Immunosuppression in Liver Transplantation

Abstract

Successful application of transplant surgery for definitive management of end-stage organ disease occurred, while our understanding of immunology was still rudimentary. Immunosuppression was developed by surgeons, about the middle of the last century, battling with biological forces that nobody understood and often in the face of opposition from those who thought they did. The primary function of the immune system—to defend the body from invasion by foreign organisms—was being ‘suppressed’, and that could only have deleterious effects! The undeniable success of transplantation however led to a considerable evolution of our knowledge of how the immune system works, especially of our understanding of mechanisms that terminate an immune attack and regulate balance within the immune system. Today, the term ‘immunomodulation’ might be better than the older ‘immunosuppression’ to describe what makes a transplant work.

Appendix

10.1.1 Questionnaire Circulated to Liver Transplant Centres in India

10.1.1.1 Practical Immunosuppression in Liver Transplant: Experience of Experts in India

Name of the Centre:

Chief Surgeon:

Hepatologist:

10.1.1.2 Standard Induction

DDLT

• Medication and dose (fixed or weight based)

• Timing

LDLT

• Medication and dose (fixed or weight based)

• Timing

Change in standard induction (if any) with:

• Renal dysfunction

• Very sick patient (High MELD/CTP score)

• Recent infection

Use of antibodies in induction:

• Basiliximab: Yes/never/selectively

• ATG: Yes/never/selectively

(If ‘yes’, or ‘selectively’ for above question, please elaborate in comments section below) ¹

10.1.1.3 Standard Maintenance

• Medication list

• Steroid taper protocol

• Choice of CNI

• Target CNI levels

• mTOR inhibitors

Different strategy in deceased donor vs live donor transplant: Yes/no

(If yes, please delineate in the comment section below) ²

Different strategy in renal dysfunction: Yes/no

(If yes, please elaborate in comments below) ³

Change in maintenance with infection pre- or immediate post-tx: Yes/no

(Please comment below) ⁴

Change in maintenance immunosuppression with HCC: Yes/no

(Please comment below) ⁵

Change in immunosuppression with early graft dysfunction (EGD)

• Primary non-function (PNF): Yes/no

(Please delineate in the comments section below) ⁶

• ‘Small for size’ (SFSS): Yes/no

(If yes, please outline in the comments section below) ⁷

• Any other reason: Yes/no

(If yes, please outline in the comments section below) ⁸

Infection Prophylaxis

• Antibiotic choice and duration:

• Antifungal choice and duration:

• PCP prophylaxis:

• CMV prophylaxis and duration

• D+/R−

• D+/R+

• D−/R+

• D−/R−

10.1.1.4 Rejection Management

AST/ALT level which would trigger a biopsy:

Biopsy rate in first-year post liver transplant:

Suspected acute cellular rejection (ACR) rate in first-year post-transplant:

Management of acute rejection with biopsy:

• Mild ACR

• Moderate ACR

• Severe ACR

Management of suspected acute rejection without biopsy:

• Steroid doses used empirically:

• Increase or add MMF: Yes/no

• Increase CNI only without empiric steroids: Yes/no

Steroid-resistant ACR encountered: Yes/no

(If yes, please outline strategy in the comments section below) ⁹

Acute antibody-mediated rejection (AMR)encountered: Yes/no

(If yes, please discuss management strategy in acute AMR in the comments section below) ¹⁰

Chronic rejections encountered: Yes/no

(If yes, please outline management strategies in chronic rejection) ¹¹

Graft vs host reaction encountered: Yes/no

Passenger lymphocyte syndrome (alloimmune haemolysis) encountered: Yes/no

(If yes, please delineate the immunosuppression strategy in this situation) ¹²

Retransplant required for immunological reasons: Yes/no

(If yes, please discuss in the comments section below) ¹³

PTLD encountered: Yes/no

Other cancers encountered: Yes/no

If yes, what were they?

Tolerance encountered (Withdrawal or significant minimization of immunosuppression): Yes/no

10.1.1.5 ABOi Liver Transplant

• Cut-off titre above which you would not consider desensitization:

• Target titre of desensitization regimen:

  IgG

  IgM

• Desensitization regimen:

Induction agents in ABOi liver transplant:

• Agent and dose

Maintenance meds, different from routine transplant: Yes/no

Antibody titre monitoring protocol

• Up to 3 months:

• Beyond 3 months:

10.1.1.6 General Opinions Based on Experience with Immunosuppression Agents in India

Preferred CNI and why:

Preferred mTORi and why:

Is hyperlipidaemia a problem with mTORi?

Is pulmonary toxicity a problem with mTORi?

Platelet count cut-off for starting MMF:

GI side effects of MMF, is it a problem?

Experience with azathioprine:

Non-compliance. Is it a problem?

Any other comments or experience you would like to share:

10.1.1.7 Comments/Important Experience Requiring to Be Shared

• 1. Use of antibodies in induction

• 2. DDLT vs LDLT maintenance therapy

• 3. Change in maintenance therapy with renal dysfunction

• 4. Change in maintenance with recent infection

• 5. Change in maintenance with HCC

• 6. PNF (please comment on definition of PNF that you use)

• 7. Small for size (SFSS)

• 8. Other reasons to change maintenance immunosuppression

• 9. Steroid resistant ACR. Management strategy

• 10. AMR management strategy

• 11. Chronic rejection management

• 12. GVHD and passenger lymphocyte (alloimmune haemolysis) syndrome

• 13. Re-transplant