Nonalcoholic Steatohepatitis Is Becoming a Top Indication for Liver Transplantation Worldwide

See Article on Page 25 Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease affecting at least a quarter of the world’s population.1 Although NAFLD and its progressive form, nonalcoholic steatohepatitis (NASH), were once regarded as a problem of the developed Western countries, NAFLD and NASH are now well recognized as important and common causes of liver disease across the globe.1 All patients with NAFLD are at increased risk of cardiovascular mortality, but patients with NASH are particularly at risk for liver‐related mortality.2 This increasing burden of NAFLD has been fueled by the epidemic of obesity, which has led to a substantial increase in the prevalence of NAFLD in the United States over the past 2 decades.5 As a result, NASH has become one of the most common etiologies of hepatocellular carcinoma (HCC) and a leading indication for liver transplantation (LT).3 This is not only true for LT candidates listed for advanced cirrhosis but also for those who are listed for HCC.8 Although the epidemic of obesity and diabetes has certainly fueled the increasing number of patients listed for LT, better characterization of cryptogenic cirrhosis as NASH cirrhosis may have contributed to this increase. The epidemic of obesity, diabetes, and NAFLD is not unique to the United States and Europe. It is estimated that over 40% of the adult population in Australia have NAFLD.2 This in large part reflects an epidemic of obesity in this region with a prevalence of obesity of 28% in Australia, 29% in New Zealand, almost 45% in Maori, and even higher in the Pacific Islands.2 Similar to the United States, these high prevalence rates have led to an increasing number of NASH patients requiring LT in Australia and New Zealand.9 The proportion of LT ascribed to NASH has been reported to have increased from 1% in the early 2000s to 6% in the mid‐2010s.9 This change is further addressed in a study reported by Calzadilla‐Bertot et al. that is published in the current issue of Liver Transplantation.10 Using data from 5000 transplant candidates obtained from the Australia and New Zealand Liver Transplant Registry, the authors demonstrated substantial increases in NASH‐related LT registrations and transplants. As in the United States until recently, hepatitis C virus (HCV) had remained the most common cited etiology for LT registration and transplant among patients with or without HCC. The rate of LT for alcohol‐related liver disease has remained stable with a decline in hepatitis B virus–related LT. On the other hand, the proportion of transplants performed for NASH increased from 0.0% in 1994 to 12.4% in 2017, making it the third‐leading indication for LT. In fact, between 2013 and 2017, although the annual rate of transplantations for HCV dropped by 9.6%, the rate of transplantations for NASH increased by 8.2%. Additionally, among listed patients with HCC, the proportion of NASH‐related HCC increased from 4% to 14%, which corresponds to a 350% increase during the study period.10 In summary, this well‐done study corroborates transplant data published from the United States. Additionally, it provides additional validity about the progressive nature of NASH throughout the world. Given that the epidemic of obesity and diabetes will continue to rise in the foreseeable future and that there are no available approved drug regimens for NASH, it is highly likely that transplant centers around the world will see increasing numbers of patients with NASH. These centers will need not only to be ready to manage these patients’ advanced liver diseases but also their associated metabolic diseases and their complications. Potential conflict of interest Nothing to report.