- Email: [email protected]
Diagnosis of primary sclerosing cholangitis - autoimmune hepatitis overlap syndrome: to score or not to score?
Journal of Hepatology2000; 33: 661-663 Printed in Denmark All rightsreserved Munksgaard Copenhagen
Copyright 8 European Association for the Study of the Liver 2000
Journalof Hepatology ISSN
0168-8278
Editorial
Diagnosis of primary sclerosing cholangitis - autoimmune hepatitis overlap syndrome: to score or not to score? Olivier Chazouilleres Hfipital Saint-Antoine, Paris, France
See Articles on pages 537-542
I
T IS GENERALLYassumed that primary
biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) share an autoimmune basis. The hallmarks of PBC and PSC are the presence of antimitochondrial antibodies (AMA) and cholangiographic abnormalities, respectively. Unfortunately, there is no single and specific diagnostic marker of AIH which is characterized by the presence of interface hepatitis on histologic examination, hypergammaglobulinemia and autoantibodies in serum. Since some of these features may occur with variable frequency and magnitude of severity in a wide range of other liver diseases, diagnosis of AIH is made from a combination of features. The International AIH Group has promulgated descriptive criteria for definite and probable diagnosis (1). In addition, a numerical scoring system has been devised that may be used in conjunction with the descriptive criteria for difficult cases or when a more objective assessment is required (1). Points are given for each feature, or deducted for conditions suggesting an alternative diagnosis. Recently, this scoring system was modified (2). PBC, PSC and AIH are generally differentiated easily on the basis of clinical, biochemical, serological, radiological and histological findings. Whereas PBC and PSC are mutually exclusive, the normally distinctive features between PBC or PSC on one hand and AIH on the other hand occasionally overlap and classification of a given patient’s chronic liver disease is difficult. Recent papers have suggested that lo-20% of patients thought to have PBC may also have AIH defined either by the presence of conventional criteria (3) Correspondence: Olivier Chazouilleres, Service d’HCpatologie, Hopital Saint-Antoine, Assistance Publique - Hopitaux de Paris, 184, rue du Faubourg Saint-Antoine, 7557 1 Paris Cedex 12, France. Tel: 1 49 28 23 80. Fax: 1 49 28 21 07. e-mail: [email protected]
and 543-548
or by using the AIH scoring system (4). An overlapping syndrome between PSC and AIH has been repeatedly reported and the term autoimmune sclerosing cholangitis has been proposed in children (5). However, the real prevalence of the so-called PSC-AIH overlap syndrome is unknown. What can one possibly conclude when faced with two reports in this issue of Journal of Hepatology that come to conflicting conclusions about the prevalence of AIH among patients with PSC? Van Buuren et al. (6) reviewed the records of 113 subjects with a diagnosis of PSC followed in the University Hospital of Rotterdam and diagnosed overlap syndrome in nine patients (8%) by using conventional descriptive criteria. Interestingly, all these patients responded to immunosuppressive therapy. By applying the revised version of the AIH scoring system, they confirmed the diagnosis of AIH in the nine patients with overlap syndrome (“definite” AIH in eight cases and “probable” AIH in one), and they found 22% of “probable” or “definite” AIH in the whole population of 113 patients. They concluded that the prevalence of AIH among patients with PSC is high. In contrast, Kaya et al. (7) evaluated 211 patients referred for PSC at the Mayo Clinic and, using the revised scoring system, found only 1.4% with “definite” AIH and 6% with “probable” AIH. They concluded that overlap of PSC and AIH occurs rarely. How could the two studies have asked the same question in large series of patients and come to different conclusions? The first possible reason is that the populations are different. Beside potential selection bias or differences in genetic backgrounds between North European and American populations, age of patients included in these series is probably a key point since it is generally assumed that this overlap syndrome mainly occurs in children or young adults. Indeed, it is likely that the patients included in the Dutch study were younger than those in the American one. In the 661
0. Clzasouillhw
former, no details are available in the whole group of 113 PSC but the mean and median (range) age of the overlap patients was 27 and 22 (7-54) years, respectively. In the latter, mean age of both overlap patients and non-overlap patients was 43 years with a small
Then, details on scores for each parameter are useful and care must be taken when comparing aggregate scores of apparently the same scoring version. For example, perinuclear antineutrophil cytoplasmic antibodies (pANCA) which are “defined autoantibodies”
standard error. A second possible
according to the scoring system (+2 points) were taken into account in the study by van Buuren et al. but not
reason
for the conflicting
con-
clusions of these two studies is that the diagnostic criteria were different. In the study by van Buuren et al., diagnosis was mainly based on conventional descriptive criteria. They obtained essentially the same results (definite AIH) by applying the modified scoring system, but detailed scores for each parameter were not given. In the study by Kaya et al., diagnosis was made exclusively by using the scoring system. At first glance both groups seem to have applied the same diagnostic criteria, at least in part. However, important issues relevant to the use of the scoring system should be underlined. First, in the literature dealing with the PSC-AIH overlap syndrome, the reader may be confused by the different versions of the so-called AIH scoring system: the 1993 and 1999 versions developed by the International AIH Group (1,2), but also “adapted” scoring systems with slight differences (8). As shown in Table 1, prevalence of overlap syndrome is strongly dependent on the version of the scoring system, ranging from 7.6% to 53.8%. The initial scoring system was modified to improve specificity. As a consequence, in most of the studies, the prevalence of “definite” AIH is the same with both scoring systems, but that of “probable” AIH is much lower (around l/3) using the modified system (7,9). Second, as discussed in the Mayo Clinic’s study, the 1999 scoring system was published using two different categories: one with a set of parameters for diagnosis of AIH and the other with “optimal additional parameters” (seropositivity for other defined autoantibodies, HLA DR3 or DRII, and response to therapy).
1
TABLE
Prevalence of autoimmune ing cholangitis according Study
Boberg (92)
et al.
hepatitis in patients with primary to the different scoring systems
Scoring system version
Number of patients
1993 1999
114
Percent scoring
scleros-
as
Definite AIH
Probable AIH
Overall AIH
1.8’%, 1X%,
33.3’!/;> 8.Wi
35.1% 10.6%
NA
NA
53.8%
Czaja (4)
adapted 1993
Kaya et al. (7)
1993 1999
211
1.9% 1.4%
I 9 .O%, 6.2’!/;>
20.9% 7.6’%1
van Bum-en et al. (6)
1993 1999
113
7.1% 7. I ‘%I
15.9% 12.4”/1,
23’!i, 19.5%
662
26
in the study from the Mayo Clinic. Third, because of the high number of scoring parameters, missing data are frequent, at least in retrospective studies. For example, only 55% of the patients from the Mayo Clinic were tested for anti-smooth muscle antibodies (ASMA). In some cases it may be hypothesized that the screening omissions could alter the results of the scoring system. Fourth, even with detailed explanatory notes for use of the scoring system, there is still room for interpretation. Indeed, points (+3) for the concurrence of inflammatory bowel disease (IBD) as an associated autoimmune disease were not allowed in the present study from the Mayo Clinic, whereas presence of IBD was taken into account in previous studies from the same institution (4,8). Last but not least, is it relevant to use the scoring system for defining cholestatic diseases ~ AIH overlap syndromes? According to the members of the International AIH group, it is yet to be determined (2). It should be remembered that the scoring system is intended mainly for research purposes. The score is also clearly useful in clinical practice for difficult cases of patients with unexplained hepatitic illness. Whether it makes sense to apply it in otherwise obvious PSC or PBC is more questionable. In spite of the drawbacks discussed above, the potential advantages of a scoring system over a clinical definition are its apparent consistency and objectivity since it is supposed to ensure uniformity of assessment and diagnosis. An excellent sensitivity (>95’%) has been demonstrated for diagnosis of pure AIH (2). However, the scoring system is tailored on the assumption that none (or only very few) of the patients with chronic cholestatic diseases also have concomitant AIH. Indeed, the International AIH group repeatedly stated that biliary lesions either preclude the diagnosis of AIH using descriptive criteria or have a strongly negative impact using the scoring system. Because of a high number of “probable” AIH using the original score in PSC patients. adjustments were made to improve specificity by increasing the weighting against biliary diseases. As expected, the prevalence of overlap syndromes fell dramatically using the revised system. In this setting, the scoring system can only identify the few patients with caricatural overlap seen as the coincidence of 2 distinct diseases. However, it may also be hypothesized that PSC (or PBC) and AIH are the ex-
Diagnosis of primary sclerosing cholangitis
treme points of autoimmune liver disease spectrum with a continuum from one disease to the other, and the scoring system would clearly underdiagnose mild forms of overlap. Finally and beyond this academic debate on classification and pathogenesis, is it really important to identify patients with PSC-AIH overlap syndrome? The answer is unambiguously yes. Effective medical therapy is not yet available for PSC but this disease is notably heterogeneous with respect to its presentation, severity and outcome. Thus it is crucial to define relatively homogeneous groups of patients with features that might be useful for assessing prognosis and planning treatment strategies. In this regard the excellent therapeutic response to immunosuppressants, in particular of the AIH-component of the overlap syndrome, as shown in different studies including that by van Buuren et al. (5,6,10), has to be underscored. Proper therapy may indeed be life-saving. Therefore, for the clinician taking care of patients with PSC, the main issue is to recognize, using simple tools, patients with “significant” overlap, in other words patients who may benefit from immunosuppressive therapy. Are the major descriptive positive criteria of AIH, i.e. presence of ASMA or interface hepatitis, relevant in this regard? Lessons can probably be drawn from the experience with PBC. Presence of ASMA or antinuclear antibodies (ANA) in AMA-positive PBC does not necessarily indicate overlap requiring a different therapy and patients with AMA-negative PBC who test ANA/ ASMA positive do not have an overlap with AIH, but rather are just AMA-negative PBC with a fair response to ursodeoxycholic acid (UDCA) (11). Presence of interface hepatitis of moderate or severe activity, a key feature of AIH, seems to be a more promising track. Indeed, it has been shown that the degree of severity of lymphocytic piecemeal necrosis and lobular inflammation in the first biopsy specimen was highly related (~KO.001) to the progression of fibrosis and development of cirrhosis in PBC patients treated with UDCA (12). This suggests that PBC patients having severe lymphocytic piecemeal necrosis and lobular inflammation (“occult” overlap) may constitute a subset of patients, in whom combination of UDCA and corticosteroids is needed to prevent disease progression (13). However, prevalence of interface hepatitis in PSC patients remains to be carefully determined (only 8% in the present study from the Mayo Clinic) and ideally, well-designed randomized trials should assess the efficacy and tolerance of immunosuppressive drugs in this subset of patients. To date, only identification of variant forms of PSC (14), including PSC-AIH overlap syndrome, has
received some degree of general acceptance. Because we have a desperate need for effective therapy, subclassification of a heterogeneous disorder such as PSC can facilitate clinical management. It is my opinion that the AIH scoring system should be interpreted with caution in routine practice despite its apparent objectivity and the “magic” power of a cut-off value. As recently underscored, a collaborative effort among multiple centers is clearly needed to develop standardized diagnostic criteria and to initiate studies of the pathogenic mechanisms, natural history and treatment of this form of autoimmune liver disease (15). In the meantime, you can score but please, don’t forget to talk to your liver pathologist!
References 1. Johnson PJ, McFarlane IG. Meeting report: International Autoimmune Hepatitis Group. Hepatology 1993; 18: 9981005. 2. Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, et al. International autoimmune hepatitis group report: review of criteria for diagnosis of autoimmune hepatitis. J. Hepato1 1999; 31: 929-38. 3. Chazouilltres 0, Wendum D, Serfaty L, Montembault S, Rosmorduc 0, Poupon R. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatology 1998; 28: 296301. 4. Czaja AJ. Frequency and nature of the variant syndromes of autoimmune liver disease. Hepatology 1998; 28: 360-5. 5. Mieli-Vergani G. Autoimmune sclerosing cholangitis: a distinct clinical entitv? J Henatol 2000; 32 (Suppl.2). 7-8 6. van Buuren HR, van Hoogstraten IIJe Terkivatan T, Schalm SW, Vleggaar FP High prevalence of autoimmune hepatitis among patients with primary sclerosing cholangitis. J Hepatol 2000; 33: 543-8. 7. Kaya M, Angulo P, Lindor KD. Overlap of autoimmune hepatitis and primary sclerosing cholangitis: an evaluation of a modified scoring system. J Hepatol 2000; 33: 53742. HA. Validation of scoring system for diag8. Czaja AJ, Carpenter nosis of autoimmune hepatitis. Dig Dis Sci 1996; 41: 305-14. 9. Boberg KM, Fausa 0, Haaland T, Holter E, Mellbye OJ, Spurkland A, et al. Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis. Hepatology 1996; 23: 1369-76. E, 10. Gohlke F, Lohse AW, Dienes HP, Lohr H, Marker-Hermann Gerken G, et al. Evidence for an overlap syndrome of autoimmune hepatitis and primary sclerosing cholangitis. J Hepatol 1996; 24: 699-705. 11. Michieletti P, Wanless IR, Katz A, Scheuer PJ, Yeaman SJ, Bassendine MF, et al. Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis. Gut 1994; 35: 260--5. 12. Degott C, Zafrani ES, Callard P, Balkau B, Poupon RE, Poupon R. Histopathological study of primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment on histology progression Hepatology 1999; 20: 1007712. of primary biliary cirrhosis resistant to 13 Poupon R. Management ursodeoxycholic acid therapy. J Hepatol 2000; 32(Supp1.2): 1920. 14. Chazouilltres 0. The variant forms of cholestatic diseases involving small bile ducts in adults. J Hepatol 2000; 32(Supp1.2): 16 18. 15. Czaja AJ, Manns MP, McFarlane IG, Hoofnagle JH. Autoimmune hepatitis: the investigational and clinical challenges. Hepatology 2000; 31: 1194200.
663
Copyright 8 European Association for the Study of the Liver 2000
Journalof Hepatology ISSN
0168-8278
Editorial
Diagnosis of primary sclerosing cholangitis - autoimmune hepatitis overlap syndrome: to score or not to score? Olivier Chazouilleres Hfipital Saint-Antoine, Paris, France
See Articles on pages 537-542
I
T IS GENERALLYassumed that primary
biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) share an autoimmune basis. The hallmarks of PBC and PSC are the presence of antimitochondrial antibodies (AMA) and cholangiographic abnormalities, respectively. Unfortunately, there is no single and specific diagnostic marker of AIH which is characterized by the presence of interface hepatitis on histologic examination, hypergammaglobulinemia and autoantibodies in serum. Since some of these features may occur with variable frequency and magnitude of severity in a wide range of other liver diseases, diagnosis of AIH is made from a combination of features. The International AIH Group has promulgated descriptive criteria for definite and probable diagnosis (1). In addition, a numerical scoring system has been devised that may be used in conjunction with the descriptive criteria for difficult cases or when a more objective assessment is required (1). Points are given for each feature, or deducted for conditions suggesting an alternative diagnosis. Recently, this scoring system was modified (2). PBC, PSC and AIH are generally differentiated easily on the basis of clinical, biochemical, serological, radiological and histological findings. Whereas PBC and PSC are mutually exclusive, the normally distinctive features between PBC or PSC on one hand and AIH on the other hand occasionally overlap and classification of a given patient’s chronic liver disease is difficult. Recent papers have suggested that lo-20% of patients thought to have PBC may also have AIH defined either by the presence of conventional criteria (3) Correspondence: Olivier Chazouilleres, Service d’HCpatologie, Hopital Saint-Antoine, Assistance Publique - Hopitaux de Paris, 184, rue du Faubourg Saint-Antoine, 7557 1 Paris Cedex 12, France. Tel: 1 49 28 23 80. Fax: 1 49 28 21 07. e-mail: [email protected]
and 543-548
or by using the AIH scoring system (4). An overlapping syndrome between PSC and AIH has been repeatedly reported and the term autoimmune sclerosing cholangitis has been proposed in children (5). However, the real prevalence of the so-called PSC-AIH overlap syndrome is unknown. What can one possibly conclude when faced with two reports in this issue of Journal of Hepatology that come to conflicting conclusions about the prevalence of AIH among patients with PSC? Van Buuren et al. (6) reviewed the records of 113 subjects with a diagnosis of PSC followed in the University Hospital of Rotterdam and diagnosed overlap syndrome in nine patients (8%) by using conventional descriptive criteria. Interestingly, all these patients responded to immunosuppressive therapy. By applying the revised version of the AIH scoring system, they confirmed the diagnosis of AIH in the nine patients with overlap syndrome (“definite” AIH in eight cases and “probable” AIH in one), and they found 22% of “probable” or “definite” AIH in the whole population of 113 patients. They concluded that the prevalence of AIH among patients with PSC is high. In contrast, Kaya et al. (7) evaluated 211 patients referred for PSC at the Mayo Clinic and, using the revised scoring system, found only 1.4% with “definite” AIH and 6% with “probable” AIH. They concluded that overlap of PSC and AIH occurs rarely. How could the two studies have asked the same question in large series of patients and come to different conclusions? The first possible reason is that the populations are different. Beside potential selection bias or differences in genetic backgrounds between North European and American populations, age of patients included in these series is probably a key point since it is generally assumed that this overlap syndrome mainly occurs in children or young adults. Indeed, it is likely that the patients included in the Dutch study were younger than those in the American one. In the 661
0. Clzasouillhw
former, no details are available in the whole group of 113 PSC but the mean and median (range) age of the overlap patients was 27 and 22 (7-54) years, respectively. In the latter, mean age of both overlap patients and non-overlap patients was 43 years with a small
Then, details on scores for each parameter are useful and care must be taken when comparing aggregate scores of apparently the same scoring version. For example, perinuclear antineutrophil cytoplasmic antibodies (pANCA) which are “defined autoantibodies”
standard error. A second possible
according to the scoring system (+2 points) were taken into account in the study by van Buuren et al. but not
reason
for the conflicting
con-
clusions of these two studies is that the diagnostic criteria were different. In the study by van Buuren et al., diagnosis was mainly based on conventional descriptive criteria. They obtained essentially the same results (definite AIH) by applying the modified scoring system, but detailed scores for each parameter were not given. In the study by Kaya et al., diagnosis was made exclusively by using the scoring system. At first glance both groups seem to have applied the same diagnostic criteria, at least in part. However, important issues relevant to the use of the scoring system should be underlined. First, in the literature dealing with the PSC-AIH overlap syndrome, the reader may be confused by the different versions of the so-called AIH scoring system: the 1993 and 1999 versions developed by the International AIH Group (1,2), but also “adapted” scoring systems with slight differences (8). As shown in Table 1, prevalence of overlap syndrome is strongly dependent on the version of the scoring system, ranging from 7.6% to 53.8%. The initial scoring system was modified to improve specificity. As a consequence, in most of the studies, the prevalence of “definite” AIH is the same with both scoring systems, but that of “probable” AIH is much lower (around l/3) using the modified system (7,9). Second, as discussed in the Mayo Clinic’s study, the 1999 scoring system was published using two different categories: one with a set of parameters for diagnosis of AIH and the other with “optimal additional parameters” (seropositivity for other defined autoantibodies, HLA DR3 or DRII, and response to therapy).
1
TABLE
Prevalence of autoimmune ing cholangitis according Study
Boberg (92)
et al.
hepatitis in patients with primary to the different scoring systems
Scoring system version
Number of patients
1993 1999
114
Percent scoring
scleros-
as
Definite AIH
Probable AIH
Overall AIH
1.8’%, 1X%,
33.3’!/;> 8.Wi
35.1% 10.6%
NA
NA
53.8%
Czaja (4)
adapted 1993
Kaya et al. (7)
1993 1999
211
1.9% 1.4%
I 9 .O%, 6.2’!/;>
20.9% 7.6’%1
van Bum-en et al. (6)
1993 1999
113
7.1% 7. I ‘%I
15.9% 12.4”/1,
23’!i, 19.5%
662
26
in the study from the Mayo Clinic. Third, because of the high number of scoring parameters, missing data are frequent, at least in retrospective studies. For example, only 55% of the patients from the Mayo Clinic were tested for anti-smooth muscle antibodies (ASMA). In some cases it may be hypothesized that the screening omissions could alter the results of the scoring system. Fourth, even with detailed explanatory notes for use of the scoring system, there is still room for interpretation. Indeed, points (+3) for the concurrence of inflammatory bowel disease (IBD) as an associated autoimmune disease were not allowed in the present study from the Mayo Clinic, whereas presence of IBD was taken into account in previous studies from the same institution (4,8). Last but not least, is it relevant to use the scoring system for defining cholestatic diseases ~ AIH overlap syndromes? According to the members of the International AIH group, it is yet to be determined (2). It should be remembered that the scoring system is intended mainly for research purposes. The score is also clearly useful in clinical practice for difficult cases of patients with unexplained hepatitic illness. Whether it makes sense to apply it in otherwise obvious PSC or PBC is more questionable. In spite of the drawbacks discussed above, the potential advantages of a scoring system over a clinical definition are its apparent consistency and objectivity since it is supposed to ensure uniformity of assessment and diagnosis. An excellent sensitivity (>95’%) has been demonstrated for diagnosis of pure AIH (2). However, the scoring system is tailored on the assumption that none (or only very few) of the patients with chronic cholestatic diseases also have concomitant AIH. Indeed, the International AIH group repeatedly stated that biliary lesions either preclude the diagnosis of AIH using descriptive criteria or have a strongly negative impact using the scoring system. Because of a high number of “probable” AIH using the original score in PSC patients. adjustments were made to improve specificity by increasing the weighting against biliary diseases. As expected, the prevalence of overlap syndromes fell dramatically using the revised system. In this setting, the scoring system can only identify the few patients with caricatural overlap seen as the coincidence of 2 distinct diseases. However, it may also be hypothesized that PSC (or PBC) and AIH are the ex-
Diagnosis of primary sclerosing cholangitis
treme points of autoimmune liver disease spectrum with a continuum from one disease to the other, and the scoring system would clearly underdiagnose mild forms of overlap. Finally and beyond this academic debate on classification and pathogenesis, is it really important to identify patients with PSC-AIH overlap syndrome? The answer is unambiguously yes. Effective medical therapy is not yet available for PSC but this disease is notably heterogeneous with respect to its presentation, severity and outcome. Thus it is crucial to define relatively homogeneous groups of patients with features that might be useful for assessing prognosis and planning treatment strategies. In this regard the excellent therapeutic response to immunosuppressants, in particular of the AIH-component of the overlap syndrome, as shown in different studies including that by van Buuren et al. (5,6,10), has to be underscored. Proper therapy may indeed be life-saving. Therefore, for the clinician taking care of patients with PSC, the main issue is to recognize, using simple tools, patients with “significant” overlap, in other words patients who may benefit from immunosuppressive therapy. Are the major descriptive positive criteria of AIH, i.e. presence of ASMA or interface hepatitis, relevant in this regard? Lessons can probably be drawn from the experience with PBC. Presence of ASMA or antinuclear antibodies (ANA) in AMA-positive PBC does not necessarily indicate overlap requiring a different therapy and patients with AMA-negative PBC who test ANA/ ASMA positive do not have an overlap with AIH, but rather are just AMA-negative PBC with a fair response to ursodeoxycholic acid (UDCA) (11). Presence of interface hepatitis of moderate or severe activity, a key feature of AIH, seems to be a more promising track. Indeed, it has been shown that the degree of severity of lymphocytic piecemeal necrosis and lobular inflammation in the first biopsy specimen was highly related (~KO.001) to the progression of fibrosis and development of cirrhosis in PBC patients treated with UDCA (12). This suggests that PBC patients having severe lymphocytic piecemeal necrosis and lobular inflammation (“occult” overlap) may constitute a subset of patients, in whom combination of UDCA and corticosteroids is needed to prevent disease progression (13). However, prevalence of interface hepatitis in PSC patients remains to be carefully determined (only 8% in the present study from the Mayo Clinic) and ideally, well-designed randomized trials should assess the efficacy and tolerance of immunosuppressive drugs in this subset of patients. To date, only identification of variant forms of PSC (14), including PSC-AIH overlap syndrome, has
received some degree of general acceptance. Because we have a desperate need for effective therapy, subclassification of a heterogeneous disorder such as PSC can facilitate clinical management. It is my opinion that the AIH scoring system should be interpreted with caution in routine practice despite its apparent objectivity and the “magic” power of a cut-off value. As recently underscored, a collaborative effort among multiple centers is clearly needed to develop standardized diagnostic criteria and to initiate studies of the pathogenic mechanisms, natural history and treatment of this form of autoimmune liver disease (15). In the meantime, you can score but please, don’t forget to talk to your liver pathologist!
References 1. Johnson PJ, McFarlane IG. Meeting report: International Autoimmune Hepatitis Group. Hepatology 1993; 18: 9981005. 2. Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, et al. International autoimmune hepatitis group report: review of criteria for diagnosis of autoimmune hepatitis. J. Hepato1 1999; 31: 929-38. 3. Chazouilltres 0, Wendum D, Serfaty L, Montembault S, Rosmorduc 0, Poupon R. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatology 1998; 28: 296301. 4. Czaja AJ. Frequency and nature of the variant syndromes of autoimmune liver disease. Hepatology 1998; 28: 360-5. 5. Mieli-Vergani G. Autoimmune sclerosing cholangitis: a distinct clinical entitv? J Henatol 2000; 32 (Suppl.2). 7-8 6. van Buuren HR, van Hoogstraten IIJe Terkivatan T, Schalm SW, Vleggaar FP High prevalence of autoimmune hepatitis among patients with primary sclerosing cholangitis. J Hepatol 2000; 33: 543-8. 7. Kaya M, Angulo P, Lindor KD. Overlap of autoimmune hepatitis and primary sclerosing cholangitis: an evaluation of a modified scoring system. J Hepatol 2000; 33: 53742. HA. Validation of scoring system for diag8. Czaja AJ, Carpenter nosis of autoimmune hepatitis. Dig Dis Sci 1996; 41: 305-14. 9. Boberg KM, Fausa 0, Haaland T, Holter E, Mellbye OJ, Spurkland A, et al. Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis. Hepatology 1996; 23: 1369-76. E, 10. Gohlke F, Lohse AW, Dienes HP, Lohr H, Marker-Hermann Gerken G, et al. Evidence for an overlap syndrome of autoimmune hepatitis and primary sclerosing cholangitis. J Hepatol 1996; 24: 699-705. 11. Michieletti P, Wanless IR, Katz A, Scheuer PJ, Yeaman SJ, Bassendine MF, et al. Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis. Gut 1994; 35: 260--5. 12. Degott C, Zafrani ES, Callard P, Balkau B, Poupon RE, Poupon R. Histopathological study of primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment on histology progression Hepatology 1999; 20: 1007712. of primary biliary cirrhosis resistant to 13 Poupon R. Management ursodeoxycholic acid therapy. J Hepatol 2000; 32(Supp1.2): 1920. 14. Chazouilltres 0. The variant forms of cholestatic diseases involving small bile ducts in adults. J Hepatol 2000; 32(Supp1.2): 16 18. 15. Czaja AJ, Manns MP, McFarlane IG, Hoofnagle JH. Autoimmune hepatitis: the investigational and clinical challenges. Hepatology 2000; 31: 1194200.
663