How Obesity Permeates Transplant Medicine

A Mathur. Liver Transplantation 2023; 29: 465-466. Open Access! Salvaging the fatty liver for transplant: is short duration NMP enough? (ed)

 “As of 2020, the Center for Disease Control (CDC) notes that 40% of the ~258 million US adults suffer from obesity. This represents just more than a 100 million people suffering from obesity. In addition, about 23 million people suffer from severe obesity with a body mass index >40 kg/m2.” Fatty liver disease (aka NAFLD), driven primarily by obesity, is a leading cause of liver transplantation. In addition, fatty liver disease is impacting the ability to treat liver failure.

“The end result of this epidemic is that we are identifying a greater proportion of organ donors with varying degrees of liver steatosis. Transplantation of steatotic livers is associated with an increased degree of ischemia-reperfusion injury (IRI) and release of inflammatory cytokines from the graft. The consequences of this can range from severe reperfusion syndromes with immediate vasoplegia and circulatory collapse to distant organ dysfunction with acute kidney injury, liver allograft dysfunction, and primary nonfunction (PNF).”

In order to try to identify suitable liver organs for transplantation, researchers are trying to identify strategies to utilize steatotic grafts safely. Patrono et al (Liver Transplantation 2023; 29: 508-502) examined the feasibility of using normothermic machine perfusion (NMP) in the setting of macrovesicular steatosis (MaS) ≥30%. They identified 10 patients who had liver transplants using NMP in patients with MaS ≥30%; 4 additional organs were not used despite NMP. 8 of 10 patients showed good liver function, representing 57% (8 of 14) of NMP fatty organs.

Another study in the same issue (NB Ha et al. Liver Transplantation 2023; 29: 476-484) showed that patients with sarcopenic obesity (=low muscle mass obesity) had high waitlist mortality of 40% compared to 21% and 12% for those with sarcopenia without obesity and for those with obesity without sarcopenia, respectively.

My take: Obesity increases the risk of fatty liver associated cirrhosis/liver failure, and is impacting the availability of suitable organs for those in need. Furthermore, in those with obesity, the presence of sarcopenia increases the risk of death on transplant waitlist.

Tucson Botanical Gardens

“More to It Than Meets the BMI”

This blog post title is quoted from a clever editorial which reviews the use of BMI and the effect of obesity with outcomes after liver transplantation (Liver Transpl 2014; 20: 253-54, related article pages 281-90.)

Key points from editorial and study:

  • Study enrolled 202 consecutive adult (mean 51 years) patients (200-2010) as part of cohort study.  Data was obtained at time of transplantation and reviewed with retrospective analysis. NAFLD was transplant indication in 7%.
  • “Use of BMI as a marker of obesity is flawed.” Authors showed only 86% agreement between calculated BMI and percent body fat as measured with DXA.
  • Patients with high BMI due to greater lean muscle mass may have improved outcomes.  Sarcopenia (loss of muscle mass) likely has greater effect on outcomes.
  • The study shows that the combination of diabetes and obesity increases the risk of complications and prolongs hospital stays (5.81 days, P<0.01).
  • Metabolic risk factors had no effect on 30-day, 1-year, or 5-year patient survival.

Another article in same issue: Liver Transpl 2014; 20: 311-22. This study retrospectively examined 148 normal-weight, 148 overweight, and 74 obese patients who underwent living donor liver transplantation. Key finding: “there were no differences in graft survival [hazard ratio (HR) =0.955] or recipient survival [HR = 0.90]” between these groups.  Obese patients do require larger grafts which can delay identifying suitable donor.

Bottomline from editorial: “this study shows us that the combination of diabetes and obesity dramatically increases the risk of complications” but not survival.  “If there comes a day when the cost of a human life is less than the cost of a 6- to 7-day hospital stay, that is the day to reckon. None of us may survive.”

Related blog post:

Sarcopenia, fatigue, and nutrition in chronic liver … – gutsandgrowth

Sarcopenia, fatigue, and nutrition in chronic liver disease

Several articles from a recent Clinical Gastroenterology and Hepatology have addressed nutritional aspects of chronic liver disease.

1. Sarcopenia?  This term refers to generalized loss of skeletal muscle.  It does not equate to malnutrition though there is significant overlap.  (Clinical Gastroenterology and Hepatology 2012; 10: 166-73 & editorial 100).  In this study, 112 adults with cirrhosis had CT scans which examined skeletal muscle at the L3 level; 40% had sarcopenia. Sarcopenia was independently associated with mortality and was not reflected in MELD score.  Patients had increased risk of death from sepsis and liver failure (HR 2.18).  Thus, sarcopenia joins hyponatremia, refractory ascites, hepatic encephalopathy as additional factors which add prognostic information to MELD score.

2. Fatigue in cirrhosis. (Clinical Gastroenterology and Hepatology 2012; 10: 174-81 & editorial 103).  Fatigue is common in cirrhosis and is multifactorial.  In this prospective study, 108 patients were evaluated with a fatigue impact scale. Fatigue improved after liver transplantation. Fatigue can be peripheral due to muscle weakness and dysfunction. And, fatigue can be central due to difficulty performing physical and mental activities.  Central fatigue is associated with an increased perceived effort for tasks and often related to depression; this type of fatigue is much more common with cirrhosis.  Although improved, fatigue often does not completely resolve with liver transplantation.

3. Nutrition recommendations. (Clinical Gastroenterology and Hepatology 2012; 10: 117-25).  A summary of nutrition recommendations in adults  with chronic liver disease is given in this article.  One common misconception is protein restriction.  This is not beneficial.  Protein recommendations are for adult patients with cirrhosis to receive 1-1.5 g/kg/day.  This amount is higher than for healthy individuals.  Protein restriction leads to protein catabolism, muscle breakdown and increases the likelihood of hepatic encephalopathy.

Additional references:

  • -Age Ageing 2010; 39: 412-23.  Sarcopenia consensus definitions in older people.
  • -Gastroenterology 2008; 134: 1741. Evaluation and management of end-stage liver disease in children. Recs vaccines due to functional asplenia/portal hypertension at age 2 for Neisseria (MCV4) or polysaccharide (MPSV4); at 6 weeks of age for pneumococcal conjugate vaccines. Reviews nutrition, varices, ascites, encephalopathy….
  • -Liver Transplant 2008; 14: 585-591. Poor growth often due to growth hormone resistance. Chronic malnutrition is a factor, but children with advanced liver dz may not grow despite adequate calories. Recs: for chronic liver dz: 130-150% of RDA based on ideal body wt; in infants 120-150 cal/kg/day. Increase MCT either thru formula or supplemental MCT.
  • -Liver Transplant 2006; 12: 1310. Review article on nutrition for OLTx patient.
  • -JPGN 2000; 30: 361. nutrition review and chronic liver disease.