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Cerebral changes in patients with liver cirrhosis detected by magnetic resonance imaging and proton magnetic resonance spectroscopy
A1070
AASLD ABSTRACTS
• ANALYSIS OF INTRAHEPATIC CYTOKINE EXPRESSION OF CHRONIC HCVINFECTED PATIENTS ACCORDING TO RESPONSE TO INTERFERON THERAPY AS. Gaweeo, D.H. Van Thiel, V. Rastgi, H.F. Otto, F. Schneider, W.J. Hofmaun. Institute of Pathology, University of Heidelberg, Germany, Oklahoma Transplantation Iesfitate, Oklahoma, USA & INOVA Institute, Falls Chttreh, USA Interferon-alpha [IFN-cq is the only effective treatment to date for chronic hepatitis C virus [FIC~ infection. However, more than 50% of chronic HCV-infected patients are insensitive to IFN-therapy, suggesting suboptimal IFN-ct iannnnomodulation. Increasing data strongly suggest the contribution of on-site laminae-mediated meehanisms to the pathogenesis of chronic hepatitis C virus [HCV] infection. Defining the leeal cytokine interactions in a possibly dysregulated irmnane response may further elucidate the ill-defined pathogenetie process of chronic HCV infection and help optimize current treatment strategies. We assessed the intrahepatic eytokine gene activity of chronic HCV-infeeted patients aceerding to response after IFN-~x therapy. The mRNA expression patterns of the 'type 1' (IL-2, IFN-?), 'type 2' QL-4, IL-5, 1L-6, IL-10), and proinflammatory eytukines (IL-113, IL-8, IL-12 p40, TNF-cq GM-CSF) including IL-2Rc~, IL-7, and TGF-151 were studied using RT-~CR in 44 liver biopsies of 29 chronic HCV-infeeted patients: before IFN-cx treatment (u=15), nonresponders (n=18) and responders (n=ll) 6 months after treatment with 3 MU lFN-ct. The definition of response was based on senun ALT levels (NE.IM 1989; 321:1501-6). IL-2 and IL-12 mRNA iranscripts were detected in 46% and 13%, respectively, of pre-treatment liver biopsies. Following IFN-ct treatment, IL-2 and IL-12 expression was enhanced in nou-responders (67% and 36%, respectively) in contrast to responders (36% and 18%). No correlation was otherwise observed in the expression patterns of other cytokines investigated. IFN-o~ has several immanomodulatory properties in addition to its direct antiviral effects. IFN-a particularly promotes cellular responses by directly stimulating eytntoxic T lymphocyte [CTL] activity and indirectly, by initiating a type 1 cytokine profile (e.g. IL-2) mediating CD8+ CTL responses, a property shared by the haman monocyte/maerophage-derived IL-12. The favorable effects of IFN-~x in controlling chronic HCV infection could be overcome by an excessive on-site CTL response through the synergistic action of IL-2, IL-12, and IFN-% potent CTL inducers. Infiltrating HCV-specific CD8+ CTLs have been identified in chronic HCV-infected haman livers and in fact, a correlative decrease of intrahepatic CD8+ T cells with serum ALT levels following beneficial IFN-cx treatment has been reported. From these data, it could be speculated that locally elaborated cytokines may induce non-specific CTL reernimaent and vigorous CTL responses contributing to liver cell injury of chronic HCV infeetion and explain an immunopathogenetic IFN-ct-resistant meehanism.
• Cerebral changes in patients with liver cirrhosis detected by magnetic resonance imaging and proton magnetic resonance spectroscopy. A. Geissler.
G. Lock*, R. Fdind, J. Sch6lmerich*, S. Feuerbach, A. Holstege*. Depts. of Radiology and Internal Medicine I, University of Regensburg, 93042 Rcgensbarg, FRG. Backaround: In patients suffering from liver cirrhosis, hepatic encephalopathy (HE) is a common problem. Diagnosis is easily made in advanced stages but may be cumbersome in sub-clinical HE. Aim of the study was the evaluation of magnetic resonance imaging (MRI) and spectroscopy (MRS) in comparison to clinical diagnosis and psychometric tests.in cirrhotic patients. Patients and methods: Included in the study were 40 patients suffering from liver cirrhosis (29m, I l L age 53+11 years, mean_+SD) and 50 normal volunteers (27m, 230. Clinical staging for HE was performed using standardized scores. For psychometric testing number connection test and line drawing test were used. All MR exams were acquired using a 1.5 T Siemens Magnetom. TI (TR 570ms/TE 15ms) and T2 (TR 3700ms/TE 80ms) weighted axial images were obtained. MRS data were acquired in an occipital mostly gray matter voxcl (l.5x2xl.5cm) and a parietal mostly white matter voxel (1.5x 1.5x 1.5cm). Creatine (CO was used as reference. Results: 32 of 40 patients had no clinical signs of HE, 14 of these patients were graded sub-clinical HE according to the results o f the psychometric tests. Bright basal ganglia were present in 28 patients and correlated significantly to porto-systemic shunting (p=0.0004). Patients with bright basal ganglia tended to have worse results in number connection tests (13=0.04). In MRS choline (not shown) and myoinositol (M1)(Tab.1) were lower in cirrhotic patients compared to normal volunteers (p<0.05, analysis of variance after Bonferroni correction). MI/Cr in white matter correlated to severity of HE (r=0.749, p< O.0001). Normal No H E subclin. H E overt HE MI/Cr white 0.637_+0.17 0.314+_0.17 0.278+_0.15 0.261+_0.09 matter MI/Cr g r a y 0.526+0.12 0,399+0.17 0.367+0.21 0.367+_0.15 matter (mean+SD) Conclusion: MRi and MRS demonstrate cerebral changes in cirrhotic patients. MI/Cr correlates to severity of HE, but a lower MI/Cr ratio is found even in patients without obvious signs of HE. Therefore, MRS offers new insights regarding cerebral changes in cirrhotic patients with and without HE.
GASTROENTEROLOGY, Vol. 108, No, 4
NOVEL IMAGING TECHNIQUE:DPI AND 3-D-DPI VERSUS CFI IN LIVER DISEASE M.Gebel,J.Bleck,A.Schneider,S.Wagner, M.Manns. Div. of Gastroenterology,Dept Internal Medicine, Medizinische Hochschule Hannover.FRG. The importance of Doppler-Power-lmaging (DPI) compared to Color Flow Imgaging (CFI) in l i v e r disease is not known.ln a prospective study i t is in ve st ig a t e d , if DPI is contributing any information superior to CFI in l i v e r disease. METHOD:63 consecutive patients (pts) with suspected l i v e r disease (hepatic tumors:18 pts,chronic hepatitis:12 pts -4 wi~h TIPS-,biliary disease:3 pts,normal livers:30 pts) were examined by CFI and DPI (3,5 MHz,VST-Masters,Diasonics;Acuson 128 color energy).Additionally 3-D-reconstruction (software by Tomtec) of DPI was carried out in 8 pts (I metastasis,2 extrahepatic tumors,2 co lla t e ra ls in portal hypertension (PH),I TIPS). RESULTS:DPI was superior to CFI in 58/63 pts (92%) with regard to the number and continuity of the visualized vessels. In 7/63 pts (II%) DPI provided valuable information as typical vascular anatomy in small FNH (2),complete visualization of TIPS lumen (2),hepatic veins (1),portal vein branches ( I ) , splenic vein (I ) in pts with PH and incomplete CFI exams. 3-D-reconstruction was most valuable and impressive in pts with TIPS (exclusion of stenosis) and co lla t e ra ls in PH (extent of l e f t gastric vein c o l l a t e r a l s ) . CONCLUSION:S/N r a t i o of DPI is clearly superior to CFI.In this study DPI added important information to CFI in II% of all pts and 21% of pts with l i v e r disease and was most valuable in pts with FNH and pts with portal hypertension.3-D-DPl can provide subtle information about spatial dimensions of the vessels.
MEDICAL LAPAROSCOPY UNDER CONSCIOUS SEDATION - A COMMUNITY HOSPITAL EXPERIENCE. Bradford Gelzayd, Jaime M. Rivera, Providence Hospital; Southfield, Michigan. Laparoscopy performed by gastroenterologists under conscious sedation has been termed medical laparoscopy (ML). The advent of surgical laparoscopy and lack of sufficient ML training outside a university hepatology program has resulted in declining use of ML by endoscopists. Recently, achievable proficiency in ML by GI fellows in training was demonstrated at a community hospital. However, administrative policy confined ML to an OR setting with unnecessary anesthesiologist support, raising cost markedly. We report our experience with ML at a small community hospital GI training program as an outpatient procedure performed in our endoscopy suite. Methods: Records from 37 ML performed between August 12, 1993 to November 18, 1994 were reviewed in regard to age, indications, complications and final diagnosis. There were 22 males and 15 females, from 19 to 75 y/o (median age 50 y/o). All procedures were performed under conscious sedation in an endoscopy suite by a senior GI fellow under supervision by one attending physician. Two circulating endoscopy nurses assisted but no ancillary anesthesia personnel were present. Indications for ML included evaluation of chronic liver disease (76%), primary metastatic cancer (8 o~), ascites of unclear etiology (5 oYo), and miscellaneous (11%). Biopsies were performed in all but two patients. Results: Chronic liver disease group included HCV (10 patients), alcoholic liver disease (4), HBV (2), HCV and HBV co-infection (1), HCV and alcoholic liver disease (1), PBC (4; one AMA negative), Non-alcoholic steatohepatitis (2), autoimmune hepatitis (2), cryptogenic cirrhosis (1), and hemochromatosis (1). No mortality or major complications (severe bleeding from liver biopsy site requiring transfusions, perforated abdominal viscus or hemobilia) were encountered. Minor complications ( 13.5 %) included: incisional ascites leakage ( 1), transient vasovagal episode (2), marked abdominal pain (1) and small incisional hematoma (1). All patients were discharged home 8 hours later except one which required less than 24 hours stay due to abdominal pain. Accurate inspection of liver surface and peritoneal integrity was accomplished with a rigid telescope. o Diagnoses established after ML: cirrhosis 9 (24 o~), chronic hepatitis 19 (51%), steatosis/steatohepatitis 3 (8%), malignancy alone 1 (3%),or miscellaneous 5 (14%). Two patients with cirrhosis had additional malignancy, either HCC or metastatic. Conclusion: ML performed in an endoscopy suite by gastroenterologists and trainees at a community hospital was safe and accurate in diagnosinn chronic liver and peritoneal disease in the~reliminat~study.
AASLD ABSTRACTS
• ANALYSIS OF INTRAHEPATIC CYTOKINE EXPRESSION OF CHRONIC HCVINFECTED PATIENTS ACCORDING TO RESPONSE TO INTERFERON THERAPY AS. Gaweeo, D.H. Van Thiel, V. Rastgi, H.F. Otto, F. Schneider, W.J. Hofmaun. Institute of Pathology, University of Heidelberg, Germany, Oklahoma Transplantation Iesfitate, Oklahoma, USA & INOVA Institute, Falls Chttreh, USA Interferon-alpha [IFN-cq is the only effective treatment to date for chronic hepatitis C virus [FIC~ infection. However, more than 50% of chronic HCV-infected patients are insensitive to IFN-therapy, suggesting suboptimal IFN-ct iannnnomodulation. Increasing data strongly suggest the contribution of on-site laminae-mediated meehanisms to the pathogenesis of chronic hepatitis C virus [HCV] infection. Defining the leeal cytokine interactions in a possibly dysregulated irmnane response may further elucidate the ill-defined pathogenetie process of chronic HCV infection and help optimize current treatment strategies. We assessed the intrahepatic eytokine gene activity of chronic HCV-infeeted patients aceerding to response after IFN-~x therapy. The mRNA expression patterns of the 'type 1' (IL-2, IFN-?), 'type 2' QL-4, IL-5, 1L-6, IL-10), and proinflammatory eytukines (IL-113, IL-8, IL-12 p40, TNF-cq GM-CSF) including IL-2Rc~, IL-7, and TGF-151 were studied using RT-~CR in 44 liver biopsies of 29 chronic HCV-infeeted patients: before IFN-cx treatment (u=15), nonresponders (n=18) and responders (n=ll) 6 months after treatment with 3 MU lFN-ct. The definition of response was based on senun ALT levels (NE.IM 1989; 321:1501-6). IL-2 and IL-12 mRNA iranscripts were detected in 46% and 13%, respectively, of pre-treatment liver biopsies. Following IFN-ct treatment, IL-2 and IL-12 expression was enhanced in nou-responders (67% and 36%, respectively) in contrast to responders (36% and 18%). No correlation was otherwise observed in the expression patterns of other cytokines investigated. IFN-o~ has several immanomodulatory properties in addition to its direct antiviral effects. IFN-a particularly promotes cellular responses by directly stimulating eytntoxic T lymphocyte [CTL] activity and indirectly, by initiating a type 1 cytokine profile (e.g. IL-2) mediating CD8+ CTL responses, a property shared by the haman monocyte/maerophage-derived IL-12. The favorable effects of IFN-~x in controlling chronic HCV infection could be overcome by an excessive on-site CTL response through the synergistic action of IL-2, IL-12, and IFN-% potent CTL inducers. Infiltrating HCV-specific CD8+ CTLs have been identified in chronic HCV-infected haman livers and in fact, a correlative decrease of intrahepatic CD8+ T cells with serum ALT levels following beneficial IFN-cx treatment has been reported. From these data, it could be speculated that locally elaborated cytokines may induce non-specific CTL reernimaent and vigorous CTL responses contributing to liver cell injury of chronic HCV infeetion and explain an immunopathogenetic IFN-ct-resistant meehanism.
• Cerebral changes in patients with liver cirrhosis detected by magnetic resonance imaging and proton magnetic resonance spectroscopy. A. Geissler.
G. Lock*, R. Fdind, J. Sch6lmerich*, S. Feuerbach, A. Holstege*. Depts. of Radiology and Internal Medicine I, University of Regensburg, 93042 Rcgensbarg, FRG. Backaround: In patients suffering from liver cirrhosis, hepatic encephalopathy (HE) is a common problem. Diagnosis is easily made in advanced stages but may be cumbersome in sub-clinical HE. Aim of the study was the evaluation of magnetic resonance imaging (MRI) and spectroscopy (MRS) in comparison to clinical diagnosis and psychometric tests.in cirrhotic patients. Patients and methods: Included in the study were 40 patients suffering from liver cirrhosis (29m, I l L age 53+11 years, mean_+SD) and 50 normal volunteers (27m, 230. Clinical staging for HE was performed using standardized scores. For psychometric testing number connection test and line drawing test were used. All MR exams were acquired using a 1.5 T Siemens Magnetom. TI (TR 570ms/TE 15ms) and T2 (TR 3700ms/TE 80ms) weighted axial images were obtained. MRS data were acquired in an occipital mostly gray matter voxcl (l.5x2xl.5cm) and a parietal mostly white matter voxel (1.5x 1.5x 1.5cm). Creatine (CO was used as reference. Results: 32 of 40 patients had no clinical signs of HE, 14 of these patients were graded sub-clinical HE according to the results o f the psychometric tests. Bright basal ganglia were present in 28 patients and correlated significantly to porto-systemic shunting (p=0.0004). Patients with bright basal ganglia tended to have worse results in number connection tests (13=0.04). In MRS choline (not shown) and myoinositol (M1)(Tab.1) were lower in cirrhotic patients compared to normal volunteers (p<0.05, analysis of variance after Bonferroni correction). MI/Cr in white matter correlated to severity of HE (r=0.749, p< O.0001). Normal No H E subclin. H E overt HE MI/Cr white 0.637_+0.17 0.314+_0.17 0.278+_0.15 0.261+_0.09 matter MI/Cr g r a y 0.526+0.12 0,399+0.17 0.367+0.21 0.367+_0.15 matter (mean+SD) Conclusion: MRi and MRS demonstrate cerebral changes in cirrhotic patients. MI/Cr correlates to severity of HE, but a lower MI/Cr ratio is found even in patients without obvious signs of HE. Therefore, MRS offers new insights regarding cerebral changes in cirrhotic patients with and without HE.
GASTROENTEROLOGY, Vol. 108, No, 4
NOVEL IMAGING TECHNIQUE:DPI AND 3-D-DPI VERSUS CFI IN LIVER DISEASE M.Gebel,J.Bleck,A.Schneider,S.Wagner, M.Manns. Div. of Gastroenterology,Dept Internal Medicine, Medizinische Hochschule Hannover.FRG. The importance of Doppler-Power-lmaging (DPI) compared to Color Flow Imgaging (CFI) in l i v e r disease is not known.ln a prospective study i t is in ve st ig a t e d , if DPI is contributing any information superior to CFI in l i v e r disease. METHOD:63 consecutive patients (pts) with suspected l i v e r disease (hepatic tumors:18 pts,chronic hepatitis:12 pts -4 wi~h TIPS-,biliary disease:3 pts,normal livers:30 pts) were examined by CFI and DPI (3,5 MHz,VST-Masters,Diasonics;Acuson 128 color energy).Additionally 3-D-reconstruction (software by Tomtec) of DPI was carried out in 8 pts (I metastasis,2 extrahepatic tumors,2 co lla t e ra ls in portal hypertension (PH),I TIPS). RESULTS:DPI was superior to CFI in 58/63 pts (92%) with regard to the number and continuity of the visualized vessels. In 7/63 pts (II%) DPI provided valuable information as typical vascular anatomy in small FNH (2),complete visualization of TIPS lumen (2),hepatic veins (1),portal vein branches ( I ) , splenic vein (I ) in pts with PH and incomplete CFI exams. 3-D-reconstruction was most valuable and impressive in pts with TIPS (exclusion of stenosis) and co lla t e ra ls in PH (extent of l e f t gastric vein c o l l a t e r a l s ) . CONCLUSION:S/N r a t i o of DPI is clearly superior to CFI.In this study DPI added important information to CFI in II% of all pts and 21% of pts with l i v e r disease and was most valuable in pts with FNH and pts with portal hypertension.3-D-DPl can provide subtle information about spatial dimensions of the vessels.
MEDICAL LAPAROSCOPY UNDER CONSCIOUS SEDATION - A COMMUNITY HOSPITAL EXPERIENCE. Bradford Gelzayd, Jaime M. Rivera, Providence Hospital; Southfield, Michigan. Laparoscopy performed by gastroenterologists under conscious sedation has been termed medical laparoscopy (ML). The advent of surgical laparoscopy and lack of sufficient ML training outside a university hepatology program has resulted in declining use of ML by endoscopists. Recently, achievable proficiency in ML by GI fellows in training was demonstrated at a community hospital. However, administrative policy confined ML to an OR setting with unnecessary anesthesiologist support, raising cost markedly. We report our experience with ML at a small community hospital GI training program as an outpatient procedure performed in our endoscopy suite. Methods: Records from 37 ML performed between August 12, 1993 to November 18, 1994 were reviewed in regard to age, indications, complications and final diagnosis. There were 22 males and 15 females, from 19 to 75 y/o (median age 50 y/o). All procedures were performed under conscious sedation in an endoscopy suite by a senior GI fellow under supervision by one attending physician. Two circulating endoscopy nurses assisted but no ancillary anesthesia personnel were present. Indications for ML included evaluation of chronic liver disease (76%), primary metastatic cancer (8 o~), ascites of unclear etiology (5 oYo), and miscellaneous (11%). Biopsies were performed in all but two patients. Results: Chronic liver disease group included HCV (10 patients), alcoholic liver disease (4), HBV (2), HCV and HBV co-infection (1), HCV and alcoholic liver disease (1), PBC (4; one AMA negative), Non-alcoholic steatohepatitis (2), autoimmune hepatitis (2), cryptogenic cirrhosis (1), and hemochromatosis (1). No mortality or major complications (severe bleeding from liver biopsy site requiring transfusions, perforated abdominal viscus or hemobilia) were encountered. Minor complications ( 13.5 %) included: incisional ascites leakage ( 1), transient vasovagal episode (2), marked abdominal pain (1) and small incisional hematoma (1). All patients were discharged home 8 hours later except one which required less than 24 hours stay due to abdominal pain. Accurate inspection of liver surface and peritoneal integrity was accomplished with a rigid telescope. o Diagnoses established after ML: cirrhosis 9 (24 o~), chronic hepatitis 19 (51%), steatosis/steatohepatitis 3 (8%), malignancy alone 1 (3%),or miscellaneous 5 (14%). Two patients with cirrhosis had additional malignancy, either HCC or metastatic. Conclusion: ML performed in an endoscopy suite by gastroenterologists and trainees at a community hospital was safe and accurate in diagnosinn chronic liver and peritoneal disease in the~reliminat~study.