Large Fragment Pre-S Deletion and High Viral Load Independently Predict Hepatitis B Relapse after Liver Transplantation

Joerg F Schlaak,Frank Wang,Hong-Shiue Chou,Chau-Ting Yeh,Ruey-Shyang Soong,Wei-Chen Lee,Tse-Ching Chen,Kun-Ming Chan,Ting-Jung Wu

doi:10.1371/journal.pone.0032189

Joerg F Schlaak, Frank Wang + Show 7 more

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https://doi.org/10.1371/journal.pone.0032189

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Journal: PLoS ONE	Publication Date: Feb 21, 2012
Citations: 36	License type: CC BY 4.0

Affiliation: Chang Gung Memorial Hospital

Abstract

Hepatitis B virus (HBV) associated end-stage liver diseases are the leading causes of liver transplantation (LT) in Taiwan. Relapse of hepatitis B occurs after LT, raising the risk of graft failure and reducing patient survival. Although several oral antiviral agents have been approved for anti-HBV treatment, lamivudine (LAM) remained to be the most widely used preventive regimen in Taiwan. While several clinical predictors have been identified for hepatitis B relapse, the predictive roles of the histopathological characteristics in liver explants as well as the genotypic features of the viruses in pre-LT serum samples have not been assessed. Between September 2002 and August 2009, 150 consecutive hepatitis B surface antigen (HBsAg) positive patients undergoing LT were included for outcome analysis following assessment of the clinicopathological and virological factors prior to LT. Kaplan-Meier analyses discovered that pre-operative LAM treatment ≤3 months; membranous distribution and higher expression of tissue HBsAg in liver explants; preoperative viral load ≧106 copies/ml; and presence of large fragment (>100 base pairs) pre-S deletion (LFpreSDel) correlated significantly with hepatitis B relapse. Multivariate Cox regression analysis showed that the presence of LFpreSDel (P = 0.001) and viral load ≧106 copies/mL (P = 0.023) were independent predictors for hepatitis B relapse. In conclusion, besides high viral load, LFpreSDel mutation is an important independent predictor for hepatitis B relapse after LT. More aggressive preventive strategies should be applied for patients carrying these risk factors.

Highlights

Hepatitis B virus (HBV) infection remains a major public health problem worldwide with approximately 2 billion people having been infected and 350 million of these patients becoming chronic carriers [1]
8 died of recurrent hepatocellular carcinoma (HCC), 4 died of acute liver failure due to hepatitis B relapse and the other 13 patients died of non-HBV related diseases including sepsis and biliary complications
The results showed that the membranous staining pattern (P = 0.035) and high expression intensity (P = 0.047) of hepatitis B surface antigen (HBsAg) in the explanted livers were associated with hepatitis B relapse (Figure 3C and D)

Summary

Introduction

Hepatitis B virus (HBV) infection remains a major public health problem worldwide with approximately 2 billion people having been infected and 350 million of these patients becoming chronic carriers [1]. Since the first successful human liver transplantation (LT) in 1963 by Starzl et al [3], LT has become the treatment of choice in eligible patients with hepatic failure or early HCC in many medical centers. Patients with active viral replication prior to transplantation are at risk of hepatitis B relapse. In patients harboring a lower viral load prior to LT, a favorable longterm outcome is generally expected. This observation led to an effective strategy to improve LT outcome through reduction of pre-transplantation HBV viral load [6]

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Conclusion