Session II- Cholangio Flashcards
what are risk factors for CCA?
In the east- parasitic infection - opisthorchis viverini and Clonorchis
In the west- PSC
intrahepatic and extra hepatic risk factors:
- cholerdocal cysts, choledocholithiasis, cirrhosis, HBV
What is the cause of death of most patients with CCA post resection?
local tumor recurrence within 2 years post resection
What is the most common subtype of CCA
perihilar –> extrahepatic (below cystic duct) –> intrahepatic
What is the standard of care for treatment of perihilar CCA in PSC and non PSC
in PSC- peri-hilar CCA should be transplant due to high risk of multifocal CCA
otherwise, perihilar CCA in non PSC should be resected. Ro or negative margin is 70-80%, 5 year OS depends on if negative margins and if negative LN
What are anatomical contraindications to resection for a perihilar non PSC CCA?
- Encaseement of PV- relative, as surgeons can now reconstruct PV
- Unilateral ductal dilation with contralateral vascular encasement
- unilateral atrophy with either contralateral ductal or vessel involvement
Can perihilar CCA be transplantable?
yes, per Mayo protocol (combines neoadjuvant chemo with LT), only for unresctable pCCA or all cases of pCCA in PSC
What is the eligibility criteria for transplant in unresectable pCCA?
Mayo protocol inclusino:
1. Diagnosis of pCCA (see other life)
2. unresectable tumor above cystic duct OR resectable pCCA in PSC
3. RADIAL (not longitudinal) diameter of 3 cm or less
4, no inta or extra hepatic mets
5. otherwise a LT candidate
What is exclusion criteria for neoadjuvant OLT in pCCA?
cannot be intrahepatic cya
no prior radiation or chemo
no prior biliary resection
no intrahepatic mets
no evidence of extra hepatic disease
CANNOT HAVE TRANSPERITONEAL BIOPSY (INCLUDING PERCUTANEOUS AND EUS GUIDED FNA). intraluminal via ecrp or transhepatic is ok, just not transperitoneal
Who does better after LT for pCCA?
PSC patients tend to do better compared to de novo (tend to be younger, dx at earlier stage, and less likely to have pathologic confirmation of CCA)
How to get MELD exception points for pCCA?
malignant stricture with one of the following:
1. aneuploidy
2. biopsy or cytology
3. evidence of mass that is <3cm Radial (extension of stricture does not count)
4. CA 19-9 >100 without evidence of cholangitis
Once transplanted for pCCA, what predicts disease free survival? What predicts recurrence
residual tumor. those with no residual tumor have the highest 5 year survival.
invovlement of LN predicts recurrence (which is why surgery is contraindicated and upfront chemo is prefered if LN involved)
you are transplanted for pCCA according to mayo protocol. but explant with high risk features. what next?
patients with high risk features on explant are often enrolled in adjuvant therapy protocol
- convert FK to mtor inhibitor after 4 weeks
- GEM/CIS month 4-10 post LT
-imaging month 4 and 12 post LT and then annual –> helps detect early disease to try and do resection and/or LRT since most will recur in the liver
What are post LT complications in pCCA?
PV stenosis (due to Radiation injury) - same rate in LDLT and DDT
HAT and stenosis
- Thrombosis is higher in DDLT than LDLT
- Stenosis is higher in DDLT than LDLT
This is because the time from radiation to transplant is shorter in LDLT, so can use the recipients native HA. In DDLT, the time is longer, so a jump graft is often needed
What is lifetime risk of CCA in PSC
6-13%
26% in those with dominant stricture
When are most patients with PSC diagnosed with CCA?
usually within 1-2 years of diagnosis of PSC (so early in disease)
How does CCA present in those with PSC?
-usually is multifocal
- do not need to have advanced fibrosis to develop CCA in PSC
When should you start to suspect CCA in those with PSC?
-worsening LFTs
- new dominant stricture, bile duct focal thickening/enhancement on MRCP
- CA 19-9 >100 (without cholangitis)
- bile duct obstruction
What is treatment for intrahepatic CCA?
resection with LAD
Ablation
TARE
transplant is contraindicated because survival is poor
What are the differences between intrahepatic CCA and HCC?
- no meld exception for iCAA
- poor prognosis with iCCA with high recurrence rate
How can you diagnose iCAA?
only be diagnosed via biopsy, not worried like you are with perihilar because everything is intrahepatic
radiologically, will see involution, bile duct dilation. If <2cm, will see early enhancement that persists. If >2cm, will see early peripheral enhancement followed by progressive enhancement of rest of lesion. LACK OF WASHOUT
What is considered early for iCCA?
single lesion <2 cm
if >2cm or more than 1 lesion –> advanced
How to use CA 19-9 in CCA?
good for prognosis, not so much for diagnosis
Can be elevated in benign biliary disease of cholangitis
Level is significantly associated with cirrhosis and LN mets
What are the Milan criteria for neuroendocrine tumors?
- Confirmed histology of G1 or G2 tumor
- Primary tumor drained by portal system (some rectal and bronchiole tumors are not drained by portal system(
- hepatic involvement of <50%
- Complete resection of primary tumor and all extra hepatic disease with stable disease od good response to therapies for at least 6 months
- age <60, relative contraindication
Where do NET metastasize to?
1/2 of NET patients develop liver mets and is OFTEN the only site of metastatic disease
majority fo time, these are unresectable
What is a hepatic angiosarcoma?
what are risk factors
3rd most common liver tumor
Risk factors: vinyl chloride, arsenic, cyclophosphamide, anabolic steroids, OCP
high mortality due to rupture and/or liver failure
Tx: resection + chemotherapy, OLT contraindicated due to poor outcomes
Can be mistaken for hemangioma, so if calling it hemangioma and esp if on periphery, think HEHE
Who does hepatic epithelial hemangioendothelioma affect?
women, middle aged
What stains should be used for hepatic epithelial hemangioendothelioma and which should be negative?
Factor VIII-related Ag, CD34, CD31
Negative for epithelial markers like cytokeratin and CEA
Must distinguish from adenocarcinoma or sarcoma
What is treatment for hepatic epitheliod hemangioendotheliuma?
resction
if >10 nodules or >4 involved hepatic segments –> LT, having mets is NOT a contraindication
anti-VEGF
What imaging is seen in hepatic epithelial hemangioendothelioma?
confluent mass with capsular retraction
looks a lot like hepatic hemangioma, so need to be sure
what does hep c cause? macro or micro steatosis?
macro
what does Wilson cause? macro or micro steatosis?
macro
what does parenteral nutrition or starvation cause? macro or micro steatosis?
macro
what does abetalipoproteinemia cause? macro or micro steatosis?
macro
unable to absorb fats, very low cholesterol, hepatomegaly, prob skinny, look for fat soluble vitamins deficiencies
what does amiodarone cause? macro or micro steatosis?
steatohepatiits
what does methotrexate cause? macro or micro steatosis?
macro
what does tamoxifen cause? macro or micro steatosis?
macro
what does steroids cause? macro or micro steatosis?
macro
what does valproate cause? macro or micro steatosis?
micro
what does antiretroviral meds cause? macro or micro steatosis?
micro
what does acute fatty liver of pregnancy? macro or micro steatosis?
micro
what does HELLP cause? macro or micro steatosis?
micro
what does inborn error of metabolism cause? macro or micro steatosis?
micro
What are the alcohol cut offs when evaluating patients with suspected NAFLD?
> 21 standard drinks on average per week in men
> 14 standard drinks on average per week in women
this is considered significant when evaluating patients with suspected NAFLD
Do you screen family members for nafld?
not currently
What helps to predict steatohepatitis in patients with NAFLD?
metabolic syndrome. this helps identify patients who may benefit from liver biopsy
What scores can help predict fibrosis in NAFLD?
NAFLD fibrosis score
and FIB 4 index (plt count, age, AST, ALT)
VCTE or MRE helpful in identifying advanced fibrosis in patients with NAFLD
Who should get a biopsy in NAFLD
presence of metabolic syndrome
NFS
FIB4
VCTE
MRE
if there are competing etiologies for HS
What should histology for NAFLD differentiate?
NAFL (steatosis)
NAFLD with inflammation
NASH with steatosis with lobular and portal inflammation and hepatocellular ballooning
When can pharmacologic treatments be used in NASH
in those with biopsy proven NASH and fibrosis
What kind of lifestyle intervention helps with NASH
hypo caloric diet (daily reduction by 500-1000 kcal) and moderate intensity exercise
what percentage of weight loss is needed to improve nash
3-5% of body weight to improve steatosis
7-10% to improve majority of histopathological features of NASH including fibrosis
Can you use metformin in NASH
no, does not improve histology
Who can pioglitazone be used in?
those with and without diabetes with BIOPSY PROVEN NASH. If not biopsy proven, should not be used
Who can vit E be given to with NASH?
daily dose of 800 IU/day
improves histology in nondiabetic adults with biopsy proven NASH
should not be used in diabetic patients or those with cirrhosis or those without biopsy
How to use omega 3 fatty acids in NASH?
should not be used as a specific treatment of NAFLD or NASH, but may be considered to treat hypertriglyceridemia in patients with NAFLD
Can statins be used in cirrhosis?
yes, esp NASH cirrhosis since there is high risk of CVD. But should be avoided in decompensated cirrhosis
Which IS drug increases risk of obesity? Which decreases risk of obesity?
Steroids increase risk of obesity
mTOR decreases risk of obesity
Which IS drug increases risk of DM
steroids> tac, cyclo> mTOR
Which IS drugs cause dyslipidemia
mTOR>cyclo>tac, steroids
which drug causes HTN
tac,cyclo>steroids>mTOR
What is the most important risk factor for NAFLD recurrence after LT
post LT BMI
What IS is absorbed in the duodenum?
tac and mTOR
where is mmm absorbed?
in stomach, so can be affected by sleeve gastrectomy. also lose stomach in RGY so also affected in Roux
what does cyclo need for absorption
bile salt
What is needed for diagnosis of iCCA?
biopsy/histopathological confirmation
How do you treat iCCA?
surgical resection for those with a single nodule in a resectable location without evidence of metastatic disease and who have adequate functional liver volume
transplant is not an option
no data on LR
What is workup for pCCA or dCCA?
cross sectional imaging for assessment of tumor extent
ERCP with biliary brushings for cytology and FISH anaylaisis
if tx is an option, avoid EUS FNA and percutaneous biopsy due to risk of tumor dissemination. If LT is not an option, then EUS FNA can be diagnostic
When should MAYO protocol be used?
if pCCA + PSC
or
pCCA in de novo (non PSC) but unresectable
What chemo is recommended in advanced CCA
gemcitabine plus cisplatin for newly diagnosed patients
if progression on gemcitabine and platinum, then FOLFOX for second line
What should you do is a lesion with arterial enhancement and portal phase washout is seen in someone without cirrhosis?
Diagnosis of HCC cannot be made by imaging in patients without cirrhosis, even if enhancement and washout are present.
So biopsy is required in these cases.
What are high risk features of HCC
size >/= 1 cm
arterial enhancement
washout
What is stage 0 BCLC
child Pugh A
single lesion <2 cm
ecog PS 0-1
Treatment:
resection
MWA or RFA
What is stage A BCLC
single or 2-3 nodules <3 cm
ECOG PS 0-1
Treatment:
Resection
OLT
RFA
MWA
TARE/TACE
SBRT
What is stage B BCLC
multinodular
ECOG PS 0-1
Child Pugh A-B
Treatment: TARE
Downsize –> OLT
What is stage c BCLC
portal vein invasion
ECOG PS 0-2
Treatment:
Sorafenib
Levatinib
Second line: nivolumab
cabozantinib
regorafenib
What is Stage D BCLC
child Pugh C
Any T, N, or M
ECOG PS >2
Treatment:
OLT
supportive care
How do you manage LR1 and LR2 lesions?
observation with imaging according to standard HCC screening
How do you manage LR3?
intermediate probability
repeat or alternative diagnostic imaging in 3-6 months
How do you manage LR4
multidisciplinary discussion for tailored workup that may include biopsy or repeat or alternative diagnostic imaging in
How do you manage LR M
malignancy but not definitive HCC
multidisciplinary discussion, but most cases will need biopsy and/or repeat/alternative diagnostic imaging in
What is eligibility for down staging to get MELD exception points?
a. one lesion >5 cm and <8 cm
b. 2-3 lesions; at least one >3, all <5, total diameter less than 8 cm
c. 4-5 lesions <3 cm, total diameter less than 8 cm
Have to be downstaged into MILAN in order to be eligible for meld exception points
What is requirement for atezo/bev
required to have EGD within 6 months and adequate control of varices
when is post transplant malignancy more common?
can occur early or late into transplant. Probability of death from malignancy increases over time
What is the most likely cancer de novo after transplant
non melanoma skin cancer
What are risk factors for solid malignancies post transplant?
age
male sex
smoking
LT for alcohol related cirrhosis or PSC
excess IS
sun exposure
Infections:
- HHV8 for kaposi sarcoma
- ebv for nasopharyngeal carcinoma
- hpv for cervical, vulvar, andal, and oropharyngeal
- hbv for hcc
Who has highest risk of CRC post transplant?
those transplanted for PSC. but also found that any one transplanted, had higher rate- but unclear if this should change surveillance guidelines
When is risk of PTLD highest?
in the first 12-18 months (prob because this is time when IS is highest)
How often should patients with PSC and IBD get colonoscopy?
annual, even post transplant
Can checkpoint inhibitor be used post transplant
with caution, graft loss seen in 1/3 of patients
What are curative therapies for HCC
resection
LT
ablative techniques
What are non curative therapies for HCC
TACE
TARE
SBRT
chemo
What is T1 lesion
one nodule < 2 cm
(remember T2= milan= 1 lesion that is 2-5 cm OR 2-3 lesions =3 cm)
What is T2 lesion
one nodule 2-5 cm
or
2-3 nodules all <3, but each has to be greater than or =1
How should patients with child Pugh A cirrhosis and early stage (T1 or T2) HCC be treated?
AASD recommends resection over RFA
What are AFP cutoffs for MELD exception points
AFP>1000 regardless of tumor size cannot get MELD exception
must be <500 after LRT to be eligible
How do you survey for HCC recurrence in post transplant patients
abdominal and chest CT scan, but timing and duration is not certain
Retreat score ** not in guideline
When is thermal ablative technique most efficacious?
when tumor is <3 cm
What is needed post ablation?
patients postulation are at high risk for recurrence and surveillance should be performed with contrast enhanced CT or MRI every 3-6 months
Should adults with cirrhosis awaiting LT and T1 HCC be treated or undergo observation?
observation with follow up imaging over treatment. Wait until they become T2 lesion so that they can get MELD exception points
Should adults with cirrhosis and T2 HCC awaiting liver transplant undergo transplant alone or transplant with bridging while waiting?
bridge to therapy (use of LRT to induce tumor death and deter tumor progression beyond Milan criteria
Should adults with advanced HCC with microvascular invasion and/or metastatic disease be treated with systemic therapy or LRT or no therapy?
systemic therapy in patients with CP A/B plus advanced bcc with microvascular invasion and/or metastatic disease
What is the MOA of CyA
forms complex with cylcophilin and this binds to calcineurin. So now after blocking calcineurin, there is inhibition of dephospho rylation of NFAT
Excreted in bile
half life of 8 hours
p450 metabolism
What is MOA of tacro?
binds to immunophilin and forms a complex and inhibits calcineurin.
25x more potent than CyA
excreted in bile
half life of 11 hours
p450 metabolisms
What are CNI side effects? (6)
nephrotoxicity (early reversible, later irreversible)
neurotoxicity (tac >cyA) ranges from seizures, Pres, HA, tremors
Diabetes (TAC.CyA)
HLD, HTN
Hair loss (TAC), gain (CyA)
HUS (Tac>cyA): low plts, hemolytic anemia, AKI
What are renal sparing protocols?
reduction of CNI exposure, but typically requires antibody induction
What is MOA of MMF
inhibits purine synthesis
potent inhibitor of B and T cells
Made SE: GI, marrow suppression, GVH like gut lesion
Stop if considering pregnancy
What is MOA of sirolimus/everolimus?
form complex with FKBP that binds to mTOR and halts cell cycle progression
blocking mTOR inhibits vascular endothelial growth factor and angiogenesis that is needed for wound healing
What black box warning for sirolimus
increased risk of HAT and death in LT recipients
What are SE of mTOR
pancytopenia
HAT
Hypertriglyceridemia
oral and GI ulcer
proteinuria (usually in those with underlying CKD)
pneumonitis
side effects are usually trough dependent so sometimes can try lowering trough
sirolumus half life is 63 hours
EVL is 30 hours half life, but usually BID dosing
excreted in bile
How are CNI, mTOR, steroids metabolized?
metabolized thought the cytochrome P450 3A4, 3a5.
So if a drug blocks the Cyp450, it will increase concentration
Substrates for the efflux transporter P-GP
What drugs increase concentration of CNI and mTOR
any drug that blocks CYp3A4/5
macrolide: clarithromycin, azithromycin
antifungals: fluconazole, verapamil
CCB: diltiazem, nifedipine,
others: reglan, protease inhibits, grapefruit juice
what drugs decrease CNI and mTOR?g
drugs that induce CYP3A4/5
antibiotics: rifampin, rifabutin
Anticonvulsants: phenytoin, carbamazepine, phenobarbital
Others: St johns wort
When does acute TCMR occur? helpful labs?
generally 5-30 days post transplant
more common in those with autoimmune, young, females, retransplant
if GGT is normal, acute rejection is unlikely. but GGT is not specific for AMR
How to differentiate between mild, moderate, and severe ACMR?
mild <50% portal tract involvement
moderate >50% portal tract involvement
severe: obliteration of central vein in addition to portal vein
How do you treat mild TCMR vs moderate to severe TCMR?
mild- increased maintenance IS without steroids
moderate/severe: steroids. If severe histopath, consider initial ATG
What is chronic rejection
progressive, obliteraly arteriopathy and intrahepatic cholangiopathy/loss
who does chronic rejection usually involve?
multiple TCMR bouts
severe TCMR with centriblobular necrosis
noncompliance
under IS
What are histologic criteria for chronic rejection
- need 8-10 portal tracts (so need at least a 2 cm biopsy piece)
Minimal criteria for CR are any of the following:
- bile duct loss affecting greater than 50% of the portal tracts
- presence of bile duct atrophy/pyknosis affecting a majority of the bile ducts with or without bile duct loss
- foam cell obliterative ateriopathy
What stain can be used for chronic rejection
CK-19- stains for bile duct. So if use stain and don’t see bile ducts, may be sign of cr
What is management of chronic rejection?
-switch cyclo to tac in early CR
- add n mTOR or MMF but little data
- consider infection prophylactic
- avoid over IS with later cases of liver synthetic dysfunction
What is associated with graft failure in chronic rejection
- bile duct loss >50%
- severe perivenular fibrosis
- foam cell clusters within sinusoids
- severe hyperbole
When to consider AMR?
-refractory rejection/steroid resistant
- restransplatn (sensitized)
- SLK
- unexplained chronic fibrosis or inflammation
How to make diagnosis of AMR
histologic findings: portal edema, ductular reaction, neutrophilia, sinusoidal inflammatory infiltration
C4d staining (lining portal vasculature and in the SINUSOIDS)
presence of DSA
What is management of AMR
antibody binding agent: IVIG
antibody removing therapy: plasmapharesis
Antibody production inhibitor: rituximab (anti CD 20)
bortezomib (proteasome inhibits - inhibits plasma cells)
eculizumab: complement inhibition (blocks injury from DSA)
What is first line therapy for aspergillous
voriconazole
amp causes renal toxicity and shake and bake
itraconazole is used for dimorphic fungi like histoplasmosis but not first line for asperfillus (for the fungi that are geographic)
How can asperillus present?
- colonization - no symptoms
- allergic bronchopulmonary aspergillosis (wheezing, IgE, treatment is inhaled steroids)
- aspergilloma, fungas ball
- invasive pulmonary aspergillosis
– in sinus
– lungs (nodules)
What is treatment of aspergillous
voriconzaole. can’t use long term because of risk of skin cancer. Can use posa for prophylactic
What is seen on biopsy for aspergillous
acute septae, think of two fingers
what causes non septet hyper at 90 degree
mucor
what is treatment of mucor
surgery (antifungals aren’t as helpful because don’t have good blood supply) + ampho
so source control + anti fungal
what is treatment for cmv pneumonitis
ganciclovir
get CMV PCR- culture results are too slow
In general: start with PO valganciclovir 900 BID for induction
can use IV ganciclovir if severe disease absorptionor if bad GI disease and concerned about
Minimum 2 weeks (3 weeks for GI) if PCR is undetectable
- cidovovir or foscarnet if resistant CMV
How can CMV present
- asymptomatic viremia
- CMV syndrome - mono like, fever, malaise, myelosuppresion
- end organ disease
- pneumonia, hepatitis, colitis, retinitis, CNS - Compartmentalized CMV- pathologic evidence of end organ disease, where serum PCR is negative, but biopsy is positive (think CMV colitis)
Who does HEV affect and what is treatment? What do you see on biopsy
affects immunocompromised
can see portal inflammation with mixed lymphoplasmacytic infiltrate
Treatment is ribavirin and to decrease IS
What is the cutoff for treating assymptomatic CMV viremia”
1500 IU/mL
What are risk factors for death >1 year post LT
male
older age
HTN
DM
pre-transplant malignancy
renal failure = strongest predictor
What is the most common metabolic complication post LT
HTN-60%
HLD and metabolic syndrome 50%
DM 30%
usually occurs 1-3 years post transplant
Which is worse for HTN, cya or tac?
CYA - slight predisposition when compared to tac
How do you treat HTN post LT
first line: calcium channel blocker: amlodipin
but if proteinuria is present–> start with ACE or ARB
second line: acei/arb
third line: beta blockers
first line combination: calcium channel blocker +ACEI/ARB
What is goal BP post LT
BP<140/90
if proteinuria present, goal <130/80
How to diagnose post LT HLD?
Fasting LDL >100
Fasting Triglycerides >200
What drugs do you need to watch in HLD post LT
statins ok
do not use sirolimus as it worries HLD
prefer tac over CSA, minimize CNI (add MMF to do so)
How do you treat hypertriglyceridemia post LT
Fasting TG>200
omega 3 fatty acids
gemfibrozil or fenofibrate
When to chose tac over CyA? when to choose Cya over tac
Cya worsens HTN and HLD
Tac worsens DM
What are meds to avoid in DM and renal dysfunction
avoid metformin
If GFR<30 –> avoid acarbose, exenatide, pramlintide, gliptins
What are the CVD risk factors?
-older age at transplant
- male
history of CAD
transplanted for NASH
post LT DM
post LT HTN
obesity
What drug should be avoided in CVD?
sirolimus
What are risk factors for chronic renal failure post LT
-peri-transplant renal failure
pre-existing CKD
- CNI
-DM
-HTN
How does CNI causes renal injury
renal vasoconstriction
What to do if on CNI and renal injury
dose reduction may prevent progression of renal injury
no clear difference between tac and CSA
What is the best strategy for renal preserving IS?
early adoption of low dose CNI + mmf
Why is it hard to use mtor + mmf
acceptable rejection but increase side effects like leukopenia and mouth ulcers
When does bone density worsen and improve?
bone density significantly declines in the 3-6 months post LT but returns to pre transplant levels by one year
When do you treat for osteoporosis post LT
T score <-2.5 or if fractures occur
T score <-2.0 and other risk factors
How do you treat osteoporosis
First line: bisphosphonates
- can cause harm to fetus, careful in pre-menopausal women
- increased osteonecrosis of jaw in patient with renal impairment
-aledronate good oral option
- zoldrndroic acid good infusion option
What are the cancers in post LT for which risk is significantly increased
non melanoma skin cancer : sun explorer, smoking, ETOH
PTLD: >50 years old, EBV negative recipient
vulvar carcinoma:
lung/head & neck cancers: tobacco and alcohol use
colorectal cancer: IBD
What is first line tx for PTLD
reduce IS
What happens to pediatric growth post LT
linear growth failure is common pre tx, but may return to normal after successful LT
Catch up growth plateaus 2-3 years post LT (steroids may delay or attenuate catch up growth)
50% pediatric recipients will ultimately have lower heights than their genetic potentials
lower psychosocial function
increase in cognitive deficits
How do you manage late HAT
41% require re-transplant (vs 71% for earlier HAT)
30% AC only
50% develop ischemic cholangitopathy
In those who are retransplanted, what are outcomes compared to initial LT
outcomes significantly worse than for initial LT
How do you make diagnosis of fibrosis cholestatic HCV
usually month 1-3
bili >6
Alk phos >5 x ULN
very high HCV RNA
absence of biliary complications
What is seen on biopsy for fibrosis cholestatic HCV
ballooning of hepatocytes in perivenular zone
little inflammation
variable bile ductular proliferation without duct loss
What are predictors of alcohol relapse post LT?
higher number of drinks per day (>10)
prior relapse despite treatment for AUD
drinking despite legal or medical consequences
poor social support
significant psychiatric co-morbidity
co-morbidt illicit drug use (does not include THC)
***not clear that any specific length of pre- LT abstinence predicts post LT abstinence
Which meds contribute to steatosis post LT
steroids
mtor>CNI
What is incidence of post LT steatosis at 1 and 5 years
1 year: 60%
5 year: 80%
What is incidence of post LT NASH
1 year 50%
5 year is 40%
What is the most important things we can do to prevent post LT death in NASH pt
manager CV risk factors
How often does AIH recur post transplant
35%
What are risk factors for recurrent AIH>?
no consistent risk factor!!!
ACR, steroid withdrawal are NOT associated with increased AIH
But acute and chronic rejection are more commonly seen in patients transplanted for AIH
those who get recurrent AIH, recurrence is even higher if re-transplanted
What percentage and when do patients with PBC recur?
20-30%
at 5 years
When does recurrent AIH usually occur
8-12% at 1 year post LT
36-68% at 5 years
Which drug has been slightly associated with recurrent PBC
Tac in small studies has been associated with recurrence of PBC
How often does PSC recur
20% at 5 years
What do you have to be mindful of when diagnosisg recurrent PSC
think about ischemic cholangiopathy
so do not diagnose <90 post LT for PSC
IC occurs relatively early post transplant and then plateaus meaning they don’t develop allograft dysfunction whereas PSC typically progresses
IC doesn’t start at year 2, but PSC can
What are risk factors for recurrent PSC
active IBD
ACR, especially repeated episodes
Cholagniocarcinoma before LT
younger recipient, older donor
Living donor LT increases risk of recurrent PSC
What is protective against recurrent PSC
pre LT colectomy
What are outcomes of re-transplant for recurrent PSC
outcomes are better than when retransplanted for other outcomes
What are recurrent rates for HCC for those transplanted WITHIN Milan criteria
10-15% HCC recurrence rate after transplant
Median time to recurrence =20 months
What are major sites of recurrence for HCC
lungs and liver
What are pre LT risk factors for rHCC
AFP: higher AFP means higher risk of rHCC
- AFP trend upward= higher risk of rHCC
If out of Milan at time of transplant, higher risk of rHCC
What are post LT risk factors for rHCC
AFP at transplant
Microvascular invasion
Largest size (cm)+ number of viable HCC nodules on explant
What is treatment of recurrent HCC
- reduce IS in general. Sirolimus/mTOR does not improve recurrence free survival
- resection or LRT is treatment of choice if singe rhCC
- when disease is more widespread, then systemic therapy is appropriate
— but avoid immune checkpoint inhibits due to risk of graft loss
Which group has higher risk for recurrence post transplant for cholangiocarcinoma
de novo cholangio has higher risk of recurrence when compared to cholangio in those with PSC
LT for PSC associated perihilar CCA has significantly increased survival compared to de novo PSC
What is post LT surveillance for HCC
in general it is CT Abdomen/Pelvis and chest every 6 months for three years post LT
based on RETREAT score and risk factors
What are risk factors for recurrent pCCA?
peri-neural or lymphovascular invasion in explant
presence of viable tumor in explant
elevated CA 19-9 at time of transplant
encasement of portal vein
What is cholestatic Hep A
protracted jaundice >3 months
T bili >10, peak levels around week 8
What is relapsing Hep A
symptoms for 3 weeks
elevated LFTs up to 12 months
of those who relapse –> 20% have more than 1 relapse
What are extra hepatic manifestations of Hep A
vasculitis, cryoglobulinemia, aplastic anemia
What can you use for cholestatic liver tests in acute viral hep
urso 300 mg BID x 3 weeks
What are the Hep A vaccines
Havrix 2 doses, 0 and 6-12 monts
VAQTA 2 doses, 0, 6-18 months
TwinRx- combined Hep A and Hep B, 0, 1, 6 months (3 doses)
or accelerated is 0,7,21,30 days + booster at 12 months (4 doses + booster)
Can patients have anti HEV without having HEV
yes, prevalence of anti HEV is 6-21% in US
How do you get HEV
swine, shellfish, deer board, blood transfusion
How do you get HEV
swine, shellfish, deer board, blood transfusion
How do you treat Hep E in immunocompromised patients
- Reduce immunosuppresion
- if HEV + after 12 weeks of reducing IS, then given ribavirin 600-1000 mg/d for for 12 weeks
- if still positive, then extend for 12 more weeks
- can check HEV in serum and stool
What mutation is most common in patients with Budd Chiari
JAK 2 *** normal blood counts do not rule out myeloproliferative disorder
What must be excluded in BCS
a space occupying lesion - can lead to compression of the vasculature (i.e.Hepatic cysts, adenomas, cystadenomas, invasive aspergillosis)
What malignancy can be seen with BCS
HCC
What are risk factors for HCC in BCS
long segment IVC thrombus
combined IVC and HV thrombus
cirrhosis
older age
*** beware- large nodules (regenerative, dysplastic) may be misinterpreted as HCC
What is SOS
circulatory dysfunction at the level of sinusoid, so occlusion of central venue but hepatic vein are patent
what is criteria for SOS, early?
After stem cell transplant 1-21 days
2 of the following three thing:
- total bili >2
-hepatomegaly or RUQ pain
- >5% weight gain from fluid
What is diagnostic criteria for SOS, late
after stem cell transplant >21 days
- Histologically proven OR
-total bili >2
- painful hepatomegaly
>5% weight gain from fluid, ascites and US evidence of SOS
What is used for prevention and treatment of SOS
Urso for prevention
Defibrotide(antithrombitic, fibrinolytic) for treatment
What chemo is associated with SOS
myeloablative
AZA
oxaliplatin
cyclophosphamide
Mephalan
***cirrhosis is a contraindication for myeloablative therapy
What are the components of MELD used for Heart Transplant candidates
only includes cr and bili
INR is not part of it because patients undergoing heart transplant are usually on warfarin
What is graft vs host disease and when does it occur
donor cytotoxic T cells against recipient tissue
occurs >1 month post OLT
What is diagnosis of GVHD
liver tests are normal
look for chimerism (person’s body contains two different sets of DNA)
What is treatment of GVHD
steroids/ decrease or stop IS
can do ruxolitinib or infliximab if steroid refractory
what are symptoms of GVHD
fever, diarrhea, rash (that is trunk and arms compared to palms and soles in post HSCT)
which vaccines are contraindicated post transplant
live
varicella (Zostavax), small pox, BCG, MMR, yellow fever, influence flu mis
How to given pneumonia vaccine post transplant
- 15 or 20 (both of these are conjugate)
- If you got 15, then give 23 (poysaccradice 1 year later).
- IF got 20, nothing is needed
What travel vaccines are contradicted in post
cholera, live thyroid, yellow fever
*** there is a inactivated typhoid that can be given
When should patients with IBD and PSC get colonoscopy after post transplant
What about PSC alone
annually
PSC alone: first year and then q5 years
What is the national organ transplant act
1984- established framework for transplantation. UNOS, OPTN, SRTR
What is the final rul
2000
established regulatory framework for OPTN (which allocates organ
he Final Rule dramatically changed the way organ donations were allocated in the United States, moving away from a system that favored geographic areas with large donor banks towards a system that prioritized a patient’s need for organ transplant over their proximity to the donor. This move reflects increased ability to successfully preserve and transfer organs for organ transplantation farther than was previously possible. This move was controversial among areas with larger donor banks because there were concerns that the rule would disincentivize organ donation. Donor banks believed donors would be less likely to donate if the organs were being transferred out of state
What did the declaration of Istanbul say
illegal to buy or sell organs, 2008
What are the five components of ethics
- beneficence- moral obligation to act for the benefit of others
- autonomy
- non maleficence- obligation not to inflict harm
- justice
- utility- benefit to most individuals
What ethics are seen in LDLT
candidate: beneficence (moral obligation to act for the benefit of others)
Donor: nonmaleficence, autonomy
What ethics are seen in organ allocation
jsutice
utility (benefit to most individuals)
What is the order of surrogate decision making
- POA
- if no POA, then spouse –> children –> family
HOw to make a diagnosis of pCCA?
positive biliary biopsy or positive cytology
if no biopsy available, either of these can be used to define pCCA
1. malignant appearing stricture + CA 19-9>100 (with no biliary obstruction)
2. malignant apeparing stricture + suspicious cytology +/- aneuploidy on FISH
3. perihilar mass with imaging features of CCA
What is Mayo protocol
only for periphilar CCA in unresectable denovo or in pCCA in PSC
- IV5FU followed by external beam radiation and brachytherapy
- Capecitabiline until transplant
- abdominal explorationfor staging right before transplant to sasess for regional LN invovlement and peritonael mets
- Liver transplant
at is chemo regiment for advanced cholangio
cis/gem
- if progresses on gem/cis, then FOLFOX
WHAT genetic alteration is associated with less aggressive tumor biology in iCCA
FGFR
KRAS- poorer prognosis
k67 in net is associated with what
what about pancferatic NET vs GI NET
worse prognosis
pancreatic NET is worse prognosis
What is basiliximab
IL2 receptor antagonist
What drugs are metabolized by p450
tacro
cyclo
mtor
steroids
What is considered prolonged WIT and prolonged CIT
WIT>40 min
CIT >12 hours
What is considered too much steatosis
> 30%
What is considered older donor age
> 70 years
What are the ways liver can sbe split for transplant
child or small adult: LLS (segment 2/3)
adult: extended RL or triage (1,4-8)
What is criteria for living donor tx
adult age 18-60
BMi <30
minimal hepatic steatosis <10%
graft size
- big enough for recipient GRWR >0.8 (graft to recipient weight)
-not too big for the donor (RLV>/= 30%
What is reperfusion syndrome
right when unclamping occurs
drop in MAP >30% within first 5 minutes after reperfusion, lasting 1 minutes
associated with high er renal dysfunction, and major CVD events
risk factors are CIT, donor age
define early allogradt dysfunction
EAD factors (>/= 1)
-bili >10 on POD 7
-INR >1.6 on POD 7
-ALT or AST >/= 2000 within first 7 days
What is Primary graft non function
irrecersible extreme result of EAD not compatible with survivial without retransplant
What is a consequence of EAD
AKI
Do we care about macro or micro when thinking about grafts
only care about macro
How to calculate GWRW?
recipient weight is 78.8 kg
right lobe is 960 cc or mL
960/1000 =0.96
(0.96/78.8)*100 = 1.21%
and since this is >0.8, would be acceptable if RLV is >30%
Galactomannan tells you what
aspergillous, tx vori
What is acyvlovir for and what is gancicylvir for
HSV- acylovir (pneumonitis rare)
CMV- gancivlori
what is HEV mistaken forand what can it lead to
mistaken for rejection
can lead to cirrhosis
Can you use hepatin for BCS
can cause HIT
what hvpg is indiciative of SOS
HVPG >10
is biopsy needed for ddx of SOS
no, not required, because it can be patchy, but rememeber HVPG >10 high specificity for
