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Commentaries

Getting an A Can Sometimes Kill You

Oldani, Graziano MD, PhD1; Toso, Christian MD, PhD1

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doi: 10.1097/TP.0000000000004005
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ABO blood group is among the most critical factors when an organ is being allocated for transplantation. It is common practice to match donor and recipient blood groups because ABO incompatibility needs special management with ABO antibody clearance and increased immunosuppression.1

The current study from Mohkam et al2 has the potential to change the way we allocate livers within the same blood group. It showed for the first time that blood group A recipients have an increased risk of developing hepatocellular carcinoma (HCC) recurrence after liver transplantation using pooled data from multiple French centers. The difference was especially observed in recipients outside Milan criteria, with blood group A recipients demonstrating almost 3 times the HCC recurrence rate of non-A recipients at 5 y (43.8% versus 15.6%).

The evidence that a particular ABO blood group could enhance the risk of developing cancer is not new. Aird et al3 were the first to observe a relationship between gastric cancer and the A blood group in 1953. Based in England, they observed that among the population with gastric cancer (3632 individuals), the prevalence of group A was higher than in the general population (44.8% versus 39.8%). Thanks to this study, investigations on the subject flourished, however, with inconclusive results,4 until recently, thanks primarily to Asian studies, able to pool large numbers of patients.

Based in China, Mao et al5 compared 4932 individuals with gastric cancer with 6158 controls, finding that individuals with group A and AB had an increased risk of developing gastric cancer compared with other blood groups (for group A: odds ratio, 1.13; P = 0.018; for group AB: odds ratio,  1.18; P = 0.024, respectively). In Taiwan,6 a significant excess cancer risk was found among subjects with the presence of the A antigen. This positive association was mainly observed in cancers from lung cancer (hazard ratio [HR], 1.88) and gastrointestinal cancer (HR, 1.25) in men, as well as liver cancer (HR, 1.69) and gastrointestinal cancer (HR, 1.49) in women.

The study of Mohkam et al investigated a relatively small population of 925 transplanted patients for HCC. To manage confounders and adjust for the heterogeneity between groups, they conducted a multivariate analysis and ran a propensity score matching. Of note, we know that the time on the waiting list can affect posttransplant HCC recurrence,7 a longer (but not excessive) time allowing for a better patient selection. In the studied population, non-A patients waited significantly longer for a transplant, which could have explained the excessive recurrence rate in the A population. However, the effects of waiting list time were eliminated by matching the groups in the propensity score.

The mechanisms involved in the observed phenomenon are far from being understood, and, as the authors pointed out in Discussion, the patterns of recurrence were not analyzed. Because ABO antigens are surface molecules that could be somehow involved in the homing of circulating cells, it could explain why beyond the Milan criteria, the recipient’s characteristics had more impact than tumor characteristics. This theory would go well along with the fact that ABO groups can determine the susceptibility to other diseases, including severe acute respiratory syndrome coronavirus 2 infections.8

Altogether Mohkam et al2 bring to light a piece of evidence that is solid enough to shake the transplant community. An increasing number of transplant centers move to less restrictive HCC selection criteria than Milan’s, and external validation of the current findings is highly needed.

REFERENCES

1. Ko EJ, Yu JH, Yang CW, et al.; Korean Organ Transplantation Registry Study Group. Clinical outcomes of ABO- and HLA-incompatible kidney transplantation: a nationwide cohort study. Transpl Int. 2017;30:1215–1225.
2. Mohkam K, Abdallah R, Merle P, et al. Influence of the ABO blood group system on hepatocellular carcinoma recurrence after liver transplantation. Transplantation. 2021.
3. Aird I, Bentall HH, Roberts JA. A relationship between cancer of stomach and the ABO blood groups. Br Med J. 1953;1:799–801.
4. Wiener AS. Controversy in human genetics. Blood groups and disease. Am J Hum Genet. 1970;22:476–483.
5. Mao Y, Yang W, Qi Q, et al. Blood groups A and AB are associated with increased gastric cancer risk: evidence from a large genetic study and systematic review. BMC Cancer. 2019;19:164.
6. Hsiao LT, Liu NJ, You SL, et al. ABO blood group and the risk of cancer among middle-aged people in Taiwan. Asia Pac J Clin Oncol. 2015;11:e31–e36.
7. Mehta N, Heimbach J, Lee D, et al. Wait time of less than 6 and greater than 18 months predicts hepatocellular carcinoma recurrence after liver transplantation: proposing a wait time “Sweet Spot”. Transplantation. 2017;101:2071–2078.
8. Franchini M, Glingani C, Del Fante C, et al. The protective effect of O blood type against SARS-CoV-2 infection. Vox Sang. 2021;116:249–250.
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