Blood folate levels and risk of liver damage and hepatocellular carcinoma in a prospective high-risk cohort.
BACKGROUND
Studies in experimental animals suggest that low folate levels may play a role in liver damage and hepatocarcinogenesis. To examine this association in humans, folate levels in blood and risk for subsequent liver damage and hepatocellular carcinoma (HCC) were assessed in a population at high risk of liver cancer in China.


METHODS
Four hundred fifteen hepatitis B surface antigen-positive participants of the Haimen City Cohort were prospectively followed between 1998 and 2002. Serum and RBC folate levels were determined at baseline. Alanine aminotransferase (ALT) and hepatitis B virus DNA levels were measured semiannually. Logistic regression modeling was used to examine the presence of hepatitis B virus DNA and HCC, whereas linear regression with a log-link function was used to examine ALT levels.


RESULTS
There was a statistically significant inverse association between serum folate level and ALT level. ALT levels decreased with each quartile increase in serum folate (adjusted odds ratio, 0.86; 95% confidence interval, 0.76-0.97 for the highest compared with the lowest quartile; Ptrend = 0.002). After exclusion of three persons with prevalent HCC, 20 (4.9%) of the 412 study participants developed HCC during follow-up, with a median time between enrollment and HCC diagnosis of 2.66 years (interquartile range, 1.8-4.1). When comparing persons in the lowest quartile RBC folate to persons in all other quartiles, the analysis found that higher RBC folate levels were associated with reduced risk of hepatocarcinogenesis (odds ratio, 0.33, 95% confidence interval, 0.13-0.86; P(trend) = 0.02).


CONCLUSIONS
This study suggests that increased folate levels in humans may be inversely associated with the development of liver damage and HCC.
Welzel
Tania M
TM
Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, NIH, EPS, Bethesda, MD 20892-7234, USA. tmwelzel@web.de
Katki
Hormuzd A
HA
Sakoda
Lori C
LC
Evans
Alison A
AA
London
W Thomas
WT
Chen
Gang
G
O'Broin
Sean
S
Shen
Fu-Min
FM
Lin
Wen-Yao
WY
McGlynn
Katherine A
KA
D000410:Alanine Transaminase / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000453:epidemiology* / Q000821:virology; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006509:Hepatitis B / Q000150:complications; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006801:Humans; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011446:Prospective Studies
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D005492:Folic Acid; D000410:Alanine Transaminase