Liver Transplant Medications

📋 Key Information Summary

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Liver transplant immunosuppression in Australia follows a triple-drug paradigm: a calcineurin inhibitor (CNI) — almost exclusively tacrolimus — plus an antimetabolite (mycophenolate mofetil) plus short-course corticosteroids.
Induction therapy with basiliximab (IL-2 receptor antagonist) is standard for most adult liver transplant recipients; antithymocyte globulin (ATG) reserved for high immunological risk or delayed renal recovery.
Tacrolimus target trough levels vary by time post-transplant: 8–12 ng/mL (months 0–3), 5–8 ng/mL (months 3–12), 4–6 ng/mL (>12 months) — individualised by rejection risk and renal function.
CYP3A4 interactions are critical: azoles (fluconazole, itraconazole), macrolides (erythromycin, clarithromycin), diltiazem, and grapefruit juice raise tacrolimus levels; rifampicin, phenytoin, and carbamazepine dramatically lower levels and must trigger pre-emptive dose doubling and frequent monitoring.
Mycophenolate mofetil (CellCept®) 1 g BD is the preferred antimetabolite; azathioprine used less commonly. mTOR inhibitors (sirolimus, everolimus) are second-line agents useful for CNI nephrotoxicity sparing and HCC recurrence reduction.
Post-transplant diabetes mellitus (NODAT) affects 10–40% of recipients; tacrolimus is a stronger risk factor than ciclosporin. Metformin is first-line; insulin may be required acutely.
CMV prophylaxis with valganciclovir is guided by donor/recipient serostatus: D+/R− (highest risk) receives 6 months; other at-risk combinations receive 3–6 months.
PJP prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is given for 6–12 months post-transplant; dapsone or atovaquone are alternatives for sulphonamide allergy.
Chronic kidney disease develops in up to 20% of recipients by 10 years — primarily CNI-mediated. Strategies include CNI minimisation, mTOR inhibitor conversion, and early nephrology referral.
De novo malignancy risk is 2–3× general population; post-transplant lymphoproliferative disorder (PTLD) is associated with EBV serostatus mismatch. Lifelong skin surveillance and UV protection are essential.
Vaccinations must be completed pre-transplant where possible (including pneumococcal, influenza, hepatitis B). Live vaccines are contraindicated post-transplant.
Aboriginal and Torres Strait Islander patients may face barriers including geographic remoteness from transplant centres, variable health literacy, and higher baseline prevalence of chronic liver disease — requiring culturally safe, multidisciplinary follow-up.

Induction & Maintenance Immunosuppression

Principles of Immunosuppressive Therapy

Liver transplant immunosuppression in Australia aims to balance rejection prevention against infection risk, malignancy, and drug toxicity. The liver is relatively immunoprivileged compared with other solid organs, allowing lower overall immunosuppressive intensity. Most centres adopt a triple-drug regimen from the outset.

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Immunosuppression intensity must be individualised: Higher levels are needed for patients with autoimmune hepatitis, primary sclerosing cholangitis, or high panel-reactive antibodies. Lower levels may suffice for hepatocellular carcinoma (HCC) in non-viral aetiologies.

Induction Therapy

Induction agents provide intense immunosuppression during the perioperative period when rejection risk is highest.

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Basiliximab

Simulect® · IL-2 receptor antagonist

Adult dose 20 mg IV on Day 0 (before reperfusion) and Day 4

Paediatric dose <35 kg: 10 mg IV × 2 doses; ≥35 kg: 20 mg IV × 2 doses

Route / frequency Intravenous infusion over 20–30 min; 2 doses total

Renal adjustment None required

PBS status ⚠ PBS Restricted Benefit — solid organ transplant

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Anti-thymocyte globulin (rabbit)

Thymoglobulin® · Polyclonal antibody

Adult dose 1–1.5 mg/kg IV daily for 3–7 days (typically 5 days)

Indications High immunological risk (re-transplant, sensitised patients), delayed graft function, steroid-resistant rejection

Route / frequency IV infusion over ≥6 hours; premedicate with paracetamol, antihistamine, corticosteroids

Key adverse effects Cytokine release syndrome, thrombocytopenia, leucopenia, increased infection risk

PBS status ✘ Not PBS listed — Authority/Hospital only

Maintenance Immunosuppression

The standard Australian maintenance regimen comprises a calcineurin inhibitor (tacrolimus) + an antimetabolite (mycophenolate mofetil) ± low-dose corticosteroids. Conversion to mTOR inhibitors is considered for CNI toxicity or HCC recurrence risk.

Calcineurin Inhibitors

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Tacrolimus (mainstay)

Prograf® · Adoport® · Tacrolimus Sandoz · Calcineurin inhibitor

Adult dose 0.05–0.1 mg/kg/day PO in 2 divided doses (BD); start within 12–24 h post-transplant

Target trough levels Months 0–3: 8–12 ng/mL; Months 3–12: 5–8 ng/mL; >12 months: 4–6 ng/mL

Paediatric dose 0.1–0.15 mg/kg/day PO BD (children often require higher weight-adjusted doses)

Renal adjustment No dose change — but reduce target trough by 1–2 ng/mL if eGFR <30 mL/min; minimise nephrotoxicity

Key adverse effects Nephrotoxicity, neurotoxicity (tremor, headache), NODAT, hypertension, alopecia, GI disturbance

PBS status ✔ PBS General Benefit

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Ciclosporin

Neoral® · Calcineurin inhibitor

Adult dose 3–5 mg/kg/day PO in 2 divided doses; target C2 level 800–1000 ng/mL (early), 500–800 ng/mL (maintenance)

When used Tacrolimus intolerance (e.g. severe neurotoxicity, refractory NODAT); lower PTLD risk profile

Key adverse effects Nephrotoxicity, hypertension, hypertrichosis, gingival hyperplasia, hyperlipidaemia

PBS status ✔ PBS General Benefit

Antimetabolites

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Mycophenolate mofetil

CellCept® · Myfortic® · Antiproliferative agent

Adult dose 1 g PO BD (total 2 g/day); reduce to 500 mg BD if GI intolerance or cytopenias

Paediatric dose 15–20 mg/kg PO BD (max 2 g/day)

Renal adjustment No formal dose reduction, but monitor for cytopenias more closely

Key adverse effects GI disturbance (diarrhoea, nausea), leucopenia, anaemia, teratogenic — effective contraception mandatory

PBS status ✔ PBS General Benefit

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Azathioprine

Imuran® · Purine analogue

Adult dose 1–2 mg/kg/day PO once daily (max 2.5 mg/kg/day)

Important Check TPMT/NUDT15 genotype before initiation — deficiency predisposes to severe myelosuppression

PBS status ✔ PBS General Benefit

mTOR Inhibitors

mTOR inhibitors (sirolimus, everolimus) are used as CNI-sparing agents or in patients with de novo or recurrent HCC. They impair wound healing and should generally be avoided in the first 4–6 weeks post-transplant.

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Sirolimus

Rapamune® · mTOR inhibitor

Adult dose Loading dose 3–5 mg PO Day 1, then 1–2 mg PO daily; target trough 5–10 ng/mL

Renal adjustment No dose change — but half-life prolonged in severe renal impairment

Key adverse effects Impaired wound healing, mouth ulcers, hyperlipidaemia, peripheral oedema, pneumonitis (rare), proteinuria

PBS status ⚠ PBS Restricted Benefit — transplant

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Everolimus

Certican® · Afinitor® · mTOR inhibitor

Adult dose 0.75 mg PO BD; target trough 3–8 ng/mL; combined with reduced-dose tacrolimus

Role in HCC Antiproliferative and anti-angiogenic properties; evidence suggests reduction in HCC recurrence post-transplant (H2354 trial data)

PBS status ⚠ PBS Restricted Benefit

Corticosteroids

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Prednisolone

Solone® · Panafcortelone® · Corticosteroid

Standard taper Intraoperative: methylprednisolone 500–1000 mg IV → Day 1: 200 mg → taper 20 mg/day to 20 mg PO → reduce by 5 mg every 2–4 weeks → aim for cessation by 3–6 months (or low-dose maintenance 5 mg/day if autoimmune liver disease)

PBS status ✔ PBS General Benefit

Acute Cellular Rejection Management

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Biopsy-confirmed acute rejection: First-line treatment is IV methylprednisolone 500–1000 mg daily for 3 days (pulse therapy). Steroid-resistant rejection: anti-thymocyte globulin (Thymoglobulin®) 1.5 mg/kg IV daily for 5–7 days. Chronic ductopenic rejection refractory to treatment may require re-transplantation.

Phase	Tacrolimus target (ng/mL)	Mycophenolate	Prednisolone
0–3 months	8–12	1 g BD	Taper from 200 mg to 20 mg
3–12 months	5–8	1 g BD (or reduce)	Taper toward 5 mg or cessation
>12 months	4–6	500 mg–1 g BD	5 mg or ceased
Autoimmune disease	6–8	1 g BD (maintain)	5 mg long-term

Drug Interactions & Monitoring

CYP3A4 Interactions — Critical Safety Issue

Tacrolimus and ciclosporin are extensively metabolised by CYP3A4 and CYP3A5 in the gut wall and liver. P-glycoprotein (P-gp) also modulates absorption. Co-administration with CYP3A4 modulators is one of the most common causes of drug-related toxicity or sub-therapeutic levels in transplant recipients.

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Rifampicin interaction: Rifampicin is a potent CYP3A4 inducer that can reduce tacrolimus trough levels by 50–80%. If rifampicin is required (e.g. for TB), increase tacrolimus dose by 2–3× baseline and monitor levels every 2–3 days until stable. Consult transplant pharmacist.

CYP3A4 Inhibitors — Raise Tacrolimus/Ciclosporin Levels

Drug / Substance	Potency	Action Required
Ketoconazole	Strong	Avoid or reduce CNI by 50–75%; monitor levels 48–72 h after initiation
Fluconazole (doses >200 mg/day)	Moderate–Strong	Reduce CNI dose by 25–50%; monitor levels every 3–5 days
Itraconazole, posaconazole, voriconazole	Strong	Reduce CNI by 50%; therapeutic drug monitoring essential
Erythromycin, clarithromycin	Moderate	Avoid if possible; use azithromycin (minimal CYP3A4 effect) instead
Diltiazem, verapamil	Moderate	Reduce CNI by 25–50%; monitor levels
Grapefruit / grapefruit juice	Moderate	Strictly avoid — inhibits intestinal CYP3A4 and P-gp
Seville oranges, star fruit	Mild–Moderate	Avoid

CYP3A4 Inducers — Lower Tacrolimus/Ciclosporin Levels

Drug	Potency	Action Required
Rifampicin (rifampin)	Strong	Double or triple CNI dose; check trough every 2–3 days; consult transplant team
Phenytoin	Strong	Double CNI dose; monitor levels frequently; consider alternative anticonvulsant (levetiracetam)
Carbamazepine	Strong	Avoid if possible — switch to levetiracetam or sodium valproate
St John's wort (Hypericum perforatum)	Strong	Strictly contraindicated — advise patients to cease all herbal supplements
Nafcillin, rifabutin	Moderate	Increase CNI dose; monitor levels every 3–5 days

Therapeutic Drug Monitoring Schedule

Time Post-Transplant	Tacrolimus Trough Frequency	Notes
0–2 weeks	Daily	Stabilise levels; adjust dose in 0.5–1 mg increments
2 weeks – 3 months	1–2× per week	Steady state; monitor renal function, glucose
3–12 months	Every 2–4 weeks	Gradual target reduction
>12 months (stable)	Every 1–3 months	Check levels after any drug interaction change
After interacting drug change	48–72 h after change, then every 2–3 days until stable	Document interaction in patient record

Adverse Effect Monitoring

Monitor

Nephrotoxicity (CNI)

Acute: afferent arteriolar vasoconstriction (reversible). Chronic: interstitial fibrosis, tubular atrophy (irreversible). Target lowest effective CNI level.

Check: eGFR, Cr, electrolytes at each visit

Monitor

Neurotoxicity

Tremor, headache, insomnia, paraesthesia, seizures (rare). Worse with high trough levels. Consider CNI dose reduction or ciclosporin switch.

Check: symptom review; MRI if posterior reversible encephalopathy suspected

Monitor

Post-Transplant Diabetes (NODAT)

Tacrolimus causes direct β-cell toxicity; incidence 10–40%. Risk factors: family history of diabetes, HCV, obesity, African descent, older age.

Check: fasting glucose / HbA1c at 1, 3, 6, 12 months then annually. Metformin first-line if eGFR >30.

Other monitoring: Blood pressure (CNI-induced hypertension — target <130/80 mmHg, use amlodipine if needed as it does not affect CNI levels; avoid diltiazem/verapamil), lipid profile (mTOR inhibitors worsen hyperlipidaemia), FBC (mycophenolate/azathioprine cytopenias), LFTs (rejection surveillance).

Post-Transplant Diabetes (NODAT) Management

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Metformin

Diabex® · Diaformin® · Biguanide

Adult dose 500 mg PO BD, titrate to 1 g BD (max 2 g/day)

Renal adjustment eGFR 30–45: max 500 mg BD; eGFR <30: contraindicated

PBS status ✔ PBS General Benefit

Infectious Prophylaxis & Long-Term Complications

CMV Prophylaxis

Cytomegalovirus (CMV) is the most important viral pathogen post-liver transplant. Prophylaxis is determined by donor (D) and recipient (R) CMV IgG serostatus.

D/R Serostatus	Risk Category	Prophylaxis	Duration
D+/R−	Highest	Valganciclovir 900 mg PO daily	6 months (some centres 12 months)
D+/R+	High	Valganciclovir 900 mg PO daily	3–6 months
D−/R+	Moderate	Valganciclovir 900 mg PO daily (or valaciclovir 2 g TDS)	3 months
D−/R−	Low	No routine prophylaxis; monitor with CMV PCR	—

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Valganciclovir

Valcyte® · Antiviral (ganciclovir prodrug)

Adult prophylaxis dose 900 mg PO once daily with food

Renal adjustment CrCl 40–59: 450 mg daily; CrCl 25–39: 450 mg every 48 h; CrCl 10–24: 450 mg twice weekly; CrCl <10: not recommended

Key adverse effects Neutropenia (monitor FBC fortnightly), thrombocytopenia, GI disturbance, teratogenic

PBS status ⚠ PBS Authority Required — transplant prophylaxis

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CMV PCR monitoring: After cessation of prophylaxis, perform CMV quantitative PCR weekly for 12 weeks (pre-emptive monitoring strategy). Rising viral load >1000 IU/mL warrants treatment with valganciclovir 900 mg BD.

PJP (Pneumocystis jirovecii) Prophylaxis

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Trimethoprim-sulfamethoxazole (TMP-SMX)

Bactrim® · Resprim® · Dihydrofolate reductase inhibitor + sulfonamide

Adult dose (prophylaxis) TMP 160 mg / SMX 800 mg (1 DS tablet) PO daily; OR 1 DS tablet 3 times per week

Paediatric dose TMP 5 mg/kg/day PO (max 320 mg TMP/day) as single daily dose or 3× per week

Duration 6–12 months post-transplant; some centres continue for 6 months after withdrawal of corticosteroids

Allergy alternative Dapsone 100 mg PO daily; OR atovaquone 1500 mg PO daily; OR aerosolised pentamidine 300 mg monthly

PBS status ✔ PBS General Benefit

Antifungal Prophylaxis

Invasive fungal infection (IFI) — predominantly Candida and Aspergillus — is a significant early post-transplant complication. Antifungal prophylaxis is recommended for high-risk patients.

High-risk criteria: Re-transplantation, reoperation, renal replacement therapy, massive transfusion (>40 units), prolonged ICU stay, choledochojejunostomy anastomosis, fulminant hepatic failure.
First-line: Fluconazole 200–400 mg PO/IV daily for 4–6 weeks (covers Candida). PBS: General Benefit.
If Aspergillus risk: Posaconazole 300 mg PO daily or voriconazole 200 mg PO BD — consult infectious diseases. Monitor CNI levels closely (strong CYP3A4 inhibition).
Low-risk patients: No routine antifungal prophylaxis; monitor clinically.

Pre-Transplant Vaccination

All vaccinations should be completed before liver transplant wherever possible. Live vaccines are contraindicated post-transplant and for 4 weeks prior if possible.

Vaccine	Pre-Transplant	Post-Transplant
Influenza (inactivated)	Yes	Yes — annually from 1 month post-transplant
Pneumococcal (PCV13 then PPSV23)	Yes — complete series	Revaccinate 3–5 years post-transplant
Hepatitis B	Yes — high-dose schedule (40 μg × 3)	Booster if anti-HBs <10 mIU/mL
Hepatitis A	Yes if non-immune	Safe post-transplant (inactivated)
COVID-19 (mRNA)	Yes — complete primary + booster	Yes — may have reduced response; additional doses recommended
MMR (live)	Yes if non-immune	Contraindicated — live vaccine
Varicella (live)	Yes if non-immune (VZV IgG negative)	Contraindicated — use aciclovir prophylaxis if exposed
Zoster (Shingrix — recombinant)	Yes if ≥50 years	Safe post-transplant (non-live); 2 doses, 2–6 months apart

Long-Term Complications

Chronic Kidney Disease

CKD develops in up to 20% of liver transplant recipients by 10 years, predominantly driven by CNI nephrotoxicity. Pre-existing renal impairment (hepatorenal syndrome), diabetes, and hypertension are contributing factors.

Strategies: CNI minimisation (target lower troughs); conversion to mTOR inhibitor (everolimus or sirolimus) with low-dose CNI; early nephrology referral if eGFR <30 mL/min.
Monitor eGFR, urine ACR, and electrolytes at every visit.
Avoid nephrotoxins (NSAIDs, iodinated contrast without hydration) and maintain adequate hydration.

Cardiovascular Disease

Metabolic syndrome is common post-transplant (incidence 40–60%) driven by corticosteroids, CNI, and mTOR inhibitors. Cardiovascular disease is now a leading cause of late mortality.

Targets: BP <130/80 mmHg, LDL <2.0 mmol/L, HbA1c <7.0% (individualised).
Statins (atorvastatin preferred — minimal CYP3A4 interaction with tacrolimus at low doses). PBS: General Benefit.
Amlodipine for hypertension (does not interact with CNI; avoid diltiazem).
Encourage physical activity, weight management, smoking cessation, and Mediterranean diet.

De Novo Malignancy

Post-transplant malignancy risk is 2–3× that of the age-matched general population. Non-melanoma skin cancer (NMSC) and post-transplant lymphoproliferative disorder (PTLD) are the most significant.

NMSC: Most common de novo malignancy. Risk increases with cumulative immunosuppression and UV exposure in Australia. Annual full skin examination by a dermatologist or trained GP; daily SPF 50+ sunscreen; protective clothing.
PTLD: Associated with EBV D+/R− mismatch and intensity of immunosuppression. Presents most commonly in the first year. Lowering immunosuppression is first-line; rituximab for CD20+ tumours; chemotherapy for refractory disease.
Solid organ tumours: Increased risk of colorectal, lung, and kidney cancers. Follow national screening programmes (bowel cancer screening from 45 years).

Recurrent Primary Disease

Certain liver diseases recur post-transplant and require specific management:

Hepatitis C: Direct-acting antivirals (DAAs) post-transplant (sofosbuvir/velpatasvir) achieve >95% SVR. PBS listed.
Hepatitis B: Hepatitis B immunoglobulin (HBIg) + nucleos(t)ide analogue (entecavir/tenofovir) — indefinite prophylaxis.
Autoimmune hepatitis: Recurrence in 20–40%. Maintain low-dose prednisolone (5 mg) and adequate immunosuppression.
Primary sclerosing cholangitis: Recurrence in 10–25%; often diagnosed on cholangiography. Associated with underlying IBD — continue colonoscopy surveillance.
Primary biliary cholangitis: Recurrence in 10–30%. Ursodeoxycholic acid (UDCA) may be continued post-transplant.
NASH / metabolic-associated steatohepatitis: Recurrence common if metabolic syndrome persists. Aggressive risk factor management.

Late Rejection

Late acute rejection (>6 months) and chronic rejection are less common but carry significant graft implications. Non-adherence with immunosuppression is the most common cause.

Maintain adequate trough levels; educate patients about adherence — particularly in adolescents.
Chronic (ductopenic) rejection: progressive loss of bile ducts; may present with cholestatic biochemistry. Treatment: optimise immunosuppression; if refractory, re-transplantation may be required.

ATSI — Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Liver disease burden

ATSI peoples experience a disproportionate burden of liver disease, including hepatitis B (endemic in some remote communities), alcohol-related liver disease, and non-alcoholic fatty liver disease (NAFLD). Access to liver transplantation is limited by geographic remoteness from tertiary transplant centres.

Geographic access

Most liver transplant centres are in metropolitan Sydney, Melbourne, Brisbane, and Perth. Patients from remote NT, QLD, and WA communities may need to relocate for months post-transplant. Telehealth and shared-care models with local AMS (Aboriginal Medical Services) are essential for ongoing monitoring of immunosuppression levels.

Cultural safety

Immunosuppression education must be culturally appropriate, using plain language and visual aids. Involve Aboriginal Health Workers and Elders in discharge planning. Respect cultural obligations regarding Sorry Business and travel that may affect clinic attendance.

Medication adherence

Complex lifelong medication regimens are challenging. Community pharmacies, Webster-pak® dosette systems, and medication management programs through AMS improve adherence. DAAs for hepatitis C should be accessible through PBS without geographic barriers.

Infectious disease

Higher baseline prevalence of chronic hepatitis B in remote communities necessitates vaccination programs and screening. Strongyloides hyperinfection risk post-transplant — screen for strongyloidiasis (and treat with ivermectin) before starting immunosuppression, particularly in patients from endemic regions (Cape York, Torres Strait, NT).

RHDAustralia guidance

Rheumatic heart disease is prevalent in ATSI communities; patients may require anticoagulation or cardiac assessment pre-transplant. Refer to RHDAustralia (www.rhdaustralia.org.au) for guidelines on managing cardiac comorbidities in transplant candidates.

📚 References

1. European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: Liver transplantation. J Hepatol. 2016;64(2):433–485.
2. Charlton M, Levitsky J, Bzowej N, et al. Liver transplantation in patients with nonalcoholic steatohepatitis: a consensus conference report. Am J Transplant. 2022;22(Suppl 1):1–34.
3. Kotton CN, Kumar D, Caliendo AM, et al. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018;102(6):900–931.
4. Transplantation Society of Australia and New Zealand (TSANZ). Organ Transplantation from Deceased Donors: Policies and Guidelines. Sydney: TSANZ; 2023.
5. Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients. Am J Transplant. 2009;9(Suppl 3):S1–S155.
6. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Australian Government Department of Health; 2023. Available at: https://immunisationhandbook.health.gov.au.
7. Australasian Society for Infectious Diseases (ASID). Guidelines for the Prevention, Diagnosis and Management of Infections in Solid Organ Transplant Recipients. Sydney: ASID; 2020.
8. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander Health Performance Framework 2020 Summary Report. Canberra: AIHW; 2020.
9. Line PD, Rela M, editors. Transplantation of the Liver. 3rd ed. Elsevier; 2015.
10. Organ and Tissue Authority (OTA). DonateLife Annual Report 2022–23. Canberra: Australian Government; 2023.
11. McKenna GJ, Trotter JF, Klintmalm E, et al. Limiting hepatocellular carcinoma recurrence after liver transplantation: is it time for mTOR inhibitor–based immunosuppression? Transplantation. 2014;97(9):931–936.
12. RHDAustralia. The 2020 Australian Guideline for Prevention, Diagnosis and Management of Acute Rheumatic Fever and Rheumatic Heart Disease. 3rd ed. Darwin: Menzies School of Health Research; 2020.
13. The Transplantation Society. Banff Schema for Allograft Rejection: 2022 Update. Am J Transplant. 2022;22(8):1873–1886.