Milk Thistle Extract Evaluated Against Cancer-Causing Liver Disease

NCI CAM Annual Report-FY10

Chronic hepatitis C is a devastating dis­ease that can lead to a variety of other illnesses including liver cancer. Avail­able therapies don’t work for everyone and can have many adverse side effects. As a result, many people with chronic hepa­titis C turn to CAM remedies, such as herbal products, noted Neal Freedman, Ph.D., M.P.H., of NCI’s Division of Cancer Epidemiology and Genetics (DCEG).

One of the herbal products used most com­monly by people with chronic liver disease is silymarin, which is an extract of the milk thistle plant Silybum marianum. Silymarin has been used to treat liver disease since the time of the ancient Greeks. However, few studies have rigorously tested the effectiveness of this herbal ingredient for chronic liver disease, and results from previous studies are inconsistent, Dr. Freedman added.

As part of a large, NIH-supported clinical trial known as the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) study*, NIH investigators asked patients about their use of CAM treatments, including silymarin. The HALT-C trial was designed primarily to test the effectiveness of long-term treatment of hepatitis C with low doses of the drug peginter­feron-alpha for patients who had not responded to previous standard-of-care therapy. At the outset of the study, investigators found that ap­proximately one-third (34 percent) of patients in the trial reported that they had used silyma­rin, and half of those patients were current users of this herbal remedy, Dr. Freedman reported.

“When we learned that silymarin use was part of the information collected in HALT-C, we thought we should examine the possible effects of silymarin use on liver disease progression, as these results could contribute to the larger scientific understanding of the role of silymarin in liver disease,” Dr. Freedman commented.

Dr. Freedman and his colleagues in DCEG studied 1,049 patients in the HALT-C trial and compared clinical outcomes for current users of silymarin, against outcomes for patients who reported former silymarin use, and patients who said they had never used silymarin. The researchers looked at two outcomes for the three groups of patients: 1) progression of liver fibrosis, which was assessed by examining liver biopsies over the course of the study; and 2) liver-related clinical outcomes, which included liver cancer (hepatocellular carcinoma), ascites (accumulation of fluid in the abdominal cavity), variceal hemorrhage (rupturing of the veins in the esophagus), or liver disease-related death.

“Fibrosis is the term used when some of the liver tissue has been destroyed and replaced by scar tissue, and cirrhosis is where most of the liver has been destroyed,” explained Dr. Freedman. “As liver disease gets worse, patients progress from fibrosis to cirrhosis, and at each step their risk of liver cancer and other adverse clinical outcomes is much higher.”

Dr. Freedman reported that patients in the HALT-C trial who were currently taking silymarin were less likely to progress from fibrosis to cirrhosis**. “However, there was no association between silymarin use and clinical outcomes, and we’re not clear why that’s the case,” he added. It could be that the follow-up period for the current study was too short to see an effect of silymarin on clinical outcomes or to determine whether silymarin affects the progression of fibrosis but not other aspects of chronic liver disease, he suggested.

Dr. Freedman noted that the main limitation of the study was that investigators lacked informa­tion on how much silymarin each patient used. “Also, as an observational study, patients using silymarin may be different from patients who are not users of the herbal remedy. For example, they may have a different stage of disease, or silymarin use may be a proxy for another ‘habit’ that has an effect,” Dr. Freedman said.

“Our results suggest that there might be an as­sociation between silymarin use and progression of liver disease, and future studies should look at this further,” he continued. “But, by itself, our study isn’t definitive and I think many more studies need to be done.” Future studies should assess exactly how much silymarin each patient is using, Dr. Freedman said, and ideally should compare patients who are randomly as­signed to take a specific dose of silymarin with patients not receiving any silymarin.