The Reply

Abstract

Smoking was not included as a variable in this study for a variety of reasons. First, we were evaluating the association between metabolic syndrome and hepatocellular carcinoma. As smoking is not part of metabolic syndrome, it did not play a part in answering our primary question. Smoking or tobacco abuse is not one of the major risk factors identified for hepatocellular carcinoma in the US at this time. It is worth recognizing, however, that cigarette smoking and tobacco use in general is known to be carcinogenic, and it would be worth evaluating in research studies on hepatocellular carcinoma risk in the future. Second, all of our variables were included based on diagnosis coding during outpatient encounters. Similar to obesity, smoking and tobacco abuse are not often represented as a diagnosis code in billing for encounters, and would likely under-represent smoking in the study population. With regard to the variables we used during this study, please refer to the Methods section of our original manuscript for description of how these variables were chosen.1Kasmari A. Welch A. Liu G. Leslie D. McGarrity T. Riley T. Independent of cirrhosis, hepatocellular carcinoma risk is increased with diabetes and metabolic syndrome: a retrospective cohort study.Am J Med. 2017; 130: 746.e1-746.e7Abstract Full Text Full Text PDF Scopus (68) Google Scholar Insurance claims data were used from the MarketScan database (Truven Health Analytics, Ann Arbor, Mich) from 2008-2012, when the identified variables were included on an insurance claim. The imperfections of this method are addressed in the Limitations section of our manuscript.1Kasmari A. Welch A. Liu G. Leslie D. McGarrity T. Riley T. Independent of cirrhosis, hepatocellular carcinoma risk is increased with diabetes and metabolic syndrome: a retrospective cohort study.Am J Med. 2017; 130: 746.e1-746.e7Abstract Full Text Full Text PDF Scopus (68) Google Scholar Severity or length of risk factor disease was unable to be identified in this study, and future research efforts will be necessary to explore this further. The mechanisms by which diabetes, hepatitis C, and cirrhosis can lead to insulin resistance and eventual hepatocellular carcinoma are addressed in the Discussion section of our manuscript.1Kasmari A. Welch A. Liu G. Leslie D. McGarrity T. Riley T. Independent of cirrhosis, hepatocellular carcinoma risk is increased with diabetes and metabolic syndrome: a retrospective cohort study.Am J Med. 2017; 130: 746.e1-746.e7Abstract Full Text Full Text PDF Scopus (68) Google Scholar Again, to address the point about smoking, this was not the focus of our study and would require future research efforts using a different patient selection method to thoroughly investigate this potential association. It is true that correlation does not mean causality. The Conclusion section of our manuscript states there is an association between type II diabetes and hypertension with hepatocellular carcinoma.1Kasmari A. Welch A. Liu G. Leslie D. McGarrity T. Riley T. Independent of cirrhosis, hepatocellular carcinoma risk is increased with diabetes and metabolic syndrome: a retrospective cohort study.Am J Med. 2017; 130: 746.e1-746.e7Abstract Full Text Full Text PDF Scopus (68) Google Scholar As we state in our Limitations section, further analysis is required to further detail this association using a different method that is not based on insurance claims data.1Kasmari A. Welch A. Liu G. Leslie D. McGarrity T. Riley T. Independent of cirrhosis, hepatocellular carcinoma risk is increased with diabetes and metabolic syndrome: a retrospective cohort study.Am J Med. 2017; 130: 746.e1-746.e7Abstract Full Text Full Text PDF Scopus (68) Google Scholar Hepatocellular Carcinoma, Diabetes, and Metabolic Syndrome: Correlation Does Not Mean CausalityThe American Journal of MedicineVol. 130Issue 9PreviewThe Limitations section of the retrospective study about hepatocellular carcinoma risk in patients with diabetes and metabolic syndrome must be completed.1 Full-Text PDF