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PLoS One. 2017 Jan 18;12(1):e0166188. doi: 10.1371/journal.pone.0166188. eCollection 2017.

Oral Medications Enhance Adherence to Surveillance for Hepatocellular Carcinoma and Survival in Chronic Hepatitis B Patients.

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Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Department of Internal Medicine and Liver Center, Ewha Womans University School of Medicine Seoul, Korea.
Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, Korea.
Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center Seoul, Korea.
Digestive Disease Center and Research Institute Department of Gastroenterology and Hepatology, Soonchunhyang University Bucheon Hospital.
Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, South Korea.
Department of Internal Medicine CHA Gangnam Medical Center, CHA University.



Regular surveillance for hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients is essential to detect HCC earlier and to improve prognosis. This study investigated whether prescription of oral medication contributes to adherence to surveillance, early tumor detection, and overall survival (OS).


A total of 401 CHB patients who were newly diagnosed with HCC were included: 134 patients received no medication (group 1), 151 received hepatoprotective agents such as ursodeoxycholic acid and silymarin (group 2), and 116 received antiviral agents (group 3) at two years before HCC diagnosis. The primary endpoint was OS, and secondary endpoints were compliance to regular surveillance and HCC status at diagnosis.


Compared to group 1, both group 2 and 3 had higher rates of good compliance to regular surveillance (defined as participation in >80% of imaging intervals being ≤6 months) (58.2%, 90.1%, and 97.4%, respectively; P<0.001), more HCC diagnosed at a very early stage (20.9%, 32.5%, and 36.2%; P = 0.019) and smaller tumor size (2.8±2.4cm, 1.9±1.1cm, and 1.8±0.9cm; P<0.001). Finally, compared to group 1, both group 2 (hazard ratio, 0.63; 95% confidence interval, 0.41-0.97; P = 0.035) and group 3 (hazard ratio, 0.40; 95% confidence interval, 0.22-0.71; P = 0.002) had significantly longer OS. In mediation analysis, prolonged OS is resulted considerably from indirect effect mediated by shorter imaging interval (>100% in group 2 and 14.5% in group 3) rather than direct effect of medication itself.


Prescription of oral medication improves compliance to surveillance and enables early detection of HCC, which is associated with enhanced survival.

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