Men with biopsy-confirmed hepatocellular adenoma have a high risk of progression to hepatocellular carcinoma: A nationwide population-based study.

BACKGROUND & AIMS: Hepatocellular adenoma is a benign liver tumour that may transform to hepatocellular carcinoma (HCC). We used data from Danish nationwide healthcare registries to investigate the incidence and prognosis of hepatocellular adenoma. METHODS: We included all patients with a hospital discharge diagnosis for benign liver tumour (ICD-10: D13.4) in 1997-2012 and a liver biopsy confirming the hepatocellular adenoma diagnosis. Follow-up began 1 year after adenoma diagnosis, to minimise the possibility that the tumour was a misdiagnosed HCC. All patients were age- and gender-matched with 50 random controls from the Danish population. We followed patients and controls with respect to HCC development, adenoma resection, and death without HCC (ie, death without having been diagnosed with HCC) through 2013. HCC diagnoses were identified in the Danish Cancer Registry. RESULTS: We included 67 patients with hepatocellular adenoma, and 58 (87%) were women. The overall incidence rate of histologically verified hepatocellular adenoma in the Danish general population was 0.07 (95% CI: 0.06-0.09) per 100 000 population per year. Fifteen patients had their adenoma resected before follow-up began, leaving 52 patients for follow-up. Men with biopsy-confirmed hepatocellular adenoma had a 10-year cumulative HCC risk as high as 60.0% (95% CI: 15.3%-87.0%). All men who developed HCC were older than 50 years at adenoma diagnosis. By contrast, none of the 44 women in the follow-up analysis developed HCC. CONCLUSION: Histologically verified hepatocellular adenoma is rare in Denmark. It is a minor concern for women, but men have a very high risk of progression to HCC.

Non-alcoholic fatty liver disease causes dissociated changes in metabolic liver functions.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a major health concern affecting 25% of the world's population. It is generally held that a fatty liver does not influence liver function, but quantitative measurements of metabolic liver functions have not been systematically performed. We aimed to study selected hepatocellular metabolic functions in patients with different stages of NAFLD. METHODS: Twenty-five non-diabetic, biopsy-proven NAFLD patients [12 with simple steatosis; 13 with non-alcoholic steatohepatitis (NASH)] and ten healthy controls were included in a cross-sectional study. Hepatocyte cytosolic function was assessed by the galactose elimination capacity (GEC), mitochondrial-cytosolic metabolic capacity by the functional hepatic nitrogen clearance (FHNC), microsomal function by the aminopyrine breath test, and excretory liver function by indocyanine green (ICG) elimination. RESULTS: GEC was 20% higher in NAFLD than in controls [3.15 mmol/min (2.9-3.41) vs. 2.62 (2.32-2.93); P = 0.02]. FHNC was 30% lower in NAFLD [23.3 L/h (18.7-28.9) vs. 33.1 (28.9-37.9); P = 0.04], more so in simple steatosis [19.1 L/h (13.9-26.2); P = 0.003] and non-significantly in NASH [27.9 L/h (20.6-37.8); P = 0.19]. Aminopyrine metabolism was 25% lower in simple steatosis [8.9% (7.0-10.7)] and 50% lower in NASH [6.0% (4.5-7.5)] than in controls [11.9% (9.3-12.8)] (P < 0.001). ICG elimination was intact. CONCLUSIONS: The hepatocellular metabolic functions were altered in a manner that was dissociated both by different effects on different liver functions and by different effects of different stages of NAFLD. Thus, NAFLD has widespread consequences for metabolic liver function, even in simple steatosis.

Metabolic liver function in humans measured by 2-18F-fluoro-2-deoxy-D-galactose PET/CT-reproducibility and clinical potential.

BACKGROUND: PET/CT with the radioactively labelled galactose analogue 2-18F-fluoro-2-deoxy-D-galactose (18F-FDGal) can be used to quantify the hepatic metabolic function and visualise regional metabolic heterogeneity. We determined the day-to-day variation in humans with and without liver disease. Furthermore, we examined whether the standardised uptake value (SUV) of 18F-FDGal from static scans can substitute the hepatic systemic clearance of 18F-FDGal (K met, mL blood/min/mL liver tissue/) quantified from dynamic scans as measure of metabolic function. Four patients with cirrhosis and six healthy subjects underwent two 18F-FDGal PET/CT scans within a median interval of 15 days for determination of day-to-day variation. The correlation between K met and SUV was examined using scan data and measured arterial blood concentrations of 18F-FDGal (blood samples) from 14 subjects from previous studies. Regional and whole-liver values of K met and SUV along with total metabolic liver volume and total metabolic liver function (total SUV, average SUV multiplied by total metabolic liver volume) were calculated. RESULTS: No significant day-to-day differences were found for K met or SUV. SUV had higher intraclass correlation coefficients than K met (0.92-0.97 vs. 0.49-0.78). The relationship between K met and SUV was linear. Total metabolic liver volume had non-significant day-to-day variation (median difference 50 mL liver tissue; P = 0.6). Mean total SUV in healthy subjects was 23,840 (95% CI, 21,609; 26,070), significantly higher than in the patients (P < 0.001). CONCLUSIONS: The reproducibility of 18F-FDGal PET/CT was good and SUV can substitute K met for quantification of hepatic metabolic function. Total SUV of 18F-FDGal is a promising tool for quantification of metabolic liver function in pre-treatment evaluation of individual patients.