[Post-transplant prophylaxis of the recurrence of lamivudine-resistant YMDD mutant hepatitis B virus in liver recipients].
Yang YangJian ZhangHuimin YiMin-qiang LuChangjie CaiXi LiNan JiangChi XuHua LiGenshu WangShuhong YiJunfeng ZhangHua JiangQing YangGuihua Chen
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Abstract:
To evaluate the prophylactic efficacy of adefovir dipivoxil (ADV) for post-transplant recurrence of hepatitis B virus (HBV) with lamivudine-resistant YMDD mutation in liver recipients.From March 2004 to May 2006, 20 patients with chronic hepatitis B associated with YMDD mutant HBV prior to liver transplantation received treatment with ADV and additional intramuscular hepatitis B immunoglobulin (HBIG) for prevention of post-transplant graft reinfection. The liver function, serum HBsAg, anti-HBs (HBIG), HBeAg, anti-HBc, anti-HBe, HBV DNA and creatinine were examined in all the patients before and after the transplantation.The median follow-up duration of these patients after the transplantation was 33.5 months. Nineteen patients survived and one patient died of recurrent hepatocellular carcinoma. There was significant difference in YMDD mutation rate between the patients with HBV-DNA over 10(6) copies/ml and those with HBV-DNA less than 10(6) copies/ml (12.4% vs 2.5%, P < 0.05). HBV-DNA was undetectable at 4 weeks after the transplantation in 95.0% of the patients (19/20) and at 6 months in one case. No recurrence of hepatitis B was detected by long-term regular testing of HBsAg, HBeAg and HBV-DNA. Serum creatinine increased in 1 case 1 year after the use of ADV.ADV offers protection against recurrence of HBV with YMDD mutation after liver transplantation with only mild nephrotoxicity, but renal function monitoring during the use of ADV is still necessary.Keywords:
Adefovir
HBeAg
Entecavir
Liver function
Hepatitis B
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Recurrent hepatitis B virus (HBV) infection remains a major cause of morbidity and mortality after liver transplantation. Recently, antiviral therapy, such as lamivudine, has become available for prophylaxis against HBV reactivation posttransplantation and for the treatment of HBV recurrent disease. We report our initial experience with lamivudine therapy in patients with precore mutant-associated HBV infection undergoing liver transplantation (n = 29). Outcomes were compared in three patient groups: group 1, precore mutant HBV infection not receiving lamivudine (n = 10); group 2, recurrent precore mutant HBV infection posttransplantation subsequently treated with lamivudine (n = 10); and group 3, HBV precore mutant patients undergoing liver transplantation and receiving lamivudine and low-dose hepatitis B immune globulin (HBIG) from the time of transplantation (n = 9). In group 1, HBV recurred in 9 of 10 patients, with subsequent graft loss in all 9 patients. In group 2, all patients developed HBV recurrence at a mean of 7.3 months posttransplantation and started lamivudine therapy at a median of 16 months posttransplantation. Follow-up on lamivudine therapy was for a median of 11 months. Six of these 10 patients developed mutations in the HBV polymerase gene associated with lamivudine resistance. There were two liver failure-related deaths in this group. In group 3 patients, there was one death from graft-versus-host disease. The remaining 8 patients have been followed up for a mean of 15.6 months posttransplantation, and all remain hepatitis B surface antigen negative and HBV DNA negative. In conclusion, lamivudine therapy in association with low-dose HBIG is effective in preventing HBV reactivation posttransplantation. Rescue therapy with lamivudine in patients with HBV recurrence is only moderately effective, with a 60% lamivudine resistance rate in patients treated for longer than 6 months.
Hepatitis B
Liver disease
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Tailored approaches have been attempted to prevent hepatitis B virus (HBV) reinfection in antibodies against hepatitis B surface antigen (HBsAg)-positive liver transplantation (LT) recipients in order to minimize the use of hepatitis B immune globulin (HBIG) and nucleoside analogues (NAs). We report the results of complete HBV prophylaxis withdrawal after a follow-up of at least 6 years in LT recipients with undetectable serum HBV DNA and intrahepatic total HBV DNA and covalently closed circular DNA at LT. We included 30 HBsAg positive, hepatitis B e antigen-negative recipients, 6 with hepatitis C virus and 7 with hepatitis D virus coinfection, who had received HBIG plus NA for at least 5 years after LT. Stepwise HBIG and NA withdrawal was performed in two 6-month periods under strict monitoring of HBV virology. All patients underwent a clinical, biochemical, and virological follow-up at 3-6 month intervals. HBV recurrence (HBsAg seroreversion ± detectable HBV DNA) occurred in 6 patients: in 1 patient after HBIG interruption and in 5 after both HBIG and NA cessation. Only 3 patients required reinstitution of HBV prophylaxis because of persistent HBV replication, and all achieved optimal control of HBV infection and did not experience clinical events. The other who recurred showed only short-lasting HBsAg positivity, with undetectable HBV DNA, followed by spontaneous anti-HBs seroconversion. An additional 15 patients mounted an anti-HBs titer, without previous serum HBsAg detectability. At the end of follow-up, 90% of patients were still prophylaxis-free, 93.3% were HBsAg negative, and 100% were HBV DNA negative; 60% had anti-HBs titers >10 IU/L (median, 143; range, 13-1000). This small series shows that complete prophylaxis withdrawal is safe in patients transplanted for HBV-related disease at low risk of recurrence and is often followed by spontaneous anti-HBs seroconversion. Further studies are needed to confirm this finding. Liver Transplantation 22 1205-1213 2016 AASLD.
Seroconversion
Hepatitis D virus
Immunosuppression
Hepatitis B
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OBJECTIVE To evaluate the effect of lamivudine on prophylaxis against hepatitis B virus(HBV) reinfection following orthotopic liver transplantation(OLT).METHODS The clinical data of 14 CLT recipients with HBV-related diseases received lamivudine(100mg/day) were retrospectively analyzed in our hospital.Hepatitis B serum markers,serum HBVDNA,and YMDD district variation were detected every two weeks.HBsAg and HBcAg in the liver specimens were examined by immunohistochemistry.Liver biopsy was conducted from the donor during operation and from the recipient postoperatively in a regular interval.RESULTS The reinfection took place in 4 patients and postoperatively(28.6%),HBV-DNA was transfered to the positive in 2 cases,and among them was 1 YMDD district produced and made a variation. Two cases with positive HBV-DNA before liver transplantation had higher HBV reinfection rate postoperatively.CONCLUSIONS Lamivudine monotherapy can effectively and definitely;preven HBV reinfection after liver transplantation HBV reinfection can produce YMDD district and make a variation again;HBV relevant diseases patient should negatively turn the HBV-DNA at the time of competent liver transplantation.
HBcAg
Hepatitis B
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Adefovir
Hepatitis B
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Adefovir
Hepatitis B
Liver disease
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Objective: To compare the effect of lamivudine alone or in combination with hepatitis B immunoglobulin (HBIG) for the prevention of hepatitis B recurrence after liver transplantation. Methods: HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were studied by enzyme-linked immunoassays(EIA), and hepatitis B virus(HBV) DNA by polymerase chain reaction(PCR). Results: Twenty-six patients with HBV-related liver diseases received liver transplantation and were given lamivudine alone or in combination with HBIG during or after the operation. All the patients were followed-up for 3～24 months. Among them, 2 died in 3 and 6 months after liver transplantation, and 4 had HBV recurrence, and the other 20 patients remaine HBsAg negative. Conclusions: Liver transplantation is a useful therapeutic mesure for patients with end-stage hepatitis B. Lamivudine in combination with HBIG is effective in the prevention of hepatitis B recurrence after liver transplantation.
HBeAg
Hepatitis B
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Hepatitis B virus (HBV) recurrence following liver transplantation (LTx) has been controllable primarily with the use of hepatitis B immune globulin (HBIg) and lamivudine (LAM). However, HBV resistance to LAM and/or HBIg has become an increasing problem prompting the use of newer antiviral agents. The purpose of our study was to investigate the association between therapy, HBV breakthrough, and allograft / patient survival in HBV-positive liver transplant recipients. We performed a retrospective review of the medical records of patients that were transplanted for HBV from June 1994 to May 2003. A total of 92 patients, positive for either hepatitis B surface antigen (HBsAg) or HBV deoxyribonucleic acid (DNA) pretransplant, received LAM monotherapy or HBIg (6 months) plus LAM therapy post-liver transplant. HBV breakthrough post-LTx was noted in 14 patients. All patients had detectable HBV DNA prior to liver transplantation; none of the patients that were HBV DNA negative prior to transplant had detectable HBV DNA posttransplant. Of these 14, 9 patients (64%) were switched from LAM to adefovir dipivoxil (ADF) and 5 patients (36%) to tenofovir disoproxil fumarate (TNV). In conclusion, pre-LTx HBV viremia should be considered in planning post-LTx prophylaxis. Trials to evaluate oral antiviral agents in combination with or without HBIg therapy are needed.
Adefovir
Viremia
Hepatitis B
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Objective To evaluate the preventive effect of combination of low-dose HBIg and Nucleoside analogues on recurrence of hepatitis B after liver transplantation. Methods Retrospectively analyzed HBV status and recurrence in patients accepting Nucleoside analogues plus low-dose HBIg as prophylaxis treatment after liver transplantation for HBV-related end-stage liver disease from December 1998 to Octomber 2009 in our center. Results In all the 1506 patients whose survival time >30 d after liver transplantation, 37 patients showed HBV recurrence, the HBV cumulative-recurrence rate of 1, 2, 3, 4, 5 and 6y was 1.3%,2. 4%,2. 7%,2. 9%,3. 7% and 4.6% respectively. The time of recurrence varied from 0. 3 to 66. 6 months (median 12. 8 months) after transplantation. Virus mutation could be tested in 9 cases of the 37 recurrence patients, including 4 YMDD cases, 2 YMDD + YIDD cases, 1 YMDD+YVDD cases, 1 YVDD case,and 1 YIDD case. Conclusions Liver transplantation is the principal therapeutic method for the patient with end-stage liver diseases related to HBV, with the effectively prophylaxis treatment to aim directly at HBV recurrence. If the patients who got HBV recurrence received targeted treatments, the situation can be controlled satisfactorily.
Key words:
Liver transplantation; Hepatitis B virus; Recurrence
Hepatitis B
Liver disease
Nucleoside analogue
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Immunosuppression
Hepatitis B
Regimen
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De novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) always progresses to chronic hepatitis because of the patients' immunocompromised status, and only a few then acquire hepatitis B surface antigen (HBsAg) seroconversion even with efficient antiviral therapy. Here we reported the case of a liver transplant recipient with de novo HBV infection who had a favorable outcome after lamivudine (LAM) and adefovir dipivoxil (ADV) antiviral therapy. The patient received OLT because of end-stage primary biliary cirrhosis and was found to have de novo HBV infection 3 months later. She was treated with LAM, and her serum HBV DNA turned undetectable 2 weeks later. However, serum HBV DNA turned detectable again after 9 months of LAM therapy and a YMDD mutation was detected. The addition of ADV was efficient to treat LAM-resistant HBV. After 3 months of combination therapy, LAM was stopped and ADV monotherapy was continued. HBsAg seroconversion was achieved after an additional 12 months. The prevention and treatment of de novo HBV infection after OLT is discussed.
Adefovir
Seroconversion
Hepatitis B
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Citations (1)