18

Chronic Hepatitis
Histopathology
SWAN N. THUNG, MICHAEL A. GERBER, and
HANS POPPER

INTRODUCTION

Chronic hepatitis is defined as a group of primary diseases of the liver charac-

terized by hepatocellular damage, inflammation, and fibrosis continuing without
improvement for at least 6 months.1-3 The disease may be attributable to viral
infections, particularly by hepatitis viruses B, B and D, parenteral NANB, drug
reactions, autoimmune processes, alcoholism, genetic diseases, chronic hepatic
allograft rejection, or unknown causes. Hepatitis A and enteric hepatitis NANB
do not cause chronic hepatitis.
The term chronic hepatitis is relatively recent. At the time that the histologic
diagnosis was almost entirely based on autopsy specimens, the process had
usually progressed to cirrhosis. Therefore, such designations as active or decom-
pensated cirrhosis were applied to instances with conspicuous inflammatory
reaction and severe clinical manifestations referable to liver disease. German
hepatologists, under the leadership of H. Kalk, one of the pioneers of laparos-
copy, used the term chronic hepatitis earlier than it was used by Anglo-American
clinicians. In the middle of this century, several factors shifted the emphasis in
nomenclature from cirrhosis to chronic hepatitis. One was the widespread use of
blind liver needle biopsy which visualized earlier stages of the disease in which

SWAN N. THUNG and HANS POPPER • The Lillian and Henry M. Stratton-Hans Popper
Department of Pathology, Mount Sinai School of Medicine of the City University of New York, New
York 10029. MICHAEL A. GERBER· Department of Pathology, Tulane University School
of Medicine, New Orleans, Louisiana 70112.

247
G. Gitnick (ed.), Modern Concepts of Acute and Chronic Hepatitis
© Plenum Publishing Corporation 1989
248 CHAPTER 18

cirrhosis was not yet or just barely visible. The second factor was the growing
application of hepatic tests, particularly of the aminotransferases, which led to
routine diagnosis or at least suspicion of milder degrees of liver injury and
permitted one to follow its evolution prospectively. This was particularly impor-
tant, since the clinical manifestations of milder degrees of chronic hepatitis are
rather nonspecific and mainly fatigability. A third factor was the development of
immunosuppressive therapy, predominantly corticosteroids. This therapy stimu-
lated the attempt to identify conditions in which it was indicated. The resulting,
originally therapeutic, classification is today, almost ironically, still the most
widely used, although the use of immunosuppressive therapy is now greatly
restricted.
The classification of chronic hepatitis is commonly based on morphologic
criteria. Clinical information is often needed for the diagnosis, particularly the
time of onset of the disease, but an accurate diagnosis is usually not possible on
clinical and biochemical grounds alone. Thus, liver biopsy is essential for the
diagnosis, but clinical information and results of biochemical tests must be taken
into account before a final diagnosis is reached.
Two main forms of chronic hepatitis have been widely accepted: (1) chronic
active hepatitis (CAH), also known as chronic aggressive hepatitis and chronic
periportal hepatitis, and (2) chronic persistent hepatitis (CPH) , also known as
chronic portal hepatitis. The major difference between these two forms is the
location of the inflammatory infiltrate. In CPH it is confined to the portal tracts,
whereas in CAH it extends into the periportal parenchyma, usually accompanied
by hepatocellular destruction and by fibrosis. This distinction plays a major role
in diagnosis and management of patients with chronic hepatitis. There are also
important differences between the prognoses for CAH and CPH, particularly
with respect to the development of cirrhosis, which may follow CAH but not
necessarily CPH.

CHRONIC ACTIVE HEPATITIS

Chronic active hepatitis is not a single entity, but rather a morphologic

reaction pattern that may be seen in liver diseases from a variety of causes.
Therefore, the etiologic factor should be specified whenever possible.
The morphologic hallmark of CAH is piecemeal necrosis (Fig. 1). This is
defined as the destruction of liver cells at an interface between parenchyma and
connective tissue together with a predominantly lymphocytic and plasma cell
infiltrate. The characteristic lesion is seen at the edge of portal tracts and septa
where various types of lymphocytes and macrophages, as well as segmented
leukocytes infiltrate the limiting hepatocellular plate. The hepatocytes undergo
gradual destruction by this process of piecemeal necrosis, as indicated by hydro-