None.

Background: The GALAD score is a serum biomarkerbased model that predicts the probability of having hepatocellular carcinoma (HCC) in patients with chronic liver disease. We aimed to assess the performance of the GALAD score in comparison with liver ultrasound for detection of HCC.Methods: A single-center cohort of 111 HCC patients and 180 controls with cirrhosis or chronic hepatitis B and a multicenter cohort of 233 early HCC and 412 cirrhosis patients from the Early Detection Research Network (EDRN) phase II HCC Study were analyzed.Results: The area under the ROC curve (AUC) of the GALAD score for HCC detection was 0.95 [95% confidence interval (CI), 0.93-97], which was higher than the AUC of ultrasound (0.82, P <0.01). At a cutoff of À0.76, the GALAD score had a sensitivity of 91% and a specificity of 85% for HCC detection. The AUC of the GALAD score for early-stage HCC detection remained high at 0.92 (95% CI, 0.88-0.96; cutoff À1.18, sensitivity 92%, specificity 79%). The AUC of the GALAD score for HCC detection was 0.88 (95% CI, 0.85-0.91) in the EDRN cohort. The combination of GALAD and ultrasound (GALADUS score) further improved the performance of the GALAD score in the single-center cohort, achieving an AUC of 0.98 (95% CI, 0.96-0.99; cutoff À0.18, sensitivity 95%, specificity 91%). a For the calculation of AUC, the continuous GALAD score is used, whereas for sensitivity and specificity, we used the GALAD cutoff. b P value looking at difference in AUC between GALAD and ultrasound.Yang et al.

Diabetes increases the risk of liver disease progression and cirrhosis development in patients with nonalcoholic steatohepatitis (NASH). The association between diabetes and the risk of hepatocellular carcinoma (HCC) in NASH patients with cirrhosis is not well quantified. All patients with the diagnosis of NASH cirrhosis seen at Mayo Clinic Rochester between January 2006 and December 2015 were identified. All adult liver transplant registrants with NASH between 2004 and 2017 were identified using the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation registry for external validation. Cox proportional hazard analysis was performed to investigate the association between diabetes and HCC risk. Among 354 Mayo Clinic patients with NASH cirrhosis, 253 (71%) had diabetes and 145 (41%) were male. Mean age at cirrhosis evaluation was 62. During a median follow‐up of 47 months, 30 patients developed HCC. Diabetes was associated with an increased risk of developing HCC in univariate (hazard ratio [HR] = 3.6; 95% confidence interval [CI] = 1.1‐11.9; P = 0.04) and multivariable analysis (HR = 4.2; 95% CI = 1.2‐14.2; P = 0.02). In addition, age (per decade, HR = 1.8; 95% CI = 1.2‐2.6; P < 0.01) and low serum albumin (HR = 2.1; 95% CI = 1.5‐2.9; P < 0.01) were significantly associated with an increased risk of developing HCC in multivariable analysis. Other metabolic risk factors, including body mass index, hyperlipidemia, and hypertension, were not associated with HCC risk. Among UNOS NASH registrants (N = 6,630), 58% had diabetes. Diabetes was associated with an increased risk of developing HCC in univariate (HR = 1.4; 95% CI = 1.1‐1.8; P < 0.01) and multivariable (HR = 1.3; 95% CI = 1.0‐1.7; P = 0.03) analysis. Conclusion: Diabetes is associated with an increased risk of HCC in patients with NASH cirrhosis.

Whether aspirin use is protective against cholangiocarcinoma (CCA) remains unclear. We determined the association between aspirin use and other risk factors for each CCA subtype individually. In a hospital-based case-control study, 2395 CCA cases (1169 intrahepatic, 995 perihilar, and 231 distal) seen at the Mayo Clinic, Rochester, MN, from 2000 through 2014 were enrolled. Controls selected from the Mayo Clinic Biobank were matched two to one with cases by age, sex, race, and residence (n 5 4769). Associations between aspirin use, other risk factors, and CCA risk were determined. Aspirin was used by 591 (24.7%) CCA cases and 2129 (44.6%) controls. There was a significant inverse association of aspirin use with all CCA subtypes, with adjusted odds ratios (AORs) of 0.35 (95% confidence interval [CI], 0.29-0.42), 0.34 (95% CI 0.27-0.42), and 0.29 (95% CI 0.19-0.44) for intrahepatic, perihilar, and distal CCA, respectively (P < 0.001 for all). Primary sclerosing cholangitis was more strongly associated with perihilar (AOR 5 453, 95% CI 104-999) than intrahepatic (AOR 5 93.4, 95% CI 27.1-322) or distal (AOR 5 34.0, 95% CI 3.6-323) CCA, whereas diabetes was more associated with distal (AOR 5 4.2, 95% CI 2.5-7.0) than perihilar (AOR 5 2.9, 95% CI 2.2-3.8) or intrahepatic (AOR 5 2.5, 95% CI 2.0-3.2) CCA. Cirrhosis not related to primary sclerosing cholangitis was associated with both intrahepatic and perihilar CCA, with similar AORs of 14. Isolated inflammatory bowel disease without primary sclerosing cholangitis was not associated with any CCA subtype. Conclusions : Aspirin use was significantly associated with a 2.7-fold to 3.6-fold decreased risk for the three CCA subtypes; our study demonstrates that individual risk factors confer risk of different CCA subtypes to different extents.

A number of novel biomarkers for hepatocellular carcinoma (HCC) have been recently identified by advanced genomic, proteomic and metabolomic technologies. New biomarkers are in development for HCC diagnosis, for prediction of patient and treatment outcomes, and for individualizing the use of targeted therapies. Nonetheless, the major current use of HCC biomarkers remains surveillance for early HCC detection, with the goal of reducing mortality from HCC. Most new HCC biomarkers are in phase 1 or 2 biomarker studies, and further investigation is needed to determine whether they have utility in clinical practice. The diagnostic or predictive performance of individual biomarkers is limited by the highly heterogeneous nature of HCC tumors. Consequently, there is no single perfect biomarker for HCC. To maximize biomarker performance, future trends in the use of biomarkers will therefore include the combination of multiple biomarkers or the combination of biomarkers with imaging, clinical parameters or other laboratory tests in diagnostic, predictive or prognostic panels. This review provides a brief update on the known and novel promising biomarkers for HCC. The challenges and key considerations in the phases of biomarker development and the application of biomarkers in clinical practice are also discussed.