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Changes in Gc-globulin (Gc) and in alpha-foetoprotein (AFP) have been shown to be related to outcome in patients with acute liver failure (ALF). Gc is a serum protein that complexes with intravascular actin released during cellular necrosis. AFP, also made by hepatocytes, is associated with hepatocellular growth and regeneration. Previously, low absolute levels or decreases over time in either AFP or Gc portended to be a poor outcome.In a retrospective analysis of the double-blind trial of intravenous N-acetylcysteine (NAC) for ALF not because of acetaminophen, sera on days 1 and 3 or days 2 and 4 following admission were available to measure AFP in 70 patients and Gc in 66 patients. Mann-Whitney U tests were performed on the admission values, the absolute change and the fractional change of AFP and Gc to compare TFS (transplant-free survival) and non-TFS (death or transplantation). Logistic regression and receiver operating characteristic (ROC) analyses were performed to evaluate the markers in comparison and in addition to King's College Criteria (KCC).Transplant-free survival patients were characterized by increases in AFP, whereas non-TFS had significantly different (negative) absolute and fractional changes (P .01). The addition of declining AFP levels to KCC improved the area under the curve in predicting non-TFS (AUC70%). Gc globulin values did not differ between TFS and non-TFS in the 2-day intervals studied (P .2).In this comparison of two prognostic markers in patients with non-acetaminophen-induced ALF, rising AFP but not rising Gc levels was associated with TFS.ClinicalTrials.gov number NCT00004467.

Background & aims This study investigates the long-term incidences and predictors of developing hepatocellular carcinoma (HCC), cirrhotic events and mortality in cirrhotic patients receiving entecavir (ETV) therapy. Methods We enrolled 481 nucleos(t)ide analogue-naive chronic hepatitis B (CHB) patients who had compensated cirrhosis upon entry and had received ETV monotherapy for >12 months. Results The 8-year cumulative incidences of developing HCC, cirrhotic events and liver-related mortality were 26.5%, 8.62% and 10.03% respectively. Multivariate analysis revealed that diabetic mellitus (DM), higher fibrosis-4 (FIB-4) and alpha-foetoprotein (AFP) levels at 12 months of treatment, and FIB-4 increase from baseline to 12 months were independent factors of HCC. FIB-4 and AFP levels at 12 months of treatment were also independent factors of cirrhotic events and mortality. FIB-4 cut-off values of 3, 3 and 5 as well as AFP cut-offs of 5, 5, and 9 ng/mL at 12 months of treatment were optimal for predicting HCC, cirrhotic events and mortality during therapy respectively. The FIB-4 and AFP levels at 12 months of treatment were assessed for the combined risk of developing clinical outcomes. The 8-year incidences of HCC, cirrhotic events and liver-related mortality in the subgroups with low FIB-4 and AFP levels were only 5.95%, 1.03% and 2.43% respectively. DM was an independent predictor of HCC and mortality. Conclusion The combination of FIB-4 and AFP levels at 12 months of treatment is a useful marker for predicting the development of HCC, cirrhotic events and mortality in compensated cirrhotic patients with CHB who are receiving ETV therapy.

Background & Aims We investigated the significance of 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET) parameters and alpha-foetoprotein (AFP) levels in patients with locally advanced hepatocellular carcinoma (LA-HCC). Methods We retrospectively analysed data of 228 patients with LA-HCC who underwent pretreatment 18F-FDG PET between January 2003 and December 2013. All patients were treated using liver-directed therapy involving radiotherapy. The maximum standardized uptake values (SUVs) and tumour-to-extratumoural liver SUV ratios were calculated, and pretreatment AFP values were obtained. Results Patients were divided into high and low maximum SUV (SUVmax) groups according to a SUV cut-off of 4.825 determined via receiver-operating characteristic analysis. High AFP level (>550 ng/mL) and high SUVmax were significant predictors of overall and progression-free survival. Better treatment responses and longer median progression-free and overall survival were observed in the low SUVmax group, compared to the high SUVmax group. Similar results were obtained for SUV ratio-based (cut-off value: 2.355) and AFP-based analyses (cut-off value: 550 ng/mL). Three risk groups were identified using the double biomarkers of SUVmax and AFP value as strong prognosticators predictive of survival outcomes. This risk stratification was identified as a prognosticator of survival outcomes, even after subgroup analyses. Furthermore, in high risk group, significantly high extrahepatic failure was shown while in low risk group, significantly low intrahepatic failure. Conclusions Clinical significance of double biomarkers, SUV and AFP, could be translated into risk stratification for LA-HCC. It could be a valuable tool for survival outcome prediction.

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