Impact of virologic breakthrough and HBIG regimen on hepatitis B recurrence after liver transplantation

B Degertekin, Steven-Huy B Han, E B Keeffe, E R Schiff, V A Luketic, R S Brown Jr, S Emre, C Soldevila-Pico, K R Reddy, M B Ishitani, T T Tran, T L Pruett, A S F Lok, NIH HBV-OLT Study Group, Natalie Bzowej, Robert Gish, Jamie Zagorsk, Tram Tran, Amy Crumley, Paul Gaglio, Maria Martin, Raymond T Chung, Diana Tsui, Marian Bihrle, Michael Ishitani, Heidi Togerson, Sukru Emre, Mark Sturdevant, Javaluyas Aniceto, Robert Perrillo, Cheryl Denham, Emmet Keeffe, Lucinda Porter, Steve Han, Pearl Kim-Hong, Val Peacock, Consuelo Soldevila-Pico, Joy Peter, Eugene Schiff, Maria Torres, Rajender Reddy, Timothy Siropaides, Timothy Pruett, Velimir A C Luketic, Stacy McLeod, Anna Lok, Bulent Degertekin, Terese Howell, Donna Harsh, Munira Hussain, Jim Imus, Morton Brown, B Degertekin, Steven-Huy B Han, E B Keeffe, E R Schiff, V A Luketic, R S Brown Jr, S Emre, C Soldevila-Pico, K R Reddy, M B Ishitani, T T Tran, T L Pruett, A S F Lok, NIH HBV-OLT Study Group, Natalie Bzowej, Robert Gish, Jamie Zagorsk, Tram Tran, Amy Crumley, Paul Gaglio, Maria Martin, Raymond T Chung, Diana Tsui, Marian Bihrle, Michael Ishitani, Heidi Togerson, Sukru Emre, Mark Sturdevant, Javaluyas Aniceto, Robert Perrillo, Cheryl Denham, Emmet Keeffe, Lucinda Porter, Steve Han, Pearl Kim-Hong, Val Peacock, Consuelo Soldevila-Pico, Joy Peter, Eugene Schiff, Maria Torres, Rajender Reddy, Timothy Siropaides, Timothy Pruett, Velimir A C Luketic, Stacy McLeod, Anna Lok, Bulent Degertekin, Terese Howell, Donna Harsh, Munira Hussain, Jim Imus, Morton Brown

Abstract

The availability of hepatitis B immune globulin (HBIG) and several oral antiviral therapies has reduced but not eliminated hepatitis B virus (HBV) recurrence. We aimed to determine the rate of HBV recurrence after orthotopic liver transplantation (OLT) in relation to virologic breakthrough pre-OLT and HBIG regimens post-OLT. Data from the NIH HBV-OLT database were analyzed. A total of 183 patients transplanted between 2001 and 2007 followed for a median of 42 months (range 1-81) post-OLT were studied. At transplant, 29% were hepatitis B e antigen (HBeAg) (+), 38.5% had HBV DNA > 5 log(10) copies/mL, 74% were receiving antiviral therapy. Twenty-five patients experienced virologic breakthrough before OLT. Post-OLT, 26%, 22%, 40% and 12% of patients received intravenous (IV) high-dose, IV low-dose, intramuscular low-dose and a finite duration of HBIG, respectively as maintenance prophylaxis. All but two patients also received antiviral therapy. Cumulative rates of HBV recurrence at 1 and 5 years were 3% and 9%, respectively. Multivariate analysis showed that listing HBeAg status and HBV DNA level at OLT were the only factors associated with HBV recurrence. In conclusion, low rates of HBV recurrence can be accomplished with all the HBIG regimens used when combined with antiviral therapy including patients with breakthrough pre-OLT as long as rescue therapy is administered pre- and post-OLT.

Figures

Figure 1. Distribution of HBIG regimens used…
Figure 1. Distribution of HBIG regimens used in each of the 15 participating centers (A–O). Only 4 centers (K, L, N, O) used one regimen
Number of patients receiving each HBIG regimen: IV high dose, IV low dose, IM low dose, and finite duration at each center is listed beneath the bars.
Figure 2
Figure 2
(A) HBV Recurrence in Relation to Indication at Transplantation -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 1%, 6%, and 9% for patients with end-stage cirrhosis; and 6%, 8% and 11% for patients with HCC; and none for patients with acute liver failure (p = 0.686). Figure 2(B): HBV Recurrence in Patients with and without Virological Breakthrough Pre-Transplant (p = 0.209). Figure 2(C): HBV Recurrence in Relation to HBeAg Status at Listing -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 10%, 15%, and 15% for patients who were HBeAg positive at listing; and 0, 2%, and 5% for those who were HBeAg negative (p = 0.010). Figure 2(D): HBV Recurrence in Relation to Serum HBV DNA Level at the Time of Transplant -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 7%, 15%, and 15% for patients with serum HBV DNA >5 log10 copies/mL at transplant; and 1%, 1%, and 3% for those with serum HBV DNA <5 log10 copies/mL (p = 0.003). Figure 2(E): HBV Recurrence in Relation to HBIG Regimens – The 5-year recurrence rates for the groups that received IV high dose, IV low dose, IM low dose, and finite duration of HBIG were 10, 3, 10, and 14, respectively (p = 0.733). The overall 5-year recurrence rate was 9%.
Figure 2
Figure 2
(A) HBV Recurrence in Relation to Indication at Transplantation -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 1%, 6%, and 9% for patients with end-stage cirrhosis; and 6%, 8% and 11% for patients with HCC; and none for patients with acute liver failure (p = 0.686). Figure 2(B): HBV Recurrence in Patients with and without Virological Breakthrough Pre-Transplant (p = 0.209). Figure 2(C): HBV Recurrence in Relation to HBeAg Status at Listing -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 10%, 15%, and 15% for patients who were HBeAg positive at listing; and 0, 2%, and 5% for those who were HBeAg negative (p = 0.010). Figure 2(D): HBV Recurrence in Relation to Serum HBV DNA Level at the Time of Transplant -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 7%, 15%, and 15% for patients with serum HBV DNA >5 log10 copies/mL at transplant; and 1%, 1%, and 3% for those with serum HBV DNA <5 log10 copies/mL (p = 0.003). Figure 2(E): HBV Recurrence in Relation to HBIG Regimens – The 5-year recurrence rates for the groups that received IV high dose, IV low dose, IM low dose, and finite duration of HBIG were 10, 3, 10, and 14, respectively (p = 0.733). The overall 5-year recurrence rate was 9%.
Figure 2
Figure 2
(A) HBV Recurrence in Relation to Indication at Transplantation -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 1%, 6%, and 9% for patients with end-stage cirrhosis; and 6%, 8% and 11% for patients with HCC; and none for patients with acute liver failure (p = 0.686). Figure 2(B): HBV Recurrence in Patients with and without Virological Breakthrough Pre-Transplant (p = 0.209). Figure 2(C): HBV Recurrence in Relation to HBeAg Status at Listing -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 10%, 15%, and 15% for patients who were HBeAg positive at listing; and 0, 2%, and 5% for those who were HBeAg negative (p = 0.010). Figure 2(D): HBV Recurrence in Relation to Serum HBV DNA Level at the Time of Transplant -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 7%, 15%, and 15% for patients with serum HBV DNA >5 log10 copies/mL at transplant; and 1%, 1%, and 3% for those with serum HBV DNA <5 log10 copies/mL (p = 0.003). Figure 2(E): HBV Recurrence in Relation to HBIG Regimens – The 5-year recurrence rates for the groups that received IV high dose, IV low dose, IM low dose, and finite duration of HBIG were 10, 3, 10, and 14, respectively (p = 0.733). The overall 5-year recurrence rate was 9%.
Figure 2
Figure 2
(A) HBV Recurrence in Relation to Indication at Transplantation -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 1%, 6%, and 9% for patients with end-stage cirrhosis; and 6%, 8% and 11% for patients with HCC; and none for patients with acute liver failure (p = 0.686). Figure 2(B): HBV Recurrence in Patients with and without Virological Breakthrough Pre-Transplant (p = 0.209). Figure 2(C): HBV Recurrence in Relation to HBeAg Status at Listing -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 10%, 15%, and 15% for patients who were HBeAg positive at listing; and 0, 2%, and 5% for those who were HBeAg negative (p = 0.010). Figure 2(D): HBV Recurrence in Relation to Serum HBV DNA Level at the Time of Transplant -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 7%, 15%, and 15% for patients with serum HBV DNA >5 log10 copies/mL at transplant; and 1%, 1%, and 3% for those with serum HBV DNA <5 log10 copies/mL (p = 0.003). Figure 2(E): HBV Recurrence in Relation to HBIG Regimens – The 5-year recurrence rates for the groups that received IV high dose, IV low dose, IM low dose, and finite duration of HBIG were 10, 3, 10, and 14, respectively (p = 0.733). The overall 5-year recurrence rate was 9%.
Figure 2
Figure 2
(A) HBV Recurrence in Relation to Indication at Transplantation -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 1%, 6%, and 9% for patients with end-stage cirrhosis; and 6%, 8% and 11% for patients with HCC; and none for patients with acute liver failure (p = 0.686). Figure 2(B): HBV Recurrence in Patients with and without Virological Breakthrough Pre-Transplant (p = 0.209). Figure 2(C): HBV Recurrence in Relation to HBeAg Status at Listing -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 10%, 15%, and 15% for patients who were HBeAg positive at listing; and 0, 2%, and 5% for those who were HBeAg negative (p = 0.010). Figure 2(D): HBV Recurrence in Relation to Serum HBV DNA Level at the Time of Transplant -- The 1, 3, and 5 year probability of HBV recurrence post-OLT was 7%, 15%, and 15% for patients with serum HBV DNA >5 log10 copies/mL at transplant; and 1%, 1%, and 3% for those with serum HBV DNA <5 log10 copies/mL (p = 0.003). Figure 2(E): HBV Recurrence in Relation to HBIG Regimens – The 5-year recurrence rates for the groups that received IV high dose, IV low dose, IM low dose, and finite duration of HBIG were 10, 3, 10, and 14, respectively (p = 0.733). The overall 5-year recurrence rate was 9%.
Figure 3
Figure 3
Post-OLT Patient Survival in Patients with and without HBV Recurrence -- The 1, 3, and 5 year probability of post-OLT patient survival was 100%, 85%, and 76% for patients with; and 95%, 93%, and 92% for those without HBV recurrence (p = 0.028).

Source: PubMed

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