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The diagnosis and classification of chronic hepatitis has undergone refinement over the past decade. A scoring system is now used to grade and classify cases based upon the degree of portal and lobular inflammatory activity and fibrosis. Previous used classifications and the current designations are listed below.

Previous Term Current Term
Chronic active hepatitis Chronic hepatitis with piecemeal (periportal) necrosis (or interface hepatitis) with or without fibrosis
Chronic persistent hepatitis Chronic hepatitis without piecemeal necrosis (or interface hepatitis)
Chronic lobular hepatitis Chronic hepatitis without piecemeal necrosis (or interface hepatitis)

When the diagnosis of chronic hepatitis is made, a causative agent or cause should be given. The most common causes include the following:

Viral Causes of Hepatitis Hepatitis B, C, D
(A and E not associated with chronic hepatitis)
Nonviral Causes of Hepatitis Drug reaction
Wilson's disease
Alpha-1-antitrypsin deficiency

Under the microscope, the degree of activity for the hepatitis can be graded using the criteria listed below.

Portal and Lobular Inflammatory Activity

Grade Pathology
0 None or minimal portal inflammation
1 Portal inflammation without necrosis and/or lobular inflammation without evidence of necrosis
2 Mild limiting plate necrosis (or mild interface hepatitis) and/or focal lobular necrosis
3 Moderate limiting plate necrosis (or moderate interface hepatitis) and/or severe focal cell necrosis (confluent necrosis)
4 Severe limiting plate necrosis (or severe interface hepatitis) and/or bridging necrosis


Stage Pathology
0 No fibrosis
1 Cofined to enlarged portal zones
2 Periportal or portal-portal septa, with intact architecture
3 Architectural distortion (septal fibrosis, bridging), without obvious cirrhosis
4 Probable or definite cirrhosis

One of the most difficult distinctions for the pathologist is between a mild chronic hepatitis and a resolving acute hepatitis. Helpful microscopic findings are listed below. The pathologist must correlate the clinical history, serologic studies, and biopsy findings to complete the diagnosis.

Histological Findings Mild Chronic Hepatitis Resolving Acute Hepatitis
Portal inflammation +++ +
Lobular inflammation + +
Hepatocyte dropout, lobular ++ +
Hepatocyte dropout, periportal +/- +/-
PAS + Diastase digestion and Kupffer cells +/- +++
Iron and Kupffer cells +/- ++
Persistent centrilobular lesion - ++



Chronic viral hepatitis B and C: an argument against the conventional classification of chronic hepatitis.

Schmid M, Flury R, Buhler H, Havelka J, Grob PJ, Heitz PU.

Department of Pathology, University of Zurich, Switzerland.

Virchows Arch 1994;425(3):221-8 Abstract quote

The classification of chronic hepatitis distinguishing benign chronic persistent hepatitis from severe chronic active hepatitis was constructed without knowledge of well-defined aetiological factors. Better understanding of the different hepatitis-viruses has shed new light on this subject. Chronic viral hepatitis B and C each show typical histological patterns.

The validity of the conventional classification has been evaluated by a comparative study of chronic viral hepatitis B and C. 130 biopsies from 110 patients with chronic hepatitis C (CH-C) proven serologically by antibodies (second generation testing) were compared with 105 biopsies from 73 patients with chronic hepatitis B (CH-B). These were scored semi-quantatively. In CH-C, lymphoid follicles and/or aggregates were found in 88.5%, fatty degeneration in 51%, bile duct lesions in 46.2%, and Mallory body-like material in the hepatocytes in 9.2%. The portal lymphocytic infiltration generally predominated over the necro-inflammatory lesions of the parenchyma. Chronic persistent hepatitis (defined by the presence of portal hepatitis) was present exclusively in CH-C. Chronic lobular hepatitis was found exclusively in CH-B.

We conclude that the histological criteria described for CH-C are highly suggestive of the diagnosis, that the artificial subdivision of chronic hepatitis into CPH and CAH is obsolete and that the histological assessment of chronic hepatitis should consist of a grading of inflammatory activity (minimal, mild, moderate, severe) and staging of fibrosis (extent of distortion of architecture). The final diagnosis should be based on the demonstration of the aetiological agent.

Histologic spectrum of cryptogenic chronic liver disease and comparison with chronic autoimmune and chronic type C hepatitis.

Goldstein NS, Kodali VP, Gordon SC.

Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, MI 48073, USA.

Am J Clin Pathol 1995 Nov;104(5):567-73 Abstract quote

Most histologic studies of cryptogenic chronic liver disease were done before the discovery of hepatitis C, and therefore encompass the histologic spectrum of this disease.

The authors report the histopathologic findings of 18 liver biopsies of presumed cryptogenic chronic liver disease patients and compared them to chronic autoimmune hepatitis and hepatitis C virus biopsies. Severe bridging fibrosis or cirrhosis was present in 55%. Eighty percent of biopsies had minimal necroinflammatory activity including those with cirrhosis; 20% had moderate activity. Histologic distinction from chronic hepatitis C was difficult in the minimally active cryptogenic chronic liver disease biopsies because 20% of biopsies had portal lymphoid follicles and 33% had macrovesicular steatosis. Chronic autoimmune hepatitis had more parenchymal necroinflammatory activity and plasma cells than did either cryptogenic chronic liver disease or chronic hepatitis C biopsies.

These findings suggest that one form of cryptogenic chronic liver disease is a persistent, low grade hepatitis that can progress to cirrhosis despite an innocuous histopathologic appearance. Pathologists should be aware that cryptogenic chronic liver disease biopsies may have minimal histologic abnormalities. These biopsies should not be reported as normal. Such cases require long-term clinical follow-up.

High incidence of hepatitis B infections among chronic hepatitis cases of unknown aetiology.

Chemin I, Zoulim F, Merle P, Arkhis A, Chevallier M, Kay A, Cova L, Chevallier P, Mandrand B, Trepo C.

INSERM U271, Lyon, France.

J Hepatol 2001 Mar;34(3):447-54 Abstract quote

BACKGROUND/AIMS: In approximately 5% of chronic liver disease cases, no aetiology can be identified. We selected sera from 50 patients with chronic hepatitis of unknown aetiology who were enrolled in this follow-up study whose aim is to gain insight into the possible role of viruses and to define potential clinical outcomes.

METHODS: Patients' sera were screened with highly sensitive polymerase chain reaction assays for hepatitis B (HBV), C, D, and G viruses and TT virus. Sera were also retested for antibodies against the core antigen of HBV.

RESULTS: Surprisingly, HBV DNA was detected in both serum and liver in 15/50 (30%) patients. Immunostaining for HBV antigens on biopsies from patients positive for HBV DNA showed HBcAg and/or HBsAg expression at low levels in 9/15 samples. Eleven of the fifteen patients were anti-HBc positive. With one exception, all patients carried HBV genomes at low levels (10(4) copies/ml or less). Histological signs of chronic liver disease were observed in all patients.

CONCLUSION: Unrecognised HBV infections may account for a high proportion of chronic hepatitis cases of unknown aetiology. Improved HBV detection tests, which appear mandatory for the diagnosis and management of non-A non-E hepatitis as well as for improved safety of transfusions and transplantations are needed.



HCV genotype and "silent" HBV coinfection: two main risk factors for a more severe liver disease.

Sagnelli E, Coppola N, Scolastico C, Mogavero AR, Filippini P, Piccinino F.

Institute of Infectious Diseases, Second University of Naples, Naples, Italy.

J Med Virol 2001 Jul;64(3):350-5 Abstract quote

To evaluate whether HCV genotype and a "silent" HBV infection may be related to a more severe clinical presentation of liver disease, 205 anti-HCV/HCV-RNA positive, HBsAg/anti-HBs negative patients with chronic hepatitis (113 males and 92 females; median age 55 years, range 18-77), were studied on presentation at the Liver Unit from January 1993 to December 1997.

Presence of serum anti-HBc, in the absence of HBsAg and anti-HBs, was considered a marker of "silent" HBV infection. Of the 205 patients, 134 had undergone percutaneous liver biopsy. Two main diagnosis groups were established: the mild liver disease group (76 patients), and the severe liver disease group (109 patients); 20 patients who had refused to undergo liver biopsy were not included in the clinical and virological evaluation because the diagnosis was uncertain. The prevalence of severe liver disease was similar in the genotype 1 and non-1 groups (61.3% of 98 patients with genotype 1 and 52.9% of 70 patients with a non-1 genotype). Instead, the 88 patients with "silent" HBV infection showed a higher percentage of severe liver disease than the 97 anti-HBc negative patients (72.7% vs. 46.4%, respectively: P < 0.0005). Of the 88 anti-HBc positive patients, the prevalence of those with severe liver disease was similar in the 32 cases with serum HBV-DNA as detected by PCR and in the 56 HBV-DNA negative (81.2% vs. 67.8%, P = 0.4). The relation between "silent" HBV infection and severe liver disease was observed both in genotype 1 and non-1 infected patients. Nevertheless, the anti-HBc negative patients infected by genotype 1 showed a severe liver disease more frequently than those infected by a non-1 genotype, with a difference that is significant to the statistical analysis (P < 0.05).

The findings suggest that "silent" HBV infection in anti-HCV positive chronic hepatitis enhances the severity of the liver disease. Evidence was also found that in patients without "silent" HBV infection there is a correlation between the presence of HCV genotype 1 and the severity of liver disease.

Mod Pathol 2000;13:679-704.

Commonly Used Terms

PAS stain-Periodic acid Schiff stain. This special stain is strongly positive for glycogen and neutral glycosaminoglycans. Diastase will digest this glycogen.

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Last Updated 10/24/2001

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