Predictive validation of qualitative fibrosis staging in patients with chronic hepatitis B on antiviral therapy

Hye Won Lee,Sang Hoon Ahn,Beom Kyung Kim,Ji Hae Nahm,Kiyong Na,Do Young Kim,Jun Yong Park,Kwang-Hyub Han,Jung Il Lee,Young Nyun Park,Seung Up Kim

doi:10.1038/s41598-019-51638-3

Abstract

The fibrosis in chronic hepatitis shows dynamic changes during antiviral therapy (AVT). We investigated whether P-I-R (progressive vs. indeterminate vs. regressive) staging is predictive of hepatocellular carcinoma (HCC) recurrence in patients with chronic hepatitis B (CHB) taking AVT who underwent resection. Patients with CHB-related HCC who underwent curative resection between 2004 and 2017 and had received ≥2 years AVT at the time of resection were eligible. Two pathologists performed P-I-R staging. In total, 104 patients with CHB-related HCC were enrolled. The mean age of the study population was 56.3 years. The mean duration of AVT at the time of resection was 62.6 months. During the follow-up period (mean, 45.5 months), 20 (19.2%) and 14 (13.5%) patients developed early and late recurrence of HCC, respectively. The cumulative incidence of late recurrence was significantly lower in patients with regressive patterns than in those with indeterminate and progressive patterns according to P-I-R staging (P = 0.015, log-rank test), although the cumulative incidence of overall recurrence according to P-I-R staging was similar. Hepatitis B virus DNA levels (hazard ratio [HR] = 3.200, P = 0.020) and the regressive P-I-R staging pattern (HR = 0.127, P = 0.047) independently predicted the risk of late recurrence. One-time assessment of the P-I-R staging at the time of curative resection in patients with CHB-related HCC receiving AVT independently predicted late HCC recurrence. Therefore, qualitative fibrosis assessment by P-I-R staging might be useful in predicting the outcomes of patients with CHB undergoing AVT.

Highlights

The fibrosis in chronic hepatitis shows dynamic changes during antiviral therapy (AVT)
After excluding 41 patients according to our exclusion criteria, 104 patients who had received ≥2 years AVT at the time of curative resection for chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) were selected for analyses
One-time P-I-R assessment predicted the risk of late HCC recurrence (P = 0.015), and the regressive fibrosis pattern of P-I-R staging was associated independently with a reduced risk of late HCC recurrence (HR = 0.127)

Summary

Introduction

The fibrosis in chronic hepatitis shows dynamic changes during antiviral therapy (AVT). Several staging systems, such as the Ishak, Metavir, and Batts systems, have been developed to evaluate the quantity of fibrosis and have been used to assess the degree of liver fibrosis in patients with chronic viral hepatitis[1,2,3,4]. Several issues have arisen regarding these semi-quantitative staging systems for liver fibrosis that render them less applicable in this era of using active and potent antiviral therapy (AVT) for patients with chronic hepatitis B (CHB) Because these staging systems were established based on histological changes in untreated patients, their applicability in patients with CHB receiving AVT is not well known. We investigated whether P-I-R staging has prognostic value in predicting HCC recurrence, a solid clinical endpoint for HCC, in patients undergoing curative resection for CHB-related HCC who had already received at least 2 years of AVT

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Results

Conclusion