Alcohol Related Liver Disease Flashcards
What is the definition of binge drinking`
Five drinks in men, four in women over two hours
What is the AUDIT?
10 questions on consumption, dependence, and any alcohol associated problems
What is AUDIT C
- How often did you have a drink containing alcohol in the past year
- How many drinks containing alcohol did you have on a typical day when you were drinking in the past year?
- How often did you have six or more drinks on one occasion in the past year?
Score >/= 4 –> intervention, referral should be offered
Which biomarkers can be prolonged in renal disease
ETG ethyl glucuronide
ETS ethyl sulfate
* so longer window of positive results after alcohol ingestion in patients with kidney disease
What is PETH?
phospholipid formed by the reaction of phosphatidylcholine with ethanol catalyzed by phospholipase D in the erythrocyte cell membrane
What is half life of PETH and what is detection time
10-14 days, but can be longer with more chronic, repeated heavy alcohol consumption.
Is not influenced by age, BMI, sex, kidney disease, or liver disease
Detection time is 2-3 weeks
What are the FDA approved medications for AUD?
- disulfiram- not recommended for patients with ALD
- Naltrexone 50 mg/d
- Acamprosate 660 mg TID
What are non FDA meds for AUD?
- Gabapentin
- Baclofen
- Topiramate
What are risk factors for ald
- alcohol dose above 1 drink/day (women) and 2 drinks/day (men)
- Pattern of consumption -daily drinking, binge drinking
- smoking cigarettes
- Women compared with men
- Genetics (PNPLA3,)
- Increased BMI
- Presence of comorbid conditions, chronic viral hepatitis, hemochromatosis, NAFLD, NASH
What are histologic features of AH?
Neutrophilic lobular inflammatio
Degenerative changes in hepatocytes (ballooning and Mallory Denk bodies)
Steatosis
Pericellular fibrosis
How to make a clinical diagnosis of AH?
- Onset of jaundice within prior 8 weeks
- Ongoing consumption of >40 (female) or >60 (male) g alcohol/day for more than six months with <60 days of abstinence before onset of jaundice
- AST>50, AST/ALT >1.5, both values <400
- Serum total bili >3.0
Definite AH: Clinically diagnosed and biopsy proven
Probable AH: Clinically diagnosed without potential confounding factors
Possible AH: Clinically diagnosed with potential confounding factors (ischemic hepatitis, drug induce, denies alcohol use, atypical lab findings)
What are components of Maddrey?
Bili
INR
Initiate steroids if >32
what are components of Lille?
Change in bili
INR
Cr
Age
Albumin
>/= 0.45 non response to steroids,
When should you start steroids in AH?
When MD > =32
MELD> 20
No contraindications:
What are genetic and environmental links to PBC?
Genetics: HLA associations + genes involved with innate immune system
Environmental: smoking, nail polish, infections
What does UDCA do in PBC?
Reduces disease progression and need for liver transplantation
What is the childhood equivalent to PBC?
There is none, it is an adult disease
Can AZA be used in AIH?
If no cirrhosis, then yes can be used. But can’t be used for induction therapy because it takes 6-8 weeks to take effect.
If compensated cirrhosis, need to check TPMT
Do not use in decompensated cirrhosis
Do not use in fulminant AIH
How do you use steroids in AIH?
Induction therapy:
-prednisolone or prednisone of 30 to 60mg/day, or up to 1 mg/kg/day as mono therapy
- combination therapy of 30 mg of red + 50 mg of AZA
Weaning:
- try to wean to Maintenace dose less than 20 mg/day
When to wean meds for AIH?
After two years of remission, can wean. Can do biopsy before withdrawing IS, because if inflammatory activity is present, relapse is almost universal, and therefore IS should be continued in the long term.
In adults, biopsy is not absolutely necessary before withdrawal. In children, it is strongly recommended
What if someone is treated for AIH, liver tests improve, but IgG remains elevated after two years of meds?
Can still try with withdrawal of meds, noting that IgG may be elevated in cases of cirrhosis
Can you use budesonide in AIH cirrhosis?
No- first pass metabolism is in the liver, and risk of PV thrombosis
What percentage of general population have a positive AMA?
0.5%
What lesion has a central scar
FNH
How to differentiate adenoma from FNH
eovist contrast
adenoma does not take up contrast, FNH does
When are adenoma at risk for rupture or transformation to HCC
when >5 cm
if <5 cm, imaging in six months. If stable, then annually. If growing >20 % increase in diameter or if >5cm –> surgical resection due to risk of hemorrhage
What is a cavernous hemangioma
benign tumor
female
multi centric
peripheral nodular arterial enhancement with fill in to center
no tx unless large/ Kasabach Merritt syndrome
if <5 cm –> no further imaging
if >5 cm, repeat imaging in 6-12 months and then if stable, no further imaging. If it grows, then repeat in 6-12 months. N oprereuiste for surgical interveion
What does FNH look like on imaging
central scar
rapid intest enhancement in arterial phase
no role in stopping OCP
What characteristic is associated with risk of malignant transformation to HCC in an adenoma
beta catenin mutation (can do stain, but clinically available too)
What happens to the biliary system in adenoma on biopsy or eovist imaging
absence of bile duct
What drug blocks signal 1
tacrolimus
What drugs inhibit purine synthesis
MMF
AZA
What drug deplete lymphocyte through complement mediated cell lysis
thymo
what is POA of pred
inhibits formation of arachidonic acid, a precursor of inflammatory cascade
NFAT
What drug blocks signal 2
anti ctla 4
What blocks signal 3
MTOR
How does HSV present post transplant
usually in first month
acute hepatitis
How does adenovirus present post transplant
respiratory symptoms, gastroenteritis, hepatitis UTI
how does Parvo B19 present post transplant
severe anemia
How can cryptococcal disease present and what must be done
What do you need to watch for
pneumonia
meningitis
disseminated
usually via lungs. but in Pulm disease, have to rule out CNS disease
rapid decreasing IS and treating with anti fungal can lead to reconstitution inflammatory syndrome
What are risk factors for PNF
female donor
advanced age donor
pre-perfusion allograft steatosis
cold ischemia time
What cytokine aids with tolerance
Il 10
Does Hep E cause ALF
not typically, but in pregnancy associated with high mortality. can cause chronic hepatitis and cirrhosis
What is treatment of Hep E
- lower IS
- ribavirin
What type of renal disease is HRS
pre-renal
due to splanchnic vasodilation
What are pressure in SOS/post sinusoidal
how is this different than sinusoidal or pre-sinusoidal
wedged- increased
free- normal
HVPG- increased
in sinusoidal, it is same pattern
in pre-sinusoidal, everything is normal
What are risk factors associated with post transplant renal dysfunction
Strongest: older age and post transplant creatinine levels
maybe female
sex
other include: pretransplant cr, hep c
How does GVHD present
rash
cytopenia
GI compliaints
What are risk factors for GVHD
0- 1- class 1 HLA
HLA DQR or more than 2 HLA class 1 was not associated with GVHD
What does baby need in a mother with high viral load of Hep B
HBIG and vaccination at birth
What is the most common pathologic finding in cystic fibrosis
hepatic steatosis
What are risks of HAT
duration of hepatectomy
aortic conduit
multiple transfusions
What are down staging rules for HCC
- residual disease has to fall into Milan
2, one lesion 5-8 cm - 2-3 lesions:
- at least one greater than 3 cm
-each lesion less than or equal to 5 cm
- total diameter of all lesions less than or equal to 8 cm - four or five lesions
- each less than 3
total diameter less than or equal to 8 cm - AFP<1000
What graft has best outcome in LDLT
no survival difference in left lobe or right lobe
What does tamoxifen do to liver
fatty liver, typically after 1-2 years
Which hep c drug cannot be given in renal dysfunction or dialysis patients
anything with soft
What can be used for treatment in someone treated with interferon and cirrhosis
soft/vela, epclusa, in cirrhosis need duration of 12weeks
What should you give household contacts of someone with Hep A
post exposure prophylaxis
for hepatitis A infection vary by age and
health status. For healthy people over 12 months
to 40 years old, hepatitis A vaccine is preferred
over IG due to likelihood of response, long-term
protection, and equivalent efficacy to IG. IG is
recommended within TWO WEEKS of exposure for
persons over 40 years old due to lack of knowledge
on vaccine performance and possibility of more
severe presentation in patients with older age.WHAT HEP
What can happen to Hep B when getting treated with DAA
can cause flare
Which hep c drugs interact with ppi
epclusa
harvoni
How do you manage someone with HbcAb+ getting four weeks of prednisone 20 mg
treat for ppl hep b during treatment and at least six month post treatment
What do you do in someone with cirrhosis who goes from Hep B eAg+ to Hep B eAb+
continue tif indefinifintiely because there is cirrhosis
if no cirrhosis, could do therapy for 12 months and then stop (consolidation)
AST ALT in the 1000’s but bili disprportionatey low
herpes,
fevers
What can you get from boar
Hep E
tx in immunocompetent patients is supportive care
immunocompromised –> ribavirin
what do you do for immunesuppresed patients who are exposed to hep a
Immunoglobulin
is particularly important to give to immunosuppressed
patients exposed to hepatitis A given the
risk of fatal hepatitis A infection and reduced
response to vaccination in this population.
WHAT DRUG INTERFERES WITH mavyret
sofo
statin
amiodarone, BB(just need to watch HR)
What does Vit E help with
steatosis and inflammation. does not improve fibrosis
what conditions are associated with microvesicular steatosis (7)
- tetracycline
- cholesterol ester storage disease
- fatty liver of pregnancy
- aspirin
- valproate / mitochondrial
- HIV meds
- cocaine
What is dubin johnson
cannot export conjugated bilirubin so marked conjugated hyperbilli at birth
black liver
normal LFTs, no liver failure
ABCC2 gene
Criger Nagar
increase in unconjugated bili
UGT1A1
type 1 is absent enzyme so more severe than type 2
Which PFIC has elevated GGT
type3
(three three more beer)
which PFIC is associated with HCC
type 2
What does urso do in PBC
reduces LDL (Not HDL)
reduces risk of variceal bleeding
reduces risk of progression
reduces risk of needing transplant
does not help with osteoporosis or fatigue (note phlebotomy does help with fatigue in HH)
What grade of HE is asterixes seen?
Mininal and Grade 1 is covert HE
Grade 2 is asterixsis and overt
Grade 4 is coma
How is overt HE defined? How is covert defined?
Grade 2
Asterixsis
Disorientation
Covert: diagnosed with psychomotor or neuropsychological testing
How do you use ammonia in HE?
Increased blood ammonia alone does not add any diagnostic, staging, or prognostic value for HE in patients with CLD. A normal value calls for diagnostic reevaluation however
What type of hemorrhage is seen in HE
Intracerebral hemorrhage is five times more likely in patients with HE. So a CT isn’t needed to diagnose HE, but should be used to rule out other diseases like a bleed
When should rifaximin be used in HE?
Not enough data for rifaximin alone, should be used in conjunction with lactulose for prevention of recurrence of HE
Rifaximin added to lactulose is the best-documented agent to maintain remission in patients who have already experienced one or more bouts of OHE while on lactulose treatment after their initial episode of OHE
What are alternative regimens for HE?
IV LOLA Oral (not IV) BCAA for additional or alternative treatment
ORAL BCAA may have more of an effect on promotion of lean body mass rather than treatment of HE
Metronidazole or neomycin for alternative treatment
What type of HE do you treat?
Overt only
How do you prevent post TIPS HE
Routine prophylaxis is NOT recommended
When can prophylactic therapy for HE be discontinued?
Under circumstances where the precipitating factors have been well controlled (i.e., infections and VB) or liver function or nutritional status improved, prophylactic therapy may be discontinued
What influences the risk of repeated episodes of HE?
- overall liver function
- body habitus/ muscle mass
- controlling precipitins factors
If these are all controlled, prophylactic therapy may be able to be stopped
What are the daily energy intakes for HE?
35-40 kcal/kg ideal body weight
What are the daily protein intake for HE?
1.2-1.5 g/kg/day
What is the most common pediatric liver tumor
hepatoblastoma
Can be asymptomatic or painful from a larger tumor
What is the best thing for survival in kids with hepatoblastoma
resection (but this has to be possible anatomically)
AFP is a great biomarker for tumor
Who does Biliary atresia affect
-neonate
- female predominance
- higher rate in non-white
What other abnormalities are seen in biliary atresia
situs inversus, splenic malformation
intestinal malrotation
cardiac anomalies
pancreatic anomalies
What is seen at birth in those with BA
elevated bilirubin on Day of life 1
What is the triangular cord sign
seen in biliary atresia
increased echogenicity along anterior wall of portal vein
What is the gold standard dx for BA? What are other helpful tests
Intraoperative cholangiogram or PTC- want to see dye go into the liver and out of intestine
U/S - triangular cord sign
HIDA - want to see good excretion into intestine
Liver biopsy- not diagnostic, will see bie duct proliferation that detects extra hepatic biliary obstruction
What is kasai
all extra hepatic biliary tissue excised
creation of roux en y
roux jejunum anatomiste to portal plate
restores bile flow
What determines need for transplant in BA after kasai
time to kasai
those who got kasai within 30 days DOL were more likely to survive with native liver than those who got kasai >90 day of life
Total bili <2 at 3 months post kasai associated with higher survival with native liver
What is the definition of ALF in peds
- absence of pre-existing liver disease
- biochemical evidence of acute liver disease
–coagulopathy not corrected by vit k
—-INR >1.5 + HE
or
INR>2 –> status 1A
Vit A deficiency
ocular changes: dry eyes and night blindness
Skin changer: poor wound healing, hyperkeratosis
growth retardation
*if not responding well to supplementation, can give zinc as well
what is therapeutic target of vit D
> 30ng/mL
How is it best to supplement vit D in children?
D3, because it has better water solubility and therefore better absorption
Vit E defiiciency
Hemolytic anemia
Nuerologic deficits (ataxia, peripheral neuropathy)
muscle pain
High doses antagonize Vit A and adversely affect wound healing and platelet function
Thiamine or B1 deficiency
dry beriberi (loss of feeling, difficulty walking, loss of muscle function)
wet beriberi (high output cardiac failure)
Wernicke/Korsakoff (confusion, ataxia, ocular abnormalities)
Niacin or B3 deficiency
pellagra: dry skin and bright red tongue
Neuro: memory loss, abnormal behavior
Pyridoxine or B6 deficiency
paresthesia, seizure
oral changes (glossitis, ulcerations)
zinc deficiency
rash
alopecia
poor wound healing
myopathy
altered sense and test
?HE
selenium deficiency
cardiomyopathy
myositis and cramps
What happens if <18 and listed, but then turn 18 while waiting for a liver
what if <18, listed, then delisted, then turn 18
-classified as 12-17
-must be registered as an adult
What can be added to steroids in severe AH
NAC
- may improve 30 day mortality
