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In This Issue: Hepatitis C
• Statins Active against HCV, Laboratory Study Shows
• Smoking May Worsen Liver Fibrosis
• Alcohol Use and Hepatitis C Treatment Outcomes
• Coffee May Help Prevent Liver Fibrosis
• Sexual Problems in Men with Hepatitis C
Statins Active against HCV, Laboratory Study Shows
Statin drugs are active against HCV in laboratory cell cultures, according to a study published in the July 2006 issue of Hepatology. Also known as HMG-CoA reductase inhibitors, statins are widely prescribed for the management of high blood cholesterol. M. Ikeda and colleagues found that fluvastatin (Lescol) demonstrated the strongest anti-HCV activity when added to an HCV “replicon” in laboratory cell cultures. Atorvastatin (Lipitor) and simvastatin (Zocor) showed moderate activity, lovastatin (Mevacor) had weak activity, and pravastatin (Pravachol) showed no activity against HCV. When added to cultures along with pegylated interferon, all the statins except pravastatin exhibited a stronger inhibitory effect on HCV replication; fluvastatin plus pegylated interferon appeared to have a synergistic anti-HCV effect. The reason for the statins’ anti-HCV activity is unclear, but the researchers suggested the drugs may block HCV replication by a specific, not-yet-identified antiviral mechanism, possibly involving mevalonate and geranylgeraniol (two compounds that play a role in the HMG-CoA reductase biosynthesis pathway). The authors concluded that statins, especially fluvastatin, “could be potentially useful as new anti-HCV reagents in combination with interferon.” While this research is still in the preclinical stage, it suggests the possibility that statins may one day be used as part of combination regimens to treat chronic hepatitis C.
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Smoking May Worsen Liver Fibrosis
Tobacco smoking may increase the risk of liver fibrosis progression in people with chronic hepatitis C, according to a study in the June 2006 issue of Clinical Gastroenterology & Hepatology. A. Dev and colleagues studied 170 subjects retrospectively selected from a database of chronic hepatitis C patients at the Scripps Clinic; more than two-thirds were men, most were white, the mean age was 47 years, and 25% were smokers. Most were participating in hepatitis C treatment trials with strict criteria regarding alcohol use (a potential confounding factor, since people who smoke may also tend to drink alcohol). The researchers found that 21% of smokers had Metavir fibrosis scores of 3 or 4, compared with 14% of nonsmokers; overall, smokers had significantly higher fibrosis scores than nonsmokers. The researchers hypothesized that low oxygen levels (hypoxia) due to smoking might lead to increased expression of vascular endothelial growth factor (VEGF) and VEGF-D and their receptors (s-Flt and s-KDR); these two cytokines promote angiogenesis (blood vessel proliferation), a key feature of liver fibrosis and tumor formation. They found that VEGF, s-Flt, and s-KDR levels did not differ significantly between smokers and nonsmokers. In a multivariate analysis, the factors that independently predicted more severe liver fibrosis were smoking, genotype 1 HCV, male sex, and increased VEGF-D levels. The authors concluded that chronic hepatitis C patients who smoke are more likely to develop liver fibrosis, and that chemicals associated with reduced oxygen “may be involved in the molecular mechanisms of fibrogenesis.”
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Alcohol Use and Hepatitis C Treatment Outcomes
It is well known that heavy alcohol use can worsen liver damage, and some past studies have shown that it also impairs response to hepatitis C treatment. But, according to a study reported in the May 2006 issue of Gastroenterology, some patients who continue to drink alcohol can achieve sustained response to interferon-based therapy. B.S. Anand and colleagues enrolled 4061 individuals with chronic hepatitis C, 726 of whom started treatment with interferon plus ribavirin. The researchers found that current or past alcohol use reduced eligibility for hepatitis C treatment. Past alcohol use (more than 12 months ago) did not affect treatment discontinuation rates or sustained virological response (SVR) rates. Recent alcohol users (within the past year) had a higher rate of treatment discontinuation compared with non-drinkers (40% vs 26%) and a slightly lower SVR rate (14% vs 20%; P = 0.06). When looking only at alcohol users who completed therapy, however, the SVR rate was similar to that of non-drinkers (25% vs 23%). The authors concluded that recent alcohol use was associated with increased treatment discontinuation and lower likelihood of achieving SVR, but that patients who used alcohol and completed treatment had a sustained response rate comparable to that of nondrinkers. They recommended that patients who use alcohol should not be automatically excluded from hepatitis C therapy, but that “additional support should be provided to these patients to ensure their ability to complete treatment.”
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Coffee May Help Prevent Liver Fibrosis
While smoking tobacco and drinking alcohol can worsen liver damage, coffee may have the opposite effect, according to a study published in the June 12, 2006 Archives of Internal Medicine. A. Klatsky and colleagues conducted a study of 125,580 health plan members without known liver disease at baseline who provided initial data between 1978 and 1985, and were followed through 2001. During the follow-up period, 330 subjects developed liver cirrhosis (199 alcoholic cirrhosis; 131 cirrhosis due to other causes such as viral hepatitis or of unknown etiology). Participants who regularly drank coffee had a lower risk of developing alcoholic cirrhosis, and the risk appeared to go down the more they drank, with a relative risk of 0.2 for those who drank four or more cups per day. The apparent protective effect of coffee was greatest among patients who consumed the largest quantities of alcohol; a similar reduction in the rate of cirrhosis was not seen among patients with nonalcoholic cirrhosis. Drinking coffee was also associated with a lower rate of ALT and AST elevation. Drinking tea was not linked with reduced cirrhosis risk, suggesting that the apparent protective effect may be attributable to another ingredient in coffee besides caffeine.
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Sexual Problems in Men with Hepatitis C
Sexual dysfunction and dissatisfaction are common among men with chronic hepatitis C and have a negative impact on quality of life, according to a study published in the June 2006 American Journal of Gastroenterology. A. Danoff and colleagues enrolled 112 HCV positive and 239 HCV negative men, who were asked to complete questionnaires to assess sexual functioning (sex drive, erectile function, ejaculation, reported sexual problems, and overall sexual satisfaction), depression, and health-related quality of life (HRQOL). Men with other medical conditions linked to sexual dysfunction (e.g., diabetes, kidney failure, prostate cancer) were not included in the study. The researchers found that men with hepatitis C reported significantly more sexual dysfunction compared with HCV negative men, and were significantly more likely to report a lack of sexual satisfaction (53.6% vs 28.9%), even after adjusting for age, marital status, socioeconomic status, and other potential confounding factors. Twice as many HCV positive men reported using sildenafil (Viagra) compared with HCV negative men (19.6% vs 9.6%). Among the men with hepatitis C, those with symptomatic liver disease and more advanced fibrosis were slightly more likely to report sexual dissatisfaction; high HCV viral load and elevated ALT were associated with greater risk of sexual problems, while Hispanic ethnicity was associated with a lower risk. Depression is often linked with sexual problems, but even among subjects without depression, HCV positive men were significantly more likely than their HCV negative counterparts to report sexual dissatisfaction (47.5% vs 11.0%). Further, men with hepatitis C who reported sexual dissatisfaction scored significantly worse on HRQOL compared with those who did not report dissatisfaction. The authors concluded that, “sexual dysfunction is highly prevalent in men with chronic HCV infection, is independent of depression, and is associated with a marked reduction in HRQOL.” The reasons for sexual problems among men with hepatitis C are unclear, and they recommended further study of biological or virological factors that may play a role.
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