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GASTROENTEROLOGY 1993;105:274-278

SPECIAL REPORTS AND REVIEWS

The Nomenclature of Chronic Active Hepatitis: An Obituary

JURGEN LUDWIG
Division of Anatomic Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota

Use of the terms chronic active hepatitis, chronic per- graph by M. Schmid in 19668 and an article by Dr.
sistent hepatitis, and chronic lobular hepatitis should Summer&ill’s group at Mayo in 1968” summarized the
be discontinued in favor of an etiologic terminology. state of affairs during that time. An international
Inflammatory activity and necrosis should be evalu- group of liver experts, including Dr. Schmid and the
ated to grade the severity of the process whereas the
late Hans Popper, published a classification of chronic
degree of fibrosis should be used to determine the
hepatitis,” which established the nomenclature for
stage of the disease. Working groups and consensus
two decades. The group again distinguished between
meetings are needed to establish a widely acceptable
current nomenclature and terminology. Once this has CAH and CPH as two separate disorders. These terms
been achieved, introduction of the new names will de- were destined to dominate the field for a quarter of a
pend on the support of the committees that compile century, with the name chronic lobular hepatitis
coding manuals and on reviewers and editors of medi- (CLH)” running a distant third. Only the term
cal journals. chronic active liver disease competed successfully for
another decade, l2 being used for both chronic active

A
viral and nonviral hepatitis.
nomenclature is a system of names used in a
scientific specialty, and a terminology is a collec- Emerging Controversies
tive name for the vocabulary used in such a field of
Originally, CPH and CAH had been defined in
science. In the case of chronic active hepatitis (CAH),
their appropriate clinical context-that is, by clinical
the nomenclature evolved foremost from observations
symptoms, laboratory abnormalities, a minimal dura-
that had been made in Germany during and after
tion of 6 months,13 as well as histology. Unfortunately,
World War II. Many soldiers who had had acute epi-
undue emphasis on morphology, in particular the pres-
sodes of jaundice, mostly during service in the former
ence or absence of piecemeal necrosis, shifted the
Soviet Union, returned with symptoms of persistent or
meaning of these names; they became biopsy diag-
recurrent liver disease. Thus, the concept of chronic
noses. Although that change has never been supported
viral hepatitis emerged.’ During the next decade, the
by an ad hoc committee, panel, or conference, it is now
fifties, a mild, nonprogressive variant of chronic viral
widely implemented. Dr. Popper, among others, recog-
hepatitis was recognized. This condition was named
nized this dilemma and proposed the use of purely
persistent hepatitis2 and later chronic persistent hepati-
morphological designations, such as periportal hepati-
tis (CPH) although for some time such cases had been
tis, to clearly distinguish between clinical disease and
considered residual hepatitis without a specific name.3
biopsy finding.“*14 Unfortunately, this approach never
The term chronic active hepatitis also was coined at
became popular among clinicians and CAH continues
that time.4 It emerged in the context of “lupoid hepati-
to be defined, in practice, by its main morphological
tis,” which became popular as a new entity in 1956’
feature, periportal inflammation with piecemeal or
although the first descriptions of that condition had
bridging necrosis. This led to the otherwise unexplain-
been published as early as 19506 and 1951.’ After it
able expansion of the list of diseases said to be capable
became clear that lupoid hepatitis had nothing to do
of causing CAH. To quote from a recent abstract dis-
with systemic lupus erythematosus, multiple syn-
cussing autoimmune hepatitis,15 “CAH is a morpho-
onyms were introduced, including chronic aggressive
hepatitis, subacute hepatitis, juvenile cirrhosis,
Abbreviations used in thispaper: CM-I, chronic lobular hepatitis;
chronic plasma cell hepatitis, and chronic active liver
CPH, chronic persistent hepatitis; PBC, primary biliary cirrhosis.
disease. Both viral infections and autoimmunity were 0 1993 by the American Gastroenterologlcal Association
considered important etiological factors. A mono- 0016-5085/93/$3.00
July 1993 NOMENCLATURE OF CAH 275

logical lesion that is seen in a number of other liver Table 1. Current Etiological Nomenclature of Chronic
Hepatitis
disorders, notably acute hepatitis A, chronic hepatitis
B, primary biliary cirrhosis, primary sclerosing cho- Chronic hepatitis (CH)
Viral (CH-B, B + D, C, or type of virus unknown)
langitis, alcohol- and drug-induced liver damage, and
Autoimmune
Wilson’s disease.” This list, with a few additions and Unclassified as to viral or autoimmune etiology
deletions, now burdens all leading textbooks; it is Drug induced (and alcoholic?)
based solely on the superficial histological resem- Biliary
Genetic
blances imparted by piecemeal necrosis, without re-
Wilson’s disease
gard to etiology or obvious morphological differences, a,-antitrypsin deficiency
such as the periodic acid Schiff stain-positive globules
in a-l-antitrypsin deficiency or copper deposition in
Wilson’s disease. (see also reference 15); the proceedings of the panel
For the name CPH, the same criticism applies as for have not yet been published], on the grounds that the
CAH although in practice CPH is rarely used to de- condition is not always active and that it is, a priori,
scribe conditions other than chronic viral hepatitis chronic. This is a valid argument but, if implemented,
and autoimmune hepatitis. However, even with this it would have far-reaching consequences because the
confinement, the designation has lost its usefulness’6 reasoning also should then be applied to conditions
because only CPH-B often (but not always) has the such as chronic hepatitis of Wilson’s disease and
implied good prognosis whereas the features of CPH-C chronic nonsuppurative destructive cholangitis of pri-
provide no assurance against progressive disease. In mary biliary cirrhosis (PBC). If this is done, paramedi-
addition, chronic hepatitis C often causes biopsy cal personnel with coding responsibilities probably
changes that are somewhere between the classic fea- would experience difficulties. For instance, they would
tures of CPH and CAH. Finally, in patients with have to know that autoimmune hepatitis is a chronic
treated autoimmune hepatitis,17 the usefulness of the hepatitis (SNOMED M43, ICD-9-CM 571.49) because
term CPH is as limited as in CPH-C. “chronic” is no longer part of the name.
Despite the above-mentioned reservations, the
Options for an Updated
name “autoimmune hepatitis” may be here to stay, and
Nomenclature with this anticipation, another option for an updated
A recommended nomenclature of diseases nomenclature for chronic hepatitis is shown in Table
should fulfill the following criteria: (1) Etiological des- 2. In this table, the adjective “chronic” is deleted as in
ignations should be used. If the etiology is unknown, autoimmune hepatitis except for diseases that also may
well-defined names should be selected. For instance, in have an acute, self-limited course. Thus, the suggestion
a terminology of cirrhosis, the name cryptogenic cir- to delete “chronic” was applied to all conditions
rhosis is acceptable but the term portal cirrhosis is where that change can be justified. The terms CAH,
not.‘* (2) The compilation should be internally logical, CPH, and CLH no longer appear among the disease
and for the use of all qualifiers, such as the adjective names although they still are listed for optional use as
“chronic,” the same rules and criteria should be ap- designations for inflammatory activity. Unclassified
plied. (3) Terms should be reasonably close to widely and mixed forms of chronic hepatitis must be consid-
used traditional names so that they are readily ac- ered in any new nomenclature and, therefore, the table
cepted. Unfortunately, criteria no. 2 and no. 3 are not shows these entries. For instance, patients with HCV
always reconcilable. (4) Terms should be Systemized antibodies also may have features of autoimmune hepa-
Nomenclature of Medicine (SNOMED) and Interna- titis or they may have a history of alcoholism. Chronic
tional Classification of Diseases (ICD) codable’” and drug hepatitis is included although the condition is
compiled in an hierarchic order. An example for a becoming quite rare.”
nomenclature that is based on these criteria is shown Autoimmune hepatitis has several subtypes based on
in Table 1. In that scheme, the term chronic hepatitis patterns of autoantibodies and clinical features; these
is used as a collective name, followed by the etiological subtypes have not been included here because a defi-
designation. Unfortunately, current practice may nite classification based on immunoserology has not
render this nomenclature obsolete because the term evolved. Nevertheless, definite autoimmune hepatitis
autoimmune CAH is being replaced by the name au- generally can be distinguished from probable manifes-
toimmune hepatitis [the recommendation was made tations of the disease or mixed forms (i.e., in some
by The International Autoimmune Hepatitis Group patients with chronic ulcerative colitis and primary
276 JURGEN LUDWIG GASTROENTEROLOGY Vol. 105. No. 1

Table 2. Option for an Updated Terminology of Chronic Hepatitis

Grade of inflammatory activitya Stage/degree of fibrosis”

Etiological designations Grade Portal Lobular Stage Degree of fibrosis


Chronic hepatitis 0 None or minimal None 1 No fibrosis or fibrosis confined
Chronic hepatitis B 1 Portal inflammation Inflammation but to enlarged portal tracts
Chronic hepatitis B and D (CPH) no necrosis 2 Periportal fibrosis or portal-to-
Chronic hepatitis C 2 Mild limiting plate Focal necrosis or portal septa but intact
Chronic viral hepatitis, type necrosis (mild acidophilic architecture
unspecified CAH) bodies 3 Septal fibrosis with
Chronic hepatitis, unclassified as to 3 Moderate limiting Severe focal cell architectural distortion; no
viral or autoimmune etiology plate necrosis damage obvious cirrhosis
(cryptogenic chronic hepatitis) (moderate CAH) 4 Probable or definite cirrhosis
Chronic hepatitis, mixed forms 4 Severe limiting Damage
Chronic drug hepatitis plate necrosis includes
Autoimmune hepatitis (severe CAH) bridging
PBC
Autoimmune cholangitis
PSC hepatitis (hepatitis associated
with PSC)
Wilson’s hepatitis (hepatitis
associated with Wilson’s
disease)
a- 1-antitrypsin deficiency hepatitis
(hepatitis associated with a- l-
antitrypsin deficiency)

NOTE. The adjective “chronic” is only used for conditions that also occur in an acute, self-limited form. Except for chronic viral hepatitis, the list
with etiological designations is not hierarchic and other conditions could be readily added.
PSC, primary sclerosing cholangitis.
‘Modified after Scheuer, 199 1. Under grade of inflammatory activity, grades 0 or 1 for portal activity and 2,3, or 4 for lobular activity correspond to
the current category of CLH. If portal and lobular changes do not correspond, the grade generally should be determined by the more severe lesion.
To distinguish stages 2 and 3 reliably, agreement on threshold criteria for “architectural distortion” must be achieved.

sclerosing cholangitis). *’ In this context, most cases of popular. Scheuer26 rightfully criticized that the index
probable autoimmune hepatitis would be placed in the “combined necroinflammatory activity with the ef-
“definite” category if they responded to steroids. fects of such activity, that is to say fibrosis, architec-
Autoimmune cholangitis, ” PBC, and primary scle- tural distortion and cirrhosis.” In other words, it com-
rosing cholangitis are included in Table 2 because bines grading with staging. Scheuer, therefore,
these conditions are both chronic hepatitic and biliary separated these two features again and in Table 2, this
diseases. This has been recognized by previous panels is reproduced with only a few modifications. As
concerned with the nomenclature of liver diseases.*’ shown, the names CAH, CPH, and CLH still could be
Indeed, to distinguish between these chronic biliary used as acceptable synonyms to indicate a degree of
and nonbiliary diseases may be difficult.23 As is the activity in an etiologically defined condition. For in-
custom, a-l-antitrypsin deficiency is on the list, but stance, the term CAH-B might remain acceptable as a
whether this is a complete etiological designation is synonym for chronic hepatitis B, moderate to severe
not quite clear; coinfection with a hepatitis virus (stage not indicated), and CPH-C would correspond to
might be required before chronic hepatitis can de- chronic hepatitis C, mild (stage 1). However, one
velop.24 would hope that these synonyms eventually will fall
into disuse.
Gradlng, Staging, and Evolving
Nomenclatures Where Do We Go From Here?
In current practice, etiological diagnoses alone The need for working groups and consensus
do not suffice because disease activity and stage also are meetings is obvious. However, care must be taken that
important, and questions in this regard, not etiological the efforts are coordinated. For instance, terms and
considerations, are commonly the indications for definitions that might be proposed by a committee of
biopsy. Among the grading schemes, the histological the American Association for the Study of Liver Dis-
activity index proposed by Knodell et a1.,25 is the most eases should agree with the recommendations of the
July 1993 NOMENCLATURE OF CAH 277

international working group on autoimmune hepati- severe chronic viral hepatitis and for Wilson’s disease).
tis.i5 The International Association for the Study of Finally, (4) the prognosis of CPH - once considered to
Liver Diseases and the World Health Organization be good in most cases-differs considerably, depend-
probably should be involved as well as the committees ing on etiology. Therefore, in the future, an etiological
concerned with SNOMED and ICD coding SO that terminology should be agreed on, supplemented by in-
recommendations can be incorporated into future dicators of inflammatory activity (grade) and stage.
coding manuals. Another Fogarty conference on stan- Also, such a new terminology should be internally
dardization of hepatobiliary nomenclature also could consistent-that is, the same rules should apply to all
be organized. 26 The 1994 World Congress of Gastroen- names (e.g., in respect to the use of the adjective
terology in Los Angeles will be another suitable “chronic”). Names could be reasonably close to cus-
forum. Finally, the editorial boards of major journals tomary usage but should reflect our current knowledge
in gastroenterology and hepatology could decisively of chronic hepatitis. The terms CAH, CPH, and CLH
promulgate the advances in terminology and nomen- still may be meaningful but only if used in conjunction
clature. Indeed, manuscript reviewers and journal edi- with etiological designations. Eventually, however,
tors could be the most effective supporters in this re- this practice should cease. With these goals in mind,
gard. Current publications clearly show the need for a working groups should be formed under the auspices
more active role of editors and reviewers; if multietio- of national and international organizations, including
logical conditions such as postnecrotic cirrhosis or the committees concerned with SNOMED and ICD
Budd-Chiari syndrome are used in juxtaposition to coding. The editorial boards of major journals in gas-
precise etiological designations, such as chronic hepati- troenterology and hepatology could decisively pro-
tis B or Wilson’s disease, communication suffers.‘8,28 mulgate the advances in terminology and nomencla-
However, we must proceed with caution and re- ture.
member that in the United States the metric system is
still considered alien, and the medical community References
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tis: Overlap with primary biliary cirrhosis and primary sclerosing Anatomic Pathology, Mayo Clinic, 200 First Street Southwest, Roch-
cholangitis. In: Czaja AJ, Dickson ER, eds. Chronic Active Hepati- ester, Minnesota 55905.