Low risk of hepatitis B virus recurrence after withdrawal of long-term hepatitis B immunoglobulin in patients receiving maintenance nucleos(t)ide analogue therapy

Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109-0362, USA.
Liver Transplantation (Impact Factor: 4.24). 03/2007; 13(3):374-81. DOI: 10.1002/lt.21041
Source: PubMed


Hepatitis B virus (HBV) recurrence rates of 0-16% had been reported in patients maintained on nucleoside analogues (NA) after hepatitis B immunoglobulin (HBIG) discontinuation after orthotopic liver transplantation (OLT). However, follow-up in most studies was short. We aimed to determine the long-term risk of HBV recurrence using this strategy. All HBV patients who received > or =7 doses of intravenous HBIG after OLT, with no HBV recurrence while receiving HBIG, and who eventually discontinued HBIG and were maintained on NA, were included. HBV recurrence was defined as HBsAg-positive or HBV DNA > or =5 log copies/mL on 2 consecutive occasions. Twenty-one patients met the inclusion criteria. Immediate post-OLT prophylaxis was combination HBIG and NA in 15 patients, whereas 6 patients received HBIG monotherapy for 62-109 months before NA was added. HBIG was discontinued a median of 26 (range, 0.2-121) months after OLT. Median follow-up post-HBIG discontinuation was 40 (range, 5-51) months. Only 1 patient, who had 12 months of HBIG and was noncompliant to NA therapy, had HBV recurrence, 34 months after HBIG discontinuation. One patient had HBV DNA of 3.3 log copies/mL 47 and 48 months after HBIG discontinuation but remained HBsAg-negative. Lamivudine-resistant mutations were detected in both patients. Probability of HBV recurrence was 0% and 9% at 2 and 4 years after HBIG discontinuation. Three patients had 1-2 episodes of transiently detectable HBV DNA. All were HBV DNA and HBsAg negative on repeated tests over a period of 2-36 months. Maintenance therapy with NA after discontinuation of long-term HBIG therapy is associated with a low risk of HBV recurrence after OLT in compliant HBV patients.

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    ABSTRACT: Liver transplantation is the best treatment option for end-stage liver disease following hepatitis B (HBV) infection. However, the high rate of recurrence of HBV infection following transplantation is a disadvantage of this option. Over the past 2 decades, the gold standard of prophylactic treatment for the prevention of HBV re-infection following liver transplantation has been the administration of low- to high-dose hepatitis B immune globulin (HBIg) along with an antiviral agent to induce passive immunity. The effectiveness of HBIg in preventing the recurrence of HBV depends on the dosage, route of administration, and duration of HBIg treatment, and the viremic status at the time of transplantation. There is currently no consensus on a standardized recommendation for therapeutic options that include HBIg administration. This review attempts to summarize the available data on the feasibility of such options. Most recent studies support the use of long-term combination therapy of HBIg and antiviral NAs (especially new agents).
    Hepatitis Monthly 03/2012; 12(3):168-76. DOI:10.5812/hepatmon.832 · 1.93 Impact Factor
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    • "High dose or long-term HBIG costs expensively and a schedule of frequent injections is very inconvenient for patients. More and more recent investigation have reported the withdraw of long-term HBIG in patients receiving maintenance nucleos(t)ide analogue and outcome seems good especially in low risk patients [27], [28]. Due to financial consideration and limitation of health insurance policy, we adopted a short-term HBIG prophylaxis protocol in combination with life-long LAM therapy in our transplantation center. "
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    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 ≥10(6) 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 ≥10(6) 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.
    PLoS ONE 02/2012; 7(2):e32189. DOI:10.1371/journal.pone.0032189 · 3.23 Impact Factor
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    • "The studies to date highlight several key points related to the HBIG discontinuation strategy. First, while initial results – first one to two years after HBIG discontinuation – may be favorable, risk of recurrence may increase over time either due to the development of viral resistance or due to non-adherence to the oral therapy [42] [44] [45]. Combining antivirals without cross-resistance reduces the risk of emergence of resistance mutations [46] [47] [48] and would appear to be critical to the success of ''antiviral only'' maintenance. "
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    ABSTRACT: Since the early 1990's, hepatitis B immune globulin (HBIG) has been central to the prevention of hepatitis B virus (HBV) recurrence after liver transplantation. When used in combination with oral nucleos(t)ide analogues, HBIG prevents reinfection with HBV in ⩾90% of transplant recipients. While HBIG is highly efficacious, its use is undermined by its high cost. Because of this limitation, there have been many studies of alternative regimens seeking to minimize the dose or duration of HBIG without sacrificing low HBV recurrence rates. Toward that goal, lower dose intramuscular HBIG in combination with oral nucleos(t)ide analogues has been shown to be highly efficacious in preventing disease recurrence and represents a significant cost savings when compared with high dose intravenous administration. The withdrawal of HBIG after a defined course of combination HBIG and oral antivirals has also been shown to be effective, particularly if combination antiviral therapy is used. The ability to achieve undetectable HBV DNA levels pre-transplantation in the majority of patients may contribute to the high efficacy of these HBIG "light" regimens. Additionally, the success of antiviral rescue therapy for those patients who fail prophylaxis and develop recurrent HBV infection post-transplant has provided the impetus to move increasingly towards HBIG-free approaches. New techniques to detect occult HBV in hepatic and extrahepatic sites may allow clinicians to define a subgroup of patients in whom withdrawal of HBIG or all prophylaxis may be applicable.
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