Antagonistic antibodies targeting coinhibitory receptors have revolutionized the treatment of cancer by inducing durable immune responses and clinical remissions in patients. In contrast, success of agonistic costimulatory antibodies has thus far been limited because of the insufficient induction of adaptive immune responses. Here, we describe a novel vaccination method consisting of a primary dendritic cell (DC) immunization followed by a composite vaccination, including an agonistic CD40 antibody, soluble antigen, and a TLR3 agonist, referred to as CoAT. In mice, DC/CoAT prime-boost vaccinations targeting either MHC class I or II neoantigens or tumor-associated antigens rendered up to 60% of the total T-cell population specific for a single tumor epitope. DC/CoAT induced durable and complete remissions of large subcutaneous tumors without detectable side effects. Thus, booster vaccinations with agonistic costimulatory antibodies represent an ideal means to amplify DC vaccinations and induce robust T-cell immune responses while providing maximum flexibility regarding the choice of antigen. .

IntroductionBetter treatment outcome of early-stage hepatocellular carcinoma (HCC) warrants employment of screening programs, in which ultrasonography (US) and serum alfa-fetoprotein (AFP) have been recommended. Considering cost-effectiveness, serum AFP has recently been withdrawn from several guidelines for HCC surveillance. However, there were limited studies on benefits of AFP for HCC surveillance in Thailand.Materials and methodsThis is a retrospective study of a proportion of HCC cases in which a diagnostic study was triggered by high serum AFP levels, but US failed to detect the lesion. Patients who received diagnostic imaging for HCC at Siriraj Hospital between January 1, 2012 and December 31, 2014 were included. All the patients must fulfill criteria for HCC surveillance according to American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of HCC 2010 or European Association for the Study of the Liver-European Organisation for Research and Treatment of Cancer (EASL-EORTC) Clinical Practice Guidelines: Management of HCC 2012. Previous diagnosis of any liver malignancy was excluded. Demographic data, underlying liver diseases, screening of AFP and US results, and definite diagnosis of HCC were recorded.ResultsOf the 452 cases who fulfilled inclusion and exclusion criteria, chronic hepatitis B, C, and alcoholic cirrhosis were accountable for 53.8, 25.9, and 7.3% respectively. Totally, 150 cases were diagnosed with HCC. Additional HCC detection rate by high serum AFP but failed US of 15.3% was demonstrated. Subgroup analysis revealed significant benefit of AFP in cirrhotic patients with chronic hepatitis B and C (p-value 0.004 and 0.002). No significant benefit was observed in cirrhosis of other causes and in noncirrhotic chronic hepatitis B.ConclusionWe reported a 15.3% additional benefit of serum AFP for HCC surveillance in conjunction with US of liver. Chronic hepatitis B and C with cirrhosis significantly derived the benefit from serum AFP screening.How to cite this article: Lersritwimanmaen P, Nimanong S. Hepatocellular Carcinoma Surveillance: Benefit of Serum Alfa-fetoprotein in Real-world Practice. Euroasian J Hepato-Gastroenterol 2018;8(1):83-87.

Background Patients with acute-on-chronic liver failure (ACLF) precipitated by hepatic injury and extrahepatic insults had distinct clinical phenotypes, and prognosis. This study aimed to validate prognostic models for ACLF and to explore their discriminative abilities in ACLF population categorized by the etiologies of precipitating events. Methods This study collected data from 343 consecutive cirrhotic patients hospitalized with the diagnosis of ACLF according to the EASL-CLIF-Consortium definition. The discrimination abilities of prognostic models at the onset of ACLF were tested with the concordance index and area under the receiver operating characteristic curve. Results Among the entire cohort, 103 patients survived with medical management, nine patients were transplanted, and 231 patients died without liver transplantation. The predictive accuracy of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) for 28-day mortality was similar to the CLIF Consortium Organ Failure (CLIF-C OF) but significantly higher than the CLIF Consortium ACLF, the Child-Turcotte-Pugh, the model for end-stage liver disease (MELD), the MELD-sodium, the integrated MELD, and the Acute Physiology and Chronic Health Evaluation II. Of note, 44 patients had acute hepatic insult triggering ACLF (hepatic-ACLF), 244 were exclusively precipitated by bacterial infection or gastrointestinal bleeding (extrahepatic-ACLF), and 55 cases had no any identifiable potential precipitating events. Patients with hepatic-ACLF had significantly higher 28-day mortality than extrahepatic-ACLF patients. The CLIF-SOFA and CLIF-C OF displayed the highest accuracy significantly outperforming other scoring systems in predicting mortality among patients with hepatic-ACLF and those with extrahepatic-ACLF. Conclusion The CLIF-SOFA and simpler CLIF-C OF are reliable measures of mortality risk in ACLF patients precipitated by either hepatic or extrahepatic insults. Both validated models could be used to stratify the risk of death and improve management of ACLF.