Liver, Pancreas and Biliary Tract
Randomised double-blinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: study description and 12-month results

https://doi.org/10.1016/j.dld.2004.06.015Get rights and content

Abstract

Background/aims. A double-blinded trial evaluating silymarin, an herbal supplement for liver disease, to prevent complications of chronic hepatitis C virus infection has not been done.

Subjects. One hundred and seventy-seven consenting residents of an Egyptian village with chronic hepatitis C virus were randomly assigned to receive either silymarin or multivitamin supplements.

Methods. Participants had baseline and follow-up clinical, ultrasound, blood tests and quality-of-life assessments. Community nurses visited weekly to ascertain compliance, distribute supplements and record adverse effects.

Results. At 12 months almost all of 141 remaining subjects reported feeling better, although symptoms and quality-of-life scores did not differ between the silymarin and multivitamin groups. Both the silymarin and vitamins were tolerated equally well; and >95% of supplements were taken by >95% of subjects. One in each group had no detectable hepatitis C virus antibodies while two in the silymarin group and three receiving multivitamins had undetectable hepatitis C virus RNA. Serum alanine aminotransferase elevations did not differ between groups. Serum hepatic fibrosis marker, hyaluronic acid and YKL-40, and abdominal ultrasound results were similar in both groups and may have progressed slightly at 12 months.

Conclusions. The recommended dose of silymarin can be safely taken for 1 year and improves symptoms and general well-being, but has no effect upon hepatitis C virus viremia, serum ALT, or serum and ultrasound markers for hepatic fibrosis. More prolonged evaluation and a higher dose may be required to ascertain whether milk thistle supplements prevent complications of chronic hepatitis C virus.

Introduction

Hepatitis C virus (HCV) is the most common cause of liver disease with a worldwide prevalence of 170 million infected persons [1], [2], [3], [4], [5]. Egypt, with a population of 69 million, is estimated to have 8–10 million inhabitants who have been infected with HCV, i.e. have antibodies to HCV (anti-HCV), and 6 million who have active viral replication, with a positive serum hepatitis C ribonucleic acid (HCV RNA) [6]. Fifty percent of this group is potential candidates for antiviral chemotherapy. However, the best currently available antiviral regimen of pegulated interferon and ribavirin is difficult to tolerate [7], [8], expensive, requires up to 48 weeks of treatment, and cures only 40–60% of a very highly selected group of patients [9], [10], [11], [12]. Therefore, antiviral therapy is unsuitable and unattainable for the majority of HCV-infected persons in Egypt and other developing countries.

Herbal supplements are frequently used to treat and prevent progression of chronic HCV infection or to reverse inflammatory and fibrotic liver disease. It is the opinion of the majority of hepatologists that silymarin, the active component of the milk thistle plant, is not only the most commonly used herbal supplement for liver disease, but is also the one most likely to be beneficial [13], [14], [15], [16]. Milk thistle has been used to treat liver disease for at least 2000 years. In Roman times, Pliny the Elder called it sillybum and recommended taking a mixture of the plant's juice and honey for ‘carrying off bile’ [14], [17], [18]. However, there are no prospective published randomised controlled trials (RCT) showing the benefits of silymarin [5], [14], [19], [20].

This is a report at 12 months of an ongoing randomised control trial to assess the safety and effect of silymarin in preventing the complications of chronic HCV infection in a rural Egyptian community. In a community-based trial, only surrogate markers of efficacy, e.g. liver aminotransferases, serum markers of fibrosis and hepatic ultrasound, are feasible. The short duration of the study also limits the expected effects of treatment on clinical outcomes but enables us to extrapolate that long-term therapeutic trials with herbal supplements are possible in underdeveloped countries with limited access to antiviral therapies. We are reporting our preliminary findings on safety, compliance and efficacy at 1 year and believe longer, large-scale community-based trials should be undertaken.

Section snippets

Subjects

The village of Sallam, 15 km north of the city of Assiut and 375 km south of Cairo up the Nile River, had 11,227 inhabitants living in 1747 households in 1998. The majority of the villagers are farmers and their families. They do not drink alcohol or abuse drugs intravenously. Human immunodeficiency virus (HIV) infection is absent in this population and the people are generally healthy and adequately fed. HCV is the most common cause of liver disease with a worldwide prevalence of 170 million

Characteristics of subjects and drop-outs

The mean age was 44.1 years with a range from 21 to 78 years; 65.5% were male. There was no statistical difference between mean age and gender of the 36 subjects who did not complete the 12-month evaluation and 141 who remained in the study. One reason for discontinuing was the development of other diseases in nine subjects that were not believed to be side effects since there were other explanations for the problem and they occurred with equal frequency in the herb and placebo groups. Seven

Discussion

This report demonstrates a double-blinded placebo control trial evaluating silymarin to prevent the complications of chronic HCV infection can safely be carried out in a rural village in Egypt. There were no adverse events from taking capsules containing 125 mg of silymarin three times per day for a year and no more symptoms than among controls taking three capsules containing a multivitamin preparation. Although there were considerable symptomatic improvements in those receiving silymarin,

Acknowledgements

This research was funded by a grant from the National Institutes of Health's National Centre for Complementary and Alternative Medicine grant no. R21AT00277. Madaus AG of Cologne, Germany provided the LegalonR and fibrosis assays were partially funded by Espinosa Fibrosis Fund. CID provided the multiple vitamin–mineral (Gericid) used as placebo and placed both compounds into capsules. Dr. Abdulla Mokhlar, the Director, and other scientists at NODCAR gave very useful support, advice and

References (35)

  • A. Pares et al.

    Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial [see comments]

    J. Hepatol.

    (1998)
  • M.G. Ghany et al.

    Progression of fibrosis in chronic hepatitis C

    Gastroenterology

    (2003)
  • G.M. Lauer et al.

    Hepatitis C virus infection

    N. Engl. J. Med.

    (2001)
  • R. Saller et al.

    The use of silymarin in the treatment of liver diseases

    Drugs

    (2001)
  • D. Schuppan et al.

    Clinical studies with silymarin: fibrosis progression is the end point

    Hepatology

    (2001)
  • F. Stickel et al.

    Antifibrotic properties of botanicals in chronic liver disease

    Hepatogastroenterology

    (2002)
  • G.T. Strickland et al.

    Role of hepatitis C infection in chronic liver disease in Egypt

    Am. J. Trop. Med. Hyg.

    (2002)
  • Cited by (0)

    View full text