ABIM Tx Hepatology cheat sheet

Indications: decompensated cirrhosis with MELD 3.0 ≥15, HCC within Milan criteria, intractable pruritus or recurrent cholangitis in PBC/PSC, acute liver failure, and selected metabolic disorders (hyperoxaluria, familial amyloid polyneuropathy, urea cycle defects).

MELD 3.0 inputs are total bilirubin, INR, serum creatinine (floor 1.0, cap 4.0 mg/dL), serum sodium (bounded 125-137 mEq/L), albumin (bounded 1.5-3.5 g/dL), and sex; output is truncated at 6 and 40; creatinine is set to 4.0 when dialysis occurred at least twice in the prior week.

MELD 3.0 applies a fixed female sex coefficient, reflecting the higher mortality of women at a given creatinine; scores are recertified at least every 30 days unless a change in clinical status restages the candidate.

Standardized MELD exception pathways exist for HCC, hepatopulmonary syndrome, portopulmonary hypertension, hilar cholangiocarcinoma, cystic fibrosis, familial amyloid polyneuropathy, and primary hyperoxaluria.

Absolute contraindications: active extrahepatic malignancy outside agreed exceptions, uncontrolled sepsis or untreated active infection, ongoing alcohol or illicit drug use without an agreed abstinence interval, severe irreversible cardiopulmonary or neurologic disease, and inability to sustain lifelong follow-up.

Hepatopulmonary syndrome diagnosis requires intrapulmonary vascular dilatation on agitated-saline contrast echocardiography plus an alveolar-arterial oxygen gradient ≥15 mm Hg (≥20 mm Hg if age >64) and PaO2 <60 mm Hg on room air; MELD exception points are granted with periodic re-review of room-air oxygenation.

Portopulmonary hypertension precludes transplant when mean pulmonary artery pressure >35 mm Hg with pulmonary vascular resistance ≥240 dyn·s·cm⁻⁵ (3 Wood units) and wedge pressure ≤15 mm Hg; treatment with vasodilators is required before listing.

Acuity circles replaced the donor service area framework: livers are offered to candidates in expanding radii from the donor hospital (250 nm, then 500 nm, then larger distances and national sharing), with pediatric status 1A/1B candidates retaining priority.

HIV infection alone is not a contraindication; transplant is generally deferred for active AIDS-defining opportunistic infection, profound CD4 depletion, or uncontrolled viral replication.

Piggyback implantation with a side-clamped caval anastomosis (and often a temporary portocaval shunt) preserves caval flow, reduces splanchnic congestion, and improves hemodynamic stability compared with full caval cross-clamping.

Postreperfusion syndrome is a ≥30% fall in mean arterial pressure (or MAP <60 mm Hg) lasting at least 1 minute within 5 minutes of reperfusion; risk increases with higher MELD, graft steatosis, and prolonged cold ischemia.

Intraoperative targets include MAP ≥65 mm Hg, norepinephrine as first-line vasopressor, hematocrit roughly 25-30%, and correction of ionized calcium, potassium, and metabolic acidosis at reperfusion.

Biliary reconstruction is duct-to-duct over a stent in most adults; Roux-en-Y hepaticojejunostomy is chosen for PSC, retransplantation, or a very short recipient duct.

Early allograft dysfunction (Olthoff criteria) is any of: peak AST or ALT >2,000 IU/L within the first 7 days, INR ≥1.6 on day 7, or total bilirubin ≥10 mg/dL on day 7.

Primary nonfunction presents within 48-72 hours with AST >5,000 IU/L, INR ≥2.5, lactic acidosis, hemodynamic instability, and absent bile; urgent retransplantation is the only definitive therapy.

Doppler ultrasound within 24 hours assesses hepatic artery patency; a normal resistive index is approximately 0.5-0.7 with systolic acceleration time <0.08 seconds, and the portal vein should show continuous hepatopetal flow.

Early immunosuppression pairs intraoperative corticosteroid with tacrolimus (trough 8-12 ng/mL) and mycophenolate; mTOR inhibitors are withheld for roughly the first 4 weeks because of hepatic artery thrombosis and impaired wound healing.

Postoperative monitoring includes lactate clearance, daily INR and transaminases, urine output, mental status, and early extubation when graft function and hemodynamics permit.

Tacrolimus binds FKBP-12 and cyclosporine binds cyclophilin; both inhibit calcineurin, preventing NFAT dephosphorylation and IL-2 transcription, thereby blocking T-cell activation.

Common tacrolimus targets are 8-12 ng/mL in the first 1-3 months and 5-8 ng/mL for maintenance; cyclosporine targets are roughly 200-300 ng/mL early and 75-150 ng/mL for maintenance (C0 or C2 depending on center).

Mycophenolate mofetil (1-2 g/day) inhibits inosine monophosphate dehydrogenase and is teratogenic; dose is reduced for neutropenia <1,000/µL, and gastrointestinal intolerance is common.

Sirolimus and everolimus inhibit mTOR and IL-2-driven proliferation; early use is associated with hepatic artery thrombosis and wound dehiscence, and they are avoided with significant proteinuria or poorly controlled hyperlipidemia.

Acute cellular rejection histology (Banff): mixed portal infiltrate with eosinophils and neutrophils, bile duct epithelial damage, and subendothelial inflammation of portal vein branches; severity is graded by the rejection activity index (0-9).

Moderate-severe acute cellular rejection is treated first with intravenous methylprednisolone 500-1,000 mg daily for 3 days; steroid-resistant episodes receive thymoglobulin, and salvage options include alemtuzumab or basiliximab.

Chronic rejection shows vanishing bile duct syndrome with ductopenia in <50% of portal tracts, foam cell arteriopathy, and centrilobular cholestasis; it is largely irreversible and is an indication for retransplantation.

ABO-incompatible grafts carry higher rates of hepatic artery thrombosis and biliary strictures; donor-specific antibodies with microvascular C4d deposition suggest antibody-mediated rejection, treated with plasmapheresis, IVIG, and rituximab plus intensified immunosuppression.

The liver is relatively tolerogenic: hyperacute rejection is rare, HLA matching is not used for allocation, and spontaneous operational tolerance is described in a minority of long-term recipients.

Biliary complications occur in 10-25% of grafts: anastomotic strictures (most common, typically within 6-12 months), bile leaks, and nonanastomotic strictures from ischemia; ERCP with balloon dilation and stenting is first-line.

Hepatic artery thrombosis occurs in 3-5% of adult grafts and presents with fever, transaminitis, bile leak, or relapsing bacteremia; early surgical revascularization may salvage the graft, otherwise retransplantation is required.

Ischemic cholangiopathy from hepatic artery thrombosis or prolonged cold ischemia produces diffuse nonanastomotic strictures and biliary casts; endoscopic therapy is usually palliative.

Renal dysfunction after transplant reflects calcineurin inhibitor nephrotoxicity, perioperative injury, and preexisting CKD; acute kidney injury requiring renal replacement occurs in about 20% and long-term dialysis dependence in 5-10%.

Combined liver-kidney listing is considered for sustained dialysis or eGFR ≤30 mL/min/1.73 m² with structural CKD, and for metabolic disease such as primary hyperoxaluria or atypical hemolytic uremic syndrome.

Cytomegalovirus risk is highest in seronegative recipients of seropositive donors (D+/R−); either valganciclovir prophylaxis for 3-6 months or preemptive PCR monitoring is used, with extended courses for the highest-risk group.

Calcineurin inhibitors cause posterior reversible encephalopathy syndrome (seizures, headache, visual loss, posterior white-matter edema) and tremor; management is dose reduction or a switch to an mTOR inhibitor or belatacept.

Post-transplant lymphoproliferative disorder is Epstein-Barr virus driven in most cases; initial management is reduction of immunosuppression, followed by rituximab and chemotherapy for nonresponders.

Late infectious risk after 6 months is dominated by community-acquired pneumonia, urinary sepsis, and reactivation in patients with ongoing high-intensity immunosuppression.

Hepatitis C recurred in nearly all recipients before direct-acting antivirals; modern DAA regimens achieve SVR above 95% after transplant, and fibrosing cholestatic hepatitis, though now uncommon, requires urgent treatment.

Hepatitis B prophylaxis with hepatitis B immunoglobulin plus a high-barrier nucleos(t)ide (entecavir or tenofovir) reduces recurrence to under 10%; low-dose HBIG with antiviral therapy is increasingly used, and antivirals alone are an option in low-risk recipients.

Recurrent PSC affects 20-30% by 5-10 years and requires nonanastomotic strictures plus compatible histology; recurrent PBC affects 10-30%, and recurrent autoimmune hepatitis 20-30%, both often responsive to re-intensified immunosuppression.

Recurrent MASLD occurs in up to 50% of recipients and tracks with weight gain, diabetes, and hyperlipidemia; progressive fibrosis is less common but contributes to late graft loss in a subset.

HCC recurrence is 8-20%, mostly within 2 years, and is predicted by explant features beyond Milan criteria, microvascular invasion, and poor differentiation; surveillance imaging is typically every 6 months.

De novo autoimmune hepatitis presents with elevated aminotransferases, autoantibodies, hypergammaglobulinemia, and interface hepatitis, and responds to corticosteroid re-introduction with azathioprine.

Return to harmful drinking after transplant for alcohol-associated liver disease occurs in 10-20%; predictors include short pretransplant abstinence, prior relapse, and limited psychosocial support.

De novo hepatitis B can occur in recipients of cores from anti-HBc-positive donors and is prevented by lifelong nucleos(t)ide prophylaxis in that setting.

Biopsy indications include unexplained elevation of transaminases, bilirubin, or alkaline phosphatase; suspected rejection; evaluation of recurrent disease; and protocol surveillance in selected centers.

The Banff rejection activity index scores mixed portal inflammation, bile duct inflammation/damage, and subendothelial venulitis 0-3 each (edema scored in some versions), giving a total of 0-9 that separates mild, moderate, and severe rejection.

Acute cellular rejection is termed indeterminate when portal inflammation is present without convincing bile duct or venous injury; management ranges from observation to corticosteroid boluses depending on biochemistry.

Chronic rejection histology: ductopenia affecting <50% of portal tracts, foam cell arteriopathy, and cholestasis with centrilobular ballooning and hepatocyte dropout.

Fibrosing cholestatic hepatitis shows cholestasis, ductular proliferation, periportal fibrosis, and minimal inflammation in the setting of high viral replication; it is described in recurrent HCV and HBV.

Macrovesicular steatosis above 30% increases primary nonfunction and early graft dysfunction; macrosteatosis above 60% generally contraindicates donation, and microvesicular steatosis carries a smaller independent risk.

Ancillary stains: C4d for antibody-mediated rejection, CK7 or CK19 for ductular reaction and duct loss, CMV immunohistochemistry, and EBER in situ hybridization for Epstein-Barr virus and PTLD.

Distinguishing recurrent HCV from rejection: HCV shows lobular inflammation, hepatocyte apoptosis, and lymphoid aggregates, whereas rejection targets bile ducts and portal veins with eosinophils.

Fibrosis staging systems in common use are METAVIR, Ishak, and the NASH Clinical Research Network scheme; the Laennec system separately grades cirrhosis architecture, useful when recurrent disease is assessed.

Contemporary adult outcomes are approximately 90% 1-year and 75% 5-year patient survival, with 1-year graft survival near 85-88% and an overall graft half-life of roughly 12-15 years.

Beyond the first year, most deaths occur with a functioning graft; leading causes are cardiovascular disease, de novo malignancy, infection, and chronic kidney disease.

Late graft loss is driven by chronic rejection, recurrent disease (historically HCV, now MASLD, PSC, and autoimmune hepatitis), and late biliary or vascular complications.

Nonadherence to immunosuppression peaks in adolescence and young adulthood and is a leading preventable cause of late acute rejection, graft loss, and death.

Post-transplant malignancy includes cutaneous squamous cell carcinoma, PTLD, and oropharyngeal and lung cancer; risk is amplified by smoking, sun exposure, and cumulative immunosuppression.

Glomerular filtration rate commonly falls 10-20 mL/min/1.73 m² within the first year; calcineurin inhibitor minimization with mycophenolate, delayed CNI initiation, or belatacept-based regimens mitigates renal decline.

Frailty, sarcopenia, and pretransplant physical function independently predict post-transplant mortality, prolonged length of stay, and discharge to a care facility beyond what MELD alone captures.

Retransplantation accounts for a minority of procedures and yields lower graft survival than primary transplant, with outcomes most influenced by MELD at retransplant and interval since the first graft.