Coffee Improves Response to Hepatitis C Treatment

SUMMARY
Drinking more coffee -- but not tea -- was associated with greater likelihood of response to hepatitis C treatment with pegylated interferon/ribavirin in the HALT-C study.

By Liz Highleyman

Over years or decades, chronic hepatitis C virus (HCV) infection can progress to severe liver disease including cirrhosis and hepatocellular carcinoma. A number of previous studies have found that higher consumption of caffeine or coffee specifically is associated with improved liver health and slower disease progression, but its relationship to hepatitis C treatment response is not fully understood.

As described in the June 2011 issue of Gastroenterology, Neal Freedman from the National Cancer Institute and colleagues looked at the relationship between coffee consumption and treatment response in the HALT-C (Hepatitis C Antiviral Long-Term Treatment against Cirrhosis) trial, which was designed to show whether long-term pegylated interferon maintenance therapy could reduce the risk of liver disease progression in non-responders.

The analysis included 885 participants with bridging fibrosis or cirrhosis (Ishak stage F3-F6) who did not achieve sustained response to prior antiviral therapy. In the HALT-C lead-in phase, they were re-treated with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day weight-adjusted ribavirin. At week 24, non-responders were randomly assigned to either discontinue treatment or continue on low dose (90 mcg/week) pegylated interferon monotherapy.

Based on food questionnaires, the researchers recorded participants' coffee consumption during the past year before re-treatment, categorizing it as none, < 1 cup per day, 1 to < 3 cups per day, or 3 or more cups per day. About 15% of patients were non-drinkers and about the same proportion drank 3 or more cups.

Treatment response was assessed at week 12 (early virologic response or EVR), week 20, week 48 (end-of-treatment response), and week 72 (sustained virologic response or SVR).

Results

People who drank 3 or more cups of coffee per day had double the drop in HCV RNA viral load from baseline compared with non-drinkers (median 4.0 vs 2.0 log, respectively).

About 60% of patients who drank the most coffee tolerated full-dose treatment, compared with about 50% of non-drinkers.

In an unadjusted analysis, the heaviest coffee drinkers were about 3 times more likely than non-drinkers to respond to treatment.

After adjusting for sex, age, race/ethnicity, alcohol use, presence of cirrhosis, AST/ALT ratio, IL28B pattern, interferon dose reduction, and other factors affecting response, people who drank the most coffee were still about twice as likely to respond to treatment:

	Early virologic response: odds ratio 2.0 for > 3 cups vs none;
	Week 20 response: odds ratio 2.1;
	End-of-treatment response: odds ratio 2.4;
	Sustained virologic response: odds ratio 1.8.

Response rates were significantly higher for heavy coffee consumers compared with non-drinkers at all time points:

	Early virologic response: 76% vs 46%, respectively;
	Week 20 response: 52% vs 26%, respectively;
	Sustained virologic response: 26% vs 11%, respectively.

These findings led the researchers to conclude, "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."
"Coffee has > 1000 compounds, any one of which could be involved in virologic response," they explained in their discussion. "One major constituent of coffee is caffeine. Although we could not distinguish caffeinated from decaffeinated coffee in our study, we found no association with consumption of black or green tea."

"It is unlikely that coffee and its constituents have a direct antiviral effect," they continued. "If so, HCV RNA levels at baseline would have been expected to be lower with greater coffee consumption. In fact, baseline levels were actually higher with greater consumption. More likely coffee would have a facilitating effect on response to peginterferon and ribavirin treatment by a mechanism yet to be understood."

Investigator affiliations: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD; New England Research Institutes, Watertown, MA; Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD; Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA; 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, MD.

6/21/11

Reference
ND Freedman, TM Curto, K Lindsay, et al (HALT-C Trial Group). Coffee consumption is associated with response to peginterferon and ribavirin therapy in patients with chronic hepatitis C. Gastroenterology 140(7):1961-1969 (abstract). June 2011.