NAFLD and liver transplantation: Current burden and expected challenges

Summary

Because of global epidemics of obesity and type 2 diabetes, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing both in Europe and the United States, becoming one of the most frequent causes of chronic liver disease and predictably, one of the leading causes of liver transplantation both for end-stage liver disease and hepatocellular carcinoma. For most transplant teams around the world this will raise many challenges in terms of pre- and post-transplant management. Here we review the multifaceted impact of NAFLD on liver transplantation and will discuss: (1) NAFLD as a frequent cause of cryptogenic cirrhosis, end-stage chronic liver disease, and hepatocellular carcinoma; (2) prevalence of NAFLD as an indication for liver transplantation both in Europe and the United States; (3) the impact of NAFLD on the donor pool; (4) the access of NAFLD patients to liver transplantation and their management on the waiting list in regard to metabolic, renal and vascular comorbidities; (5) the prevalence and consequences of post-transplant metabolic syndrome, recurrent and de novo NAFLD; (6) the alternative management and therapeutic options to improve the long-term outcomes with particular emphasis on the correction and control of metabolic comorbidities.

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.

NAFLD is becoming the leading cause of liver transplantation for both end-stage liver disease and hepatocellular carcinoma in the United States.

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.