NAFLD is becoming the leading cause of liver transplantation for both end-stage liver disease and hepatocellular carcinoma in the United States.
ReviewNAFLD and liver transplantation: Current burden and expected challenges
Introduction
Since its first description in the early 1980s as “a poorly understood and hitherto unnamed liver disease” [1], non-alcoholic fatty liver disease (NAFLD) has considerably evolved and progressively gained recognition among hepatologists, and has become, 30 years later, one of the most common causes of chronic liver disease [2], [3], [4]. Owing to its association with insulin resistance and metabolic risk factors, NAFLD is now considered the “hepatic manifestation” of metabolic syndrome (MS) and closely mirrors the global epidemics of obesity and type 2 diabetes [5], [6], [7], [8]. In addition, NAFLD is the most common cause of elevated transaminases in the general population [2], [9], [10], [11]. The prevalence of NAFLD in the general population ranges from 20% to 30% in Europe [12], [13] and is as high as 46% in the United States [14]. Although initially considered as a disease of developed countries, due to emerging economies and adoption of a sedentary lifestyle and Western diet, the disease is also becoming increasingly prevalent in developing countries [11], [15], [16]. Nevertheless, because of the lack of reliable non-invasive diagnostic methods suitable for screening the general population, the real prevalence of NAFLD is likely still underestimated [11], [17], [18], [19].
The spectrum of NAFLD covers two entities: simple steatosis and steatohepatitis (NASH), which is a progressive, fibrotic liver disease evolving to cirrhosis and its complications: hepatocellular carcinoma (HCC) and end-stage liver disease (ESLD) potentially requiring liver transplantation (LT). Owing to its increasing prevalence worldwide and to its recognition as a progressive severe liver disease, NAFLD has become the second leading cause of liver LT in the United States [20]. The absolute number of LT performed is roughly 6000 per year in both Europe and the United States [21], [22]. However, the frequency of transplant for NAFLD has steadily increased and is expected to continue to do so, while that for other etiologies of chronic liver disease have decreased or remained unchanged in recent years [20], [23]. If the pool of donors decreases, these trends will probably further accentuate the gap between the needs of patients with ESLD and the availability of donors.
In light of the growing impact of NAFLD on all facets of LT the purpose of this review is to discuss NAFLD in the context of LT, with particular emphasis on its rising frequency as an indication for LT, the outcome and management of patients with NAFLD on the waiting list, its impact on the LT donor pool, short and long-term outcomes after LT for patients with NAFLD, and finally, optimal management options.
Section snippets
NAFLD as a common cause of cryptogenic cirrhosis, end-stage liver disease and hepatocellular carcinoma
For many years there was no recognition of a possible link between cardiometabolic risk factors and the development of “cryptogenic cirrhosis”, i.e., cirrhosis without an identifiable cause [24]. As a result cryptogenic cirrhosis was responsible for 3–30% of cirrhosis cases in the past series [25]. For the first time Powell et al. reported a gradual loss of steatosis during the progression of NASH towards cirrhosis, thus suggesting that some cases of “cryptogenic” cirrhosis may in fact be due
Short and long-term outcomes and overall survival
The current results of LT in general are excellent, with 1-, 3-, and 6-month survival of 94%, 91%, and 88% respectively. The critical period after LT is the first 6 months with 49% of deaths and 65% of re-transplantations occurring during this time interval [22].
Obesity, type 2 diabetes and CV morbidities are frequently associated with NAFLD and may also have a negative impact on short and long-term outcomes after LT. There have been several studies reporting conflicting results on the effects
How to optimize the outcome of NAFLD patients undergoing LT
Because of the increasing prevalence of NAFLD and its impact on LT, efforts should be done both to facilitate the access of patients with NAFLD to LT and to prevent them developing metabolic-related complications following LT.
Conclusion
NAFLD has a multifaceted impact on LT that extends to both transplant recipients and organ donors. The increasing prevalence of NAFLD along with the prevalence of obesity and diabetes will likely result in a higher proportion of steatotic livers proposed for LT. Therefore, the LT community will have to face the choice of either accepting lower quality steatotic livers with possibly higher post-LT complication rates and inferior outcomes, or to discard these livers with the risk of further
Conflict of interest
The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
Authors’ contributions
Raluca Pais, Sidney Barritt, and Vlad Ratziu: wrote the manuscript; Raluca Pais, Vlad Ratziu, and Filomena Conti: manuscript design and conception; Yvon Calmus, Olivier Scatton, Thomas Runge, Pascal Lebray, Thierry Poynard: critical revision of the manuscript.
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These authors share senior authorship.