Influence of Donor and Recipient Genetic Polymorphisms on Graft Steatosis After Liver Transplant

Influence of Donor and Recipient PNPLA3 and MBOAT7 Gene Polymorphisms on Graft Liver Steatosis After Living Donor Liver Transplant for Metabolic Dysfunction-associated Steatohepatitis (MASH) Related Cirrhosis

MASH (Metabolic Dysfunction-associated Steatohepatitis) is among the most common indications for liver transplantation.The metabolic syndrome persists after liver transplant and is often further exacerbated among MAFLD patients, thereby leading to recurrence of MAFLD in the allograft. MAFLD is a complex phenotype, dynamic interactions between both genetic and environmental factors are likely to shape disease susceptibility and progression.

Genetic and epidemiological studies, indicates strong heritability of hepatic fat content.Family studies demonstrate that first degree relatives of patients with MAFLD are at a much higher risk of the disease than the general population.Most of the data available is regarding Deceased Donor Liver Transplant and Western population.Most studies have studied single gene variant but fatty liver is a polygenic trait.No study was done exclusively in MASH recipients.

In this study we aim to study the effect of recipient and donor PNPLA3, MBOAT7 gene variations, and other clinical & laboratory data on graft liver steatosis in liver transplant recipients. We also propose to compare the outcomes of genetically related donors vs unrelated donors, to know the influence of genetic factors vis-a-vis environmental factors.

MASH (Metabolic Dysfunction-associated Steatohepatitis) is among the most common indications for liver transplantation.The metabolic syndrome persists after liver transplant and is often further exacerbated among MAFLD patients, thereby leading to recurrence of MAFLD in the allograft. MAFLD is a complex phenotype, dynamic interactions between both genetic and environmental factors are likely to shape disease susceptibility and progression.

Genetic and epidemiological studies, indicates strong heritability of hepatic fat content.Family studies demonstrate that first degree relatives of patients with MAFLD are at a much higher risk of the disease than the general population.

PNPLA3 isoleucine to methionine substitution at position 148 is the most robust and well replicated genetic variant associated with MAFLD. MBOAT7 was recently associated with the risk of MAFLD, inflammation and fibrosis. Furthermore, it was recently linked to progression of MAFLD to HCC.

Most of the data available on donor and recipient PNPLA3 and MBOAT7 gene polymorphisms is with regards to Deceased Donor Liver Transplant and Western population. There are contradictory conclusions in different studies. Most studies have studied single gene variant but MAFLD is a polygenic trait. No study exclusively in MASH related CLD recipients. A study in the setting of LDLT gives us an opportunity to assess both genotypic and phenotypic (environmental) factors. Hence this study is being done in a high volume liver transplant center in India, in the setting of LDLT which gives us an opportunity to assess both genotypic and phenotypic (environmental) factors.

Inclusion Criteria:

• All LDLT recipients with MASH related CLD and their donors who underwent their surgery at ILBS at least 3 years prior to the onset of this study.

Exclusion Criteria:

• Pediatric (<18 years)
• Transplants for ALF/ ACLF