Hepatic Function Test Results Research Articles

Oleuropein ameliorates hyperlipidemia, oxidative stress, inflammatory and liver dysfunction biomarkers, in streptozotocin-induced diabetic rats

Diabetes mellitus (DM) is a serious threat factor for chronic liver disorders and the development of nonalcoholic steatohepatitis into cirrhosis. However, numerous pharmacological actions of olive polyphenol have been discovered, with oleuropein being a primary phenolic substance found in olive leaves, olive oil, and olive fruit (Olea europaea). Our goal is to identify the impacts of oleuropein on lipid measurements, oxidative stress, serum leptin, adiponectin levels, inflammatory status, and hepatic dysfunctions in a male rat model with streptozotocin (STZ)-induced DM. Oleuropein was orally administered to diabetic rats at a 5 mg/kg bw/day dose for 15 days. Diabetic rats treated with oleuropein demonstrated improved hepatic function test results (ALT, AST, alkaline phosphatase, and bilirubin), while activity of the low liver glucose-6-phosphate dehydrogenase (G6PDH) increased. Moreover, serum triacylglycerol, very low-density lipoprotein, low-density lipoprotein, and total cholesterol (TC) were considerably reduced, while high-density lipoprotein increased markedly. In addition, serum antioxidative enzymes such as glutathione peroxidase, catalase, glutathione-S-transferase, and superoxide dismutase increased, as well as glutathione levels. Lipid peroxidation levels were lower than those in the STZ control group. Treating diabetic rats with oleuropein not only resulted in decreased serum leptin and increased adiponectin levels but also had a substantial inhibitory effect on the elevated COX-2 and TNF-α mRNA expression levels in the livers of the STZ group. In conclusion, oleuropein has shown promising results in mitigating hyperlipidemia, oxidative stress, inflammation, and hepatic dysfunction biomarkers in diabetic rats.

Efficacy, safety, and tissue penetration of solithromycin in Japanese patients with otorhinolaryngological infections

ObjectiveTo assess the efficacy, safety, and tissue penetration of solithromycin for the treatment of otorhinolaryngological infections, we conducted three studies: a tissue penetration study with patients scheduled to undergo otorhinolaryngological tissue removal, an open-label study comprising patients with otitis media, pharyngitis, laryngitis, and tonsillitis, and a non-inferiority study compared with high-dose cefcapene-pivoxil (CFPN-PI). MethodsTissue penetration study; 17 patients with chronic rhinosinusitis, chronic otitis media, chronic tonsillitis, or palatine tonsillar hypertrophy, who required resection or removal of their tissue, were enrolled. Solithromycin was administered orally, and otorhinolaryngological tissues were collected 3.5–6 h after drug administration; blood was collected within 15 min before and after drug administration. The collected tissues and blood concentrations were measured at a central laboratory. Open-label study; 55 patients who were diagnosed with acute otitis media, laryngopharyngitis, or tonsillitis were enrolled. Solithromycin was administered orally 800 mg on Day 1, while on days 2–7, 400 mg of the drug was administered once daily. The primary endpoint is the clinical response at Test-of-Cure (TOC: 5–10 days after completion) Non-inferiority study; 283 patients with acute rhinosinusitis or acute exacerbation of chronic rhinosinusitis were randomized into either the solithromycin group or CFPN-PI group. Solithromycin was administered 800 mg once daily on Day 1 and 400 mg once daily while on Days 2–7 in solithromycin group, and CFPN-PI was administered 150 mg three times a day while on Days 1–7 in CFPN-PI group. The primary endpoint is the clinical response at TOC. ResultsIn the tissue penetration study, the tissue concentration ratios (tissue concentration/plasma concentration) of solithromycin were 4.19 in the sinonasal mucosa, 1.33 in the middle ear mucosa, and 6.12 in the palatine tonsil tissue. In the open-label study, the efficacy rates at the TOC were 97.0 % for acute otitis media, 100 % for laryngopharyngitis, and 81.8 % for tonsillitis. In the non-inferiority study comprising patients with rhinosinusitis, the efficacy rate at the TOC was 87.7 % for solithromycin and 89.7 % for CFPN-PI. The difference in the efficacy rate (95 % confidence interval) was -2.0 % (-9.4 % to 5.4 %), verifying the non-inferiority of solithromycin to CFPN-PI. The most common adverse events in patients administered solithromycin were diarrhea (20.7 %), nausea and nasopharyngitis (3.6 %,), pharyngitis and elevated hepatic function test results (3.1 %), and abnormal hepatic function (2.1 %). ConclusionBased on the findings, it is suggested that solithromycin is useful for the treatment of otorhinolaryngological infections.

Periodontitis links to concurrent metabolic disorders and abnormal liver function in pregnant women.

This cross-sectional study investigated the association of periodontitis with the metabolic status and hepatic function in pregnant women. Full-mouth periodontal conditions, metabolic profiles, and hepatic function were assessed in 219 self-reported healthy pregnant females. The association of periodontal status with the systemic parameters was evaluated by parametric and non-parametric tests, and multivariate logistic regression analysis. Overall, periodontal status was positively associated with the metabolic profiles and hepatic function test results. The subjects with periodontitis exhibited higher levels of body mass index (BMI) (p < 0.01) and serum aspartate transaminase (AST) (p < 0.05), elevated diastolic blood pressure (DBP) (p < 0.05), and lower levels of high-density lipoprotein cholesterol (p < 0.05) than those of the counterparts. The periodontitis severity was strongly correlated with BMI and AST levels, and the extent of periodontal inflammation was related to DBP (p < 0.01). The periodontitis patients at 34-36 gestational weeks showed higher blood pressure and AST levels than those of non-periodontitis subjects (p < 0.05). Our findings on the notable links of periodontitis to concurrent metabolic disorders and abnormal liver function in pregnant women highlight the need of proactive integration of regular periodontal screening and healthcare in maternal programs for promoting optimal health and wellbeing of mothers-to-be and newborns.

Increased Insulin Resistance in Hepatitis-C Infection-Association with Altered Hepatic Function Testing.

Introduction: Hepatitis C virus (HCV) infection is a serious global public health problem. It is estimated that 2% to 3% of the world’s population is infected with the virus. It was found that chronic hepatitis C is an independent predictor of the development of type 2 diabetes mellitus. Infection with HCV or the inflammatory response to HCV infection likely contributes to the development of insulin resistance (IR), which increases the risk of developing type 2 diabetes in the long term. This study aimed to assess the insulin resistance in hepatitis C and its correlation with various metabolic parameters. Materials and Methods: This cross-sectional observational study was conducted at a tertiary care hospital in North India in the Department of Internal Medicine with hepatitis C-positive patients attending an out-patient or in-patient department. We took a total of 100 patients aged > 18 years and divided them into two groups: Group A with hepatitis C (cases) and Group B without hepatitis C (controls). There were a total of 50 hepatitis C patients and 50 patients without hepatitis C. Results: A total of 100 patients were included in the present study after obtaining informed consent. There was a significantly higher level of serum ferritin and insulin in group A patients than group B patients. There was a positive correlation of insulin resistance with the serum insulin, ferritin levels, cholesterol, LDL and triglyceride level and a negative correlation with the serum HDL level. The incidence of insulin resistance was positively correlated with changes in fibrosis in the liver due to the hepatitis C infection. Conclusions: From our study, we found that there is an increased incidence of insulin resistance in the patients with hepatitis-C infection, and insulin resistance is associated with the presence of altered hepatic function test results.

Systemic involvement of acute generalized exanthematous pustulosis: a retrospective study on 58 patients

Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction characterized by rash with sterile pustules, high fever and elevated circulating neutrophil counts. To investigate the frequency and clinical features of AGEP systemic involvement. This retrospective study included all patients hospitalized in our department between 2000 and 2010 with a discharge diagnosis of AGEP. Patients had to fulfil the following criteria: (i) a specific EuroSCAR score > 4 and (ii) biological and radiological work-up available. Among the 58 patients enrolled, 10 had at least one systemic involvement: hepatic function test results were abnormal for seven; six had renal insufficiency; two developed acute respiratory distress, with one patient's bronchoalveolar lavage fluid containing many neutrophils but no microorganisms; one was agranulocytotic. Mean peripheral neutrophil counts and mean C-reactive protein levels were elevated significantly in patients with systemic involvement. Amoxicillin rechallenge and hospitalization duration were associated with systemic involvement. AGEP systemic involvement was observed in 17% of cases studied, including liver, kidney, bone-marrow and lung involvement. Outcomes were favourable after drug withdrawal, and symptomatic and topical steroid treatments. The neutrophil count-systemic involvement association may suggest a role for neutrophils in AGEP systemic involvement. Physicians should be aware of the possibility of systemic involvement in AGEP and should actively look for signs of extracutaneous reactions.

Subchronic toxicity of rebaudioside A

The safety of the stevia-derived sweetener, rebaudioside A (CAS No. 58543-16-1), was evaluated in two oral toxicity studies. In a 4-week study, Wistar rats were administered rebaudioside A at dietary concentrations of 0, 25,000, 50,000, 75,000 and 100,000 ppm. The NOAEL, including an evaluation of testes histopathology, was determined to be 100,000 ppm. In the 13-week study, Wistar rats were administered rebaudioside A at dietary concentrations of 0, 12,500, 25,000 and 50,000 ppm. Reductions in body weight gain attributable to initial taste aversion and lower caloric density of the diet were observed in high-dose male and females groups. Inconsistent reductions in serum bile acids and cholesterol were attributed to physiological changes in bile acid metabolism due to excretion of high levels of rebaudioside A via the liver. All other hepatic function test results and liver histopathology were within normal limits. Significant changes in other clinical pathology results, organ weights and functional observational battery test results were not observed. Macroscopic and microscopic examinations of all organs, including testes and kidneys, were unremarkable with respect to treatment-related findings. The NOAEL in the 13-week toxicity study was considered to be 50,000 ppm or approximately 4161 and 4645 mg/kg body weight/day in male and female rats, respectively.

Reduced Argatroban Doses After Coronary Artery Bypass Graft Surgery

The Food and Drug Administration-approved argatroban dose for heparin-induced thrombocytopenia (HIT) is 2 microg/kg/min (0.5 microg/kg/min in hepatic impairment), adjusted to achieve activated partial thromboplastin time (aPTT) 1.5-3 times baseline. Recent data suggest that reduced doses are required after cardiovascular surgery. To characterize dosing requirements, aPTTs, factors affecting dosage, and clinical outcomes in patients administered argatroban after coronary artery bypass graft (CABG) surgery. Charts of 39 patients who underwent CABG surgery and were administered argatroban postoperatively for laboratory-confirmed HIT (n = 25), antibody-negative suspected HIT (n = 10), or previous HIT requiring anticoagulation (n = 4) were retrospectively reviewed. Patient characteristics, argatroban dosing information, aPTTs (target range 45-90 sec), and outcomes were summarized. Regression analyses explored potential effectors of dosage. Patient features, argatroban dosing patterns, and aPTTs were similar among groups. Many patients had laboratory evidence of some hepatic and/or renal dysfunction (median [range] bilirubin 1.0 [0.3-8.0] mg/dL, creatinine clearance 47 [18-287] mL/min). Overall, median argatroban doses were 0.5 microg/kg/min initially and 0.6 microg/kg/min during therapy (median duration 5.3 days). After argatroban initiation, aPTTs were greater than 90 seconds at first assessment in 4 patients (3 with abnormal hepatic function test results) initially administered 0.5, 1, 2, and 2 microg/kg/min, respectively. Within approximately 16 hours of therapy, 33 (85%) patients achieved consecutive therapeutic aPTTs. No association was detected between mean dose during therapy and preoperative ejection fraction, routine hepatic or renal function test results (other than blood urea nitrogen [BUN]), or surgery type. A clinically insignificant association existed between dose and BUN: there was an approximately 0.15 microg/kg/min dose decrease for each 10 mg/dL BUN increase. One patient developed thrombosis, 1 underwent finger amputation, 7 died (5 after argatroban cessation), and 4 had significant bleeding. These findings suggest that reduced initial argatroban doses (eg, 0.5 microg/kg/min), adjusted to achieve therapeutic aPTTs, provide rapid, adequate anticoagulation in postoperative CABG patients with presumed or previous HIT. Prospective study of reduced initial dosing in this setting is warranted.

Clinical study of cefpirome sulphate in obstetric and gynaecological infections.

Cefpirome sulphate is a fourth-generation cephem antibiotic, which has a broad spectrum of antibacterial activity against Gram-positive and -negative bacteria, and is highly stable to beta-lactamase. Cefpirome sulphate was administered to 166 patients with obstetric or gynaecological infections, and its clinical and antibacterial effect was evaluable in 139. Excluding seven patients who violated the study protocol by receiving concomitant drugs, the safety of cefpirome sulphate was assessed in 159 patients. In the 139 patients in whom efficacy was evaluated, the improvement rate was 80.6% (112/139) and the eradication rate 72.6% (45/62). The eradication rate for bacteria isolated from the patients at the start of the study was 84.7% (111/131). No resistance to cefpirome sulphate was observed in Enterococcus faecalis or Bacteroides species. Systemic erythema and nausea each occurred in one patient, and nine patients showed abnormal hepatic function test results. These results suggest that cefpirome sulphate is effective in the treatment of obstetric and gynaecological infections and has a good side-effect profile.

Hepatic involvement in systemic mast cell disease

Thirteen patients with systemic mast cell disease were studied in order to define the hepatic changes in this disease and to correlate the histologic lesions in the liver with the clinical findings. These patients often presented with multisystem disorders and 10 had hepatomegaly. Microscopically, the liver tissues in all patients showed fibrosis and chronic inflammatory cellular infiltration with plasma cells, lymphocytes, eosinophils, and mononuclear fibroblast-like cells in the portal area. The hepatic sinusoids were not significantly involved. A histologic diagnosis of systemic mast cell disease is seldom entertained in liver biopsy specimens embedded in paraffin and stained with hematoxylineosin, but can be facilitated in biopsy specimens embedded in plastic such as methacrylate. Tissue mast cells in the cellular infiltrate can be demonstrated best by special staining techniques with Giemsa, toluidine blue, and chloroacetate esterase. The severity of the histologic changes in the liver does not correlate well with the size of the liver or biochemical changes in the blood. Abnormal serum biochemical values were noted primarily in those with dehydration caused by diarrhea and vomiting, and in those with malnutrition. Hepatic function test results were usually normal, except for alkaline phosphatase level, which was elevated in all 13 patients. Although the clinical significance of hepatic involvement in systemic mast cell disease cannot be established with certainty in this study, it is believed that the prognosis of systemic mast cell disease is most intricately related to the systemic effects of mast cell involvement in many other organs, and not to hepatic involvement per se.

Treatment of acute gout with oxaprozin

Fifty patients with acute gouty arthritis entered into an 8-day multicenter open study designed to evaluate the efficacy and safety of Oxaprozin, a new nonsteroidal antiinflammatory drug (NSAID). Patients received 1,800 mg of Oxaprozin daily in two divided doses (1,200 mg in the morning and 600 mg in the evening) for 2 days, followed by 1,200 mg daily until pain was relieved. Based on evaluation of pain intensity recorded on patient diary cards, 84% of the patients ( P < .001) showed improvement during the 24 hours after receiving at least 2 doses (1,800 mg) of Oxaprozin. At the final clinical visit, 93% reported improvement ( P < .001 ). Fourteen patients reported adverse effects, but only two discontinued treatment for that reason. Five patients discontinued because of an unsatisfactory response. A significant decrease ( P < .001) from baseline occurred in mean total leukocyte count by the eighth day, probably due to the antiinflammatory effect of Oxaprozin. No clinically significant changes in renal or hepatic function test results or vital signs were observed. Oxaprozin was found to be effective and safe in the treatment of patients with acute gout.

Lactic Acidosis and Liver Disease

Both acute and chronic hepatic insufficiency can result in lactate accumulation and lactic acidosis; data from both types of patients were compared. In the chronic group, an acute precipitating event was identified in seven of nine subjects. Four had sepsis and three had gastrointestinal hemorrhage. In these patients, results from most tests of hepatic function were not altered dramatically. There were no long-term survivors in this group. In contrast, patients with acute hepatic failure had striking alterations in their results of hepatic function tests. Notable prolongation of the prothrombin time was always present initially and antedated other abnormalities of hepatic function. Three of seven patients in this group survived. Hypoglycemia was seen in both groups and in two subjects with acute hepatic insufficiency, glucose administration alone resulted in rapid lowering of lactate levels.

Hepatitis B Surface Antigen and Antibody in Asymptomatic Blood Donors

Seventy-two volunteer blood donors who had hepatitis B surface antibody (anti-HBS) were studied and compared with 115 carriers of hepatitis B surface antigen (HBSAg). Anti-BHS-positive donors gave a history of greater possible exposure to hepatitis B virus, there was a lower male-female ratio, and they had a much lower frequency of abnormal hepatic function test results. Those who were positive by counterimmunoelectrophoresis (CIEP), which indicated a high titer of antibody (greater than 1:2,000 as measured by passive hemagglutination assay [PHA], also had an ethnic origin similar to that of the donor panel, ie, predominantly Canadian and northern European. The HBSAg carriers, on the other hand, had a high frequency of origin from Mediterranean and Far Eastern countries. Low-antibody-titer (positive PHA but negative CIEP) donors had ethnic origins that more closely approximated those of HBSAg carriers.

Changes in portal circulation after biliary obstruction in dogs

<h2>Summary</h2> Eighteen mongrel dogs were studied before and at three and four week intervals after common bile duct ligation in regard to changes in results of hepatic function tests and histology, portal pressures, and the degree of portasystemic shunting of differently labelled 15 ± 5 and 25 ± 5 μ particles injected into the portal vein. The demonstration of sinusoidal dilatation and increased intrahepatic portasystemic shunting at the 15 μ level in the majority of dogs by the fourth week of biliary obstruction, and its correlation with changes in portal pressure, are discussed in the light of the irreversible decreases in effective liver blood flow previously reported by one of the authors.

Jaundice Associated With Bacteremia

In seven patients with clinical jaundice associated with bacteremia, hepatic function tests gave variable results; only hyperbilirubinemia was universally present. Values for serum alkaline phosphatase and glutamic oxaloacetic transaminase activity, when determined, were inconstant. Bacteremia was due to various gram-positive and gram-negative organisms, one patient having mixed flora. Pathologic hepatic changes were principally those of cholestasis, Kupffer cell hyperplasia, fatty metamorphosis, and focal necrosis of parenchymal cells; in most patients these changes were thought to represent nonspecific reactive hepatitis. In all patients, autopsy or surgical exploration demonstrated a normal biliary tract with no gross pathologic process involving the liver. Six of the seven died of the underlying illness and associated bacteremia. In the one survivor, the results of hepatic function tests became normal.

Hepatic function tests in heavy drinkers among workmen.

The influence of alcoholic intake on hepatic function was investigated in two groups of apparently healthy workmen. In laborers at a fish market, there was no significant difference of hepatic function tests between those with and without the habit of high alcohol intake. The dietary surveys showed rather increased protein intake in the heavy drinkers. As it is conceivable that these results are associated with the particular condition of the fish market laborers who can eat a lot of fish, a further investigation was carried out with employees engaged in sedentary works at an electric power company. Though abnormal bromsul-phalein test was generally high in its incidence in this group of workers and the results were not so clear-cut as in the former group, the incidence of abnormal bromsulphalein test was similar or only slightly higher in the heavy drinkers as compared with non-heavy drinkers or abstainers. Protein intake was not decreased in the heavy drinkers. Thus, the results of hepatic function tests in heavy drinkers in these worker groups are quite different from those in heavy drinkers visiting the hospital. This difference is explained by the absence of protein deficiency in the heavy drinkers of the worker groups. From these results, the critical quantity of alcohol to cause hepatic injury is discussed.

STUDIES ON POST-TRANSFUSION HEPATITIS

(1) Post-transfusion hepatitis occurred in eleven paients out of eighty-two in-patients received transfusion with whole blood or blood plasma during recent five years.(2) Incidence of the hepatitis was related to the total amount of blood transfused. Posttransfusion hepatitis occurred more frequently among the patients transfused larger amount of bood.(3) There was no significant difference between the incidence of post-transfusion hepatitis in the patients transfused with fresh blood and that with stored blood only.(4) Changes in the results of hepatic function tests were followed during the course of the hepatitis in these patients. Serum GPT level was higher than SGOT at the onset of jaundice and recovery of SGPT level to normal ranges was delayed as compared with that of SGOT. Increase in serum iron level with decrease in UIBC was observed in these cases.