High incidence of hepatocellular carcinoma and postoperative complications in patients with nonalcoholic steatohepatitis as a primary indication for deceased liver transplantation

Abstract

Background and aims Nonalcoholic steatohepatitis (NASH) is an increasingly prevalent indication for liver transplantation (LT) across the world. The relative outcomes following transplantation are poorly described in this cohort. We aimed to analyze the incidence and outcome of LT for NASH as compared with other indications. Patients and methods This is a retrospective analysis of 513 patients who underwent deceased-donor, adult LT between 2002 and 2012 as recorded at the Medical University of Innsbruck, Austria. Results The prevalence of NASH cirrhosis as indication for liver transplantation was 12.7% (65/513). Patient survival in patients with NASH was comparable to other indications, including alcohol-induced liver steatosis (ALD) and hepatitis C virus (HCV) (P=0.208). Patients with NASH were older, had a higher model of end-stage liver disease score and a higher BMI, but patient survival and graft survival were equivalent to other indications. Patients with hepatocellular carcinoma (HCC) as primary indication for liver transplantation showed significantly inferior overall survival as compared with the other indications (P=0.003). Patients with NASH had coexisting HCC in 53.7% of cases, whereas HCC in ALD, HCV and other indications was prevalent in 31.2, 47.7, and 34.5%, respectively (P<0.0001). Patients with NASH had a higher incidence of advanced HCCs (outside the Milan criteria) than patients with ALD, HCV, and other indications (P=0.034). Postoperative complications were significantly higher in the NASH cohort (P=0.048). Conclusion In this single-center LT database analysis, patients with NASH have a higher incidence and a more rapid progression of HCC as well as an increased incidence of postoperative complications. Our findings warrant confirmation by others.

Liver Grafts with Major Extended Donor Criteria May Expand the Organ Pool for Patients with Hepatocellular Carcinoma

“…Major morbidity rates were comparable in HCC patients with cirrhosis, who received maEDC and no-maEDC grafts, and transplanting grafts with ≥1 maEDC bore no risk for early allograft dysfunction, primary nonfunction, or 30-day graft failure in these recipients. The morbidity and retransplant rates are comparable with those already reported [39,40,41]. Grafts with ≥1 maEDC were associated with a reduced short-term graft survival, but they did not affect one-year patient survival and one-year patient survival after censoring for death with functioning graft.…”

Mechanisms of nonalcoholic fatty liver disease and implications for surgery

“…The shortand long-term results examined in various studies was similar between NAFLD/NASH and non-NAFLD/NASH, including alcoholic liver disease, HBV, cryptogenic cirrhosis, and primary biliary cholangitis/primary sclerosing cholangitis (PBC/PSC). Remarkably, overall survival showed no significant difference [77,78,[86][87][88][89][90]. Interestingly, post-transplant survival was shown to be higher compared with HCV-associated LT whereas no difference was seen between NASH-associated and alcoholic liver disease-related LT [90,91].…”

“…When comparing the results of HCC related LT, no difference was found between NASH-and non-NASH-associated HCC-related LT. Rather, there was a trend towards a favorable outcome for NASH-associated HCC-related LT [87,89]. The prevalence of HCC in NASH-associated LT was higher compared with non-NASH-associated LT [78,87,88]. Interestingly, when subclassifying non-NASH-associated HCC on explant pathology, Agopian et al showed a significantly higher prevalence of HCC in recipients with HCV and HBV, a similar prevalence in recipients with alcoholic liver disease and a lower prevalence in recipients with PBC/ PSC when comparing with recipients with NASH [90].…”

“…As discussed in this review, NAFLD patients on the waiting list for LT are more likely to present with obesity, older age, higher cardiovascular risk, and metabolic comorbidities. While the presence of higher peri-/postoperative complication rates in NAFLD patients, mainly cardiovascular events and mortality, remain controversial, long-term postoperative mortality showed no difference between NAFLD/NASH and non-NAFLD/NASH-related LT [57,59,78,[86][87][88]. The shortand long-term results examined in various studies was similar between NAFLD/NASH and non-NAFLD/NASH, including alcoholic liver disease, HBV, cryptogenic cirrhosis, and primary biliary cholangitis/primary sclerosing cholangitis (PBC/PSC).…”

Nonalcoholic steatohepatitis recurrence after liver transplant

“…In one study involving 588 liver transplant recipients, of which 9.4% were transplanted for NASH, post-transplant allograft steatosis was not associated with post-transplant survival (28). Although studies have shown worse outcomes with patients being transplanted NASH related HCC as well as patients being re-transplanted for NASH, no such data exists with NASH recurrence post-transplant (28)(29)(30). Hence, till further prospective data is generated it would be prudent to assume that survival is not influenced by recurrence of NASH.…”