Circulating Biomarkers for the Early Diagnosis and Management of Hepatocellular Carcinoma with Potential Application in Resource-Limited Settings

Abstract

Hepatocellular carcinoma (HCC) is among the world's third most lethal cancers. In resource-limited settings (RLS), up to 70% of HCCs are diagnosed with limited curative treatments at an advanced symptomatic stage. Even when HCC is detected early and resection surgery is offered, the post-operative recurrence rate after resection exceeds 70% in five years, of which about 50% occur within two years of surgery. There are no specific biomarkers addressing the surveillance of HCC recurrence due to the limited sensitivity of the available methods. The primary goal in the early diagnosis and management of HCC is to cure disease and improve survival, respectively. Circulating biomarkers can be used as screening, diagnostic, prognostic, and predictive biomarkers to achieve the primary goal of HCC. In this review, we highlighted key circulating blood- or urine-based HCC biomarkers and considered their potential applications in resource-limited settings, where the unmet medical needs of HCC are disproportionately highly significant.

Keywords: circulating biomarkers; early detection; hepatocellular carcinoma; liver cancer; low-to-middle-income countries (LMICs); resource-limited settings.

Figure 1

Circulating biomarkers of HCC. Shown are two types of circulating biomarkers (blood and urine, a focus of this review), the proposed strategies to reduce the cost of testing, and their potential applications in LRS for HCC screening, diagnosis, and management.