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Defining the alcoholic liver transplant population: Implications for future research
EDITORIAL
Defining the Alcoholic Liver Transplant Population: Implications for Future Research Andrea DiMartini, Robert Weinrieb, Tonya Lane, Nancy Day, and John Fung
F
or almost 2 decades, clinical researchers have been reporting on outcomes of patients who undergo transplantation for alcohol-related liver disease. The results of a majority of these studies have helped dispel misconceptions about these patients, as well as show the success of transplantation in this population. Overall short-term survival is as good or better than that for patients who undergo transplantation for other types of liver disease.1,2 In addition, studies show that by 5 years posttransplantation, the rates of return to drinking for these patients can be low (20% to 30%) compared with the rates of alcohol relapse after alcohol rehabilitation in alcohol-dependent persons (60% to 80%).3,4 Because the literature shows consensus regarding survival and relapse in this patient population, we propose moving beyond these fundamental outcomes toward the investigation and prediction of posttransplantation alcoholrelated events. Standardization of psychiatric diagnoses has resulted in improvements not only in the clinical diagnosis of mental illness, but in accurate diagnosis for research purposes. Investigations of alcoholic liver disease (ALD) and transplantation would also benefit from the use of standardized diagnoses. For transplant physicians and clinicians, 2 diagnoses must be simultaneously considered when examining a patient with a history of excessive alcohol use: the pathophysiological diagnosis of ALD and the psychiatric diagnosis of alcoholism. Clarifying these diagnoses is essential to accurately investigating outcome data. The purpose of this article is to discuss the importance of this distinction, as well as methods to establish these diagnoses and how to implement them in a research setting.
From Transplantation Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA. Address reprint requests to Andrea DiMartini, MD, Western Psychiatric Institute and Clinics, 3811 O’Hara St, Pittsburgh, PA 15213. Telephone: 412-383-3166; FAX: 412-383-4846; E-mail: [email protected] Copyright © 2001 by the American Association for the Study of Liver Diseases 1527-6465/01/0705-0012$35.00/0 doi:10.1053/jlts.2001.23915
428
Pathological Versus Psychiatric Diagnoses The pathophysiological diagnosis of ALD requires that the patient have sufficient exposure to alcohol to warrant a physical diagnosis of ALD. However, because this term is used for the spectrum of disease from alcoholic hepatitis to alcoholic cirrhosis, it is important to make the distinction between these processes. This is especially important because alcoholic hepatitis is believed to be a contraindication to transplantation,5 in part because of the implication of recent alcohol use and patients may recover without the need for transplantation. Diagnostic criteria for ALD is not commonly reported in the transplant literature. Although centers may rely on similar criteria to make the diagnosis of ALD, there can be wide variations in the choice and relative importance of those criteria.6 The diagnosis of alcoholism is a psychiatric (behavioral) diagnosis (i.e., alcohol dependence or alcohol abuse) and is separate from the diagnosis of ALD. In most cases, patients will have both a physical and a psychiatric diagnosis. However, a patient could have a physical diagnosis of ALD without the psychiatric diagnosis of alcohol dependence or vice versa (Fig. 1). The psychiatric diagnosis of alcohol dependence may be present in only 75% of all patients undergoing liver transplantation evaluation for ALD.7-9 Alcohol abuse is considered a less severe form of alcoholism, and predictions of relapse and treatment outcomes from the general alcoholic population are generally based on those individuals with a diagnosis of alcohol dependence. Until further research has clarified whether transplant recipients have unique risk factors for alcohol use posttransplantation, we must rely on risk factors identified from the general alcoholic population. Therefore, to investigate the impact of such risk factors on posttransplantation alcohol use, the specific psychiatric diagnosis of alcohol dependence first needs to be established.
Diagnosing ALD Ethanol Threshold Criteria Although the pathological stages of ALD are well established, the amounts of ethanol consumption necessary to develop the lesion are variable. The threshold amount
Liver Transplantation, Vol 7, No 5 (May), 2001: pp 428-431
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eases that could also lead to liver failure (31% to 50% in some studies).14-16 In these cases, the contribution of alcohol to the eventual liver failure may be uncertain or a cofactor for progressive injury by another cause. In particular, the increasing prevalence of viral hepatitis in the population of patients with ALD has lead to the discovery of the complex interactions between alcohol and hepatitis C. Alcohol may accelerate the activity and damage caused by hepatitis C, and in these cases, the exact cause may be impossible to determine. For these patients, a lesser amount of alcohol exposure may be required to lead to cirrhosis. Complications Using Histopathologic Characteristics
Figure 1. Overlap of psychiatric versus physical diagnoses in patients with ALD and alcohol dependence. (SE, sufficient ethanol exposure; ESALD, end-stage ALD; TX, liver transplant; AD, alcohol dependence.)
of ethanol exposure required to cause end-stage liver disease has been estimated both as a total lifetime exposure (600 kg for men, 150 to 300 kg for women)10 and habitual intake (80 g/d in men, 20 g/d in women).11 However, even with this type of heavy consumption, the rate of development of cirrhosis was only 20% in men who drank the equivalent of two 6-packs of beer daily for 10 years.11 In the original report by Lelbach12 on the development of alcoholic cirrhosis, the lifetime incidence approached only 50% among men who drank excessively (defined as 227 g of pure ethanol or nearly 1/5 of a gallon of hard liquor daily) for more than 2 decades. Therefore, only a percentage of those who drink excessively develop cirrhosis, whereas some who claim to drink modestly may develop the lesion. Inconsistencies in the risk for cirrhosis by level of alcohol consumption may be caused by lack of controlling for body size, sex, alcohol consumption patterns (frequency and temporal patterns),13 genetics, infections with other hepatotropic viruses, immunologic factors, or nutritional status.11 Nevertheless, end-stage ALD typically results from 10 to 20 years of heavy drinking. Determining the exact contribution of alcohol to the development of cirrhosis in this population is confounded by a high incidence of concomitant liver dis-
Histological features characteristic of alcoholic damage (micronodular cirrhosis, steatosis, Mallory’s bodies, perivenular pericellular fibrosis), although not pathognomonic for ALD, could support the diagnosis but still need to be corroborated by the clinical history. In addition, making the diagnosis of ALD by histopathologic examination is complicated by the evolution of the histological features as the disease progresses. Although the most common pathological characteristic of ALD is micronodular cirrhosis, nearly 90% of alcoholic and nonalcoholic micronodular cirrhosis will evolve toward a macronodular pattern, with a median conversion time of approximately 2 years.17 After years of abstinence and without earlier biopsy specimens for comparison, the final histological examination of the explanted liver might be indeterminate for a specific disease. A recent study from our center of patients who underwent transplantation for ALD found that only 45% had such features suggestive of ALD in their explanted livers.18 A survey of 69 US liver transplant programs found that psychiatric (93% of programs), transplant physician (80% of programs), and nonphysician evaluations (93% of programs) were very important in making the diagnosis of ALD compared with liver histological characteristics (34% of programs) or biochemical evidence of alcohol (63% of programs).6 This suggests that the importance of the clinical history compared with histological characteristics is widely recognized; however, the quantity, frequency, and duration of alcohol use are not being reported.
Diagnosing Alcohol Dependence Clear diagnostic criteria are available for the psychiatric diagnoses. The classification of an alcohol addiction depends on stringent criteria, including social, psycho-
430
DiMartini et al
logical, occupational, behavioral, physiological, and duration criteria. These criteria are specified in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) or the International Classification of Diseases, Tenth Revision. These diagnoses are not commonly reported in the transplant literature, most likely because nonpsychiatric physicians are unfamiliar with the psychiatric diagnoses. Most transplant centers have physicians and/or clinicians who evaluate and make these clinical diagnoses. A recent survey of 69 US liver transplant programs found that 83% of centers have a psychiatrist or addiction medicine specialist routinely evaluate each patient with ALD. Unfortunately, in only 68% of these centers did this person offer a diagnosis or detailed case history.6 Even so, trained clinicians may misclassify psychiatric clinical diagnoses if not using structured instruments. In addition, patients may feel compelled to underreport or minimize their history to be accepted as a transplant candidate.19
Solutions for the Future To accurately identify the specific population to be researched, all patients with a primary or secondary diagnosis of ALD should undergo a clinical evaluation to determine the correct psychiatric diagnosis of alcohol abuse or dependence. Optimally, all liver transplant patients should be screened for alcohol disorders. Any patient could have a prior history of substance abuse and/or dependence that is not believed to have contributed to the liver disease, yet would place them at risk for posttransplantation relapse. For research purposes, these disorders can be verified using such standardized instruments as the Structured Clinical Interview for DSM-IV (SCID)20 or the Diagnostic Interview Schedule.21 The identification of ALD is more complex, but could begin with the clinical history of sufficient alcohol exposure supplemented by histopathologic evaluation. Establishing threshold criteria, such as the total lifetime exposure reported by Maher,10 could provide the basis for the physical diagnosis of ALD. Additionally, adopting threshold exposure criteria would alleviate the possibility of misclassifying patients with comorbid liver diseases. Using threshold exposure criteria would require a full characterization of the alcohol consumption history by quantity, frequency, and duration. Information on changes in patterns of drinking would also be important because patients commonly increase their drinking over time as tolerance develops. Although a good clinical interview may provide the best approximation of a patient’s alcohol consumption, a
standardized instrument would serve to specify and standardize this information. One such measure, the Cognitive Lifetime Drinking History (CLDH),22 would capture the precision necessary to compare drinking histories with morbidity (e.g., ALD). The CLDH identifies quantity, frequency, duration, and the changes in drinking patterns over time. Both the SCID and CLDH require administration by a trained interviewer. Detailed information about the extent of the drinking history, amount of alcohol consumed, and duration of pretransplantation sobriety would provide important information not only to confirm the diagnosis of ALD, but also to investigate the potential effect of pretransplantation ethanol exposure on the development of long-term medical sequella (i.e., risk for cancer)23 and posttransplantation morbidity and mortality. However, if the posttransplantation outcome of interest is a behavioral outcome, such as relapse to alcohol use, then the psychiatric diagnosis is needed. Alcohol dependence is the diagnosis linked to the risk for future alcohol consumption and pathological drinking. Future efforts should be directed at standardization of physical and psychiatric diagnoses. Without clear diagnostic definitions of ALD and alcohol dependence, we cannot generalize research results to other transplant centers. With these measures in place, data can be combined across centers for the statistical power that prior studies have been lacking.
References 1. Belle SH, Beringer KC, Deter KM. Liver transplantation for alcoholic liver disease in the United States 1988 to 1995. Liver Transpl Surg 1997;3:212-219. 2. DiMartini AF, Jain A, Irish W, Fitzgerald MG, Fung JJ. Liver transplantation in alcoholic and non-alcoholic cirrhosis: Survival according to UNOS status, medical variables, and sobriety. Transplantation 1998;66:298-302. 3. Vaillant GE. The natural history of alcoholism and its relationship to liver transplantation. Liver Transpl Surg 1997;3:304-310. 4. Lucey MR. Liver transplantation for alcoholic liver disease: A progress report. Graft 1999;2(suppl):S73-S79. 5. Shakil O, Pinna A, Demetris J, Lee R, Fung J, Rakela J. Survival and quality of life after liver transplantation for acute alcoholic hepatitis. Liver Transpl Surg 1997;3:240-244. 6. Everhart J, Beresford T. Liver transplantation for alcoholic liver disease: A survey of transplantation programs in the United States. Liver Transpl Surg 1997;3:220-226. 7. Beresford TP. Overt and covert alcoholism. In: Lucey MR, Merion RM, Beresford TP (eds). Liver Transplantation and the Alcoholic Patient. Cambridge, UK: Cambridge University Press, 1994:12-13. 8. Beresford TP. Predictive factors for alcoholic relapse in the selection of alcohol-dependent persons for hepatic transplant. Liver Transpl Surg 1997;3:280-291.
Defining Alcoholic Liver Transplant Population
9. DiMartini AF, Day N, Dew MA, Lane T, Jain A. Outcome of liver transplantation in alcoholic cirrhosis [abstract 198]. Liver Transpl Surg 1999;5:C51. 10. Maher JJ. Alcoholic liver disease. In: Feldman M, Scharschmidt B, Sleisenger M (eds) Gastrointestinal and Liver Diseases. Philadelphia, PA: Saunders, 1998:1199-1214. 11. Diehl AM. Alcoholic liver disease. Liver Transpl Surg 1997;3: 206-211. 12. Lelbach WK. Cirrhosis in the alcoholic and its relation to the volume of alcohol abuse. Ann N Y Acad Sci 1975;252:85-105. 13. Parrish KM, Higuchi S, Dufour MC. Alcohol consumption and the risk of developing liver cirrhosis: Implications for future research. J Substance Abuse 1991;3:325-335. 14. Hoofnagle JH, Kresina T, Fuller RK, Lake JR, Lucey MR, Sorrell MF, Beresford TP. Liver transplantation for alcoholic liver disease: Executive statement and recommendations. Summary of a National Institutes of Health workshop held December 6-7, 1996, Bethesda, Maryland. Liver Transpl Surg 1997;3:347-350. 15. Levy MT, Chen JJ, McGuinness PH, Koorey D, Sheil AGR, McCaughan GW. Liver transplantation for hepatitis C-associated cirrhosis in a single Australian centre: Referral patterns and transplant outcomes. J Gastroenterol Hepatol 1997;12:453-459. 16. Lucey MR. Alcohol injury in the transplanted liver. Liver Transpl Surg 1997;3(suppl 1):S26-S31.
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17. Fauerholdt L, Schlichting P, Christensen E, Poulsen H, Tygstrup N, Juhl E. Conversion of micronodular cirrhosis into macronodular cirrhosis. Hepatology 1983;3:928-931. 18. Bellamy COC, DiMartini AM, Ruppert K, Jain A, Dodson F, Torbenson M, et al. Liver transplantation for alcoholic cirrhosis: Long term follow-up and impact of disease recurrence. Transplantation (in press). 19. Weinrieb RM, O’Brien CP. Current research in the treatment of alcoholism in liver transplant recipients. Liver Transpl Surg 1997;3:328-336. 20. Williams JBW, Gibbon M, First MB, Spitzer RL, Davies M, Borus J, et al. The structured clinical interview for DSM-III-R (SCID). Arch Gen Psychiatry 1992;49:630-636. 21. Robins LN, Helzer J, Croughan J, Ratcliff KS. The NIMH Diagnostic Interview Schedule: Its history, characteristics, and validity. Arch Gen Psychiatry 1981;45:1069-1077. 22. Russell M, Marshall JR, Trevisan M, Freudenheim J, Chan AWK, Markovic N, et al. Test-retest reliability of the Cognitive Lifetime Drinking History. Am J Epidemiol 1997;146;975-981. 23. Jain A, Reyes J, Kashyap R, Rohal S, Abu-Elmagd K, Starzl T, Fung J. What have we learned about primary liver transplantation under tacrolimus immunosuppression? Long-term follow-up of the first 1000 patients. Ann Surg 1999;230:441-448; discussion 448-449.
Defining the Alcoholic Liver Transplant Population: Implications for Future Research Andrea DiMartini, Robert Weinrieb, Tonya Lane, Nancy Day, and John Fung
F
or almost 2 decades, clinical researchers have been reporting on outcomes of patients who undergo transplantation for alcohol-related liver disease. The results of a majority of these studies have helped dispel misconceptions about these patients, as well as show the success of transplantation in this population. Overall short-term survival is as good or better than that for patients who undergo transplantation for other types of liver disease.1,2 In addition, studies show that by 5 years posttransplantation, the rates of return to drinking for these patients can be low (20% to 30%) compared with the rates of alcohol relapse after alcohol rehabilitation in alcohol-dependent persons (60% to 80%).3,4 Because the literature shows consensus regarding survival and relapse in this patient population, we propose moving beyond these fundamental outcomes toward the investigation and prediction of posttransplantation alcoholrelated events. Standardization of psychiatric diagnoses has resulted in improvements not only in the clinical diagnosis of mental illness, but in accurate diagnosis for research purposes. Investigations of alcoholic liver disease (ALD) and transplantation would also benefit from the use of standardized diagnoses. For transplant physicians and clinicians, 2 diagnoses must be simultaneously considered when examining a patient with a history of excessive alcohol use: the pathophysiological diagnosis of ALD and the psychiatric diagnosis of alcoholism. Clarifying these diagnoses is essential to accurately investigating outcome data. The purpose of this article is to discuss the importance of this distinction, as well as methods to establish these diagnoses and how to implement them in a research setting.
From Transplantation Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA. Address reprint requests to Andrea DiMartini, MD, Western Psychiatric Institute and Clinics, 3811 O’Hara St, Pittsburgh, PA 15213. Telephone: 412-383-3166; FAX: 412-383-4846; E-mail: [email protected] Copyright © 2001 by the American Association for the Study of Liver Diseases 1527-6465/01/0705-0012$35.00/0 doi:10.1053/jlts.2001.23915
428
Pathological Versus Psychiatric Diagnoses The pathophysiological diagnosis of ALD requires that the patient have sufficient exposure to alcohol to warrant a physical diagnosis of ALD. However, because this term is used for the spectrum of disease from alcoholic hepatitis to alcoholic cirrhosis, it is important to make the distinction between these processes. This is especially important because alcoholic hepatitis is believed to be a contraindication to transplantation,5 in part because of the implication of recent alcohol use and patients may recover without the need for transplantation. Diagnostic criteria for ALD is not commonly reported in the transplant literature. Although centers may rely on similar criteria to make the diagnosis of ALD, there can be wide variations in the choice and relative importance of those criteria.6 The diagnosis of alcoholism is a psychiatric (behavioral) diagnosis (i.e., alcohol dependence or alcohol abuse) and is separate from the diagnosis of ALD. In most cases, patients will have both a physical and a psychiatric diagnosis. However, a patient could have a physical diagnosis of ALD without the psychiatric diagnosis of alcohol dependence or vice versa (Fig. 1). The psychiatric diagnosis of alcohol dependence may be present in only 75% of all patients undergoing liver transplantation evaluation for ALD.7-9 Alcohol abuse is considered a less severe form of alcoholism, and predictions of relapse and treatment outcomes from the general alcoholic population are generally based on those individuals with a diagnosis of alcohol dependence. Until further research has clarified whether transplant recipients have unique risk factors for alcohol use posttransplantation, we must rely on risk factors identified from the general alcoholic population. Therefore, to investigate the impact of such risk factors on posttransplantation alcohol use, the specific psychiatric diagnosis of alcohol dependence first needs to be established.
Diagnosing ALD Ethanol Threshold Criteria Although the pathological stages of ALD are well established, the amounts of ethanol consumption necessary to develop the lesion are variable. The threshold amount
Liver Transplantation, Vol 7, No 5 (May), 2001: pp 428-431
Defining Alcoholic Liver Transplant Population
429
eases that could also lead to liver failure (31% to 50% in some studies).14-16 In these cases, the contribution of alcohol to the eventual liver failure may be uncertain or a cofactor for progressive injury by another cause. In particular, the increasing prevalence of viral hepatitis in the population of patients with ALD has lead to the discovery of the complex interactions between alcohol and hepatitis C. Alcohol may accelerate the activity and damage caused by hepatitis C, and in these cases, the exact cause may be impossible to determine. For these patients, a lesser amount of alcohol exposure may be required to lead to cirrhosis. Complications Using Histopathologic Characteristics
Figure 1. Overlap of psychiatric versus physical diagnoses in patients with ALD and alcohol dependence. (SE, sufficient ethanol exposure; ESALD, end-stage ALD; TX, liver transplant; AD, alcohol dependence.)
of ethanol exposure required to cause end-stage liver disease has been estimated both as a total lifetime exposure (600 kg for men, 150 to 300 kg for women)10 and habitual intake (80 g/d in men, 20 g/d in women).11 However, even with this type of heavy consumption, the rate of development of cirrhosis was only 20% in men who drank the equivalent of two 6-packs of beer daily for 10 years.11 In the original report by Lelbach12 on the development of alcoholic cirrhosis, the lifetime incidence approached only 50% among men who drank excessively (defined as 227 g of pure ethanol or nearly 1/5 of a gallon of hard liquor daily) for more than 2 decades. Therefore, only a percentage of those who drink excessively develop cirrhosis, whereas some who claim to drink modestly may develop the lesion. Inconsistencies in the risk for cirrhosis by level of alcohol consumption may be caused by lack of controlling for body size, sex, alcohol consumption patterns (frequency and temporal patterns),13 genetics, infections with other hepatotropic viruses, immunologic factors, or nutritional status.11 Nevertheless, end-stage ALD typically results from 10 to 20 years of heavy drinking. Determining the exact contribution of alcohol to the development of cirrhosis in this population is confounded by a high incidence of concomitant liver dis-
Histological features characteristic of alcoholic damage (micronodular cirrhosis, steatosis, Mallory’s bodies, perivenular pericellular fibrosis), although not pathognomonic for ALD, could support the diagnosis but still need to be corroborated by the clinical history. In addition, making the diagnosis of ALD by histopathologic examination is complicated by the evolution of the histological features as the disease progresses. Although the most common pathological characteristic of ALD is micronodular cirrhosis, nearly 90% of alcoholic and nonalcoholic micronodular cirrhosis will evolve toward a macronodular pattern, with a median conversion time of approximately 2 years.17 After years of abstinence and without earlier biopsy specimens for comparison, the final histological examination of the explanted liver might be indeterminate for a specific disease. A recent study from our center of patients who underwent transplantation for ALD found that only 45% had such features suggestive of ALD in their explanted livers.18 A survey of 69 US liver transplant programs found that psychiatric (93% of programs), transplant physician (80% of programs), and nonphysician evaluations (93% of programs) were very important in making the diagnosis of ALD compared with liver histological characteristics (34% of programs) or biochemical evidence of alcohol (63% of programs).6 This suggests that the importance of the clinical history compared with histological characteristics is widely recognized; however, the quantity, frequency, and duration of alcohol use are not being reported.
Diagnosing Alcohol Dependence Clear diagnostic criteria are available for the psychiatric diagnoses. The classification of an alcohol addiction depends on stringent criteria, including social, psycho-
430
DiMartini et al
logical, occupational, behavioral, physiological, and duration criteria. These criteria are specified in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) or the International Classification of Diseases, Tenth Revision. These diagnoses are not commonly reported in the transplant literature, most likely because nonpsychiatric physicians are unfamiliar with the psychiatric diagnoses. Most transplant centers have physicians and/or clinicians who evaluate and make these clinical diagnoses. A recent survey of 69 US liver transplant programs found that 83% of centers have a psychiatrist or addiction medicine specialist routinely evaluate each patient with ALD. Unfortunately, in only 68% of these centers did this person offer a diagnosis or detailed case history.6 Even so, trained clinicians may misclassify psychiatric clinical diagnoses if not using structured instruments. In addition, patients may feel compelled to underreport or minimize their history to be accepted as a transplant candidate.19
Solutions for the Future To accurately identify the specific population to be researched, all patients with a primary or secondary diagnosis of ALD should undergo a clinical evaluation to determine the correct psychiatric diagnosis of alcohol abuse or dependence. Optimally, all liver transplant patients should be screened for alcohol disorders. Any patient could have a prior history of substance abuse and/or dependence that is not believed to have contributed to the liver disease, yet would place them at risk for posttransplantation relapse. For research purposes, these disorders can be verified using such standardized instruments as the Structured Clinical Interview for DSM-IV (SCID)20 or the Diagnostic Interview Schedule.21 The identification of ALD is more complex, but could begin with the clinical history of sufficient alcohol exposure supplemented by histopathologic evaluation. Establishing threshold criteria, such as the total lifetime exposure reported by Maher,10 could provide the basis for the physical diagnosis of ALD. Additionally, adopting threshold exposure criteria would alleviate the possibility of misclassifying patients with comorbid liver diseases. Using threshold exposure criteria would require a full characterization of the alcohol consumption history by quantity, frequency, and duration. Information on changes in patterns of drinking would also be important because patients commonly increase their drinking over time as tolerance develops. Although a good clinical interview may provide the best approximation of a patient’s alcohol consumption, a
standardized instrument would serve to specify and standardize this information. One such measure, the Cognitive Lifetime Drinking History (CLDH),22 would capture the precision necessary to compare drinking histories with morbidity (e.g., ALD). The CLDH identifies quantity, frequency, duration, and the changes in drinking patterns over time. Both the SCID and CLDH require administration by a trained interviewer. Detailed information about the extent of the drinking history, amount of alcohol consumed, and duration of pretransplantation sobriety would provide important information not only to confirm the diagnosis of ALD, but also to investigate the potential effect of pretransplantation ethanol exposure on the development of long-term medical sequella (i.e., risk for cancer)23 and posttransplantation morbidity and mortality. However, if the posttransplantation outcome of interest is a behavioral outcome, such as relapse to alcohol use, then the psychiatric diagnosis is needed. Alcohol dependence is the diagnosis linked to the risk for future alcohol consumption and pathological drinking. Future efforts should be directed at standardization of physical and psychiatric diagnoses. Without clear diagnostic definitions of ALD and alcohol dependence, we cannot generalize research results to other transplant centers. With these measures in place, data can be combined across centers for the statistical power that prior studies have been lacking.
References 1. Belle SH, Beringer KC, Deter KM. Liver transplantation for alcoholic liver disease in the United States 1988 to 1995. Liver Transpl Surg 1997;3:212-219. 2. DiMartini AF, Jain A, Irish W, Fitzgerald MG, Fung JJ. Liver transplantation in alcoholic and non-alcoholic cirrhosis: Survival according to UNOS status, medical variables, and sobriety. Transplantation 1998;66:298-302. 3. Vaillant GE. The natural history of alcoholism and its relationship to liver transplantation. Liver Transpl Surg 1997;3:304-310. 4. Lucey MR. Liver transplantation for alcoholic liver disease: A progress report. Graft 1999;2(suppl):S73-S79. 5. Shakil O, Pinna A, Demetris J, Lee R, Fung J, Rakela J. Survival and quality of life after liver transplantation for acute alcoholic hepatitis. Liver Transpl Surg 1997;3:240-244. 6. Everhart J, Beresford T. Liver transplantation for alcoholic liver disease: A survey of transplantation programs in the United States. Liver Transpl Surg 1997;3:220-226. 7. Beresford TP. Overt and covert alcoholism. In: Lucey MR, Merion RM, Beresford TP (eds). Liver Transplantation and the Alcoholic Patient. Cambridge, UK: Cambridge University Press, 1994:12-13. 8. Beresford TP. Predictive factors for alcoholic relapse in the selection of alcohol-dependent persons for hepatic transplant. Liver Transpl Surg 1997;3:280-291.
Defining Alcoholic Liver Transplant Population
9. DiMartini AF, Day N, Dew MA, Lane T, Jain A. Outcome of liver transplantation in alcoholic cirrhosis [abstract 198]. Liver Transpl Surg 1999;5:C51. 10. Maher JJ. Alcoholic liver disease. In: Feldman M, Scharschmidt B, Sleisenger M (eds) Gastrointestinal and Liver Diseases. Philadelphia, PA: Saunders, 1998:1199-1214. 11. Diehl AM. Alcoholic liver disease. Liver Transpl Surg 1997;3: 206-211. 12. Lelbach WK. Cirrhosis in the alcoholic and its relation to the volume of alcohol abuse. Ann N Y Acad Sci 1975;252:85-105. 13. Parrish KM, Higuchi S, Dufour MC. Alcohol consumption and the risk of developing liver cirrhosis: Implications for future research. J Substance Abuse 1991;3:325-335. 14. Hoofnagle JH, Kresina T, Fuller RK, Lake JR, Lucey MR, Sorrell MF, Beresford TP. Liver transplantation for alcoholic liver disease: Executive statement and recommendations. Summary of a National Institutes of Health workshop held December 6-7, 1996, Bethesda, Maryland. Liver Transpl Surg 1997;3:347-350. 15. Levy MT, Chen JJ, McGuinness PH, Koorey D, Sheil AGR, McCaughan GW. Liver transplantation for hepatitis C-associated cirrhosis in a single Australian centre: Referral patterns and transplant outcomes. J Gastroenterol Hepatol 1997;12:453-459. 16. Lucey MR. Alcohol injury in the transplanted liver. Liver Transpl Surg 1997;3(suppl 1):S26-S31.
431
17. Fauerholdt L, Schlichting P, Christensen E, Poulsen H, Tygstrup N, Juhl E. Conversion of micronodular cirrhosis into macronodular cirrhosis. Hepatology 1983;3:928-931. 18. Bellamy COC, DiMartini AM, Ruppert K, Jain A, Dodson F, Torbenson M, et al. Liver transplantation for alcoholic cirrhosis: Long term follow-up and impact of disease recurrence. Transplantation (in press). 19. Weinrieb RM, O’Brien CP. Current research in the treatment of alcoholism in liver transplant recipients. Liver Transpl Surg 1997;3:328-336. 20. Williams JBW, Gibbon M, First MB, Spitzer RL, Davies M, Borus J, et al. The structured clinical interview for DSM-III-R (SCID). Arch Gen Psychiatry 1992;49:630-636. 21. Robins LN, Helzer J, Croughan J, Ratcliff KS. The NIMH Diagnostic Interview Schedule: Its history, characteristics, and validity. Arch Gen Psychiatry 1981;45:1069-1077. 22. Russell M, Marshall JR, Trevisan M, Freudenheim J, Chan AWK, Markovic N, et al. Test-retest reliability of the Cognitive Lifetime Drinking History. Am J Epidemiol 1997;146;975-981. 23. Jain A, Reyes J, Kashyap R, Rohal S, Abu-Elmagd K, Starzl T, Fung J. What have we learned about primary liver transplantation under tacrolimus immunosuppression? Long-term follow-up of the first 1000 patients. Ann Surg 1999;230:441-448; discussion 448-449.