Circulating predictive and diagnostic biomarkers for hepatitis B virus-associated hepatocellular carcinoma

Abstract

Chronic hepatitis B virus (HBV) infected patients have an almost 100-fold increased risk to develop hepatocellular carcinoma (HCC). HCC is the fifth most common and third most deadly cancer worldwide. Up to 50% of newly diagnosed HCC cases are attributed to HBV infection. Early detection improves survival and can be achieved through regular screening. Six-monthly abdominal ultrasound, either alone or in combination with alpha-fetoprotein serum levels, has been widely endorsed for this purpose. Both techniques however yield limited diagnostic accuracy, which is not improved when they are combined. Alternative circulating or histological markers to predict or diagnose HCC are therefore urgently needed. Recent advances in systems biology technologies have enabled the identification of several new putative circulating biomarkers. Although results from studies assessing combinations of these biomarkers are promising, evidence for their clinical utility remains low. In addition, most of the studies conducted so far show limitations in design. Attention must be paid for instance to different ethnicities and different etiologies when studying biomarkers for hepatocellular carcinoma. This review provides an overview on the current understandings and recent progress in the field of diagnostic and predictive circulating biomarkers for hepatocellular carcinoma in chronically infected HBV patients and discusses the future prospects.

Comparison of clinical features and outcomes between HBV-related and non-B non-C hepatocellular carcinoma

“…Although serum viral markers are important for HCC screening, ethnicity is another important factor [43]. A study has suggested that ethnicity plays an important role in the diagnosis and treatment of HCC [44].…”

Stopping nucleos(t)ide analogue treatment in Caucasian hepatitis B patients after HBeAg seroconversion is associated with high relapse rates and fatal outcomes

“…Chronic hepatitis B virus (HBV) infections are a major global health problem, affecting 250 million people worldwide. 1,2 Clinical presentation remains often subclinical for decades, but serious liver-related complications and liver-related death develop in one-fourth of all untreated patients. 1,3 Standard oral treatment consists of nucleos(t) ide analogues (NA) and suppresses, but does not eradicate the virus.…”

Biomarkers in Diagnosis and Prediction of Hepatocellular Carcinoma Recurrence (Review)

“…In spite of the fact that AFP has already been used in clinical practice for over 50 years, this biomarker remains most widely used to predict the development and monitor the efficacy of HCC treatment [5,31,39,40]. AFP represents a glycoprotein with a 70 kDa molecular mass synthetized by endodermal cells of the fetal yolk sac and later by the embryonic hepatocytes [86].…”

“…AFP exists in three glycosylated isoforms [5,7], and each possesses different capability to bind with lectin (lens culinaris agglutinin, LCA): AFP-L1 (non-LCA-bound fraction), AFP-L2 (weakly bound fraction), and AFP-L3 (LCA-bound fraction). AFP-L1 increases in chronic hepatitis and LC, whereas the elevation of AFP-L3 level is noted in tumor processes in the liver [17,86]. Predominance of AFP-L3 in the total AFP level by more than 10-15% allows HCC to be suspected at an early stage of its development.…”

“…GPC3 belongs to a family of glypicans-proteoglycans. GPC3 is bound to the cellular membrane with a glycosyl-phosphatidyl-inositol anchor [3,63] An independent significance of the GPC3 for HCC diagnosis is restricted due to low Se [61,86]. GPC3 is increased in 1/3 of patients with normal AFP indices in the blood [64].…”