- Email: [email protected]
AST Ratio to Laparoscopic Liver Biopsy in Patients with Liver Disease
AASLD Abstracts
M1571
M1573
Relaxin: An Antifibrotic Hormone in Patients with Liver Disease Nandini Channabasappa, Marlyn J. Mayo
Comparison of TRANSIENT ELASTOGRAPHY, APRI Score, ALT/AST Ratio to Laparoscopic Liver Biopsy in Patients with Liver Disease Chakradhar M. Reddy, Srinivas Gaddam, Carmine G. Nudo, Zvi Leibovici, Luis A. ServinAbad, Maria D. De Medina, Lennox J. Jeffers, Eugene Schiff
Background: Relaxin is an insulin-like polypeptide hormone with tissue remodeling and antifibrotic properties. Relaxin was originally described as a hormone of pregnancy, but recent findings suggest that it is also an important regulator of extracellular matrix remodeling outside of the reproductive system. Relaxin binds to hepatic stellate cells causing reduced collagen synthesis and increased action of tissue metalloproteinases. Hypothesis: Serum relaxin 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 inflammation and fibrosis. Methods: In this study, In Vivo serum relaxin concentrations were measured in primary biliary cirrhosis patients (PBC) (N=76), hepatitis C patients (HCV) (N=60), and healthy controls (N=30) using a commercially available ELISA kit. Stage of hepatic fibrosis was determined by liver biopsy in the PBC and HCV patients and was scored using the Ishak scale of fibrosis. Serial serum relaxin concentrations were measured annually in the PBC patients over a 15 year period. Serum relaxin levels were compared between groups using the Mann Whitney Rank Sum test and correlated with the stage of fibrosis using the Spearman Rank Order correlation. Results: Serum relaxin concentrations in patients with liver 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 63.5 pg/ml vs. 43.4 pg/ml, P=0.002), but HCV patients still had higher serum relaxin concentrations than the control group (mean 43.4 pg/ml vs. 21.0 pg/ml, P=0.018). There was no correlation between relaxin concentration and stage of hepatic fibrosis (r= -0.131). Serum relaxin concentrations were either stable or rose very slowly over a period of 15 years (mean increase 2.59 pg/ml per year). The subset of PBC patients with concomitant limited sclerosis had higher relaxin concentrations than the PBC patients without limited sclerosis (mean 90.0 pg/ml vs. 33.5 pg/ml, p=0.020). Conclusions: This is the first study measuring serum relaxin in patients with liver disease. We found that levels are higher in patients with liver disease than without liver disease. Other systemic diseases that cause fibrosis (such as limited sclerosis in the PBC group) also appear to increase relaxin levels. These findings support the hypothesis that relaxin is secreted in patients with ongoing fibrogenesis. We believe relaxin acts as an endogenous counter regulatory hormone for scar formation and may have therapeutic potential as an anti-fibrotic agent.
Background: Liver biopsy remains the gold standard method to assess the degree of liver fibrosis. The accuracy of biopsies is limited by intraobserver and sampling variability. Laparoscopic liver biopsy (LLB) reduces sampling variability, but still has its risks. Objective of non-invasive measures is to substitute liver biopsy. Aim: The purpose of this study was to evaluate the accuracy of the non-invasive measures such as transient elastography (Fibro Scan®, Echosens, France), aspartate aminotransferase (AST) to platelet ratio index score and (AST) / alanine aminotransferase (ALT) ratio to LLB. Methods: Charts of patients who had transient elastography (TE) and a LLB done from November 2004 to September 2007 were reviewed. All the patients with necessary laboratory parameters to calculate APRI and AST/ALT ratio were included. Spearman's correlation analysis and AUROC curves were used to analyze the data. Results: Six out of the available 95 patients were excluded form the analysis as the necessary data was unavailable. Out of the included 89 patients, average age was 51 years and 51% were females. Reasons for patients who underwent LLB; 65 % for hepatitis C (HCV), 10% for elevated liver chemistries, 9% for hepatitis B (HBV), 7% for non alcoholic steato-hepatitis and 10% for other reasons. APRI score >1 was correlated to staging (r = 0.44, p = 0.01) and grading (r = 0.38, p = 0.01). AST/ALT ratio >1 was not correlated to staging (r = 0.11, p = 0.32) or grading (r = 0.03, p = 0.78). APRI >1 was correlated to TE (r = 0.36, p = <0.01) while AST/ALT >1 was not (r = 0.02, p = 0.89). In patients 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, 0.73 for APRI >1 and 0.61 for AST/ALT >1. With F ≥3, sensitivity for APRI >1 (61.1) was almost the 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 70.1 and 82.1 respectively. In subgroup analysis, TE and APRI score performed well. In 53 patients 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 equal for TE (0.68) and APRI >1 (0.74). Overall AST/ALT ratio performed poorly in all comparisons except the non-HCV cirrhotics, the AUROC was 0.74. Conclusions: The APRI score was approximately as sensitive as the TE on all analysis, but less specific than the TE. TE is superior to the APRI score in assessing liver fibrosis.
M1572 AST/ALT, APRI, and Magnetic Resonance Elastography for Detection of Advanced Fibrosis in Clinical Practice Jayant A. Talwalkar, John B. Gross, Sudhakar Venkatesh, Meng Yin, James Glockner, Naoki Takahashi, Patrick S. Kamath, Richard L. Ehman
M1574
Background: A substantial need exists for identifying noninvasive methods to detect hepatic fibrosis. Readily available serum markers are ideal yet novel imaging methods may also be useful within clinical practice. However, direct comparisons between theses modalities have not been extensive. Aims: To compare the diagnostic accuracy of AST/ALT, APRI, and liver stiffness measurement by MR elastography (MRE) for detecting clinically significant hepatic fibrosis. Methods: Patients were referred for MRE within clinical practice between February 2007 and November 2007. Liver biopsy within 1 year of MRE was required in patients with stages F0-F3 hepatic fibrosis. Compensated cirrhosis was defined by histology (stage 4) or clinical criteria. Overt clinical manifestations of portal hypertension, previous therapy for underlying liver disease, and HCC were exclusion criteria. Serum AST, ALT, and platelet count 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 calculated for each index. ROC curve analysis was used to define performance across varying diagnostic thresholds. Results: 78 patients comprised the study cohort. Liver stiffness measurement was obtained in all patients (100%). The mean age was 53 ± 14 years (range, 2177) 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 the detection of clinically significant hepatic fibrosis (F2-F4), liver stiffness measurement by MRE was superior to APRI > 0.5 and APRI > 1.5. For the detection of cirrhosis (F4), liver stiffness 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 than serum AST/ALT and APRI at recommended cut-off values in clinical practice.
INTRODUCTION: Hyperventilation in cirrhosis may be due to either hypoxia or direct respiratory centre stimulation by certain substances which are otherwise metabolized by the normal liver.(1,2) Hypoxia in cirrhosis is due to multifactorial such as intrapulmonary vasodilatation/shunt(IPVS),defective diffusion capacity(DLCO<80%),impaired ventilationperfusion mismatch and mechanical causes like pleuraleffusion,ascites,etc. AIMS & METHODS: Aim: To find out the relationship between hyperventilation with IPVS,(Aa)O2,DLCO and substances such as progesterone and lactic acid. Methods: Out of one hundred cirrhotic patients registered in the liver clinic, thirty three patients were nonsmoking men without pulmonary diseases & ascites were included in this study. All underwent transcutaneous 2D contrast echocardiography, pulmonary function tests, arterial blood gas analysis, oxygen dissociation curve plotting and estimation of blood progesterone and lactic acid RESULTS: Thirty three cirrhotic men with a mean age of 41.84 + 11.4 years. Out of them, 6 and 27 belonged to Child's A & B respectively. Etiology of cirrhosis was ethanol in 18 patients, viral in 8 & others in 8 men. Out of 33 patients, 29 (87.87%) had abnormal DCLO, 17(51.51%) had elevated (A-a)O2, 19(57.57%) had IPVD. The mean PaCO2 was 28.27 + 7.6, 28.74 + 5.6 & 31.53 + 5.9 respectively and which indicated hyperventilation resulting in respiratory alkalosis. Mean value of P50 of the oxygen dissociation curve was 25.41 + 1.1, 25.24 + 0.7 & 25.28 + 1.0 respectively i.e., there was a left sided shift which also confirms alkalosis respectively. Four patients (13.79%) had mild hypoxemia (PaO2 60 to 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 of either defective diffusion capacity or elevated (A-a)O2 or presence of IPVD or presence of elevated progesterone, lactic acid in the blood or combination of all which tries to keep PaO2 in the normal range. Results
AASLD Abstracts
Understanding Pathophysiology of Hyperventilation in Cirrhosis Joye Varghese, Arun Kumar Muthusamy, Sowmya Sowmya S, Jayanthi Venkatraman
A-796
M1571
M1573
Relaxin: An Antifibrotic Hormone in Patients with Liver Disease Nandini Channabasappa, Marlyn J. Mayo
Comparison of TRANSIENT ELASTOGRAPHY, APRI Score, ALT/AST Ratio to Laparoscopic Liver Biopsy in Patients with Liver Disease Chakradhar M. Reddy, Srinivas Gaddam, Carmine G. Nudo, Zvi Leibovici, Luis A. ServinAbad, Maria D. De Medina, Lennox J. Jeffers, Eugene Schiff
Background: Relaxin is an insulin-like polypeptide hormone with tissue remodeling and antifibrotic properties. Relaxin was originally described as a hormone of pregnancy, but recent findings suggest that it is also an important regulator of extracellular matrix remodeling outside of the reproductive system. Relaxin binds to hepatic stellate cells causing reduced collagen synthesis and increased action of tissue metalloproteinases. Hypothesis: Serum relaxin 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 inflammation and fibrosis. Methods: In this study, In Vivo serum relaxin concentrations were measured in primary biliary cirrhosis patients (PBC) (N=76), hepatitis C patients (HCV) (N=60), and healthy controls (N=30) using a commercially available ELISA kit. Stage of hepatic fibrosis was determined by liver biopsy in the PBC and HCV patients and was scored using the Ishak scale of fibrosis. Serial serum relaxin concentrations were measured annually in the PBC patients over a 15 year period. Serum relaxin levels were compared between groups using the Mann Whitney Rank Sum test and correlated with the stage of fibrosis using the Spearman Rank Order correlation. Results: Serum relaxin concentrations in patients with liver 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 63.5 pg/ml vs. 43.4 pg/ml, P=0.002), but HCV patients still had higher serum relaxin concentrations than the control group (mean 43.4 pg/ml vs. 21.0 pg/ml, P=0.018). There was no correlation between relaxin concentration and stage of hepatic fibrosis (r= -0.131). Serum relaxin concentrations were either stable or rose very slowly over a period of 15 years (mean increase 2.59 pg/ml per year). The subset of PBC patients with concomitant limited sclerosis had higher relaxin concentrations than the PBC patients without limited sclerosis (mean 90.0 pg/ml vs. 33.5 pg/ml, p=0.020). Conclusions: This is the first study measuring serum relaxin in patients with liver disease. We found that levels are higher in patients with liver disease than without liver disease. Other systemic diseases that cause fibrosis (such as limited sclerosis in the PBC group) also appear to increase relaxin levels. These findings support the hypothesis that relaxin is secreted in patients with ongoing fibrogenesis. We believe relaxin acts as an endogenous counter regulatory hormone for scar formation and may have therapeutic potential as an anti-fibrotic agent.
Background: Liver biopsy remains the gold standard method to assess the degree of liver fibrosis. The accuracy of biopsies is limited by intraobserver and sampling variability. Laparoscopic liver biopsy (LLB) reduces sampling variability, but still has its risks. Objective of non-invasive measures is to substitute liver biopsy. Aim: The purpose of this study was to evaluate the accuracy of the non-invasive measures such as transient elastography (Fibro Scan®, Echosens, France), aspartate aminotransferase (AST) to platelet ratio index score and (AST) / alanine aminotransferase (ALT) ratio to LLB. Methods: Charts of patients who had transient elastography (TE) and a LLB done from November 2004 to September 2007 were reviewed. All the patients with necessary laboratory parameters to calculate APRI and AST/ALT ratio were included. Spearman's correlation analysis and AUROC curves were used to analyze the data. Results: Six out of the available 95 patients were excluded form the analysis as the necessary data was unavailable. Out of the included 89 patients, average age was 51 years and 51% were females. Reasons for patients who underwent LLB; 65 % for hepatitis C (HCV), 10% for elevated liver chemistries, 9% for hepatitis B (HBV), 7% for non alcoholic steato-hepatitis and 10% for other reasons. APRI score >1 was correlated to staging (r = 0.44, p = 0.01) and grading (r = 0.38, p = 0.01). AST/ALT ratio >1 was not correlated to staging (r = 0.11, p = 0.32) or grading (r = 0.03, p = 0.78). APRI >1 was correlated to TE (r = 0.36, p = <0.01) while AST/ALT >1 was not (r = 0.02, p = 0.89). In patients 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, 0.73 for APRI >1 and 0.61 for AST/ALT >1. With F ≥3, sensitivity for APRI >1 (61.1) was almost the 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 70.1 and 82.1 respectively. In subgroup analysis, TE and APRI score performed well. In 53 patients 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 equal for TE (0.68) and APRI >1 (0.74). Overall AST/ALT ratio performed poorly in all comparisons except the non-HCV cirrhotics, the AUROC was 0.74. Conclusions: The APRI score was approximately as sensitive as the TE on all analysis, but less specific than the TE. TE is superior to the APRI score in assessing liver fibrosis.
M1572 AST/ALT, APRI, and Magnetic Resonance Elastography for Detection of Advanced Fibrosis in Clinical Practice Jayant A. Talwalkar, John B. Gross, Sudhakar Venkatesh, Meng Yin, James Glockner, Naoki Takahashi, Patrick S. Kamath, Richard L. Ehman
M1574
Background: A substantial need exists for identifying noninvasive methods to detect hepatic fibrosis. Readily available serum markers are ideal yet novel imaging methods may also be useful within clinical practice. However, direct comparisons between theses modalities have not been extensive. Aims: To compare the diagnostic accuracy of AST/ALT, APRI, and liver stiffness measurement by MR elastography (MRE) for detecting clinically significant hepatic fibrosis. Methods: Patients were referred for MRE within clinical practice between February 2007 and November 2007. Liver biopsy within 1 year of MRE was required in patients with stages F0-F3 hepatic fibrosis. Compensated cirrhosis was defined by histology (stage 4) or clinical criteria. Overt clinical manifestations of portal hypertension, previous therapy for underlying liver disease, and HCC were exclusion criteria. Serum AST, ALT, and platelet count 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 calculated for each index. ROC curve analysis was used to define performance across varying diagnostic thresholds. Results: 78 patients comprised the study cohort. Liver stiffness measurement was obtained in all patients (100%). The mean age was 53 ± 14 years (range, 2177) 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 the detection of clinically significant hepatic fibrosis (F2-F4), liver stiffness measurement by MRE was superior to APRI > 0.5 and APRI > 1.5. For the detection of cirrhosis (F4), liver stiffness 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 than serum AST/ALT and APRI at recommended cut-off values in clinical practice.
INTRODUCTION: Hyperventilation in cirrhosis may be due to either hypoxia or direct respiratory centre stimulation by certain substances which are otherwise metabolized by the normal liver.(1,2) Hypoxia in cirrhosis is due to multifactorial such as intrapulmonary vasodilatation/shunt(IPVS),defective diffusion capacity(DLCO<80%),impaired ventilationperfusion mismatch and mechanical causes like pleuraleffusion,ascites,etc. AIMS & METHODS: Aim: To find out the relationship between hyperventilation with IPVS,(Aa)O2,DLCO and substances such as progesterone and lactic acid. Methods: Out of one hundred cirrhotic patients registered in the liver clinic, thirty three patients were nonsmoking men without pulmonary diseases & ascites were included in this study. All underwent transcutaneous 2D contrast echocardiography, pulmonary function tests, arterial blood gas analysis, oxygen dissociation curve plotting and estimation of blood progesterone and lactic acid RESULTS: Thirty three cirrhotic men with a mean age of 41.84 + 11.4 years. Out of them, 6 and 27 belonged to Child's A & B respectively. Etiology of cirrhosis was ethanol in 18 patients, viral in 8 & others in 8 men. Out of 33 patients, 29 (87.87%) had abnormal DCLO, 17(51.51%) had elevated (A-a)O2, 19(57.57%) had IPVD. The mean PaCO2 was 28.27 + 7.6, 28.74 + 5.6 & 31.53 + 5.9 respectively and which indicated hyperventilation resulting in respiratory alkalosis. Mean value of P50 of the oxygen dissociation curve was 25.41 + 1.1, 25.24 + 0.7 & 25.28 + 1.0 respectively i.e., there was a left sided shift which also confirms alkalosis respectively. Four patients (13.79%) had mild hypoxemia (PaO2 60 to 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 of either defective diffusion capacity or elevated (A-a)O2 or presence of IPVD or presence of elevated progesterone, lactic acid in the blood or combination of all which tries to keep PaO2 in the normal range. Results
AASLD Abstracts
Understanding Pathophysiology of Hyperventilation in Cirrhosis Joye Varghese, Arun Kumar Muthusamy, Sowmya Sowmya S, Jayanthi Venkatraman
A-796