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Mechanistic Deep Dive
MELD-Na Calculation
- Bilirubin + INR + creatinine + sodium
- 90-day mortality predictor
- Replaced wait-time system 2002
MELD 3.0 (2023)
- Adds female sex coefficient
- Albumin
- Better discrimination
- Used by UNOS
Acute-on-Chronic Liver Failure (ACLF)
- Cirrhosis + acute precipitant
- Multi-organ failure
- High mortality
- ICU + LT evaluation
- CLIF-C scoring
Recent Trials & Updates
Machine Perfusion
- Normothermic + hypothermic
- DBD + DCD expansion
- Improved outcomes
Early LT for Severe AH
- Mathurin 2011
- US protocols (ELITAH)
- Strict psychosocial
- 6-month rule challenged
DCD Liver Transplant
- Donation after circulatory death
- Comparable outcomes in select donors
- Increasing utilization
HBV Post-Transplant
- Antivirals + HBIG combination
- Recurrence reduced to < 5%
- Lifelong therapy
Xenotransplantation
- Pig liver early trials 2024
- Multiple gene edits
- Limited duration so far
High-Yield Specialist Points
Tacrolimus Practical
- Trough 8-10 ng/mL early, 5-8 long-term
- CYP3A4 metabolism (interactions)
- Side effects: nephrotoxicity, neurotoxicity, hyperglycemia, hyperkalemia, tremor, hyperestrogenism
MMF Side Effects
- Diarrhea
- Leukopenia
- Anemia
- Use mycophenolic acid (Myfortic) for GI intolerance
mTOR Inhibitors
- Sirolimus, everolimus
- For CNI nephrotoxicity, HCC recurrence prevention, CAV
- Side effects: edema, hyperlipidemia, mouth ulcers, wound healing
CMV Tissue Invasive
- Esophagitis, gastritis, colitis, hepatitis, pneumonia, retinitis
- Treatment: ganciclovir IV 5 mg/kg q12h à 2-3 weeks â valganciclovir oral
EBV + PTLD Monitoring
- Monthly EBV PCR first year
- Reduction of IS first-line
- Rituximab for CD20+
- Chemo for aggressive
Skin Cancer Post-LT
- SCC most common
- UV protection essential
- Annual dermatology
- Voriconazole â SCC risk
Liver-Specific Drug Interactions
- Tacrolimus + azoles (â levels â fluconazole, voriconazole, itraconazole)
- Tacrolimus + macrolides (â levels)
- Tacrolimus + CCBs (diltiazem â)
- Grapefruit â levels
- Rifampin â levels
- Phenytoin â levels
- St. Johnâs wort â levels
Vaccinations Post-LT
- Inactivated only
- Annual flu, pneumococcal, COVID, RSV
- Avoid live (MMR, varicella, yellow fever, shingles live)
- Hepatitis A + B if susceptible
Pregnancy After LT
- Generally OK after 1-2 yr stable
- IS adjustment (avoid MMF â teratogenic)
- Higher pre-eclampsia, preterm risks
- Multidisciplinary
Cardiovascular Risk Post-LT
- Top cause of late mortality
- Aggressive management of HTN, lipids, DM
- Statins, ACE/ARB liberally
Renal Function Decline
- CNI nephrotoxicity
- 25-30% develop ESRD
- mTOR inhibitor switch for some
Pearls
- MELD-Na or MELD 3.0 for allocation
- Milan Criteria for HCC
- Mayo Protocol for hilar CCA
- Tacrolimus + MMF + prednisone standard
- CMV, EBV, PCP important infections
- HCV curable post-LT with DAAs
- HBV prevented with antivirals + HBIG
- PSC recurrence 30%+; PBC 20-30%; AIH common
- Outcomes: 1-yr 90%, 5-yr 75%, 10-yr 60%
- Living donor predominant in Taiwan