Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several first-generation nucleoside analogues have been tested against chronic hepatitis B virus (HBV) infection, but trials were unsuccessful or accompanied by toxicity. Recently, oral second-generation nucleoside analogues have been developed that have potent activity against HBV. The best-studied compound so far is lamivudine ((-)2'-deoxy-3'-thiacytidine; 3TC). Lamivudine is an inhibitor of reverse transcriptase (RT) activity and is in clinical use in human immunodeficiency virus (HIV)-infected individuals. As several studies on the use of lamivudine for hepatitis B show, the development of resistance in the viral polymerase under lamivudine treatment, however, causes a significant clinical problem. All other drugs in advanced clinical development for HBV are nucleosides; cross-resistance is therefore expected in most cases. The history of HIV treatment demonstrates that new classes of drugs, the protease inhibitors and non-nucleosidic inhibitors of RT, allowed for a longer-term clinical benefit when used in combination with nucleoside analogues. The development of non-nucleosidic compounds with different modes of action therefore appears very important for the treatment of chronic hepatitis B as well.
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PMID:Development of resistance and perspectives for future therapies against hepatitis B infections: lessons to be learned from HIV. 1088 29

Although antiviral prophylaxis with lamivudine monotherapy appears to reduce post-liver transplantation recurrence of hepatitis B virus (HBV) infection, breakthrough infections occur in at least 20% of the patients because of the development of drug resistance. Combined lamivudine and intravenous hepatitis B immune globulin (HBIG) therapy (10,000-IU doses) may reduce this risk, but its use is limited by cost ( approximately US $45,000/yr) and availability. We report the experience at liver transplant centers in Australia and New Zealand in which lamivudine has been used in combination with much lower doses of HBIG than used in conventional HBIG prophylaxis. Lamivudine, 100 mg/d, was administered to hepatitis B surface antigen (HBsAg)-positive candidates on listing for transplantation and was continued posttransplantation. HBIG, 400 or 800 IU, was administered intramuscularly (IM) daily for 1 week from transplantation and monthly thereafter. Thirty-seven HBsAg-positive patients underwent transplantation using this protocol. Thirty-six of these patients were HBV DNA positive by polymerase chain reaction (PCR) or hybridization assay. Thirty-four patients had chronic HBV, 2 patients had hepatitis B and C, and 1 patient had hepatitis B, C, and D. Five patients died within 1 month of transplantation and are not included in the analysis. Mean follow-up in the remaining 32 patients was 18.4 months (range, 5 to 45 months). Treatment was well tolerated, with no significant adverse events. Thirty-one of 32 patients were HBsAg negative, and all 32 patients were HBV DNA negative by PCR at latest follow-up. The cost of treatment was US $967 for lamivudine and between $2,290 and $4,480/yr for IM HBIG. Lamivudine and low-dose HBIG treatment prevents posttransplantation recurrence of hepatitis B and is likely to be more cost-effective than high-dose HBIG regimens.
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PMID:Combination low-dose hepatitis B immune globulin and lamivudine therapy provides effective prophylaxis against posttransplantation hepatitis B. 1091 63

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.
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PMID:Lamivudine after hepatitis B immune globulin is effective in preventing hepatitis B recurrence after liver transplantation. 1091 64

Many nucleoside analogues have been investigated for the treatment of chronic hepatitis B. Some were withdrawn because of significant adverse effects and some are still in the early stage of clinical assessment. Lamivudine has been demonstrated to have consistent efficacy and safety in large-scale, phase III clinical trials. It has achieved a milestone in the treatment of chronic hepatitis B and is now commercially available in many countries. Being a potent inhibitor of hepatitis B viral replication, it achieved around 18% HBeAg seroconversion in HBeAg-positive patients after 1 year of therapy. HBeAg seroconversion is a good endpoint for therapy and has been shown to be 80% durable. The response was better among patients with raised pretreatment alanine aminotransferase levels. Liver necro-inflammation and fibrosis improved significantly after 1 year. Further improvement on extended therapy was observed together with an incremental increase in HBeAg seroconversion. Similar efficacy was demonstrated in HBeAg-negative viraemic patients. The main drawback is the emergence of drug-resistant variants starting from the sixth to ninth month of treatment. This can be associated with varying degrees of relapse of disease activity and may offset the benefit of therapy. With extended therapy, drug-resistant variants continue to emergence at a rate of around 20% per year. Adefovir dipivoxil and entacavir are nucleoside or nucleotide analogues shown to suppress both the wild-type and lamivudine-resistant virus. Combination of these nucleoside/nucleotide analogues with immune modulators may be the answer to eradicate the virus in short-term therapy and avoid the issue of drug resistance.
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PMID:Nucleoside analogues in the treatment of chronic hepatitis B. 1092 83

We report the case study of a 1-year-old girl who was perinatally infected with both hepatitis B (HBV) and HIV viruses. The clinical presentation and treatment are described. We examined the interaction between the 2 viruses and the possible effects of the interaction on the development of each virus and on treatment. Our findings demonstrate that combined HIV and HBV infections intensified deterioration, as the HBV liver disease aggravated the HIV infection. The medication of choice was Lamivudine, since it prevents the transcription of both viruses.
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PMID:[Perinatal co-infection with hepatitis B and HIV viruses--reciprocal effect of the disease and the treatment]. 1095 7

Hepatitis B infection of a liver allograft can have serious consequences including a negative influence on the probability of survival. Therefore, there is a need for very effective antiviral therapy for transplant recipients. In this article the early experience with nucleoside analogue antiviral agents, both to prevent and to treat hepatitis B in liver allografts, is reviewed. There are several important characteristics of these agents that are already apparent. Ganciclovir and famciclovir have limited efficacy in treating infections when they are used alone. These compounds might be beneficial if used after resistance develops to other drugs or when used in combination with other agents. Lamivudine is effective for about two-thirds of patients in preventing and treating hepatitis B infection in allografts. Hepatitis B immune globulin (HBIg) is known to increase the efficacy of lamivudine in preventing infection. A large study to further characterize this combination therapy is being organized. Resistance to famciclovir and lamivudine can occur if they are used alone for a long time. In order to lower the incidence of drug resistance, it may be necessary to utilize combinations of nucleoside analogues.
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PMID:Antiviral therapy to prevent and treat hepatitis B virus infection in hepatic allografts. 1096 61

It has been suggested that hepatitis B e antigen (HBeAg) seroconversion after lamivudine therapy is durable in Caucasians with chronic hepatitis B (CHB). However, little is known whether it is also durable in endemic areas of hepatitis B virus (HBV) infection. We evaluated the posttreatment durability of lamivudine-induced HBeAg seroconversion and the predictive factors for relapse in Korean patients with CHB. We retrospectively analyzed 98 HBeAg-positive patients with CHB who were treated with lamivudine between August 1996 and December 1997. Lamivudine was given at a dose of 150 mg per day. After HBeAg seroconversion, lamivudine was continued for an additional 2 to 4 months, and posttreatment monitoring continued for up to 24 months. HBeAg seroconversion was achieved in 34 of the 98 patients (34.7%). The mean duration of treatment in these seroconverters was 9.3 +/- 3.0 months. During the follow-up period, the cumulative relapse rates at 1 year and 2 years posttreatment were 37.5% and 49.2%, respectively. Most relapses were accompanied by elevation of serum alanine transaminase (94%) and reappearance of HBeAg (81%). Pretreatment serum HBV DNA levels and the duration of additional lamivudine therapy after HBeAg seroconversion were 2 independent predictive factors for posttreatment relapse. In conclusion, lamivudine-induced HBeAg seroconversion was not durable in this endemic area. And the duration of additional lamivudine therapy after HBeAg seroconversion significantly affected the posttreatment relapse. Further studies are needed to determine the duration of lamivudine and to elucidate the cause of high relapse after HBeAg seroconversion in endemic areas of HBV.
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PMID:Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea. 1100 26

Lamivudine therapy induces improvements in chronic hepatitis B in a high proportion of patients, but prolonged therapy is limited by the development of viral resistance. We analyzed clinical responses and virologic resistance in 27 patients treated continuously with lamivudine for 2 to 4 years. Serum transaminases, hepatitis B virus (HBV) DNA by both branched DNA (bDNA) signal amplification and quantitative polymerase chain reaction were monitored at 4- to 8-week intervals. Virologic resistance to lamivudine was confirmed by the presence of mutations in the YMDD motif of the polymerase gene by restriction fragment-length polymorphism analysis. Serum HBV-DNA levels decreased rapidly in all treated patients, falling by 4 to 5 logs within 1 year. Transaminase levels also decreased and were normal in 70% of patients at 1 year, at which point liver histology had improved in 81% of patients. Viral resistance began to emerge after 8 months of therapy, eventually developing in 14 patients, including 76% of hepatitis B e antigen (HBeAg)-positive patients but only 10% of HBeAg-negative patients. Lamivudine withdrawal led to reappearance of wild-type HBV species, but retreatment led to more rapid reappearance of the mutant virus. Clinical, serum biochemical, and histologic improvements were maintained in the 13 patients who did not develop resistance. Thus, long-term therapy with lamivudine resulted in maintained improvements in virologic, biochemical, and histologic features of disease in most patients with HBeAg-negative chronic hepatitis B and in the subgroup of HBeAg-positive patients with high serum transaminase levels. A high rate of resistance limited efficacy, particularly in patients who remained HBeAg positive on therapy.
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PMID:Long-term therapy of chronic hepatitis B with lamivudine. 1100 36

We evaluated the safety and efficacy of long-term lamivudine monotherapy in a group of 25 patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. Lamivudine was administered in a daily dose of 150 mg for a mean of 26 +/- 7 months and was well tolerated. No patient lost hepatitis B surface antigen (HBsAg). The rate of initial biochemical response increased from 88% at 6 months to 96% at 12 months of therapy, but it progressively decreased thereafter; the biochemical remission rate was 68% at 18 months, 59. 5% at 24 months, and 42.5% at >/=30 months. Alanine transaminase (ALT) increased to higher than the baseline levels in 8 of the 11 patients with a biochemical breakthrough reaching acute hepatitis levels in 6 of them. Acute icteric hepatitis developed in one patient. The virologic remission rate assessed by a sensitive quantitative polymerase chain reaction (PCR) assay was 68% at both 6 and 12 months, decreasing thereafter to 52% at 18 months and to 41. 6% at both 24 and >/=30 months. Virologic breakthroughs were always persistent and preceded ALT elevations by a median of 4 (3-24) months. YMDD mutants were detected in all patients with a virologic breakthrough. In conclusion, in patients with HBeAg-negative chronic hepatitis B, long-term lamivudine therapy is safe and is associated with high biochemical and virologic response rates at the end of the first year. However, response rates tend to decrease with time and breakthroughs due to YMDD mutants accumulate. ALT activity during breakthroughs often exceeds the baseline and may reach even acute hepatitis levels.
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PMID:Efficacy of long-term lamivudine monotherapy in patients with hepatitis B e antigen-negative chronic hepatitis B. 1100 33

Currently seven viruses, A, B, C, D, E, G and transfusion transmitted virus (TTV), are recognised in the hepatitis virus alphabet. Hepatitis G virus and TTV probably do not cause liver disease in humans. Hepatitis A and E usually cause a self-limiting hepatitis followed by complete recovery but occasionally cause fulminant hepatic failure. Hepatitis B and C are major public health problems worldwide due to their sequelae of chronic hepatitis, cirrhosis and primary liver cancer. Chronic hepatitis C is a particular health issue for Western Europe already, accounting for 40% of end-stage cirrhosis and 30% of liver transplants. The contribution of hepatitis C to chronic liver disease is predicted to rise in the future. Vaccines can prevent hepatitis A and B. Interferon alpha is effective treatment in 25-30% of patients with chronic hepatitis B or C. The prospects for treating chronic hepatitis B have been improved by the introduction of reverse transcriptase inhibitors. Lamivudine is the first drug of this class to be licensed. The optimal use of these new drugs is currently being studied. The success rate for treating chronic hepatitis C can be raised to about 40% with combination therapy of interferon alpha and ribavirin. A large research effort to discover new antiviral agents against hepatitis C is already giving the prospect of more effective therapies in the next few years.
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PMID:Virus hepatitis update. 1119 85


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