Precancer antiviral treatment reduces microvascular invasion of early-stage Hepatitis B-related hepatocellular carcinoma

Kai Liu,Xinwei Yang,Jicheng Duan,Mengchao Wu,Jiahe Yang,Hu Liu,Yanxin Chang

doi:10.1038/s41598-019-39440-7

Abstract

The impact of antiviral therapy before tumorigenesis on microvascular invasion (MVI) of Chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) is still unknown. In this retrospective cohort study 3,276 HCC patients with early-stage who underwent curative resection were included. We investigated the effect of precancer antiviral therapy on the pathology, especially MVI, of CHB-related HCC. MVI occurrence rates of CHB-related HCC stratified by histopathologic inflammation grades of G1, G2, and G3 were 30.4%, 34.7%, and 38.6%, respectively, compared to 19.8% for CHB-negative HCC. Patients who received standard antiviral treatment showed much lower rates of MVI, higher tumor capsule integrity, less frequent satellite micronodules and lower AFP level compared to the no antiviral group. Moreover, precancer antiviral therapy prolonged the disease-free survival (DFS), which are also proved to be independent indicators of DFS. In addition, we show that antivirals may suppress early progression of HCC primarily by inhibition of HBV viral load, and influencing the expression levels of CK18, GPC3, OPN and pERK. Hence, we demonstrate that precancer antivirals significantly reduce the MVI rate of CHB-related HCC, reduce malignancy of early-stage HCC, and improve HCC prognosis. Thus, this study confirms the importance of antiviral therapy for CHB patients.

Highlights

The impact of antiviral therapy before tumorigenesis on microvascular invasion (MVI) of Chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) is still unknown
Of the 3,276 total HCC patients (Table 1, Supplementary Information) of early-stage according to BCLC and Milan criteria, defined as a single HCC ≤ 5 cm in the maximum diameter, MVI was detected in 30.4% (98/322), 34.7% (784/2262), and 39.9% (240/601) of tumors with histopathologic grades of G1, G2, and G3, respectively
The serial progression of hepato-carcinogenesis occurs according to a sequence of inflammation, fibrosis, and tumorigenesis, which is known as the hepatic inflammation-fibrosis-cancer axis (IFC axis)

Summary

Introduction

The impact of antiviral therapy before tumorigenesis on microvascular invasion (MVI) of Chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) is still unknown. In this retrospective cohort study 3,276 HCC patients with early-stage who underwent curative resection were included. We demonstrate that precancer antivirals significantly reduce the MVI rate of CHB-related HCC, reduce malignancy of early-stage HCC, and improve HCC prognosis. Microvascular invasion (MVI) has been extensively demonstrated as an independent risk factor for adverse outcomes such as early recurrence following curative liver resection or transplantation in HCC patients. The relationship and mechanisms between antiviral treatment before tumorigenesis (i.e. precancer antiviral therapy) and MVI occurrence in CHB-related HCC, especially at the early stage, are still under studied. Characteristic Patients Sex male female Age (years) Tumor size (cm) GS staging HBsAg(−) G1 G2 G3

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Conclusion