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BACKGROUND: Low-vacuum scanning electron microscopy (LVSEM) enables the detailed three-dimensional imaging of archival tissues without special pretreatments. The clinical utility of LVSEM in the assessment of liver diseases has not yet been defined. So, we investigated the utility of LVSEM imaging in morphological assessments of normal and diseased liver tissues, with a focus on reticulin structures. METHODS: Formalin-fixed tissue samples of two normal livers and two hepatocellular carcinomas with background regenerative nodules/areas were stained with platinum blue stain or silver-impregnated using Watanabe’s method and then comparatively observed under LVSEM. We also evaluated the applicability of LVSEM imaging of liver tissues to a quantitative analysis using a digital image analysis technique. RESULTS: Optimal high-resolution images of reticulin structures were obtained using 10-μm-thick silver-impregnated sections. Reticulin fibers were clearly observed to run dendritically around sinusoids in normal livers, and markedly increased in regenerative nodules/areas. Normal reticulin frameworks were lost in hepatocellular carcinoma, leaving a few fragments of reticulin fibers within tumors. Moreover, when a quantitative analysis was applied to these images, we successfully demonstrated a significantly higher reticulin fiber density in regenerative nodules/areas than in the normal liver (P < 0.05). CONCLUSION: We not only obtained detailed three-dimensional images of reticulin structures in various liver tissues by LVSEM combined with silver impregnation but also showed their applicability to a quantitative analysis. The method presented herein may be applied to future studies for the more accurate diagnosis and better classification/risk stratification of various liver diseases.

Chronic active Epstein–Barr virus (CAEBV) infection is a rare disease, mainly affecting children, typically characterized by persistent infectious mononucleosis (IM)-like symptoms. We describe an adult case of CAEBV without IM-like symptoms, which was indistinguishable from autoimmune hepatitis (AIH). A 60-year-old woman with liver damage was diagnosed with AIH (International Diagnostic Score: 16 points). She had been treated with prednisolone for three years; however, her transaminases had never normalized. She was admitted for another liver biopsy due to repeated high fevers and worsening of her liver damage over two months. Her EBV-DNA copy number was 2.9 × 10(4) copies/μg DNA, and EBV-encoded small RNA1-positive lymphocytic infiltration was observed in both the present and previously collected (three years ago) liver tissue samples. This case implies that hepatic involvement in a CAEBV without IM-like symptoms is difficult to distinguish from AIH and may be misdiagnosed. In some steroid resistant AIH cases, evaluating for CAEBV may be valuable.