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Accuracy and reproducibility of prognosis of liver cirrhosis and reproducibility of the indication to liver transplantation
HEPATOLOGYVoI. 34, No. 4, Pt. 2, 2001
AASLD ABSTRACTS
649A
1907
1908
QUALITY OF LIFE MEASURES A N D SELF-ASSESSED BODY CHANGES IN THE SEQUENCE OF LIVER DISEASE, CIRRHOSIS A N D TRANSPLANTATION. Eckhard Leitke, Med School of Hannover, Hannover Germany; Su-
EARLY RECIDIVISM OF DRINKING IS PREVALENT IN RELAPSERS AFTER LIVER TRANSPLANTATION FOR ALCOHOLIC CIRRHOSIS. ASSOCIATION OF RELAPSE W I T H NON-COMPLIANCE A N D REJECTION. M
sanne Ahrberg, Med School Hannover, Hannover Germany; Uwe Tiedge, B Nashan, J Klempnauer, H L Tillmann, Michael Manns, G Brabant, Christian Trautwein, Med School of Hannover, Hannover Germany
Hurtova,Jc Duclos-Vallee, V Karam, F Saliba, C Guettier, C Feray, H Bismuth, D Samuel, Paul Brousse Hospital, Villejuif France
Patients with liver cirrhosis might suffer from a dramatic impairment of endocrine homeostasis and quality" of life. The sequence of these extrahepatic manifestations are, however, still not well defined and might start long before liver cirrhosis and endstage disease has been reached. In addition, the extent to which these changes might reverse after liver transplantation as the only curative treatment for liver cirrhosis today has yet not been sufficiently studied. The impairment of general and sexual well being as well as seE-assessed body changes indicative for endocrine disturbances were determined by standardized questionaires in 28 men with histological defined precirrhotic liver disease (due to chronic hepatitis), 49 men with liver cirrhosis and 53 men after transplantation and compared cross sectionally. All items showed a stepwise decline from non-cirrhotic to cirrhotic patients (p<0.0001). The majority of men with liver cirrhosis showed decreased sexual and general well being. However, also a substantial proportion of men with non-cirrhotic liver disease reported impaired libido, erectile function and measures of general well being respectively, as well as body changes normally associated with liver cirrhosis. Loss of body hair, muscle mass or breast enlargement were reported by 12 %, 8 % and 36% of men with non-cirrhotic liver disease and 22 %, 25 % and 60 % of men with cirrhosis, respectively. Dependent on the measures assessed, improvement was reported differently in men after transplantation. The results suggest that impairment of general and sexual well being as well as body changes such as breast enlargement, loss of muscle mass or body hair indicating endocrine disturbances start early in a still non-cirrhotic stage of liver disease and might reverse differently after liver transplantaton.
Alcoholic cirrhosis is one of the first indications for orthotopic liver transplantation (OLT) accounting for 30 % of liver transplantations in Europe. This study evaluates the alcohol relapse rate in patients transplanted for alcoholic liver disease (ALD) in our centre between January 1987 and May 2000. Methods : We retrospectively examined charts of 108 patients, (91 males (M), 17 females (F)), mean age at LT 50.4 + 8.5 yrs (31-68). The alcohol recurrence was detected by interviews, clinical and biological indicators of alcohol intake and histological examination. Routine biopsies were performed at 1, 2, 5 and 10 years. Eight patients died during the first 6 months post LT. Only the survivors were considered for the assessment of relapse rate. Results : Twentythree (21.2%) patients (17 M and 6 F) relapsed alcoholism, 5 of them in a transient manner. The mean delay of relapse was 2 . 5 +- 1.6 yrs (0,25-6>TS) after OLT ; in most of the cases (14, i.e. 62.6%) it occured during the first 2 years. There was no significant difference between the delay of relapse in male and females (2.7 and 2.6 yrs, respectively), nor in the mean period of pretransplantation abstinence between relapsers (1.2 yrs) and abstinents (2.2 yrs, n.s). Moderate to severe steatosis was found in all the relapsed patients who had liver biopsy during their follow up, i.e. all but one. Moreover, three patients had a biopsy-proven acute alcoholic hepatitis on the graft, two of them a severe form. None of the patients developed cirrhosis on the graft, but 11 (17.6%) had severe fibrosis. Compared to those with no alcohol relapse, the relapser patients had more often signs of chronic ductopenic rejection: (30.4 vs 11.1%), p=0.04. Three patients of the relapser group were not compliant with the immunosuppressive treatment, whereas there were no such cases in the abstinence group. Mean follow-up period was 6 + 2.5 (2-10) in the recurrence and 4,0 --- 2.8 (0,5-14) yrs in the abstinence group. Survival rate at 1 and 5 yrs was 85.8 % and 62.2 %, respectively. Twenty-five patients, 22% of the relapser group and 26% of the abstinence group died, mostly de novo cancer or septic complications. Conclusions : early recurrence is prevalent in our population, therefore the follow-up during the first three years has to be intensified. Relapse is associated with non-compliance to immunosuppressive treatment and may induce rejection.
1909
1910
CORRELATION OF BODY MASS INDEX A N D ACUTE-ON-CHRONIC LIVER FAILURE. Ali Canbay, Shiyao Chen, Massimo Malago, Robert Gie-
ACCURACY A N D REPRODUCIBILITY OF PROGNOSIS OF LIVER CIRRHOSIS A N D REPRODUCIBILITY O F THE I N D I C A T I O N TO LIVER TRANSPLANTATION. Gennaro D'Amico, Ospedale V Cervello, Palermo,
seler, Marc Karliova, Guido Gerken, Christoph Broelsch, Ulrich Treichel, University Hospital Essen, Essen Germany Background: Acute liver failure (ALF) is characterized by acute liver insufficiency, hepatorenal syndrome, and hepatic encephalopathy and is termed acute-on-chronic liverfailure (AOC) when developed on a chronic background. We therefore examined whether the sex, age, or body mass index (BMI) of such patients might reveal a significant correlation with the development of AOC. Patients and Results: Throughout a 3.5-year period of from 1998 to 2001, the 34 patients included in this study fulfilled the ALF criteria according to Clichy and Kings College Hospital. Patients (65 o~ females; 35og males) had a mean age of 37.9 _+ 12.6 years and were subdivided into two groups, i.e. ALl: (n = 18) without signs of pre-existing liver disease, and AOC (n = 16) with chronic liver disease which had been either established or diagnosed after treatment. Drug toxicity, which was mostly due to acetaminophen, was the main cause of liver failure (52.9% of all patients). Other causes included viral hepatitis (26.5%) and acute excessive ethanol abuse (11.8%). Six patients (17.6%) died in the course of the study. Of twelve patients (35.3%) who had received an OLT one needed to be re-engrafted and two deceased before the end of the study. Sixteen patients suffered from established chronic hepatopathy including NASH, fatty liver, chronic ethanol abuse, or chronic hepatitis B. A highly significant difference between AOC and ALF patients was only apparent for the BMI (p < 0.002; cf. Table). Specifically, ten (62.5%) of the AOC patients revealed a BMI of >25. Age dependency was less significant. Of interest, the liver-specific enzymes had not been detectably elevated prior to the onset of AOC. Conclusion: According to our data, 47% of all ALF patients actually suffer from AOC and reveal a tendency towards increased mortality. Moreover, and despite inapparent laboratory parameters, patients with an elevated BMI (as well as higher age) are more likely to develop AOC, when challenged by acute risk factors such as the hepatitis viruses or drugs with potential hepatotoxicity. We thus recommend patients with a BM1 of >25 and/or with >35 years of age to be monitored at tight intervals so as to prevent the onset of AOC and the increased risk of fatal outcome. Comparison of patients with liver failure within two 9reaps , ALF (n = 18) AOC (n = 16}
Sex Age BMI Causes OLT treatment
Male Female Drugs Non-drug
5 {27,8%) I3 (72.2%) 34.9±10,5 22.4 ± 2.6 11 (51.1%) 7 (38.9%)
7 (43.8%) 9 (56.3%) 41.3± 14,3 27.1 ± 4.8 7 (43,8%) 9 (56.3%)
Yes
10 (55.6%)
2 (12.5%)
P value
0,331§ 0.1545 0,0025 0,311§ 0,009§
8 (44.4%) 14 (87,5%) Survival Fatal 2 (I I. 1%) 4 (25.0%) 0.387# ...........,Nive.. 16 (8.8.9%) 12 (75.0%1 ALF: acute liver failure, AOC: acute-on-chronicliver faiture, BMI: body mass index, § ChiSquare, $ StudentT-Test, # Fisher's Exac~Test No
Palermo Italy; Ilaria Tarantino, Ospedale V Cervello, Palermo Italy; Alberto Morabito, Institute of Biometrics, Milano, Milano Italy; Piermaria Battezzati, Ospedale San Paolo, Milano, Milano Italy; Linda Pasta, Ospedale V Cervello, Palermo Italy; Luigi Pagliaro, Clinica Medica R, University Palermo, Palermo Italy Background. Although a number of accurate prognostic indicators of cirrhosis have been reported, the reproducibility and accuracy of prognosis in the individual patient has never been assessed. Aim. To assess the reproducibility and accuracy of prognosis in liver cirrhosis. Methods. Individual data at clinical presentation of 75 random patients (28 decompensated) from an ongoing study of the clinical course of cirrhosis were made available for prognostic assessment in 13 centers involved in orthotopic liver transplantation in Europe and USA. Each participant center reported the prediction on the 2-year survival and the decision on the inclusion of each patient in a transplantation waiting list. The accuracy of the reported predictions was assessed by comparison with the true outcome, which was known for all patients. The reproducibility of the prediction across the participating centres was assessed by the K-statistics. Results. Overall, accuracy of the prediction of 2-year survival was 0.78; the interobserver agreement beyond chance was 0.53 for survival prediction and 0.38 for the inclusion in a transplantation list. Corresponding figures for compensated patients were 0.71, 0.41 and 0.31 and for decompensated patients 0.73, 0.39 and 0.29. Variables significantly"associated with predictive error were age, comorbidity, ascites and encephalopathy; variables associated with reduction of interobserver agreement were age, alcohol, hepatocellular carcinoma and previous bleeds. Conclusions. Although the overall predictive accuracy is fair, interobserver agreement for prognosis of cirrhosis and inclusion in transplantation list is low, suggesting that known prognostic indicators are variably applied in the individual patient.
AASLD ABSTRACTS
649A
1907
1908
QUALITY OF LIFE MEASURES A N D SELF-ASSESSED BODY CHANGES IN THE SEQUENCE OF LIVER DISEASE, CIRRHOSIS A N D TRANSPLANTATION. Eckhard Leitke, Med School of Hannover, Hannover Germany; Su-
EARLY RECIDIVISM OF DRINKING IS PREVALENT IN RELAPSERS AFTER LIVER TRANSPLANTATION FOR ALCOHOLIC CIRRHOSIS. ASSOCIATION OF RELAPSE W I T H NON-COMPLIANCE A N D REJECTION. M
sanne Ahrberg, Med School Hannover, Hannover Germany; Uwe Tiedge, B Nashan, J Klempnauer, H L Tillmann, Michael Manns, G Brabant, Christian Trautwein, Med School of Hannover, Hannover Germany
Hurtova,Jc Duclos-Vallee, V Karam, F Saliba, C Guettier, C Feray, H Bismuth, D Samuel, Paul Brousse Hospital, Villejuif France
Patients with liver cirrhosis might suffer from a dramatic impairment of endocrine homeostasis and quality" of life. The sequence of these extrahepatic manifestations are, however, still not well defined and might start long before liver cirrhosis and endstage disease has been reached. In addition, the extent to which these changes might reverse after liver transplantation as the only curative treatment for liver cirrhosis today has yet not been sufficiently studied. The impairment of general and sexual well being as well as seE-assessed body changes indicative for endocrine disturbances were determined by standardized questionaires in 28 men with histological defined precirrhotic liver disease (due to chronic hepatitis), 49 men with liver cirrhosis and 53 men after transplantation and compared cross sectionally. All items showed a stepwise decline from non-cirrhotic to cirrhotic patients (p<0.0001). The majority of men with liver cirrhosis showed decreased sexual and general well being. However, also a substantial proportion of men with non-cirrhotic liver disease reported impaired libido, erectile function and measures of general well being respectively, as well as body changes normally associated with liver cirrhosis. Loss of body hair, muscle mass or breast enlargement were reported by 12 %, 8 % and 36% of men with non-cirrhotic liver disease and 22 %, 25 % and 60 % of men with cirrhosis, respectively. Dependent on the measures assessed, improvement was reported differently in men after transplantation. The results suggest that impairment of general and sexual well being as well as body changes such as breast enlargement, loss of muscle mass or body hair indicating endocrine disturbances start early in a still non-cirrhotic stage of liver disease and might reverse differently after liver transplantaton.
Alcoholic cirrhosis is one of the first indications for orthotopic liver transplantation (OLT) accounting for 30 % of liver transplantations in Europe. This study evaluates the alcohol relapse rate in patients transplanted for alcoholic liver disease (ALD) in our centre between January 1987 and May 2000. Methods : We retrospectively examined charts of 108 patients, (91 males (M), 17 females (F)), mean age at LT 50.4 + 8.5 yrs (31-68). The alcohol recurrence was detected by interviews, clinical and biological indicators of alcohol intake and histological examination. Routine biopsies were performed at 1, 2, 5 and 10 years. Eight patients died during the first 6 months post LT. Only the survivors were considered for the assessment of relapse rate. Results : Twentythree (21.2%) patients (17 M and 6 F) relapsed alcoholism, 5 of them in a transient manner. The mean delay of relapse was 2 . 5 +- 1.6 yrs (0,25-6>TS) after OLT ; in most of the cases (14, i.e. 62.6%) it occured during the first 2 years. There was no significant difference between the delay of relapse in male and females (2.7 and 2.6 yrs, respectively), nor in the mean period of pretransplantation abstinence between relapsers (1.2 yrs) and abstinents (2.2 yrs, n.s). Moderate to severe steatosis was found in all the relapsed patients who had liver biopsy during their follow up, i.e. all but one. Moreover, three patients had a biopsy-proven acute alcoholic hepatitis on the graft, two of them a severe form. None of the patients developed cirrhosis on the graft, but 11 (17.6%) had severe fibrosis. Compared to those with no alcohol relapse, the relapser patients had more often signs of chronic ductopenic rejection: (30.4 vs 11.1%), p=0.04. Three patients of the relapser group were not compliant with the immunosuppressive treatment, whereas there were no such cases in the abstinence group. Mean follow-up period was 6 + 2.5 (2-10) in the recurrence and 4,0 --- 2.8 (0,5-14) yrs in the abstinence group. Survival rate at 1 and 5 yrs was 85.8 % and 62.2 %, respectively. Twenty-five patients, 22% of the relapser group and 26% of the abstinence group died, mostly de novo cancer or septic complications. Conclusions : early recurrence is prevalent in our population, therefore the follow-up during the first three years has to be intensified. Relapse is associated with non-compliance to immunosuppressive treatment and may induce rejection.
1909
1910
CORRELATION OF BODY MASS INDEX A N D ACUTE-ON-CHRONIC LIVER FAILURE. Ali Canbay, Shiyao Chen, Massimo Malago, Robert Gie-
ACCURACY A N D REPRODUCIBILITY OF PROGNOSIS OF LIVER CIRRHOSIS A N D REPRODUCIBILITY O F THE I N D I C A T I O N TO LIVER TRANSPLANTATION. Gennaro D'Amico, Ospedale V Cervello, Palermo,
seler, Marc Karliova, Guido Gerken, Christoph Broelsch, Ulrich Treichel, University Hospital Essen, Essen Germany Background: Acute liver failure (ALF) is characterized by acute liver insufficiency, hepatorenal syndrome, and hepatic encephalopathy and is termed acute-on-chronic liverfailure (AOC) when developed on a chronic background. We therefore examined whether the sex, age, or body mass index (BMI) of such patients might reveal a significant correlation with the development of AOC. Patients and Results: Throughout a 3.5-year period of from 1998 to 2001, the 34 patients included in this study fulfilled the ALF criteria according to Clichy and Kings College Hospital. Patients (65 o~ females; 35og males) had a mean age of 37.9 _+ 12.6 years and were subdivided into two groups, i.e. ALl: (n = 18) without signs of pre-existing liver disease, and AOC (n = 16) with chronic liver disease which had been either established or diagnosed after treatment. Drug toxicity, which was mostly due to acetaminophen, was the main cause of liver failure (52.9% of all patients). Other causes included viral hepatitis (26.5%) and acute excessive ethanol abuse (11.8%). Six patients (17.6%) died in the course of the study. Of twelve patients (35.3%) who had received an OLT one needed to be re-engrafted and two deceased before the end of the study. Sixteen patients suffered from established chronic hepatopathy including NASH, fatty liver, chronic ethanol abuse, or chronic hepatitis B. A highly significant difference between AOC and ALF patients was only apparent for the BMI (p < 0.002; cf. Table). Specifically, ten (62.5%) of the AOC patients revealed a BMI of >25. Age dependency was less significant. Of interest, the liver-specific enzymes had not been detectably elevated prior to the onset of AOC. Conclusion: According to our data, 47% of all ALF patients actually suffer from AOC and reveal a tendency towards increased mortality. Moreover, and despite inapparent laboratory parameters, patients with an elevated BMI (as well as higher age) are more likely to develop AOC, when challenged by acute risk factors such as the hepatitis viruses or drugs with potential hepatotoxicity. We thus recommend patients with a BM1 of >25 and/or with >35 years of age to be monitored at tight intervals so as to prevent the onset of AOC and the increased risk of fatal outcome. Comparison of patients with liver failure within two 9reaps , ALF (n = 18) AOC (n = 16}
Sex Age BMI Causes OLT treatment
Male Female Drugs Non-drug
5 {27,8%) I3 (72.2%) 34.9±10,5 22.4 ± 2.6 11 (51.1%) 7 (38.9%)
7 (43.8%) 9 (56.3%) 41.3± 14,3 27.1 ± 4.8 7 (43,8%) 9 (56.3%)
Yes
10 (55.6%)
2 (12.5%)
P value
0,331§ 0.1545 0,0025 0,311§ 0,009§
8 (44.4%) 14 (87,5%) Survival Fatal 2 (I I. 1%) 4 (25.0%) 0.387# ...........,Nive.. 16 (8.8.9%) 12 (75.0%1 ALF: acute liver failure, AOC: acute-on-chronicliver faiture, BMI: body mass index, § ChiSquare, $ StudentT-Test, # Fisher's Exac~Test No
Palermo Italy; Ilaria Tarantino, Ospedale V Cervello, Palermo Italy; Alberto Morabito, Institute of Biometrics, Milano, Milano Italy; Piermaria Battezzati, Ospedale San Paolo, Milano, Milano Italy; Linda Pasta, Ospedale V Cervello, Palermo Italy; Luigi Pagliaro, Clinica Medica R, University Palermo, Palermo Italy Background. Although a number of accurate prognostic indicators of cirrhosis have been reported, the reproducibility and accuracy of prognosis in the individual patient has never been assessed. Aim. To assess the reproducibility and accuracy of prognosis in liver cirrhosis. Methods. Individual data at clinical presentation of 75 random patients (28 decompensated) from an ongoing study of the clinical course of cirrhosis were made available for prognostic assessment in 13 centers involved in orthotopic liver transplantation in Europe and USA. Each participant center reported the prediction on the 2-year survival and the decision on the inclusion of each patient in a transplantation waiting list. The accuracy of the reported predictions was assessed by comparison with the true outcome, which was known for all patients. The reproducibility of the prediction across the participating centres was assessed by the K-statistics. Results. Overall, accuracy of the prediction of 2-year survival was 0.78; the interobserver agreement beyond chance was 0.53 for survival prediction and 0.38 for the inclusion in a transplantation list. Corresponding figures for compensated patients were 0.71, 0.41 and 0.31 and for decompensated patients 0.73, 0.39 and 0.29. Variables significantly"associated with predictive error were age, comorbidity, ascites and encephalopathy; variables associated with reduction of interobserver agreement were age, alcohol, hepatocellular carcinoma and previous bleeds. Conclusions. Although the overall predictive accuracy is fair, interobserver agreement for prognosis of cirrhosis and inclusion in transplantation list is low, suggesting that known prognostic indicators are variably applied in the individual patient.