title: Rapid Alanine Aminotransferase Normalization with Entecavir and Hepatocellular Carcinoma in Hepatitis B Virus-Associated Cirrhosis.
abstract: Sustained abnormal serum alanine aminotransferase (ALT) levels can increase the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B.
  
  
  
  This study is aimed to confirm the impact of rapid ALT normalization (≤30 IU/L) on HCC risk in patients with hepatitis B virus (HBV)-associated cirrhosis after entecavir (ETV) commencement.
  
  
  
  A total of 578 treatment-naïve patients with HBV-associated cirrhosis (mean age 51 ± 9 years, male sex 63.3%) were treated with ETV for more than 1 year. Serum ALT and HBV DNA levels were measured at three time points (baseline, 6, and 12 months after ETV commencement) and subjected to risk factor analysis.
  
  
  
  Median follow-up after ETV commencement was 43 (12-98) months. Cumulative incidences of HCC at 1, 3, 5, and 7 years were 0.3, 8.5, 19.5, and 30.6%, respectively. Univariate Cox regression analysis showed that older age, abnormal ALT at 6 months or 12 months, and lower platelet count were significant risk factors for HCC. However, gender, HBeAg positivity, abnormal ALT levels or HBV DNA levels at baseline, and detectable HBV DNA at 6 or 12 months were not risk factors. Multivariate analysis showed that older age (P < 0.001), abnormal ALT at 12 months (P = 0.006), and lower platelet count (P = 0.034) were the risk factors for HCC.
  
  
  
  Abnormal serum ALT levels after ETV commencement are significant risk factor for HCC. Therefore, ALT should be rapidly normalized to minimize the risk of HCC development in patients with HBV-associated cirrhosis.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, 21, Namdong-daero 774 beon-gil, Namdong-gu, Incheon, 21565, South Korea.
authors.forename: Eui Joo
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Korea University Medical College, Korea University Guro Hospital, 97 Gurodong-gil, Guro-gu, Seoul, 08308, South Korea.
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Yeon
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, 21, Namdong-daero 774 beon-gil, Namdong-gu, Incheon, 21565, South Korea. kos@gilhospital.com.
authors.forename: Oh Sang
authors.initials: OS
authors.lastname: Kwon
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, 21, Namdong-daero 774 beon-gil, Namdong-gu, Incheon, 21565, South Korea.
authors.forename: Heon Nam
authors.initials: HN
authors.lastname: Lee
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, 21, Namdong-daero 774 beon-gil, Namdong-gu, Incheon, 21565, South Korea.
authors.forename: Seung Kak
authors.initials: SK
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Korea University Medical College, Korea University Guro Hospital, 97 Gurodong-gil, Guro-gu, Seoul, 08308, South Korea.
authors.forename: Seong Hee
authors.initials: SH
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Korea University Medical College, Korea University Guro Hospital, 97 Gurodong-gil, Guro-gu, Seoul, 08308, South Korea.
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Byun
authors.affiliation: Department of Internal Medicine, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1 Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul, 05030, South Korea.
authors.forename: Jeong Han
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1 Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul, 05030, South Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, Korea University Medical College, Korea University Ansan Hospital, 123 Jeokgeum-ro, Danwon-Gu, Ansan-Si, Gyeonggi-Do, 15355, South Korea.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Suh
authors.affiliation: Department of Internal Medicine, Korea University Medical College, Korea University Ansan Hospital, 123 Jeokgeum-ro, Danwon-Gu, Ansan-Si, Gyeonggi-Do, 15355, South Korea.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Yim
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, 21, Namdong-daero 774 beon-gil, Namdong-gu, Incheon, 21565, South Korea.
authors.forename: Yun Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, 21, Namdong-daero 774 beon-gil, Namdong-gu, Incheon, 21565, South Korea.
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000367:Age Factors; D000410:Alanine Transaminase / Q000032:analysis / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000097:blood* / Q000209:etiology; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010976:Platelet Count / Q000706:statistics & numerical data; D011379:Prognosis; D056910:Republic of Korea / Q000453:epidemiology; D018570:Risk Assessment
chemical_list: D000998:Antiviral Agents; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase
keywords: Alanine aminotransferase; Cirrhosis; Entecavir; Hepatitis B virus; Hepatocellular carcinoma