Alcoholic liver disease and NAFLD Flashcards
What is the histologic spectrum of liver damage?
NAFL
NASH
Cirrhosis
What other condition is NAFLD associated with?
Metabolic syndrome.
- obese
- T2D
- HTN
- hyperlipidemia
What are the major risk factors for cirrhosis in a pt with NASH
Age > 45-50
obesity
diabetes
Why is NASH + fibrosis so much worse than NAFl?
30% will progress to cirrhosis in 5-10 yrs. Compared to 3%
What’s the pathophysiology behind the link btw metabolic syndrome and NAFLD?
Excess fat: produces too much TNF-alpha and too little adiponectin. Causes steatosis, cell death, inflammation, and insulin resistance
What does TNF do?
proinflammatory: promotes apoptosis, recruits WBCs, and insulin resistance
What does adiponectin do?
anti-inflammatory agent.
- inhibits FA uptake
- Stimulates FA oxidation
- Enhances insulin sensitivity
What blood tests would you see in NAFLD?
AST and ALT elevated but less than 10x upper limit of normal.
- Negative tests for other disease
- Positive for metabolic syndrome markers
What do you need to give a prognosis for NAFLD?
Biopsy.
- -Steatosis alone=benign
- -Steatohepatitis=high risk for cirrhosis
- -If cirrhotic, high morbidity+mortality
What lab tests can help determine severity of disease in NAFLD?
- HIGH AST/ALT ratio (levels themselves are NOT helpful)
- thrombocytopenia in cirrhotic liver
- Later on…high bili, low albumin means interfering with normal fxn of liver
How might abdominal imaging help in NAFLD?
Can show fatty liver, but NOT steatohepatitis.
- -Good for HCC
- -MAY help with cirrhosis by finding other sequealae (splenomegaly etc)
How do you treat NAFLD?
weight loss and exercise
- -bariatric surgery (but massive weight loss can worsen histology)
- -Treat metabolic syndrome/diabetes/hyperlipidemia
- Vitamin E if no heart disease
- Monitor for cirrhosis and portal HTN and HCC
Treatment for steatosis/NASH/cirrhosis on histology in NAFLD
Steatosis: just diet/exercise
NASH: Trial + vitamin E+diet/exercise
Cirrhosis: Treat portal HTN, screen for HCC
Decompensated: Liver transplant/trial
What factors (aside from genetics) can increase your risk of alcoholic liver injury?
- Amount of alcohol and duration (but most people who drink heavily do NOT get liver dz)
- Wine is better (bad study!)
- Binge drinking is worse
- Females increased risk for same alcohol amount
- Ethnicity–worse for hispanic males
What is the relationship btw HCV and alcoholic liver dz
Pts w/ both HCV and liver dz: --younger onset --More severe histology --increased risk of cirrhosis --increased risk of HCC Take home: there is no SAFE amount of alcohol to drink if u have HCV
What other concurrent dzs predispose to alcoholic liver dz?
Pts who have the C282Y gene mutation in HFE gene
—And obesity!
What are the two pathways of ethanol metabolism?
- oxidative (Alchohol dehydrogenase)
- -NAD+–>NADH - microsomal (cytochrome P450 converts ethanol to acetaldehyde) enzyme oxidation at higher ethanol concentrations
- -NADPH–>NADP+
Why do you want to be careful in giving lots of tylenol to an alcoholic?
Upregulated MEOS p450 system means faster conversion of tylenol to toxic metabolites
Where else would you find alcohol dehydrogensease (besides liver)?
In da stomach
Which part of the liver is affected first in alcoholic liver dz? describe how alcohol causes damage.
- Centrilobular hypoxia: zone of hypoxia around central veins. Decreased oxygen delivery to central veins b/c ethanol metabolism consumes oxygen
- Neutrophil infiltration and activation: reactive oxygen species produced by NADPH oxidase activating kupffer cells
- acetaldehyde stimulates collagen
- TNF and IL-6: necrosis and further inflammation
What are the findings in alcoholic fatty liver?
None…usually asymptomatic. May have elevated LFTs/GGT
What are the histological findings of alcoholic hepatitis?
- PMN infiltrate/spotty necrosis
- mallory denk bodies
- balloon cells
- steatosis
What labs might you see in alcoholic hepatitis?
AST is twice ALT
- High GGT, AP, bili, INR,
- decreased albumin
- High WBC
- thrombocytopenia
- anemia
What calculations can predict prognosis in alcoholic hepatitis?
Modified Discrimination Function: >32 is worrisome
=4.6 (PT-control) + serum bili
OR
MELD: >18 is worrisome.
=creatinine, bilirubin and INR
How do you treat alcoholic hepatitis?
- Supportive care
- Corticosteroids
- Pentoxifylline
- LIVER TRANSPLANT
When can u use prednisone?
mDF score of 32+ OR hepatic encephalopathy. Do NOT use if infections, Gi bleeding or renal failure present
How does pentoxifylline work?
Inhibits TNF alpha…a mediator of inflammation
