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Impaired lung fuction after liver transplantation: Role of the membrane factor and reduced function of respiratory muscles
AASLDA1497
April 2000
study entry; positive anti-HCV antibodies and positive HCV RNA levels ( Amplicor" Roche). A liver biopsy was performed prior to the entry of the trial. Other causes of chronic liver disease were excluded. ALT levels and qualitative HCV RNA were performed at week 4 and 8. Adverse events and drop out rate were compared between group A and B. Results. Pretreatment, there is no significant difference in age, gender, ALT level, genotype ( genotype I: 78 % in group A, 82 % in group B) or histology between group A and B. At week 4 and 8, there is no significant difference in the number of patients with normal ALT level between group A and B. However at week 4 and 8, there are significant more patients in group A with undetectable HCV RNA levels ( undetectable HCV RNA at week 4: group A: 48.6 % versus group B: 30.8 %, p=O.OOI; undetectable HCV RNA level at week 8: group A: 66.5 % versus group B: 47.1 %, p
6770 CLINICAL AND HISTOLOGICAL FEATURES IN NONALCOHOLIC STEATOHEPATITS. C. A. Vargas, S. Behar, J. Cortes-Ruiz, E. J. Hernandez, Gastroenterology Group of South Florida, Miami, FL. Nonalcoholic steatohepatitis (NASH) is a common cause of asymptomatic elevation of liver enzymes which can be associated with progressive and irreversible liver injury. Although the pathogenesis of this entity remains unclear it has been associated to obesity, diabetes mellitus, and hyper triglyceridernia. Aim: Define the clinical spectrum of NASH and correlate the clinical features with the histological findings. Method: Patients were referred for evaluation of abnormal liver enzymes for more than six months. These patients had a complete data on demographics, clinical history, laboratory and histology. All test for viral hepatitis, autoimmune liver diseases. metabolic liver diseases were performed. Liver biopsy was obtained in all patients. Results: There were forty-two patients classified as having NASH on the basis of absence of a significant alcohol abuse, toxic medications, negative tests for hepatitis Band C, and compatible histology (steatosis, necrosis, inflammation, fibrosis or cirrhosis). The mean age was 47 years and the sex distribution was M:F 1.1: I. The ALT/AST> I was observed in 92% of the patients. Factors associated to NASH were: Hyperlipidemia in 42%, obesity in 26%, and diabetes mellitus in 16% of patients. Elevated serum ferritin was observed in 20%. Liver biopsy revealed steatosis in different degrees in all patients. Inflammation was observed in 47%, Periportal fibrosis in II % and cirrhosis was seen in 10% of the patients. Conclusion: NASH is commonly associated with hyperlipidemia, obesity and diabetes mellitus. A significant proportion of the patients have fibrosis and cirrhosis suggesting that NASH may no longer be considered a benign liver condition.
6771 OROCECAL TRANSIT TIME IN GALLSTONE PATIENTS AND IN OBESE PATIENTS BEFORE AND AFTER VERY LOW CALORIE DIET. Nicola Villanova, Maurizio Ventrucci, Davide Festi, Antonio Colecchia, Gian Luca Cornia, Francesco Azzaroli, Giuseppe Mazzella, Enrico Roda, Univ of Bologna, Bologna, Italy; Univ of Chieti, Chieti, Italy. Orocecal transit time(OCTT) may be involved in gallstone formation. Aim: To compare OCTT with respect to normal subjects in: gallstone patients; obese gallstone patients; obese patients (without gallstones) before and after a very low calorie diet (VLCD).Methods:We studied 53 normal subjects (N), 20 non-obese gallstone patients (G), 32 obese patients without gallstones (0), and II obese gallstone patient(OG). Moreover, 8 of the obese patients without gallstones underwent a l-rnonth VLCD(577 kcal/ day, 17 g/fat/day)(O-VCLD). We studied OCTT by the standard lactulose breath test (BTL) and by starch breath H2 test (100 g/starch) (BTS).Results: All the different groups of patients had significantly slower OCTT than normal subjects (Table). BTS showed additional OCTT delay when 0 was compared with G, OG and O-VLCD (table). BTL confirmed an OCTT delay after VLCD (table). Conclusions: obesity, cholesterol gallstones and severe dieting give rise to a significant delay in OCTT. These data confirm a pathophysiological link between intestinal motility and the biliary tract.
OClT
N
0
G
OG
O·VLCD
BTL (min±SE) BTS (min±SE)
884±61
1241±11.3
aoe 243±129
3463±14.3
138.5±15.3 0 4355±207
1405±187 0 418.6±12.1
2025±30A
ex
a
uPX
ux
ap
ap
ax 425±146
a p
6772 USE OF LAMIVUDlNE IN HEPATITIS B PATIENTS UNDERGOING LIVER TRANSPLANTATION. Chun-Tao Wai, Seng-Gee Lim, Kang-Hoe Lee, Wan-Ching Chow, CheeKiat Tan, John Isaac, K. Prabhakaran, Kai-Chah Tan, National Univ Hosp, Singapore. Hepatitis B related cirrhosis is the commonest indication of adult liver transplantation in Singapore. HBIG, Lamivudine or combination of both has been shown to be effective in preventing Hepatitis B recurrence post transplant. However, the high cost of HBIG hinders its widespread usage. This study aims to review our experience with the use of lamivudine monotherapy in prevention of Hepatitis B recurrence in Hepatitis B patients undergoing liver transplantation. METHODS Status of the HBsAg and HBV DNA in patients undergoing liver transplantation for Hepatitis B related cirrhosis with or without hepatocellular carcinoma (HCC) in Singapore were reviewed retrospectively. RESULTS 10 patients underwent liver transplantation for Hepatitis B related cirrhosis (2 had HCC). None had fibrosing cholestatic hepatitis. 1 recipient died of sepsis at 9 days and another died of HCC recurrence at 7 months post transplant. Among the 8 survivors, 6 were positive for HBV DNA prior to the transplant. All 8 received lamivudine tablet 100mg daily for a mean period of 38 weeks (range 18-48) prior to the transplant. After liver transplant, at a mean follow-up of 62 weeks (range 5-123), all were still positive for HBsAg, 3 of the 8 were positive for HBV DNA (detected at I", 19'hand 104'hweek post transplant). Proportion of patients with positive HBV DNA increased with time. Status of the HBV DNA was listed in the table below. Transarninases in those with positive HBV DNA were within normal range. CONCLUSION Despite the use of lamivudine perioperatively, HBV DNA became detectable in most patients post liver transplant. Though none of our patients developed fibrosing cholestatic hepatitis or abnormal liver function, the long term outcome remains to be seen. Other strategies are needed to provide better HBV prophylaxis for post transplant Hepatitis B recurrence.
Status ofHBV DNA Post Tiver Transplant Time posttransplant, weeks Proportion of patients with+veHBV DNA
1/8(13%)
26
52
110
3/7(43%)
2/4(50%)
213(67%)
6773
IMPAIRED LUNG FUCTION AFTER LIVER TRANSPLANTATION: ROLE OF THE MEMBRANE FACTOR AND REDUCED FUNCTION OF RESPIRATORY MUSCLES. Klaus Walldorf, Ralf Ewert, Christian Witt, Marco Boehm, Patrick Rogalla, R. Reibis, Herbert Lochs, Mathias Plauth, Medicine Clin, Gastroenterologie, Charite, Berlin, Germany; Deutsches Herzzentrum, Berlin, Germany; Medicine Clin, Charite, Berlin, Germany. In long-term survivors after orthotopic liver transplantation (OLT) a reduction in diffusion capacity has been observed, despite normal findings in high resolution computed tomography (HR-CT). Also. a reduction in muscle mass has been found to persist after OLT. The aim of this study was to explore the role of alterations in the alveolo-capillary membrane and pulmonary capillary blood volume as causes of impaired diffusion capacity and the role of impaired respiratory muscle function as a cause of decreased cardiopulmonary efficiency in this patient group. Methods: Diffusion capacity of carbon monoxide (TLCO), membrane factor (Dm), pulmonary capillary blood volume (Qc), ventilatory drive (PO.IIPO.1 max), maximal inspiratory pressure (PImax) and the maximal 0ruptake during exercise (V0 2max) were determined in 38 patients 67.7::':18.7 mo after OLT and expressed as percent of predicted values from age and sex matched healthy controls. Echocardiography and HR-CT of the lungs were made to control for potential cardiac or pulmonary interstitial pathology. Results: 8/38 (21%) patients had a marked reduction «80% predicted) in TLCO (mean 92.4::':15.6 %predicted, p
April 2000
study entry; positive anti-HCV antibodies and positive HCV RNA levels ( Amplicor" Roche). A liver biopsy was performed prior to the entry of the trial. Other causes of chronic liver disease were excluded. ALT levels and qualitative HCV RNA were performed at week 4 and 8. Adverse events and drop out rate were compared between group A and B. Results. Pretreatment, there is no significant difference in age, gender, ALT level, genotype ( genotype I: 78 % in group A, 82 % in group B) or histology between group A and B. At week 4 and 8, there is no significant difference in the number of patients with normal ALT level between group A and B. However at week 4 and 8, there are significant more patients in group A with undetectable HCV RNA levels ( undetectable HCV RNA at week 4: group A: 48.6 % versus group B: 30.8 %, p=O.OOI; undetectable HCV RNA level at week 8: group A: 66.5 % versus group B: 47.1 %, p
6770 CLINICAL AND HISTOLOGICAL FEATURES IN NONALCOHOLIC STEATOHEPATITS. C. A. Vargas, S. Behar, J. Cortes-Ruiz, E. J. Hernandez, Gastroenterology Group of South Florida, Miami, FL. Nonalcoholic steatohepatitis (NASH) is a common cause of asymptomatic elevation of liver enzymes which can be associated with progressive and irreversible liver injury. Although the pathogenesis of this entity remains unclear it has been associated to obesity, diabetes mellitus, and hyper triglyceridernia. Aim: Define the clinical spectrum of NASH and correlate the clinical features with the histological findings. Method: Patients were referred for evaluation of abnormal liver enzymes for more than six months. These patients had a complete data on demographics, clinical history, laboratory and histology. All test for viral hepatitis, autoimmune liver diseases. metabolic liver diseases were performed. Liver biopsy was obtained in all patients. Results: There were forty-two patients classified as having NASH on the basis of absence of a significant alcohol abuse, toxic medications, negative tests for hepatitis Band C, and compatible histology (steatosis, necrosis, inflammation, fibrosis or cirrhosis). The mean age was 47 years and the sex distribution was M:F 1.1: I. The ALT/AST> I was observed in 92% of the patients. Factors associated to NASH were: Hyperlipidemia in 42%, obesity in 26%, and diabetes mellitus in 16% of patients. Elevated serum ferritin was observed in 20%. Liver biopsy revealed steatosis in different degrees in all patients. Inflammation was observed in 47%, Periportal fibrosis in II % and cirrhosis was seen in 10% of the patients. Conclusion: NASH is commonly associated with hyperlipidemia, obesity and diabetes mellitus. A significant proportion of the patients have fibrosis and cirrhosis suggesting that NASH may no longer be considered a benign liver condition.
6771 OROCECAL TRANSIT TIME IN GALLSTONE PATIENTS AND IN OBESE PATIENTS BEFORE AND AFTER VERY LOW CALORIE DIET. Nicola Villanova, Maurizio Ventrucci, Davide Festi, Antonio Colecchia, Gian Luca Cornia, Francesco Azzaroli, Giuseppe Mazzella, Enrico Roda, Univ of Bologna, Bologna, Italy; Univ of Chieti, Chieti, Italy. Orocecal transit time(OCTT) may be involved in gallstone formation. Aim: To compare OCTT with respect to normal subjects in: gallstone patients; obese gallstone patients; obese patients (without gallstones) before and after a very low calorie diet (VLCD).Methods:We studied 53 normal subjects (N), 20 non-obese gallstone patients (G), 32 obese patients without gallstones (0), and II obese gallstone patient(OG). Moreover, 8 of the obese patients without gallstones underwent a l-rnonth VLCD(577 kcal/ day, 17 g/fat/day)(O-VCLD). We studied OCTT by the standard lactulose breath test (BTL) and by starch breath H2 test (100 g/starch) (BTS).Results: All the different groups of patients had significantly slower OCTT than normal subjects (Table). BTS showed additional OCTT delay when 0 was compared with G, OG and O-VLCD (table). BTL confirmed an OCTT delay after VLCD (table). Conclusions: obesity, cholesterol gallstones and severe dieting give rise to a significant delay in OCTT. These data confirm a pathophysiological link between intestinal motility and the biliary tract.
OClT
N
0
G
OG
O·VLCD
BTL (min±SE) BTS (min±SE)
884±61
1241±11.3
aoe 243±129
3463±14.3
138.5±15.3 0 4355±207
1405±187 0 418.6±12.1
2025±30A
ex
a
uPX
ux
ap
ap
ax 425±146
a p
6772 USE OF LAMIVUDlNE IN HEPATITIS B PATIENTS UNDERGOING LIVER TRANSPLANTATION. Chun-Tao Wai, Seng-Gee Lim, Kang-Hoe Lee, Wan-Ching Chow, CheeKiat Tan, John Isaac, K. Prabhakaran, Kai-Chah Tan, National Univ Hosp, Singapore. Hepatitis B related cirrhosis is the commonest indication of adult liver transplantation in Singapore. HBIG, Lamivudine or combination of both has been shown to be effective in preventing Hepatitis B recurrence post transplant. However, the high cost of HBIG hinders its widespread usage. This study aims to review our experience with the use of lamivudine monotherapy in prevention of Hepatitis B recurrence in Hepatitis B patients undergoing liver transplantation. METHODS Status of the HBsAg and HBV DNA in patients undergoing liver transplantation for Hepatitis B related cirrhosis with or without hepatocellular carcinoma (HCC) in Singapore were reviewed retrospectively. RESULTS 10 patients underwent liver transplantation for Hepatitis B related cirrhosis (2 had HCC). None had fibrosing cholestatic hepatitis. 1 recipient died of sepsis at 9 days and another died of HCC recurrence at 7 months post transplant. Among the 8 survivors, 6 were positive for HBV DNA prior to the transplant. All 8 received lamivudine tablet 100mg daily for a mean period of 38 weeks (range 18-48) prior to the transplant. After liver transplant, at a mean follow-up of 62 weeks (range 5-123), all were still positive for HBsAg, 3 of the 8 were positive for HBV DNA (detected at I", 19'hand 104'hweek post transplant). Proportion of patients with positive HBV DNA increased with time. Status of the HBV DNA was listed in the table below. Transarninases in those with positive HBV DNA were within normal range. CONCLUSION Despite the use of lamivudine perioperatively, HBV DNA became detectable in most patients post liver transplant. Though none of our patients developed fibrosing cholestatic hepatitis or abnormal liver function, the long term outcome remains to be seen. Other strategies are needed to provide better HBV prophylaxis for post transplant Hepatitis B recurrence.
Status ofHBV DNA Post Tiver Transplant Time posttransplant, weeks Proportion of patients with+veHBV DNA
1/8(13%)
26
52
110
3/7(43%)
2/4(50%)
213(67%)
6773
IMPAIRED LUNG FUCTION AFTER LIVER TRANSPLANTATION: ROLE OF THE MEMBRANE FACTOR AND REDUCED FUNCTION OF RESPIRATORY MUSCLES. Klaus Walldorf, Ralf Ewert, Christian Witt, Marco Boehm, Patrick Rogalla, R. Reibis, Herbert Lochs, Mathias Plauth, Medicine Clin, Gastroenterologie, Charite, Berlin, Germany; Deutsches Herzzentrum, Berlin, Germany; Medicine Clin, Charite, Berlin, Germany. In long-term survivors after orthotopic liver transplantation (OLT) a reduction in diffusion capacity has been observed, despite normal findings in high resolution computed tomography (HR-CT). Also. a reduction in muscle mass has been found to persist after OLT. The aim of this study was to explore the role of alterations in the alveolo-capillary membrane and pulmonary capillary blood volume as causes of impaired diffusion capacity and the role of impaired respiratory muscle function as a cause of decreased cardiopulmonary efficiency in this patient group. Methods: Diffusion capacity of carbon monoxide (TLCO), membrane factor (Dm), pulmonary capillary blood volume (Qc), ventilatory drive (PO.IIPO.1 max), maximal inspiratory pressure (PImax) and the maximal 0ruptake during exercise (V0 2max) were determined in 38 patients 67.7::':18.7 mo after OLT and expressed as percent of predicted values from age and sex matched healthy controls. Echocardiography and HR-CT of the lungs were made to control for potential cardiac or pulmonary interstitial pathology. Results: 8/38 (21%) patients had a marked reduction «80% predicted) in TLCO (mean 92.4::':15.6 %predicted, p