Cigarette smoking and serum liver enzymes: the role of alcohol and inflammation.
OBJECTIVE
Smoking may affect the liver through inflammatory pathways and may aggravate the pathogenic effects of alcohol on the liver. We have examined the relationship between cigarette smoking and liver enzymes and the role of alcohol and C-reactive protein (CRP), a marker of inflammation.


METHODS
The subjects consisted of 4595 men aged 40-59 y with no history of coronary heart disease drawn from general practices in 24 British towns.


RESULTS
Cigarette smoking was significantly associated with increased levels of gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) (P < 0.0001) and was inversely associated with increased aspartate aminotransferase (AST) after adjustment for alcohol intake, body mass index and physical activity. Compared with never smokers, heavy cigarette smokers (> or =40/day) were associated with increased odds of elevated GGT (> or =23 IU/L) (adjusted odds ratio [OR] 1.56 [1.08, 2.27]), which was abolished after adjustment for CRP (adjusted OR 1.27 [0.87, 1.86]). There was a significant interaction between smoking and alcohol on GGT. In the absence of heavy drinking, there was no association between smoking and GGT after adjustment for CRP. Among heavy drinkers, smoking was associated with increased levels of GGT independent of CRP. Smoking was associated with increased odds of elevated ALP (> or =11 IU/L) (adjusted OR 3.95 [2.77, 5.62]), which persisted after adjustment for CRP and white cell count (adjusted OR 2.90 [1.99-4.23]), possibly reflecting increased bone cell activity.


CONCLUSIONS
The findings suggest that cigarette smoking does not cause liver injury, but may enhance the effects of alcohol on liver cell injury in heavy drinkers.
Department of Primary Care and Population Health, UCL Medical School, Royal Free Campus, London, UK. goya@pcps.ucl.ac.uk
S Goya
SG
Wannamethee
A Gerald
AG
Shaper
D000328:Adult; D000438:Alcohols / Q000009:adverse effects*; D000469:Alkaline Phosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000009:adverse effects*; D005723:gamma-Glutamyltransferase / Q000097:blood
D000438:Alcohols; D015415:Biomarkers; D002097:C-Reactive Protein; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase