Liver Transplantation for Nonalcoholic Fatty Liver Disease

Liver transplantation has emerged as a vital intervention for patients with advanced nonalcoholic fatty liver disease (NAFLD), particularly in its inflammatory form known as nonalcoholic steatohepatitis (NASH). The global rise in obesity and metabolic syndrome has driven NAFLD to become one of the leading indications for transplantation, surpassing viral and alcoholic liver diseases in many regions. While outcomes of transplant for NAFLD-related cirrhosis often match or exceed those for other aetiologies in terms of graft and patient survival, these patients face unique challenges: recurrence or de novo development of steatosis in the graft, accelerated fibrosis, heightened cardiovascular risk and metabolic complications such as post-transplant diabetes. Advances in molecular profiling, risk stratification and minimally invasive diagnostics have begun to inform peri- and post-transplant management. Optimising immunosuppression regimens, monitoring metabolic parameters and targeting pathways involved in wound healing and extracellular matrix remodelling are central to improving long-term outcomes. A multidisciplinary approach that integrates hepatology, endocrinology and surgery is critical for addressing the complex interplay between metabolic dysfunction and graft health.

Research from Nature Portfolio

Recent investigations have leveraged plasma and tissue biomarkers to anticipate graft outcomes in recipients of transplants for NASH cirrhosis. A proteomic analysis of the plasma degradome has identified peptide signatures derived predominantly from extracellular matrix proteins that distinguish patients at risk of developing post-transplant fibrosis. These degradome profiles, derived through advanced mass spectrometry, offer promising minimally invasive biomarkers for early stratification and intervention. Complementary work has explored the role of insulin resistance and adipokine alterations in the pathogenesis of graft steatosis. Imaging techniques such as controlled attenuation parameter quantification have been correlated with changes in circulating leptin, adiponectin and insulin, underscoring the central role of metabolic derangements in post-transplant steatosis and providing potential targets for therapeutic modulation.

Liver Transplantation for Nonalcoholic Fatty Liver Disease publication trend

The graph below shows the total number of articles in liver transplantation for nonalcoholic fatty liver disease across all publications each year (not limited to Nature Index journals).

Technical terms

Nonalcoholic fatty liver disease (NAFLD): Spectrum of liver conditions characterised by excessive hepatic fat accumulation in the absence of significant alcohol intake.

Nonalcoholic steatohepatitis (NASH): Progressive form of NAFLD involving hepatocyte injury, inflammation and varying degrees of fibrosis.

Metabolic dysfunction-associated steatotic liver disease (MASLD): Revised nomenclature emphasising metabolic risk factors in steatotic liver disease.

Extracellular matrix (ECM): Network of proteins and glycoproteins providing structural support to tissues and undergoing remodelling in fibrosis.

Degradome: Collection of peptide fragments generated through protein degradation, used as a biomarker of tissue remodelling.

Controlled attenuation parameter (CAP): Ultrasound-based metric for quantifying hepatic fat content noninvasively.

Insulin resistance: Impaired response of tissues to insulin leading to elevated blood glucose and metabolic dysregulation.

References

1. Transcriptomic changes in liver transplant recipients with non-alcoholic steatohepatitis indicate dysregulation of wound healing. Frontiers in Endocrinology (2023).
2. The plasma degradome reflects later development of NASH fibrosis after liver transplant. Scientific Reports (2023).
3. The Outcomes of Liver Transplantation in Severe Metabolic Dysfunction-Associated Steatotic Liver Disease Patients. Biomedicines (2023).
4. Outcomes of liver transplantation for non-alcoholic steatohepatitis: A European Liver Transplant Registry study. Journal of Hepatology (2019).
5. Risk of de novo post-transplant type 2 diabetes in patients undergoing liver transplant for non-alcoholic steatohepatitis. BMC Gastroenterology (2015).
6. Hepatic steatosis and liver fat contents in liver transplant recipients are associated with serum adipokines and insulin resistance. Scientific Reports (2020).