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Hepatitis B virus (HBV) vaccination is recommended for individuals with chronic liver disease. However, the response to standard doses of hepatitis B vaccines in such individuals has been poor. The aim of the present study was to assess the response to high-dose short-interval HBV vaccination in individuals with chronic liver disease of different aetiologies. A total two hundred and 24 subjects with chronic liver disease (138 chronic active hepatitis and 86 cirrhosis) and 26 healthy controls were vaccinated using a high-dose (40 μg) short-interval (monthly for 3 consecutive months) HBV vaccination schedule.One hundred and thirty-eight of the 224 subjects with chronic liver disease (62%) seroconverted to anti-HBs antibody positivity (>10 mIU/mL) after the third dose of vaccine as compared with 24 of the 26 controls (92%) (P < 0.01). The response rate was reduced in individuals with cirrhosis (36/86, 42%), particularly in alcohol-induced cirrhosis (2/17, 12%), as compared with individuals with chronic hepatitis (102/138, 74%) (P < 0.001). No significant HBV vaccination-related adverse effects were seen in individuals with or without cirrhosis as well as in the controls.High-dose short-interval HBV vaccination is safe and efficacious in individuals with chronic liver disease. The response to HBV vaccination is reduced in cirrhotics, particularly those with alcoholic cirrhosis. These data suggest that HBV vaccination should be accomplished early in an individual cause of chronic liver disease prior to the development of cirrhosis.