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)

Lamivudine has been shown to be effective in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, but its long-term efficacy and the rate of resistant mutations in patients with HBeAg-negative chronic hepatitis B is less clear. Twenty-nine patients with HBeAg-negative chronic hepatitis B, who have received lamivudine for at least 1 year were studied to determine the antiviral response, the rate and pattern of lamivudine-resistant mutations, and the effect of lamivudine-resistant mutations on HBeAg status. The mean duration of treatment was 21 +/- 7 months. Before treatment, core promoter variant was detected in 16 (55%) patients and precore stop codon variant in 18 (62%) patients. Serum hepatitis B virus (HBV) DNA was detected by solution hybridization assay in 62%, 4%, and 24% and by polymerase chain reaction (PCR) assay in 100%, 31%, and 40% at months 0, 6, and 24, respectively. The cumulative rates of detection of lamivudine-resistant mutations after 1 and 2 years of treatment were 10% and 56%, respectively. In addition to the duration of treatment, core promoter mutation was associated with the selection of lamivudine-resistant mutants. Three patients with lamivudine-resistant mutations had reversion of the precore stop codon mutation; in 2 patients this was accompanied by the reappearance of HBeAg. We found that lamivudine-resistant mutants were detected at similar rates in patients with HBeAg-negative as in patients with HBeAg-positive chronic hepatitis B. Additional changes in other parts of the HBV genome may restore the replication fitness of lamivudine-resistant mutants.
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PMID:Evolution of hepatitis B virus polymerase gene mutations in hepatitis B e antigen-negative patients receiving lamivudine therapy. 1105 72

Lamivudine is effective in inhibiting hepatitis B virus (HBV) replication, and its clinical use in patients with chronic hepatitis B is associated with improvements in serum aminotransferase levels and liver histopathologic characteristics. Few data are available on its use in patients with advanced liver disease. We report on the outcomes of 5 patients with hepatic decompensation caused by chronic hepatitis B treated long term with lamivudine. All patients were adult white men seropositive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) before therapy. All 5 patients had biopsy-proven cirrhosis with clinical and biochemical evidence of hepatic decompensation. Two patients had Child's class C cirrhosis; 2 patients, class B; and 1 patient, class A (although this patient had persistent portasystemic encephalopathy and developed variceal bleeding). HBV DNA became undetectable in all patients and remained so throughout the study. Both patients with Child's class C and 1 patient with class B cirrhosis had significant clinical improvement. Child-Pugh scores improved from 12 to 7 and 11 to 7 in the 2 patients with Child's class C cirrhosis, and the patient with class B cirrhosis had complete resolution of troublesome encephalopathy. Serum aminotransferase, albumin, and total bilirubin levels improved significantly in 3 of 5 patients. One patient with Child's class B cirrhosis underwent orthotopic liver transplantation at week 13 after dramatic increases in liver tests and clinical worsening. The patient subsequently cleared HBeAg and HBsAg from serum posttransplantation. In conclusion, prolonged therapy with lamivudine resulted in improved serum biochemical values and loss of HBV DNA in patients with decompensated cirrhosis. Clinical improvements, reflected in Child-Pugh classification and functional status, may also occur, particularly among those with Child's class C disease initially.
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PMID:Clinical improvement in patients with decompensated liver disease caused by hepatitis B after treatment with lamivudine. 1108 57

Orthotopic liver transplantation (OLT) for hepatitis B virus (HBV) infection was limited until recently by poor graft and patient outcomes caused by recurrent HBV. Long-term immunoprophylaxis with hepatitis B immune globulin (HBIG) dramatically improved post-OLT survival, but recurrent HBV still occurred in up to 36% of the recipients. More recently, combination HBIG and lamivudine has been shown to effectively prevent HBV recurrence in patients post-OLT. The aim of the current study is to determine long-term outcome and cost-effectiveness of using combination HBIG and lamivudine compared with HBIG monotherapy in patients who undergo OLT for HBV. A retrospective chart review identified 59 patients administered combination HBIG and lamivudine and 12 patients administered HBIG monotherapy as primary prophylaxis against recurrent HBV. Lamivudine, 150 mg/d, was administered orally indefinitely. HBIG was administered under a standard protocol (10,000 IU intravenously during the anhepatic phase, then 10,000 IU/d intravenously for 7 days, then 10,000 IU intravenously monthly) indefinitely. A decision-analysis model was developed to evaluate the potential economic impact of prophylaxis against HBV with combination therapy compared with monotherapy. Recurrent HBV was defined as the reappearance of hepatitis B surface antigen (HBsAg) after its initial disappearance post-OLT. In the combination-therapy group, no patient redeveloped serum HBsAg or HBV DNA during mean follow-ups of 459 and 416 days, respectively. In the monotherapy group, 3 patients (25%) had reappearance of HBsAg in serum during a mean follow-up of 663 days. Combination therapy resulted in a dominant, cost-effective strategy with an average cost-effectiveness ratio of $252,111/recurrence prevented compared with $362,570/recurrence prevented in the monotherapy strategy. Combination prophylaxis with HBIG and lamivudine is highly effective in preventing recurrent HBV, may protect against the emergence of resistant mutants, and is significantly more cost-effective than HBIG monotherapy with its associated rate of recurrent HBV.
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PMID:An efficacy and cost-effectiveness analysis of combination hepatitis B immune globulin and lamivudine to prevent recurrent hepatitis B after orthotopic liver transplantation compared with hepatitis B immune globulin monotherapy. 1108 61

Prophylaxis of Recurrent Hepatitis B. 1. Although standard prophylaxis with antibody to hepatitis B surface antigen immunoglobulins (HBIG) is effective, it is difficult to administer and must be administered indefinitely. 2. Preemptive therapy with lamivudine reduces the early risk for recurrence after transplantation, but maintenance with either famciclovir or lamivudine has been ineffective in sustaining remission. 3. The combination of preemptive lamivudine with HBIG prophylaxis may be the most effective treatment to prevent hepatitis B virus reinfection. Treatment of Recurrent Hepatitis B. 1. Interferon-alpha, ganciclovir, and famciclovir have not been helpful. 2. Lamivudine appears promising, but its long-term efficacy is unproven; in immunosuppressed transplant recipients, the rate of emergence of YMDD mutants is high and accelerated, and their emergence is aggravated by consistent liver morbidity.
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PMID:Posttransplantation prevention and treatment of recurrent hepatitis B. 1108 85

Treatment of chronic hepatitis B is directed at interrupting the natural history and clinical outcomes of the disease. It needs to take into account the virology and replication cycle of the hepatitis B virus (HBV), and the host immune response to HBV. Long term follow-up of patients treated with interferon supports the paradigm that a sustained, major suppression of HBV replication, particularly that associated with hepatitis B e antigen (HBeAg) seroconversion, interrupts the natural history of hepatitis B. The availability of potent but well tolerated and orally available HBV antivirals, of which lamivudine is the prototype, has allowed clearer treatment objectives to be formulated. These are: temporary or permanent reduction of hepatitis (necroinflammatory) activity, arrest of fibrotic progression, prevention of cirrhosis and liver failure, and prevention of recurrent HBV infection after liver transplantation. Lamivudine has good medium term efficacy in achieving each of these objectives. The only significant problem for the longer term is emergence of antiviral resistance conferred by mutations in the YMDD (tyrosine-methionine-aspartic acid-aspartic acid) motif of the HBV reverse transcriptase. As a result, contentious issues remain about defining when antiviral therapy is indicated, whether to treat for a defined interval or indefinitely, and when to stop treatment if HBeAg seroconversion is not achieved. Some personal views are expressed in this review. Among newer HBV antivirals in clinical studies, adefovir dipivoxil, entecavir and emtricitabine appear to be at least as potent as lamivudine in suppressing HBV replication. Famciclovir appears less potent. In vitro studies show that YMDD mutations confer cross-resistance between lamivudine, emtricitabine and beta-L-Fd4C (L-2',3'-didehydro-dideoxy-5-fluorocytidine). However, adefovir dipivoxil, lobucavir, entecavir, DAPD (beta-D-2,6-diaminopurine dioxolane) and possibly clevudine (L-FMAU) suppress replication of YMDD mutant HBV, as well as wildtype. Preliminary studies indicate clinical efficacy of adefovir dipivoxil once resistance to lamivudine has developed. Immunomodulatory approaches to treatment of chronic hepatitis B are conceptually attractive, but newer agents used to date (thymalfasin, interleukin-12, therapeutic vaccines) have not demonstrated sufficient efficacy for widespread use. The next challenge for HBV treatment is to use antivirals in combination and/or in cyclical therapy to reduce the emergence of drug resistance and increase efficacy, particularly to achieve sustainable post-treatment suppression of hepatitis B.
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PMID:Clinical potential of emerging new agents in hepatitis B. 1108 96

The management of acute HBV infection is supportive. Specific treatment is not indicated for HBV carriers because they often have no evidence of liver injury, and, further, do not respond to currently available therapies. Interferon monotherapy is best indicated for patients with chronic replicating HBV infection and evidence of chronic hepatitis. There is an increased likelihood of clearing HBsAg with interferon monotherapy as compared to lamivudine. Lamivudine is an oral nucleoside analog that is better tolerated than interferon. The clinical situations for its use are far more than interferon monotherapy. Lamivudine should be used in patients with decompensated cirrhosis and also in transplantation, both before and after transplantation. The post-transplant use of hepatitis B immune globulin (HBIG) and lamivudine combination therapy may be better for recipients who are identified in a replicative phase prior to transplantation. Hepatitis B coinfection with one or more viruses, HCV, HDV, or HIV, may occur. Both interferon and lamivudine have been useful in these patients. However, the data are sparse and heterogeneous. Therapy with one or both drugs will have to be tailored to the clinical situation. Combination therapy with immunomodulatory and/or antiviral drugs are what we will be looking toward in the future.
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PMID:Hepatitis B. 1109 30

Development of resistance is a major issue in antiviral treatment of hepatitis B reinfection after liver transplantation. Antiviral combination therapy is discussed for therapy or prevention of this breakthrough of viral replication. Eight patients were enrolled into this retrospective analysis after liver transplantation for chronic hepatitis B infection. All had reinfection of the graft and breakthrough of HBV during consecutive famciclovir and lamivudine monotherapy. Subsequently a combination therapy with lamivudine and interferon-alpha 2a (group I, n = 4) or lamivudine and famciclovir (group II, n = 4) was initiated. Combination therapy was started 61 months (group I) and 25 months (group II) after liver transplantation. It markedly reduced the viral replication rate in all patients despite lamivudine resistance. In group I three of four patients and in group II two of four patients became HBV-DNA negative. Two long-term responders were observed in group I, and none in group II. No patient became HBsAg negative or lost HbeAg. Pretreatment elevated ALT and AST levels were significantly reduced. No severe complications, and especially no rejection episodes, occurred. Lamivudine in combination with other antiviral agents, especially interferon-alpha, might be a therapeutic option for hepatitis B reinfection after liver transplantation. Suppression of virus replication to the point of undetectable values is possible even in patients with lamivudine-resistant virus mutations.
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PMID:Antiviral combination therapy for lamivudine-resistant hepatitis B reinfection after liver transplantation. 1111 32

Seventy-seven liver transplant candidates were enrolled in a multicenter study in which patients were treated with lamivudine (100 mg daily) without the adjunctive use of hepatitis B immune globulin. Treatment was begun while patients awaited liver transplantation and continued after transplantation. All were hepatitis B surface antigen (HBsAg) positive, and 61% had detectable hepatitis B e antigen (HBeAg) and HBV DNA when treatment was begun. Forty-seven underwent liver transplantation and 30 did not. Median study participation was 38 months (range, 2.7-48.5) in the transplanted patients and 26 months (range, 0.1-37) in the nontransplanted group. Twenty-five of 42 (60%) transplanted patients with 12 or more weeks of posttransplantation follow-up were HBsAg negative at the last study visit. At treatment week 156, 13 of 22 (59%) remained HBsAg negative, and all 9 reinfected patients were HBV-DNA positive before treatment. In the nontransplanted patients, HBeAg was initially detectable in 20 of 27 (74%) but this decreased to 3 of 17 (18%) after 104 weeks of treatment, and significant improvement in biochemical parameters was observed. HBV-DNA polymerase mutants were detected in 15 (21%) and 6 (20%) of the transplanted and nontransplanted patients, respectively. When compared with historical cohorts, lamivudine-treated patients appeared to have improved survival, and transplanted patients had a decrease in the rate of recurrent HBV infection. Lamivudine therapy was partially effective in preventing recurrent HBV infection when given before and after transplantation. Thus, future trials using a combination of HBIg and lamivudine are needed to assess the optimal prophylactic therapy.
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PMID:A multicenter United States-Canadian trial to assess lamivudine monotherapy before and after liver transplantation for chronic hepatitis B. 1117 45

Hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) is associated with a high recurrence rate and poor prognosis. This is the first study of the efficacy of long-term lamivudine therapy for patients with HBV infection after OLT. Eight patients (5 men, 3 women) aged 35 to 63 years (mean, 50 years) with HBV infection after OLT (6 patients, recurrent infection; 2 patients, de novo infection) were treated with lamivudine, 100 mg/d, on a compassionate-use basis. Before treatment, all had detectable HBV DNA in serum, and 5 patients (62.5%) had detectable serum hepatitis Be antigen (HBeAg). Duration of treatment was 24 to 50 months (mean, 36 months). Patients were monitored for serum alanine aminotransferase level (ALT), HBV DNA (by hybridization), hepatitis B surface antigen (HBsAg), and HBeAg before and after therapy, and liver histological findings were scored for inflammation and fibrosis. After treatment, 3 patients (32.5%) had undetectable HBV DNA by hybridization assay. None of the patients lost serum HBeAg and HBsAg, except for 1 patient who lost serum HBeAg and became serum antibody to HBeAg-positive. Serum ALT levels normalized in 5 patients (62.5%). Blinded histological assessment showed improvement in 1 patient, no change in 2 patients, and worsening in 5 patients. YMDD variants of HBV were detected in 5 patients (62.5%) within 9 to 20 months (mean, 13 months) of lamivudine therapy. Of these, 2 patients (40%) had hepatic failure (1 patient died of massive variceal bleed) and 3 patients remain clinically stable. Lamivudine therapy was continued in the latter patients. Although lamivudine is a potentially effective therapy for HBV infection after OLT, emergence of high mutation rates with long-term therapy, histological progression, and the possibility of hepatic failure point to the need to investigative combinations of antiviral therapy.
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PMID:Long-term experience with lamivudine therapy for hepatitis B virus infection after liver transplantation. 1117 94

Hepatitis B is one of the most common infectious diseases in the world. It has been estimated that 350 million people worldwide are chronic hepatitis B virus (HBV) carriers. The global prevalence of chronic HBV infection varies widely, from high ( > 8%, e.g., Africa, Asia and the Western Pacific) to intermediate (2-7% e.g., Southern and Eastern Europe) and low (< 2%, e.g., Western Europe, North America and Australia). The predominant routes of transmission vary according to the endemicity of the HBV infection. In areas of high endemicity, perinatal transmission is the main route of transmission, whereas in areas of low endemicity, sexual contact amongst high-risk adults is predominant. Between one-third and one-quarter of people infected chronically with HBV are expected to develop progressive liver disease (including cirrhosis and primary liver cancer). Although mass vaccination programs have begun to control the spread of HBV infection, therapeutic intervention is the only option for those with established chronic HBV-associated liver disease. Until recently, the only treatment for chronic hepatitis B was the immune modulator, interferon (IFN) alpha. However, IFN alpha treatment has several disadvantages; it is expensive, it must be administered by injection, there are side-effects, and IFN alpha is poorly tolerated. Lamivudine, a nucleoside analogue, is the first effective, and well tolerated, oral treatment for chronic hepatitis B. In conclusion, although we are still some way from eradicating or curing chronic hepatitis B, the advent of lamivudine allows new populations to benefit from therapy and helps to address the global public health problem of hepatitis B.
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PMID:Hepatitis B--an important public health issue. 1121 23


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