Association of nucleos(t)ide analogue therapy with reduced risk of hepatocellular carcinoma in patients with chronic hepatitis B: a nationwide cohort study.
OBJECTIVE
Treatment for hepatitis B virus infection reduces the risk of hepatocellular carcinoma (HCC). However, the long-term protective effects for subgroups of patients with chronic hepatitis B are unclear.


METHODS
We conducted a retrospective nationwide cohort study using data from Taiwan's National Health Insurance Research Database (from January 1, 1997, through December 31, 2010). Cumulative incidences were calculated and multivariable analyses were carried out after adjusting for competing mortality. Propensity scores were used to match 21,595 patients with chronic hepatitis B who received nucleoside analogue therapy for at least 90 days (treated cohort) with 21,595 untreated patients with chronic hepatitis B (controls), who received hepatoprotectants for at least 90 days. Data were collected from the treated cohort for a mean period of 3.46 years and from controls for 5.24 years.


RESULTS
The treated cohort had a significantly lower 7-year incidence of HCC (7.32%; 95% confidence interval [CI], 6.77%-7.87%) than controls (22.7%; 95% CI, 22.1%-23.3%; P < .001). After adjusting for competing mortality and other confounders, nucleos(t)ide analogue treatment was associated with a reduced risk of HCC, with an adjusted hazard ratio of 0.37 (95% CI, 0.34-0.39; P < .001). Sensitivity analyses confirmed the association between nucleos(t)ide analogue treatment and reduced risk of HCC. Age, sex, cirrhosis, and diabetes mellitus modified this association.


CONCLUSIONS
Based on a retrospective, nationwide study in Taiwan, nucleoside analogue therapy use is associated with reduced risk of HCC in patients with chronic hepatitis B virus infection.
Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Public Health and Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan; Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan.
Chun-Ying
CY
Wu
School of Medicine, Fu Jen Catholic University, Taipei, Taiwan; Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan. Electronic address: jawtown@gmail.com.
Jaw-Town
JT
Lin
School of Medicine, Fu Jen Catholic University, Taipei, Taiwan.
Hsiu J
HJ
Ho
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine and Genomic Research Center, National Yang-Ming University, Taipei, Taiwan; Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan.
Chien-Wei
CW
Su
Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Public Health and Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan.
Teng-Yu
TY
Lee
Institute of Clinical Medicine and Genomic Research Center, National Yang-Ming University, Taipei, Taiwan.
Shen-Yung
SY
Wang
Institute of Clinical Medicine and Genomic Research Center, National Yang-Ming University, Taipei, Taiwan.
Chuhui
C
Wu
Institute of Clinical Medicine and Genomic Research Center, National Yang-Ming University, Taipei, Taiwan; Translational Research Division, Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: jcwu@vghtpe.gov.tw.
Jaw-Ching
JC
Wu
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D015331:Cohort Studies; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009705:Nucleosides / Q000627:therapeutic use*; D009711:Nucleotides / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D016896:Treatment Outcome
D009705:Nucleosides; D009711:Nucleotides
Antiviral Agent; HBV; Hepatoma; NHIRD