Elias Allara

The ALBI grade provides objective hepatic reserve estimation across each BCLC stage of hepatocellular carcinoma

BACKGROUND & AIMS Overall survival (OS) is a composite clinical endpoint in hepatocellular carcinoma (HCC) due to the mutual influence of cirrhosis and active malignancy in dictating patients mortality. The ALBI grade is a recently described index of liver dysfunction in hepatocellular carcinoma, based solely on albumin and bilirubin levels. Whilst accurate, this score lacks cross-validation, especially in intermediate stage HCC, where OS is highly heterogeneous. METHODS We evaluated the prognostic accuracy of the ALBI grade in estimating OS in a large, multi-centre study of 2426 patients, including a large proportion of intermediate stage patients treated with chemoembolization (n=1461) accrued from Europe, the United States and Asia. RESULTS Analysis of survival by primary treatment modality confirmed the ALBI grade as a significant predictor of patient OS after surgical resection (p<0.001), transarterial chemoembolization (p<0.001) and sorafenib (p<0.001). Stratification by Barcelona Clinic Liver Cancer stage confirmed the independent prognostic value of the ALBI across the diverse stages of the disease, geographical regions of origin and time of recruitment to the study (p<0.001). CONCLUSIONS In this large, multi-centre retrospective study, the ALBI grade satisfied the criteria for accuracy and reproducibility following statistical validation in Eastern and Western HCC patients, including those treated with chemoembolization. Consideration should be given to the ALBI grade as a stratifying biomarker of liver reserve in routine clinical practice. LAY SUMMARY Liver failure is a key determinant influencing the natural history of hepatocellular carcinoma (HCC). In this large multi-centre study we externally validate a novel biomarker of liver functional reserve, the ALBI grade, across all the stages of HCC.

Validation of the Hepatoma Arterial Embolization Prognostic Score in European and Asian Populations and Proposed Modification

BACKGROUND & AIMS Transarterial chemoembolization (TACE) is used to treat hepatocellular carcinoma (HCC), but it is a challenge to predict patient survival. The hepatic arterial embolization prognostic (HAP) score has been shown to predict which patients will have shorter survival times and should not undergo TACE. We aimed to validate this scoring system in a prospective study of patients in Europe and Asia. METHODS We evaluated the prognostic accuracy of the HAP score in estimating overall survival (OS) of 126 patients with HCC who received TACE in the United Kingdom or Italy (training set) from 2001 through 2013. We also analyzed data from 723 patients treated in Korea and Japan (validation set), including 79 with newly diagnosed HCC, who underwent TACE in Korea or Japan from 2004 through 2013. Response to TACE was determined based on computed tomography analysis. OS was calculated from the time of the first TACE until death or the last follow-up evaluation. RESULTS OS was associated with hypoalbuminemia, α-fetoprotein level greater than 400 ng/mL, and tumor size greater than 7 cm at diagnosis (P < .01), but not a bilirubin level greater than 17 umol/L (P > .05), in both data sets. The lack of association between OS and bilirubin level was confirmed using receiver operating characteristic analysis. We developed a modified version of the HAP score, based on the level of albumin and α-fetoprotein and tumor size, which predicted OS with increased accuracy in the training and validation cohorts. CONCLUSIONS In a multicenter validation study, we developed a modified version of the HAP that predicts survival of patients with HCC treated with TACE in Europe and Asia. This system might be used to identify patients with HCC most likely to benefit from TACE in clinical practice.

Combined sequential use of HAP and ART scores to predict survival outcome and treatment failure following chemoembolization in hepatocellular carcinoma: a multi-center comparative study

Background The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is variable, despite a myriad of prognostic markers. We compared and integrated the established prognostic models, HAP and ART scores, for their accuracy of overall survival (OS) prediction. Results In both training and validation sets, HAP and ART scores emerged as independent predictors of OS (p<0.01) with HAP achieving better prognostic accuracy (c-index: 0.68) over ART (0.57). We tested both scores in combination to evaluate their combined ability to predict OS. Subgroup analysis of BCLC-C patients revealed favorable HAP stage (p<0.001) and radiological response after initial TACE (p<0.001) as positive prognostic factors. Patients and Methods Prognostic scores were studied using multivariable Cox regression and c-index analysis in 83 subjects with Barcelona Clinic Liver Cancer (BCLC) A/B stage from UK and Italy (training set), and 660 from Korea and Japan (validation set), all treated with conventional TACE. Scores were further validated in an separate analysis of patients with BCLC-C stage disease (n=63) receiving initial TACE. Conclusion ART and HAP scores are validated indices in patients with intermediate stage HCC undergoing TACE. The HAP score is best suited for screening patients prior to initial TACE, whilst sequential ART assessment improves early detection of chemoembolization failure. BCLC-C patients with low HAP stage may be a subgroup where TACE should be explored in clinical studies.

The albumin-bilirubin grade uncovers the prognostic relationship between hepatic reserve and immune dysfunction in HIV-associated hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of liver‐related mortality in people living with HIV, where co‐infection with hepatotropic viruses accelerates the course of chronic liver disease.

Lipoprotein Signatures of Cholesteryl Ester Transfer Protein and HMG-CoA Reductase Inhibition

Background CETP inhibition reduces vascular event rates but confusion surrounds its low-density lipoprotein (LDL)-cholesterol effects. We sought to clarify associations of genetic inhibition of CETP on detailed lipoproteins. Methods and Results We used variants associated with CETP (rs247617) and HMGCR (rs12916) expression in 62,400 Europeans with detailed lipoprotein profiling from nuclear magnetic resonance spectroscopy. Genetic associations were scaled to 10% lower risk of coronary heart disease (CHD). Associations of lipoprotein measures with risk of incident CHD in three population-based cohorts (770 cases) were examined. CETP and HMGCR had near-identical associations with LDL-cholesterol concentration estimated by Friedewald-equation. HMGCR had a relatively consistent effect on cholesterol concentrations across all apolipoprotein B-containing lipoproteins. CETP had stronger effects on remnant and very-low-density lipoprotein cholesterol but no effect on cholesterol concentrations in LDL defined by particle size (diameter 18–26 nm) (-0.02SD 95%CI: -0.10, 0.05 for CETP versus -0.24SD, 95%CI -0.30, -0.18 for HMGCR). CETP had profound effects on lipid compositions of lipoproteins, with strong reductions in the triglyceride content of all highdensity lipoprotein (HDL) particles. These alterations in triglyceride composition within HDL subclasses were observationally associated with risk of CHD, independently of total cholesterol and triglycerides (strongest HR per 1-SD higher triglyceride composition in very-large HDL 1.35; 95%CI: 1.18, 1.54). Conclusion CETP inhibition does not affect size-specific LDL cholesterol but may lower CHD risk by lowering cholesterol in other apolipoprotein-B containing lipoproteins and lowering triglyceride content of HDL particles. Conventional composite lipid assays may mask heterogeneous effects of lipid-altering therapies.

Medium- and long-term health effects of earthquakes in high-income countries: a systematic review and meta-analysis.

Background Accurate monitoring of population health is essential to ensure proper recovery after earthquakes. We aimed to summarize the findings and features of post-earthquake epidemiological studies conducted in high-income countries and to prompt the development of future surveillance plans. Methods Medline, Scopus and six sources of grey literature were systematically searched. Inclusion criteria were: observational study conducted in high-income countries with at least one comparison group of unexposed participants, and measurement of health outcomes at least 1 month after the earthquake. Results A total of 52 articles were included, assessing the effects of 13 earthquakes that occurred in eight countries. Most studies: had a time-series (33%) or cross-sectional (29%) design; included temporal comparison groups (63%); used routine data (58%); and focused on patient subgroups rather than the whole population (65%). Individuals exposed to earthquakes had: 2% higher all-cause mortality rates [95% confidence interval (CI), 1% to 3%]; 36% (95% CI, 19% to 57%) and 37% (95% CI, 29% to 46%) greater mortality rates from myocardial infarction and stroke, respectively; and 0.16 higher mean percent points of glycated haemoglobin (95% CI, 0.07% to 0.25% points). There was no evidence of earthquake effects for blood pressure, body mass index or lipid biomarkers. Conclusions A more regular and coordinated use of large and routinely collected datasets would benefit post-earthquake epidemiological surveillance. Whenever possible, a cohort design with geographical and temporal comparison groups should be used, and both communicable and non-communicable diseases should be assessed. Post-earthquake epidemiological surveillance should also capture the impact of seismic events on the access to and use of health care services.