Transarterial therapies for hepatocellular carcinoma.

Transarterial therapies for hepatocellular carcinoma are considered palliative and should be offered to patients with intermediate stage multinodular disease without extra-hepatic metastases and sufficient liver reserve. They mainly include transarterial chemoembolisation and transarterial embolisation. While transarterial therapy is now a validated treatment for unresectable HCC, there is still a lack of conclusive evidence as to which type and schedule is the optimal procedure. This is mainly due to the lack of standardisation. Combining local therapies or intra-arterial therapies with systemic targeted therapies might prove more effective strategies in the future. In the present article, we review transarterial therapies and critically comment on their indications, complications and outcomes.

Leucocyte ratios are biomarkers of mortality in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure.

BACKGROUND: In patients with cirrhosis, progression to acute decompensation (AD) and acute-on-chronic liver failure (ACLF) has been associated with poor prognosis. Differential leucocyte ratios might predict mortality in systemic inflammatory conditions. AIM: To evaluate differential leucocyte ratios as prognostic biomarkers in patients with cirrhosis. METHODS: Patients with AD and ACLF were recruited from four centres in three countries. Peripheral blood differential leucocytes were measured (three centres using flow cytometry) on hospital admission and at 48 hours. Ratios were correlated to model for end-stage liver disease (MELD), chronic liver failure-sequential organ failure (CLIF-SOFA), suspected/culture-positive bacterial infection and survival. RESULTS: Nine hundred twenty-six patients (562 (61%) male, median age 55 (25-94) years) were studied. Overall, 350 (37%) did not survive to hospital discharge. Neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR) were elevated in patients with AD and ACLF who died during their hospital stay. On multivariate analysis NLR retained statistical significance independently of CLIF-SOFA or MELD. NLR >30 was associated with an 80% 90-day mortality in patients with ACLF but not AD. On sensitivity analysis for subgroups (alcohol-related liver disease and suspected sepsis), NLR and MLR retained statistically robust accuracy for the prediction of mortality. Significant predictive accuracy was only observed in centres using flow cytometry. CONCLUSION: Leucocyte ratios are simple and robust biomarkers of outcome in ACLF, which are comparable to CLIF-SOFA score but dependent on leucocyte quantification method. NLR and MLR may be used as screening tools for mortality prediction in patients with acutely deteriorating cirrhosis.

Management of metabolic syndrome and cardiovascular risk after liver transplantation.

Cardiovascular events are the second most prevalent cause of non-hepatic mortality in liver transplant recipients. The incidence of these events is projected to rise because of the growing prevalence of non-alcoholic steatohepatitis as a transplant indication and the ageing population of liver transplant recipients. Recipients with metabolic syndrome are up to four times more likely to have a cardiovascular event than recipients without, therefore prevention and optimal treatment of the components of metabolic syndrome are key in reducing the risk of these events. Although data on the treatment of metabolic comorbidities specifically in liver transplant recipients are scarce, there is detailed guidance from learned societies that mostly mirrors the guidance for patients at increased cardiovascular risk in the general population. In this Review, we discuss the management of the components of metabolic syndrome following liver transplantation and provide practical stepwise guidance. We also emphasise the need for adequately powered studies for the treatment of metabolic comorbidities in liver transplant recipients.

ART and science in using transarterial chemoembolization for retreating patients with hepatocellular carcinoma.

Intermediate stage hepatocellular carcinoma (HCC) comprises of a highly heterogeneous patient population, both in terms of liver function and tumour burden. Transarterial chemoembolization (TACE) is the treatment of choice for this subgroup of patients, provided that liver function is relatively preserved. Not all patients respond to an initial session of TACE, and further session might impair liver function. The ART score consists of an increase of AST >25%, increase of Child-Pugh of one or two points and absence of radiological tumour response and helps identify patients that would not benefit from further TACE sessions. We critically appraise the use of this score, particularly in terms of patient selection and timing of calculation of its variables. Once sufficiently validated, it can become a safe, objective and accurate clinical tool in everyday practice.

Adaptive immunity in hepatocellular carcinoma: prognostic and therapeutic implications.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and has a poor prognosis. Host immunity can either protect or promote tumor growth by the predominance and activation of certain subsets of immune cells. It has been established that antigens such as AFP, MAGE, glypican 3 and NY-ESO, which are highly expressed in HCC, are potential targets for T-cell responses. Several studies have come to the conclusion that cytotoxic T-cell infiltration of the tumors is indicative of a better survival, whereas the predominance of suppressor cells is associated with a worse outcome and lower survival rates. Finally, certain therapeutic strategies, including radiofrequency ablation and chemoembolization, can enhance the release and exposure of tumor antigens, which might help to overcome the immune tolerance towards the tumor. Therefore, such immune-stimulating therapeutic interventions in combination with immunotherapy strategies represent a promising future approach for HCC treatment.