Hepatitis-B-virus resistance to lamivudine given for recurrent infection after orthotopic liver transplantation

Bartholomew, Maria; Jansen, Robert W.; Jeffers, Lennox J.; Reddy, K. Rajender; Johnson, Lance C.; Bunzendahl, H.; Condreay, Lynn D.; Tzakis, Andreas G.; Schiff, Eugene R.; Brown, Nathaniel

doi:10.1016/s0140-6736(96)02266-0

Cited by 426 publications

(312 citation statements)

References 15 publications

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“…A smaller case series of 3 patients with HBV treated with lamivudine posttransplantation revealed development of asymptomatic YMDD variant HBV at 9 to 10 months. 51 In immunocompetent patients receiving lamivudine for 52 weeks in the treatment of chronic hepatitis B, 14% to 32% developed YMDD variant HBV. 54 These variants usually first appear after 36 weeks of treatment.…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of hepatitis B viral mutations

et al. 2000

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Section: Discussionmentioning

confidence: 99%

Clinical relevance of hepatitis B viral mutations

et al. 2000

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“…Although none of these drugs can clear the infection, they can stop the virus from replicating, thus minimizing liver damage. Among the antiviral drugs, lamivudine (LAM, Figure 1(a)), a cytosine nucleoside analogue, has shown good results in the treatment of HBV infection in human beings [4,5]. Once phosphorylated to active metabolites, lamivudine can inhibit the HBV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis.…”

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confidence: 99%

Preparation and cellular uptake of PLGA particles loaded with lamivudine

et al. 2012

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Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles loaded with lamivudine and coated with bovine serum albumin (BSA) were prepared via a double emulsion method. The influences of experiments parameters such as volume of inner aqueous phase, concentration of organic phase and ultrasonication time on the particle size and drug entrapment efficiency were investigated, obtaining PLGA particles with a diameter of ~260 nm and drug entrapment efficiency of ~35%. The particles were observed by scanning electron microscopy and transmittance electron microscopy, showing a core-shell structure. BCA assay found that 58 mg BSA was present on/in 1 g LPB particles. The loaded lamivudine showed a burst release at beginning and sustained release until 24 h in physiological conditions. Low pH could accelerate the release of lamivudine from PLGA particles, making the PLGA particles potential intelligent intracellular drug carriers. The PLGA particles were readily internalized into the human liver cells within a short time and increased gradually with the prolongation of incubation time regardless of the loading of lamivudine. The particles either resided within lysosomes or transferred to cytoplasm, but could not enter into the cell nucleus. The cell viability was not significantly influenced in the presence of the particles regardless of lamivudine encapsulation, suggesting that this kind of particles may be a good candidate for the intracellular anti-hepatitis B drug delivery.PLGA, lamivudine, cell uptake, intracellular distribution, drug delivery Citation:Wang B, Chen G Q, Mao Z W, et al. Preparation and cellular uptake of PLGA particles loaded with lamivudine.

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“…21,22 However, high rates of lamivudine-resistant escape mutants have been reported in transplant recipients, therefore limiting its effectiveness as a single prophylactic agent for long-term use. [23][24][25][26][27] The characteristic mutation involves a base-pair substitution in the highly conserved YMDD motif in subdomain C of the DNA polymerase, where methionine 552 is replaced by either isoleucine (YIDD mutant) or valine (YVDD mutant). The same mutations have been found in the HIV reverse-transcriptase gene for HIV-infected patients receiving lamivudine treatment.…”

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 resistance to lamivudine given for recurrent infection after orthotopic liver transplantation

Cited by 426 publications

References 15 publications

Clinical relevance of hepatitis B viral mutations

Clinical relevance of hepatitis B viral mutations

Preparation and cellular uptake of PLGA particles loaded with lamivudine

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

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