BACKGROUND:

PON1 is an HDL-associated enzyme having antioxidant activity. PON1 is synthesized in the liver, and there is decreased synthesis of PON1 with increased lipid peroxidation. The study was carried with the aim of establishing whether chronic liver disease (CLD) produced any significant changes in serum arylesterase (AE) and lactonase activities of PON. The second objective was to determine whether there was any correlation between serum AE and lactonase activities and the various routine liver function tests. The usefulness of adding serum lactonase and AE activity to standard liver function tests was analyzed by multiple logistic regression analysis. Finally, the diagnostic efficacy or analytical performance of AE and lactonase in assessing patients with CLD was determined using 'receiver operating characteristic' (ROC) plot.

METHODS:

The study group consisted of 120 subjects; 60 were patients with liver disease out of which 40 were having chronic alcoholic liver disease and 20, acute viral hepatitis B, and 60 were healthy controls. Serum PON1 lactonase activity was measured manually using dihydrocoumarin, and AE activity was measured using phenylacetate as substrate. Liver function tests (bilirubin, albumin, AST, ALT, alkaline phosphatise) were done by standard technique.

RESULT:

The serum lactonase and AE activities were decreased significantly in patients with chronic alcoholic liver disease (p < 0.001, p < 0.001) and acute viral hepatitis B (p < 0.001, p < 0.001). Both measurements showed higher efficiency in testing liver dysfunction in multivariate regression analysis. Model 1 consisted of bilirubin, albumin, AST, ALT, and alkaline phosphatase, R2 = 0.912. Model 2 consisted of model 1+arylesterase having higher R2 = 0.0.954, and model 3 consisted of model 1+lactonase having R2 = 0.962. ROC plots demonstrated a high diagnostic accuracy for serum PON1 lactonase (area under ROC curve = 0.982) and serum PON1 arylesterase (area under ROC curve = 0.986).

CONCLUSION:

Low PON1 lactonase and AE activity were found in acute viral hepatitis B and in chronic alcoholic hepatitis.

SESSION TYPE: Miscellaneous Cases IIPRESENTED ON: Tuesday, October 23, 2012 at 11:15 AM - 12:30 PM

INTRODUCTION:

The short-term prognosis of pulmonary embolism (PE) depends on haemodynamic status of the patient. Risk stratification becomes very critical especially for normotensive patients. We present a case of submassive PE with concomitant right ventricle (RV) thrombus.

CASE PRESENTATION:

43 year-old male without any significant medical history who presented with two-week history of progressive dyspnea on exertion, chest tightness and right calf pain. Risk factors were obesity (BMI=42.4) and driving 416 miles days before symptom onset. Physical examination revealed an obese male with increased work of breathing. He was normotensive with a heart rate of 128, respiratory rate of 22 and oxygen saturation of 95% on 2 Liters of oxygen. His lungs were clear to auscultation bilaterally in all fields and cardiac exam was pertinent for a loud S3 gallop. He had a non-erythematous, swollen and tender right calf. Chest computed tomography with intravenous contrast revealed extensive emboli in the proximal branches of his pulmonary artery (Figure 1). Doppler ultrasound of his right lower extremity showed a deep vein thrombosis. Surface echocardiogram showed RV strain and free-wall hypokinesis, RV systolic pressure of 78mmHg, right atrium pressure of 20mmHg and a large RV thrombus (Figure 2). EKG pattern confirmed sinus tachycardia with an S1, Q3, T3 morphology and right-axis deviation. Admission labs were remarkable for troponin 0.37, BNP 629pg/mL, D-dimer 8934ng/mL, alkaline phosphatase 95unit/L, ALT 76unit/L and AST 51unit/L. He was immediately bolused with unfractionated heparin and continued on an infusion prior to being transferred to the medical ICU. Given his significant clot burden in both the pulmonary circulation and RV, pulmonary embolectomy was considered, however we elected to administer 24-hour continuous systemic thrombolytic therapy through a pulmonary artery catheter. He developed mild epistaxis which did not require interruption of thrombolytic infusion. He remained hemodynamically stable with improvement of his tachycardia and dyspnea. His troponin, liver transaminases and BNP improved suggesting improvement of RV strain. Maximum D-dimer value was &gt;15,000ng/mL after thrombolytic infusion which was attributed to clot dissolution.

DISCUSSION:

Our case illustrates the complex decision making regarding aggressive medical versus surgical treatment strategies in managing a normotensive patient with submassive PE and large RV thrombus. It also highlights the need for risk stratification of confirmed acute PE.

CONCLUSIONS:

Prompt administration of continuous systemic thrombolytics resulted in improved morbidity and mortality in our patient.1) Sanchez O, Trinquart L, Colombet I, et al. Prognostic value of right ventricular dysfunction in patients with haemodynamically stable pulmonary embolism: a systematic review. European heart journal 2008; 29:1569-1577DISCLOSURE: The following authors have nothing to disclose: Milan Patel, Timothy Udoji, Kenneth LeeperNo Product/Research Disclosure InformationEmory University, Atlanta, GA.

SESSION TYPE: Non Pulmonary Critical Care PostersPRESENTED ON: Wednesday, October 24, 2012 at 01:30 PM - 02:30 PM

PURPOSE:

Complications of primary non-function after orthotopic liver transplant (OLT) can be managed by total hepatectomy to avoid toxic liver syndrome as bridge therapy to re-transplantation. Postoperative critical care of these patients is challenging. We present the largest case series of critically ill anhepatic patients awaiting re-transplantation. Continuous venovenous hemofiltration (CVVH) was utilized to control volume status and maintain metabolic homeostasis.

METHODS:

A retrospective chart review was completed on eight patients admitted to the surgical ICU after unsuccessful OLT in an anhepatic state to await re-transplantation between 2006 and 2010. Upon admission to the ICU, patients were on mechanical ventilation and placed on CVVH using a polysulfone filter. Lab tests were repeated every six hours and changes to CVVH replacement fluid and balance were adjusted accordingly. The retrospective data was recorded prior to the start of CVVH and before re-transplantation to examine changes in lab values during the anhepatic phase. Data is reported as mean±SD and was analyzed using a Student's paired t-Test with a two-tailed distribution. A p-value &lt;0.05 was considered significant.

RESULTS:

As expected, ALT decreased by an average of 607±588 (p=0.02), and AST by 1781±2130 (p=0.05). The pH increased from 7.17±0.08 to 7.32±0.14 (p=0.02). Serum lactate remained constant (14.4±7.6 mmol/L pre-CVVH, and 14.4±8.4 mmol/ L prior to re-transplant). There were no significant changes in INR (3.2±1.3, 2.2±0.6), glucose (124±39, 145±45 mg/dL), Na (146±4, 139±9 mEq/L), K (4.6±0.7, 4.4±0.6 mEq/L), and iCa (1.1±0.1, 1.17±0.4 mmol/L).

CONCLUSIONS:

Seven of the eight patients were successfully bridged to re-transplantation. The mean time to re-transplantation was 39.1±17.4 hours. The longest anhepatic period was 65.7 hours. Patients can be successfully managed using CVVH in the anhepatic state until a new donor liver is available.

CLINICAL IMPLICATIONS:

Without the use of liver support systems, anhepatic patients were kept metabolically stable utilizing CVVH.DISCLOSURE: The following authors have nothing to disclose: Roozehra Khan, Ronaldo Go, Sumit Kapoor, Ananda Dharshan, Marjan Rahmanian, Anthony Manasia, Adel Bassily-Marcus, Roopa Kohli-Seth, John Oropello, Ernest BenjaminNo Product/Research Disclosure InformationMount Sinai Hospital, New York, NY.

IL-37 is a new anti-inflammatory cytokine that plays an important role in protecting against tissue injury during infections via limiting immune and inflammatory reactions. This study aimed at determining serum IL-37 concentrations and HBeAg seroconversion in chronic hepatitis B virus (HBV) patients during Telbivudine (LDT) treatment. The serum levels of IL-37 were determined using enzyme-linked immunosorbent assay (ELISA) in 40 chronic hepatitis B virus infection (CHB) patients (HBeAg positive), 30 chronic hepatitis C virus infection (CHC) patients [25 with spontaneously resolved hepatitis C virus (SR-CHC)], and 30 healthy controls (HCs). Anti-inflammatory cytokines such as IL-2 and IL-10 were measured using cytometric bead array, and the concentrations of clinical parameters such as serum hepatitis B surface antigen (HBsAg), hepatitis B nucleocapsid antigen (HBeAg), alanine transaminase (ALT), aspartate transaminase (AST), HBV DNA, and hepatitis C virus (HCV) RNA loads were measured. It was found that the serum levels of IL-37 were higher in chronic HBV patients with high virus loads, but the association was not statistically significant. The serum levels of IL-37 were decreased in HBeAg seroconverted CHB patients after 48 weeks of LDT treatment. The serum levels of IL-37 had no significant difference in CHC patients compared with SR-HCV and HCs. The levels of anti-inflammatory cytokine, IL-2 and IL-10, were lower in CHB and CHC patients than the HC, but IL-2 levels increased after LDT treatment in CHB patients. The concentrations of serum IL-37 in CHB and CHC patients with abnormal levels of serum ALT (>50 U/L) or AST (>40 U/L) were significantly higher than CHB, CHC patients with normal levels of ALT (<50 U/L) or AST (<40 U/L). These results suggest that IL-37 may play a significant role in the immune response of CHB patients with HBeAg seroconversion. The serum levels of IL-37 are associated with liver damage in CHB patients.

BACKGROUND AND AIMS:

Magnetic resonance imaging (MRI)-estimated proton-density-fat-fraction (PDFF) is a novel imaging- based biomarker that allows fat mapping of the entire liver,whereas MR spectroscopy (MRS)-measured PDFF provides biochemical measure of liver fat in small regions-of-interest. Cross-sectional studies have shown that MRI-estimated PDFF correlates with MRS-measured PDFF. The aim of this study is to show the utility of MRI-estimated PDFF to assess quantitative changes in liver fat by three-way comparison between MRI-estimated PDFF and MRS-measured PDFF with liver histology-determined steatosis grade at two-time points in patients with nonalcoholic-fatty-liver-disease (NAFLD).

METHODS:

50 biopsy-proven NAFLD patients who participated in a randomized trial; underwent paired evaluation with liver biopsy, MRI-estimated and MRS-measured PDFF of the liver at baseline and 24 weeks.

RESULTS:

The mean (±SD) age and body-mass-index were 48 (±11.7) years and 31(±6.5) kg/m(2) , respectively. MRI-estimated PDFF showed robust correlation with MRS-measured PDFF both at week 0 and week 24 (r: 0.98; P<0.0001 for both). Cross-sectionally, MRI-estimated-PDFF and MRS-measured-PDFF increased with increase inhistology-determined steatosis grade both at week 0 and week 24 (P< 0.05 for all). Longitudinally, patients who had a decrease (≥1%) or increase (≥1%) in MRI-estimated-PDFF (and confirmed by MRS-measured PDFF) showed a parallel decrease or increase in their body weight, serum ALT and AST levels at week 24, respectively.(P< 0.05 ). This small amount of increase or decrease in liver fat could not be quantified on histology.

CONCLUSION:

In this longitudinal study, MRI-estimated PDFF correlates well with MRS-measured-PDFF and is more sensitive than histology-determined steatosis grade in quantifying increase or decrease in liver fat content. Therefore, it may be used to quantify changes in liver fat in future clinical trials. (HEPATOLOGY 2013.).

The goal of our study is to investigate the contribution of promoter DNA methylation of α-adducin (ADD1) gene to the risk of essential hypertension (EH). Using the bisulphite pyrosequencing technology, DNA methylation levels of five CpG dinucleotides on ADD1 promoter were measured among 33 EH cases and 28 healthy controls. Significantly higher ADD1 DNA methylation levels were observed in the females than in the males (CpG1: P = 0.016; CpG2-5: P = 0.021). A breakdown analysis by gender showed that lower CpG1 methylation was associated with an increased risk of EH in females (adjusted P = 0.042). A much more significant association between lower CpG2-5 methylation levels and the increased risk of EH was found in males (adjusted P = 0.008). CpG1 methylation was inversely correlated with age in females (r = -0.407, P = 0.019) but not in males. ADD1 CpG1 and CpG2-5 methylation levels were significantly lower in post-menopausal (>50 years) women than pre-menopausal (≤50 years) women (CpG1: P = 0.006; CpG2-5: P = 0.034). A significant interaction between CpG1 methylation and age was found in females (CpG1*age: P = 0.029). CpG2-5 methylation was shown as a significant predictor of EH in males [area under curve (AUC) = 0.855, P = 0.001], in contrast that CpG1 methylation was a trend toward indicator in females (AUC = 0.699, P = 0.054). In addition, significant differences were observed between males and females for alanine aminotransferase (ALT, P = 0.001), aspartate aminotransferase (AST, P = 0.005) and uric acid (P<0.001). The concentration of AST was inversely correlated with ADD1 CpG2-5 methylation levels in female controls (r = -0.644, P = 0.024). These observations may bring new hints to elaborate the pathogenesis of EH.

BACKGROUND & AIMS:

The characteristics of nonalcoholic fatty liver disease (NAFLD) in elderly patients are unknown. Therefore, we aim to examine the differences between elderly and non-elderly patients with NAFLD, and to identify determinants of nonalcoholic steatohepatitis (NASH) and advanced fibrosis (bridging fibrosis or cirrhosis) in elderly patients.

METHODS:

This isa cross-sectional analysis of adult participants who were prospectively enrolled in the NASH Clinical Research Network studies. Participants were included based upon availability of the centrally reviewed liver histology data within one year of enrollment, resulting in 61 elderly (aged ≥ 65 years) and 735 non-elderly (18-64 years) participants. Main outcomes were presence of NASH and advanced fibrosis.

RESULTS:

Compared to non-elderly patients with NAFLD, elderly patients had a higher prevalence of NASH (56% versus 74%, P=0.02), and advanced fibrosis (25% versus 44%, P=0.002), respectively. Compared to non-elderly patients with NASH, elderly patients with NASH had higher rates of advanced fibrosis (35% versus 52%, P=0.03), as well as other features of severe liver disease including presence of ballooning degeneration, acidophil bodies, megamitochondria, and Mallory-Denk bodies (P≤0.05 for each). Inmultivariable-adjusted logistic regression analyses, independent determinants of NASH in elderly patients included higher AST (odd ratio (OR)=1.12, P=0.007) and lower platelets (OR= 0.98, P=0.02); and independent determinants of advanced fibrosis included higher AST (OR=1.10, P=0.002), lower ALT value (OR= 0.91, P=0.001) and an increased odds of having low HDL (OR=12.62, P=0.004).

CONCLUSIONS:

Elderly patients are more likely to have NASH and advanced fibrosis than non-elderly patients with NAFLD. Liver biopsy may be considered in elderly patients and treatment should be initiated in those with NASH and advanced fibrosis. (HEPATOLOGY 2013.).

Moderate caloric restriction prolongs lifespan. Changes in oxidative stress and hormesis may be involved in this process. The aim of this study is to examine the effects of different levels of chronic caloric restriction (CR) and acute fasting on stress response and oxidative stress parameters in rat liver and plasma. Forty-two rats were divided into groups: control group, calorie-restricted groups with intake of 80-90%, 60-70%, 40-50%, 20-30% of daily caloric needs and acute fasting group. To determine alanine aminotransferase (ALT), aspartate aminotransferase (AST) and superoxide dismutase (SOD) activity, concentration of corticosterone, nitrites and nitrates (NOx), malondialdehyde (MDA) and glutathione (GSH), liver samples and blood were collected. Increase in plasma corticosterone concentration and AST and ALT activity was found in severe CR. Ingestion 40-50% daily caloric needs or less increased liver MDA and NOx concentration and decreased SOD activity. Ingestion 60-70% daily caloric needs increased Mn-SOD activity, GSH and NOx. In acute fasting group and group taking 20-30% daily caloric needs, GSH was significantly lower than in control group. Severe CR and acute fasting increase oxidative damage and decrease antioxidative capacity of hepatocytes. Moderate CR increases antioxidative capacity of hepatocytes due to increase in Mn-SOD activity and GSH concentration, which might have a role in anti-aging and hormetic mechanism of CR.

The rapidly developing field of nanotechnology is becoming a potential source for human exposure to nanoparticles. Titanium dioxide (TiO2) nanoparticles have been widely produced in industrial processes for several years. The aim of this study was to investigate the effects of TiO2 nanoparticles on plasmatic biochemical parameters and the emotional behavior in adult Wistar rats. Rats were treated by intraperitoneal injection of TiO2 nanoparticles (20-30 nm) at a dose of 25 mg/kg. For toxicity evaluation of nanoparticles sample, body weight, organ coefficient, blood biochemistry panel assay (AST, ALT, LDH, uric acid, creatinine, and glucose content) and emotional behavior parameters were determined. Sub-acute TiO2 nanoparticles treatment decreased the body weight, but increased the relative brain weight. Biochemical assessment in plasma samples showed that TiO2 nanoparticles injection increased uric acid concentration and AST activity in rats. However, the same treatment decreased the creatinine level, but had no effect on glucose concentration, ALT and LDH activity. The emotional behavior of control and treated rats was tested in elevated plus-maze. Interestingly, our results showed that TiO2-treated rats spent more time in the secured closed arms and entered the anxiogenic open arms less frequently than control. Our results suggest that TiO2 nanoparticles intoxication could altered biochemical parameters related to changes in organ function and leads to emotional behavior impairment of rats.

Magnesium isoglycyrrhizinate (MI) has been complementarily used for restoring the hepatic impairments caused by taxol plus platinum based chemotherapies in China. Due to the hepatic dependence of paclitaxel elimination, this pilot clinical study aimed to investigate the influence of MI on the pharmacokinetics of paclitaxel in epithelial ovarian cancer patients. During the standard chemotherapy of intravenous paclitaxel (125 mg/m(2) infused over a 3-h period) and intraperitoneal cisplatin (60 mg/m(2)) for patients with FIGO stage II epithelial ovarian cancer, 9 each of total 18 patients were respectively treated with intravenous MI (100 mg) or vehicle control for 4 days. Plasma paclitaxel was analyzed by HPLC and the pharmacokinetic parameters were calculated with non-compartmental analysis. The hematological, hepatic and renal status was monitored before and 3 days after paclitaxel administration. It was observed the terminal t 1/2 and MRT of paclitaxel were significantly (p = 0.002 and 0.001) reduced by MI, respectively, from 11.0 ± 2.2 and 5.6 ± 1.0 h to 7.7 ± 1.7 and 4.0 ± 0.3 h. Hematological toxicity indicated by platelet count and hepatic events marked with ALT, AST and γ-GT were significant in both groups. In spite of the insignificance of decreased system exposure of paclitaxel and recovered hepatic function by MI, they did correlate with each other. It was therefore deduced that the liver toxicities of paclitaxel plus cisplatin chemotherapy potentially decrease hepatic elimination and increase system exposure of paclitaxel, and the recovery of liver function by MI helps to restore hepatic clearance of paclitaxel. The clinical significance of this pharmacokinetic interaction requires further studies with larger population size.