TREATMENT OF HEPATITIS B-RELATED POLYARTERITIS NODOSA WITH FAMCICLOVIR AND INTERFERON ALFA-2B.

Kruger M; Böker KH; Zeidler H; Manns MP; Department of Gastroenterology and Hepatology, Medizinische Hochschule Hannover, Germany. J Hepatol, 1997 Apr, 26:4, 935-9

BACKGROUND: The association between polyarteritis nodosa and viral hepatitis B infection is well established and still remains a therapeutic challenge. Famciclovir--a new nucleoside analog--has a broad spectrum of antiviral activity against herpes viruses and the human hepatitis B virus. CASE REPORT: A 56-year-old man with hepatitis B-related polyarteritis nodosa presented with symptoms correlating to high levels of HBV DNA. The patient did not respond to treatment with steroids (prednisolone started with 100 mg daily) and two courses of interferon alfa-2b (5 x 10(6) units 3 times per week for 6 months). Therefore, a combination therapy of interferon alfa-2b (5 x 10(6) units 3 times per week) and famciclovir (500 mg tid, orally) was started; 5 mg daily prednisolone was given at this time. Under this regimen HBV DNA rapidly declined, with a reduction of 79% after the first week (HBV DNA 53 pg/ml), and 88% after the second week (29 pg/ml), accompanied by a significant improvement in clinical symptoms. After 1 year of famciclovir treatment, HBeAg-anti-HBe seroconversion was noted; HBsAg still remained positive. Long-term famciclovir therapy has been continued at a reduced dose of 125 mg tid for 3 years now. HBV DNA values have been stable below 100 pg/ml, transaminases have normalized and clinical symptoms of polyarteritis nodosa have disappeared. CONCLUSIONS: Famciclovir has been successfully administered to a patient with hepatitis B-related polyarteritis nodosa. A reduction in viral replication and an improvement of symptoms were noted within 4 weeks of starting famciclovir. The oral nucleoside analog famciclovir is effective and well tolerated, even in long-term therapy, and might offer new treatment options in immunosuppressed patients for whom hepatitis B replication is critical for the disease process.

PRETRANSPLANT FAMCICLOVIR AS PROPHYLAXIS FOR HEPATITIS B VIRUS RECURRENCE AFTER LIVER TRANSPLANTATION.

Singh N; Gayowski T; Wannstedt CF; Wagener MM; Marino IR; Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Veterans Affairs Medical Center, Pennsylvania 15240, USA. Transplantation, 1997 May 27, 63:10, 1415-9

Liver transplantation in patients with detectable hepatitis B virus (HBV) DNA is associated with a high rate of HBV recurrence and detectable HBV DNA is often considered a contraindication for live transplantation. Famciclovir, an oral form of the purine nucleoside penciclovir, has been shown to inhibit HBV replication. This pilot study was conducted to determine whether a 6-month course of famciclovir, administered before transplantation, was effective in inhibiting HBV replication in patients with end-stage liver disease caused by HBV and detectable HBV DNA and to assess the posttransplant clinical and virologic outcome of patients becoming HBV DNA negative with famciclovir prior to transplantation. All eight patients enrolled were hepatitis B surface antigen (HBsAg) positive; their HBV DNA levels at baseline ranged from 4.3 to 25,321 pg/ml (mean 3,661 pg/ml). Six of the eight patients were also seropositive for HBeAg. An initial decline in HBV DNA titers occurred in all patients; however, only 25% (two of eight) of the patients became HBV DNA negative before transplantation and underwent liver transplantation. Seroconversion to hepatitis B surface antibody (HBsAb) (and HBeAb in HBeAg-positive patient) was demonstrated at the conclusion of famciclovir in the transplanted patients. Both patients remain HBV DNA negative at nearly 2 years of follow-up after transplantation. HBV DNA remained detectable in 63% (five of eight) of the patients. The mean HBV DNA level for patients who became HBV DNA negative was 5.1 pg/ml versus 424 pg/ml in nonresponders. Adverse effects attributable to famciclovir were not observed in any of the patients. Future studies should assess the predictors of response to famciclovir so that patients likely to achieve good virologic outcome can be targeted for such a therapy.

FAMCICLOVIR THERAPY FOR RECURRENT HEPATITIS B VIRUS INFECTION AFTER LIVER TRANSPLANTATION

Haller GW; Bechstein WO; Neuhaus R; Raakow R; Berg T; Hopf U; Neuhaus P; Department of Surgery, Virchow Clinic, Humboldt University of Berlin, Germany. Transpl Int, 1996, 9 Suppl 1:, S210-2

Between November 1993 and June 1995 18 patients received oral famciclovir (3 x 500 mg) for treatment of hepatitis B virus (HBV) reinfection after liver transplantation. Reinfection was defined as the reoccurrence of HBsAg in the serum. In the first 15 patients, famciclovir therapy was initiated after clinical signs of graft hepatitis, whereas the last 3 patients received treatment immediately after HBV-DNA was detected. Famciclovir was well-tolerated in all patients. HBV-DNA values were decreased to undetectable levels in 8 out of 18 patients. Clinical status improved in 7 patients, whereas 5 patients remained unchanged and 6 patients progressed to deteriorating graft function and death. When famciclovir was initiated early after reinfection, a response rate of approximately 66% was observed. Late onset of therapy in patients with fulminant hepatitis generally failed to provide any clinical benefit.

NEW THERAPIES FOR CHRONIC HEPATITIS B

Hoofnagle JH; Lau D; Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda 20892, USA. J Viral Hepat, 1997, 4 Suppl 1:, 41-50

Currently, the only therapy of proven benefit in chronic hepatitis B is interferon-alpha which leads to a long-term benefit in only one-third of patients. New therapies for hepatitis B fall into three categories; antiviral chemotherapy, immunomodulation with cell-based therapies, vaccines or cytokines, and gene therapy such as with antisense oligonucleotides, ribozymes or viral mutants. The most promising immediate approach to therapy is with the new nucleoside antivirals--lamivudine and famciclovir. These drugs are well absorbed orally, result in profound inhibition of circulating hepatitis B virus, and, in some cases, loss of hepatitis B e antigen and improvement in serum aminotransferases. Controlled trials of long-term famciclovir and lamivudine therapy currently underway aim to show whether these drugs are safe and can provide sustained inhibition of viral replication and attentant improvement in liver disease.

NEW FINDINGS ON THE ETIOPATHOGENESIS AND CLINICAL MANIFESTATIONS OF EPSTEIN-BARR VIRUS INFECTIONS

Brkic S; Jovanovic; Klinika za infektivne i dermatoveneroloske bolesti, Medicinski fakultet, Novi Sad. Med Pregl, 1996, 49:5-6, 194-8

Epstein-Barr virus is an ubiquitous member of the human herpes virus family. A specific antigen structure of the Epstein-Barr virus was discovered in the last decade. It was possible to diagnose some unusual clinical manifestations of EBV infections and its clinical course by different serologic analyses (immunofluorescent tests, immunoenzyme assay and polymerase chain reaction). This is very important in cases of atypical primary infections (hepatitis, meningoencephalitis), chronic mononucleosis and lymphoproliferative disorders and nasopharyngeal carcinoma. Famciclovir, a new antiviral agent (peroral form of penciclovir) may play an important role in the therapy of these infections.

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