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Risk factors associated with rebleeding and recurrence following endoscopic vairiceal ligation
A1286 AASLD ABSTRACTS • L0360 RISK FACTORS ASSOCIATED WITH REBLEEDING AND RECURRENCE FOLLOWING ENDOSCOPIC VAIRICEAL LIGATION. J.H. Lee. S.Y. Oh, K.C. Koh, P.L. Rbee, J. Kim, J.C. Rhee, K.W. Choi. Dept. of Medicine, Sung Kyun Kwan University College of Medicine, Samsung Medical Center, Seoul, Korea. Aims: Rebleeding and recurrence of varices are frequent problems following endoscopic variceal ligation (EVL). However, few data are available on the risk factors associated with rebleeding and recurrence. Our aims were to elucidate the clinical features and risk factors associated with rebleeding and recurrence. Methods: One-hundred and eight patients who had undergone EVL due tO bleeding esophageal varices were included in the study. EVL was performed with the Stiegman-Goff endoscopic ligator at 2 week intervals until the varices are eradicated or reduced to grade 1 without red color sign (defined as successful EVL), followed by gastroscopy every 3 months. Rebleeding was defined using the descriptions from the Second Baveno International Consensus Meeting, in 1995. Recurrence was defined as increments of varices to grade 2 or greater or appearance of red color sign on follow-up examinations. The Kaplan-Meier method was used to determine the rebleeding and recur rate. The log rank test and Cox regression test were used for univariate and multivariate analysis of risk factors, respectively. Results: 1) The most common cause of rebleeding within 2 weeks from the EVL was esophageal ulcer (50%); whereas, the most common cause of rebleeding after 2 weeks was recurrent varices (38%). 2) In univariate analysis, persistence of esophageal ulcer at 2 weeks after the first EVL was associated with rebleeding (p=0.01); whereas, age, Child class, grade and extent of varices, presence of gastric varices and/or portal hypertensive gastropathy, total number of bands and sessions for successful EVL were not (p>0.05). Persistence of esophageal ulcer at 2 weeks after the first EVL was associated with rebleeding also in multivariate analysis (relative risk 5.87, p=0.01). 3) In univariate analysis, grade (p=0.01) and extent (p=0.01) of varices were related to recurrence; whereas, age, Child class, presence of gastric varices and/or portal hypertensive gastropathy, total number of bands and sessions for successful EVL were not (p>0.05). In multivariate analysis, grade of varices was the only risk factor associated with recurrence (relative risk 3.76, p=0.01). Conclusions: 1) Persistence of esophageal ulcer at second week after the first EVL was associated with rebleeding. 2) Frequent follow-up endoscopic examinations are necessary in patients who present with high grade of varices since risk of recurrence is high even after successful EVL. L0361 DIAGNOTIC EFFICACY OF COMPUTED TOMOGRAPHY DURING ARTERIAL PORTOGRAPHY (CTAP) IN IDIOPATHIC PORTAL HYPERTENSION. Moonho Lee. M.D.. Ilkwun Chung, M.D., Hongsoo Kim, M.D., Sangheum Park, M.D., Sunjoo Kim, M.D., Kunsoo Han, M.D.* Department of internal medicine and interventional radiology*, Soonchunbyang university, Chonan hospital, Chonan, Korea. Background: idiopathic portal hypertension(IPH) is a rare and idiopathic disease characterized with splenomegaly, anemia and portal hypertension, excluding liver cirrhosis, hematologic disease, parasitic disease and occlusion of hepatic and extrahepatic portal vein. The pathopbysinlogy shows portal fibrosis and scar formation by thrombosis of small portal branch, dilatation or occlusion of periportal vessel and loss of adjacent hepatic parenchyme. The diagnostic difficulty has been well known because there were no characteristic findings on abdominal CT or ultrasonography. We want to know the diagnostic efficacy of superior mesenteric arterial portography (SMA-P) and computerized tomography during arterial portography (CTAP) in IPH Subject and method: Three patients who were diagnosed as IPH by clinical characteristics and liver histology were included during March 1995 to July 1997 in S0onchunhyang University, Chonan hospital. We compared and analyzed image findings of SMA-P and CTAP, and efficacy of diagnostic value was evaluated. Result: 1) tram line sign along with intrahepatic portal tract and narrowing or occlusion of portal vein were noticed in CTAP of all cases. 2) aberrant fine portal vasculature of nearby occluded portal vein was noted in all SMA-P and CTAP findings. 3) CTAP can trace occluded portal vein which didn't appear in portography. 4) CTAP can show remaining portion of normal portal branch in portal vein paucity on SMA-P. Conclusion: SMA-P portography and CTAP can evaluate the state of intrahepatic portal vein well. CTAP can show occluded portal vein which can't be evaluated on portography, and can show small intrahepatic portal branch correctly. We think that CTAP is an effective method in understanding pathophysiology and diagnosis of Banti's syndrome. L0362 MALLORY BODIES AND VIRAL HEPATITIS C. C.B. Leevy, M. Patel, K. Zierer, C.M. Leevy, B. Koneru and P. Zweil. Sammy Davis, Jr., National Liver Institute and New Jersey Medical School Liver Center, Newark, NJ. Mallory Bodies (MBs) identified by antibodies to CK8, C18, Ubiquitin and MB3 (a mouse non keratin epitope) activate NF~:B to increase cytokines and chemokines in a variety of liver disorders. Their quantity is increased by
GASTROENTEROLOGYVol. 114, No. 4 adrenal steroids (Hepatology 26:151a 1997), decreased by Vitamin D3 (Hepatology 1996) and prevented by lack of cytokeratin 8 (Hepatology 26:182A 19 977). MBs were identified by the leukocyte M.I.F. test and liver biopsies in patients with alcoholic hepatitis, a third of whom also had viral hepatitis C. Studies were undertaken to determine the incidence and pathophysiologic effects of MBs in subjects with hepatitis C without alcoholism. Twenty-five patients with end-stage disease were evaluated before and after liver transplantation. Explanted liver showed necrosis, steatosis, inflammation and fibrosis, with or without lobular distortion. MBs were not readily identified by light microscopy in some specimens; 10 exhibited this protein when tissue was incubated with the MB 3 monoclonal antibody, washed with PBS, stained with FITC Fab fragment and examined by fluorescence microscopy. There was no correlation between the quantity of MBs serum HCV-RNA; hepatocyte dysfunction, cytokines or in-vitro hepatic DNA synthesis. Short term post-transplant biopsies without progressive disease did not show MBs despite persistent viremia. Conclusions: Mallory bodies identified by the antibodies to a nonkeratin epitope are present in chronic hepatitis C without alcoholism. They may also contribute to progressive liver injury in addition to that produced by the hepatitis C virus. L0363 HEPATIC MACROPHAGES ARE ASSOCIATED WITH FIBROSIS IN HEREDITARY HEMOCHROMATOSIS. K.L. Leicester 1,3, J.K. Olynyk l, E.M. Brunt 2, R.S. Britton 3, B.R. Bacon 3. Dept of Medicine 1, University of Western Australia, Australia; Dept of Pathology 2, Division of Gastroenterology and Hepatology 3, Saint Louis University School of Medicine, St Louis, MO. In patients with hereditary hemochromatosis (HH), chronic iron overload can lead to hepatic fibrosis and cirrhosis. The transdifferentiation of hepatic stellate cells to an activated phenotype plays a key role in fibrogenesis. Hepatic macrophages/monocytes are potential sources of profibrogenic factors, but the role that these cells play in iron-induced fibrogenesis in HH patients is unclear. Aim: The aim of this study was to determine the relationship between hepatic macrophages/monocytes,activated hepatic stellate ceils and fibrosis in HH patients. Methods: Liver specimens from HH patients were immunostained for CD68 (macrophage/monocyte marker) and a-smooth muscle actin (SMA) (marker of activated hepatic stellate cells), and the number of cells expressing these antigens was determined. Fibrosis was determined by routine histologic methods. HH was diagnosed by standard clinical criteria including hepatic iron concentration (HIC), hepatic iron index (HII), genetic analysis and histologic iron staining. Immunohistochemistry was accomplished using a biotin/streptavidin peroxidase system, and TrueBlue chromogen. The hepatic population of CD68-positive cells was assessed by counting 5 random fields (160x) using a standard grid, and the values were averaged. Zonal distribution of CD68-positive cells was also determined. SMA expression was graded on a progressive scale from 0 to 3. Results: Patients ranged in age from 30 to 72 yr. The range of HIC was 436 to 25,090 ~ag/g)dry weight (mean =12,960 ~tg/g) and of HII was 1.6 to 12.1 (mean = 5.1). Changes in HIC did not strongly influence the number of CD68-positive cells. However, a three-fold increase in CD68-positive ceils was observed in livers containing elevated SMA expression. In biopsies with extensive SMA staining and fibrosis, the majority of the CD68-positive cells, particularly iron-loaded macrophages,were located in and around the fibrous tissue. Conclusions: Increased numbers of hepatic macrophages/monocytes were associated with activated hepatic stellate cells and fibrous tissue in HH. This suggests that hepatic macrophages may play a role in stellate cell activation, leading to fibrosis in patients with HH. L0364 PLASMA AND LYMPH OF PATIENTS WITH AND WITHOUT MULTIPLE ORGAN FAILURE INHIBIT ENDOTOXIN-INDUCED CYTOKINE RELEASE. L.C.J.M.Lemaire 1,2, T. van der Poll? J.J.B. van Lanschot, 1 W.A. Buurman, 3 S.J.H. van Deventer 2, D.J. Gouma. 1 Dept. of Surgery I and the Laboratory for Experimental Internal Medicine 2, Academic Medical Center, University of Amsterdam, Amsterdam, and the Dept. of Surgery, 3 University Hospital Maastricht, Maastricht, The Netherlands. In critically ill patients, lipopolysaccharide (LPS) tolerance has been described, characterized by a state of a reduced capacity of mononuclear ceils to produce cytokines upon e x vivo stimulation with LPS. The precise mechanisms are unclear, although part is caused by soluble mediators in plasma. Besides plasma, lymph is an important body compartment involved in LPS transport. The effect of lymph on LPS-induced cytokine production is unknown. Aim: To determine the capacity of lymph to influence LPS-induced cytokine production. Concentrations of factors known to modulate LPS-toxicity (lipopolysaecharide-binding protein (LBP), bactericidal/permeability increasing protein (BPI) and IL-10), were measured in lymph and plasma, to obtain insight into the possible role of these proteins in LPS tolerance. Methods & Results: Lymph and plasma of patients with multiple organ failure (MOF, n=8) and of patients without multiple organ failure (controls, n=7) was simultaneously collected. Lymph of MOF-patients was pooled, as
GASTROENTEROLOGYVol. 114, No. 4 adrenal steroids (Hepatology 26:151a 1997), decreased by Vitamin D3 (Hepatology 1996) and prevented by lack of cytokeratin 8 (Hepatology 26:182A 19 977). MBs were identified by the leukocyte M.I.F. test and liver biopsies in patients with alcoholic hepatitis, a third of whom also had viral hepatitis C. Studies were undertaken to determine the incidence and pathophysiologic effects of MBs in subjects with hepatitis C without alcoholism. Twenty-five patients with end-stage disease were evaluated before and after liver transplantation. Explanted liver showed necrosis, steatosis, inflammation and fibrosis, with or without lobular distortion. MBs were not readily identified by light microscopy in some specimens; 10 exhibited this protein when tissue was incubated with the MB 3 monoclonal antibody, washed with PBS, stained with FITC Fab fragment and examined by fluorescence microscopy. There was no correlation between the quantity of MBs serum HCV-RNA; hepatocyte dysfunction, cytokines or in-vitro hepatic DNA synthesis. Short term post-transplant biopsies without progressive disease did not show MBs despite persistent viremia. Conclusions: Mallory bodies identified by the antibodies to a nonkeratin epitope are present in chronic hepatitis C without alcoholism. They may also contribute to progressive liver injury in addition to that produced by the hepatitis C virus. L0363 HEPATIC MACROPHAGES ARE ASSOCIATED WITH FIBROSIS IN HEREDITARY HEMOCHROMATOSIS. K.L. Leicester 1,3, J.K. Olynyk l, E.M. Brunt 2, R.S. Britton 3, B.R. Bacon 3. Dept of Medicine 1, University of Western Australia, Australia; Dept of Pathology 2, Division of Gastroenterology and Hepatology 3, Saint Louis University School of Medicine, St Louis, MO. In patients with hereditary hemochromatosis (HH), chronic iron overload can lead to hepatic fibrosis and cirrhosis. The transdifferentiation of hepatic stellate cells to an activated phenotype plays a key role in fibrogenesis. Hepatic macrophages/monocytes are potential sources of profibrogenic factors, but the role that these cells play in iron-induced fibrogenesis in HH patients is unclear. Aim: The aim of this study was to determine the relationship between hepatic macrophages/monocytes,activated hepatic stellate ceils and fibrosis in HH patients. Methods: Liver specimens from HH patients were immunostained for CD68 (macrophage/monocyte marker) and a-smooth muscle actin (SMA) (marker of activated hepatic stellate cells), and the number of cells expressing these antigens was determined. Fibrosis was determined by routine histologic methods. HH was diagnosed by standard clinical criteria including hepatic iron concentration (HIC), hepatic iron index (HII), genetic analysis and histologic iron staining. Immunohistochemistry was accomplished using a biotin/streptavidin peroxidase system, and TrueBlue chromogen. The hepatic population of CD68-positive cells was assessed by counting 5 random fields (160x) using a standard grid, and the values were averaged. Zonal distribution of CD68-positive cells was also determined. SMA expression was graded on a progressive scale from 0 to 3. Results: Patients ranged in age from 30 to 72 yr. The range of HIC was 436 to 25,090 ~ag/g)dry weight (mean =12,960 ~tg/g) and of HII was 1.6 to 12.1 (mean = 5.1). Changes in HIC did not strongly influence the number of CD68-positive cells. However, a three-fold increase in CD68-positive ceils was observed in livers containing elevated SMA expression. In biopsies with extensive SMA staining and fibrosis, the majority of the CD68-positive cells, particularly iron-loaded macrophages,were located in and around the fibrous tissue. Conclusions: Increased numbers of hepatic macrophages/monocytes were associated with activated hepatic stellate cells and fibrous tissue in HH. This suggests that hepatic macrophages may play a role in stellate cell activation, leading to fibrosis in patients with HH. L0364 PLASMA AND LYMPH OF PATIENTS WITH AND WITHOUT MULTIPLE ORGAN FAILURE INHIBIT ENDOTOXIN-INDUCED CYTOKINE RELEASE. L.C.J.M.Lemaire 1,2, T. van der Poll? J.J.B. van Lanschot, 1 W.A. Buurman, 3 S.J.H. van Deventer 2, D.J. Gouma. 1 Dept. of Surgery I and the Laboratory for Experimental Internal Medicine 2, Academic Medical Center, University of Amsterdam, Amsterdam, and the Dept. of Surgery, 3 University Hospital Maastricht, Maastricht, The Netherlands. In critically ill patients, lipopolysaccharide (LPS) tolerance has been described, characterized by a state of a reduced capacity of mononuclear ceils to produce cytokines upon e x vivo stimulation with LPS. The precise mechanisms are unclear, although part is caused by soluble mediators in plasma. Besides plasma, lymph is an important body compartment involved in LPS transport. The effect of lymph on LPS-induced cytokine production is unknown. Aim: To determine the capacity of lymph to influence LPS-induced cytokine production. Concentrations of factors known to modulate LPS-toxicity (lipopolysaecharide-binding protein (LBP), bactericidal/permeability increasing protein (BPI) and IL-10), were measured in lymph and plasma, to obtain insight into the possible role of these proteins in LPS tolerance. Methods & Results: Lymph and plasma of patients with multiple organ failure (MOF, n=8) and of patients without multiple organ failure (controls, n=7) was simultaneously collected. Lymph of MOF-patients was pooled, as