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Lamivudine Monotherapy (lamivudine + monotherapy)
Selected AbstractsLamivudine monoprophylaxis and adefovir salvage for liver transplantation in chronic hepatitis B: A seven-year follow-up study,,JOURNAL OF MEDICAL VIROLOGY, Issue 2 2009Jenny L. Limquiaco Abstract In Asia Pacific countries, lamivudine is used frequently as the sole prophylaxis for hepatitis B virus (HBV) recurrence after liver transplantation due to financial consideration. The aim was to evaluate the long-term outcome of lamivudine monoprophylaxis with adefovir salvage for liver transplantation in chronic hepatitis B. Consecutive chronic hepatitis B patients who received liver transplantation from 1999 to 2003 and with at least 12 months follow up were studied. Lamivudine monotherapy was used for antiviral prophylaxis and adefovir was added as salvage treatment for recurrence of HBV. Twenty-four patients were followed up for 272 (76,372) weeks post-liver transplantation. HBV recurrence developed in seven patients with cumulative probabilities of 8%, 13%, 28%, 35%, 35%, and 49% in 1, 2, 3, 4, 5, and 6 years. At the time of recurrence of HBV, the HBV DNA level was 910,244 (363 to 9,×,108) copies/ml. On direct sequencing, four patients had rtM204I mutation and three patients HBV DNA levels were too low for sequencing. Six patients had elevated ALT (two patients had ALT >1,000 IU/L and jaundice) but none had hepatic encephalopathy. After adefovir treatment for 150 (91,193) weeks, six (86%) patients had normal ALT. HBV DNA was undetectable in two (29%) patients, 100,1,000 copies/ml in two (29%) patients and 10,000,100,000 copies/ml in three (43%) patients on last visit. No genotypic resistance to adefovir was detected. Lamivudine followed by adefovir salvage is effective for prophylaxis of recurrence of HBV after liver transplantation up to 7 years. J. Med. Virol. 81:224,229, 2009. © 2008 Wiley-Liss, Inc. [source] Combination therapy with lamivudine and famciclovir for chronic hepatitis B,infected Chinese patients: A viral dynamics studyHEPATOLOGY, Issue 2 2000George Ka Lau M.D. In vitro studies have shown that lamivudine and penciclovir (the active metabolite of famciclovir) act synergistically to inhibit hepatitis B virus (HBV) replication. We compared the effectiveness of HBV viral suppression by lamivudine monotherapy versus lamivudine plus famciclovir combination therapy in Chinese patients with chronic HBV infection. Twenty-one Chinese hepatitis B e antigen (HBeAg)-positive patients, with detectable HBV DNA (Digene Hybrid Capture II), were randomized to receive either lamivudine 150 mg/d orally (group 1, 9 patients) or lamivudine 150 mg/d plus famciclovir 500 mg 3 times a day orally (group 2, 12 patients) for 12 weeks, with a follow-up period of at least 16 weeks. Serial serum HBV-DNA levels were determined and a mathematical model with provision for incomplete inhibition of virus production during therapy was applied to analyze the dynamics of viral clearance. The mean antiviral efficacy was significantly greater in group 2 than in group 1 (0.988 ± 0.012 vs. 0.94 ± 0.03, P = .0012). HBV DNA returned to pretreatment level within 16 weeks after the end of initial treatment in 4 patients (66.7%) in group 1 and none in group 2 (P = .08), who remained HBeAg positive and received no further treatment after week 12. Hence, in Chinese chronic HBeAg-positive patients, combination therapy using lamivudine and famciclovir was superior to lamivudine monotherapy in inhibiting HBV replication. Further studies of longer duration are needed to define whether combination therapy will increase the HBeAg seroconversion rate and decrease the rate of emergence of lamivudine-resistant variants. [source] Long-term outcome of tenofovir disoproxil fumarate use against hepatitis B in an HIV-coinfected cohortHIV MEDICINE, Issue 5 2009G Alvarez-Uria Objectives Tenofovir disoproxil fumarate (TDF) is active against hepatitis B virus (HBV) and HIV. However, the long-term efficacy of tenofovir disoproxil fumarate (TDF) is not well known and the appearance of resistance is a major concern. We have studied the efficacy of TDF against HBV in patients treated at an Infectious Diseases Unit. Methods We carried out a retrospective observational study of the efficacy of TDF against HBV replication in a cohort of 52 HIV-coinfected patients who received TDF for at least 6 months. Results The median duration of follow-up of TDF treatment was 34 months. Forty-one patients (79%) were positive for HBV envelope antigen (HBeAg) and 35 had received previous lamivudine monotherapy for a median duration of 32 months. Virological breakthrough was observed in nine cases (17%). At the end of the follow-up period, HBV DNA levels were <1000 copies/mL in 42 patients (81%) and <200 copies/mL in 31 patients (60%). There were no significant differences between the lamivudine-naïve and lamivudine-experienced groups. In the lamivudine-experienced group, the duration of previous lamivudine monotherapy was associated with failure to achieve HBV DNA levels <200 copies/mL (P=0.036). Adding lamivudine or emtricitabine to TDF did not improve virological suppression. In 39 patients who achieved <200 HBV DNA copies/mL during TDF treatment, virological breakthrough was seen only in two patients (5%) after a median follow-up duration of 39.7 months. Conclusions TDF was able to control HBV replication in most HIV-coinfected patients after a median follow-up duration of 34 months, regardless of previous lamivudine treatment. However, a sizeable proportion of patients developed virological breakthrough. [source] Combination therapy of thymosin alpha-1 and lamivudine for HBeAg positive chronic hepatitis B: A prospective randomized, comparative pilot studyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2008Hyun Woong Lee Abstract Background and Aim:, Monotherapy of lamivudine, interferon-alpha (IFN-,), and thymosin alpha-1 (T,1) is unlikely to be sufficient for the eradication of a chronic hepatitis B virus (HBV) infection. The aim of our study is to elucidate whether the combination of T,1 and lamivudine is superior to lamivudine monotherapy in hepatitis B e antigen (HBeAg) positive naïve patients with chronic hepatitis B. Methods:, Sixty-seven patients were assigned to two different groups in a randomized manner. The combination group (n = 34) received T,1 (1.6 mg subcutaneously, twice a week) and lamivudine (100 mg orally, daily) for 24 weeks, followed by continuous lamivudine therapy. The monotherapy group (n = 33) received lamivudine monotherapy continuously. Results:, The incidence of HBeAg seroconversion at 24 weeks was 26.5% (9/34) in the combination group and 6.1% (2/33) in the monotherapy group (P = 0.024). However, there was no statistically significant difference between 26.5% (9/34) in the combination group and 12.1% (4/33) in the monotherapy group at 52 weeks (P = 0.138). The emergence of viral breakthrough gradually increased to 35.3% (12/34) in the combination group, and to 21.2% (7/33) in the monotherapy group at 52 weeks (P = 0.201). Conclusions:, The combination treatment of T,1 and lamivudine did not have an obvious benefit of virological and biochemical response as compared to the lamivudine monotherapy during the combination period. In addition, after the cessation of T,1 treatment, the combination therapy did not prevent the occurrence of viral and biochemical breakthroughs. [source] HIV-1 replication capacity and genotype changes in patients undergoing treatment interruption or lamivudine monotherapy,JOURNAL OF MEDICAL VIROLOGY, Issue 2 2008Nicola Gianotti Abstract The objective of this study was to investigate the mechanisms underlying the virological and immunological changes occurring in failing HIV-1 infected patients undergoing treatment interruption or lamivudine monotherapy (the E-184V Study). Associations were sought between the de-selection of individual reverse transcriptase and protease resistance mutations and replication capacity recovery, HIV-RNA changes, and immunological changes. The replication capacity recovery was defined as the ratio between the replication capacity at weeks 24 or 48, and that measured at baseline. The replication capacity recovery, which was evaluable in 21 patients at week 24 and in 18 at week 48, was significantly higher in the treatment interruption than in the lamivudine group at week 24 (P,=,0.002). Forty-eight week replication capacity recovery was greater when the 184V (P,=,0.023), the 41L (P,=,0.02), or the 215Y mutation (P,=,0.037) were deselected at week 12. A greater reduction in the CD4+/CD8+ ratio at week 48 (P,=,0.038) was observed as the 184V mutation was deselected and the de-selection of the 184V mutation at week 12 was the only independent predictor of the change of the CD4+/CD8+ ratio at week 48 from baseline at multivariable analysis (F -value,=,6.72, P,=,0.021). In conclusion, among patients undergoing treatment interruption or lamivudine monotherapy, the recovery of HIV-1 replication capacity was associated with the de-selection of reverse transcriptase mutations. The de-selection of the 184V mutation predicts independently a reduction in the CD4+/CD8+ ratio. J. Med. Virol. 80:201,208, 2008. © 2007 Wiley-Liss, Inc. [source] Prevention of recurrent hepatitis B post,liver transplantationLIVER TRANSPLANTATION, Issue 10B 2002Anna S.F. Lok MD 1Factors associated with a lower rate of recurrent hepatitis B post,liver transplantation (LT) are negative hepatitis B e antigen and/or serum hepatitis B virus DNA pre-LT, hepatitis D virus superinfection, and fulminant hepatitis B. 2Long-term intravenous hepatitis B immune globulin (HBIG) monotherapy can reduce the overall rate of recurrent hepatitis B to 20% to 35%. 3Long-term lamivudine monotherapy is associated with a risk for drug resistance and overall 3-year rate of recurrent hepatitis B of 40% to 50%. 4Combination prophylaxis with HBIG and lamivudine can reduce the overall rate of recurrent hepatitis B to 0% to 10%. 5The dose and duration of HBIG therapy needed when used in combination with lamivudine may be lower, but the optimal regimen remains to be determined. 6Lamivudine resistance before LT is associated with an increased risk for recurrent hepatitis B post-LT. 7A cost-effective prophylactic regimen to prevent recurrent hepatitis B should be tailored according to risk. [source] Transmission of hepatitis B infection from hepatitis B core antibody,positive liver allografts is prevented by lamivudine therapyLIVER TRANSPLANTATION, Issue 6 2001Andy S. Yu Donor shortage has led to the use of hepatitis B core antibody (anti-HBc)-positive (anti-HBc+) liver allografts for patients in need of relatively urgent orthotopic liver transplantation (OLT). Because anti-HBc+ allografts transmit hepatitis B virus (HBV) infection at a high rate, effective prophylaxis is required. We assessed the effectiveness of lamivudine in preventing HBV transmission by anti-HBc+ allografts. Between March 1996 and March 2000 at Cedars-Sinai Medical Center (Los Angeles, CA), 15 of 169 patients (8.9%) received liver allografts from anti-HBc+ donors. Six patients were hepatitis B surface antigen (HBsAg)+ (group 1), and 9 patients were HBsAg negative (HBsAg,; group 2) before OLT. All patients were administered lamivudine, 100 or 150 mg/d, orally after OLT. Patients who were HBsAg+ before OLT also were administered hepatitis B immunoglobulin (HBIG) prophylaxis. Hepatitis B serological tests were performed on all patients, and HBV DNA was determined in liver tissues in 10 patients. All 15 patients remained HBsAg, at their last follow-up 2 to 40 months (mean, 17 months) post-OLT. All patients in group 1 had antibody to HBsAg (anti-HBs) titers greater than 250 mIU/mL post-OLT (mean follow-up, 20 months; range, 7 to 40 months). Of the 2 patients in group 1 who underwent liver biopsy after OLT, 1 patient had detectable hepatic HBV DNA despite being anti-HBs+ and HBsAg,. Among the patients in group 2, none acquired anti-HBc or HBsAg. Hepatic HBV DNA was undetectable in the 7 patients in group 2 who underwent liver biopsy after OLT. Anti-HBc+ allografts can be safely used in patients who undergo OLT for chronic hepatitis B and susceptible transplant recipients if prophylaxis with combination HBIG and lamivudine or lamividine alone is administered after OLT, respectively. However, more data are needed to determine the efficacy of lamivudine monotherapy in preventing transmission of HBV infection from anti-HBc+ liver allografts to susceptible recipients. [source] Lamivudine after hepatitis B immune globulin is effective in preventing hepatitis B recurrence after liver transplantationLIVER TRANSPLANTATION, Issue 4 2000S. Forrest Dodson MD The prevention of recurrent hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) with hepatitis B immunoglobulin (HBIG) is expensive and requires indefinite parenteral administration. Lamivudine is a nucleoside analogue capable of inhibiting HBV replication. The aim of this study is to determine the efficacy of lamivudine in the prevention of recurrent HBV infection after a course of HBIG in patients who were hepatitis B surface antigen (HBsAg) positive and hepatitis Be antigen (HBeAg) negative before OLT. Patients at high risk for recurrent HBV infection (HBeAg positive and HBV DNA positive) were excluded. Thirty HBsAg-positive, HBeAg-negative patients underwent OLT from January 1993 to June 1997. All 30 patients were administered HBIG after OLT and, after 2 years, were given the option of continuing with HBIG or switching to lamivudine. Five patients were excluded: 3 patients were lost to follow-up and 2 patients died of technical complications. Three patients terminated HBIG therapy at 8, 24, and 29 months after OLT, and reinfection with HBV occurred in 1 patient. Six patients elected to continue HBIG therapy for life; 1 patient died of melanoma and the remaining 5 patients are HBsAg negative, with an average follow-up of 73 months. Sixteen patients were converted to lamivudine after a course of HBIG, and all 16 patients are HBsAg negative, with an average follow-up of 51 months after OLT. Five patients have been on lamivudine monotherapy for more than 24 months. These results suggest that lamivudine administered after a posttransplantation course of HBIG can effectively prevent the recurrence of HBV infection in patients who are HBsAg positive and HBeAg negative before OLT. [source] Outcome of lamivudine resistant hepatitis B virus mutant post-liver transplantation on lamivudine monoprophylaxisCLINICAL TRANSPLANTATION, Issue 3 2004Henry Lik-Yuen Chan Abstract:, Background:, We aimed to investigate the clinical outcome of patients who develop lamivudine resistant hepatitis B virus mutants (YMDD mutants) after liver transplantation. Methods:, Patients who received liver transplantation for hepatitis B-related liver diseases from 1999 to 2002 were studied. All patients received lamivudine monotherapy before and after liver transplantation. HBsAg and HBV DNA were regularly monitored, and YMDD mutation was detected by direct sequencing. Results:, Twenty patients were followed up for median 94 wk (range: 15,177 wk) post-liver transplantation. Six patients developed YMDD mutants, and the cumulative probability of developing YMDD mutations post-liver transplantation was 21% in 1 yr and 34% in 2 yr. One patient developed YMDD mutants before liver transplantation and died of hepatitis reactivation and liver failure 15 wk post-transplantation. The other five patients developed YMDD mutants 32,72 wk after liver transplantation. Two of them developed severe hepatitis which responded promptly to adefovir dipivoxil. The remaining three patients with YMDD mutants had minimal to mild hepatitis. The cumulative survival for patients with YMDD mutants was 83% and 28% at 1 and 2 yr, respectively. Only one patient who did not develop YMDD mutants died at week 119 due to chronic rejection. The post-transplant survival for patients with YMDD mutants was significantly poorer than those without YMDD mutants (log rank test p = 0.083). Conclusions:, The emergence of YMDD mutants after liver transplantation on lamivudine monoprophylaxis had wide range of clinical presentations and was associated with increased mortality. [source] | ||||||||||