TY - JOUR
T1 - Smoking and severity of hepatic fibrosis in nonalcoholic fatty liver disease
AU - Zein, Claudia O.
AU - Unalp, Aynur
AU - Colvin, Ryan
AU - Liu, Yao Chang
AU - McCullough, Arthur J.
N1 - Funding Information:
This study involved analysis of data collected as part of the multicenter Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) [20] . The NASH CRN is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). General information about the network and clinical, laboratory, and histological observations in this well characterized patient cohort have been reported [20,21] . Extensive information is gathered in every subject including demographic characteristics, anthropomorphic measurements, smoking history, alcohol consumption history, medical history, medication use, laboratory tests, and liver biopsy results. Among its goals, the NASH CRN seeks the generation of hypotheses that would lead to the use of database resources in order to further elucidate the pathogenesis of NAFLD and to identify determinants of disease progression and severity [20] . There were 1091 adult subjects enrolled in the NASH CRN studies between October 2004 and February 2008 who had liver biopsies. These 1091 subjects constitute the current study population. As of the date of this analysis, that number represents over 90% of the NASH CRN subjects with available liver biopsy.
Funding Information:
This work was supported by grants from the National Institutes of Health to the NASH Clinical Research Network ( U01DK61718 , U01DK61728 , U01DK61731 , U01DK61732 , U01DK61734 , U01DK61737 , U01DK61738 , U01DK61730 , U01DK61713 ) and, in part, by the intramural program of the National Cancer Institute. Other grant support includes the following National Institutes of Health Clinical and Translational Science Awards: UL1RR024989 , UL1RR024128 , M01RR000750 , UL1RR024131 , M01RR000827 , UL1RR025014 , M01RR000065 . Dr. Claudia O. Zein is supported by Grant No. KL2 RR024990 from the National Center for Research Resources (NCRR) , a component of the NIH and NIH Roadmap for Medical Research.
PY - 2011/4
Y1 - 2011/4
N2 - Background & Aims: Although many predictors of disease severity of nonalcoholic fatty liver disease (NAFLD) have been proposed, studies of the potential effects of specific environmental exposures on human NAFLD are lacking. Smoking increases insulin resistance. Given the pathophysiological role of insulin resistance in NAFLD, characterization of the influence of smoking in NAFLD is warranted. The aim of this paper was to study the potential association between cigarette smoking and advanced fibrosis in NAFLD. Methods: All adults enrolled in the NASH CRN studies, between October 2004 and February 2008, who had liver biopsies, were included (n = 1091). Advanced fibrosis was defined as stages 3-4. Analyses were performed. Results: Significant bivariate associations were demonstrated between advanced fibrosis and age, gender, ethnicity, diabetes, and smoking history. History of smoking ≥10 pack-years was more common (p <0.0001) among patients with advanced fibrosis. Multivariate analysis demonstrated an association between smoking history of ≥10 pack-years and advanced fibrosis (OR = 1.63). Among non-diabetics, history of ≥10 pack-years was associated with an OR of 2.48 for advanced fibrosis. High frequencies of advanced fibrosis were observed among diabetics (with or without ≥10 pack-years history) and non-diabetics with ≥10 pack-years history as compared to non-diabetics without significant smoking history. Conclusions: Smoking history was associated with advanced liver fibrosis in this large multicenter cohort of NAFLD patients. The results indicate that smoking may enhance the progression of NAFLD partly through its effect on insulin resistance. Our results are consistent with recent animal studies suggesting that cigarette smoke may aggravate fatty liver. To our knowledge, this is the first study to show that cigarette smoking is associated with increased fibrosis severity in human NALFD, suggesting it may accelerate disease progression. These results may support a formal recommendation of smoking cessation in patients with NAFLD.
AB - Background & Aims: Although many predictors of disease severity of nonalcoholic fatty liver disease (NAFLD) have been proposed, studies of the potential effects of specific environmental exposures on human NAFLD are lacking. Smoking increases insulin resistance. Given the pathophysiological role of insulin resistance in NAFLD, characterization of the influence of smoking in NAFLD is warranted. The aim of this paper was to study the potential association between cigarette smoking and advanced fibrosis in NAFLD. Methods: All adults enrolled in the NASH CRN studies, between October 2004 and February 2008, who had liver biopsies, were included (n = 1091). Advanced fibrosis was defined as stages 3-4. Analyses were performed. Results: Significant bivariate associations were demonstrated between advanced fibrosis and age, gender, ethnicity, diabetes, and smoking history. History of smoking ≥10 pack-years was more common (p <0.0001) among patients with advanced fibrosis. Multivariate analysis demonstrated an association between smoking history of ≥10 pack-years and advanced fibrosis (OR = 1.63). Among non-diabetics, history of ≥10 pack-years was associated with an OR of 2.48 for advanced fibrosis. High frequencies of advanced fibrosis were observed among diabetics (with or without ≥10 pack-years history) and non-diabetics with ≥10 pack-years history as compared to non-diabetics without significant smoking history. Conclusions: Smoking history was associated with advanced liver fibrosis in this large multicenter cohort of NAFLD patients. The results indicate that smoking may enhance the progression of NAFLD partly through its effect on insulin resistance. Our results are consistent with recent animal studies suggesting that cigarette smoke may aggravate fatty liver. To our knowledge, this is the first study to show that cigarette smoking is associated with increased fibrosis severity in human NALFD, suggesting it may accelerate disease progression. These results may support a formal recommendation of smoking cessation in patients with NAFLD.
KW - Alcohol
KW - Liver fibrosis
KW - Nonalcoholic fatty liver disease
KW - Predictors
KW - Smoking
UR - http://www.scopus.com/inward/record.url?scp=79952701706&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952701706&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2010.07.040
DO - 10.1016/j.jhep.2010.07.040
M3 - Article
C2 - 21126792
AN - SCOPUS:79952701706
SN - 0168-8278
VL - 54
SP - 753
EP - 759
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -