs), particularly gamma-glutamyl transferase (GGT). We postulate that the factors predisposing to cirrhosis in alcoholics and to liver enzyme abnormality in drinkers are similar, and that biochemical LFTs could therefore be useful as markers of risk of alcoholic liver disease in excessive drinkers. Data from participants in twin and twin-family studies on alcohol use and dependence were used to identify 1,003 people who had reported excessive alcohol intake (28 drinks or more per week). A total of 962 of these provided blood for biochemical tests at the same time. Body mass index (BMI) and biomarkers of metabolic syndrome, inflammation, and iron stores were used in logistic regression with abnormality in serum GGT, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) as outcomes. We conducted genome-wide association analyses for GGT, ALT, and AST separately in the group reporting excessive alcohol intake (N=951) and a low-intake group reporting 14 drinks or fewer per week (N=8,716), and compared results. Abnormal GGT and ALT among excessive drinkers were associated with higher BMI, triglycerides, insulin, uric acid, C-reactive protein, ferritin, and transferrin saturation; and with lower high-density-lipoprotein cholesterol. Abnormal AST was associated with triglycerides, ferritin, and transferrin saturation. ALT was significantly associated with variants at reported genetic loci for alcoholic liver disease (PNPLA3, rs738409, p=0.0076; TM6SF2, rs10401969, p=0.0076; HSD17B13, rs10433879, p=0.0024). Known risk factors for alcoholic cirrhosis including obesity and markers of metabolic syndrome, iron overload and inflammation are associated with liver enzyme abnormality in excessive drinkers.

THE PROTECTIVE EFFECTS OF ECHINOPS HETEROPHYLLUS AQUEOUS EXTRACT AGAINST METHOTREXATE-INDUCED HEPATOTOXICITY IN RABBITS

Objective: The aim of this study was to investigate antioxidant and hepatoprotective properties of Iraqi Echinops heterophyllus aqueous crude extract and its flavonoid fraction against methotrexate (MTX)-induced hepatotoxicity in rabbits.Methods: MTX-induced hepatotoxicity by administration of 20 mg/kg MTX intraperitoneally for 3 successive days was used as animal model, and animals were arrayed in four groups with eight animals in each group: Group 1 was the healthy control, Group 2 - the negative control receiving MTX only, Group 3 received MTX+crude extract of E. heterophyllus, and Group 4 administered MTX+flavonoid fraction of E. heterophyllus. The study duration was 10 days; at day 11, animals were sacrificed, and the blood samples were obtained for the measurement of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, total protein, and albumin as well as ELISA assay of the oxidative stress markers such as glutathione (GSH) and malondialdehyde (MDA). The liver was dissected and processed for histopathological investigation and scoring. Statistical analysis was performed to investigate the significance of each result.Results: The study results revealed severe liver damage due to MTX administration in the negative control (induced-non treated) group in comparison with healthy group, also there was significant hepatoprotective effect after administration of the crude extract of E. heterophyllus, and flavonoid fraction from E. heterophyllus shown after biochemical liver function tests and anti-oxidant properties demonstrated by the measurement of oxidative stress markers MDA and GSH. The crude extract of E. heterophyllus shown superior hepatoprotective and antioxidant effect. Histopathological scoring showed a remarkable decrease in the scores of the treatment groups in comparison with the high score in the MTX only treated group.Conclusions: MTX administered in a dose of 20 mg/kg for 3 successive days causes marked liver injury, while treatment with the crude extract and flavonoid fraction of E. heterophyllus significantly ameliorates MTX-induced liver damage, although the crude extract of E. heterophyllus seems to have the most hepatoprotective properties.