HTHSCI 1DT3 Lecture Notes - Lecture 9: Rituximab, Chemotherapy, Covalent Bond
23 Jun 2018
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Acute cellular rejection
Acute cellular rejection does occur
This occurs within days/weeks and is T cell-mediated
direct cytotoxicity and cytokine-derived pathways are activated
Diagnosis is by biopsy showing: mixed portal infiltration (mononuclear infiltrate containing
activated lymphocytes, neutrophyls and eosinophils), bile duct inflammation/damage, vasculitis.
Treatment is with steroids / immunosuppression e.g. ATG = anti-thymocyte globulin if normal
steroids don’t work
Acute rejection, if recurrent, is a predictor of chronic rejection, however it has been linked to
better outcomes, and is readily treatable
Immunosuppressants used after transplantation
Corticosteroids: known to enter nucleus and decrease transcription of pro-inflammatory
mediators, cause broad and organ-specific immunosuppression
Calcineurin/IL-2 inhibitors: decrease T cell proliferation as they inhibit IL-2 secretion
Examples include tacrolimus / cycosporin
Sirolimus/rapamycin: inhibits response to IL-2 (thus similarly inhibiting T cell proliferation) by
binding FKBP12 and thus inhibiting the mTor pathway by binding mTor complex 1
Anti-metabolites: mycophenolate mofetil is used or added to tacrolimus when tacrolimus
impairs renal function
Early post-transplant infection <6months
1. Bacterial infections affect 50% of liver transplant patients; risk increased by Iv lines, wounds;
include bile infections, ruine infections, respiratory tract infections, septicaemia
2. Particularly susceptible to fungal infections (75% Candida, 25% Aspergillus; these confer high
mortality); risk factors for fungal infection include: renal failure/dialysis, surgical factors like long
transplantation time, hepatic failure, early fungal colonisation
3. Viruses such as CMV, EBV and herpes viruses can reactivate if previous exposure has caused
subclinical infection
Hence prophylactic antibiotics for bacteria, and CMV prophylaxis for high-risk patients (e.g. if donor
has CMV Ig and recipient is CMV IgG-), potential for VZV vaccination and HSV prophylaxis if CMV
prophylaxis not being undertaken
Treatments aside from BACTERIAL INFECTIONS – ABX:
HSV acyclovir
CMV Valganciclovir
VZV Vaccination / valascyclovir
Candida Amphotericin B / fluconazole
Aspergillus Vorinconazole / amphotericin B
PCP Trimethoprim / sulphamethoxazole
toxoplasma Trimethoprim / sulphamethoxazole
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