Hepatitis B virus with antigenically altered hepatitis B surface antigen is selected by high-dose hepatitis B immune globulin after liver transplantation

Protzer, Ulrike; Naumann, U; Bartenschlager, Ralf; Berg, Thomas; Hopf, U.; Büschenfelde, Karl‐Hermann Meyer zum; Neuhaus, P.; Gerken, Guido

doi:10.1002/hep.510270138

Cited by 254 publications

(180 citation statements)

References 43 publications

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“…Only 1 patient (NR21) selected a mutation (P120T) on FCV, which has been associated with failure of HBIg prophylaxis. [29][30][31][32][33] However, 1 nonresponder (NR24) reverted this mutation P120T on FCV.…”

Section: Analysis Of the Hbv-dna Polymerase Region A To E On Lammentioning

confidence: 97%

“…From previous studies, we know that certain amino acid changes are associated with failure of HBIg immunoprophylaxis. [29][30][31][32][33] Before the start of nucleoside analogue therapy, 8 patients (PR11, NR22, NR24, R01, R02, PR16, PR19, NR26) (Tables 11, 12, and 13) also showed such mutations within the S-gene. These mutations were a G145R mutation associated with a D144E mutation of the HBsAg corresponding to a W501E mutant of the HBV-DNA polymerase in 2 patients (R01, NR22), and a P120T mutation corresponding to a T476N mutation of the HBV-DNA polymerase in 6 (R01, PR11, NR24, PR 16, PR19, NR26), of whom 1 (R01) also had the G145R and D144E mutations.…”

Section: Analysis Of the Hbv-dna Polymerase Region A To E On Lammentioning

confidence: 99%

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Mutational pattern of hepatitis B virus on sequential therapy with famciclovir and lamivudine in patients with hepatitis B virus reinfection occurring under hbig immunoglobulin after liver transplantation

Tillmann¹,

Trautwein²,

Bock³

et al. 1999

Hepatology

127

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Famciclovir (FCV) and lamivudine (LAM) reduce viral replication in patients with recurrent hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT).Eighteen of 20 patients with insufficient response to FCV were treated with 100 mg LAM daily after OLT. These patients had shown nonresponse (n ‫؍‬ 5), partial response (n ‫؍‬ 7), or breakthrough (n ‫؍‬ 6) during FCV therapy. Despite passive immunoprophylaxis with hepatitis B immunoglobulin after liver transplantation, HBV reinfection had occurred in 14 of 15 transplanted patients. HBV-DNA levels and the regions A to E of the HBV-DNA polymerase gene were analyzed before and after treatment failure to either therapy. Within 4 weeks on LAM, all but 1 patient showed a 95% average reduction of the HBV-DNA level. As with FCV, we did not observe any severe side-effects attributable to LAM. However, 7 patients developed a breakthrough within 12, 29 (n ‫؍‬ 2), 32, 37, 54, and 145 weeks under treatment with LAM associated with the methionine-to-valine signature mutation (M552V) in the YMDD motif in all. With FCV, no unique, but a dominant, resistance pattern with the L528M mutation was identified for patients with breakthrough under FCV. In contrast, nonresponders or patients with partial response to FCV did not exhibit such mutations. Our results indicate that the L528M mutation is a risk factor for LAM breakthrough, because breakthrough during LAM occurred earlier in patients with this mutation (50 ؎ 10 weeks vs. 120 ؎ 21 weeks). Because breakthrough on either treatment is frequent for this specific group of patients, the use of combination therapy should be explored. (HEPATOLOGY 1999;30:244-256.)Hepatitis B virus (HBV) infection affects more than 300 million people worldwide. The infection frequently leads to cirrhosis and hepatocellular carcinoma. Orthotopic liver transplantation (OLT) is a therapeutic option for end-stage liver disease. Results of liver transplantation for HBV-related end-stage liver disease are worse compared with other benign indications for liver transplantation, 1 because HBV reinfection often runs a severe course in liver graft recipients, 2,3 with an estimated 3-year survival of only 54%. 4 Treatment with passive immunoprophylaxis with hyperimmunoglobulin against hepatitis B surface antigen (HBIg) has improved the outcome of these patients. 5 In some patients, in particular if pretransplantation replication levels were high, this regime fails to prevent recurrence of HBV. Thus, additional treatment options are needed for these patients .6 Two new oral nucleoside analogues, lamivudine (LAM) and famciclovir (FCV), have been reported as potent inhibitors of hepadnaviral replication in vitro 7,8 and in vivo. 9-12 HBV replicates via an intermediate RNA step through the process of reverse transcription. As a consequence, the mutation rate in the HBV genome is increased compared with other DNA viruses as a result of the lack of proofreading activity in the viral polymerase. Nonresponse or resistance to nucleoside analogues can be rel...

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Section: Analysis Of the Hbv-dna Polymerase Region A To E On Lammentioning

confidence: 97%

Section: Analysis Of the Hbv-dna Polymerase Region A To E On Lammentioning

confidence: 99%

Mutational pattern of hepatitis B virus on sequential therapy with famciclovir and lamivudine in patients with hepatitis B virus reinfection occurring under hbig immunoglobulin after liver transplantation

Tillmann¹,

Trautwein²,

Bock³

et al. 1999

Hepatology

127

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“…It contains a major hydrophilic region (MHR) which ranges from amino acid 99 to 169 [36]. The MHR contains a highly conserved region called the 'a' determinant, which contains the majority of epitopes for HBsAg [37]. These epitopes are generally the central target for protective humoral immunity against HBV.…”

Section: Genomementioning

confidence: 99%

Serological and molecular epidemiological outcomes after two decades of universal infant hepatitis B virus (HBV) vaccination in Nunavut, Canada

Huynh¹,

Minuk

Uhanova

et al. 2017

Vaccine

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“…[5][6][7][8][9][10][11][12] Graft reinfection may be caused by inadequate neutralization because of overwhelming amounts of HBV or break-through infection by escape HBV surface protein mutants. 15,16 Recently, long-term survival and HBV recurrence data using IV HBIG prophylaxis were reported by Samuel et al 17 Excluding patients with delta hepatitis and fulminant liver failure, 89 patients with HBV cirrhosis underwent OLT. An excellent actuarial 10-year survival of 72.8% was reported in this group.…”

confidence: 99%

Intramuscular hepatitis B immune globulin combined with lamivudine for prophylaxis against hepatitis B recurrence after liver transplantation

et al. 1999

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Immunoprophylaxis using intravenous (IV) hepatitis B immune globulin (HBIG) decreases the recurrence of hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). However, IV HBIG is expensive, has significant side effects, and is inconvenient to administer. An alternative approach for prophylaxis using intramuscular (IM) HBIG and oral lamivudine was prospectively evaluated in this study. Ten consecutive patients with cirrhosis with HBV infection who underwent OLT were included in this study. Nine of 10 patients received lamivudine, 150 mg/d, for an average duration of 8.6 months before OLT. Two of 10 patients with detectable HBV DNA at the time of OLT received 10,000 U (45 mL) of IV HBIG daily for 7 consecutive days, followed by 5 mL of IM HBIG weekly for the next 3 weeks, then every 3 weeks. The other 8 patients were HBV DNA negative at OLT and received one dose of IV HBIG (45 mL) during surgery, followed by 5 mL of IM HBIG weekly for 4 weeks, then every 3 weeks. All patients received lamivudine, 150 mg/d, after OLT. During a mean follow-up of 15.6 months, 9 of 10 patients achieved a protective hepatitis B surface antibody (HBsAb) titer greater than 200 IU/L and had no evidence of HBV recurrence. One patient failed to develop an adequate HBsAb titer and developed histological and virological evidence of recurrence. One patient died unrelated to HBV recurrence. Our preliminary data suggest that this combination prophylaxis with IM HBIG and lamivudine is effective and potentially cost saving.

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Hepatitis B virus with antigenically altered hepatitis B surface antigen is selected by high-dose hepatitis B immune globulin after liver transplantation

Cited by 254 publications

References 43 publications

Mutational pattern of hepatitis B virus on sequential therapy with famciclovir and lamivudine in patients with hepatitis B virus reinfection occurring under hbig immunoglobulin after liver transplantation

Mutational pattern of hepatitis B virus on sequential therapy with famciclovir and lamivudine in patients with hepatitis B virus reinfection occurring under hbig immunoglobulin after liver transplantation

Serological and molecular epidemiological outcomes after two decades of universal infant hepatitis B virus (HBV) vaccination in Nunavut, Canada

Intramuscular hepatitis B immune globulin combined with lamivudine for prophylaxis against hepatitis B recurrence after liver transplantation

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