Histological and Immunohistochemical Findings in Two Subtypes of Hepatitis B Related Acute Liver Failure




Choo, Vincent

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BACKGROUND: Acute liver failure (ALF) occurs when rapid-onset, severe liver cell damage results in coagulopathy and encephalopathy. Multiple etiologies yield a remarkably similar syndrome including acetaminophen overdose, drug-induced liver injury, and Hepatitis B Virus (HBV) infection. ALF in the setting of HBV occurs in 1% of primary acute HBV infections (AHBV-ALF), but can also evolve during chronic HBV infection (CHBV-ALF), particularly in reactivation, when patients receive immunosuppressive or cancer chemotherapy. OBJECTIVE: To determine whether differences between the two varieties of HBV-ALF, primary acute HBV infection and reactivation of HBV, are reflected in differences in HBV immunohistochemical bio-markers in liver: HBV core antigen (HBcAg) & HBV surface antigen (HBsAg). METHODS: A total of 21 patients from the Acute Liver Failure Study Group (ALFSG) were identified as having sufficient liver tissue for the staining panel required. Samples were immunostained using dye-labeled antibodies for HBV core antigen (HBcAg) and HBV surface antigen (HBsAg). We performed routine hematoxylin & eosin (H&E) staining for overall morphology (degree of necrosis, presence of plasma cells) and reviewed clinical history to stratify each case as either AHBV-ALF (primary infection, N=11) or CHBV-ALF (reactivation, N=10). For H&E, we assessed number of plasma cells, percent tissue necrosis, and degree of collapse. Eleven biopsies had <25% viable hepatocytes, making further analysis of staining patterns unsuccessful. The remaining acute HBV cases had very little, if any, HBsAg staining and variable levels of nuclear HBcAg staining. In contrast, one CHBV-ALF case had intense staining for both HBsAg and HBcAg, probably related to the presence of immunosuppression. SUMMARY/CONCLUSION: Immunohistochemical staining of liver biopsies/explants revealed scant viable hepatocytes in more than half, limiting assessment of location of viral products within cells. In general, when assessment was possible, AHBV-ALF demonstrated little to no HBsAg and variable amounts of HBcAg staining. Immunosuppression leads to much higher levels of HBV proteins within hepatocytes, and perhaps suggests that the virus is directly cytotoxic in this setting. By the time of liver transplantation, virtually all HBsAg had disappeared from hepatocytes in AHBV-ALF, but high quantities of HBsAg and HBcAg were found in immunosuppressed patients with reactivation. These two forms of acute liver failure due to hepatitis B have remarkably different pathogenetic phenotypes.

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The 55th Annual Medical Student Research Forum at UT Southwestern Medical Center (Monday, January 17, 2017, 2-5 p.m., D1.600)

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Choo, V., Peng, L., Dao, D. Y., Hameed, B., Lee, W. M. & ALFSG (2017, January 17). Histological and immunohistochemical findings in two subtypes of Hepatitis B related acute liver failure. Poster session presented at the 55th Annual Medical Students Research Forum, Dallas, TX. Retrieved from https://hdl.handle.net/2152.5/4016

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