Coffee Consumption Is Associated With Response to Peginterferon and Ribavirin Therapy in Patients With Chronic Hepatitis C

Gastroenterology
Volume 140, Issue 7, June 2011, Pages 1961-1969

Neal D. Freedman , Teresa M. Curto^‡, Karen L. Lindsay^§, Elizabeth C. Wright, Rashmi Sinha, James E. Everhart^¶ and HALT-C TRIAL GROUP

^‡ New England Research Institutes, Watertown, Massachusetts

Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland

Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland

^§ Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California

^¶ Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland

Received 20 November 2010;

accepted 18 February 2011.

Available online 2 March 2011.

Background & Aims

High-level coffee consumption has been associated with reduced progression of pre-existing liver diseases and lower risk of hepatocellular carcinoma. However, its relationship with therapy for hepatitis C virus infection has not been evaluated.

Methods

Patients (n = 885) from the lead-in phase of the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial recorded coffee intake before retreatment with peginterferon α-2a (180 μg/wk) and ribavirin (1000–1200 mg/day). We assessed patients for early virologic response (2 log₁₀ reduction in level of hepatitis C virus RNA at week 12; n = 466), and undetectable hepatitis C virus RNA at weeks 20 (n = 320), 48 (end of treatment, n = 284), and 72 (sustained virologic response; n = 157).

Results

Median log₁₀ drop from baseline to week 20 was 2.0 (interquartile range [IQR], 0.6–3.9) among nondrinkers and 4.0 (IQR, 2.1–4.7) among patients that drank 3 or more cups/day of coffee (P trend <.0001). After adjustment for age, race/ethnicity, sex, alcohol, cirrhosis, ratio of aspartate aminotransferase to alanine aminotransferase, the IL28B polymorphism rs12979860, dose reduction of peginterferon, and other covariates, odds ratios for drinking 3 or more cups/day vs nondrinking were 2.0 (95% confidence interval [CI]: 1.1–3.6; P trend = .004) for early virologic response, 2.1 (95% CI: 1.1–3.9; P trend = .005) for week 20 virologic response, 2.4 (95% CI: 1.3–4.6; P trend = .001) for end of treatment, and 1.8 (95% CI: 0.8–3.9; P trend = .034) for sustained virologic response.

Conclusions

High-level consumption of coffee (more than 3 cups per day) is an independent predictor of improved virologic response to peginterferon plus ribavirin in patients with hepatitis C.

Keywords: Liver Fibrosis; Diet; Risk Factor; Caffeine

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; FFQ, food frequency questionnaire; HALT-C, Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial; HCV, hepatitis C virus; HOMA2, homeostatic model assessment score of insulin resistance; IQR, interquartile range; LDL, low-density lipoprotein

Article Outline

Materials and Methods

Patient Population

Assessment of Coffee and Tea Consumption

Assessment of Outcomes

Statistical Analysis

Results

Discussion

Acknowledgements

References

Conflicts of interest This author discloses the following: Dr Lindsay was a consultant and received research support from Hoffmann-La Roche, Inc. (now Genentech) during this study and is now an employee of Tibotec, Inc. (a subsidiary of Johnson and Johnson), Titusville, NJ.The remaining authors disclose no conflicts.

Funding This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (contract numbers are listed in the Acknowledgments). Additional support was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed in the Acknowledgments). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc. (now Genentech), through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. This research was also supported in part by the Intramural Research Program of the National Cancer Institute. The funding organizations had no role in the design and conduct of the study; the collection, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript.

Reprint requests Address requests for reprints to: Neal Freedman, PhD, MPH, Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS/320, MSC 7232, Rockville, Maryland 20852. fax: (301) 496-682.

Source

Figure 1. Stratified analysis of the association of baseline coffee intake with week 20 virologic response in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial. Odds ratios shown are for an increase in coffee consumption of 1 drink per day and are adjusted for age (continuous), sex, race/ethnicity (white, African American, Hispanic, other), alcohol use (current, former, and never), cirrhosis at baseline, genotype 1, aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio (continuous), log hepatitis C virus (HCV) RNA level at baseline (continuous), previous use of ribavirin, hemoglobin (continuous), neutrophils (continuous), platelets (continuous), categories of peginterferon medication dose during first 20 weeks of treatment (≥98%–100%, ≥80%–<98%, ≥60%–<80%, and <60%), and rs12979860 genotype (TT, CT, CC). Median values were used to define cut-points for the starred characteristics. Black diamond indicates the overall point estimate. Black circles, squares, and triangles represent the point estimate for each indicated subgroup. Horizontal lines represent 95% confidence intervals (CI). The solid vertical line indicates an odds ratio of 1. P values are for the interaction between coffee intake and each stratifying variable and are taken from the Wald test for the cross-product term of each stratifying variable and continuous coffee intake.

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Table 1. Association of Coffee Intake With Baseline Variables
AST/ALT, aspartate aminotransferase/alanine aminotransferase; HCV, hepatitis C virus; HDL, high-density lipoprotein; HOMA2, homeostatic model assessment score of insulin resistance; IQR, interquartile range; SF-36, Short Form-36.
^a Mantel-Haenszel test for trend for categorical variables; Jonckheere-Terpstra test for trend for continuous variables; and χ² test for race/ethnicity.
^b Data not available for all participants: alcohol drinking available for 881 patients; serum total cholesterol for 847; serum high-density lipoprotein cholesterol for 845; HOMA2 score for 857; Physical Function SF-36 score for 884 patients; rs12979860 genotype for 792 patients; rs8099917 genotype for 794 patients.

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Table 2. Association of Coffee Intake With Log Hepatitis C Virus RNA Level
HCV, hepatitis C virus; IQR, interquartile range.
^a Jonckheere-Terpstra test for trend.
^b Log HCV RNA level was available for 885 patients at baseline, 860 patients at week 12, and 846 patients at week 20.

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Table 3. Association Between Coffee Intake and Virologic Response
CI, confidence interval; OR, odds ratio; SVR, sustained virologic response.
^a Adjusted for age (continuous), sex, race/ethnicity (white, African American, Hispanic, other), alcohol use (current, former, and never), cirrhosis at baseline, genotype 1, aspartate aminotransferase/alanine aminotransferase ratio (continuous), log hepatitis C virus RNA level at baseline (continuous), previous use of ribavirin, hemoglobin (continuous), neutrophils (continuous), platelets (continuous), categories of peginterferon medication dose during first 20 weeks of treatment (≥98%–100%, ≥80%–<98%, ≥60%–<80%, and <60%), and rs12979860 genotype (TT, CT, CC).

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