Chronic viral hepatitis type B with “ground glass” cells Chapter 2 Viral Hepatitis 1 Chronic viral hepatitis type B with “ground glass” cells Case 2.7

Clinical Presentation 2 Viral Hepatitis 2 Clinical Presentation A 40-year-old man who was known to have chronic hepatitis type B presented to liver clinic with slightly abnormal liver tests. His risk factors included a history of unprotected sex and drug use. Ultrasound showed a fibrotic possibly cirrhotic liver with no masses.

Laboratory Values Course in Hospital Serologies: AST: 40 ALT: 68 2 Viral Hepatitis 3 Laboratory Values Serologies: HBsAg positive HBeAg negative Anti-HBe positive HBV DNA 1433 IU/L Anti-HCV negative Anti-HAV positive AST: 40 ALT: 68 Alk Phos: 71 Total Bilirubin: 0.9 Total Protein: 7.7 Albumin: 4.9 α-Fetoprotein: 2.9 Course in Hospital Although the liver tests were only mildly abnormal, a biopsy was performed for staging of the disease.

2 Viral Hepatitis 4 Pathology Severe bridging fibrosis was present without distinct regenerative nodule formation, with mild portal and minimal periportal interface inflammatory activity (a). The parenchyma showed numerous “ground glass” cells within many of the lobules (b), with no definite necroinflammatory change. Figure 2.7(a) Figure 2.7(b)

2 Viral Hepatitis 5 Pathology Immunoperoxidase stain for HBsAg showed prominent 4+ cytoplasmic staining (c, d) with HBcAg negative. Figure 2.7(c) Figure 2.7(d)

2 Viral Hepatitis 6 Diagnosis Chronic viral hepatitis type B with bridging fibrosis, relatively inactive, with numerous “ground glass” cells

2 Viral Hepatitis 7 Comment In this example of chronic HBV, aminotransferases were only mildly abnormal, the HBV DNA was minimally elevated, and the biopsy showed little necroinflammatory activity. Although this points towards an inactive disease, the degree of chronicity with fibrosis cannot confidently be assessed without a biopsy, as even when the albumin is normal (as in this case), severe fibrosis and even cirrhosis may occur. Of note also is that when disease activity is minimal and HBcAg immunoperoxidase stain is negative, the HBsAg can still be positive and often prominent; in the present case almost all of the hepatocytes showed a ground glass appearance on H&E stain with HBsAg immunoperoxidase stain showing 4+ positive cytoplasmic staining. “Ground glass” cells represent proliferation of the 22 nm HBsAg particles in the endoplasmic reticulum of the hepatocyte, and can be seen in from ½ to ¾ of patients with chronic HBV infection; importantly, they are not a feature seen in acute HBV infection.