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Presentation date

Summer 8-12-2021

College, Institute, or Department

Internal Medicine

Faculty Mentor

Dr. Natalia Osna

Research Mentor

Dr. Natalia Osna

Abstract

Hepatitis B Virus (HBV) is an infection that specifically targets hepatocytes and persistence of infection leads to inflammation and liver injury. The metabolism of alcohol is also known to cause injury and inflammation in the liver. The extent of liver damage can be analyzed by determining the pressure of the tissue with an ultrasound. As you go from a healthy liver to a fibrotic liver, the pressure increases from around 2 kPa to greater than 12.5 kPa. Previous studies have found that liver stiffness affects the primary hepatocyte function and cell interaction, but the exact mechanism behind the combined role of liver stiffness and alcohol in HBV infection is still unclear. This study aimed to determine the effect of liver stiffness and alcohol metabolism on HBV infection pathogenesis. To accomplish this aim, we used a soft and stiff liver model engineered specifically to a 2 kPa (healthy liver tissue) and 25 kPa pressure (fibrotic liver tissue). HBV transfected HepG2.2.15 cells were plated on these liver model plates. To mimic alcohol metabolism, the cells were exposed to Acetaldehyde Generating System (AGS). Results showed that liver stiffness significantly increased HBV infection markers and decreased the interferon alpha signaling by up regulating USP-18. In addition, liver stiffness increased inflammasome and pro-fibrotic markers in HBV transfected cells. The combination of alcohol metabolism with liver stiffness potentiated the HBV infection. We conclude that liver stiffness impairs interferon alpha signaling thereby increasing HBV persistence, which leads to liver inflammation and fibrosis. This study of the liver environment’s role in HBV infection and alcohol metabolism paves the way to new treatment options for patients as well as introduces more accurate lab models for research.

Keywords

Liver Stiffness, Alcohol, Hepatitis B Virus, Interferon∝ Signaling, USP18, STAT-1

Role of Liver Stiffness and Alcohol on HBV Infection Pathogenesis

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