Background: Acetaminophen is widely used for pain relief, but is known to cause liver injury in cases of overdose. Previously, the maximum dose in Japan was 1500 mg/day, which was much lower than those in other countries. In 2011, the approved maximum dose was changed to 4000 mg/day in Japan, raising concerns over the safety of its use in Japanese patients. Therefore, we performed an epidemiological study to examine the safety of acetaminophen. In this study, we analyzed the data from a special drug use surveillance on elevation of liver function tests in Japanese patients, to assess drug-induced liver injury (DILI) of high-dose acetaminophen.
Methods: Patients who were treated with a high dose (2400 to 4000 mg/day) of acetaminophen for 4 to 24 weeks were included. Data were collected from the hospital medical information systems of 87 hospitals, from which consecutive eligible patients between January 2011 and April 2013 were identified. An abnormal liver function test (LFT) was defined as elevated alanine transaminase (ALT) level greater than 3 times the upper limit of the normal range. The prevalence of abnormal LFT was calculated, and correlation with background factors was analyzed using logistic regression.
Results: A total of 703 cases that met the inclusion criteria were analyzed. Abnormal LFT findings were observed in 22 cases (3.1%), and causality with acetaminophen could not be ruled out in 7 cases (1.0%). A logistic regression analysis showed that abnormal LFT findings correlated significantly with the presence of concomitant disease, a history of allergic disease, the duration of treatment, and on-demand use.
Conclusion: The prevalence of elevated ALT level among Japanese patients treated with acetaminophen was almost identical to that reported in other countries. However, a significant relationship between abnormal LFT and some clinical factors including the duration of treatment was found. However, this study had a limitation of inadequate patient population, suggesting a need to collect data continuously in Japan.

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Purpose: Plasma fibrinogen level is known to be a risk factor for cardiovascular disease. G/A in the −455 locus of the β-fibrinogen promoter region, especially the A allele, was previously shown to be associated with elevated plasma fibrinogen levels in middle-aged Caucasians. In Japan, the association between β-fibrinogen promoter −455 G/A polymorphism and plasma fibrinogen level in healthy young subjects has not been investigated. In this study, we evaluated the association of β-fibrinogen gene polymorphism with plasma fibrinogen level in healthy young subjects.
Methods: The subjects consisted of 136 consecutive healthy young Japanese males and females, aged from 19 to 27 years (average 20 ± 1 years). The genotype of position −455 in the β-fibrinogen promoter was analyzed using the PCR-RFLP method.
Results and Conclusion: The G/G^-455, G/A^-455 and A/A^-455 genotype frequencies were as follows: G/G 104 (0.77) (33 males, 71 females), G/A 29 (0.21) (11 males, 18 females) and A/A 3 (0.02) (1 male, 2 females). Since the frequency of A/A was very low, we divided subjects into two groups: G group consisting of G/G, and A group consisting of A/G and A/A. Because there was gender difference in plasma fibrinogen level, each genotype group was subdivided into two groups by sex. The plasma fibrinogen levels in the four groups were as follows; female G group, 236 ± 48 mg/dL; male G group, 195 ± 35 mg/dL; female A group, 243 ± 32 mg/dL; and male A group, 228 ± 30 mg/dL. Plasma fibrinogen level in male subjects with the G/G genotype was significantly lower than the levels in the other three groups. The results of this study suggest that males in A group and females in A and G groups have to maintain a lifestyle that does not elevate fibrinogen level.

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