Peroxisome proliferator-activated receptor activity correlates with poor survival in patients resected for hepatocellular carcinoma.

BACKGROUND/PURPOSE: Few clinically useful biomarkers are known to predict prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the correlation between PPAR activity and ALDH7A1 expression and their prognostic significance using RNA sequencing in patients undergoing liver resection for HCC. METHODS: We included patients undergoing liver resection for HCC at a tertiary referral center for hepato-pancreato-biliary surgery between May 2014 and January 2018. PPAR activity and ALDH7A1 expression were evaluated by RNA sequencing and correlated with overall survival, recurrence and histological features. RESULTS: We included 52 patients with a median follow-up of 20.9 months, predominantly males (88.5%) with a single tumor (84.6%) in a non-cirrhotic liver (73.1%). Three-year overall survival was 48.6% in patients with a specific PPAR target gene expression profile (cancer cluster 3) compared with 81.7% in controls (P = .04, Log-rank test). This remained significant (odds ratio 14.02, 95% confidence interval 1.92-102.22, P = .009) when adjusted for age, cirrhosis, microvascular invasion, number of tumors and free resection margins. ALDH7A1 expression was not correlated with PPAR or any outcomes. CONCLUSION: PPAR activity in a subset of tumor samples was associated with reduced overall survival indicating that PPAR may be a valuable prognostic biomarker.

Nonalcoholic fatty liver disease is an increasing indication for liver transplantation in the Nordic countries.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease(NAFLD) is the second most common cause of liver transplantation in the US. Data on NAFLD as a liver transplantation indication from countries with lower prevalences of obesity are lacking. We studied the temporal trends of NAFLD as an indication for liver transplantation in the Nordic countries, and compared outcomes for patients with NAFLD to patients with other indications for liver transplantation. METHOD: Population-based cohort study using data from the Nordic Liver Transplant Registry on adults listed for liver transplantation between 1994 and 2015. NAFLD as the underlying indication for liver transplantation was defined as a listing diagnosis of NAFLD/nonalcoholic steatohepatitis, or cryptogenic cirrhosis with a body mass index ≥25 kg/m2 and absence of other liver diseases. Waiting time for liver transplantation, mortality and withdrawal from the transplant waiting list were registered. Survival after liver transplantation was calculated using multivariable Cox regression, adjusted for age, sex, body mass index and model for end-stage liver disease. RESULTS: A total of 4609 patients listed for liver transplantation were included. NAFLD as the underlying indication for liver transplantation increased from 2.0% in 1994-1995 to 6.2% in 2011-2015 (P = .01) and was the second most rapidly increasing indication. NAFLD patients had higher age, model for end-stage liver disease and body mass index when listed for liver transplantation, but overall survival after liver transplantation was comparable to non--NAFLD patients (aHR 1.03, 95% CI 0.70-1.53 P = .87). CONCLUSION: NAFLD is an increasing indication for liver transplantation in the Nordic countries. Despite more advanced liver disease, NAFLD patients have a comparable survival to other patients listed for liver transplantation.