acyclovir and Hepatitis--Chronic

Topics: Acyclovir; Hepatitis B; Hepatitis C; Hepatitis D; Hepatitis, Chronic; Humans; Interferons; Prednisolone; Vidarabine; Vidarabine Phosphate; Zidovudine

Topics: Acyclovir; Adrenal Cortex Hormones; Combined Modality Therapy; Drug Evaluation; Hepacivirus; Hepatitis C; Hepatitis, Chronic; Humans; Interferon Type I; Pilot Projects; Recombinant Proteins

Topics: Acyclovir; Adrenal Cortex Hormones; Hepatitis B; Hepatitis C; Hepatitis, Chronic; Hepatitis, Viral, Human; Humans; Interferons; Ribavirin

Topics: Acyclovir; Adrenal Cortex Hormones; Antiviral Agents; Drug Therapy, Combination; Hepatitis B; Hepatitis, Chronic; Humans; Interferons; Prognosis; Vidarabine

The realization that spontaneous loss of viral replication in chronic hepatitis B virus carriers was associated with remission, by whatever criteria, led directly to the search for agents or combinations of agents capable of abbreviating the duration of viral replication. Of those assessed to date, only alpha-interferons have gained wide acceptance as single-agent therapy. Treatment must be for three months on an alternate-day basis; on this regimen, at least one third of patients will develop clinical and biochemical evidence of an exacerbation of hepatitis followed by rapid clearance from serum of all markers of viral replication, and in some cases, also of hepatitis B surface antigen. A large proportion of carriers remains insensitive to alpha-interferons, however, and studies based on the combination of interferons with other agents that have proved less effective, but with different modes of action, are in progress and appear promising.

Topics: Acyclovir; Clinical Trials as Topic; Hepatitis B; Hepatitis B virus; Hepatitis, Chronic; Humans; Interferon Type I; Vidarabine; Virus Replication

Topics: Acyclovir; Adrenal Cortex Hormones; Combined Modality Therapy; Drug Evaluation; Hepacivirus; Hepatitis C; Hepatitis, Chronic; Humans; Interferon Type I; Pilot Projects; Recombinant Proteins

The realization that spontaneous loss of viral replication in chronic hepatitis B virus carriers was associated with remission, by whatever criteria, led directly to the search for agents or combinations of agents capable of abbreviating the duration of viral replication. Of those assessed to date, only alpha-interferons have gained wide acceptance as single-agent therapy. Treatment must be for three months on an alternate-day basis; on this regimen, at least one third of patients will develop clinical and biochemical evidence of an exacerbation of hepatitis followed by rapid clearance from serum of all markers of viral replication, and in some cases, also of hepatitis B surface antigen. A large proportion of carriers remains insensitive to alpha-interferons, however, and studies based on the combination of interferons with other agents that have proved less effective, but with different modes of action, are in progress and appear promising.

Topics: Acyclovir; Clinical Trials as Topic; Hepatitis B; Hepatitis B virus; Hepatitis, Chronic; Humans; Interferon Type I; Vidarabine; Virus Replication

For patients with chronic hepatitis B e (HBe)-positive hepatitis, long-term results of pilot studies with lymphoblastoid interferon-alpha, acyclovir, or a combination, and of a randomized controlled trial of interferon/desciclovir combination therapy are presented. HBe seroconversion was observed in more than 40 percent of patients treated with combination therapy, 30 percent with interferon therapy, 18 percent with acyclovir, and 0 percent with no treatment. HBe reactivation occurred in two patients with cirrhosis. Hepatitis B surface seroconversion followed HBe seroconversion in 11 to 30 percent of treated patients. HBe seroconversion was significantly related to initial low levels of viral replication and to transient aminotransferase elevation during the second half of the interferon treatment of 16 weeks. Clinical improvement and persistent normalization of aspartate aminotransferase was observed in all patients with HBe seroconversion. Conversion to a state of virus latency (HBe negative) mostly occurred after therapy, suggesting that the specific immunologic host response had been brought about by the suppression of virus replication through antiviral agents. Recommendations for selection of patients for antiviral combination therapy are made on the basis of these long-term results.

Topics: Acyclovir; Adult; Clinical Trials as Topic; Drug Therapy; Female; Follow-Up Studies; Hepatitis B; Hepatitis, Chronic; Humans; Interferon Type I; Male; Pilot Projects; Prodrugs; Random Allocation; Time Factors

The possible enhancement effect of acyclovir or its prodrug descyclovir in combination with human lymphoblastoid interferon (Wellferon) was studied in three trials with a total of 146 patients with chronic hepatitis B; a pilot study (Study 1; n = 12), two randomized controlled studies, one with a combination of descyclovir and interferon (Study 2; n = 36) and the other using acyclovir and interferon (Study 3; n = 98). The results from Study 1 and 2 showed that combination therapy with interferon and acyclovir or descyclovir (n = 25) was associated with a 40% HBe+ seroconversion rate, compared to 30% with interferon treatment alone (n = 10), 18% with acyclovir alone (n = 11) and 0% with no treatment (n = 18). Preliminary results from Study 3 on rate of HBe-seroconversion are similar to previous studies. Antiviral therapy with interferon and acyclovir or its prodrug, have resulted in significantly enhanced HBe seroconversion. The intravenous acyclovir component of combination therapy is however cumbersome and research should be directed towards finding an oral anti-hepatitis drug.

Topics: Acyclovir; Adolescent; Adult; Aged; Combined Modality Therapy; Hepatitis B; Hepatitis B e Antigens; Hepatitis, Chronic; Humans; Interferon Type I; Middle Aged; Prodrugs

Topics: Acyclovir; Adult; Antiviral Agents; Drug Therapy, Combination; Female; Hepatitis B; Hepatitis B e Antigens; Hepatitis, Chronic; Humans; Interferon Type I; Male

In a previous study a partial inhibition of viral replication was observed in HBeAg-positive patients after acyclovir (ACV) treatment. To assess those results and to evaluate different treatment regimens, a randomized controlled trial with ACV given at 45 mg/kg/day by continuous infusion (in 5 patients) or by intermittent 8-hourly infusion (in 6 patients) for 28 days versus placebo has been performed in 20 patients affected by chronic hepatitis positive for both HBsAg and HBeAg for at least 6 months. Patients were stratified for sex, presence of cirrhosis and homosexual activity. Modest inhibition of serum DNA polymerase activity was observed after intermittent ACV treatment but not with the continuous infusion. After a 8-12 months follow-up, 2 of 10 of the ACV-treated patients and 3 of the controls had become HBeAg-negative, with 1 and 2 seroconversions to anti-HBe in the treated and placebo group respectively. No adverse effects were observed in ACV-treated patients after continuous infusion, but 2 of 6 patients who received intermittent therapy had to stop treatment, because of abdominal colics and elevation of the serum creatinine. Our data confirm that ACV partially inhibits viral replication in HBeAg-positive patients but without significantly affecting the rate of seroconversion to anti-HBe.

Topics: Acyclovir; Adult; Clinical Trials as Topic; Female; Hepatitis B; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis, Chronic; Humans; Male; Middle Aged; Random Allocation; Virus Replication

A clearer view of the natural history of chronic hepatitis B virus (HBV) infection has permitted recognition of a phase of viral replication associated with progressive liver damage, and one of absent replication when the disease is inactive and when continued presence of hepatitis B surface antigen (HBs) is due to the integration of viral genes with the host genome. These two phases can be identified by HBe antigenaemia and anti-HBe, respectively. Several active antiviral drugs are available and may significantly benefit certain HBe Ag-positive groups. The antiviral activity of vidarabine and its analogues and of alpha-interferons is established, and insight is being gained into factors that predict response. In general, results depend on duration of infection, and integrity of the patient's immune response. Anti-HBe positive carriers usually need no treatment, but in those with continuing low-level HBV replication or delta superinfection antiviral therapy, although of unproven value, may be tried. In patients without HBV or hepatitis delta virus (HDV) replication who have signs of active disease, immunosuppressants may be tried with benefit.

Topics: Acyclovir; Clinical Trials as Topic; Hepatitis B; Hepatitis B Antibodies; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis D; Hepatitis, Chronic; Humans; Interferon Type I; Vidarabine

In a retrospective study we investigated the antiviral effect of alpha-interferon in 100 patients with chronic hepatitis B who were treated in controlled trials conducted in Rotterdam (1985-1990). The aim of the treatment was to induce viral latency as indicated by HBeAg seroconversion. Alpha-interferon was administered in a dose of 5 mega-units per day subcutaneously. Sixty-two patients received alpha-interferon for 16 weeks combined with a second antiviral agent (acyclovir or descyclovir) while the other 38 patients were treated with alpha-interferon monotherapy during 20 to 34 weeks. Follow-up continued until 1 year after the start of therapy. Thirty-eight per cent of the patients exhibited an HBeAg seroconversion and 9% exhibited an HBsAg seroconversion indicating a complete eradication of the virus. After 1 year transaminase levels were normalised in 70% of the patients with HBeAg seroconversion compared with 22% in those without seroconversion (p less than 0.05). The combination therapy for 16 weeks and the alpha-interferon monotherapy of longer duration resulted in HBeAg seroconversion rates of 29% and 53%, respectively (p less than 0.05). The predominant adverse effects were fatigue, flue-like illness and leukopenia. Serious side effects such as seizures, psychosis and peripheral neuropathy occurred in seven patients. Side effects led to a dose reduction in 26% of the patients. Alpha-interferon is effective in terminating the virus replication in chronic hepatitis B. However, both the common mild and the uncommon major side effects necessitate intensive patient monitoring during alpha-interferon treatment.

Topics: Acyclovir; Adult; Aged; Female; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis, Chronic; Humans; Interferon-alpha; Liver Function Tests; Male; Middle Aged; Prodrugs; Retrospective Studies

Eleven patients in early stages of chronic active hepatitis B (CAH-B) were treated for weeks or months with a natural or recombinant human interferon alpha (Hu IFN alpha). Changes of serum levels of selected hepatitis B virus (HBV) markers were observed after Hu IFN alpha administration. Increase of HBsAg level accompanied by more or less simultaneous HBeAg level depression was the most interesting observation. These changes were well expressed in 5 reactive patients only; they usually ceased after withdrawal of IFN therapy. Reaction of the remaining 6 patients was either poor or not demonstrable. The possible mechanism for HBsAg/HBeAg serum level changes during the IFN therapy of CAH-B is discussed.

Topics: Acyclovir; Adrenal Cortex Hormones; Combined Modality Therapy; Hepatitis B; Hepatitis B Antibodies; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis, Chronic; Humans; Immunoglobulin M; Immunotherapy; Interferon Type I; Time Factors; Transfer Factor

Topics: Acyclovir; Azathioprine; Chronic Disease; Drug Evaluation; Drug Therapy, Combination; Hepatitis; Hepatitis, Chronic; Hepatitis, Viral, Human; Humans; Prednisone; Vidarabine

Topics: Acyclovir; Antiviral Agents; Drug Therapy, Combination; Hepatitis, Chronic; Humans; Interferons; Virus Replication

Acyclovir only demonstrated activity in CAH patients with low HBV replication (DNA-p less than or equal to 80 cpm). In those, oral acyclovir 4 g/day for 4 months was able to permanently inhibit DNA-p in 5/5 cases without significant side-effects.

Topics: Acyclovir; Hepatitis B; Hepatitis B virus; Hepatitis D; Hepatitis, Chronic; Humans; Interferons; Vidarabine; Virus Replication

Chronic hepatitis B patients with active viral replication were treated with acyclovir, either orally 800 mg 4 times daily, or intravenously 15 mg/kg twice daily; duration of treatment was 4 weeks. A second course of intravenous acyclovir (15 mg/kg twice daily for 2 weeks) was given to 5 patients in combination with intramuscular lymphoblastoid alpha-interferon treatment (2.5 MU/m2, once daily). Oral acyclovir had no detectable effect on DNA-polymerase or HBeAg. Intravenous acyclovir alone depressed HBV replication and HBeAg, followed by prolonged negativity of DNA-polymerase in 4 out of 11 patients. Combination therapy of acyclovir with interferon had a significantly greater fall in DNA-polymerase and HBeAg than acyclovir alone. Apart from thrombophlebitis, therapy with acyclovir was tolerated well provided fluid intake was more than 2 litres daily. The combination therapy of acyclovir with interferon appears the most promising for conversion of a state of active viral replication into virus latency.

Topics: Acyclovir; Hepatitis B; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis, Chronic; Humans; Interferon Type I; Male; Virus Replication

Patients with chronic hepatitis B and active viral replication had no change in DNA-polymerase (DNA-p) and HBeAg when treated with weekly injections of lymphoblastoid alpha-interferon (IFN) for 4-10 weeks. Daily IFN (2.5 MU/m2 for a period of 4 weeks) was associated with a significant fall (P less than 0.05) in DNA-p but not in HBeAg; DNA-p remained or became negative in 3 out of 10 patients after stopping therapy. Combination of IFN and intravenous acyclovir (ACV, 15 mg/kg twice daily) led to a significantly greater fall in DNA-p and HBeAg, while tolerance of the combination therapy was excellent. Four out of 5 patients became DNA-p-negative and three HBeAg-negative; subsequently two became HBsAg-negative with anti-HBs. We conclude that weekly IFN appears ineffective. Daily IFN depressed hepatitis B virus replication, but does not change markedly the natural course of the disease. Combination therapy with ACV may be more effective than IFN alone and is well tolerated.

Topics: Acyclovir; DNA-Directed DNA Polymerase; Hepatitis B; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis, Chronic; Humans; Interferon Type I; Male; Virus Replication

Ten patients were entered into an open study of interferon (IFN) 'induction' and oral acyclovir (ACV) 'maintenance' therapy. They received 5 Mega units (Mu)/m2 IFN by intramuscular injection daily for 3 days, followed by 7.5 Mu/m2 IFN daily for 7 days. IFN therapy was then discontinued and a 6-week course of oral ACV at a dose of 800 mg 4 times daily commenced. At 6 months, 2 patients had become HBeAg-negative and 1 had developed anti-HBe. Elimination of HBeAg in these patients was accompanied by return of serum liver function tests to normal. There was a statistically significant inhibition of DNA polymerase levels after the 1st week of IFN therapy, which then slowly increased to pretreatment values over 8 weeks. There were no significant adverse effects of ACV therapy, while fever, 'flu-like illness', fatigue, anorexia, and leucopenia were the main side-effects observed during the course of IFN which necessitated dose reduction in 7 patients. Combination therapy appears to effectively inhibit viral replication, although the 'maintenance' effect of oral ACV is minimal. A more effective drug to combine with IFN is needed.

Topics: Acyclovir; Female; Hepatitis B; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis, Chronic; Humans; Interferon Type I; Male; Virus Replication