An investigation into how hepatitis C status affects fibrosis stage and progression among Alaska Native people with non-alcoholic fatty liver disease

PROJECT SUMMARY/ABSTRACT – Research Project 1: “An investigation into how hepatitis C status affects fibrosis stage and progression among Alaska Native people with non-alcoholic fatty liver disease” Chronic liver disease and cirrhosis (CLD) is the sixth leading cause of death among Alaska Native (AN)

people. Between 2014 and 2018 the CLD mortality rate among AN people was 3.1 times the CLD mortality rate for the U.S. all races population. The two most common types of CLD in the U.S. are fatty liver disease and hepatitis C. The co-occurrence of hepatitis C virus (HCV) and fatty liver is associated with more rapid

progression to liver fibrosis and hepatocellular carcinoma (HCC) and results in worse outcomes than either condition alone. We will assemble a cohort of AN people diagnosed with non-alcoholic fatty liver disease (NAFLD), including AN people with and without a current or previous diagnosis of HCV, to determine how

infection with HCV modifies liver fibrosis, liver disease risk markers, and liver-related health outcomes among AN people with NAFLD. Aim 1: Assemble a well-characterized cohort of AN people with NAFLD to investigate differences in clinical characteristics, risk factors, self-reported symptoms, and liver-related outcomes based on HCV status. We will

stratify participants by HCV status for comparisons of baseline clinical characteristics, risk factors, self-reported symptoms, and liver-related outcomes including liver cancer and liver failure. Aim 2: Compare fibrosis stage and progression by HCV status among AN people with NAFLD. Fibrosis increases

the risk of liver failure and creates a permissive environment for liver cancer. We will use vibration-controlled transient elastography (VCTE) to measure the presence and amount of liver fibrosis at time of study enrollment. We will also evaluate annualized change in fibrosis using available historic VCTE measurements. We will stratify

on HCV status to compare VCTE measurements at time of enrollment as well as annualized rates of change. We will also investigate associations between these measures and clinical characteristics, risk factors, self- reported symptoms, and liver-related outcomes. The long-term goal for this research program is to reduce the burden of disease among AN people with NAFLD

by improving secondary prevention of adverse liver-related outcomes. A critical barrier to preventing these adverse outcomes is knowing which AN people with NAFLD are most likely to progress to advanced fibrosis or cirrhosis. This initial project focuses on the interaction between NAFLD and HCV in AN people. Better

understanding the interaction between NAFLD and HCV is crucial because they are the two most common types of chronic liver disease in the U.S. and the two leading indicators for liver transplant. Furthermore, recent studies suggest that NAFDL and HCV may have an additive or synergistic effect on liver injury.