Hepatotoxicity induced by herbs and medicines used to induce weight loss

In the last few years, a considerable number of reports have been published on hepatotoxicity associated with herbal products attributed with weight-reducing properties. Clinical expression of hepatotoxicity has ranged from symptoms of self-limiting hepatitis, indistinguishable from those caused by the hepatitis viruses, to forms of fulminant hepatitis causing death or requiring liver transplantation. These products, which are sold as dietary products or supplements, do not undergo the safety tests required of drugs before their release on to the market. To prevent the toxic effects of herbal products, the general public should be made aware of their harmful effects and since the benefits of these products have not been demonstrated avoid their use, while physicians should strongly discourage patients from taking these products. Authorization of the commercialization of all these natural products should be strictly regulated to minimize the harm they can cause.     

HIV and liver diseases: recent clinical advances

Because the life expectancy of patients infected with HIV has been prolonged, liver diseases have assumed far greater importance as a cause of morbidity and mortality in these patients. Given the shared risks of transmission, patients who have HIV often are coinfected with hepatotrophic viruses such as hepatitis C and hepatitis B. Further, antiretroviral therapy (ART) used by patients who have HIV is often hepatotoxic, contributing to liver damage. With increasing immunosuppression caused by AIDS, patients who have HIV have to deal with these issues and the increased risk of infection with opportunistic viral, fungal, bacterial, and protozoal pathogens. In addition, steatosis and lipodystrophy now are recognized more commonly in patients who have HIV, particularly in the setting of ART. Thus, understanding of liver diseases in the setting of HIV infection becomes an important focus in caring these individuals. There have been numerous advances in the treatment of liver disease in patients who have HIV, particularly in treating viral hepatitis C and B. This article reviews various liver manifestations in patients who have HIV and the recent advances in diagnostic and therapeutic options.     

Natural health product-HIV drug interactions: a systematic review

The use of natural health products (NHPs) within the HIV community is high. Several NHPs have demonstrated interactions with HIV medications that could contribute to drug failure. We aimed to conduct a systematic review of clinical trials examining NHP-HIV drug interactions and their methodological characteristics. We searched electronic databases and unpublished resources independently, in duplicate. Nine studies were identified, eight clinical pharmacokinetics trials and one population-pharmacokinetics trial. Investigators studied four different herbal medicines (St John's wort, garlic, goldenseal and milk thistle) and one vitamin (vitamin C). Significant interactions were observed with St John's wort, garlic and vitamin C. However, methodological challenges exist to making the results directly generalizable to patients. This review finds that important drug level changes exist when NHPs are combined with HIV medications. Considering patient values and the implications of these studies, further research is urgently required to determine the extent of interactions with other commonly used NHPs.     

A randomized trial of Chinese herbal medicines for the treatment of symptomatic hepatitis C

BACKGROUND: Many patients with the hepatitis C virus (HCV) cannot be successfully treated with interferon-based regimens. Chinese herbal medicines have been widely prescribed for HCV in Asia, and many infected patients in the United States have used these agents. However, data to support the efficacy of these medications are limited and, to our knowledge, no published trials have been conducted in a US population. METHODS: In a double-blinded design, 45 patients with HCV and fatigue were randomized to receive a combination of Chinese herbal medications or a matched placebo for 12 weeks. The main outcome measures were changes in health-related quality of life using the role physical and vitality scale scores from the validated Hepatitis Quality of Life Questionnaire and alanine aminotransferase levels. In addition, other Hepatitis Quality of Life Questionnaire variables, HCV load, and adverse effects were monitored. RESULTS: In patients with HCV, the herbal medications had no effect on any quality-of-life variables, as measured by the Hepatitis Quality of Life Questionnaire. In addition, no significant changes in alanine aminotransferase or serum HCV RNA levels were noted. No significant adverse effects were observed. CONCLUSIONS: In this study, a regimen of Chinese herbal medicines did not improve quality of life, liver chemistry results, or viral load in a cohort of patients with HCV. Patients and practitioners should remain cautious about the use of herbal medicines for HCV, because studies have not shown a clear benefit of these agents.     

Adverse effects of herbal treatment of cardiovascular disease: what the physician must know

The increasing use of herbal products by patients with cardiovascular disease represents a clinical challenge to physicians. The use of herbal products is increasing in our society, and less than 50% of patients using herbal products report this information to their physicians. In addition, physicians often lack the knowledge base for herbal medications to effectively counsel patients regarding adverse effects and potential herb-drug interactions. This article reviews Western and traditional Chinese herbs that are commonly used by patients with cardiovascular diseases, herbs noted to have adverse cardiovascular effects, and herbs that may potentially interact with commonly prescribed cardiovascular medications.     

Prevalence and predictors of herbal medication use in veterans with chronic hepatitis C

OBJECTIVE: Herbal therapies are used by a substantial proportion of persons in the United States, and use of these supplements may be even higher in those with chronic liver disease. The aims of this study were to prospectively determine the proportion of US veterans with chronic hepatitis C that are currently taking vitamins and herbal medications and to evaluate factors associated with use of herbal preparations. METHODS: Patients with hepatitis C who were seen in the gastroenterology, infectious disease, and primary care clinics at the VA New York Harbor Healthcare System were invited to participate in this prospective study. For comparison, healthy patients without hepatitis C were enrolled from the primary care clinics at the same medical center. Patients were interviewed by trained research coordinators who obtained detailed demographic and clinical data, as well as information on the use of antioxidants (vitamin C and E), multivitamins, and herbal medications. RESULTS: Use of vitamin C (34.8% vs. 19.6%, P < 0.001), vitamin E (25.8% vs. 13.2%, P < 0.001), multivitamins (43.6% vs. 28.0%, P < 0.001), and herbal therapies (21.0% vs. 10.4%, P < 0.001) was significantly higher in the 500 patients with hepatitis C compared with the 250 healthy controls. The most common herbal medications taken by hepatitis C patients were milk thistle (12.2%), ginseng (4.6%), and echinacea (3.0%). After adjusting for age and gender, multivariate logistic regression identified 12 or more years of education (OR 2.7; 95% CI 1.6-4.3; P < 0.001) and annual income of at least 20,000 US dollars (OR 2.0; 95% CI 1.3-3.2; P = 0.004) as the only significant predictors of herbal medication use in patients with hepatitis C. CONCLUSIONS: The use of herbal preparations is prevalent among veterans with chronic hepatitis C, especially those with higher levels of education and higher incomes. Obtaining a detailed medical history and documentation of the use of these supplements is critical to determine the potential for herbal-drug interactions and hepatotoxicity.     

Hepatitis associated with Chinese herbs

Traditional Chinese herbal medicines are widely available in Western society and are popular as a form of 'natural' alternative medicine. Their use is increasing, as they are perceived to be free of side effects, but they remain largely unregulated. We describe two patients who suffered severe hepatitis, one of whom died, after taking Chinese herbal remedies for minor complaints. We also review the English-language literature on hepatitis associated with Chinese herbs. Two products appear to be implicated frequently: Jin bu huan was taken by 11 patients, and Dictamnus dasycarpus was taken by six patients, including both fatal cases. It is difficult to provide conclusive evidence of what caused hepatitis, as these products are mixtures that may contain adulterants. These cases highlight not only the potential dangers of these products to consumers but also the need for greater control of their manufacture and use.     

Herbal medicine in the treatment of liver diseases.

Herbal drugs have become increasingly popular and their use is widespread. Licensing regulations and pharmacovigilance regarding herbal products are still incomplete and clearcut proof of their efficacy in liver diseases is sparse. Nevertheless, a number of herbals show promising activity including silymarin for antifibrotic treatment, phyllantus amarus in chronic hepatitis B, glycyrrhizin to treat chronic viral hepatitis, and a number of herbal combinations from China and Japan that deserve testing in appropriate studies. Apart from therapeutic properties, reports are accumulating about liver injury after the intake of herbals, including those advertised for liver diseases. Acute and/or chronic liver damage occurred after ingestion of some Chinese herbs, herbals that contain pyrrolizidine alkaloids, germander, greater celandine, kava, atractylis gummifera, callilepsis laureola, senna alkaloids, chaparral and many others. Since the evidence supporting the use of botanicals to treat chronic liver diseases is insufficient and only few of them are well standardised and free of potential serious side effects, most of these medications are not recommended outside clinical trials. Particularly with regard to the latter, adequately powered randomised-controlled clinical trials with well-selected end points are needed to assess the role of herbal therapy for liver diseases.     

The viral safety of intravenous immunoglobulin

Human immunoglobulin for intravenous (IV) use has an established safety record with regard to transmission of hepatitis B virus. The bulk of available evidence also suggests that the human immunodeficiency virus (HIV) is not transmitted by IV immunoglobulin. There has been one report, however, of isolation of HIV from two patients with hypogammaglobulinaemia who had been treated with several immunoglobulin products. Certain IV immunoglobulin products have transmitted non-A, non-B (NANB) hepatitis but careful clinical assessment of recipients of other products suggests that non-infective preparations can be made. Interpretation of available data most likely to be correct is that contamination with NANB is reduced but not eliminated by cold-ethanol fractionation and that the use of further virucidal procedures in the finishing of immunoglobulin products will confer a higher degree of safety.     

Single (B or C), dual (BC or BD) and triple (BCD) viral hepatitis in HIV-infected patients in Madrid, Spain

INTRODUCTION: There are very limited data about the prevalence of multiple hepatitis virus infections in HIV infected individuals. In HIV uninfected individuals with triple BCD hepatitis, hepatitis D virus (HDV) appears to be the dominant virus. However, in HIV infected patients with triple hepatitis it is not known if HDV replication inhibits hepatitis B virus (HBV) and/or hepatitis C virus (HCV) replication. METHODS: We calculated the prevalence of single (B or C), dual (BC) and triple (BCD) hepatitis in 423 HIV-infected patients with positive HCV serum antibodies and/or positive serum HBsAg. In patients with multiple infections we performed an evaluation of serum markers of HBV, HCV and HDV replication. RESULTS: The prevalence of multiple hepatitis was 4.7% (95% confidence interval, 2.7-6.7%). Multiple hepatitis occurred only among patients who acquired HIV through injection drug use. The most common multiple hepatitis was triple BCD. Patients with hepatitis BC and past or chronic hepatitis D were significantly more likely to have cirrhosis and a negative serum HBeAg and HCV PCR than patients with single hepatitis B or hepatitis C. Patients with chronic hepatitis D showed uniform suppression of HBV and HCV replication markers. CONCLUSIONS: In our geographic area approximately 5% of HIV infected patients with hepatitis suffer multiple hepatitis virus infection. In patients with triple hepatitis BCD virus infection, HDV appears to be the dominant virus causing inhibition of both HBV and HCV replication.     

Trials of antihypertensive therapies in children.

Clinical trials assessing the safety, effectiveness and pharmacokinetics of new antihypertensive medications have been numerous as new classes of medications have been developed and brought to market over the past two decades. However, very few clinical trials have been initiated and completed in children with hypertension. Excluding diuretics, only one antihypertensive medication marketed within the past 20 years has any pediatric pharmacokinetic or dosing information published in the drug label and none have a pediatric indication. There are many reasons that these studies have not been done. Summation of the data collected in large epidemiologic studies that establish normal blood pressure and define hypertension using casual measurements have been a relatively recent event in pediatrics. Although ambulatory blood pressure measurement has been studied for the past decade there is still uncertainty with respect to the standardization of devices, measurement technique and normal values in a multi-racial pediatric population. As a result, no large scale, industry-sponsored clinical trials involving antihypertensive therapy have employed this measurement technique in children. In recognition of this problem, US Congress passed the Food and Drug Administration Modernization Act in 1997. Among the many provisions of this law, the US Food and Drug Administration (FDA) is required to publish a list of approved drugs for which additional information may prove beneficial for children. This law and subsequent action by the FDA also provides a mechanism by which manufacturers may gain six months of additional market exclusivity if adequate and well-controlled pediatric trials are completed and submitted to the FDA in response to a formal written request for these studies. Because such studies have not been previously undertaken and the new rules provide a significant financial incentive, written requests have been issued for pediatric studies involving more than a dozen antihypertensive agents. The FDA published a sample written request for oral antihypertensives in children and several potential study designs were presented.     

Complementary and alternative medicine in inflammatory bowel diseases: what is the future in the field of herbal medicine?

The use of complementary and alternative medicine is wide-spread not only in Eastern countries, but also in the Western world. Despite the increasing evidence on the harmful effects induced by several naturopathic/homeopathic products, patients seem to appreciate these remedies, in particular because they consider them to be absolutely safe. This same phenomenon is common among inflammatory bowel disease (IBD) patients. As a result there is a significant request for scientific data to evaluate both the efficacy and safety of these remedies, and to support the use of such medications as adjuvant treatments to biological and synthetic drugs. We aimed to review the current evidence on efficacy and safety of some natural products that are believed to be effective in inflammatory bowel disease. Further perspectives for the clinical use of herbal products and strategies for improving knowledge about herbal products in IBD are also discussed.     

The use of generic medications for hepatitis C

Hepatitis C, hepatitis B, HIV, TB and malaria are the five major causes of infectious disease death worldwide. In a breakthrough that rivals the invention of penicillin, drugs that cure hepatitis C, with minimal side effects and high success rates, have reached the market, but, in what must be one of the greatest tragedies of modern times, these life‐saving medications are not being deployed on a mass scale. Pharmaceutical patents are gifted to private corporations by governments for the dual purposes of protecting R&D expenditure and encouraging innovation. Unfortunately the monopoly pricing power these patents provision currently lacks adequate checks and balances, is open to abuse, and is quite clearly being abused. The sort of legislative changes required to deliver on the original goals of pharmaceutical patents will take years or even decades to eventuate. Parallel importation of generic medication offers hope to the millions of patients with HCV unable to afford access to vastly overpriced originator medications. Doctors prescribing and monitoring patients taking generics can take comfort from the fact that the REDEMPTION trial results show, like the HIV generics that came before them, that HCV generics deliver robust clinical results.     

Herbal remedies in gastroenterology

Complementary and alternative medicine (CAM) is presently not considered to be part of conventional medicine. Nevertheless, an estimated 51% of patients with gastrointestinal disorders have tried some from of CAM. Indeed, 10% of alternative medicines are being used for digestive symptoms. After prayer or spiritual healing, herbal medicine is the second most common CAM therapy. While herbal products make numerous health-related claims, those that have been systematically evaluated are unfortunately few. The modern gastroenterologist must be up to date with the regulations, side effects, and possible benefits of specific herbal products used in patients with gastrointestinal disorders.     

High hepatotoxicity rate seen among HAART patients

Evidence continues to mount showing that HIV patients receiving antiretroviral treatment are at high risk for hepatotoxicity. The National Institutes of Health presented findings on liver toxicity among 10,011 HIV patients at the first International AIDS Society conference. The retrospective analysis shows that liver toxicity is associated with all classes of antiretroviral medications in use, and not just with regimens containing nevirapine or hydroxyurea, the two drugs about which the FDA recently issued hepatotoxicity warnings.