Module 2 Chapter 7 Flashcards
ETOH is metabolized by two pathways
Alcohol dehydrogenase (ADH) metabolizes alcohol to acetaldehyde and then metabolized to acetate MEOS (microsomal ethanol oxidizing system) = cytochrome P450 enzymes (CYP2E1) not generate free radicals leading to oxidative stress
Clinical presentations of steatosis or steatohepatitis
Clinical presentations of steatosis or steatohepatitis
Clinical presentations of steatosis or steatohepatitis
clinical presentations of alcoholic hepatitis
- followed by prolonged drinking - jaundice, stigmata of liver disease like ascites, spider nevi, hepatomegaly, hepatic encephalopathy, fever, edema, etc. - AST and ALT are minimally elevated, with GGT HIGH - ALP elevated (cholestasis) - Liver dysfunction with increased bilirubin, increased INR, decreased albumin, and increased creatinine (renal dysfunction) - increased WBC - need to do biopsy
What features would you see in steatohepatitis
neutrophils and Mallory hyaline
outline the progression/natural history of alcoholic fatty liver disease.
o 90-95% who drink alcohol above the safe thresholds will have steatosis (fat) in liver
o 20% with steatosis will have steatohepatitis (fat and inflammation)
Biopsy shows neutrophil infiltration and Mallory Hyaline
o Fibrosis (which often will line the sinusoids) will develop in 10-20% of those with steatosis
versus 40-50% of those with steatohepatitis
This can be influenced by female sex and genetics with presence of specific single
nucleotide polymorphisms (SNPs) or the HFE gene mutations [see Chapter 8.1]
o Up to 20% with fibrosis will progress to cirrhosis
This can be influenced by coexisting viral hepatitis, HIV, obesity or smoking
General treatment for alcohol fatty liver disease and alcoholic hepatitis
- abstinence from further alcohol
- alcoholic hepatitis; nutritional support, prednisone (reduce inflmaation), pentoxifylline* but studies found that prednisone is better!
Risks that predispose someone to NAFLD
Risks include obesity (central), type 2 diabetes mellitus (DM), dyslipidemia
Obesity is defined by body mass index (BMI) = height (metres)2 / weight (kg) BMI > 30 is obese
Frequently seen with the metabolic syndrome
- Waist circumference >102 cm in men or >88 cm in women
- High density lipoprotein (HDL) <1.0 mmol/L in men or <1.3 mmol/L in women
Other causes (should be considered and ruled out before diagnosing NAFLD)
Alcohol
HCV
WD
Starvation
Total Parenteral Nutrition
Metabolic: lipodystrophy, abetalipoproteinemia
Pregnancy including acute fatty liver disease
Medications like methotrexate, tamoxifen, steroids, or HAART for HIV
Pathology and Physiology of NAFLF
- metabolic syndrome leads to insulin resistance
The adipose tissue in those with central obesity is metabolically active and releases many
inflammatory cytokines and other hormones which lead to the complications including
hypertension, coronary heart disease, diabetes and NAFLD
Pathology is very similar to alcoholic liver disease with a spectrum from simple steatosis
(non-alcoholic fatty liver or NAFL) to non-alcoholic steatohepatitis (NASH), to fibrosis and
finally NASH-related cirrhosis
clinical presentation of NAFLD
similar to alchol related fatty liver disease. Gotta eliminate alcohol as a cause.
- ASt>ALT
- GGT is often high
- elevated ferritin
- may present with cirrhosis or its complications.
Natural hisotry of NAFLD
o NAFLD patients have increased overall mortality compared to controls with cardiovascular
disease being the leading cause of death
o NASH (but not NAFL) is associated with increased liver related mortality
Patients may present with cirrhosis or its complications [see Chapter 14]
o NASH related cirrhosis may have a lower risk of HCC than with viral hepatitis
- gotta look at a fibroscan and get a NAFLD Fibrosis score to determine who to biopsy
Treatment for NAFLD
- weightloss through diet and exercise
- management fo diabetes (metforin)
- vitamin E
- Bariatric surgery is the best treatment for morbidly obese.
