Risk of hepatocellular carcinoma in Danish outpatients with alcohol-related cirrhosis

Background and aims: Accurate estimates of the risk of hepatocellular carcinoma (HCC) in patients with cirrhosis are important for clinical decisions about HCC surveillance. We described HCC risk among outpatients with alcoholic cirrhosis and contrasted the risk of death from HCC with the risk of death from variceal bleeding or trauma.Methods: This was a nationwide, registry-based historical cohort study between 2006 and 2018. We included all Danish outpatients with a hospital diagnosis of alcoholic cirrhosis, except those with cancer, those with chronic viral hepatitis or autoimmune liver disease, and those older than 80 years. We followed them through 2018 and described the cumulative risk of HCC and the cumulative risk of death from HCC, variceal bleeding, or trauma.Results: Of the 4553 included patients, 181 developed HCC and 2274 died. The cumulative risk of HCC was 0.9% (95% confidence interval [CI] 0.7 to 1.3) after 1 year, 3.6% (95% CI 3.0 to 4.2) after 5 years, and 6.0% (95% CI 5.1 to 7.0) after 10 years, or approximately 0.7% per year. Male gender, older age, and decompensated cirrhosis predicted a higher HCC risk. After 10 years, 6.9% of deaths in the cohort could be attributed to HCC, whereas 6.5% could be attributed to variceal bleeding, and 5.0% to trauma.Conclusions: In 2006–2018, Danish outpatients with alcoholic cirrhosis had an HCC risk of 0.7% per year, and they were nearly as likely to die from variceal bleeding or from trauma as from HCC. The implications are that many potentially harmful examinations are required for every HCC found through surveillance, so interventions targeting the prevention of other causes of death might be more cost-effective

Effects of statins and aspirin on HCC risk in alcohol-related cirrhosis: nationwide emulated trials

Background and Aims: Observational studies have shown an association between statin or aspirin use and a decreased risk of HCC, but the effects of a well-defined treatment strategy remain unknown. We emulated trials of the effects of continuous statin or aspirin use on HCC risk in patients with cirrhosis due to alcohol-related liver disease (ALD cirrhosis).Approach and Results: We specified target trials for statins and, separately, aspirin and emulated them using Danish health care registries. All eligible patients with ALD cirrhosis diagnosed in 2000–2018 were included in either an exposed or an unexposed arm. Patients were followed until HCC or death without HCC. The 5-year risk of HCC was estimated using marginal structural models with inverse probability weighting. Using statins continuously for 5 years compared with not using statins resulted in a relative risk (RR) of HCC of 0.67 (95% CI: 0.45–0.91). The RR of death without HCC was 0.69 (95% CI: 0.65–0.77). For aspirin, the RR was 1.05 (95% CI: 0.60–1.42) for HCC and 1.02 (95% CI: 0.95–1.09) for death without HCC.Conclusions: In patients with ALD cirrhosis, 5 years of continuous statin use resulted in a 33% RR reduction of HCC (number needed to treat = 94) and a 31% RR reduction of death without HCC (number needed to treat = 7). Such strong causal effects are implausible and best explained by uncontrollable confounding, highlighting the need for randomized trials. Aspirin use likely does not affect the risk of HCC or death without HCC

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

Abstract 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