Prediction of hepatocellular carcinoma (HCC) risk is an urgent unmet need in patients with nonalcoholic fatty liver disease (NAFLD). In cohorts of 409 patients with NAFLD from multiple global regions, we defined and validated hepatic transcriptome and serum secretome signatures predictive of long-term HCC risk in patients with NAFLD. A 133-gene signature, prognostic liver signature (PLS)–NAFLD, predicted incident HCC over up to 15 years of longitudinal observation. High-risk PLS-NAFLD was associated with IDO1 ⁺ dendritic cells and dysfunctional CD8 ⁺ T cells in fibrotic portal tracts along with impaired metabolic regulators. PLS-NAFLD was validated in independent cohorts of patients with NAFLD who were HCC naïve (HCC incidence rates at 15 years were 22.7 and 0% in high- and low-risk patients, respectively) or HCC experienced (de novo HCC recurrence rates at 5 years were 71.8 and 42.9% in high- and low-risk patients, respectively). PLS-NAFLD was bioinformatically translated into a four-protein secretome signature, PLSec-NAFLD, which was validated in an independent cohort of HCC-naïve patients with NAFLD and cirrhosis (HCC incidence rates at 15 years were 37.6 and 0% in high- and low-risk patients, respectively). Combination of PLSec-NAFLD with our previously defined etiology-agnostic PLSec-AFP yielded improved HCC risk stratification. PLS-NAFLD was modified by bariatric surgery, lipophilic statin, and IDO1 inhibitor, suggesting that the signature can be used for drug discovery and as a surrogate end point in HCC chemoprevention clinical trials. Collectively, PLS/PLSec-NAFLD may enable NAFLD-specific HCC risk prediction and facilitate clinical translation of NAFLD-directed HCC chemoprevention.

Most CT/MRI and CEUS LI-RADS major features had independent associations with hepatocellular carcinoma; arterial phase hyperenhancement and washout had the strongest associations whereas, for CT/MR... Background The Liver Imaging Reporting and Data System (LI-RADS) assigns a risk category for hepatocellular carcinoma (HCC) to imaging observations. Establishing the contributions of major features...

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare primary liver tumor, which has overlapping imaging features with mass forming intra-hepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). Previous studies reported imaging features more closely resemble ICC and the aim of our study was to examine the differential MRI features of cHCC-CC and ICC with emphasis on enhancement pattern observations of gadolinium enhanced MRI. Institutional review board approval with consent waiver was obtained for this retrospective bi-centric study. Thirty-three patients with pathologically proven cHCC-CC and thirty-eight patients with pathologically proven ICC, who had pre-operative MRI, were identified. MRI images were analyzed for tumor location and size, T1 and T2 signal characteristics, the presence/absence of: cirrhosis, intra-lesional fat, hemorrhage/hemosiderin, scar, capsular retraction, tumor thrombus, biliary dilatation, degree of arterial enhancement, enhancement pattern, pseudocapsule and washout. Associations between MRI features and tumor type were examined using the Fisher’s exact and chi-square tests. Strong arterial phase enhancement and the presence of: washout, washout and progression, intra-lesional fat and hemorrhage were all strongly associated with cHCC-CC (P < 0.001). While cHCC-CC had a varied enhancement pattern, the two most common enhancement patterns were peripheral persistent (n = 6) and heterogeneous hyperenhancement with washout (n = 6), compared to ICC where the most common enhancement patterns were peripheral hypoenhancement with progression (n = 18) followed by heterogeneous hypoenhancement with progression (n = 14) (P < 0.001). The cHCC-CC enhancement pattern seems to more closely resemble HCC with the degree of arterial hyperenhancement and the presence of washout being valuable in differentiating cHCC-CC from ICC. However the presence of washout and progression, in the same lesion or a predominantly peripheral /rim hyperenhancing mass were also seen as important features that should alert the radiologist to the possibility of a cHCC-CC.