Leukemia (Blood Cancer)

Non-Alcoholic fatty liver disease 

Non-alcoholic fatty liver disease is actually a spectrum of diseases going from least to most severe steatosis, steatohepatitis, fibrosis, and finally cirrhosis. Non-alcoholic fatty liver disease results from fat deposition in the liver which is unrelated to alcohol or viral causes typically it affects individuals with metabolic syndrome which includes a combination of three of the five following diagnoses obesity, hypertension, diabetes, hypertriglyceridemia, and hyperlipidemia given how common metabolic syndromes become it's not surprising that the rate of non-alcoholic fatty liver disease has also increased dramatically. 

It's a massive problem growing in lockstep with expanding waistlines affecting about three-quarters of all obese individuals including many children although the exact mechanism of non-alcoholic fatty liver disease isn't clear insulin resistance seems to play an important role over time insulin receptors on various tissues including the liver become less responsive to insulin and as a result, the liver goes into a mode where it increases fat storage and decreases fatty acid oxidation that means decreased secretion of lipids into the bloodstream in the form of lipoproteins and increased synthesis and uptake of free fatty acids from the blood a process called steatosis.

Steatosis causes fat droplets to form within hepatocytes some of which become large enough to cause the hepatocytes to swell up with fat and push the nuclei to the edge of the cell you can even see this on a histopathology slide of the liver all these white circles are large deposits of fat zooming out and looking at the liver you see widespread steatosis which makes the liver appear large soft yellow and greasy over time that fat in the hepatocytes becomes vulnerable to degradation unsaturated fatty acids or fatty acids that have at least one double bond in their carbon chain have hydrogen atoms that are especially vulnerable to initiators like reactive oxygen species like the hydroxyl radical which has an unpaired electron.

In this example, the hydroxyl radical pairs with the vulnerable lipid hydrogen to make water and a fatty acid radical the fatty acid radical is unstable and reacts with non-radicals including molecular oxygen and undamaged fatty acids this goes on until one radical species reacts with another radical species which terminates the reaction this process damages lipid membranes leading to things like mitochondrial dysfunction and eventually cell death generates inflammation and together the process of steatosis and inflammation is referred to as steatohepatitis, in the absence of alcohol this is called non-alcoholic steatohepatitis or NASH in addition to bloating and dying hepatocytes, there might be additional histopathologic changes like the presence of Mallory denk bodies which are tangles of intermediate filaments that can be seen in the cytoplasm of hepatocytes the mechanism though for how this form is still unclear hepatocyte damage also attracts neutrophils into the liver tissues and finally chronic Seattle hepatitis can cause liver stellate cells to lay down fibrotic tissue causing the disease to be classified as fibrosis.

            As the process of fibrosis continues the overall architecture of the liver changes to the point where the disease is classified as cirrhosis even at the advanced stage of steatohepatitis an individual might have no symptoms and when there are symptoms they're often vague, like fatigue or malaise. Once there's significant liver damage though there can be hepatomegaly or enlargement of the liver, pain in the right upper quadrant of the abdomen, jaundice, and even an accumulation of fluid in the peritoneal cavity called ascites. Because hepatocytes are being destroyed there can be an increase in liver enzymes like aspartate transaminase or AST and to a greater extent alanine transaminase or ALT classically progression of steatosis to steatohepatitis and then to cirrhosis causes an increase in the ALT and sometimes AST.

In contrast, alcoholic liver injury generally causes a big increase in AST and a more modest increase in ALT giving an AST to ALT ratio generally greater than 2. If non-alcoholic fatty liver disease is suspected a diagnosis can be made with imaging studies like Ultrasound a Ct Scan or an MRI to look for fatty infiltrates, in addition, a biopsy of the liver can be done to confirm the diagnosis and assess the severity of the disease. Generally speaking a liver with more than five percent fat content is considered abnormal steatosis and to a lesser degree, steady hepatitis is generally reversible by addressing the underlying cause although that's generally not the case. Once fibrosis and cirrhosis are set in the goal is to reverse the factors that contribute to insulin resistance mainly through a healthy diet and an active lifestyle as well as medications to control blood glucose levels if needed.  

All right as a quick recap non-alcoholic fatty liver disease happens when fat is deposited in the liver a process called steatosis inflammation from steatosis can lead to steatohepatitis and chronic steatohepatitis can lead to fibrosis and ultimately to cirrhosis. This spectrum of disease is thought to be caused by insulin resistance and depending on the stage of the disease it can be reversed with careful attention to diet and exercise as well as with medications to help control blood glucose levels.

 

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