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

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.

The progress and prospects of routine prophylactic antiviral treatment in hepatitis B-related hepatocellular carcinoma

“…Zimmerman et al demonstrated that hepatitis B immunoglobulin (HBIG) and lamivudine prophylactic antiviral treatment can significantly decrease viral recurrence as well as HCC recurrence, improving the post-transplantation survival rate [40]. Considering the high cost of high dose or long-term HBIG treatment, Wu et al adopted a short-term HBIG prophylaxis protocol in combination with life-long lamivudine therapy in their transplantation center; however, the overall HBV relapse rate was higher compared to other high dose or long term HBIG treatments [41]. Short-term HBIG and life-long lamivudine prophylaxis may only be effective in patients without high viral loads.…”

Comparison of pre-S1/S2 variations of hepatitis B virus between asymptomatic carriers and cirrhotic/hepatocellular carcinoma-affected individuals

“…The deletions that were recognized in the present study were located in T-cell and B-cell epitopes, which may cause evasion of the virus from immune recognition, as shown to happen naturally by another study [17]. Moreover, deletion of small sequences from a pre-S region is also associated with an occult HBV state in patients with genotype C [17, 26, 27].…”

“…Regarding the clinical relevance of pre-S1/S2 deletions with infection outcome, Wu et al [27] demonstrated that large fragment deletions reduced the necro-inflammatory grade in relapsing liver failure, an indication of slower disease progression. As large-fragment deletions were also frequent in the ASC patients in the present study, we hypothesize that reducing the pathogenesis is involved in the establishment of an ASC state.…”

Genomic Diversity of Hepatitis B Virus Infection Associated With Fulminant Hepatitis B Development

“…The clinical outcome as well as the graft survival in HBV LT recipients has been improved. This significant step in LT is particularly an effective strategy of HBIG prophylactic therapy alone or in combination with preoperative antiviral agents followed by indefinite treatment ( 85 ). However, the emergence of nucleot (s) ide resistant mutants in the polymerase and HBIG escape mutants in the surface gene can lead to an adverse clinical outcome and a graft failure.…”