Famvir
[Experimental study on the effect of combination therapy with lamivudine and famciclovir against duck hepatitis B virus in vivo]

[Article in Chinese]

Chen Y, Guo S, Qi Z, Huang A.

Institute for Viral Hepatitis, Chongqing University of Medical Sciences, Chongqing 400010, China.

OBJECTIVE: To study the antiviral effect of combination therapy with the nucleoside analog lamivudine and famciclovir on duck hepatitis virus (DHBV) in vivo. METHODS: The Chongqing duck hepatitis B model was treated with lamivudine and famciclovir by intragastric administration for 4 weeks. DHBV DNA and DHBsAg in serum were observed by serum dot-blot hybridization and ELISA. ALT and AST in serum were also detected. Histological observation on the duck liver was done simultaneously. The trial was contrasted with a single acyclovir (ACV), famciclovir (FCV), or Lamivudine (3TC). RESULTS: Combination therapy with Lamivudine and famciclovir could significantly reduce the serum DHBV DNA level. After stopping the treatment for 1 week, serum DHBV DNA level did not return significantly. The change of DHBsAg was similar to DHBV DNA. The level of ALT, AST, and the features of liver histopathology in combination-treated ducks were not different from those in control ducks. CONCLUSIONS: The study confirms that combination therapy is superior to single antiviral agent in vivo for ducks with chronic DHBV carrier.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11602049&dopt=Abstract famciclovir Famvir



Famvir
Preoperative antiviral treatment and postoperative prophylaxis in HBV-DNA positive patients undergoing liver transplantation.

Seehofer D, Rayes N, Naumann U, Neuhaus R, Muller AR, Tullius SG, Berg T, Steinmuller T, Bechstein WO, Neuhaus P.

Department of Visceral and Transplant Surgery, Charite Campus Virchow, Augustenburger Platz 1, D-13353 Berlin, Germany.

BACKGROUND: Despite passive immunoprophylaxis a significant number of patients, especially if hepatitis B virus (HBV) DNA is positive prior to transplantation, develop HBV recurrence. This number might be reduced by lowering viral replication pretransplant with antiviral agents and by postoperative combination of antiviral agents and passive immunoprophylaxis. PATIENTS AND METHODS: A total of 74 HBV-DNA positive patients who underwent liver transplantation between 9/88 and 4/00 were analyzed retrospectively. Before lamivudine or famciclovir were available, in total 40 patients did not receive any preoperative antiviral therapy. Since 11/93, 17 patients were treated with famciclovir 1500 mg daily, after 4/96 17 patients with lamivudine 150 mg daily prior liver transplantation. Posttransplant all patients received passive immunoprophylaxis aiming at a titer of more than 100 U/liter. In the 34 patients with preoperative antiviral therapy an additional prophylaxis with the respective antiviral agent was applied. RESULTS: Under preoperative famciclovir and lamivudine 30 and 71% of patients became HBV-DNA negative, respectively. Actuarial reinfection rate 2 years after liver transplantation was 48% without antiviral prophylaxis, which was not statistically different from 55% under perioperative famciclovir therapy. In contrast only 18% developed HBV recurrence under perioperative lamivudine treatment. During both antiviral regimens neither pre nor posttransplant severe side effects were observed. CONCLUSION: Perioperative application of famciclovir is not recommendable, whereas lamivudine seems to lower recurrence rates significantly. Whether the observed effect is due to pre- or postoperative application remains to be addressed in further studies. In addition the long-term course has to be awaited.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11685107&dopt=Abstract famciclovir Famvir



Famvir
Failure of combination therapy with lamivudine and famciclovir following lamivudine monotherapy for hepatitis B virus infection in patients coinfected with human immunodeficiency virus-1.

Matthews GV, Pillay D, Cane P, Ratcliffe D, Gazzard B, Nelson M.

Department of HIV Medicine, Chelsea & Westminster Hospital, SW10 9NH London, United Kingdom.

Individuals coinfected with human immunodeficiency virus 1 (HIV-1) and hepatitis B virus (HBV) often receive treatment with an antiretroviral regimen including lamivudine. Lamivudine monotherapy for HBV may lead to drug-resistant mutations in a significant number of patients. The virological and biochemical responses of 8 patients coinfected with HBV/HIV-1 treated with both lamivudine and famciclovir were studied. Patients exhibiting HBV viral rebound at 1 year were analyzed for the emergence of HBV polymerase mutations. Only 1 patient had no prior exposure to lamivudine. Addition of famciclovir to the treatment regimen resulted in a median fall in HBV DNA level of 0.33 log(10) at 3 months and an overall rise in HBV DNA level of 3 log(10) at 12 months. The only patient in whom durable viral suppression and HBV e antigen seroconversion were noted began receiving lamivudine and famciclovir simultaneously. HBV polymerase gene sequencing identified resistance-associated mutations in 6 of 7 patients with viral rebound. Sequential nucleoside analogue therapy is unlikely to be successful in achieving long-term suppression of HBV replication, and combination therapy should be considered at treatment initiation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11698987&dopt=Abstract famciclovir Famvir



Famvir
Occurrence and clinical outcome of lamivudine-resistant hepatitis B infection after liver transplantation.

Seehofer D, Rayes N, Steinmuller T, Muller AR, Settmacher U, Neuhaus R, Radke C, Berg T, Hopf U, Neuhaus P.

Department of General, Visceral, and Transplant Surgery, Campus Virchow, Humboldt University of Berlin, Germany. daniel.seehofer charite.de

Lamivudine treatment of hepatitis B after orthotopic liver transplantation (OLT) is often accompanied by fast viral-resistance formation. Although no clinical data are available, in vitro data indicate that lamivudine-resistant reinfection has a mild course because of defective viral replication. Between 1996 and 1999, a total of 34 patients were treated with lamivudine because of hepatitis B recurrence after OLT. All patients developed reinfection despite long-term passive immunoprophylaxis with hepatitis B immunoglobulin, diagnosed by positive hepatitis B surface antigen and positive hepatitis B virus (HBV) DNA. Before treatment with lamivudine, 21 of these patients underwent a course of famciclovir and developed resistance. Monthly laboratory tests and sequential liver biopsies were performed during the follow-up period. Nineteen of 34 patients (56%) developed lamivudine resistance during the follow-up period of 12 to 49 months. One- and 3-year graft survival rates after the diagnosis of lamivudine resistance were 89% and 66%, respectively. In most cases, lamivudine resistance was associated with high viral replication (3,012 +/- 574 pg/mL 1 month after the diagnosis of lamivudine resistance); however, liver enzyme levels were only moderately elevated (alanine aminotransferase [ALT], 45 +/- 16 U/L). Only 3 patients (15%) showed a rapid increase in ALT level to more than 500 U/L within 3 months after resistance developed. All other patients had mildly elevated liver enzyme levels during the first 6 to 8 months after lamivudine resistance. In the later course, liver enzyme levels increased in most patients. Fourteen patients with elevated transaminase levels were switched to lamivudine plus interferon alfa (n = 8) or lamivudine plus famciclovir therapy (n = 6). This combination was successful in most cases, decreasing HBV DNA and liver enzyme levels. Four patients with lamivudine resistance died during follow-up, only 1 patient because of HBV reinfection. In addition, 2 patients underwent retransplantation because of hepatitis B cirrhosis of the first graft. Compared with historic courses of wild-type recurrence, lamivudine-resistant reinfection is characterized by a milder clinical course. Fulminant cases were not observed; however, in three cases, chronic liver failure developed. The combination of different antivirals diminished viral replication after lamivudine resistance. In the future, new antiviral agents, such as adefovir, might further expand therapeutic options.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11699034&dopt=Abstract famciclovir Famvir



Famvir
Experimental studies on the antiviral agent famciclovir in Behcet's disease symptoms in ICR mice.

Sohn S, Bang D, Lee ES, Kwon HJ, Lee SI, Lee S.

Laboratory of Cell Biology, Ajou University Institute for Medical Sciences, Suwon 442-721, Korea. sohnsh madang.ajou.ac.kr

BACKGROUND: Chronic oral aphthae, recurrent genital ulcers and uveitis are the three main manifestations of Behcet's disease (BD). The aetiopathogenesis of BD is still obscure, but herpes simplex virus (HSV) is one of the possible causal factors. Various kinds of drugs, including immunosuppressants and aciclovir have been used in treatment, but effectiveness is variable. OBJECTIVES: To demonstrate the efficacy of famciclovir, an antiviral compound that acts against HSV, varicella-zoster virus and hepatitis B virus, in a murine model of BD. METHODS: Using the HSV-induced BD mouse model, famciclovir was administered variously before and after inoculation or from the day of lesion occurrence, with appropriate controls. Ulceration of the mouth and genital skin and eye involvement were monitored. In addition, spleen cytokine expression was measured by polymerase chain reaction. RESULTS: Pretreatment and concurrent treatment did not affect the occurrence of BD, but treatment from the appearance of lesions was effective in improving BD and preventing recurrence. After famciclovir, interleukin 2 expression correlated with the recurrence of BD symptoms. CONCLUSIONS: This model suggests the possible role of immune response to viral infection in the development and activation of BD. The study provides a rationale for clinical trials of famciclovir in the human form of BD.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11736905&dopt=Abstract famciclovir Famvir