To the Editor: We read with great interest the article by Shajahan et al. entitled “Lessons learnt from living donor liver transplantation with ABO-incompatibility: A single-centre experience from southern India” [1] recently published on Indian Journal of Gastroenterology. ABO-incompatible living donors liver transplantation (ABO-I LDLT) represents a precious opportunity to shorten the waiting time for surgery, avoiding the disease progression that might occur waiting for an ABO-compatible living or deceased donor. However, ABO-I LDLT is still associated with a high risk of antibody-mediated rejection (AMR), lower patient and graft survival and a high risk of vascular thrombosis and ischemic bile duct complications if compared to ABO-compatible LT. The study of Shajahan et al. represents the largest report of ABO-I LDLT from India, even if the sample size is still small. The authors retrospectively analyzed data of 12 patients undergone ABO-I LDLT using Rituximab and preoperative plasmapheresis for desensitisation, adjusting doses after facing a very high mortality rate in the first 7 patients (5 deaths), mostly due to septic complications. Rituximab, a murine/human monoclonal chimeric antibody against CD20 depleting B-lymphocytes, has traditionally been used to treat haematological malignancies and autoimmune diseases. More recently, it has been gained interest as an immunomodulatory agent in solid organ transplantations. [2] Although if current literature is more and more supporting the effectiveness of Rituximab in antibody-mediated rejection (AMR) as a desensitizing regimen, several reports have shown that concerns still remain in the high incidence of complication rates, such as biliary strictures, ischemic-type biliary lesions and postoperative infections. [3,4,5] Particularly this latter complication afflicted the study of Shajahan et al. who faced a dramatically high rate of postoperative infections involving 9 out of 12 patients, of whom 5 died due to overwhelming sepsis from multidrug-resistant pathogens. Several works such as a Japanese multicenter study have demonstrated that multiple or large Rituximab doses significantly increase the incidence of infection [3], advocating for a “minimization” of the desensitizing protocols. Even if authors have reduced the Rituximab doses after the first 7 cases, the overall septic complications and morality rates still remain very high (75% and 50% respectively), raising the issue of the desensitizing regimen’s adequacy. Actually, different modalities of Rituximab free immunosuppressive regimens to prevent AMR have been successfully reported in literature, such as the use of high-dose polyclonal intravenous immunoglobulin associated with plasmapheresis without the use of steroid pulses or monoclonal antibodies, or even of everolimus-based immunosuppressive regimen under a strict monitoring of anti-A/B antibodies titres [6,7]. In conclusion, we strongly believe that more and more efforts should be make to minimize the desensitization regimen in ABO-I LDLT in order to reduce the rates of septic complications and improve patients’ and grafts’ survival. Moreover, prospective studies with bigger sample sizes are required to validate the Indian ABO-I LDLT experience.

Comment on “Lessons learnt from living donor liver transplantation with ABO-incompatibility: A single-center experience from southern India”

Gianardi Desirée
Primo
;
Di Franco Gregorio
Secondo
;
Palmeri Matteo;Bianchini Matteo;Furbetta Niccolò
Penultimo
;
Morelli Luca
Ultimo
2019-01-01

Abstract

To the Editor: We read with great interest the article by Shajahan et al. entitled “Lessons learnt from living donor liver transplantation with ABO-incompatibility: A single-centre experience from southern India” [1] recently published on Indian Journal of Gastroenterology. ABO-incompatible living donors liver transplantation (ABO-I LDLT) represents a precious opportunity to shorten the waiting time for surgery, avoiding the disease progression that might occur waiting for an ABO-compatible living or deceased donor. However, ABO-I LDLT is still associated with a high risk of antibody-mediated rejection (AMR), lower patient and graft survival and a high risk of vascular thrombosis and ischemic bile duct complications if compared to ABO-compatible LT. The study of Shajahan et al. represents the largest report of ABO-I LDLT from India, even if the sample size is still small. The authors retrospectively analyzed data of 12 patients undergone ABO-I LDLT using Rituximab and preoperative plasmapheresis for desensitisation, adjusting doses after facing a very high mortality rate in the first 7 patients (5 deaths), mostly due to septic complications. Rituximab, a murine/human monoclonal chimeric antibody against CD20 depleting B-lymphocytes, has traditionally been used to treat haematological malignancies and autoimmune diseases. More recently, it has been gained interest as an immunomodulatory agent in solid organ transplantations. [2] Although if current literature is more and more supporting the effectiveness of Rituximab in antibody-mediated rejection (AMR) as a desensitizing regimen, several reports have shown that concerns still remain in the high incidence of complication rates, such as biliary strictures, ischemic-type biliary lesions and postoperative infections. [3,4,5] Particularly this latter complication afflicted the study of Shajahan et al. who faced a dramatically high rate of postoperative infections involving 9 out of 12 patients, of whom 5 died due to overwhelming sepsis from multidrug-resistant pathogens. Several works such as a Japanese multicenter study have demonstrated that multiple or large Rituximab doses significantly increase the incidence of infection [3], advocating for a “minimization” of the desensitizing protocols. Even if authors have reduced the Rituximab doses after the first 7 cases, the overall septic complications and morality rates still remain very high (75% and 50% respectively), raising the issue of the desensitizing regimen’s adequacy. Actually, different modalities of Rituximab free immunosuppressive regimens to prevent AMR have been successfully reported in literature, such as the use of high-dose polyclonal intravenous immunoglobulin associated with plasmapheresis without the use of steroid pulses or monoclonal antibodies, or even of everolimus-based immunosuppressive regimen under a strict monitoring of anti-A/B antibodies titres [6,7]. In conclusion, we strongly believe that more and more efforts should be make to minimize the desensitization regimen in ABO-I LDLT in order to reduce the rates of septic complications and improve patients’ and grafts’ survival. Moreover, prospective studies with bigger sample sizes are required to validate the Indian ABO-I LDLT experience.
2019
Gianardi, Desirée; DI FRANCO, Gregorio; Palmeri, Matteo; Bianchini, Matteo; Furbetta, Niccolò; Morelli, Luca
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/994080
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