Liver transplantation (LT) is widely recognized as the treatment of choice for decompensated chronic liver disease and acute liver failure arising from various etiologies, including autoimmune chronic liver disease. Because the donor organ is perceived as foreign by the recipient’s immune system, lifelong immunosuppressants—such as calcineurin inhibitors, mycophenolate mofetil, and steroids—are required to prevent immune-mediated rejection. However, these medications can lead to a range of short-term and long-term complications, including metabolic syndrome (hypertension, diabetes mellitus, and dyslipidemia), infections, and malignancies [1,2].

The liver possesses a unique characteristic among solid organ transplants—immunotolerance. In some cases, LT recipients can discontinue immunosuppressive therapy without compromising graft function, while still maintaining adequate antimicrobial defense. This promising attribute underscores the potential for enhancing posttransplant care, as between 20% and 40% of LT recipients may achieve graft tolerance after cessation of immunosuppression [3].

In identical monozygotic twins, a complete match of DNA allows for transplantation without the need for immunosuppression. To date, only seven case reports of living donor LT (LDLT) among identical twins have been published (Table 1). Herein, we report a case of LDLT between identical twins performed for autoimmune hepatitis (AIH)-related decompensated chronic liver disease.

Informed consent for publication was obtained from the patient. A 45-year-old woman was diagnosed with decompensated autoimmune chronic liver disease, with a Child-Turcotte-Pugh score of 8B and a Model for End-Stage Liver Disease score of 16. A LDLT was planned with her identical twin sister serving as the donor. The donor exhibited no clinical signs of autoimmune disease, and her liver function tests along with other biochemical parameters were within normal limits. DNA was isolated from buccal swab samples, and autosomal DNA analysis was performed to confirm the relationship. Specific short tandem repeats (STRs) were analyzed to determine the degree of relatedness, and the comparison of STR profiles revealed a siblingship probability of 99.99%. Both the donor and recipient demonstrated similar intrahepatic anatomy—specifically, Michel’s type I arterial anatomy and a Nakamura type C portal vein. Imaging of the recipient also revealed the presence of shunts, including a coronary shunt and a shunt along the ligamentum teres. The recipient underwent LDLT with a modified right lobe graft. During the operation, 500 mg of intravenous methylprednisolone was administered. Postoperatively, she received tapering doses of intravenous methylprednisolone along with tacrolimus. Immunosuppression was discontinued after 1 week, and the steroid dose was gradually tapered. She was discharged home after 2 weeks, and at over 2 years of follow-up, she remains well on low-dose steroids.

Immunosuppressants are essential for the success of LT, both during and after the procedure, as they suppress immune activity and significantly reduce the risk of organ rejection. This ensures optimal function of the transplanted liver and enhances the overall outcome for the recipient. The dosages of these medications are adjusted as needed to minimize the risk of infections and other complications associated with a weakened immune system. In this patient, 500 mg of intravenous methylprednisolone was administered during the operation for its anti-inflammatory effects, which reduced the inflammatory response and decreased the risk of ischemia-reperfusion injury. Additionally, methylprednisolone helped stabilize hemodynamics, manage potential allergic reactions during surgery, and lower the risk of graft dysfunction [9].

Long-term use of immunosuppressants can lead to several side effects that vary by medication and individual patient. The risk of developing hypertension may increase from 15% to 70%, and the incidence of type 2 diabetes mellitus can rise from 15% to 40%. Dyslipidemia affects up to 70% of recipients, while more than 50% may develop chronic kidney disease, with over 20% progressing to stage 4 within 5 years. Consequently, the risk of cardiovascular complications increases significantly, accounting for up to 20% of mortality and morbidity in this population [10–12]. Liver transplant recipients also face a markedly higher risk of cancers—both lymphoproliferative and solid organ malignancies—which occur two to thirty times more frequently than in the general population [13]. The dosage and duration of immunosuppressive therapy are significant risk factors [2,14]. In such cases, reducing or withdrawing immunosuppression is often attempted as a salvage intervention to restore antitumor immune responses and improve cardiovascular risk, metabolic profile, and kidney function. Nonetheless, these benefits must be carefully weighed against the potential risks of rejection and allograft dysfunction.

Immunotolerance in LT recipients refers to the successful discontinuation of immunosuppression while preserving graft function and preventing rejection. This phenomenon is particularly noteworthy because the liver has intrinsic properties that promote tolerance. Several factors may contribute to immunotolerance in LT patients. One factor is the transfer of passenger donor immune cells to the recipient, which establishes a state of microchimerism. A second factor is the production of soluble donor major histocompatibility complex class I molecules by the liver, which neutralize preformed antibodies and inhibit T cell activation. A third contributing factor is the liver’s large size and regenerative capacity, which enhance its resistance to rejection-related damage [15]. Nevertheless, most LT recipients experience immunological rejection and require long-term immunosuppressive medication until alloreactivity decreases over time, leading to a state of tolerance [16]. Understanding and promoting immunotolerance remains a significant area of research, as it may lead to improved outcomes for transplant recipients, a reduced need for lifelong immunosuppression, and a lower risk of infection and other complications.

According to published data, weaning from immunosuppression may be possible in up to 40% of liver recipients [17]. Two prospective cohorts investigated the impact of withdrawing immunosuppressive therapy on tolerance development. High-risk groups for rejection were excluded, such as patients with autoimmune liver diseases, recent LT recipients, and those with acute or chronic rejection or METAVIR scores of III–IV. After 3 years of follow-up, 40% of the European cohort tolerated the withdrawal of immunosuppressive therapy. The recipient’s age and the time elapsed since LT were key predictors of developing tolerance [18,19]. Additionally, male gender and a lower human leukocyte antigen (HLA) mismatch between the donor and recipient were noted as factors favoring tolerance [19,20]. In our patient, the absence of an HLA mismatch supports this theory.

Human monozygotic twins arise from the splitting of a single zygote into two embryos, an event that occurs in approximately one in every 250 live births worldwide [21]. Monozygotic twins are genetically identical and share the same gender unless mutations occur during in utero development. It is important to note that monozygosity cannot be definitively established by standard transplant HLA matching alone, as approximately 25% of dizygotic twins share identical transplant HLA haplotypes. Polymerase chain reaction (PCR) amplification of genomic DNA extracted from oral epithelial cells via buccal swabs is used to assess allelic concordance between twins [22]. PCR-based STR profiling—the method used in our patient—is a relatively new and cost-effective technique for DNA fingerprinting that provides accurate results [23].

Reports on the rates of recurrent AIH vary significantly, ranging from 7% to 41% [24]. Research suggests that maintaining patients on low-dose steroids can help reduce the likelihood of recurrence. A retrospective analysis of 73 AIH patients maintained on long-term low-dose steroids, according to the transplant center protocol, demonstrated recurrence rates of 0%, 4%, 6%, and 11% at 1, 3, 5, and 10 years, respectively. Moreover, there was no significant increase in the rates of sepsis or osteoporosis compared to post-LT patients who were not on steroids [25]. In our case, the recipient received low-dose oral steroids for the prevention of recurrent AIH and maintained normal liver function during more than 2 years of follow-up.

Thus far, seven cases of LDLT between identical twins performed without immunosuppression have been reported (Table 1). In this case, over 2 years of posttransplant monitoring have demonstrated that both the recipient and donor remain in excellent health. Liver chemistry tests have consistently shown near-normal results, and the postoperative course has been free of rejection, infection, or medication toxicity. Transplantation between identical twins is advantageous because it provides an immune-compatible organ, thereby reducing the risk of rejection. Consequently, LDLT between identical twins offers significant immunological benefits. Currently, there is no well-established treatment strategy specifically for LT recipients who are identical monozygotic twins; however, given their shared genetic profile, the risk of rejection is anticipated to be minimal. Both previous studies and our findings indicate that there is little to no need for postoperative immunosuppressive medications.

No potential conflict of interest relevant to this article was reported.

Conceptualization: KH, KM, PS, VV. Data curation: KH, YY, TK, AA. Formal analysis: KH, YY, TK. Investigation: KH, YY, TK, AA. Methodology: KH, YY, TK. Visualization: KH, YY, TK, AA. Writing–original draft: KH, KM, PS, NKG, AA, VV. Writing–review & editing: KH, KM, NKG, PS, AA, VV. All authors read and approved the final manuscript.