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sM1571

Relaxin: An Antifibrotic Hormone in Patients with Liver DiseaseNandini Channabasappa, Marlyn J. Mayo

Background: Relaxin is an insulin-like polypeptide hormone with tissue remodeling andantifibrotic properties. Relaxin was originally described as a hormone of pregnancy, butrecent findings suggest that it is also an important regulator of extracellular matrix remodelingoutside of the reproductive system. Relaxin binds to hepatic stellate cells causing reducedcollagen synthesis and increased action of tissue metalloproteinases. Hypothesis: Serumrelaxin levels will be higher in patients with liver disease than in the general population,due to the activation of anti-fibrotic pathways in persons with ongoing hepatic inflammationand fibrosis. Methods: In this study, In Vivo serum relaxin concentrations were measuredin primary biliary cirrhosis patients (PBC) (N=76), hepatitis C patients (HCV) (N=60), andhealthy controls (N=30) using a commercially available ELISA kit. Stage of hepatic fibrosiswas determined by liver biopsy in the PBC and HCV patients and was scored using theIshak scale of fibrosis. Serial serum relaxin concentrations were measured annually in thePBC patients over a 15 year period. Serum relaxin levels were compared between groupsusing the Mann Whitney Rank Sum test and correlated with the stage of fibrosis using theSpearman Rank Order correlation. Results: Serum relaxin concentrations in patients withliver disease were higher than the control population (mean 63.5pg/ml vs. 21.0 pg/ml,P<0.001). PBC patients had higher relaxin concentrations than HCV patients (mean 63.5pg/ml vs. 43.4 pg/ml, P=0.002), but HCV patients still had higher serum relaxin concentra-tions than the control group (mean 43.4 pg/ml vs. 21.0 pg/ml, P=0.018). There was nocorrelation between relaxin concentration and stage of hepatic fibrosis (r= -0.131). Serumrelaxin concentrations were either stable or rose very slowly over a period of 15 years (meanincrease 2.59 pg/ml per year). The subset of PBC patients with concomitant limited sclerosishad higher relaxin concentrations than the PBC patients without limited sclerosis (mean90.0 pg/ml vs. 33.5 pg/ml, p=0.020). Conclusions: This is the first study measuring serumrelaxin in patients with liver disease. We found that levels are higher in patients with liverdisease than without liver disease. Other systemic diseases that cause fibrosis (such as limitedsclerosis in the PBC group) also appear to increase relaxin levels. These findings supportthe hypothesis that relaxin is secreted in patients with ongoing fibrogenesis. We believerelaxin acts as an endogenous counter regulatory hormone for scar formation and may havetherapeutic potential as an anti-fibrotic agent.

M1572

AST/ALT, APRI, and Magnetic Resonance Elastography for Detection ofAdvanced Fibrosis in Clinical PracticeJayant A. Talwalkar, John B. Gross, Sudhakar Venkatesh, Meng Yin, James Glockner,Naoki Takahashi, Patrick S. Kamath, Richard L. Ehman

Background: A substantial need exists for identifying noninvasive methods to detect hepaticfibrosis. Readily available serum markers are ideal yet novel imaging methods may also beuseful within clinical practice. However, direct comparisons between theses modalities havenot been extensive. Aims: To compare the diagnostic accuracy of AST/ALT, APRI, and liverstiffness measurement by MR elastography (MRE) for detecting clinically significant hepaticfibrosis. Methods: Patients were referred for MRE within clinical practice between February2007 and November 2007. Liver biopsy within 1 year of MRE was required in patients withstages F0-F3 hepatic fibrosis. Compensated cirrhosis was defined by histology (stage 4) orclinical criteria. Overt clinical manifestations of portal hypertension, previous therapy forunderlying liver disease, and HCC were exclusion criteria. Serum AST, ALT, and plateletcount were used at the time of liver biopsy if MRE was done > 48 hours later. Sensitivity,specificity, positive predictive value (PPV), and negative predictive value (NPV) were calcu-lated for each index. ROC curve analysis was used to define performance across varyingdiagnostic thresholds. Results: 78 patients comprised the study cohort. Liver stiffness meas-urement was obtained in all patients (100%). The mean age was 53 ± 14 years (range, 21-77) with 59% women. Liver disease etiologies were nonalcoholic fatty liver disease (NAFLD)(46%), hepatitis B and C (36%), autoimmune/cholestatic liver disease (10%), and alcohol(5%). Distribution of fibrosis stage was 0-1 in 22%, 2-3 in 20%, and 4 in 58%. For thedetection of clinically significant hepatic fibrosis (F2-F4), liver stiffness measurement byMRE was superior to APRI > 0.5 and APRI > 1.5. For the detection of cirrhosis (F4), liverstiffness measurement by MRE was also superior to AST/ALT > 1, APRI > 1.0, and APRI >2.0. Conclusion: Liver stiffness measurement by MRE has greater diagnostic accuracy thanserum AST/ALT and APRI at recommended cut-off values in clinical practice.

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M1573

Comparison of TRANSIENT ELASTOGRAPHY, APRI Score, ALT/AST Ratio toLaparoscopic Liver Biopsy in Patients with Liver DiseaseChakradhar M. Reddy, Srinivas Gaddam, Carmine G. Nudo, Zvi Leibovici, Luis A. Servin-Abad, Maria D. De Medina, Lennox J. Jeffers, Eugene Schiff

Background: Liver biopsy remains the gold standard method to assess the degree of liverfibrosis. The accuracy of biopsies is limited by intraobserver and sampling variability. Laparo-scopic liver biopsy (LLB) reduces sampling variability, but still has its risks. Objective ofnon-invasive measures is to substitute liver biopsy. Aim: The purpose of this study was toevaluate the accuracy of the non-invasive measures such as transient elastography (FibroScan®, Echosens, France), aspartate aminotransferase (AST) to platelet ratio index scoreand (AST) / alanine aminotransferase (ALT) ratio to LLB. Methods: Charts of patients whohad transient elastography (TE) and a LLB done from November 2004 to September 2007were reviewed. All the patients with necessary laboratory parameters to calculate APRI andAST/ALT ratio were included. Spearman's correlation analysis and AUROC curves were usedto analyze the data. Results: Six out of the available 95 patients were excluded form theanalysis as the necessary data was unavailable. Out of the included 89 patients, average agewas 51 years and 51% were females. Reasons for patients who underwent LLB; 65 % forhepatitis C (HCV), 10% for elevated liver chemistries, 9% for hepatitis B (HBV), 7% fornon alcoholic steato-hepatitis and 10% for other reasons. APRI score >1 was correlated tostaging (r = 0.44, p = 0.01) and grading (r = 0.38, p = 0.01). AST/ALT ratio >1 was notcorrelated to staging (r = 0.11, p = 0.32) or grading (r = 0.03, p = 0.78). APRI >1 wascorrelated to TE (r = 0.36, p = <0.01) while AST/ALT >1 was not (r = 0.02, p = 0.89). Inpatients with fibrosis (F4) the AUROC was 0.84 for TE, 0.82 for APRI>1 and 0.59 for AST/ALT >1. For patients with stage 3 or greater fibrosis (F ≥3) AUROC was 0.82 for TE, 0.73for APRI >1 and 0.61 for AST/ALT >1. With F ≥3, sensitivity for APRI >1 (61.1) was almostthe same as TE (58.3). For F4 sensitivity for APRI >1 (81.3) was equal to that of TE (81.3).Specificity with F ≥3 was 91.5 for TE and 76.6 for APRI >1; Specificity with F4 was 70.1and 82.1 respectively. In subgroup analysis, TE and APRI score performed well. In 53patients with HCV (11 cirrhotic and 42 non-cirrhotic), AUROC was almost equal for TE(0.92) and APRI >1(0.87). Similarly in the non-HCV subgroup, AUROC was almost equalfor TE (0.68) and APRI >1 (0.74). Overall AST/ALT ratio performed poorly in all comparisonsexcept the non-HCV cirrhotics, the AUROC was 0.74. Conclusions: The APRI score wasapproximately as sensitive as the TE on all analysis, but less specific than the TE. TE issuperior to the APRI score in assessing liver fibrosis.

M1574

Understanding Pathophysiology of Hyperventilation in CirrhosisJoye Varghese, Arun Kumar Muthusamy, Sowmya Sowmya S, Jayanthi Venkatraman

INTRODUCTION: Hyperventilation in cirrhosis may be due to either hypoxia or directrespiratory centre stimulation by certain substances which are otherwise metabolized by thenormal liver.(1,2) Hypoxia in cirrhosis is due to multifactorial such as intrapulmonaryvasodilatation/shunt(IPVS),defective diffusion capacity(DLCO<80%),impaired ventilation-perfusion mismatch and mechanical causes like pleuraleffusion,ascites,etc. AIMS &METHODS: Aim: To find out the relationship between hyperventilation with IPVS,(A-a)O2,DLCO and substances such as progesterone and lactic acid. Methods: Out of onehundred cirrhotic patients registered in the liver clinic, thirty three patients were nonsmokingmen without pulmonary diseases & ascites were included in this study. All underwenttranscutaneous 2D contrast echocardiography, pulmonary function tests, arterial blood gasanalysis, oxygen dissociation curve plotting and estimation of blood progesterone and lacticacid RESULTS: Thirty three cirrhotic men with a mean age of 41.84 + 11.4 years. Out ofthem, 6 and 27 belonged to Child's A & B respectively. Etiology of cirrhosis was ethanolin 18 patients, viral in 8 & others in 8 men. Out of 33 patients, 29 (87.87%) had abnormalDCLO, 17(51.51%) had elevated (A-a)O2, 19(57.57%) had IPVD. The mean PaCO2 was28.27 + 7.6, 28.74 + 5.6 & 31.53 + 5.9 respectively and which indicated hyperventilationresulting in respiratory alkalosis. Mean value of P50 of the oxygen dissociation curve was25.41 + 1.1, 25.24 + 0.7 & 25.28 + 1.0 respectively i.e., there was a left sided shift whichalso confirms alkalosis respectively. Four patients (13.79%) had mild hypoxemia (PaO2 60to 80 mm of Hg); one (3.3%) had severe hypoxemia (PaO2 < 60mm of Hg) and the rest(82.9%) had normal PaO2. The lactic acid and progesterone were elevated in 13(39.39%)& 16 (48.48%) patients respectively CONCLUSION: Hyperventilation was the effect ofeither defective diffusion capacity or elevated (A-a)O2 or presence of IPVD or presence ofelevated progesterone, lactic acid in the blood or combination of all which tries to keepPaO2 in the normal range.Results