Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease closely associated with central obesity, dyslipidemia, insulin resistance and diabetes. This disease starts from simple steatosis and can progress through nonalcoholic steatohepatitis (NASH) to fetal fibrosis, cirrhosis and hepatocyte carcinoma.
KBI has developed the NHP models of NAFLD and NASH with all the pathological hallmarks as seen in humans by feeding the KBI designed high fat diet over 2 years. The monkeys are first screened for obesity, dyslipidemia, insulin resistance, diabetes and hypertension to characterize the stage of their NAFLD (Fig 1). KBI can provide NASH animals at different grades and stages for different needs and designs.
Figure 1. Screening process for NAFLD and NASH. Based on the NASH Clinical Research Network (Hepatology 2011,53:810-820). The monkeys with in 2 or more metabolic dysfunctions are then selected for liver biopsy to examine histopathological lesion and fibrosis.
Figure 3. Scoring of fibrosis of liver biopsy. Liver fibrosis is determined by assessing the biopsy specimens stained with Sirius Red. Approximately 60% of the monkeys with metabolic syndrome induced by the KBI high fat diet develop NASH, among which 30% exhibit histological liver fibrosis.
KBI can also monitor the progression and regression of NASH by various noninvasive state-of-the-art imaging technologies, including ultrasound elastography (for liver stiffness, Fig 4), MRI-derived proton density of fat fraction (MRI-PDFF for liver fat, Fig 5) and MRI T1 mapping (for liver fibrosis) by measuring extracellular volume (ECV) (Fig 7 & 8).
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