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

doi:10.1111/j.1872-034X.2011.00785.x

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

Hepatol Res. 2011 May;41(5):405-16. doi: 10.1111/j.1872-034X.2011.00785.x. Epub 2011 Mar 21.

Authors

Haruhiko Kobashi¹, Yasuhiro Miyake, Fusao Ikeda, Tetsuya Yasunaka, Ken Nishino, Akio Moriya, Jyunichi Kubota, Shinichiro Nakamura, Akinobu Takaki, Kazuhiro Nouso, Gotaro Yamada, Kazuhide Yamamoto

Affiliation

¹ Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama Department of Clinical Research, Center for Liver Disease, Kawasaki Hospital, Kawasaki Medical School, Kawasaki Department of Internal Medicine, Tsuyama Central Hospital, Tsuyama, Japan.

PMID: 21435126
DOI: 10.1111/j.1872-034X.2011.00785.x

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 6 months in CHB and every 3 months 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 4.25 years (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 10 ng/mL.

Conclusion: NA exerted a long-term efficacy and improved hepatic reservation in CHB and cirrhosis. After NA treatment, AFP dropped to lower than 10 ng/mL with marked elevation of specificity, leading to an earlier detection of HCC.