Long-term outcome and hepatocellular carcinoma development in chronic hepatitis B or cirrhosis patients after nucleoside analog treatment with entecavir or lamivudine

Haruhiko Kobashi, Yasuhiro Miyake, Fusao Ikeda, Tetsuya Yasunaka, Ken Nishino, Akio Moriya, Jyunichi Kubota, Shinichiro Nakamura, Akinobu Takaki, Kazuhiro Nouso, Gotaro Yamada, Kazuhide Yamamoto

Research output: Contribution to journalArticle

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Abstract

Aim: We conducted this prospective study to elucidate the long-term outcome and incidence of hepatocellular carcinoma (HCC) development after nucleos(t)ide analog (NA) treatment in patients with chronic hepatitis B (CHB) or cirrhosis. Methods: CHB or cirrhosis patients without past NA treatment or HCC were started on entecavir (ETV) or lamivudine (LVD), and prospectively followed up with monthly blood tests, and with abdominal imaging every 6months in CHB and every 3months in cirrhosis patients. Results: A total of 256 subjects with CHB (n=194) or cirrhosis (n=62) received ETV (n=129) or LVD (n=127) for 4.25years (range: 0.41-10.0). After NA treatment, serum HBV DNA, alanine aminotransferase and α-fetoprotein (AFP) dropped significantly, along with significant increases in serum albumin and prothrombin time. Drug-resistance developed in 60 cases in the LVD group and in only one case in the ETV group. HCC developed in 35 patients, and the incidence at years 1, 3, 5, 7 and 10 was significantly higher in patients with cirrhosis (8.1%, 17.5%, 43.2%, 46.7% and 53.4%, respectively) than chronic hepatitis (1.6%, 3.5%, 3.5%, 7.1% and 29.6%, respectively), with no difference between ETV and LVD. After NA treatment, the sensitivity/specificity for HCC of AFP and des-γ-carboxy prothrombin (DCP) was 45.7%/97.3% and 33.3%/96.2%, respectively, with the specificity of AFP being higher than at baseline (64.4%), at the cut-off of 10ng/mL. Conclusion: NA exerted a long-term efficacy and improved hepatic reservation in CHB and cirrhosis. After NA treatment, AFP dropped to lower than 10ng/mL with marked elevation of specificity, leading to an earlier detection of HCC.

Original languageEnglish
Pages (from-to)405-416
Number of pages12
JournalHepatology Research
Volume41
Issue number5
DOIs
Publication statusPublished - May 2011

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Lamivudine
Chronic Hepatitis B
Nucleosides
Fetal Proteins
Hepatocellular Carcinoma
Fibrosis
Transaminases
Therapeutics
Prothrombin Time
Incidence
Hematologic Tests
Prothrombin
Chronic Hepatitis
Alanine Transaminase
Drug Resistance
Serum Albumin
entecavir
Prospective Studies
Sensitivity and Specificity
Liver

Keywords

  • α-fetoprotein
  • Chronic hepatitis B
  • Entecavir
  • Hepatitis B virus
  • Hepatocellular carcinoma
  • Lamivudine

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases

Cite this

Long-term outcome and hepatocellular carcinoma development in chronic hepatitis B or cirrhosis patients after nucleoside analog treatment with entecavir or lamivudine. / Kobashi, Haruhiko; Miyake, Yasuhiro; Ikeda, Fusao; Yasunaka, Tetsuya; Nishino, Ken; Moriya, Akio; Kubota, Jyunichi; Nakamura, Shinichiro; Takaki, Akinobu; Nouso, Kazuhiro; Yamada, Gotaro; Yamamoto, Kazuhide.

In: Hepatology Research, Vol. 41, No. 5, 05.2011, p. 405-416.

Research output: Contribution to journalArticle

Kobashi, Haruhiko ; Miyake, Yasuhiro ; Ikeda, Fusao ; Yasunaka, Tetsuya ; Nishino, Ken ; Moriya, Akio ; Kubota, Jyunichi ; Nakamura, Shinichiro ; Takaki, Akinobu ; Nouso, Kazuhiro ; Yamada, Gotaro ; Yamamoto, Kazuhide. / Long-term outcome and hepatocellular carcinoma development in chronic hepatitis B or cirrhosis patients after nucleoside analog treatment with entecavir or lamivudine. In: Hepatology Research. 2011 ; Vol. 41, No. 5. pp. 405-416.
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abstract = "Aim: We conducted this prospective study to elucidate the long-term outcome and incidence of hepatocellular carcinoma (HCC) development after nucleos(t)ide analog (NA) treatment in patients with chronic hepatitis B (CHB) or cirrhosis. Methods: CHB or cirrhosis patients without past NA treatment or HCC were started on entecavir (ETV) or lamivudine (LVD), and prospectively followed up with monthly blood tests, and with abdominal imaging every 6months in CHB and every 3months in cirrhosis patients. Results: A total of 256 subjects with CHB (n=194) or cirrhosis (n=62) received ETV (n=129) or LVD (n=127) for 4.25years (range: 0.41-10.0). After NA treatment, serum HBV DNA, alanine aminotransferase and α-fetoprotein (AFP) dropped significantly, along with significant increases in serum albumin and prothrombin time. Drug-resistance developed in 60 cases in the LVD group and in only one case in the ETV group. HCC developed in 35 patients, and the incidence at years 1, 3, 5, 7 and 10 was significantly higher in patients with cirrhosis (8.1{\%}, 17.5{\%}, 43.2{\%}, 46.7{\%} and 53.4{\%}, respectively) than chronic hepatitis (1.6{\%}, 3.5{\%}, 3.5{\%}, 7.1{\%} and 29.6{\%}, respectively), with no difference between ETV and LVD. After NA treatment, the sensitivity/specificity for HCC of AFP and des-γ-carboxy prothrombin (DCP) was 45.7{\%}/97.3{\%} and 33.3{\%}/96.2{\%}, respectively, with the specificity of AFP being higher than at baseline (64.4{\%}), at the cut-off of 10ng/mL. Conclusion: NA exerted a long-term efficacy and improved hepatic reservation in CHB and cirrhosis. After NA treatment, AFP dropped to lower than 10ng/mL with marked elevation of specificity, leading to an earlier detection of HCC.",
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AU - Yasunaka, Tetsuya

AU - Nishino, Ken

AU - Moriya, Akio

AU - Kubota, Jyunichi

AU - Nakamura, Shinichiro

AU - Takaki, Akinobu

AU - Nouso, Kazuhiro

AU - Yamada, Gotaro

AU - Yamamoto, Kazuhide

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AB - Aim: We conducted this prospective study to elucidate the long-term outcome and incidence of hepatocellular carcinoma (HCC) development after nucleos(t)ide analog (NA) treatment in patients with chronic hepatitis B (CHB) or cirrhosis. Methods: CHB or cirrhosis patients without past NA treatment or HCC were started on entecavir (ETV) or lamivudine (LVD), and prospectively followed up with monthly blood tests, and with abdominal imaging every 6months in CHB and every 3months in cirrhosis patients. Results: A total of 256 subjects with CHB (n=194) or cirrhosis (n=62) received ETV (n=129) or LVD (n=127) for 4.25years (range: 0.41-10.0). After NA treatment, serum HBV DNA, alanine aminotransferase and α-fetoprotein (AFP) dropped significantly, along with significant increases in serum albumin and prothrombin time. Drug-resistance developed in 60 cases in the LVD group and in only one case in the ETV group. HCC developed in 35 patients, and the incidence at years 1, 3, 5, 7 and 10 was significantly higher in patients with cirrhosis (8.1%, 17.5%, 43.2%, 46.7% and 53.4%, respectively) than chronic hepatitis (1.6%, 3.5%, 3.5%, 7.1% and 29.6%, respectively), with no difference between ETV and LVD. After NA treatment, the sensitivity/specificity for HCC of AFP and des-γ-carboxy prothrombin (DCP) was 45.7%/97.3% and 33.3%/96.2%, respectively, with the specificity of AFP being higher than at baseline (64.4%), at the cut-off of 10ng/mL. Conclusion: NA exerted a long-term efficacy and improved hepatic reservation in CHB and cirrhosis. After NA treatment, AFP dropped to lower than 10ng/mL with marked elevation of specificity, leading to an earlier detection of HCC.

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