Skip to main content Accessibility help
×
×
Home

Sex difference in liver-related mortality and transplantation associated with dietary cholesterol in chronic hepatitis C virus infection

  • Lei Yu (a1), Chihiro Morishima (a2) and George N. Ioannou (a1) (a3)

Abstract

Dietary cholesterol induces hepatic inflammation and fibrosis in animals. We aimed to determine whether dietary cholesterol affects liver-related mortality in hepatitis C virus (HCV)-infected patients. We performed a retrospective cohort study using extended follow-up data from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial. The study included HCV patients with advanced fibrosis and compensated cirrhosis. The analysis included 657 patients who completed two FFQ. We assessed whether cholesterol intake, measured in mg/4184 kJ (mg/1000 kcal) of energy intake, was associated with liver-related death or transplantation. In 4·7 (sd 1·6) years, the incidence of liver-related death (n 46) or transplantation (n 52) was 31·8/1000 person-years. The relationship between cholesterol intake and liver-related death or transplantation was significantly different between men and women (test for interaction, P value=0·01). Each higher quartile of cholesterol intake was associated with an increased risk for liver-related death or transplantation in women (adjusted hazard ratio (AHR) 1·83; 95 % CI 1·12, 2·99; P trend=0·02), but not in men (AHR 0·96; 95 % CI 0·76, 1·22; P trend=0·73). Compared with women whose cholesterol intake was within the recommended guidelines (300 mg/d with a 8368 kJ (2000 kcal) diet), women who consumed more cholesterol had significantly increased risk for liver-related death or transplantation (AHR 4·04; 95 % CI 1·42, 11·5). High dietary cholesterol was associated with an increased risk for liver-related death and transplantation in HCV-infected women with advanced fibrosis or compensated cirrhosis. Future studies should assess whether reducing cholesterol intake, among women who consume an excessive amount, can decrease HCV-related mortality.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Sex difference in liver-related mortality and transplantation associated with dietary cholesterol in chronic hepatitis C virus infection
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Sex difference in liver-related mortality and transplantation associated with dietary cholesterol in chronic hepatitis C virus infection
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Sex difference in liver-related mortality and transplantation associated with dietary cholesterol in chronic hepatitis C virus infection
      Available formats
      ×

Copyright

Corresponding author

* Corresponding author: L. Yu, email leiy@medicine.washington.edu

References

Hide All
1. Mohd Hanafiah, K, Groeger, J, Flaxman, AD, et al. (2013) Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology 57, 13331342.
2. Davis, GL, Alter, MJ, El-Serag, H, et al. (2010) Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology 138, 513521.
3. Poynard, T, Bedossa, P & Opolon, P (1997) Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 349, 825832.
4. Wiese, M, Berr, F, Lafrenz, M, et al. (2000) Low frequency of cirrhosis in a hepatitis C (genotype 1b) single-source outbreak in Germany: a 20-year multicenter study. Hepatology 32, 9196.
5. Seeff, LB, Miller, RN, Rabkin, CS, et al. (2000) 45-year follow-up of hepatitis C virus infection in healthy young adults. Ann Intern Med 132, 105111.
6. Wanless, IR, Belgiorno, J & Huet, PM (1996) Hepatic sinusoidal fibrosis induced by cholesterol and stilbestrol in the rabbit: 1. Morphology and inhibition of fibrogenesis by dipyridamole. Hepatology 24, 855864.
7. Teratani, T, Tomita, K, Suzuki, T, et al. (2012) A high-cholesterol diet exacerbates liver fibrosis in mice via accumulation of free cholesterol in hepatic stellate cells. Gastroenterology 142, 152164.
8. Perlemuter, G, Sabile, A, Letteron, P, et al. (2002) Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis. FASEB J 16, 185194.
9. Iqbal, J, Rudel, LL & Hussain, MM (2008) Microsomal triglyceride transfer protein enhances cellular cholesteryl esterification by relieving product inhibition. J Biol Chem 283, 1996719980.
10. Hussain, MM, Rava, P, Walsh, M, et al. (2012) Multiple functions of microsomal triglyceride transfer protein. Nutr Metab (Lond) 9, 14.
11. Tabas, I (2002) Consequences of cellular cholesterol accumulation: basic concepts and physiological implications. J Clin Invest 110, 905911.
12. Di Bisceglie, AM, Shiffman, ML, Everson, GT, et al. (2008) Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. N Engl J Med 359, 24292441.
13. Yu, L, Morishima, C & Ioannou, GN (2013) Dietary cholesterol intake is associated with progression of liver disease in patients with chronic hepatitis C: analysis of the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis trial. Clin Gastroenterol Hepatol 11, 16611666.
14. Di Bisceglie, AM, Stoddard, AM, Dienstag, JL, et al. (2011) Excess mortality in patients with advanced chronic hepatitis C treated with long-term peginterferon. Hepatology 53, 11001108.
15. Ishak, KG (1994) Chronic hepatitis: morphology and nomenclature. Mod Pathol 7, 690713.
16. Freedman, ND, Everhart, JE, Lindsay, KL, et al. (2009) Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C. Hepatology 50, 13601369.
17. Everhart, JE, Lok, AS, Kim, HY, et al. (2009) Weight-related effects on disease progression in the hepatitis C antiviral long-term treatment against cirrhosis trial. Gastroenterology 137, 549557.
18. Morishima, C, Shiffman, ML, Dienstag, JL, et al. (2012) Reduction in hepatic inflammation is associated with less fibrosis progression and fewer clinical outcomes in advanced hepatitis C. Am J Gastroenterol 107, 13881398.
19. Lee, WM, Dienstag, JL, Lindsay, KL, et al. (2004) Evolution of the HALT-C Trial: pegylated interferon as maintenance therapy for chronic hepatitis C in previous interferon nonresponders. Control Clin Trials 25, 472492.
20. Block, G, Thompson, FE, Hartman, AM, et al. (1992) Comparison of two dietary questionnaires validated against multiple dietary records collected during a 1-year period. J Am Diet Assoc 92, 686693.
21. Hu, FB, Stampfer, MJ, Rimm, E, et al. (1999) Dietary fat and coronary heart disease: a comparison of approaches for adjusting for total energy intake and modeling repeated dietary measurements. Am J Epidemiol 149, 531540.
22. Cox, D (1972) Regression models and life tables. J R Stat Soc Series B Stat Methodol 34, 187202.
23. Willett, WC, Howe, GR & Kushi, LH (1997) Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 65, Suppl. 4, 1220S1228S discussion 1229S–1231S.
24. Brown, CC, Kipnis, V, Freedman, LS, et al. (1994) Energy adjustment methods for nutritional epidemiology: the effect of categorization. Am J Epidemiol 139, 323338.
25. Savard, C, Tartaglione, EV, Kuver, R, et al. (2013) Synergistic interaction of dietary cholesterol and dietary fat in inducing experimental steatohepatitis. Hepatology 57, 8192.
26. Kainuma, M, Fujimoto, M, Sekiya, N, et al. (2006) Cholesterol-fed rabbit as a unique model of nonalcoholic, nonobese, non-insulin-resistant fatty liver disease with characteristic fibrosis. J Gastroenterol 41, 971980.
27. Turley, SD, Schwarz, M, Spady, DK, et al. (1998) Gender-related differences in bile acid and sterol metabolism in outbred CD-1 mice fed low- and high-cholesterol diets. Hepatology 28, 10881094.
28. McKinlay, SM, Bifano, NL & McKinlay, JB (1985) Smoking and age at menopause in women. Ann Intern Med 103, 350356.
29. Everson, GT, McKinley, C & Kern, F Jr (1991) Mechanisms of gallstone formation in women. Effects of exogenous estrogen (Premarin) and dietary cholesterol on hepatic lipid metabolism. J Clin Invest 87, 237246.
30. Tooze, JA, Subar, AF, Thompson, FE, et al. (2004) Psychosocial predictors of energy underreporting in a large doubly labeled water study. Am J Clin Nutr 79, 795804.
31. Koepsell, TD (2003) Epidemiologic Methods: Studying the Occurence of Illness. Oxford: Oxford University Press.
32. Thompson, F & Subar, A (2008) Dietary assessment methodology. In Nutrition in the Prevention and Treatment of Disease, 2nd ed. Chapter 1, pp. 3–39 [AM Coulston and CJ Boushey, editors]. Burlington, MA: Elsevier Academic Press.
33. Petta, S, Marchesini, G, Caracausi, L, et al. (2013) Industrial, not fruit fructose intake is associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients. J Hepatol 59, 11691176.
34. Jacobson, IM, Gordon, SC, Kowdley, KV, et al. (2013) Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 368, 18671877.
35. Kowdley, KV, Lawitz, E, Poordad, F, et al. (2014) Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. N Engl J Med 370, 222232.
36. Makiyama, A, Itoh, Y, Kasahara, A, et al. (2004) Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma after a sustained response to interferon therapy. Cancer 101, 16161622.
37. Reau, NS & Jensen, DM (2014) Sticker shock and the price of new therapies for hepatitis C: is it worth it? Hepatology 59, 12461249.
38. Holmberg, SD, Spradling, PR, Moorman, AC, et al. (2013) Hepatitis C in the United States. N Engl J Med 368, 18591861.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Type Description Title
WORD
Supplementary materials

Yu supplementary material
Tables S1-S5

 Word (52 KB)
52 KB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed