Rescue liver transplantation for liver failure with extrahepatic metastases: An ethical and clinical framework informed by two cases

Abstract

BACKGROUND

Liver transplantation (LT) is traditionally contraindicated in patients with active extrahepatic metastases due to concerns regarding futility, donor risk, organ allocation fairness, and limited post-transplant survival. However, in rare and extreme situations, acute hepatic failure becomes immediately life-threatening and no alternative life-saving therapy exists.

AIM

To report two rescue LT cases undertaken for end-stage hepatic failure despite persistent extrahepatic metastases, and to construct an ethical-clinical decision framework applicable to similar exceptional scenarios.

METHODS

We conducted a retrospective review of two patients who underwent rescue LT for hepatic failure with extrahepatic metastases. Clinical course, decision-making processes, donor consent procedures, and post-transplant outcomes were examined. Integrating these cases with existing literature, we developed a structured ethical and clinical decision framework.

RESULTS

One patient received a living donor graft after undergoing an enhanced informed-consent process that emphasized voluntariness, proportionality of risk, and understanding of the non-curative intent. The other patient received a deceased-donor graft, which proceeded after institutional review and confirmation that transplantation represented the only life-saving option. Postoperatively, both patients recovered normal liver function and were discharged with improved quality of life. The hepatoblastoma patient survived for 17 months post-LT, and the breast cancer patient for 9 months, with stable graft function but progressive extrahepatic disease. Both families expressed deep gratitude and satisfaction with the decision to pursue LT.

CONCLUSION

Although survival was limited, rescue LT allowed meaningful additional life in selected patients and was consistent with ethically defensible decision-making grounded in autonomy, beneficence, and compassion. However, such interventions must remain exceptional and require rigorous donor safeguards and transparent deliberation. Our proposed decision framework may support clinicians facing similar extreme scenarios and inform future discussions on exceptional indications for LT.

Key Words: Liver transplantation; Extrahepatic metastases; Hepatic failure; Contraindications; Surgical ethics

Core Tip: Rescue liver transplantation (LT) is generally considered futile in patients with extrahepatic metastases, yet in rare situations acute liver failure not tumor progression poses the true immediate threat to life. This study describes two such exceptional cases and proposes a structured ethical-clinical decision framework integrating futility assessment, donor safety, allocation fairness, and values-aligned consent. Our model outlines when rescue LT may be ethically and clinically defensible, emphasizing that its value lies in restoring hepatic function and providing meaningful time not oncologic cure.

INTRODUCTION

Liver transplantation (LT) is generally contraindicated in patients with active or metastatic extrahepatic malignancies due to expected poor oncologic outcomes and concerns regarding donor risk, organ allocation fairness, and overall futility[1].

The presence of metastatic disease has been viewed as a marker of systemic spread, rendering curative intent futile. As a result, transplant candidacy has been strictly limited to patients with localized hepatic disease and favorable tumor biology.

However, real-world practice occasionally encounters exceptional scenarios in which acute hepatic failure becomes immediately life-threatening, and no alternative therapy can prevent imminent death. In such cases, the primary ethical question shifts from: “Can LT cure malignancy?” to “Is LT justified as a rescue intervention to prevent avoidable and imminent death?”. The decision to transplant in the setting of extrahepatic metastases remains controversial. Ethical concerns regarding futility, organ scarcity, and deviation from established guidelines often provoke criticism from the medical community[2].

Recent developments in oncology, perioperative management, and post-transplant immunosuppressive strategies have expanded survival in selected patients even with advanced cancers. Yet, there is no established ethical or clinical framework to guide decision-making in the rare situation where LT is considered purely as a life-saving measure for hepatic failure in patients with persistent metastatic disease. Here, we present two patients who underwent rescue LT under exceptional circumstances and propose a structured framework that integrates ethical principles, donor protection, futility assessment, and multidisciplinary decision-making.

MATERIALS AND METHODS

The study included two patients who underwent LT at National Cancer Center, Korea. Both patients’ medical records were reviewed retrospectively. The study was approved by the Institutional Review Board (No. NCC2025-0266) with a waiver of informed consent due to the retrospective nature of the study. All LT procedures, including both donor and recipient surgeries, were performed by a single in-house surgeon.

Both patients received induction therapy with basiliximab [20 mg on the day of surgery and on postoperative day (POD) 4]. Maintenance immunosuppression consisted of corticosteroids, tacrolimus, and mycophenolate mofetil, with corticosteroids tapered over 1 month. Routine infection prophylaxis included ticarcillin-clavulanate for 1 week, fluconazole for 1 month, and trimethoprim-sulfamethoxazole for 1 year. Cytomegalovirus antigenemia assays were performed according to protocol; however, universal prophylaxis was not administered postoperative monitoring was performed with daily liver function tests and Doppler ultrasonography during hospitalization. Abdominal computed tomography scans were obtained weekly until POD 21. Following discharge, patients underwent regular follow-up visits at the outpatient clinic.

RESULTS

Case 1: Rescue deceased-donor liver retransplantation for acute liver failure in recurrent hepatoblastoma with extrahepatic metastases

Case 1 involved a young adult with recurrent hepatoblastoma who underwent rescue deceased-donor liver retransplantation for acute liver failure nearly nine years after a prior living-donor LT. A 25-year-old man with a long-standing history of recurrent hepatoblastoma presented to the emergency department on March 12, 2022 with jaundice, progressive confusion, abdominal distension, and decreased urine output. Laboratory studies demonstrated severe hyperbilirubinemia, coagulopathy, and progressive azotemia, findings consistent with acute hepatic failure with concomitant renal dysfunction (hepatorenal physiology) (total bilirubin 30.1 mg/dL, creatinine 6.55 mg/dL, international normalized ratio = 2.30).

He was admitted to the intensive care unit. During hospitalization he developed variceal hemorrhage due to portal hypertension; emergency endoscopic variceal ligation achieved hemostasis. Despite control of bleeding, his overall status deteriorated with hepatic encephalopathy, refractory ascites, and oliguria, necessitating continuous renal replacement therapy (CRRT). Given the grave prognosis, the team discussed hospice transition, potential CRRT withdrawal, and do-not-resuscitate status with the patient and family. After a multidisciplinary conference involving the oncology and transplant teams, the patient and family elected to pursue LT as a last-resort intervention. His model for end-stage liver disease (MELD) score was 39.

Following expedited approval and allocation, deceased-donor LT was performed on March 30, 2022 (POD 0) under emergency conditions (Figure 1A-C). The immediate postoperative course was uncomplicated; liver function normalized, renal replacement was discontinued, and the patient was discharged home on POD 23 (April 22, 2022) with appropriate immunosuppression and oncologic follow-up arranged.

Figure 1 Pre- and post-transplant imaging and explant specimens in two patients undergoing rescue liver transplantation. A: Pre-transplant contrast-enhanced computed tomography (CECT) of case 1 showing multifocal hepatic tumor burden; B: Explanted liver from case 1 demonstrating multiple well-circumscribed yellowish nodules consistent with treated and viable hepatoblastoma; C: Post-transplant CECT of case 1 showing normal graft enhancement; D: Pre-transplant CECT of case 2 showing diffuse metastatic involvement of the liver; E: Explanted liver from case 2 demonstrating diffuse bosselated metastatic replacement; F: Post-transplant CECT of case 2 showing homogeneous graft enhancement.

His prior oncologic history began at age 9 (July 2006) when a persistent cough led to imaging that revealed a large hepatic mass with lung metastases; the alpha-fetoprotein level was 1210 ng/mL, confirming hepatoblastoma. He underwent an extended left hemihepatectomy on August 14, 2006, followed by seven cycles of multi-agent chemotherapy (cisplatin, doxorubicin, 5-fluorouracil, interferon-α) and subsequently the VICE regimen (vincristine, ifosfamide, carboplatin, etoposide). Between 2008 and 2012, he developed multiple intrahepatic and extrahepatic recurrences managed with radiofrequency ablation; irinotecan plus 5-fluorouracil; hepatic resections of segments 6 and 7; and, in 2009, an S1 tumorectomy with intraoperative radiofrequency ablation followed by docetaxel, cisplatin, and capecitabine. Additional procedures included excision of omental deposits, para-aortic lymphadenectomy, and resection of retroperitoneal disease. Owing to unresectable hepatic recurrence, he received right-lobe living donor LT from his mother on August 30, 2013. Two pulmonary metastasectomies were performed on April 24, 2015 and December 8, 2015. With intrahepatic recurrence in 2021, he was treated with oxaliplatin, vincristine, and topotecan, followed by lenvatinib. After recovery from the emergency LT, he underwent resection of a 4^th-rib lesion and pulmonary metastasectomy on POD 118 (July 26, 2022), followed by multiple cycles of systemic chemotherapy through POD 412 (May 16, 2023). He was readmitted on POD 511 (August 23, 2023) with progressive metastatic disease complicated by worsening hepatic and renal failure, and died of multi-organ failure on POD 522 (September 2, 2023).

Case 2: Rescue living-donor LT for acute-on-chronic liver failure in metastatic breast cancer

Case 2 involved rescue living-donor LT undertaken to avert imminent death from acute-on-chronic liver failure in a patient with metastatic breast cancer. A 40-year-old woman was referred for LT after a four-month hospitalization for acute hepatic failure superimposed on metastatic involvement of the liver and lungs. She presented with hepatic encephalopathy, massive ascites, and a total bilirubin of 23 mg/dL; her MELD score was 25. She had originally been diagnosed eight years earlier, in May 2016, at an outside hospital with right breast invasive ductal carcinoma (cT2N3M0, human epidermal growth factor receptor 2-positive, androgen receptor 7/8, 30%). Core needle biopsy confirmed ductal histology. She received six cycles of neoadjuvant TCHP (docetaxel, carboplatin, trastuzumab, and pertuzumab), followed by definitive breast surgery, adjuvant radiotherapy, and tamoxifen. Between March 2018 and January 2019, she developed metastatic disease involving the lung (March 2018), liver (April 2018), and right femur (Jane 2019).

No curative oncologic options were available and medical management failed to reverse decompensation. After multidisciplinary discussion with oncology and transplantation teams and thorough counseling of the patient and family, LT was considered the only life-saving option. Given the urgency of her condition, she underwent right-lobe living donor LT with her mother as the donor on April 24, 2024 (POD 0), for acute-on-chronic liver failure (Figure 1D-F). The immediate postoperative course was uncomplicated, with normalization of liver function. She was discharged on POD 55 (June 18, 2024) on maintenance immunosuppression, and systemic therapy was resumed with trastuzumab, a gonadotropin-releasing hormone agonist, letrozole, and lorlatinib, as directed by the treating oncologist.

She experienced approximately eight months of relative clinical stability with preserved graft function, followed by progressive decline characterized by recurrent infections (including pneumonia), cachexia, and tumor progression. She died of progressive metastatic disease complicated by pneumonia on POD 257 (January 5, 2025).

DISCUSSION

These two cases illustrate the rare use of LT as rescue therapy to avert imminent death from liver failure in the presence of active systemic metastatic disease (Table 1). In both patients, liver failure not tumor progression posed the immediate life-threatening condition. Case 1 achieved prolonged, multimodal control of hepatoblastoma over 17 years, including approximately 10 years after the first transplant and 17 months after an emergent second transplant. The decision to proceed with deceased-donor retransplantation was approved only after repeated discussions by a multidisciplinary team and national regulatory oversight confirmed that liver failure not oncologic progression was the proximate and unavoidable cause of imminent death, and that no alternative intervention would have prevented mortality. This was recognized explicitly as a non-generalizable, resource-sensitive exception rather than an indication for broader application. By contrast, case 2 experienced temporary stabilization of liver function and survived 9 months, reflecting limited oncologic benefit when systemic disease remains active.

Table 1 Clinical characteristics and outcomes of the two patients undergoing rescue liver transplantation.

Feature	Case 1: Hepatoblastoma	Case 2: Breast cancer
Age/sex at rescue LT	25-year-old male	40-year-old female
Primary tumor and year	Hepatoblastoma (2006; lung metastases at diagnosis)	HER2-positive invasive ductal carcinoma (2016; cT2N3M0; AR 7/8, 30%)
Cause of liver failure	Acute-on-chronic liver failure due to recurrent hepatic tumors and graft dysfunction	Acute hepatic failure from massive metastatic infiltration
Extrahepatic metastases at LT	Lung and bone	Lung and bone
Oncologic status at LT	Slowly progressive, unresectable recurrence	Progressive systemic metastases
Timing of rescue LT	Rapid deterioration requiring emergent DDLT (March 2022; prior LDLT 2013)	Acute liver failure with encephalopathy requiring LDLT (April 2024)
Immediate post-LT course	Graft function normalized; later rib/Lung metastasectomy + chemotherapy	Graft function normalized; systemic therapy resumed
Survival after rescue LT	17 months	9 months
Primary determinant of outcome	Aggressive tumor biology with repeated extrahepatic recurrence	Continued systemic progression
Cause of death	Multiorgan failure due to advanced malignancy	Pneumonia and cancer progression
Key point	LT prevented imminent death but did not modify tumor trajectory	LT restored hepatic function but conferred only transient benefit

LT: Liver transplantation; LDLT: Living donor liver transplantation; DDLT: Deceased donor liver transplantation; AR: Androgen receptor; HER2: Human epidermal growth factor receptor 2.

These contrasting trajectories underscore the complexity and controversy surrounding LT in the presence of extrahepatic metastases and highlight the need for structured, transparent decision-making. To synthesize our experience and inform future practice, we propose a structured ethical-clinical framework to guide exceptional-indication decisions for rescue LT. A seven-step ethical-clinical algorithm summarizing this framework is presented in Figure 2, integrating futility assessment, donor protection, institutional oversight, and values-aligned consent into a coherent decision pathway. It is important to emphasize that this framework is descriptive rather than prescriptive, and does not, in itself, justify the use of a deceased-donor graft in the setting of metastatic disease. Such decisions must remain exceptional and be grounded in individualized, iterative multidisciplinary deliberation, rather than interpreted as algorithmic endorsement.

Figure 2 Seven-step ethical-clinical algorithm outlining an exceptional pathway for rescue liver transplantation in patients with imminent death from liver failure and active extrahepatic metastases. LT: Liver transplantation; INR: International normalized ratio.

Active extrahepatic malignancy has long been regarded as an absolute contraindication to LT, largely on ethical rather than evidence-based grounds[3]. Nonetheless, select exceptions already exist: For instance, current Organ Procurement and Transplantation Network/National Liver Review Board policy for hepatic epithelioid hemangioendothelioma states that extrahepatic disease is not an absolute barrier to LT or MELD exception[4]. Registry analyses further suggest that limited extrahepatic involvement does not uniformly worsen post-LT survival[5].

By contrast, in metastatic breast cancer and other common epithelial solid tumors, published “rescue LT” experiences for liver failure have required liver-limited disease at the time of transplant; representative modern reports explicitly performed exhaustive staging to exclude extrahepatic spread before LT[6]. Similar “rescue” LT has been described for selected neuroendocrine tumors (e.g., VIPoma), but again without active extrahepatic disease at transplantation[7].

To our knowledge (search through November 20, 2025), there are no prior reports describing LT undertaken in the presence of active distant extrahepatic metastases specifically for rescue from hepatic failure in either hepatoblastoma or metastatic breast cancer. Prior pediatric hepatoblastoma series emphasize clearance/control of extrahepatic disease before LT (regional hilar nodal involvement has been reported in select living-donor LT cases, but unresolved distant metastases were not accepted at transplant)[8]. Within this context, our two cases appear to be among the first to detail rescue LT despite known distant extrahepatic metastases at the time of transplantation, and should be interpreted cautiously alongside the field’s prevailing contraindication paradigm[3].

Historically, a 5-year survival of approximately 50% has been regarded as a pragmatic benchmark to justify indications for deceased-donor LT[9,10], largely informed by allocation ethics rather than biologic necessity. More stringent targets (e.g., ≥ 70% 5-year survival in selected hepatocellular carcinoma frameworks) have been proposed in specific contexts[11]. However, such benchmarks do not account for the substantial heterogeneity in post-transplant outcomes, which are influenced by perioperative risk, underlying disease biology, and patient-specific factors. Consequently, reliance on a single survival threshold may be insufficient to capture the complex clinical and ethical considerations that inform end-of-life decision-making in exceptional cases.

Living donor LT introduces additional ethical complexity, as exposing a healthy donor to operative risk may appear difficult to justify when oncologic benefit is limited. Rather than avoidance, an ethically defensible approach requires rigorous protection of donor autonomy through enhanced informed consent, including explicit discussion of non-curative intent, proportionality of risk, and voluntariness. In case 2, the decision to pursue LT arose from shared multidisciplinary judgment and was recommended by the patient’s oncologist of more than eight years, in the setting of imminent death from liver failure and absence of any alternative life-saving therapy. When coupled with robust safeguards and values-aligned consent from both donor and family, respecting donor autonomy may ethically justify living donor LT as a rescue measure in such exceptional circumstances.

It is also critical to stress that LT is never performed based on patient or family request alone. Our institutional process requires coordinated psychosocial assessment, multidisciplinary evaluation (surgery, hepatology, oncology, anesthesia, psychiatry, social work), national regulatory approval, and comprehensive informed consent. This structure ensures that decisions are ethically grounded, medically justified, and transparent. Beyond these procedural safeguards, it is essential to acknowledge the substantial clinical risk and prognostic uncertainty inherent to rescue LT in the presence of active metastatic disease. Immunosuppression may accelerate oncologic progression, perioperative morbidity remains significant, and long-term survival is highly unpredictable. These realities underscore that such interventions must remain exceedingly rare, considered only when liver failure poses an imminent and otherwise unavoidable threat to life.

These cases illustrate that some patients and families may prioritize short-term restoration of hepatic function despite a limited oncologic prognosis, reflecting individualized goals of care rather than expectations of cure. In such end-stage scenarios, the clinical value of rescue LT may reside in temporary hepatic recovery and a finite period of medically meaningful survival, rather than in durable oncologic benefit.

This perspective highlights the tension between rigid contraindication frameworks and individualized, patient-centered decision-making. It challenges the transplant community to reconsider fixed survival thresholds, to more explicitly integrate donor safety into ethical deliberation, and to recognize that meaningful clinical value may, in selected circumstances, be achieved through restoration of hepatic function even when oncologic cure is unattainable. In both cases, the decision to proceed with LT was aligned with the patients’ values and goals of care, and was understood by families as an effort to preserve meaningful time rather than to achieve prolonged survival.

CONCLUSION

These cases challenge the assumption that extrahepatic metastatic disease must remain an absolute contraindication to LT. In both patients, LT functioned solely as rescue therapy preventing imminent death from liver failure while not altering the underlying oncologic trajectory. The divergent outcomes (extended multimodal control after sequential LTs in case 1 vs 9-month survival in case 2) illustrate that systemic tumor biology, rather than transplantation, determines prognosis. We do not advocate routine expansion of LT indications. Instead, we propose an exceptional and transparent pathway in which LT may be ethically and clinically defensible when death from liver failure is imminent, when a multidisciplinary team judges the procedure medically appropriate and confirms that a realistic post-transplant plan exists, when allocation ethics for deceased donors or safety requirements for living donors are rigorously upheld, and when fully informed, values-aligned consent is obtained. Prospective registry studies are needed to clarify outcomes, refine selection, and better characterize the role of rescue LT in this rare and ethically complex population. Until then, such interventions should remain exceptional, carefully governed, and centered on patient values.

ACKNOWLEDGEMENTS

We sincerely thank the oncology team for their thoughtful referral and unwavering commitment to the patient’s care. We are also deeply grateful to the two patients and their families, who entrusted us with this final hope and gave their courageous consent for surgery under profoundly difficult circumstances.