Original Contribution
Number of portal tract macrophages correlates with the modified hepatic activity index in chronic hepatitis C infection

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Abstract

The Ishak modified hepatic activity index (mHAI) is widely used to score disease activity in chronic hepatitis C infection. However, the scoring of the mHAI components is subjective and prone to interobserver variation. Liver injury results in increased numbers of portal tract macrophages, which are easily identified via periodic acid–Schiff with diastase digestion stain. Evaluation of 30 liver biopsies from patients with chronic hepatitis C revealed increasing numbers of portal tract macrophages as scores of liver inflammation increased. Specifically, the number of PASD-positive portal tract macrophages per centimeter of biopsy length correlated with the level of portal inflammation and total mHAI score, and these correlations were statistically significant (P = .039 and .029, respectively). Although the portal macrophage count appeared to correlate with the interface activity and lobular necroinflammatory score, this did not meet statistical significance (P = .073 and .079, respectively). Interobserver agreement by κ analysis was greater for the portal macrophage count than for any individual component of the mHAI score. In summary, the number of periportal ceroid-laden macrophages correlates with liver inflammation as measured using the mHAI, with better interobserver agreement. This technique may serve as a useful adjunct to the mHAI in the assessment of liver injury in hepatitis C.

Introduction

Chronic hepatitis C infection is a common disease in the United States, with an estimated 3.2 million chronically infected people [1]. The long-term sequelae of this disease include progressive hepatic fibrosis, which ultimately leads to cirrhosis. In fact, hepatitis C virus (HCV)–related cirrhosis is one of the most common causes of liver failure leading to transplantation in the United States [2].

Liver biopsies are used not only to initially assess the degree of liver inflammation and fibrosis but also to follow the progression of liver damage in chronic disease and to determine the appropriateness of antiviral therapy [3]. A number of different scoring systems have been used in the past, including the Ishak modified hepatic activity index (mHAI) [4]. This grading scheme is widely used to score disease activity in chronic hepatitis C infection. However, the scoring of the mHAI components is subjective and is prone to interobserver variation [5].

Injury to the liver parenchyma has been shown to result in increased numbers of portal tract macrophages [6], [7], which are easily identified via periodic acid–Schiff with diastase digestion (PASD) stain of the liver. We hypothesized that the number of PASD-positive portal tract macrophages is related to the mHAI in chronic hepatitis C infection and that this score may provide a quantitative and more reproducible measure of disease activity when compared with the traditional Ishak scoring system.

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Materials and methods

Thirty consecutive needle core liver biopsies performed in 2005 on patients with chronic hepatitis C infection were retrieved, including hematoxylin and eosin, PASD, and trichrome-stained slides. Patients with concurrent human immunodeficiency virus infection or clinical suspicion of autoimmune hepatitis, alcoholism, or non–alcoholic fatty liver disease (NAFLD) were excluded from evaluation.

The 30 biopsies were independently reviewed by 2 pathologists and scored using the mHAI system, and the

Results

Portal tract macrophages containing PASD-positive pigment were identified in all liver biopsies examined, with an increased number in biopsies with increased portal inflammation (Fig. 1). The number of portal tract PASD-positive macrophages per centimeter of biopsy length was found to be associated with the level of portal inflammation (P = .039) and total summed mHAI score (P = .029) (Fig. 2A, D). The number of portal tract PASD macrophages appeared to be related to the level of interface

Discussion

A number of grading schemes have been used to attempt to quantify the amount of acute and chronic liver damage in hepatitis C infection. These grading systems typically use variables that are semiquantitative in nature. As such, the interobserver variability in scoring is generally poor [8]. This includes the Ishak scoring system used in this experiment [5], [9]. κ Values for the mHAI in published work have reached only as high as 0.69, but only when deviance of one categorical level for each

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