Lamivudine as initial treatment for chronic hepatitis B in the United States

Jules L. Dienstag, Eugene R Schiff, Teresa L. Wright, Robert P. Perrillo, Hie Won L Hann, Zachary Goodman, Lynn Crowther, Lynn D. Condreay, Mary Woessner, Marc Rubin, Nathaniel A. Brown

Research output: Contribution to journalArticle

1290 Citations (Scopus)

Abstract

Background: Although the nucleoside analogue lamivudine has shown promise in patients with chronic hepatitis B, long-term data on patients from the United States are lacking. Methods: We randomly assigned previously untreated patients with chronic hepatitis B to receive either 100 mg of oral lamivudine or placebo daily for 52 weeks. We then followed them for an additional 16 weeks to evaluate post-treatment safety and the durability of responses. The primary end point with respect to efficacy was a reduction of at least 2 points in the score on the Histologic Activity Index. On this scale, scores can range from 0 (normal) to 22 (most severe abnormalities). Results: Of the 143 randomized patients, 137 were included in the efficacy analysis: 66 in the lamivudine group and 71 in the placebo group. The other six patients were excluded at the base-line visit because of the absence of a documented history of hepatitis B surface antigen for at least six months. After 52 weeks of treatment, lamivudine recipients were more likely than placebo recipients to have a histologic response (52 percent vs. 23 percent, P<0.001), loss of hepatitis B e antigen (HBeAg) in serum (32 percent vs. 11 percent, P=0.003), sustained suppression of serum hepatitis B virus (HBV) DNA to undetectable levels (44 percent vs, 16 percent P<0.001), and sustained normalization of serum alanine amino-transferase levels (41 percent vs. 7 percent, P<0.001), and they were less likely to have increased hepatic fibrosis (5 percent vs. 20 percent, P=0.01). Lamivudine recipients were also more likely to undergo HBeAg seroconversion, defined as the loss of HBeAg, undetectable levels of serum HBV DNA, and the appearance of antibodies against HBeAg (17 percent vs. 6 percent, P=0.04). HBeAg responses persisted in most patients for 16 weeks after the discontinuation of treatment. Lamivudine was well tolerated. Self-limited post-treatment elevations in serum alanine aminotransferase were more common in lamivudine recipients: 25 percent had serum alanine aminotransferase levels that were at least three times base-line levels, as compared with 8 percent of placebo recipients (P=0.01). The clinical condition of all patients remained stable during the study. Conclusions: In U.S. patients with previously untreated chronic hepatitis B, one year of lamivudine therapy had favorable effects on histologic, virologic, and biochemical features of the disease and was well tolerated. HBeAg responses were usually sustained after treatment.

Original languageEnglish
Pages (from-to)1256-1263
Number of pages8
JournalNew England Journal of Medicine
Volume341
Issue number17
DOIs
StatePublished - Oct 21 1999
Externally publishedYes

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Lamivudine
Chronic Hepatitis B
Hepatitis B e Antigens
Serum
Placebos
Therapeutics
Alanine Transaminase
Hepatitis B virus
DNA
Hepatitis B Surface Antigens
Transferases
Nucleosides
Alanine
Reference Values
Fibrosis
Safety
Antibodies
Liver

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Dienstag, J. L., Schiff, E. R., Wright, T. L., Perrillo, R. P., Hann, H. W. L., Goodman, Z., ... Brown, N. A. (1999). Lamivudine as initial treatment for chronic hepatitis B in the United States. New England Journal of Medicine, 341(17), 1256-1263. https://doi.org/10.1056/NEJM199910213411702

Lamivudine as initial treatment for chronic hepatitis B in the United States. / Dienstag, Jules L.; Schiff, Eugene R; Wright, Teresa L.; Perrillo, Robert P.; Hann, Hie Won L; Goodman, Zachary; Crowther, Lynn; Condreay, Lynn D.; Woessner, Mary; Rubin, Marc; Brown, Nathaniel A.

In: New England Journal of Medicine, Vol. 341, No. 17, 21.10.1999, p. 1256-1263.

Research output: Contribution to journalArticle

Dienstag, JL, Schiff, ER, Wright, TL, Perrillo, RP, Hann, HWL, Goodman, Z, Crowther, L, Condreay, LD, Woessner, M, Rubin, M & Brown, NA 1999, 'Lamivudine as initial treatment for chronic hepatitis B in the United States', New England Journal of Medicine, vol. 341, no. 17, pp. 1256-1263. https://doi.org/10.1056/NEJM199910213411702
Dienstag, Jules L. ; Schiff, Eugene R ; Wright, Teresa L. ; Perrillo, Robert P. ; Hann, Hie Won L ; Goodman, Zachary ; Crowther, Lynn ; Condreay, Lynn D. ; Woessner, Mary ; Rubin, Marc ; Brown, Nathaniel A. / Lamivudine as initial treatment for chronic hepatitis B in the United States. In: New England Journal of Medicine. 1999 ; Vol. 341, No. 17. pp. 1256-1263.
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abstract = "Background: Although the nucleoside analogue lamivudine has shown promise in patients with chronic hepatitis B, long-term data on patients from the United States are lacking. Methods: We randomly assigned previously untreated patients with chronic hepatitis B to receive either 100 mg of oral lamivudine or placebo daily for 52 weeks. We then followed them for an additional 16 weeks to evaluate post-treatment safety and the durability of responses. The primary end point with respect to efficacy was a reduction of at least 2 points in the score on the Histologic Activity Index. On this scale, scores can range from 0 (normal) to 22 (most severe abnormalities). Results: Of the 143 randomized patients, 137 were included in the efficacy analysis: 66 in the lamivudine group and 71 in the placebo group. The other six patients were excluded at the base-line visit because of the absence of a documented history of hepatitis B surface antigen for at least six months. After 52 weeks of treatment, lamivudine recipients were more likely than placebo recipients to have a histologic response (52 percent vs. 23 percent, P<0.001), loss of hepatitis B e antigen (HBeAg) in serum (32 percent vs. 11 percent, P=0.003), sustained suppression of serum hepatitis B virus (HBV) DNA to undetectable levels (44 percent vs, 16 percent P<0.001), and sustained normalization of serum alanine amino-transferase levels (41 percent vs. 7 percent, P<0.001), and they were less likely to have increased hepatic fibrosis (5 percent vs. 20 percent, P=0.01). Lamivudine recipients were also more likely to undergo HBeAg seroconversion, defined as the loss of HBeAg, undetectable levels of serum HBV DNA, and the appearance of antibodies against HBeAg (17 percent vs. 6 percent, P=0.04). HBeAg responses persisted in most patients for 16 weeks after the discontinuation of treatment. Lamivudine was well tolerated. Self-limited post-treatment elevations in serum alanine aminotransferase were more common in lamivudine recipients: 25 percent had serum alanine aminotransferase levels that were at least three times base-line levels, as compared with 8 percent of placebo recipients (P=0.01). The clinical condition of all patients remained stable during the study. Conclusions: In U.S. patients with previously untreated chronic hepatitis B, one year of lamivudine therapy had favorable effects on histologic, virologic, and biochemical features of the disease and was well tolerated. HBeAg responses were usually sustained after treatment.",
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T1 - Lamivudine as initial treatment for chronic hepatitis B in the United States

AU - Dienstag, Jules L.

AU - Schiff, Eugene R

AU - Wright, Teresa L.

AU - Perrillo, Robert P.

AU - Hann, Hie Won L

AU - Goodman, Zachary

AU - Crowther, Lynn

AU - Condreay, Lynn D.

AU - Woessner, Mary

AU - Rubin, Marc

AU - Brown, Nathaniel A.

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N2 - Background: Although the nucleoside analogue lamivudine has shown promise in patients with chronic hepatitis B, long-term data on patients from the United States are lacking. Methods: We randomly assigned previously untreated patients with chronic hepatitis B to receive either 100 mg of oral lamivudine or placebo daily for 52 weeks. We then followed them for an additional 16 weeks to evaluate post-treatment safety and the durability of responses. The primary end point with respect to efficacy was a reduction of at least 2 points in the score on the Histologic Activity Index. On this scale, scores can range from 0 (normal) to 22 (most severe abnormalities). Results: Of the 143 randomized patients, 137 were included in the efficacy analysis: 66 in the lamivudine group and 71 in the placebo group. The other six patients were excluded at the base-line visit because of the absence of a documented history of hepatitis B surface antigen for at least six months. After 52 weeks of treatment, lamivudine recipients were more likely than placebo recipients to have a histologic response (52 percent vs. 23 percent, P<0.001), loss of hepatitis B e antigen (HBeAg) in serum (32 percent vs. 11 percent, P=0.003), sustained suppression of serum hepatitis B virus (HBV) DNA to undetectable levels (44 percent vs, 16 percent P<0.001), and sustained normalization of serum alanine amino-transferase levels (41 percent vs. 7 percent, P<0.001), and they were less likely to have increased hepatic fibrosis (5 percent vs. 20 percent, P=0.01). Lamivudine recipients were also more likely to undergo HBeAg seroconversion, defined as the loss of HBeAg, undetectable levels of serum HBV DNA, and the appearance of antibodies against HBeAg (17 percent vs. 6 percent, P=0.04). HBeAg responses persisted in most patients for 16 weeks after the discontinuation of treatment. Lamivudine was well tolerated. Self-limited post-treatment elevations in serum alanine aminotransferase were more common in lamivudine recipients: 25 percent had serum alanine aminotransferase levels that were at least three times base-line levels, as compared with 8 percent of placebo recipients (P=0.01). The clinical condition of all patients remained stable during the study. Conclusions: In U.S. patients with previously untreated chronic hepatitis B, one year of lamivudine therapy had favorable effects on histologic, virologic, and biochemical features of the disease and was well tolerated. HBeAg responses were usually sustained after treatment.

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