The prevalence of NAFLD has continued to increase as the obesity epidemic continues. The rate of progression from NAFLD to the development of NASH or end stage liver disease is unknown. However, the frequency of NASH in patients listed for transplantation in North America has been previously determined to be 2.9%[17
]. This is likely an underestimate as this number was based on data collected from the 1990s, whereas in the last decade the rates of obesity and metabolic syndrome have increased dramatically. A more recent analysis of data from the Scientific Registry of Transplant Recipients (SRTR) reported that the rate had increased to 3.5%[18
]. In our series, 12.3% of patients have NASH as the diagnosis leading to liver failure requiring transplantation. NASH as a primary diagnosis in patients being listed or transplantation has continued to increase at our centre.
The natural history of NAFLD ranging from reversible steatosis to steatohepatitis with hepatic fibrosis (NASH), and ultimately the possibility of developing HCC has been previously described[19
]. In small previously published North American series of patients transplanted for NASH, HCC was found in 22% (2/9) of patients[20
]. In our series of 102 patients with NASH cirrhosis, 16.7% had HCC at the time of transplantation. This is a similar rate to the 22.6% of our HCV cirrhotic patients requiring transplantation, another well known high risk group for developing HCC. The high incidence of HCC in NASH patients undergoing liver transplantation suggests that these patients are at high risk of developing HCC and should undergo frequent ultrasound surveillance in a similar fashion to that performed in patients with HCV.
It has also been shown that patients with NASH are less likely to be listed for transplantation due to comorbidities, a justifiable practice given suboptimal results in NASH patients possessing theses comorbidities[10
]. However in selected NASH patients receiving liver transplantation, others have shown that 5 year disease free survival after transplantation was significantly better than disease free survival in the C and B viral groups, 66%, 29% and 39% respectively[21
]. More recent studies have suggested there is no difference in 1 year and 3 year survival between patients transplanted for NASH and those transplanted for other indications[22
]. The outcome in patients with HCV is clearly affected by possible recurrence of HCV cirrhosis however NASH patients are also at risk for recurrence of NASH cirrhosis with some studies suggesting the incidence of recurrent NASH being as high as 25%[23-25
Patients with NASH and HCC post-transplant outcomes have not been previously investigated compared to patients with HCV and HCC (another group in which HCC is commonly seen). In previous studies looking at patients undergoing liver resection for HCC, cumulative survival after resection was comparable among HCV-HCC and NASH-HCC patient groups[21
In our study a significantly higher proportion of HCV-HCC patients had vascular invasion as well as poorly differentiated tumours compared to the NASH-HCC group. Vascular invasion is the strongest predictor of recurrence in patients with HCC[26
In the present study a trend of poorer recurrence free survival was seen in HCV-HCC patients compared to NASH-HCC who underwent a Liver transplantation. The higher proportion of patients with vascular invasion and poorly differentiated tumours may at least in part account for this difference in recurrence free survival. Based on our results it therefore appears that NASH associated HCC might be a less aggressive form of HCC compared with HCV associated HCC. It must also be entertained that some of the sickest NASH patients may not be listed for transplantation because of significant comorbidities or poor operative candidacy.
Limitations of the present study include its single centre nature as well as the lack of generalizability to non-transplant NASH and HCC populations due to the unique social and biologic factors of patients approved for transplantation.
In summary in those where NASH progresses to cirrhosis, there is a significant proportion that go on to develop HCC suggesting these individuals should undergo aggressive screening protocols directed toward the early detection of HCC, in a similar fashion to patients with HCV-cirrhosis. Patients with NASH-HCC undergoing liver transplantation also appear to be older than HCV-HCC patients undergoing liver transplantation. In appropriately selected patients with NASH and HCC post-transplant outcomes equal if not better than patients with HCV-HCC (another group in which HCC is commonly seen). This may be related to less vascular invasion and less poorly differentiated pathology.