INTRODUCTION

In North America and Europe, deceased donor liver transplantation is the standard of care for patients with end-stage liver disease.1,2 According to the Organ Procurement and Transplantation Network (OPTN) and the Scientific Registry of Transplant Recipients liver annual data report, liver transplant volume continues to grow, registering a record number of 9,234 transplants performed in the United States in 2021, mainly from deceased donors (93.8%).3 Nonetheless, adult candidates on the liver waiting list are still considerable, and although mortality has decreased in the past decade, it is still high.3 This pushed the transplant community to consider other strategies to increase the organ donor pool, such as donation after cardiac death, split livers, older donors, or living donor liver transplantation (LDLT).4 LDLT is an established practice in Asian countries, which is also growing in Western countries, representing 5.6% of all adult liver transplants in the United States in 2021.1,3,4 Donor safety is the primary concern because liver donors, ideally, should not have any complication. However, it involves performing a major surgery with considerable risks.2,5 The mortality rate for living liver donors has been reported to be 0.1%–0.5%, whereas morbidity rates vary between 21% and 47%, although most complications are minor and overcomeable.6–9 With the creation of the OPTN Living Donor Committee recommendations, data on long-term outcomes are growing, focusing mainly on donor quality of life (QoL), morbidity, and mortality, with little emphasis on medical complications.10

CASE REPORT

A 60-year-old woman with a history of type 2 diabetes, hypertension, and left liver lobectomy for LDLT for her daughter with end-stage liver disease due to biliary atresia at the age of 33, in Belgium, presented to the Emergency Department with sudden hematemesis. There was no personal or familial history of autoimmune diseases, and she denied recent illnesses or changes in her usual medication (only antihypertensive and glucose-lowering drugs) and alcohol or drug use. Her physical examination, besides paleness of the skin and mucosae and a heart rate of 115 bpm, was unremarkable. Laboratory findings were as follows: hemoglobin 9.3 g/dL, platelets 105,000/μL, International Normalized Ratio 1.4, total bilirubin 0.5 mg/dL, albumin 3.2 g/dL, aspartate aminotransferase 205 U/L, alanine aminotransferase 260 U/L, gamma-glutamyltransferase 106 U/L, and alkaline phosphatase 50 U/L. Abdominal ultrasound found dysmorphic right liver lobe with morphologic features suggestive of cirrhosis. After hemodynamic resuscitation with crystalloid fluids, she underwent urgent upper endoscopy, which showed 4 large esophageal varices with multiple red spots and active bleeding on one of them, promptly submitted to variceal band ligation and medical treatment with terlipressin and ceftriaxone. Differential diagnosis was started. Viral hepatitis was excluded, and laboratory data revealed elevated immunoglobulin G serum levels (24.45 g/L) and positive antinuclear antibodies with a titer of 1:160. Transjugular liver biopsy showed architectural distortion with thick fibrotic septa containing, mild to moderate lymphoid inflammatory infiltrate, without recognizable plasma cells, and mild and focal interface hepatitis compatible with cirrhosis of possible autoimmune hepatitis (AIH) etiology, scoring a total of 7 points according to the simplified AIH scoring system (Figure 1). Prednisolone 0.5 mg/kg daily was started and gradually tapered to a lower dose, and azathioprine was added. Reassessment at 4 weeks after initiation of treatment with more than 50% decrease of serum transaminases and a complete biochemical response (CBR) was achieved at 6 months. Transient liver elastography at CBR showed liver stiffness compatible with advanced chronic liver disease (34.8 kPa) and absence of steatosis (controlled-attenuation parameter [CAP] 190 dB/m). At the time of her last evaluation, she maintained good liver function with no new decompensation events.

Figure 1.:

Transjugular liver biopsy: (a) hepatic cirrhosis with broad fibrous septa (Masson trichrome, 20×), (b) moderate mononuclear cell inflammation (hematoxylin and eosin, 40×), and (c) mild interface hepatitis (hematoxylin and eosin, 100×).

DISCUSSION

When it comes to long-term risks for LDLT, most studies were focused on surgical complications and, more recently, QoL. As previously mentioned, there has been an increasing number of reports on long-term QoL of donors in LDLT across Western and Eastern countries. Almost all of them agree that donors long-term QoL is as good as of the general population.6,8,11,12 Reports documenting on donor's long-term liver function after donation are scarce, and to our knowledge, there are none past the first decade postdonation. Fewer studies have reported on laboratory results beyond the first year of postdonation. Nonetheless, all of them reported no significant differences between liver function tests and liver enzymes before and after donation, except for platelet count that was consistently lower after donation.4,5,12–14 Despite a median follow-up time of ∼6 years, the number of enrolled patients in these studies was small at start and decreases after 1 year of follow-up. A recent study from Abdel-Khalek et al followed-up more than 200 patients over a median period of 117 months (∼9.7 years) and found that liver donors had normal liver function and enzymes at the end of follow-up, yet neither had statistical significance.8

In AIH, more than half of patients present as asymptomatic or with nonspecific symptoms and almost one-third already has advanced fibrosis on histology at diagnosis.15 This highlights the need for concomitant follow-up of liver enzymes and function tests because a vast number of liver diseases, such as AIH, present as asymptomatic or with subtle symptoms that can be easily ignored by the patient and not accounted as QoL modifiers.

Considering the patient personal history and risk factors for steatotic liver disease, Metabolic Dysfunction-Associated Steatohepatitis was also considered in the differential diagnosis, but liver biopsy found no significant steatosis. Moreover, it is known that accuracy of CAP measurement is significantly reduced and should be interpreted with caution in patients with AIH and inflammatory activity. After resolution of acute hepatitis, CAP values and its diagnostic performance increase, with an optimal cut-off for detection of steatosis of 288.0 dB/m.16 In our patient, during follow-up and after achieving CBR, CAP values persisted below 200 dB/m. Taken together, and considering the immunoglobulin G elevation, positive antinuclear antibodies, and response to immunosuppression, we found the diagnosis of AIH more likely.

Our patient had no previous follow-up at our hospital; however, primary health care blood test records show a fluctuating liver enzyme pattern 6 years before our first encounter and 21 years after left liver lobectomy. She also had an abdominal ultrasound reporting a dysmorphic right liver lobe 1 year before the first episode of decompensation; however, we found no records of referral to a national health system hepatologist.

To our knowledge, this is the first case of AIH in a liver living donor. Several factors have been proposed to alter the risk of developing autoimmune hepatitis, but we were unable to identify any possible trigger.17 Many of these factors are speculative or unconfirmed, and we cannot correlate previous hepatectomy with probability of developing AIH nor is our intention. Our patient, apparently, kept good liver function for more than 20 years. The OPTN recommends that all live donors maintain, within possible, follow-up at the transplant clinic for at least 2 years before discharge, although an extension could be considered depending on cost coverage for laboratory tests.10 In line with OPTN recommendations, current guidelines for LDLT recommend that all liver donors should have regular clinical follow-up for at least 2 years and preferably for life.1,8 Changes in our patients' liver enzymes started long before the first episode of decompensation which, considering her personal history, should have prompt swift referral to an hepatologist for initial liver disease work-up.

DISCLOSURES

Author contributions: B. Canhão and J. Madaleno: drafted the main manuscript text. B. Canhão, J. Madaleno, and A. Simão: treated the patient in ward. A. Cipriano made the histological diagnosis. All authors provided important intellectual input and critically revised the manuscript. All authors accepted the final version of the manuscript. B. Canhão is the article guarantor.

Financial disclosure: None to report.

Informed consent was obtained for this case report.

REFERENCES 1. Manas D, Burnapp L, Andrews PA. Summary of the British transplantation society UK guidelines for living donor liver transplantation. Transplantation. 2016;100(6):1184–90. 2. Barbetta A, Aljehani M, Kim M, et al. Meta-analysis and meta-regression of outcomes for adult living donor liver transplantation versus deceased donor liver transplantation. Am J Transpl. 2021;21(7):2399–412. 3. Kwong AJ, Ebel NH, Kim WR, et al. OPTN/SRTR 2021 annual data report: Liver. Am J Transplant. 2023;23(2 Suppl 1):S178–S263. 4. Gorgen A, Goldaracena N, Zhang W, et al. Surgical complications after right hepatectomy for live liver donation: Largest single-center western world experience. Semin Liver Dis. 2018;38(2):134–44. 5. Castedal M, Andersson M, Polanska-Tamborek D, Friman S, Olausson M, Fehrman-Ekholm I. Long-term follow-up of living liver donors. Transplant Proc. 2010;42(10):4449–54. 6. Darwish Murad S, Fidler JL, Poterucha JJ, et al. Longterm clinical and radiological follow‐up of living liver donors. Liver Transplant. 2016;22(7):934–42. 7. Ladner DP, Dew MA, Forney S, et al. Long-term quality of life after liver donation in the adult to adult living donor liver transplantation cohort study (A2ALL). J Hepatol. 2015;62(2):346–53. 8. Miller CM, Durand F, Heimbach JK, et al. The international liver transplant society guideline on living liver donation. Transplantation. 2016;100(6):1238–43. 9. Abdel-Khalek EE, Abdel-Wahab M, Elgazzar MH, et al. Long-term follow-up of living liver donors: A single-center experience. Liver Transplant. 2022;28(9):1490–9. 10. Procedures to collect post donation follow up data from living donors–OPTN. Organ Procurement and Transplantation Network (https://optn.transplant.hrsa.gov/professionals/by-topic/guidance/procedures-to-collect-post-donation-follow-up-data-from-living-donors/). Accessed July 6, 2023. 11. Vargas PA, McCracken EKE, Mallawaarachchi I, et al. Donor morbidity is equivalent between right and left hepatectomy for living liver donation: A meta-analysis. Liver Transplant. 2021;27(10):1412–23. 12. Akamatsu N, Hasegawa K, Nojiri K, et al. Long-term quality of life of living liver donors: A Japanese nationwide survey. Liver Transplant. 2022;28(11):1800–3. 13. Dew MA, Butt Z, Humar A, DiMartini AF. Long-term medical and psychosocial outcomes in living liver donors. Am J Transplant. 2017;17(4):880–92. 14. Trotter JF, Gillespie BW, Terrault NA, et al. Laboratory test results after living liver donation in the adult-to-adult living donor liver transplantation cohort study. Liver Transplant. 2011;17(4):409–17. 15. Mack CL, Adams D, Assis DN, et al. Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the American association for the study of liver diseases. Hepatology. 2020;72(2):671–722. 16. Steinmann S, Hartl J, Weidemann S, et al. Accuracy of controlled attenuation parameter measurement for the detection of steatosis in autoimmune liver diseases. JHEP Rep. 2023;5(12):100898. 17. Muratori L, Lohse AW, Lenzi M. Diagnosis and management of autoimmune hepatitis BMJ. 2023;380:e070201.