non-alcoholic fatty liver disease Flashcards
What some types of non-alcoholic liver disease (ie. kinds of changes)
bland fatty liver (>55 mg triglyceride or >5% of hepatocytes), NASH (non-alcoholic steatohepatitis), cirrhosis
Epidemiology of NAFLD
a growing problem, since it is related to obesity.
Highest in hispanics, then caucasians, then African Americans.
With what diseases is NAFLD associated?
obesity (about 95% of ppl with BMI over 40 have NAFLD), DM2, CV and cerebrovascular disease (very important!), osteoarthritis and sleep apnea, and extra-hepatic malignancies (esophagus, pancreas, breast, colon, endometrium)
How does NAFLD present?
- Potentially from mild AST/ALT elevations- but many ppl w NAFLD have “normal” transaminases
- Incidentally on imaging: ultrasound, CT, and MR in and out of phase.
- Complications of the disease like cirrhosis, liver failure, CA.
Dx of NAFLD
chronically elevated ALT and/or signs of fatty liver on ultrasound, AND you’ve excluded alcohol, AND you have clinical or biochemical signs of insulin resistance. Biopsy is required for definitive dx but is only rarely performed. Biopsy may distinguish btw bland fatty liver and NASH and may assess the degree of fibrosis.
NASH diagnostic criteria (with biopsy)
NASH on liver biopsy plus 3 of the following: BMI >35, presence of type II DM, higha ALT, ALT/AST about 1, age >45 or obesity for more than 20 yrs
Basic pathogenesis of NAFLD to NASH
imbalance btw triglyceride acquisition and loss. major factors: diet, obesity, fructose (which causes lipogenesis in the liver). High insulin levels in the body promote fat storage in the liver (no insulin, no steatosis). Once this hit (fat in liver) has occurred, a second hit must occur before we see steatohepatitis. Fat oxidation is the key seconds step because it triggers inflammation. Fat oxidation is related to genetics (adiponutrin), gut bacteria, cytokines, and ER stress.
How does NASH lead to liver cirrhosis? What makes this process occur faster?
chronic inflammation –> activated stellate cells. When activated, stellate cells make collagen –> cirrhosis. process is faster in pts who also drink, smoke, have sleep apnea, iron overload, or viral hepatitis.
However, even once cirrhosis occurs, progression to end stage liver failure and CA is slower in NAFLD than in alcoholic liver disease or viral liver disease.
Natural hx of NAFLD. What is the major cause of death in pts with NAFLD without cirrhosis?
simple steatosis doesn’t always progress to NASH and will regress with weight loss. NASH may develop into cirrhosis in 15-20 yrs. Once it does, pts with NASH develop cancer or liver failure in 10 yrs about 40% of the time.
Deaths in NAFLD without cirrhosis are largely due to CV disease and extrahepatic malignancies.
What is the connection btw insulin resistance and obesity/DM2 and NAFLD?
NAFLD is just the hepatic manifestation of metabolic syndrome. Insulin promotes lipogenesis in the liver, though it doesn’t stop hepatic glucose synthesis. A pt with insulin resistance will have HIGH levels of insulin, so their livers will make high levels of fat.
Steatosis disappears in pts with portal HTN and cirrhosis, b/c pts have decreased hepatic blood flow and decr. insulin exposure.
Steatosis only occurs in pts with insulin- steatosis is not seen in pts with type I DM who don’t have insulin resistance.
Lifestyle modificaitons and bariatric surgery for NAFLD
weight loss over 7% improves NAS scores and reduces hepatic steatosis- but fibrosis doesn’t change with (this level of) weight loss. 7% weight loss is very hard to achieve.
Bariatric surgery: reverses steatosis, NASH and fibrosis in pre-cirrhotic pts. Surgery can cause liver failure if the pts had bridging fibrosis/early cirrhosis: consider biopsy before surgery in advanced disease.
Alcohol and vit. E in NAFLD management
alcohol: slightly protective against metabolic syndrome at very low doses, but generally we recommend less alcohol, sine moderate-to-high levels of alcohol promote progression of NAFLD and incr. risk of HCC.
Vitamin E: may help with steatosis, but be judicious: increased all-cause mortality may be seen with vitamin E.
What drugs might I prescribe for NAFLD?
Statins! Statins reduce CV risk and are safe in NAFLD.
metformin is an insulin-sensitizing agent that is helpful in pts with diabetes.
ACE-Is and ARBs may be protective.
What else should I think about in pts with NAFLD?
monitor and caution pts about CV risk, even if they don’t have DM2. Give statins!
Watch comorbidities like HTN, sleep apnea, dyslipidemia, and kidney issues (NAFLD can affect the kidney).
