Alcohol withdrawal/Alcohol Liver Disease, NAFLD, and NASH Flashcards
What is the CAGE questionnaire?
Tool for detecting individuals more likely to be abusing alcohol and therefor at a greater risk for alcohol withdrawal
>/= positive answers in an increased likelihood of alcohol abuse with a sensitivity of 71% and specificity of 90%
What does the C stand for in CAGE questionnaire?
Do you ever feel the need to Calm down on your alcohol use?
What does the A stand for in CAGE questionnaire?
Have you ever been Annoyed by others telling you that you drink too much?
What does the G stand for in CAGE questionnaire?
Have you ever felt Guilty about your drinking or something you did while were drinking?
What does the E stand for in CAGE questionnaire?
Do you ever have an Eye opened?
What are the different stages of alcohol poisoning with increasing doses?
Sedation Sleep Unconsciousness Coma Surgical anesthesia Fatal respiratory depression
What neurotransmitters does alcohol affect?
Endogenous opiates, GABA, glutamine, DA and seotonin
What is GABA
Major inhibitory neurotransmitter
Acute intoxication causes a release of GABA
Alcohol withdrawal can be considered a GABA deficient state
What is glutamate?
Major excitatory neurotransmitter in the brain that is linked with memory formation and learning
Alcohol decreases the binding ability of glutamate to NMDA
Chronic users upregulate NMDA receptors
What is DA?
Reward system of the brain
Acute ingestion causes an increase in synaptic DA
What is serotonin?
Contributes to the nausea associated with alcohol
Might also affect the happiness that one feels while consuming alcohol
What are the s/sx of alcohol intoxication?
Sx - slurred speech, ataxia, sedated or unconcious
Signs - nystagmous, tachycardia, diaphoresis, or hyperthermia
How much ethanol is required to raise BAC?
14 grams of ethanol increases the BAC 0.02-0.025% in an average 70 kg male
What are the beverage equivalents in alcohol consumption?
14 grams of ethanol =
12 oz can of beer
4 oz glass of wine
1.5 oz shot of whiskey
What are the diagnostic tests for alcohol consumption?
BAC
Full toxicologic screen to rule out other substances
CMP to evaluate electrolyte imbalances and deficiencies
CT on any patient w/focal neurologic findings, failure to improve, new onset seizures, or altered mental status is out of proportion to degree of intoxication
What are SE of BAC 0.02-0.09%?
Euphoria Loss of shyness Feeling of well-being Relaxation Lower inhibition Minor impairment of reasoning and memory Slight impairment of balance Speech Vision Reaction time and hearing Judgement and self-control are reduced
What are the SE of BAC 0.10-0.24%?
Significant impairment of motor coordination and loss of good judgement
Speech can be slurred
Gross motor impairment
Lack of physical control
Euphoria is reduced and dysphoria is beginning to appear
Nausea begins to appear
The drinker is commonly referred to as a “sloppy drunk”
What are the SE of BAC 0.25-0.40%
Needs assistance in walking, total mental confusion, and loss of consciousness
What are the SE of BAC > 0.40%?
Onset of coma
Possible death caused by respiratory arrest
What is PK of alcohol?
Ethanol is absorbed w/in 5-10 minutes
Serum peak concentration are 30-90 minutes after consumption
On average the BAC is lowered by 15-22 mg/dl per hour in a non-tolerant individual
Ethanol follows zero order kinetics
How is alcohol metabolized?
90% metabolized by alcohol dehydrogenase in the liver to acetaldehyde which is further broken down to acetate by aldehyde dehydrogenase
Remaining 10% by catalase and 2E1
Acetaldehyde is a known toxin to the liver, pancreas, brain and GIT
What may be present after 2-3 days of withdrawal?
Delirium tremens (DTs): Hallucinations Delirium Fever Tachycardia - May lead to death
What is tremulousness?
Tremors
Shaking
Quivering
What are the minor and major stages of alcohol withdrawal?
Minor: 1
Major: 2,3,4
What are the SE of stage 1 alcohol withdrawal?
Autonomic hyperactivity
Tremulousness (6-8h)
What are the SE of stage 2 alcohol withdrawal?
Hallucinations
Hallucinosis (10-30h)
What are the SE of stage 3 alcohol withdrawal?
Neuronal excitation
Seizures (6-48h)
What are the SE of stage 4 alcohol withdrawal?
Delirium tremens Delirium tremens (2-5 days)
What is the backbone of treatment for alcohol withdrawal?
Benzos (manage sx and avoid progression to the more serious stages of withdrawal)
What is the MOA for benzos in alcohol withdrawal?
Increase the frequency of the opening of the GABA chloride channel, allowing more GABA to enter
What is the MOA for phenobarbital in alcohol withdrawal?
Barbiturates allow the GABA chloride channel to stay open longer
What medications may be used synergistically for alcohol withdrawal?
Benzos and phenobarbital
What is the last line agent for pts refractory to phenobarbital or benzos?
Propofol - allows the opening of the GABA chloride channel to stay open without the presence of GABA
What is the treatment for sx-triggered alcohol withdrawal pts with sx?
Only when the patient is HAVING sx
Results in shorter treatment duration, potentially avoids, and allow for individualized treatment
Lorazepam 1-2 mg every hour as needed when a structured assessment scale indicates that the sx are moderate to severe
What is the treatment for fixed schedule alcohol withdrawal patients?
Benzo given regularly at a fixed dose interval - has been used for years
Longer duration and higher doses
Lorazepam 1-2 mg IV/PO/IM every 8 hours decreasing the dose every 1-2 days as tolerated
Do we treat seizures d/t alcohol withdrawal?
Typically no - seizures are of short duration and finish before treatment can be given
Yes in status epilepticus seizures
How do we treat status epilepticus seizures in alcohol withdrawal?
Benzos w/phenobarb until etiology is confirmed
Then increase dose of benzo w/slow taper can be used during detox to prevent future seizure acitivty
What are other treatments for pts with acute alcohol withdrawal?
Thiamine 100mg IV/IM for max of 5 days Folic acid 1mg QD x 3-5 days IV fluids Hyperactivity treatment: clonidine 0.05-0.03 mg/day as PO/transdermal patch Antipsychotics
What is thiamine used to prevent in acute alcohol withdrawal?
Wenicke-Korsakoff syndrome
In what order is thiamine used for pts with acute alcohol withdrawal?
Before or with glucose, otherwise it worsens Wenicke-Korsakoff syndrome
When are antipsychotics used in pts with acute alcohol withdrawal?
Agitation
Unresponsiveness to benzos
Hallucinations/delusions
What medications are used for long term abstinence after detoxification?
Naltrexone
Acamprosate
Disulfiram
Dosing of Naltrexone for long term abstinence?
PO: Day 1: 25 mg, Day 2 and on: 50mg
IM: 380 mg IM q4wk
For 6-12 weeks w/counseling
What are the ADRs for Naltrexone?
Syncope
CNS
GI
Arthralgias
What are the cautions for Naltrexone?
Hepatic dysfunction
What is the dosing for acamprosate?
666mg PO TID (renal adjustment for CrCl <50)
What is acamprosate MOA?
Decreased glutamate activity in the CNS
Decreased activity at the NMDA receptor
What is the ADR for acamprosate?
Diarrhea
What is disulfiram’s MOA?
Inhibits alcohol dehydrogenase
What does disulfiram cause in patients who drink alcohol?
Flushing Throbbing HA N/V Sweating Hypotension Confusion
What are the DDIs for disulfiram?
Oral anticoagulants
Phenytoin
Isoniazid
What is the most common phase of alcohol liver disease?
Fatty liver
What is the common cause of fatty liver?
Binge/chronic drinkers
What is the least common phase of alcohol liver disease
Chronic alcoholic progress
What are the most important RFs for alcohol liver disease?
Quantity and duration
What is a co-morbidity of alcohol liver disease that increase the risk of cirrhosis?
HCV
How much alcohol does it take and for how many years for the development of alcohol liver disease?
Men: > 60-90 g/day for 10 years
Women: > 20-40 g/day for 10 years
What is the presentation of Alcohol liver disease?
RUQ pain Nausea Discomfort Jaundice Portal HTN Ascites Variceal bleeding (may be present)
What are the labs seen in alcohol liver disease?
Modest elevations of AST/ALT/GGT in alcoholic steatosis
Elevated triglycerides, hypercholesterolemia, elevated bilirubin
In alcoholic hepatitis: AST/ALT are elevated 2-7 fold
AST/ALT > 2
How do we diagnose alcohol liver disease?
Presentation
Lab features
Ultrasound
Liver biopsy
What is the prognosis of alcohol liver disease?
Potentially reversible
Estimated with the MDF score (>32 is poor prognosis) or the MELF ( >18 is poor prognosis) and should be considered for treatment
What is the preferred treatment for alcohol liver disease?
Preferred: Prednisone 40 mg/kg/d for 4 weeks then taper
Alternate: Pentoxifylline 400mg po TID for 4 weeks (for pts who cannot tolerate corticosteroids)
What is the Lille Model?
Determines if prednisone is effective (at day 3 and 7) or if it should be DCd
What are the two types of non-alcoholic fatty liver disease?
NAFL
NASH (non-alcoholic steatophepatitis)
What is NAFLD?
Hepatic steatosis with no evidence of secondary causes of fat accumulation in the liver
What are the common causes of secondary hepatic steatosis?
Macrovascular steatosis
Microvascular steatosis
What are the macrovascular steatosis causes?
Excessive alcohol consumption Hep C genotype 3 Wilson's disease Lipodystrophy Starvation Parenteral nutrition Abetalipoproteinemia Medications (amiodarone, MTX, tamoxifen, corticosteroids)
What are the microvascular steatosis causes?
Reye's syndrome Medications (valproate, anti-retroviral medicines) Acute fatty liver of pregnancy HELLP syndrome Inborn errors of metabolism
What is NAFLD strongly associated with
Insulin resistance (most important)
Obesity
Diabetes
Hyperlipidemia
What are the RFs for NAFLD?
Obesity
T2DM
Dyslipidemia
Metabolic syndrome
What are RFs that have emerging association with NAFLD?
Polycystic ovarian syndrome Hypothyroidism Obstructive sleep apnea Hypopituitarianism Hypogonadism Pancreato-duodenal resection
What is a common deficiency in NAFLD?
Vit D - associated with the risk of NASH in patients with NALFD
What are the s/sx of NAFLD?
Usually no sx
Only common sign is mildly elevated liver transaminases (2-3x ULN); AST/ALT ratio is usually less than 1
How is NAFLD diagnosed?
Hepatic steatosis via imaging or histology
There is no significant alcohol consumption
There are not other competing etiologies for hepatic steatosis
There are no co-existing causes for chronic liver disease (hemochromatosis, autoimmune liver disease, chronic viral hepatitis, Wilson’s disease)
How do we differentiate NAFL/NASH?
Presence of metabolism syndrome is a strong predictor for the presence of steatohepatitis
Biopsy is gold standard but is costly and risky
NOT IMAGING
Non-invasive methods being studied
What are the non-invasive methods for differentiating NAFL/NASH?
Microbiota assessment from stool sample; 3 genera of bacteria are associated with NASH and fibrosis
NAFLD fibrosis score
Vibration Controlled Transient Elastography
What does the NAFLD fibrosis score look at?
Utilizes age, BMI, hyperglycemia, plt count, albumin, AST/ALT ratio
What is the vibration control transient elastography?
Point of care test
MRE with protein density fat fraction
Enhanced liver fibrosis scale (ELF)
How do we manage NAFLD/NASH?
Lifestyle modifications
Insulin sensitizing agents
Hepatic oxidative stress reduction
Others
What are insulin sensitizing agents?
Pioglitazone 30 mg QD - for biopsy proven NASH but long term safety and efficacy unknown
- May improve or resolve NASH
- No evidence to support use in NASH/NAFLD PLUS other chronic liver diseases (chronic HCV or primary biliary cirrhosis)
- Rosiglitazone not effective
- Metformin not recommended
How do we treat hepatic oxidative stress reduction
Vitamin E 900 IU - improves histology
First line therapy for proven NASH in non-diabetic pts
Not currently recommended in NASH for diabetics, NAFLD w/o biopsy, NASH cirrhosis, cryptogenic cirrhosis
What are other treatments for NASH/NAFLD?
Ursodeoxycholic acid (UDCA) - not recommended Omega-3 fatty acids - premature to recommend for treatment but may be considered first line agents to treat hypertriglyceridemia in patients with NAFLD
What medication is in the pipeline for NASH/NAFLD?
Elafibranor
Agonist of the peroxisome proliferator-activated receptor alpha and gamma that play a role in fatty acid transport, oxidation, glucose homeostasis, and anti-inflammatory activities
What are other recommendations for pts with NASH/NAFLD?
Bariatric surgery - premature to recommend for NALF/NASH
Alcohol use should be avoided
Statin use in both NAFL/NASH
How do we treat NALFD in childhood?
Intensive lifestyle modification is first line
Vit E 800 IU/d offers histological benefit for biopsy proven NASH or borderline NASH but additional confirmatory studies are needed before it can be recommended for clinical practice
What are the three phases of alcohol liver disease?
Fatty liver
Chronic Alcohol progress
Cirrhosis
