Systematic review: the prognostic role of alpha‐fetoprotein following liver transplantation for hepatocellular carcinoma

Abstract

Summary Background Liver transplantation (LT) offers a possible cure for carefully selected patients with hepatocellular carcinoma (HCC). Studies report that preoperative alpha‐fetoprotein (AFP) is a prognostic indicator that can predict survival and recurrence in these patients. Aim To undertake a systematic review of available literature on preoperative AFP as a predictor of survival and recurrence following LT for HCC. Methods A literature search was performed using Medline, Embase, Cochrane Library, CINAHL and Google scholar databases to identify studies reporting AFP as a prognostic marker in LT for HCC. Primary outcomes of interest were overall survival and recurrence. Secondary outcomes were correlation of pre‐LT AFP with vascular invasion and grade of tumour differentiation. Results A total of 13 studies met the inclusion criteria (12 159 patients). The majority were male (9603, 78.9%). All were observational studies and only one prospective. Methodological quality was rated as poor for all studies, with selection and observer bias apparent for most cohorts. Reported survival rates and recurrence rates varied widely between the studies although overall demonstrated better outcomes for those with lower (<1000 ng/mL) pre‐LT AFP levels. Similarly, rates of vascular invasion and poor tumour differentiation were higher in those with high pre‐LT AFP levels. Conclusions A quantity of AFP >1000 ng/mL is associated with poorer outcomes from liver transplantation for hepatocellular carcinoma. The quality of studies was generally poor and precluded valid statistical meta‐analysis. There is a need to improve the performance and reporting of primary prognostic studies to facilitate high quality systematic review and meta‐analysis.

Assessment of the correlation between serum prolidase and alpha-fetoprotein levels in patients with hepatocellular carcinoma

“…There was also a relationship between AFP levels and the tumor number, similar to the other studies [37,40] . Moreover, macrovascular invasion was not associated with high AFP levels, contrary to previous studies [38,39] . There were only nine patients (13.2%) with macrovascular invasion, which was insufficient to produce powerful statistical results.…”

“…Furihata et al [37] observed a significant correlation between serum AFP levels and both size and number of HCCs. Furthermore, AFP elevation in HCC was associated with macrovascular invasion in some studies [38,39] . In the present study, serum AFP levels were correlated with tumor size, which is consistent with the results of previous studies [5,35,36] .…”

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

“…Retrospective LT AFP level increase > 15 µg/L per month Lower OS This study showed the negative impact on the outcome of AFP levels increases in patients undergoing LT Lower RFS Higher recurrence rate Hakeem et al [61] 12159…”

“…In a large Chinese retrospective cohort, high serum AFP level correlated with larger HCC size, vascular invasion and low tumor differentiation [57] . Previous studies showed that AFP levels could be useful to predict recurrence after surgery [58,59] , liver transplantation [60][61][62] . The value of AFP as a prognostic marker was reported in several studies evaluating sorafenib in advanced HCC.…”

Role of inflammatory markers as hepatocellular cancer selection tool in the setting of liver transplantation

“…Currently, several biomarkers are utilized in clinical practice, but both the AASLD and an international consensus (15,20) describe biomarkers as an area of future study. Alpha fetoprotein (AFP) (21)(22)(23)(24) and proteins induced by vitamin K absence II (PIVKA-II) (25-28) have been extensively studied and validated as predictors of HCC outcomes. However, there are patients who do not produce either biomarker and still have high risk of recurrence (29,30).…”