Combined liver-lung transplantation: Indications, outcomes, current experience and ethical Issues

doi:10.1016/j.trre.2018.11.002

Transplantation Reviews

Volume 33, Issue 2, April 2019, Pages 99-106

https://doi.org/10.1016/j.trre.2018.11.002 Get rights and content

Highlights

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Combined liver-lung transplantation is a rare but life-saving procedure.
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There are special anesthesia and surgical considerations given the higher risk surgical candidates with multisystem disease.
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A variety of successful operative techniques have been described.
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Combined transplant has demonstrated similar results compared to isolated organ transplant.
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It is important to develop criteria for appropriate patient selection and a rigorous multiorgan allocation policy.

Abstract

Combined liver-lung transplantation (CLLT) is a rare, life-saving procedure to treat concomitant lung and liver disease. There have been 93 combined lung and liver transplantations performed in the United States since 1994. Techniques include both lung first and liver first sequential transplants with selective extracorporeal circulation of either thoracic or abdominal portions, with either end-to-end or Roux-en-Y choledochojejunostomy for biliary reconstruction. This review evaluates the existing literature regarding combined lung and liver transplantation (CLLT), describing the candidates, operation, perioperative complications, associated management strategies, and recommendations for immunosuppressive therapy and follow up.

Introduction

There have been 103 combined lung and liver transplantations (CLLT) performed in the United States to date, the first performed in 1994 at the University of Illinois Medical Center. In the decade following this inaugural operation, only 17 CLLT were performed, and it remains a relatively rare procedure [1], comprising <0.01% of the 12,749 multiorgan transplants that have occurred in the United States since 1988 (Fig. 1) [2]. These 103 surgeries were all performed at high-volume centers: Houston Methodist Hospital (14), Duke University (15), Cleveland Clinic Foundation (10), University of Pennsylvania (10), St. Louis Children's Hospital (7), Texas Children's (7), and University of Pittsburg (7), while the remaining 21 centers performed 5 or fewer CLLT each [1]. There is a dearth of published literature on CLLT, largely comprised of single or two patient case studies; the largest published cohort is a single-center study by the Hannover group (Salman, n = 25), followed by single-center US groups (Arnon, n = 15; Barshes, n = 11; Yi, n = 8) [[3], [4], [5], [6]].

Despite its rarity, CLLT serves as a last recourse for those patients with end-stage lung disease complicated by concomitant liver disease, in whom survival is not expected with single organ transplantation alone. Combined liver-lung transplantation is most commonly indicated in cystic fibrosis accompanied by cirrhotic liver disease [7]. Given the limited experience with CLLT, there is immense variability in patient cohort, selection criteria, surgical technique, anesthesia protocols, and postoperative management. Moreover, posttransplant immunosuppressive protocols tend to vary from center to center, and in light of the ever-growing understanding of transplant immunobiology, the pattern of induction and maintenance therapy continues to change [8,9]. This review examines the current literature regarding combined liver-lung transplants, most of which were retrospective case series or single transplant center analyses. Though this necessarily limits the generalizability of recommendations, we review the existing medical literature and discuss the indications, procedure, and outcome to assist clinicians in evaluating patients for CLLT.

Section snippets

Indications

Associated conditions such as hepatopulmonary syndrome and portopulmonary hypertension exemplify the complex relationship between liver and lung, wherein common sequelae of primary pathologies of either organ include a heterogeneous group of complications for the other [10]. As such, combined transplant candidates comprise a diverse patient cohort of both pediatric and adult patients with congenital or acquired disease [10]. Indications for CLLT include end-stage lung disease with concomitant

Patient candidacy

There is limited description of appropriate pre-transplant evaluation of patients requiring CLLT, though the typical approach is independent evaluation for each organ. Most authors describe CF patients with known bacterial colonization [[12], [13], [14]] who presented with severely compromised pulmonary function requiring supplemental oxygen or mechanical ventilation, and liver complications such as history of gastrointestinal bleed [14]. Yi et al. report that CLLT candidacy was first

Operation

While there are proposed variations to the surgical approach and anesthesia protocols for CLLT, the sequence of transplantation for all reviewed studies were lungs first, followed by liver from the same donor. Coordination of the thoracic abdominal teams is critical in the process of operative planning. Lungs were preserved in low potassium dextran solution (Perfadex) and liver in University of Wisconsin solution (UW) [6,12]. The commonly described technique is to perform sequential bilateral

Perioperative challenges and complications

CLLT presents a particular challenge for anesthesia, as the liver and lung transplant have opposing anesthetic goals regarding optimal volume resuscitation and ventilation (Table 2) [13]. Therefore, cooperation and coordination between teams is essential for operative success. Post reperfusion syndrome is a well-established intraoperative complication of liver transplantation, defined as a decrease in mean arterial pressure (MAP) >30% below baseline and lasting for at least 1-min during the

Follow up, maintenance, and surveillance

There are few descriptions regarding specific postoperative maintenance and surveillance regimens. Grannas et al. report regular follow up in outpatient clinics with routine labs, chest radiographs, pulmonary function tests, and abdominal ultrasound evaluation [7]. Yi and colleagues performed surveillance bronchoscopy weekly until one month, followed by every 2-weeks for three months, then every month for a year [6]. Characteristic changes in LFTs with histologic confirmation have been used for

Outcomes

Arnon etal. examined outcomes of combined liver and lung transplants in patients with CF and found that patient and graft survival at 1- and 5-years for isolated lung transplant and CLLT were comparable (patient survival: LT 83.9%, 75.7% versus CLLT 80%, 80%; graft survival: LT 76.1%, 67% versus CLLT 80%, 80%) [4]. Similarly, patient survival after CLLT versus OLT are also reported to be comparable at 30-day, 1-, 3- and 5-years (CLLT: 79%, 79%, and 63% versus OLT: 83.2%, 76.4% and 71.1%;

Conclusion

Combined lung-liver transplantation necessitates mobilization and coordination between two organ transplant programs in order to optimize patient outcomes. Pulmonary and liver failure secondary to cystic fibrosis remains the most common indication for combined thoracic organ-liver surgery, which poses specific challenges as these patients are higher risk surgical candidates given their complex multisystem disease processes. The perioperative pulmonary and hepatic insults, followed by long term

Conflict of interest

None of the authors received remuneration, reimbursement, or honorarium in the production of this manuscript and have no conflicts of interest to report.

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Citation Excerpt :
Patients with combined pulmonary and hepatic dysfunction may be considered for simultaneous combined lung-liver transplantation (CLLT) to address multiorgan dysfunction. The majority of these cases are for cystic fibrosis, and the small series evaluating CLLT predominately represent this diagnosis.83–87 Etiologies that lead to CLLT are summarized in Table 3.
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Review articleCombined liver-lung transplantation: Indications, outcomes, current experience and ethical Issues

Highlights

Abstract

Introduction

Section snippets

Indications

Patient candidacy

Operation

Perioperative challenges and complications

Follow up, maintenance, and surveillance

Outcomes

Conclusion

Conflict of interest

J Heart Lung Transplant

J Surg Res

Transplant Proc

J Cardiothorac Vasc Anesth

J Hepatol

J Cyst Fibros

Chest

Transplant Proc

J Cardiothorac Vasc Anesth

J Thorac Cardiovasc Surg

Lancet Respir Med

Am J Transplant

Anesthesiol Clin North America

Am J Transplant

Am J Transplant

Am J Transplant

Am J Transplant

J Hepatol

J Thorac Cardiovasc Surg

Am J Transplant

J Heart Lung Transplant

Am J Transplant

Am J Transplant

Am J Transplant

Am J Transplant

Am J Transplant

Adv Anesth

Acta Anaesthesiol Taiwan

Liver and combined lung and liver transplantation for cystic fibrosis: analysis of the UNOS database

Pediatr Transplant

Review article
Combined liver-lung transplantation: Indications, outcomes, current experience and ethical Issues