From Digestive Disease Week 2007: Statins demonstrated to have benefit in treatment of hepatitis C virus

New research presented at the Digestive Disease Week 2007 regarding the effect of statins on hepatitis C infection.

Key Points

The results of several studies of the effect of statins on hepatitis C infection were presented at Digestive Disease Week 2007, May 19 to May 24, 2007, in Washington, District of Columbia.

The data were compelling enough to warrant further prospective studies of statins for the treatment of hepatitis C, according to Ted Bader, MD, VA Medical Center, University of Oklahoma, Oklahoma City.

In 2003, researchers reported that lovastatin administered to human hepatoma cells significantly reduced the normal hepatitis C virus (HCV) RNA replication rate by 70% after 24 hours and by 95% after 72 hours regardless of viral genome variation.

Statins regulate cholesterol by blocking the mevalonate pathway, which is also responsible for maintaining a cell membrane protein composition conducive to HCV replication. However, the authors noted that lovastatin would have to be delivered to the liver in doses much higher than are currently used in order to achieve a reduction in HCV replication, which raises concerns about toxicity.

Researchers have investigated the effect of statins on hepatitis C for several years, but the treatment is not approved by FDA. In fact, use of many statins is contraindicated in patients with active liver disease. However, FDA recently removed this contraindication from the package inserts of 3 statin agents, and literature reports indicate that only approximately 10% of patients experience deviations in ALT levels with statin use and that any elevation is often temporary, Dr Bader said.

Dr Bader conducted an FDA- and Institutional Review Board-approved study to assess the antiviral effects of fluvastatin in 12 patients with chronic hepatitis C. The patients received an 80-, 160-, 240-, or 320-mg dose of fluvastatin daily for 14 days; ALT and bilirubin levels were assessed. Three patients with abnormal ALT levels at baseline experienced significant improvement with statin treatment, and all 9 patients with normal baseline ALT levels remained within the normal range. There were no significant changes in bilirubin levels.

Dr Bader compared these results with those from a retrospective analysis of the VA Medical Center database and discovered that of 60 patients with hepatitis C, 13 began statin treatment with abnormal ALT values; 12 of these patients experienced improved ALT levels with statin treatment. The remaining 47 patients with hepatitis C had normal ALT levels when statin treatment was initiated, and 45 of these patients maintained normal ALT levels throughout the trial. Two patients developed mildly abnormal ALT levels, but both reported heavy alcohol use.

"The data not only support the lack of harm in this situation, but also seem to suggest a possible salutary effect that needs further study," Dr Bader said.

A retrospective analysis of 104 patients with hepatitis C who received PI+R versus 30 patients who received PI+R plus a statin (simvastatin, n=25; lovastatin, n=2; atorvastatin, n=2; or fluvastatin, n=1) was conducted to measure sustained viral response rates. Overall, a pooled analysis demonstrated a 63% sustained viral response among patients receiving PI+R plus a statin versus a 37% sustained viral response among patients receiving PI+R only (P=.009). The effect was most pronounced for patients with HCV genotype 1 (P=.014), which is the most difficult type of hepatitis C to treat, Dr Bader said.

Fluvastatin has recently demonstrated a strong synergistic inhibitory effect on HCV RNA replication when used in vitro and combined with interferon. Atorvastatin and simvastatin have demonstrated moderate inhibitory effect, lovastatin has demonstrated a weak inhibitory effect, and pravastatin is not associated with any anti-HCV activity.

SOURCES

Ye J, Wang C, Sumpter R, Brown MS, Goldstein JL, Gale M. Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Natl Acad Sci USA. 2003;100:15865–15870.

Ikeda M, Abe K, Yamada M, Dansako H, Naka K, Kato N. Different anti-HCV profiles of statins and their potential for combination therapy with interferon. Hepatology. 2006;44:117–125.