Improved Outcome of Orthotopic Liver Transplantation for Chronic Hepatitis B Cirrhosis With Aggressive Passive Immunization

McGory, Robb W; Ishitani, Michael B.; Oliveira, Walter; Stevenson, William; McCullough, Christopher; Dickson, Rolland C.; Caldwell, Stephen H.; Pruett, Timothy L.

doi:10.1097/00007890-199605150-00013

Cited by 274 publications

(212 citation statements)

References 20 publications

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“…Other investigators have reported that a fixed dose regimen of HBIG may be insufficient to maintain constant titers of anti-HBs in these patients. 18 Two of the three patients who had no S mutation post-OLT were hepatitis B e antigen-and HBV-DNA-positive (by hybridization assay) pre-OLT, and were reinfected shortly after (1 and 2 months) transplantation. Reinfection in these patients may have occurred because of inadequate neutralization of circulating virus or release of virus from extrahepatic reservoirs.…”

Section: Discussionmentioning

confidence: 90%

See 1 more Smart Citation

Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis

Ghany¹,

Ayola²,

Villamil³

et al. 1998

Hepatology

307

225

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Early studies found that orthotopic liver transplantation (OLT) for hepatitis B virus (HBV)-related liver failure was associated with a very high rate of reinfection and severe and rapidly progressive liver disease, resulting in a significant decrease in graft and patient survival compared with patients transplanted for other causes of liver disease. 1,2 Various measures have been tried in an attempt to reduce the rate of reinfection. The most promising results have come from the use of long-term (Ն 6 months) high-dose hepatitis B immune globulin (HBIG). 3,4 However, this regimen is expensive, and a significant reduction in the rate of reinfection is mainly seen in patients who have nonreplicative infection pre-OLT. Reinfection despite HBIG immunoprophylaxis may be caused by inadequate neutralization of overwhelming amounts of wildtype HBV, or to breakthrough infection by immune escape mutants.The major B-cell epitopes of hepatitis B surface antigen (HBsAg) have been shown to reside in the 'a' determinant region located at amino acid positions 124-149. 5,6 This region is conformational and is thought to consist of two loops held by disulfide bridges between cysteines 124 and 137, and cysteines 138 and 147. 7 The second loop is more conserved and confers most of the antigenicity of the 'a' determinant; this loop is sometimes referred to as the major hydrophilic region (MHR). HBV can be classified into four major subtypes: adr, adw, ayr, and ayw. Antibodies to the 'a' determinant confer protection against all subtypes of HBV. 8 Mutations in the HBV S gene have been reported in OLT recipients who developed HBV reinfection despite prophylaxis with monoclonal or polyclonal hepatitis B surface antibody (anti-HBs). McMahon et al. found amino acid substitutions in the 'a' determinant in all three patients who were reinfected despite monoclonal anti-HBs prophylaxis, 9 while the incidence of mutations in the 'a' determinant in OLT recipients who were reinfected despite HBIG prophylaxis varied from 0% to 33%. 10-12 Some of these mutations, including the glycine-to-arginine substitution at codon 145, have been shown to decrease binding to monoclonal antiHBs, suggesting that the breakthrough infections were caused by immune escape mutants. 9,11,13 The number of patients cited in the above studies ranged from three to seven patients; therefore, the significance of S escape mutants in HBV reinfection post-OLT remains unclear. It is also possible that additional mutations may be present in the HBV S gene outside the 'a' determinant in patients who received polyclonal anti-HBs (HBIG). Unfortunately, there are very few data on the sequence in the rest of the S gene. In addition, to date, there are no data on the reversibility of these mutations after withdrawal of HBIG therapy.

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Section: Discussionmentioning

confidence: 90%

“…Thirteen patients (patients 1-13) became HBsAg-positive again while they were still receiving HBIG; 7 (patients [14][15][16][17][18][19][20] became HBsAg-positive after discontinuation of HBIG. Reinfection occurred after a mean of 8.5 Ϯ 1.5 months (range, 1-20 months) post-OLT.…”

Section: Methodsmentioning

confidence: 99%

Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis

Ghany¹,

Ayola²,

Villamil³

et al. 1998

Hepatology

307

225

View full text Add to dashboard Cite

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“…Initially, only 2 of 27 patients (7%) became reinfected with HBV, but in a subsequent analysis, 9 of 39 patients (23%) developed allograft infection despite an increase in minimum target levels of anti-HBs to 500 IU/L for the first 6 months and 150 IU/L thereafter. 16,22 HBIG use continues to be limited by breakthrough reinfection in 10% to 20% of cases. 23 The mechanism by which HBIG monotherapy controls the recurrence of disease is poorly understood.…”

Section: Hbigmentioning

confidence: 99%

A concise update on the status of liver transplantation for hepatitis B virus: The challenges in 2002

Vargas

Dodson

Rakela

2002

Liver Transplantation

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Historical PerspectiveI n the early 1970s, results of OLT for chronic HBV infection were hampered by recurrent infection with the host HBV strain and subsequent allograft failure caused by recurrent hepatitis. 1-4 Even in these very early days of hepatic transplantation, distinct patterns of hepatic injury were noted. 4,5 Specifically, chronic lobular hepatitis similar to pre-OLT HBV was described in a large proportion of patients with recurrence. Ten percent to 30% of patients developed the newly named fibrosing cholestatic hepatitis, characterized histologically by thin perisinusoidal bands of fibrosis extending from portal tracts to surround plates of ductular-type epithelium; prominent cholestasis, ground-glass transformation, and ballooning of hepatocytes with cell loss; and mild mixed inflammatory reaction. 6 The clinical behavior of fibrosing cholestatic hepatitis reflected rapid graft dysfunction and progression to cirrhosis. 7 In the next decade, prophylaxis was attempted unsuccessfully with low-dose hepatitis B immune globulin (HBIG) administered for less than 3 months after OLT. 8,9 The Hanover group subsequently adjusted HBIG dosages to maintain the hepatitis B surface antigen (HbsAg) antibody (anti-HBs) titer at greater than 100 IU/L for a minimum of 6 months after OLT. 10

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“…Subsequently, the use of high doses of intravenous (IV) hepatitis B immune globulin (HBIG) after OLT reduced HBV recurrence and improved survival. [5][6][7][8][9][10][11][12] Investigators of the European Concerted Action of Viral Hepatitis project 5 reported a 75% rate of HBV recurrence after OLT in patients receiving no prophylaxis or very short-term HBIG treatment and a 33% rate in patients receiving long-term HBIG prophylaxis. The benefit appeared to be greatest among patients with negative HBV DNA and hepatitis Be antigen (HBeAg) before OLT.…”

confidence: 99%

“…13,14 Furthermore, reinfection of the graft by HBV may still occur despite IV HBIG. [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.…”

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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Improved Outcome of Orthotopic Liver Transplantation for Chronic Hepatitis B Cirrhosis With Aggressive Passive Immunization

Cited by 274 publications

References 20 publications

Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis

Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis

A concise update on the status of liver transplantation for hepatitis B virus: The challenges in 2002

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

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