Home Archive Vol 36, No.2, 2010 Original papers Semiquantitative Methods of Assesment of Severity in Viral Hepatitis C

Semiquantitative Methods of Assesment of Severity in Viral Hepatitis C


(1) Sport and Physical Education Faculty, University of Craiova; (2) Laboratory of Pathology, Emergency County Hospital Craiova; (3) Department of Pathology, University of Medicine and Pharmacy of Craiova

ABSTRACT The aim of this study was to investigate 402 liver biopsies from patients with serologically confirmed chronic viral hepatitis C. We investigated histopathological aspects of this lesions, regarding the intralobularly and portal necroinflammatory activity (HAI score) and fibosis (Meavir score) which can  help to decrease variability of the assessment of results.

KEY WORDS Viral Hepatitis C, 


Chronic hepatitis is defined as a clinical-pathological syndrome with multiple etiology, with varying degrees of hepatocellular necrosis and inflammation and progression to fibrosis. It is definedas persistence of the clinical, laboratory and histological changes, without improvement, for at least 6 months.

Liver biopsy is a fundamentally important procedure in assessing acute and chronic   liver pathology. In 1981, Knodell et al propose a objective and reproducible numerical score for the asymptomatic chronic hepatitis. This system can be considered one of the first attempts at standardization of liver bipsies and marked the transition to a new classification of chronic viral hepatitis (5).

Material and method

Our study included 402 liver biopsies from patients with serologically confirmed chronic viral hepatitis C. Liver tissue fragments were processed according to standard histology protocol: they were fixed in formalin 10%, embedded in paraffin, sectioned at 5 microns and stained hematoxylin-eosine and Van Gieson.


Activity score:

A0 = no activity

A1 = mild activity

A2 = moderate activity

A3 = severe activity

Fibrosis score:

F0 = no fibrosis

F1 = portal fibrosis without septa

F2 = portal fibrosis with few septa

F3 = numerous septa without cirrhosis

F4 = cirrhosis

The scoring systems used Histologic Activity Index (HAI) described by Knodell and modified by Ishak (4) which quantifies the necroinflammatory activity between 0 and 18 and fibrosis from 0 to 6, and Metavir score. The Metavir score, described especially for patients with chronic hepatitis C, grading represents the activity level or amount of inflammatory infiltrate, and is rated from 0 to 3, and stage represents  the amount of fibrosis, rated from 0 to 4 (1).

Results and discussions

Within the studygroup of patients, age ranged between 22 and 68 years (mean = 49.18 years) and females were more frequently affected (F:M = 2,16:1). Most cases ranged between 51 and 60 years - 181 Cases.

Using HAI and Metavir scores the 402 liver biopsies of patients with C virus infection were distributed as follows:

- 148 cases were minimally active chronic hepatitis;

- 178 cases were moderately active chronic hepatitis,

- 47 cases with severe chronic active hepatitis;

- cases 29 with cirrhosis.

The distribution of cases with chronic hepatitis C according to lesions described by HAI and Metavir scoring systems is shown in table.

Table 1. The distribution of cases with chronic hepatitis C according to severity

Type of hepatitis




Minimally active chronic hepatitis

51 cases

97 cases

148 cases

Moderately active chronic hepatitis

56 cases

122 cases

178 cases

Severe chronic active hepatitis

11 cases

35 cases

46 cases


11 cases

19 cases

30 cases


128 cases

274 cases

402 cases

Minimal active chronic hepatitis was present in 148 cases, representing 36.81% of the 402 hepatitis C cases; 97 cases belonged to females and extreme ages were represented by 28 and 63 years and were women.

Histological interpretation of the 148 liver biopsies showed a HAI score between 2 and 9, grading ranging between 1 and 6, and stage between 0 and 3.

Piecemeal necrosis  was present only in some portal tracts, or in 97 cases, in one segment of the perimeter of the portal tract. Intralobulare changes were minimal and consisted of small foci of hepatocyte necrosis with reduced inflammatory reaction. Fibrosis was present only in the portal tracts.

Figure 1: Intralobular inflammation with the presence of small foci of necrosis and steatosis, HE stain, 200x

Liver changes seen as Metavir score were:

- A1 - absent or mild necroinflammatory activity (at least one focus per lobe of necroinflammation, piecemeal necrosis absent or altered periportal plate, inflammation only in some portal tracts,  steatosis 10% of hepatocytes);

- F0, F1, F2 or F3 - absent or portal fibrosis without septa or portal with rare septa.

Figure 2: Minimally active chronic hepatitis A1F1. Dilated sinusoids, Gordon Szekely stain, 100x

Metavir score of lesions of minimally active chronic hepatitis is shown in table 2.

Table  2. Grading and staging of minimally active chronic hepatitis C cases according to Metavir score


No cases









Moderately active chronic hepatitis was present in 178 cases, representing 44.27% of the 402 cases. Female gender was dominant with 122 cases, and patients were aged between 27 and 64 years.

Moderately active chronic hepatitis was characterized by dense portal and periportal inflammation and extensive piecemeal necrosis, affecting 50% of the circumference of almost all the portal tracts, and lobular necrosis and inflammation were significant, with damage of 1/3-2/3 the lobe. The liver parenchyma showed moderate lymphocytic infiltrate in the portal tracts and portal fibrosis. Intralobular moderate inflammatory infiltrate was present.

Figure 3: Moderately active chronic hepatitis A2F2,  HE stain, 100x

Table 3. Grading and staging of moderately active chronic hepatitis C cases according to Metavir score


No cases







HAI score was between 9 and 15 (grading: 7-9 and staging: 2-5) and the Metavir score was A2 and F1, F2 or F3:

- A2 - piecemeal necrosis around all portal tracts, several inflammatory necrotic foci or diffuse alteration of the periportal plate in all portal tracts;

- F1, 2 or 3 - portal fibrosis without septa or portal fibrosis with rare or many septa.

Severe chronic active hepatitis was present in 46 cases, representing 11.44% of all cases in our study. Like in the other subtypes there was a female predominance - 35 cases. HAI score ranged between 12 and 20 (grade: 10-15, stage: 2-5) and Metavir score was A3 F2 or A3F3 and presented the following histological changes:

- A3 - piecemeal necrosis around all portal tracts and several necroinflammatory  foci or diffuse alteration  of the periportal plate in all portal tracts;

- F2 or 3 - portal fibrosis with rare or many septa

Table 4.  Grading and staging of severe active chronic hepatitis C cases according to Metavir score


Număr cases





Cases were characterized by piecemeal necrosis in almost all periportal circumferences and along the fibrous septa. Bridging necrosis was masked by porto-portal fibrous septa. Passive septa are the result of collapse due to confluent necrosis and coexist with active septa.  The lobular alteration interested over 2/3 of lobules.

Figure 4: Severe active chronic hepatitis A3F3, HE stain, 100x

Arhitectural alterations due to fibrosis characterised the presence of cirrhosis ( 30 cases) and they were accompanied by different grades of activity. In 3 cases there was an important necroinflammatory activity. In all cases the lobular arhitecture was erased with the formation of nodules surrounded by fibrosis.


Table 5. Grading and staging of cases of cirrhosis according to Metavir score

Scor Metavir

Număr cases







Figure 5: Cirrhosis A2F4, VG stain, 40x

Because chronic hepatitis have a variety of progressive clinical pictures, there was a  need for their classification which would help establish a proper diagnosis.

The initial 1960 classification (chronic persistent hepatitis, chronic active hepatitis - moderate and severe - cirrhosis) has become an inadequate tool since the identification of etiological factors. Thus, in 1994 this classification was replaced by a predominant etiological classification supplemented by the use of scores (3).

Currently scores are used to evaluate liver biopsies before treatment, monitoring treatment and evaluation of effects in clinical trials for new therapies (7).

In the investigation of histological sections two components were followed:

- Grade - scoring of the necroinflammatory lesions including different types and degrees of hepatocellular damage and the location and extension of the inflammatory process.

- Stage - extension of fibrosis and structural changes, inluding the development of cirrhosis.

Scoring is a semiquantitative method because although the results are expressed in numbers, they don’t represent measurements,  and these figures can not be used for statistical analysis (2). In the medical literature various proposals have emerged for the classification of necroinflammatory activity and extension of fibrosis, which creates difficulties in comparing results.

In our study we used the modified HAI score, considered to be useful in evaluating patients with inflammatory liver disease. Description and quantification of inflammatory activity of liver diseases is an important step in diagnosis, especially for determining appropriate therapy (6).

With the use of HAI, critical comments have appeared, the most important being the fact that necroinflammatory activity and fibrosis are two distinct processes, which do not always evolve in parallel and need to be evaluated separately, thus calculating a score for grading (intensity of necroinflammation) and one for staging (fibrosis extension).


In our study we used both scores (HAI and Metavir) for the evaluation of all cases. We also  specified, when using the HAI score, the contribution of each component in the total score, as this helps to decrease variability of the assessment of results.

Given the importance of semiquantitative scoring of chronic viral hepatitis especially for therapeutic application protocol, this is an ongoing concern of specialists in liver disease.


1.     Bedossa P, Poynard T, The METAVIR Cooperative Study Group, An alogrithm for the grading of activity in chronic hepatitis C. Hepatology 1996; 24:289-93.

2.     Cross SS, Grading and scoring in histopathology. Histopathology 1998; 33:99-106.

3.     International Working Party. Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party supported by the World Congresses of Gastroeneterology, Los Angeles 1994, Am J Gastroenterol 1994; 89:S177-S181.

4.     Ishak KG, Baptista A, Bianchi L, et al., Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 66-9.

5.     Knodell RG et al.; Formulation and application of a numerical scoring system for assessing histological activity in asymtomatic chronic active hepatitis. Hepatology 1981, 1:431.

6.     Miyuki Nakaji, Yoshitake Hayashi, Toshiaki Ninomiya et al., Histological grading and staging in chronic hepatitis: Its practical correlation, Pathology International 2002, 52(11): 683-90.

7.     Scheuer P, Lefkowitch JH, Liver Biopsy Interpretation. 6th ed. London: WB Saunders; 2000, p:161-2.



Correspondence Adress: Ana Maria Kese, PhD candidate, Sport and Physical Education Faculty, University of CraiovaDolj, Romania e-mail anamakese@yahoo.com,

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