Fatty Liver Disease: Pathophysiology By Susanna Heinze January 2017 These brief notes and the diagram on the next page are intended to accompany the youtube video on my channel.

What is it? 

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Fatty liver disease occurs when the liver begins to store too many triglycerides (fats) in the liver cells (hepatocytes). o Originally believed to be caused exclusively by excessive alcohol consumption, we now know that excessive calories and/or excessive fructose, can damage the liver and lead to diminished liver function. The early stages of the disease are reversible by weight loss and/or a reduction in alcohol intake. o There comes a point when the disease becomes irreversible. Damage to the liver has become so great that continued degeneration of function may lead to liver failure. Diagnosis usually involves an MRI to visualize enlargement of the liver and blood work to assess current liver function. o An exciting new diagnostic tool is the Fibroscan, which is a noninvasive tool that assesses the degree of stiffness of the liver.

Pathophysiology: 

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Normal hepatocytes store excessive free fatty acids, and fructose in the form of trigylcerides (fats). Byproducts of alcohol metabolism increase fat storage in the liver. o Metformin, a medication prescribed in type II diabetes, can increase insulin sensitivity and therefore decrease the free fatty acids entering the liver. Excessive caloric intake and/or alcohol consumption over years can cause large droplets of fat to accumulate. We call this stage steatosis. o If observed microscopically (from a biopsy), these macrovesicles of lipids appear to crowd the cell’s nucleus against the side of the cell! o A Fibroscan can estimate the degree of fat accumulation o This stage is quite reversible, usually by reduction of calories and/or alcohol intake. The fatty hepatocytes begin to lose function and die. Dead cells are replaced with collagen fibers (scar tissue). We call this liver fibrosis. o Caffeine appears to inhibit liver fibrosis. o A Fibroscan can estimate the degree of liver stiffness to estimate how much scarring has occurred. If inflammation becomes chronic in the damaged cells, the liver can reach the final stage: steatohepatitis (fatty deposits and liver inflammation). In its worst state, it is called cirrhosis of the liver. o Non-alcoholic steatohepatitis (NASH) is the term for the disease when the patient is not a drinker. Pathologically, whether the disease began due to alcohol or other causes, they are nearly identical.