The burden of hepatocellular carcinoma (HCC) is highest in East Asia and Africa, although its incidence and mortality are rapidly rising in the United States and Europe. With the implementation of hepatitis B vaccination and hepatitis C treatment programmes worldwide, the epidemiology of HCC is shifting away from a disease predominated by viral hepatitis-an increasing proportion of cases are now attributable to non-alcoholic steatohepatitis. Surveillance using ultrasound, with or without alpha-fetoprotein, every 6 months has been associated with improved early detection and improved overall survival; however, limitations in implementation lead to a high proportion of HCC being detected at late stages in clinical practice. Herein, we review the current state of HCC surveillance and highlight areas for future research, including improved risk stratification of at-risk patients, surveillance tools with higher sensitivity and specificity for early HCC, and interventions to increase surveillance utilisation.

We confirmed a reduction in critical events, liver-related or not, in a prospective study of patients with HCV infection and compensated cirrhosis included in the CirVir cohort who achieved an SVR. We found an SVR to reduce overall mortality and risk of death from liver-related and non-liver-related causes. A longer follow-up evaluation is required to accurately describe and assess specific risk factors for complications in this population.

Among all the software packages available for discriminant analyses based on projection to latent structures (PLS-DA) or orthogonal projection to latent structures (OPLS-DA), SIMCA (Umetrics, Umeå Sweden) is the more widely used in the metabolomics field. SIMCA proposes many parameters or tests to assess the quality of the computed model (the number of significant components, R2, Q2, pCV-ANOVA, and the permutation test). Significance thresholds for these parameters are strongly application-dependent. Concerning the Q2 parameter, a significance threshold of 0.5 is generally admitted. However, during the last few years, many PLS-DA/OPLS-DA models built using SIMCA have been published with Q2 values lower than 0.5. The purpose of this opinion note is to point out that, in some circumstances frequently encountered in metabolomics, the values of these parameters strongly depend on the individuals that constitute the validation subsets. As a result of the way in which the software selects members of the calibration and validation subsets, a simple permutation of dataset rows can, in several cases, lead to contradictory conclusions about the significance of the models when a K-fold cross-validation is used. We believe that, when Q2 values lower than 0.5 are obtained, SIMCA users should at least verify that the quality parameters are stable towards permutation of the rows in their dataset.

Infections ACLF Death Different clinical courses of acutely decompensated cirrhosis Pre-ACLF Unstable decompensated cirrhosis Stable decompensated cirrhosis 0 90 180 270 360 Days Highlights Patients with acutely decompensated cirrhosis without ACLF develop 3 different clinical courses. Patients with pre-ACLF develop ACLF within 90 days and have high systemic inflammation and mortality. Patients with unstable decompensated cirrhosis suffer from complications of severe portal hypertension. Patients with stable decompensated cirrhosis have less frequent complications and lower 1-year mortality risk.

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Analysis of data from the ANRS CO12 CirVir cohort reveals that the apparent increase in HCC incidence observed in patients with cirrhosis treated with DAAs compared with patients who achieved SVR following an IFN therapy can be explained by patient characteristics (age, diabetes, reduced liver function) and lower screening intensity.

Alcohol-related liver disease is the most prevalent type of chronic liver disease worldwide, accounting for 30% of hepatocellular carcinoma (HCC) cases and HCC-specific deaths. Alcohol has been associated with an increased risk of several malignancies, this risk starting at doses as low as 10 g/1 unit/day. The carcinogenic process includes direct acetaldehyde toxicity through the formation of protein and DNA adducts, an increased production of reactive oxygen species, changes to lipid peroxidation and metabolism, inflammation and an impaired immune response and modifications to DNA methylation. A high annual incidence of HCC has been observed in large European cohorts of patients with alcoholic cirrhosis, reaching 2.9%, with numerous host factors modulating this risk (age, gender, liver failure, genetic polymorphisms affecting oncogenic pathways). Because of impaired surveillance and poor patient compliance, HCC is often detected late in patients with chronic liver disease of alcoholic aetiology. This delay in detection, which is frequently made in the context of advanced liver cirrhosis rather than in surveillance programmes, results in more advanced HCC that is less amenable to curative treatment. Consequently, patients with alcohol-related HCC generally have a worse prognosis than those with non-alcoholic HCC.