Monika Raman, PSG College of Technology, Coimbatore
At the moment, around 80% of grafts are obtained from donors after brain death (DBDs). However, brain death (BD) significantly decreases liver graft tolerance to preservation/reperfusion damage and graft survival. In DBDs receivers, the levels of a phospholipid, glycogen, ATP, and growth factor (VEGFA, HGF, and IGF1) in hepatic damage and failure are increased compared to non-DBD recipients.
In clinical liver transplantation (LT), the lack of hepatic graft donors, and subsequently the increase in waiting lists for LT, have encouraged hospitals to modify their criteria for the acceptance of marginal donor organs, such as steatotic liver grafts.
Steatosis is known to be a major donor feature when it comes to predicting post-transplant outcomes, with up to 50% of deceased donor livers predicted to be steatotic. Compared to non-steatotic livers, hepatic steatosis is associated with a higher risk of organ malfunction and primary non-function. Progress in this field would help to lower the likelihood of post-LT dysfunction or failure, as well as shorten LT waiting lines.
Intestinal inflammation resulting from hepatic I/R
Hepatic ischemia-reperfusion (I/R) combination with LT can result in pathological intestine changes and multiple organ failure. This is due to intestinal congestion in the recipient during the anhepatic phase of liver graft implantation and the release of pro-inflammatory mediators into the circulation following reperfusion from the damaged liver. It has been proven that intestinal microbiota imbalances can exacerbate proinflammatory pathways, resulting in intestinal inflammation and damage.
In light of this, a vast body of scientific evidence suggests that reducing intestine inflammation and damage caused by hepatic I/R has a good impact on the quality of liver grafts and postoperative outcomes following LT. Polysaccharides and lipids, on the other hand, are the most prevalent ingredient in most diets. Polysaccharides/glucose and different lipids can also affect gut microbial diversity and, and consequently affect gut health.
Can the nutritional treatment be performed?
Previous findings from I/R trials of partial hepatectomy (PH) suggest that lipid therapy offers the same protection as glucose in non-steatotic livers. Meanwhile, lipid therapy is the preferred choice for reducing the harmful consequences of liver surgery in the context of steatosis.
Taken together, these findings concerning lipid/glucose therapy effects, as well as on polysaccharide/glucose and lipid effects in intestinal health, support the hypothesis that nutritional support (whether glucose/lipid emulsion treatment) not only protects against local (livers) injury caused by I/R but may also protect remote organs against harmful effects.
If this is the case, nutritional treatment for liver transplants might preserve them both directly and indirectly by alleviating the intestinal inflammation caused by hepatic I/R.
Given these findings and the strong link between the gut and the liver, we cannot rule out the potential that intestine injury and dysbiosis in LT recipients might affect liver transplant viability and, as a result, decrease liver function in DBD LT recipients.
As a result, Micó-Carnero and colleagues at the IDIBAPS in Barcelona, Spain, hope to tackle the problem. “We evaluated the possible advantages that occur from the injection of either glucose or lipids in steatotic and non-steatotic LT from DBDs,” said Micó-Carnero, the lead author of this study. They also elucidated whether these effects might be explained by improvements in intestinal inflammation and damage, as well as the maintenance of gut flora.
Nutritional treatment in steatotic and non-steatotic LT from DBDs
“To the best of our knowledge, this is the first study to show that neither glucose nor lipid therapy protects non-steatotic livers from DBD damage in the LT,” said Casillas-Ramrez, co-author of this study. Unchanged levels of ATP, glycogen, phospholipids, and growth factors linked to this treatment in non-steatotic livers from DBD.
In contrast, they discovered that the administration of lipids to steatotic grafts of DBDs protected from damage and lower ATP and glycogen levels, while simultaneously enhancing phospholipid levels, but this was not the case with glucose treatment. Increases in growth factors linked to this treatment in steatotic livers from DBD.
“In all recipients from DBDs, intestinal inflammation and damage (measured by mucosal damage, LPS, TLR4, vascular permeability, IL-10, TNF, MPO, IL1, MDA, etc.,.) were not shown,” stated Caballeria-Casals, one of the co-authors. In such instances, changes in gut microbiota would be irrelevant because no inflammation or damage to the intestine was observed following LT in any of the groups studied.
They concluded that lipid treatment was the best nutritional support for protecting steatotic LT from DBDs from hepatic damage; the advantages were independent of changes in the recipient’s intestine.
Their main goal was to uncover previously unknown pathophysiological mechanisms in steatotic and non-steatotic LT from DBDs, as well as new strategies that could be used in LT from DBDs, all while working in an environment where cadaveric donors account for more than 80% of transplants and more than 50% of donors, have hepatic steatosis.
Their findings show that nutritional treatment has the potential to enhance the postsurgical outcomes of steatotic liver transplants from DBD that would otherwise get rejected for transplantation. As a result, more grafts may be available for LT, resulting in a shorter waiting list.
These findings are of great scientific and clinical significance because they open the door to new pharmaceutical treatments for steatotic LT from DBDs that have never been described before.
Also read: The Rarest Type of Blood In The World: Rh-null
Source: Micó-Carnero, M., Casillas-Ramírez, A., Caballeria-Casals, A., Rojano-Alfonso, C., Sánchez-González, A., & Peralta, C. (2021). Role of dietary nutritional treatment on hepatic and intestinal damage in transplantation with steatotic and non-steatotic liver grafts from brain dead donors. Nutrients, 13(8), 2554. https://doi.org/10.3390/nu13082554
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About the author: Monika Raman is an undergraduate student pursuing her final year B. Tech in Biotechnology. She is an enthusiastic Biotech student aspiring for an opportunity to develop skills and grow professionally in the research field. Extremely motivated and possess strong interpersonal skills.
Read some of her published articles at BioXone:
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