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Review Article

Normothermic Liver

International Journal of Medical Research and Review

2025 Volume 13 Number 2 Apr-Jun
Publisherwww.medresearch.in

Challenges and Opportunities in Normothermic Liver Perfusion: A Standard Research Review from an Indian Perspective

Kothwala D1, Durani O2, Jithendran A3*, Gautam K4
DOI:https://doi.org/10.17511/ijmrr.2025.i02.05

1 Kothwala Deveshkumar, Meril Medical Innovations Private Limited, Vapi, Gujarat, India.

2 Durani Ovesh, Meril Medical Innovations Private Limited, Vapi, Gujarat, India.

3* Jithendran Arshith, Meril Medical Innovations Private Limited, Vapi, Gujarat, India.

4 Gautam Khushbu, Meril Medical Innovations Private Limited, Vapi, Gujarat, India.

Liver transplantation is the only definitive treatment for end-stage liver disease and acute liver failure; however, the shortage of viable donor organs remains a critical challenge. Conventional static cold storage (SCS), while widely used, is associated with ischemia-reperfusion injury, leading to suboptimal graft function. Normothermic liver perfusion (NLP) has emerged as an advanced preservation technique that mimics physiological conditions, thereby reducing cellular injury, extending preservation times, and improving organ viability. Studies have demonstrated that NLP enhances graft recovery, facilitates viability assessment, and increases the utilization of marginal donor livers. Despite these advantages, the implementation of NLP in India is hindered by high costs, infrastructure limitations, and the need for specialized expertise. However, with increased investment in healthcare, research collaborations, and regulatory support, NLP could revolutionize liver transplantation in India by improving transplant outcomes and expanding the donor pool. This review explores the clinical benefits, challenges, and potential pathways for integrating NLP into India’s organ transplantation framework, highlighting the need for strategic policy interventions, cost-effective solutions, and workforce training to enable widespread adoption.

Keywords: Normothermic Liver Perfusion, Liver Transplantation, Organ Preservation, India, Challenges, Opportunities

Corresponding Author How to Cite this Article To Browse
Jithendran Arshith, Meril Medical Innovations Private Limited, Vapi, Gujarat, India.
Email: 		Kothwala D, Durani O, Jithendran A, Gautam K, Challenges and Opportunities in Normothermic Liver Perfusion: A Standard Research Review from an Indian Perspective. Int J Med Res Rev. 2025;13(2):20-26.
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https://ijmrr.medresearch.in/index.php/ijmrr/article/view/1540

Manuscript Received Review Round 1 Review Round 2 Review Round 3 Accepted
2025-02-05 2025-02-13 2025-02-21 2025-03-01 2025-03-09
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© 2025by Kothwala D, Durani O, Jithendran A, Gautam Kand Published by Siddharth Health Research and Social Welfare Society. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License https://creativecommons.org/licenses/by/4.0/ unported [CC BY 4.0].

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Jithendran A et al. Challenges and Opportunities in Normothermic Liver Perfusion

Introduction

Liver transplantation remains the only definitive therapeutic option for patients suffering from end-stage liver disease and acute liver failure [1]. However, the availability of viable donor organs continues to pose a significant challenge, limiting the number of transplants that can be performed annually [2]. Conventional static cold storage (SCS) has been widely utilized as the gold standard for organ preservation. Despite its widespread adoption, SCS is associated with ischemia-reperfusion injury, which may lead to suboptimal graft function and negatively impact post-transplantation outcomes [3].

An alternative preservation technique, normothermic liver perfusion (NLP), has been introduced to mitigate ischemic injury by mimicking physiological conditions, thereby enabling extended preservation times and improving graft viability [4]. NLP involves maintaining the liver in a metabolically active state by providing oxygenated perfusate, essential nutrients, and controlled temperature conditions, which collectively reduce cellular injury and enhance graft recovery [5]. Studies have demonstrated that NLP facilitates the assessment of organ viability before transplantation, thereby increasing the utilization of marginal and previously discarded livers [6]; [3].

Despite its evident advantages, the implementation of NLP in India presents unique challenges. One of the primary limitations is the high cost associated with acquiring and maintaining NLP technology, which may hinder its widespread adoption in resource-limited settings [7].

Furthermore, the successful deployment of NLP requires specialized training for healthcare professionals, as well as the establishment of appropriate infrastructure to support ex-situ organ perfusion [8]. The requirement for highly skilled personnel and advanced technological resources poses a barrier to the widespread integration of NLP into the existing organ transplantation framework in India.

Nevertheless, opportunities for the adoption of NLP in India remain promising. Increased investment in healthcare infrastructure, coupled with government and private sector initiatives, could facilitate the incorporation of NLP into transplant programs [9].

Additionally, the potential for improved organ utilization rates and enhanced post-transplant outcomes may justify the economic investment in NLP technology. Collaborative efforts between healthcare institutions and research organizations could further advance the development of cost-effective NLP solutions tailored to the Indian healthcare landscape [10]

In conclusion, while NLP represents a significant advancement in liver preservation and transplantation, its implementation in India is challenged by economic constraints, the need for specialized expertise, and infrastructural limitations. However, with strategic investments and collaborative initiatives, the integration of NLP into India's organ transplantation programs may become a feasible and beneficial endeavour, ultimately improving transplant outcomes and patient survival rates [11].

Literature Review

Normothermic liver perfusion (NLP) has emerged as a revolutionary approach to preserving and assessing donor livers for transplantation. Unlike conventional cold storage, which relies on hypothermia to slow cellular metabolism, NLP maintains the organ in a physiologically active state by mimicking in vivo conditions, offering several advantages in terms of graft viability and post-transplant outcomes [12], [13]. This method enables continuous monitoring of organ function, potentially expanding the donor pool by facilitating the use of marginal livers [14].

Studies in developed countries have highlighted the efficacy of NLP in reducing ischemia-reperfusion injury and improving transplant success rates. For instance, a multicenter randomized trial demonstrated that NLP significantly reduced early allograft dysfunction compared to static cold storage [15]. Moreover, NLP enables metabolic reconditioning, potentially improving the quality of suboptimal grafts [16]. In the Indian context, the potential for NLP is considerable, given the country’s unique challenges in organ transplantation. India faces a significant disparity between organ demand and availability, with a cadaveric donation rate of only 0.52 per million population [17]. Factors such as delayed retrieval times, limited infrastructure for organ preservation, and a high prevalence of fatty liver disease exacerbate this gap [18].


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Jithendran A et al. Challenges and Opportunities in Normothermic Liver Perfusion

NLP could address some of these challenges by enabling the utilization of extended-criteria donors and improving organ transport logistics, especially in geographically diverse regions.

Despite these advantages, the adoption of NLP in India is hindered by high costs, limited technical expertise, and the need for substantial infrastructural investment [19]. Additionally, ethical concerns regarding the use of marginal livers and the lack of standardized protocols pose further barriers [20] Nevertheless, pilot studies conducted in India have shown promising outcomes, suggesting that NLP can be a viable alternative with appropriate adaptations to local conditions [21].

Emerging technologies, such as machine perfusion systems customized for Indian scenarios, could potentially reduce costs and improve accessibility [22]. Future research should focus on developing cost-effective NLP models and integrating them into India’s existing organ transplantation framework to bridge the gap between innovation and implementation.

Results

The findings from the review highlight the following key aspects:

  • Clinical Outcomes: Studies indicate that NLP reduces ischemia-reperfusion injury, decreases the risk of early allograft dysfunction, and enhances post-transplant survival rates [11], [13], [14].
  • Technological Advancements: Continuous improvements in perfusion devices, including portable and automated NLP systems, have expanded its applicability [23], [24], [15].
  • Economic Feasibility: NLP is associated with high upfront costs, which pose a barrier to its widespread adoption in resource-limited settings like India [17], [23].
  • Regulatory Landscape: India lacks standardized guidelines for NLP, necessitating policy interventions to facilitate its integration into clinical practice.
  • Training and Expertise: The implementation of NLP requires specialized training for transplant surgeons and perfusionists, which is currently limited in India.

Discussion

Challenges in NLP Adoption in India

1. Financial Constraints:

  • NLP machines and perfusion solutions are expensive, making them inaccessible to many transplant centres.
  • The high cost of disposables and maintenance further adds to the financial burden.

2. Infrastructure and Logistics:

  • Most transplant centres in India rely on static cold storage due to a lack of necessary infrastructure for NLP.
  • Transporting and maintaining NLP machines require logistical improvements.

3. Regulatory and Ethical Considerations:

  • NLP is a relatively new technology, and India lacks a regulatory framework for its standardization and implementation.
  • Ethical concerns regarding prolonged ex-vivo organ perfusion and viability assessment need to be addressed.

4. Training and Workforce Development:

  • NLP requires skilled professionals for device operation and organ assessment.
  • Limited training programs for transplant surgeons and perfusionists hinder adoption.

Opportunities for NLP in India

1. Improving Organ Utilization:

  • NLP can revive marginal donor livers, increasing the donor pool and reducing waitlist mortality.
  • It enables better organ assessment before transplantation, reducing the risk of graft failure.

2. Enhancing Research and Innovation:

  • Collaboration between healthcare institutions, universities, and medical device companies can lead to cost-effective, India-specific NLP solutions.
  • Government initiatives and funding can support research in organ perfusion technologies.

3. Public-Private Partnerships:

  • Partnerships between government agencies and private healthcare providers can improve access to NLP.

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Jithendran A et al. Challenges and Opportunities in Normothermic Liver Perfusion

  • Subsidized programs and insurance
  • overage can make NLP financially viable.

4. Policy and Regulatory Framework Development:

  • Establishing guidelines for NLP use in liver transplantation can streamline its integration into clinical practice.
  • The inclusion of NLP in national transplant programs can facilitate its widespread adoption.

Conclusion

Normothermic Liver Perfusion represents a paradigm shift in organ preservation and transplantation. While India faces significant challenges in implementing this technology, the potential benefits outweigh the obstacles. By addressing financial constraints, enhancing infrastructure, and developing regulatory frameworks, India can successfully integrate NLP into its liver transplant programs. Encouraging research, fostering collaborations, and investing in workforce training will be crucial steps toward making NLP a standard practice in India, ultimately improving patient outcomes and transplant success rates [19] [21] [22] Studies have demonstrated the efficacy of NLP in improving liver graft viability, reducing ischemia-reperfusion injury, and increasing the utilization of marginal donor livers [25] [13] [12]. The integration of this technology in high-risk donor liver transplantation has shown promising results [14]. However, the cost of implementation remains a significant hurdle, necessitating the development of cost-effective perfusion systems suited for the Indian healthcare ecosystem. [22] Ethical considerations, regulatory support, and public awareness are also critical factors in ensuring the successful adoption of NLP in India [20] [17]. With concerted efforts from policymakers, clinicians, and researchers, NLP can become a transformative solution for liver transplantation in India, addressing the country's growing burden of end-stage liver disease [18]; [26].

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