Combination chemotherapy for hepatitis B virus: The final solution?

Shaw, Timothy J.; Locarnini, Stephen

doi:10.1053/jhep.2000.16181

Cited by 40 publications

(25 citation statements)

References 38 publications

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“…A potential solution in the future, as more nucleoside or nucleotide analogues become available in the armamentarium against chronic HBV, 28 is to combine 2 or more of these agents for patients with decompensated HBV-cirrhosis with the hope that this treatment strategy may decrease the frequency of drug resistance and thus maintain long-term clinical response. 29 In conclusion, our results suggest that lamivudine is beneficial in a selected subgroup of patients with severely decompensated cirrhosis caused by actively replicating HBV infection. The improvement in hepatic function may be of sufficient magnitude to abrogate the urgent need of OLT in some patients and confer a survival advantage.…”

Section: Discussionmentioning

confidence: 56%

Lamivudine Treatment Is Beneficial in Patients With Severely Decompensated Cirrhosis and Actively Replicating Hepatitis B Infection Awaiting Liver Transplantation: A Comparative Study Using A Matched, Untreated Cohort

et al. 2001

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Uncontrolled studies have suggested a beneficial effect of lamivudine in patients with decompensated cirrhosis caused by replicating hepatitis B virus (HBV). We analyzed the outcome of lamivudine treatment in 23 consecutive patients with severely decompensated HBV-cirrhosis defined as a Child-Pugh-Turcotte (CPT) score of >10, and compared with a historical untreated control group of 23 patients matched for age, gender, and baseline CPT score. Significant clinical response, defined as a decrease in the CPT score by >3 points, was observed in 14 of 23 (60.9%) treated patients versus none of the controls (P < .0001). The median change in CPT scores was ؊3.0 (range, ؊6 to ؉3) in the treated group versus ؉1.0 in the controls (range, ؊1 to ؉2) (P ‫؍‬ .016). Orthotopic liver transplantation (OLT) was performed in 34.8% of treated patients (median, 3.5; range, 1-32 months), versus 73.9% of controls (median, 3.0; range, 1-14 months) (P ‫؍‬ .04). Excluding transplanted patients, there were no deaths in the treated group versus 6 deaths in the control group (P ‫؍‬ .009). Time to death or OLT was significantly longer in treated patients than in controls (P < .001). Two patients developed lamivudine resistance after 9 and 12 months, respectively. Our results suggest that lamivudine significantly improves hepatic function in over half of the patients with decompensated cirrhosis and replicating HBV, and may confer a survival advantage. However, the small sample size and the use of a retrospective control cohort preclude drawing definitive conclusions. Lamivudine, the (Ϫ) enantiomer of 3Ј-thiacytidine (Epivir), is a nucleoside analogue that inhibits DNA synthesis by terminating the nascent proviral DNA chain through interference with the reverse transcriptase activity of hepatitis B virus (HBV) DNA polymerase. Two large multicenter, placebo-controlled studies have shown lamivudine to be effective in suppression of HBV DNA and improving histology in immunocompetent patients with well-compensated liver disease caused by chronic HBV infection. 1,2 These 2 studies have reported that 16% to 17% of these patients achieved seroconversion from hepatitis B e antigen (HBeAg) to hepatitis B e antibody (HBeAb), 1,2 which is thought to be the most important marker for sustained virologic remission after discontinuation of lamivudine. 3 The use of lamivudine in patients with decompensated HBV-cirrhosis has been reported in several uncontrolled studies, 4-8 including a previous report from our center. 6 Although the efficacy of lamivudine in stabilizing liver function and improving Child-Pugh score has been suggested, 5-7 the impact of lamivudine on survival and need for orthotopic liver transplantation (OLT) has not been previously examined. The lack of an untreated control group in these studies also makes it difficult to exclude selection bias as an explanation for the observed benefits of lamivudine in patients with decompensated HBV-cirrhosis.We report here our experience using lamivudine in a selected group of patients with severely de...

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Section: Discussionmentioning

confidence: 56%

Lamivudine Treatment Is Beneficial in Patients With Severely Decompensated Cirrhosis and Actively Replicating Hepatitis B Infection Awaiting Liver Transplantation: A Comparative Study Using A Matched, Untreated Cohort

et al. 2001

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“…59 It is relevant to this issue that in treatment of HIV infections, resistance has developed as a result of ineffective suppression of viral replication, ie, resistance cannot occur without replication. 60 Hence, the use of more potent nucleoside analogues is desirable. Several new nucleoside analogues, including adefovir dipivoxil, 61 entecavir, 62 and emtricitabine, 63 have been found to be effective in suppressing HBV replication.…”

Section: Discussionmentioning

confidence: 99%

High hepatitis B virus (HBV) DNA viral load as the most important risk factor for HBV reactivation in patients positive for HBV surface antigen undergoing autologous hematopoietic cell transplantation

Lau

Leung

Fong

et al. 2002

Blood

211

143

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“…43,44 Following the lessons learned from treating human immunodeficiency virus infection, resistance typically develops as a result of ineffective suppression of viral replication (i.e., no resistance with no replication). 45 Hence, the use of more potent nucleoside analogues, ideally in combination regimens with at least additivity or preferably synergistic effects, should be considered for these patients in the future. 45,46 HEPATOLOGY, September 2002 …”

Section: Discussionmentioning

confidence: 99%

“…45 Hence, the use of more potent nucleoside analogues, ideally in combination regimens with at least additivity or preferably synergistic effects, should be considered for these patients in the future. 45,46 HEPATOLOGY, September 2002 …”

Section: Discussionmentioning

confidence: 99%

Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation

et al. 2002

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Exacerbation of hepatitis B virus (HBV) is a serious cause of morbidity and mortality in hepatitis B surface antigen (HBsAg)-positive patients undergoing transplantation. Our aim was to evaluate the effectiveness of lamivudine to prevent hepatitis due to exacerbation of HBV in HBsAg-positive patients treated with allogeneic hematopoietic cell transplantation. We studied 20 consecutive HBsAg-positive recipients of allogeneic hematopoietic cell transplantation who received lamivudine 100 mg daily starting one week before transplantation until week 52 after transplantation (group 1). Serial serum alanine aminotransferase and HBV DNA levels were measured before and after transplantation at 4-to 8-week intervals for the first year and then 4-to 12-week intervals. Their virologic and clinical outcomes were compared with 20 case-matched recipients who did not receive any antiviral therapy to HBV (anti-HBV) before and after hematopoietic cell transplantation (group 2). After transplantation, 9 patients (45%) in group 2 and one patient (5%) in group 1 had hepatitis due to exacerbation of HBV (P < .008), with 3 hepatic failures in group 2 and none in group 1. The one-year actuarial probability of survival without hepatitis due to exacerbation of HBV was higher in group 1 than group 2 (94.1% vs. 54.3%, P ‫؍‬ .002). By multivariate Cox analysis, preemptive use of lamivudine effectively reduced hepatitis due to exacerbation of HBV (adjusted hazards ratio, 0.09; P ‫؍‬ .021). I n an endemic area for chronic hepatitis B infection, exacerbation of this virus is a serious cause of morbidity and mortality in patients undergoing cytotoxic or immunosuppressive therapy. 1,2 Careful prospective serologic testing has shown that liver damage due to exacerbation of hepatitis B virus (HBV) is a 2-stage process. The initial stage occurs during intense cytotoxic or immunosuppressive therapy and is characterized by enhanced viral replication, as reflected by increases in serum levels of HBV DNA, hepatitis B e antigen, and HBV DNA polymerase, which presumably results in widespread infection of hepatocytes. The second stage is related to restoration of immune function following withdrawal of cytotoxic or immunosuppressive therapy, which causes rapid immune-mediated destruction of infected hepatocytes. Clinically, this may lead to hepatitis, hepatic failure, and even death. [3][4][5] In keeping with these observations, our recent data suggest that a high pretreatment level of serum HBV DNA is the single most important factor for exacerbation of HBV after intense immunosuppression. 6 In the past few decades, hematopoietic cell transplantation has been established as the standard treatment of various hematologic and oncologic problems. 7 In areas such as Southeast Asia, where HBV infection is prevalent, hematopoietic cell transplantation might be complicated by HBV-related morbidity and mortality. 8 The pre-heAbbreviations: HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; anti-HBV, antibody to hepatitis B virus; PCR, polymerase chain ...

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Combination chemotherapy for hepatitis B virus: The final solution?

Cited by 40 publications

References 38 publications

Lamivudine Treatment Is Beneficial in Patients With Severely Decompensated Cirrhosis and Actively Replicating Hepatitis B Infection Awaiting Liver Transplantation: A Comparative Study Using A Matched, Untreated Cohort

Lamivudine Treatment Is Beneficial in Patients With Severely Decompensated Cirrhosis and Actively Replicating Hepatitis B Infection Awaiting Liver Transplantation: A Comparative Study Using A Matched, Untreated Cohort

High hepatitis B virus (HBV) DNA viral load as the most important risk factor for HBV reactivation in patients positive for HBV surface antigen undergoing autologous hematopoietic cell transplantation

Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation

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