Abnormal liver functions associated with occupational exposure to dimethylformamide and hepatitis B virus

N,N-Dimethylformamide (DMF) has excellent properties and is used intensivel y in the production of synthetic leather and resins. It has caused hepatoxi city in human and animal studies. Hepatitis B virus (HBV) and hepatitis C v irus infections are reported to be the major causes of chronic liver diseas es (including liver cirrhosis and liver cancer) in Taiwan. This study exami ned the dose-response relationship of the observed abnormal liver function among the DMF-exposed workers and the interactions among DMF, other chemica l exposures, HBV infection, and potential confounders on liver abnormalitie s. The average DMF exposure concentration was 11.6 ppm (median, 5.9 ppm; ra nge, 0.1 to 86.6 ppm); 65 of 176 workers (36.9%) had high (>10 ppm) DMF exp osure, 37 (21%) had middle (>5 ppm, less than or equal to 10 ppm) exposure, and 74 (42%) had low (less than or equal to5 ppm) exposure. There were 24 of 65 abnormal liver function test results (LFTs) (36.9%) (elevations of ei ther glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, or gamma-glutamyl transpeptidase) among the workers with high DMF exposure, 10 or 37 abnormal LFTs (27%) among workers with middle DMF exposure, and 1 1 of 74 abnormal LFTs (22%) among workers with low DMF exposure. Compared w ith the workers having low DMF exposure, the HBV, drinking, body mass index (BMI), sex, duration of employment, epichlorohydrin, and toluene exposure adjusted odds ratios (ORs) (and 95% confidence intervals [CIs]) for abnorma l LFTs were 1.62 (0.61, 4.28) for workers with middle DMF exposure and 2.93 (1.27, 6.8) for those with high DMF exposure, and there was a significant dose response between DMF exposure and the prevalence of abnormal LFTs (P = 0.006). There were significant associations between abnormal LFTs and HBV carriers (adjusted OR: 3.11; 95% CI: 1.29, 7.5; P = 0.01) and between abnor mal LFTs and increased BMI (adjusted OR: 2.2; 95% CI: 1.02, 4.72; P = 0.041 ). Ultrasonography showed significant associations between chronic liver di seases and HBV carrier status, increased BMI, and high cumulative (>100 ppm -years) DMF exposure (respectively, adjusted OR: 9.58, 95% CI: 1.79, 51.4, P = 0.007; adjusted OR: 13.2, 95% CI: 1.32, 132, P = 0.025; and adjusted OR : 6.2, 95% CI: 1.14, 34.1, P = 0.032). Drinking and BMI were significantly associated with fatty liver (respectively, adjusted OR: 4.9, 95% CI: 1.39, 17.3, P = 0.012; and adjusted OR: 7.93, 95% CI: 1.6, 39.3, P = 0.01). In co nclusion, this study demonstrated that (1) a significant dose-response rela tionship existed between liver function abnormalities and DMF exposure amon g workers in Taiwan, (2) HBV carrier status or increased BMI had synergisti c effects with DMF in causing liver abnormalities (abnormal LFTs and clinic al chronic liver diseases).