Showing posts with label Milk thistle. Show all posts
Showing posts with label Milk thistle. Show all posts

Thursday, May 17, 2018

Hepatitis C and Dietary Supplements


Hepatitis C and Dietary Supplements
Most consumers assume that herbs and botanical products in dietary supplements are safe, however they are not regulated by the FDA, in addition these products can interact with prescription drugs, over-the-counter drugs, and other dietary supplements.

As an example milk thistle is the most commonly used herbal supplement in the United States for liver problems, including viral hepatitis. If you are interested in learning more about the science behind milk thistle, probiotics, zinc, or other commonly used supplements, check out the National Center for Complementary and Integrative Health (NCCIH) website, in particular the following publication: Hepatitis C and Dietary Supplements, updated this month.

Wednesday, September 6, 2017

Mediterranean Diet and Antioxidant Formulation in Non-Alcoholic Fatty Liver Disease: A Randomized Study

Nutrients
Effect of Mediterranean Diet and Antioxidant Formulation in Non-Alcoholic Fatty Liver Disease: A Randomized Study
Ludovico Abenavoli 1,*, Marta Greco 1, Natasa Milic 2, Francesca Accattato 1, Daniela Foti 1, Elio Gulletta 1 and Francesco Luzza 1 1 Department of Health Sciences, University “Magna Græcia”, 88100 Catanzaro, Italy 2 Department of Pharmacy, University of Novi Sad, 21000 Novi Sad, Serbia * Received: 3 July 2017 / Accepted: 8 August 2017 / Published: 12 August 2017

Abstract:
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, characterized by liver fatty acid accumulation and fibrosis, not due to excessive alcohol consumption. Notably, nutritional habits have been reported to be implicated in the onset and severity of the hepatic damage, while the Mediterranean diet has shown beneficial effects on NAFLD. Free radicals and oxidative stress were suggested to be involved in the pathogenesis and progression of NAFLD, and several data highlighted the efficacy of antioxidant supplementation in its treatment. The aim of this study was to compare the effects of the Mediterranean diet, with or without an antioxidant complex supplement, in overweight patients suffering from NAFLD. In this prospective study, fifty Caucasian overweight patients were randomized into three groups (Groups A–C). A personalized moderately hypocaloric Mediterranean diet was prescribed to all patients included in the A and B groups. In addition to the diet, Group B was administered antioxidant supplementation daily and for the period of six months. Group C did not have any type of treatment. The study proved that the Mediterranean diet alone or in association with the antioxidant complex improved anthropometric parameters, lipid profile and reduced hepatic fat accumulation and liver stiffness. However, Group B patients, in which the diet was associated with antioxidant intake, showed not only a significant improvement in insulin sensitivity, but also a more consistent reduction of anthropometric parameters when compared with Group A patients. Taken together, these results support the benefit of antioxidant supplementation in overweight patients with NAFLD.

Discussion Only
Full Text Available Online
Despite the rapidly growing recognition of NAFLD over the last few decades, the treatment of this condition remains debated [39,40]. In the clinical management of NAFLD patients, a dietary change and increased physical exercise are essential to reduce body weight, in order to improve metabolic parameters and normalize the biochemical blood profile, as well as transaminase levels [24]. The “ideal” treatment for NAFLD should reduce the liver damage and its progression by reducing anthropometric parameters, by improving insulin resistance and impairment in glucose and lipid metabolism and by reducing the cytokine-mediated pathophysiological link between adipose tissue and liver [41]. The traditional Mediterranean diet is a dietary pattern that was associated with favorable health impact, in particular on cardiovascular diseases, cancer and in the treatment of metabolic syndromes [42]. Carotenoids, fibers and folic acid, which are basic components of this diet, can play a pivotal role in preventing or slowing down the oxidative stress process. In addition, vegetables, which are the staple foods included in the Mediterranean diet, are the main source of phytosterols, known as natural cholesterol-lowering agents, reducing cardiovascular risk [43,44].
Several pharmaceutical agents are currently being evaluated for the treatment of NAFLD, and NASH in particular. However, no single therapy has been approved so far [23,45]. On this basis, the beneficial effects of complementary medicine, and particularly of herbal extracts, on NAFLD patients have received increasing attention in the last few years. The use of this approach has many advantages, including worldwide availability, minimal reported side effects and wide application due to low treatment costs [46].

However, literature data are often inconclusive on this topic, due to the high number of biases found in many trials and to the limited number of studies testing single herbal remedies [47].

In the last two decades, several studies have emphasized the benefits in the NAFLD treatment of Silybum marianum, commonly called milk thistle (MT), a plant native to the Mediterranean area, which has been used for many centuries to treat liver diseases [48,49]. The active complex of MT is a lipophilic extract from the seeds of the plant, and it is composed by three flavonolignan isomers, silybin, silydianin and silychristin, collectively called silymarin.

Studies of patients with NAFLD showed that silymarin treatment was associated with positive changes in insulin resistance and transaminase serum levels [50,51]. Loguercio et al., in a multicenter phase III double-blind clinical trial, showed that MT extracts, after 12 months, led to an improvement of insulin resistance, liver enzymes and liver histology, without any increase in body weight in NAFLD patients [52]. More recently, in a randomized clinical study, we have found out that Mediterranean diet, in association with silymarin and other antioxidants, is able to induce, after six months, significant changes in glucose and lipid metabolism [53].

According to these data, in our cohort, we demonstrated an improvement of BMI, waist and hip circumference, TG, total cholesterol and LDL-C serum level in all patients who followed the Mediterranean diet for a period of six months (Group A and B). The diet also led to the decrease of intra-hepatic fat accumulation, evaluated by the FL index, and of liver stiffness, assessed by TE. However, in the overweight NAFLD Group B patients, who followed the Mediterranean diet in association with BIL antioxidant treatment, we reported the statistical reduction of the HOMA-IR and the TyG index, two surrogate indexes widely used to evaluate insulin resistance.

The changes in glucose and lipid metabolism described in Group B can be explained also by the presence of chlorogenic acid, one component of the BIL complex. Chlorogenic acid is one of the most abundant polyphenols in the human diet. It is contained in coffee, fruits and vegetables and displays many biological properties, such as antidiabetic effects by stimulating glucose uptake in both insulin-sensitive and insulin-resistant adipocytes and by improving early fasting glucose and insulin responses [54]. The metabolic changes observed in our study can be explained by the synergic action of the Mediterranean diet in association with chlorogenic acid and silymarin.

Another component of the BIL complex is protopine, an isoquinoline alkaloid present in Fumaria officinalis, with antioxidant and choleretic properties that inhibit the production of pro-inflammatory cytokines [55]. Our data suggest that protopine could be a potential candidate for NAFLD treatment.
The increase in oxidative stress and free radical production observed in NAFLD lead not only to increased consumption of glutathione, the major intra-cellular antioxidant, but it also reduces the activity of s-adenosyl-l-methionine, the main biological methyl donor and a precursor of glutathione, essential for protecting antioxidant pathways [56]. Recent studies suggest that the reduction of glutathione levels, in combination with lower ATP availability due to mitochondrial deregulation, leads to an unbalance of reactive oxygen species production and to the subsequent progression of hepatic injury [57]. In this context, the administration of reduced glutathione and methionine can help to restore the oxidative balance.

The BIL antioxidant complex treatment alone, not in association with physical activity and a calorie-controlled diet, is not effective in improving insulin resistance. However, our data confirm the possible therapeutic role of this antioxidant complex as a complementary approach to the treatment of overweight NAFLD patients and in particular in the management of insulin resistance in NAFLD-related pathologies.

An important goal for modern hepatologists is to find effective non-invasive diagnostic approaches to NAFLD. In the last two decades, non-invasive diagnostic modalities for NAFLD have been investigated. On the basis of literature data, three non-invasive methods have been employed in the present study for the evaluation of NAFLD. In addition to the US examination, in particular, the FL index and TE have been used to assess respectively hepatic fat accumulation and liver stiffness. The FL index is an accurate and easy to employ predictor score to define steatosis presence that utilizes routine measurements in clinical practice such as a BMI, waist circumference, triglycerides and γGT [36]. In this way, the clinical use of the FL index is useful to identify patients with NAFLD to include in an outpatient lifestyle change program. The data on the reduction of hepatic fat accumulation were also confirmed by the reduction of the Hamaguchi score at the US examination in Groups A and B, compared to Group C.

TE is a non-invasive tool for the evaluation of liver damage that demonstrated good accuracy in quantifying the levels of hepatic stiffness and to define fibrosis, in patients with liver diseases and in particular with NAFLD [37]. This technique is reliable, fast and reproducible, with a good intra- and inter-observer agreement, thus allowing for population-wide screening and disease follow-up.
Finally, our study clearly shows that patients following a balanced diet and taking the antioxidant complex had a more significant attenuation of insulin resistance, hepatic fat accumulation and liver stiffness than patients following the diet alone. These results supported the effectiveness of the BIL complex to reduce liver fatty acid infiltration and its related damages, by positively influencing the mitochondrial function and by reducing oxidative stress.

6. Conclusions
Our study confirms that the Mediterranean diet can improve anthropometric parameters and lipid profile and can contribute to reducing hepatic fat accumulation and liver stiffness. Moreover, the association of this dietetic regimen with antioxidant supplementation can contribute to improving the insulin sensitivity parameters. These data support a possible role of antioxidant supplementation as a coadjuvant therapy in patients with NAFLD.
Full Text Available Online

Wednesday, June 28, 2017

The Liver - Super Foods & Supplements

Liver Super Foods



Published on May 30, 2017
Source - American Liver Foundation Great Lakes Division



In The News
Go Easy on the Avocado Toast: ‘Good Fat’ Can Still Be Bad for You, Research Shows
By on

Thursday, January 26, 2017

Review - Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years

Molecules 2017, 22(2), 191; doi:10.3390/molecules22020191
Review
Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years
Alessandro Federico *, Marcello Dallio and Carmelina Loguercio           
Department of Clinical and Experimental Medicine, Second University of Naples, 80131 Naples, Italy

Received: 6 December 2016 / Accepted: 18 January 2017 / Published: 24 January 2017 

View Full-Text Article

Abstract:
Silymarin is the extract of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation. It also has a direct antiviral effect associated with its intravenous administration in hepatitis C virus infection. With respect to alcohol abuse, silymarin is able to increase cellular vitality and to reduce both lipid peroxidation and cellular necrosis. Furthermore, silymarin/silybin use has important biological effects in non-alcoholic fatty liver disease. These substances antagonize the progression of non-alcoholic fatty liver disease, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction. Silymarin is also used in liver cirrhosis and hepatocellular carcinoma that represent common end stages of different hepatopathies by modulating different molecular patterns. Therefore, the aim of this review is to examine scientific studies concerning the effects derived from silymarin/silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma.

Keywords: silymarin; silybin; antioxidants; alcoholic liver disease; viral hepatitis; non-alcoholic fatty liver disease; hepatocellular carcinoma

Continue to full text article @ Molecules

About This Journal
Molecules (ISSN 1420-3049, CODEN: MOLEFW) is an open access journal covering all aspects of organic chemistry. Originally conceived as a forum for papers on synthetic organic chemistry and natural product chemistry, like the field, Molecules has evolved over its 20 years, with increasing numbers of papers on more theoretical subjects, physical organic chemistry, nanomaterials and polymer chemistry and applied studies. All articles are peer-reviewed and published continuously upon acceptance. Molecules is published by MDPI, Basel, Switzerland.

Tuesday, May 10, 2016

5 Things You Should Know About Dietary Supplements for Hepatitis C


National Institutes of Health
On This Blog
June 2018
NIH launches HerbList, app with information about safety and effectiveness of herbal products

May 2018
Hepatitis C and Dietary Supplements 

Hepatitis C Is Our Featured Topic
5 Things You Should Know About Dietary Supplements for Hepatitis C
Clinical Digest:
Hepatitis C and Dietary Supplements  
Several dietary and herbal supplements have been studied for hepatitis C, and substantial numbers of people with hepatitis C have tried herbal supplements. For example, a survey of 1,145 participants in the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) trial found that 23 percent of the participants were using herbal products. Although participants reported using many different herbal products, silymarin (milk thistle) was by far the most common. However, no dietary supplement has been shown to be efficacious for hepatitis C.

This issue provides information on the evidence base of several dietary supplements studied for hepatitis C.
Continue reading...

Thursday, August 14, 2014

August Hepatitis Newsletters;The good, the bad and the ugly of the new treatments for hepatitis C virus

Hepatitis C Newsletters

Welcome to this months edition of Hepatitis Newsletters, published by advocacy groups devoted to increasing awareness and information about viral hepatitis.

Sit back and enjoy a review of July and August news with articles covering everything from Milk Thistle, conditions outside the liver, to new drugs to treat hepatitis C.

We begin with this months issue of "Annals of Hepatogly" with an article addressing the cost of new HCV therapies.

The good, the bad and the ugly of the new treatments for hepatitis C virus
September - October, 2014
Vol. 13 Issue 5

The good, the bad and the ugly of the new treatments for hepatitis C virus
The cost of new hepatitis C treatments
Karen V. Silva-Vidal, Nahum Méndez-Sánchez. Liver Research Unit ...

Reducing the cost of new hepatitis C drugs
An index of current articles expressing concerns about the pricing of Gilead's Sovaldi.

In case you missed it, this week a new section was added to AASLD/IDSA Hepatitis C guidelines; When and in Whom to Initiate HCV Therapy.

The American Association for the Study of Liver Disease (AASLD) and the Infectious Diseases Society of America (IDSA), in collaboration with the International Antiviral Society-USA (IAS-USA), today released the latest section of their website, www.hcvguidance.org, which assists clinicians treating patients with hepatitis C virus (HCV). The new section is titled, "When and in Whom to Initiate HCV Therapy.

With the addition of the new section, www.hcvguidance.org now offers clinicians information on how to prioritize treatment for those patients who will derive the most benefit or will have the greatest impact on limiting further HCV transmission. Highest priority should be given to patients with advanced fibrosis with compensated cirrhosis and liver transplant recipients and high priority given to patients at high risk for liver-related complications and severe extra-hepatic HCV complications. The guidance provides further detailed information on additional conditions that warrant prioritization of treatment.
Continue reading...

Article published in MedPageToday

Guidelines: Treat Sickest HCV Patients First

Published: Aug 11, 2014

Patients with less advanced fibrosis but other life-threatening complications, such as cryoglobulinemia, should also be at the head of the list for new direct-acting treatment regimens, Jensen told MedPage Today during a teleconference on the new guidelines.

The societies launched their guidelines in January to help physicians cope with an expected demand for treatment as new regimens reach the clinic.

Unusually, the guidelines are online and under constant revision, making them a "living document" that can cope with a rapidly changing field, according to Michael Saag, MD, of the University of Alabama at Birmingham, the guidelines co-chair for IAS-USA.

The latest addition, reporters were told, is a section on when -- and in which patients -- to initiate therapy.

An estimated 3 million to 4 million Americans have chronic HCV and about half are not aware of it. Many will develop advanced liver disease or liver cancer.

The advent of the novel direct-acting agents -- the first were approved in 2011 -- offers the possibility of eradicating the disease in a "very high percentage" of patients, Jensen said.

The guidelines argue that all patients with chronic HCV could benefit from treatment -- but some need it more urgently than others, he added. Not all patients "can receive treatment immediately upon the approval of new agents," he said. "From a clinical perspective, we are most concerned with those with severe liver disease," he said. The guidelines do not directly address the issue of the cost of the some of the new agents, which has raised concern about the impact on the healthcare system if many thousands of patients seek therapy.

"We hope that the cost issues will be sorted out in another venue," Jensen said, "but it's really patient-directed care that we're concerned about."

"We understand that the system is struggling because these medications are expensive," Saag added, "and we need to provide some at least indirect guidance on who has the highest priority."

The CDC is currently recommending that all Americans born from 1945 to 1965 be tested at least once for HCV, since studies suggest that about 2 million of them have the virus.

One goal of the guidelines is to create a larger clinical workforce capable of treating patients with HCV, especially if that testing takes hold and a large number of people suddenly begin demanding treatment.

"There aren't enough hepatologists in the United States to see all these patients," Saag said. "These guidelines will be able to help educate not only those who are very expert in the field about new and emerging treatment trends, but also to educate those who are perhaps new to the treatment of hepatitis C."

Bloggers Corner


Lucinda K. Porter, RN
Hepatitis C and Milk Thistle
A patient wrote to me this week, asking what I thought of a particular protocol purporting to cure hepatitis C. The protocol uses a variety of herbs, mostly milk thistle. I told her that I don’t believe that herbs can cure hepatitis C. I think that when used appropriately, herbs may help a variety of ailments, but when it comes to curing hepatitis C, we haven’t yet found an herbal path..

Opiferum
Watching the world get better

August Newsletters

http://www.projectinform.org 

Project Inform believes it is possible to create the first generation free of HIV and hepatitis C within the next decade. To achieve that dream, we focus our work in four areas: drug development, bio-medical prevention, education and health care access.

Project Inform launches new provider toolkit for screening hepatitis C in people living with HIV
This month, Project Inform launched “A Toolkit for Screening, Counseling and Patient Education: Hepatitis C Infection and People Living with HIV,” which includes materials for medical providers and other health care staff as well as patient fact sheets.

It is estimated that at least 300,000 people or 25% of those living with HIV are also infected with hepatitis C. HCV-related liver disease is the leading non-AIDS cause of death in HIV-infected patients, and HCV disease progression is more rapid in this group, making detection of both acute and chronic hepatitis C extremely important in clinical practice.

To request a free copy of the toolkit, fill out the order form here, or email Andrew Reynolds, Hepatitis C Education Manager, at areynolds@projectinform.org.

Project Inform can help clients and patients living with co-infection, or who are at risk of HCV infection, with additional educational materials and services. Our three-booklet Health and Wellness series for patients living with HIV and HCV is one resource. You can order sets here.

Additionally, providers can direct patients to the national hepatitis C helpline, HELP-4-HEP at 1-877-Help-4-Hep (877-435-7443). Trained counselors and health educators are available to talk with your patients Monday-Friday, 9am to 7pm EST. You can also order HELP-4-HEP posters, brochures and tear pads here.

Project Inform’s wrap-up from World Hepatitis Day 2014
In honor of World Hepatitis Day, which is observed on July 28 every year and is one of only four disease-specific days recognized by the World Health Organization (the others being tuberculosis, malaria, and HIV), Project Inform participated in two events in Washington, DC. The first…

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HELP-4-HEP (hepatitis C helpline)
Toll-free at 1-877-435-7443 Monday–Friday, 9am–7pm (Eastern Time). 
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Toll-free at 1-800-822-7422 Monday–Friday, 10am–4pm (Pacific Time), call-back service only. English only. 

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The HCV Advocate newsletter is a valuable resource designed to provide the hepatitis C community with monthly updates on events, clinical research, and education. 

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HCV Advocate Newsletter

August Newsletter

In This Issue:


Alan Franciscus, Editor-in-Chief
This month Alan discusses Daklinza and Sunpreva from BMS, AbbVie's 3D, the Olysio/Sovaldi combination and the side effects of some of these new medications. 
Read more...


Lucinda K. Porter, RN
Lucinda reviews studies on genotype 3, cirrhosis and cancer; HCV and end-stage kidney disease; alternatives to liver biopsy, and testing policy. 
Read more...


Lucinda K. Porter, RN
This month Lucinda talks about hepatic encephalopathy, and what happens when liver disease hijacks the brain.
Read more...


Alan Franciscus, Editor-in-Chief
This month Alan talks about extrahepatic manifestations of hepatitis C, such as vasculitis, glomerulonephritis, cryoglobulinemia and non-Hodgkin lymphoma and the need for physician awareness of these conditions—especially now that the new treatments are becoming available.
Read more...

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Hep is an award-winning print and online brand for people living with and affected by viral hepatitis. Offering unparalleled editorial excellence since 2010, Hep and HepMag.com are the go-to source for educational and social support for people living with hepatitis.

August News

August 13, 2014
When Positive Hep C Tests Go Unconfirmed, Care Can Go Awry
In the event that individuals receive an unconfirmed positive test for hep C, they are subject to cracks in the health care system and potentially unnecessary care.

August 11, 2014
New Clinical Guidelines Prioritize Care Among Hep C Patients
Two clinical groups have issued new hepatitis C treatment guidelines that instructs clinicians on how to prioritize care among patients seeking a cure.

August 06, 2014
Donors Only Reaching 7% of Global Harm Reduction Needs
Major international donors are only spending 7 percent of the estimated funding needed to support harm reduction for injection drug users worldwide.

Program for Drug-Using Couples Lowers Hep C and Risky Sex Rates
An intervention for couples who use drugs lowers their risk of contracting hepatitis C virus as well as raises their rate of condom use.

August 04, 2014
Olysio-Sovaldi Cures High Rates of Hepatitis C Genotype 1
Twelve weeks of Olysio (simeprevir) and Sovaldi (sofosbuvir) cures high rates of genotype 1 of hepatitis C without the need for ribavirin.

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July/August 2014 Edition - Not Yet Published....
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The hepc.bull, has been “Canada’s hepatitis C journal” since the late 1990′s and has been published nonstop since 2001. The monthly newsletter contains the latest research results, government policy changes, activities and campaigns you can get involved in, articles by patients and caregivers, and a list of support groups plus other useful links.

August Newsletter

In This Issue
RX&D Rebuttal /Review 2 New Drug
Co-infection: Bob’s Story / Hep C News 
RhoGAM/ Marathon News / Percuro 2
What is a Fibroscan? 

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The New York City Hepatitis C Task Force is a city-wide network of service providers and advocates concerned with hepatitis C and related issues. The groups come together to learn, share information and resources, network, and identify hepatitis C related needs in the community. Committees form to work on projects in order to meet needs identified by the community. 

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August Newsletter

In this Newsletter

New Provider Resources
Updated City Health Information (CHI): Diagnosing and Managing Hep C: Clinical guidance for medical providers.

Updated Hep C Dear Colleague Letter from the NYC Commissioner of Health.New Video PSA | Protect Your Family: Get Tested for Hepatitis B. 30 sec in English, CantoneseMandarin, Korean & Vietnamese.

Hep C: Get Tested, Get Cured! 32 second video illustrating the risks of Hep C, and the importance of testing and treatment. Share widely!


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Current Issue (Vol. 8 No. 8 August 2014): Download PDF Or View Interactive Issue

In This Issue
Fewer than 10% of HCV patients finish treatment
Sofosbuvir achieves SVR12 in patients with HCV + HIV
Interferon-free regimens yield 96%-100% SVRs
Everolimus fails to improve HCC survival

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Our mission is to educate the general public about hepatitis C and to provide resources and support for those affected by the virus. Hep C Connection offers a helpline to answer your questions regarding hepatitis C (HCV). You can expect respect, patience & understanding, in clear, jargon-free language from our staff & volunteers. Call 1-800-522-HEPC (4372) today!

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In This Issue
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Articles of Interest
Financial Resources
Featured Clinical Trials

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Welcome to the new HCV Action website, the home of the UK’s hepatitis C professional community. Browse our tailored resource libraries, view our case study map or find out more information, here.

The HCV Action network brings together health professionals from across the patient pathway, including GPs, specialist nurses, clinicians, drug action teams, public health practitioners, prison healthcare staff and commissioners. We provide resources for commissioners, medical and drug services professionals, promoting good practice in HCV care across the UK.Visit their new website, here. 

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South Asian community: get advice on hep C at the Birmingham Mela
Scottish study: hepatitis C in the gay community

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The Hepatitis Foundation International is dedicated to liver health and the prevention of liver related diseases. We inform and educate by making available reliable and up-to-date facts. We want you to make well-informed decisions for yourself and your loved ones' health and well-being. We are proud to present this website as your personal Internet gateway to hepatitis information and liver care.


In This Issue Of Health-e Bytes
HFI In The Know

Health Observances
Advocacy Alert
World Hepatitis Day
Lifestyle

HFI Launches Patient Registry
Grand Rounds
Science, Research and Medical Updates

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A monthly newsletter from the National Institutes of Health, part of the U.S. Department of Health and Human Services

News
Scientists detail urgent research agenda to better understand, address chronic disease toll
Health care systems that keep HIV patients from dying early in low- and middle-income nations need urgently to be repurposed to treat the chronic diseases that many of these patients now have, experts say.

Featured In The August Issue

Illustration of a patient being treated in a hospital room.Surviving Sepsis
Taming a Deadly Immune Response

Many people have never heard of sepsis, but it’s one of the top 10 causes of disease-related death in the U.S.

Read more about sepsis.

Can You Recognize a Heart Attack or Stroke?
What To Do When Every Moment CountsIllustration of a woman steadying herself against a wall while a concerned passerby makes a call for help.

How would you react to a medical emergency? When it comes to life-threatening conditions like heart attack or stroke, every minute counts. 




Healthy You

Hepatitis C - Understanding The Liver, and Cirrhosis
Watch a few innovative videos offering a better understanding of HCV, how the liver works, possible disease complications, and a quick look at treatment, brought to you by Armando Hasudungan and Joe Galati, M.D.

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Just So You Know

"HCV Next" Is In The News

Published August 11, 2014

University at Buffalo experts in the Division of Gastroenterology, Hepatology and Nutrition are contributing co-authors to HCV Next, the first multidisciplinary publication focused exclusively on the hepatitis C virus.

In Case You Missed It.....
Millennials, Drugs and HCV
HCV Next, July/August 2014


Available in print and on the Healio.com website, the magazine offers context and perspective on the latest research developments. It is designed to inform and educate an estimated 10,000 specialty and general physicians who diagnose and treat HCV.

Content also helps patients understand the disease and new treatment options that may be available to them.

Collaboration, Communication Among Specialists is Key

“With the rapid pace of drug development in HCV as well as the development of regional centers of excellence in hepatology — such as we have recently established here at UB within clinics — there is a tremendous need for rapid dissemination of new information for physicians of all specialties,” notes Andrew H. Talal, MD, MPH, professor of medicine and a member of the HCV Next editorial board.

“HCV Next is attempting to fill that void.”

“Contributing to this publication offers an excellent opportunity to promote the faculty and trainees here at UB on the national stage as leaders in the field,” he adds.

“It also helps establish UB as a leader in the eyes of the pharmaceutical industry, which can help attract clinical trials, allowing us to offer cutting-edge therapies to patients before they are widely available.”

In a May/June 2014 HCV Next interview, co-chief medical editor Ira M. Jacobson, MD, emphasized the importance of collaboration and open communication among liver and infectious disease doctors and addiction medicine specialists to address the multiple needs of patients.

Jacobson, the medical director of the Center for the Study of Hepatitis C in New York City, notes that Talal has led efforts to create physical spaces where patients are seen by multidisciplinary specialists.

At Buffalo General Medical Center, for example, “our liver clinic involves gastrointestinal fellows, pharmacists, internists, hepatologists and addiction medicine specialists who all see patients with various forms of liver disease,” says Talal. “We also have research nurses who consult with potential subjects for clinical trials.”

UB Items Discuss Pregnancy, Abnormal Proteins

In addition to Talal, HCV Next co-authors have included the following UB faculty members and physician-trainees in the gastroenterology, hepatology and nutrition fellowship program:
Manoj Kumar, MD, MPH, clinical assistant professor
Thomas C. Mahl, MD, clinical professor and interim chief of the division
Anthony D. Martinez, MD, clinical associate professor
Alia Hasham, MD, fellow
Sandeep T. Samuel, MD, fellow

Talal, Kumar and Hasham co-authored the patient profile, “The Challenge of Pregnancy in HCV Infection,” in the magazine’s premiere January/February 2014 issue.

“Since pregnancy modifies host-virus interactions, it is crucial to understand clinical manifestations of the infection and its effect on the overall magnitude of the disease, its diagnosis and management,” notes Talal.

“Physicians also should understand the effect of pregnancy on HCV immunity and appreciate the factors that influence mother-to-child viral transmission.”

Samuel, Talal and Martinez co-authored “Current Concepts on the Patient With HCV and Cryoglobulinemia,” a patient profile in the March/April issue. The article discusses current best practices for treating HCV patients with abnormal blood proteins.

Hasham and Mahl collaborated on “The Patient With NAFLD and Chronic HCV” for the July/August issue. This patient profile discusses diagnosis and care for HCV patients with non-alcoholic fatty liver disease.

Need for HCV Information Will Likely Grow

According to the World Health Organization, more than 150 million people carry the virus and more than 350,000 people die every year from HCV-related liver disease.

The need for HCV information will likely grow, as newly approved treatments are adopted and evolve.

In addition, more people are expected to be diagnosed with the infection, as new U.S. Centers for Disease Control and Prevention guidelines call for screening all people born between 1945 and 1965. A New York State law now requires health care providers to offer HCV screening to patients in this age group.

Magazine Published 6 Times Each Year

HCV Next is published every other month by the New Jersey-based SLACK Incorporated, publisher of Infectious Disease News.

Topics include diagnostics, practice management issues, drug interactions and the treatment of patients with comorbidities.

Stay healthy and happy, until next time.

Always Tina 

Saturday, February 15, 2014

2014 - Complementary and alternative medications in hepatitis C infection

Complementary and alternative medications in hepatitis C infection

Good afternoon folks, welcome to another edition of Weekend Reading.

On this fine Saturday a couple review articles evaluating the safety and efficacy of treating HCV using complementary and alternative medicine is our topic.

Sadly, we know not everyone can tolerate the currently available treatments, nor does everyone respond. Recently, two oral agents simeprevir and sofosbuvir were FDA approved, improving cure rates with shorter treatment duration and for some people even without interferon.

Over the last few years with grave desperation we have witnessed an era where new agents are rapidly being developed to eradicate this serious disease. Possibly Gilead's combination pill - consisting of both agents sovaldi and ledipasvir, may hold great promise. Gilead's clinical trials seem encouraging, for example in one trial deemed ION 2 that included 440 treatment-experience or difficult to treat genotype one patients, (88) with cirrhosis; SVR rates were at 93.6 percent after 12 weeks of therapy - while the cure rate rose to 99.1 percent with 24 weeks of treatment.

Last week Gilead filed for U.S. approval of Ledipasvir/Sofosbuvir Fixed-Dose Combination Tablet for Genotype 1 Hepatitis C

Again, not everyone who needs HCV treatment will be cured, and not everyone who needs treatment will be treated, thus complementary and alternative medications will be part of the equation aimed at trying to control symptoms or in some aspect manage HCV, especially in developing countries.

Complementary Health Approaches
Previously, The National Institutes of Health reported many people living with the virus try complementary approaches to manage HCV, such as massage, deep breathing exercises, meditation, progressive relaxation, and yoga, others use complementary and alternative medications, especially dietary supplements. Although these alternative options may offer therapeutic benefits, no complementary or alternative medications has been shown to be effective against the hepatitis C virus.

Review Articles
The first article provided below; "Complementary and alternative medications in hepatitis C infection," published in World J Hepatol, 2014 January, offers a look at the therapeutic potential of complementary and alternative medications (CAM), and drug interactions between medical and complementary treatments, including drug-CAM interactions which may lead to a reduced therapeutic effect when used with HCV oral drugs simeprevir and sofosbuvir.

A second review article; Management of chronic hepatitis C in patients with contraindications to anti-viral therapy, published this year in Alimentary Pharmacology & Therapeutics, provides information on alternative treatments for people who cannot tolerate or decide against interferon-based treatments. In the article researchers reported on life interventions which were associated with biochemical improvement, and treatments that had anti-inflammatory and/or anti-fibrotic effects. However, they found other alternatives such as (ribavirin monotherapy, amantadine, silibinin, vitamin supplementation, etc.) did not have any beneficial effect or need to be tested in larger clinical studies, view the full article, here.

Complementary and alternative medications in hepatitis C infection

World J Hepatol 2014 January 27; 6(1): 9-16
Published online 2014 January 27. doi: 10.4254/wjh.v6.i1.9.

Dina L Halegoua-De Marzio and Jonathan M Fenkel. Dina L Halegoua-De Marzio, Jonathan M Fenkel, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, United States Author contributions: Halegoua-De Marzio DL and Fenkel JM both outlined, researched the topics wrote, and wrote the manuscript.

Abstract
Chronic hepatitis C (CHC) infection affects almost 3% of the global population and can lead to cirrhosis, liver failure, and hepatocellular carcinoma in a significant number of those infected. Until recently, the only treatments available were pegylated interferon and ribavirin, which traditionally were not very effective and have considerable side effects. For this reason, interest in complementary and alternative medications (CAM) in the management of hepatitis C has been investigated. Some CAM has demonstrated therapeutic potential in chronic hepatitis C treatment. Unfortunately, some CAM has been shown to have the potential to cause drug-induced liver injury. This article will review and evaluate many of the natural molecules that interact with the hepatitis C virus (HCV) life cycle and discuss their potential use and safety in HCV therapy, as well as highlight some important interactions between medical and complementary treatments.

Core tip: Over the last 10 years there has been a substantial increase in reports of natural compounds displaying anti-viral activity against hepatitis C. At this time, there is no firm evidence supporting complementary and alternative medications for hepatitis C virus infection. Due to a limited number of trials and small numbers of subjects included in them, it is not possible to fully evaluate the risk of adverse events connected with the use of these products.

INTRODUCTION
Hepatitis C virus (HCV) infection affects an estimated 180 million people globally and is a leading cause of chronic hepatitis, cirrhosis, and liver cancer[1,2]. To prevent the complications of chronic hepatitis C (CHC), the goal of therapy is complete viral eradication. For the past decade, a combination of pegylated interferon-α (peg-IFN) and ribavirin was used to treat CHC with disappointing viral eradication rates. These rates were particularly suboptimal in patients with genotype 1 HCV, which is responsible for approximately 60% of worldwide infections[3]. Sustained virological response (SVR) rates for genotype 1 HCV are approximately 40% following 48 wk of peg-IFN/ribavirin and are even lower in patients with HIV co-infection, high baseline viral load, advanced fibrosis, or those of African descent[4-7].

The life cycle of HCV can be divided into three major steps: (1) entry of the virus into its target cells by receptor-mediated endocytosis; (2) cytoplasmic and membrane-associated replication of the RNA genome; and (3) assembly and release of the progeny virions[8]. In recent years, there has been improvement in SVR rates with the development and approval of the first HCV-specific direct-acting antiviral agents (DAAs), namely boceprevir and telaprevir[9,10]. In contrast to the non-specific antiviral activity of peg-IFN and ribavirin, DAA are designed to inhibit viral proteins involved in the HCV life cycle. Still, the first DAAs require coadministration with peg-IFN and ribavirin, and many patients remain intolerant to treatment-associated side effects, including fevers, influenza-like symptoms, headache, cytopenias, fatigue, anorexia, rash, and depressive symptoms.

CAM is being used increasingly across the globe for many chronic diseases[11,12]. The Cochrane Library included nearly 50 systematic reviews of complementary medicine interventions as of 2003[13]. Many people turn to CAM when conventional medicine fails, or they believe strongly in its effectiveness. During the last few years, a substantial increase of reports on natural compounds displaying an anti-HCV activity has been published. There is data that some of these medicinal herbs might have therapeutic potential in CHC, or may alleviate side effects of conventional therapy[13]. CAM use is common among people with CHC. A survey of 1145 participants in the National Institutes of Health (NIH)-supported HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) trial found that 23% of the participants used herbal products[14]. Although sometimes thought by the public to be safer then conventional therapy, there are many reports about liver toxicity and other adverse events from some herbal products[11,15].

The aim of this review is to evaluate the efficacy and safety of treating HCV infection using complementary and alternative medicine.

MEDICINAL HERBAL AND DIETARY SUPPLEMENTS WITH ANTI-HCV ACTIVITY 

Silymarin
An extract of the milk thistle plant, silymarin (Silybum marianum), has been used to treat chronic liver disease since the time of the ancient Greeks[16]. Owing to its purported hepatoprotective properties, it is the most commonly used herbal product by individuals with chronic liver disease in the United States[16,17]. A recent publication from the HALT-C study group indicated that 33% of patients with CHC and cirrhosis reported current or past use of silymarin[14]. A follow-up study found silymarin use among CHC patients was associated with reduced progression from fibrosis to cirrhosis, but had no impact on clinical outcomes[16].

The major active component of silymarin, silibinin (a mixture of the two diastereoisomers silybin A and silybin B), is thought to be responsible for silymarin’s hepatoprotective properties[18]. Silymarin appears to inhibit HCV infection at two or more different levels: (1) it inhibits HCV replication in cell culture; and (2) it displays anti-inflammatory and immunomodulatory actions that may contribute to its hepatoprotective effect[19,20]. The inhibition of HCV replication has been attributed to inhibitory action on the NS5B RNA-dependent RNA polymerase.

Clinical studies that have evaluated milk thistle for a variety of liver diseases have yielded inconsistent results and low bioavailability of oral silymarin components[21]. Studies with IV silibinin have shown substantial antiviral effect against HCV in liver transplant recipients, and even in nonresponders with good safety outcomes[22-24]. Although oral administration of silymarin is not effective for the treatment of HCV, intravenous silibinin formulation may represent a future potential therapeutic option.

Green tea extract
Green tea, made from the unfermented leaves of Camellia sinensis, is comprised of several polyphenolic compounds called catechins, and can be concentrated into a green tea extract (GTE). Epigallocatechin-3-gallate (EGCG) is the most abundant and potent catechin contained within GTE, comprising typically approximately 40% of the total polyphenol content[25]. EGCG is a potent inhibitor of HCV entry in primary human hepatocytes independent of the genotype, by blocking virus attachment. This novel inhibitor may provide a new approach to prevent HCV infection, especially in the setting of liver transplantation of chronically infected HCV patients[26,27]. Beyond its antiviral effect on HCV, EGCG may have potential use as a chemopreventative agent for hepatocellular cancer as EGCG may inhibit cancer cell growth. This mechanism of action is thought to be due to tyrosine kinase inhibition and modulation of target gene expression associated with induction of apoptosis and cell cycle arrest in cancer cells[28-34].

GTE is a common ingredient in several dietary supplements, some of which have been withdrawn from the market due to safety concerns. An example of this is Exolise (Arkopharma, France), a weight loss supplement containing high EGCG levels that was withdrawn from the market in April 2003 due to 13 cases of attributable liver injury[35]. Between 1966 and 2008, 216 case reports of toxicity with green tea extracts were identified by the United States Pharmacopeia, of which 34 were concerning for liver toxicity[36]. Recent animal studies with high doses of GTE and EGCG have described dose-dependent hepatotoxicity resulting in severe morbidity and mortality[37]. However, chronic moderate to high dose daily GTE and EGCG use in healthy human volunteers, and selected patients with cirrhosis, was safe and did not impair liver function[38-40]. Although GTE may be very useful in further treatment of CHC and prevention of HCC, its hepatotoxic potential must be acknowledged and monitored carefully in future studies.

Naringenin

HCV associates with β-lipoproteins [very low density lipoprotein (vLDL) and low-density lipoprotein (LDL)] circulating in blood[41]. In addition, HCV replication can be up-regulated by fatty acids and inhibited by statins; this suggests an interaction between HCV, cholesterol, and lipid metabolism[42]. Recent research has found that of HCV secretion is dependent on both apolipoprotein B (ApoB) expression and vLDL assembly in a chromosomally integrated complementary DNA (cDNA) model of HCV secretion[43].

Naringenin is the predominant flavanone present in the grapefruit and is responsible for its bitter taste. Naringenin has been shown to reduce cholesterol levels both in vitro and in vivo[44,45]. Furthermore, naringenin inhibits ApoB secretion by reducing the activity and the expression of the microsomal triglyceride transfer protein (MTP) and the acyl-coenzyme A cholesterol acyltransferase 2 (ACAT)[44,46]. Due to the close link between HCV assembly/secretion and lipoprotein metabolism, there has been extensive study on the impact of naringenin on the secretion of HCV particles[43]. A dose-dependent decrease of core protein, HCV-positive strand RNA, infectious particles, and ApoB has been observed in the supernatant of infected primary hepatocytes in culture after naringenin treatment[43]. Overall, naringenin blocked the assembly of intracellular infectious viral particles without affecting intracellular levels of the viral RNA or protein. Although still at the cell culture phase, naringenin may offer new insight into a promising and novel HCV therapeutic target.

Glycyrrhizin
Glycyrrhizin, a natural compound extracted from the roots of Glycyrrhiza glabra, has been used for more than 20 years as a treatment for chronic hepatitis[47]. It has been used for many centuries in traditional Chinese medicine as an anti-allergic agent. Because of its sweet taste it is also used as a food additive, for example in beverages and licorice[48]. In an attempt to use glycyrrhizin as a treatment for “allergic” hepatitis it was found to lower the transaminases. In a study by Suzuki et al[49] in 1977, plasma transaminases activity improved significantly with glycyrrhizin in patients with chronic liver disease compared to a placebo group.

The mechanism by which glycyrrhizin improves the biochemistry and histology in liver disease is unknown. It is thought to have anti-inflammatory, antioxidant and immunomodulatory activities. Due to this there has been much interest in use of glycyrrhizin in CHC. In the only randomized clinical trial of glycyrrhizin, ALT levels declined modestly during treatment, compared with placebo, but this was not sustained after cessation of treatment and there was no significant effect on HCV RNA levels[50]. In the another trial, statistically significant differences in liver enzyme levels, but not viral loads, between treatment groups were identified during treatment, however, again no sustained response occurred at follow-up[51]. Use of glycyrrhizin is not without side effects. It has been found to cause pseudo-aldosteronism, manifested by sodium retention, hypokalemia and hypertension[52]. Cardiac arrhythmia and acute rhabdomyolysis due to severe hypokalemia caused by excess licorice consumption have also been reported[52-54].

Oxymatrine
Oxymatrine is the major alkaloid extract from the root of sophora flavescens, a deciduous shrub native to China, Japan, South Korea and Russia. It is reported to have antiviral activity against HCV in cell cultures and in animal studies[55-57]. Clinical studies have shown that oxymatrine has some hepatoprotective activity in alcohol toxicity and hepatitis B infection, but not carbon tetrachloride, acetaminophen or cadmium chloride-induced acute hepatitis[58,59].


Oxymatrine is considered to be an antifibrotic, likely through inhibition of lipid peroxidation[60-62]. In a study of HCV-infected subjects randomized subjects to receive either an intramuscular injection of oxymatrine 600 mg/d or other support products such as oral vitamins 47% of the treated cases had complete HCV viral suppression after 3 mo, compared with only 5% in the control group[61]. No serious adverse events were reported. The treated group had significantly more ALT normalizations than the control group in the first 2 mo, but this improvement waned by the end of the third month of treatment. While treatment with oxymatrine holds promise, it is difficult to draw conclusions from the small studies currently available.

Traditional chinese herbal medications
The primary goal of Chinese traditional medicine is to create wholeness and harmony within a person, allowing the mind/body/spirit to heal itself. There have been several randomized clinical trials of traditional Chinese medicine in the treatment of hepatitis C, however, the methodological quality of these studies is generally considered poor[63-70].

In two trials of herbal formulations in combination with interferon-alfa, there was a trend toward greater clearance of HCV RNA and ALT normalization with the combination treatment compared with patients receiving monotherapy[63,64]. In the only placebo-controlled trial of solo therapy with traditional Chinese medicine, a significant reduction in ALT levels during treatment occurred, though no virologic effect was identified[69]. Detailed descriptions of adverse events were not provided for most of these trials. The safety of these medicines is unclear due to the individualized nature of many of the herbal compounds involved, the large number of different herbs in each formulation, and the relatively small number of subjects within each clinical trial.

Vitamin D
The traditional role of Vitamin D (Vit D) was thought to be based upon its interaction in calcium homeostasis, via regulation of intestinal calcium absorption and of bone health. However, over the last several years Vit D has been shown to have a much more complex role in many other host functions, including its interaction with chronic hepatitis C. 25-OH Vit D is made in the liver via cytochrome P450 (CYP27A1) activated hydroxylation of Vit D, brought into the body either by intestinal absorption or endogenous synthesis through sun-exposed skin. It is then converted to 1.25 OH Vit D (calcitriol) in the kidneys, the most active form, where it becomes available to bind to Vit D receptors throughout the body[71,72].

A growing body of clinical evidence has demonstrated an increased prevalence of Vit D deficiency in patients with CHC. As such, Vit D supplementation has been proposed as an adjunct to current standard regimens for treatment of hepatitis C[72]. One study found that mean 25-OH Vit D serum levels were significantly lower in CHC (25 μg/L) than in the controls (43 μg/L)[73]. Importantly, low Vit D has been linked to increased fibrosis and impaired sustained virologic response (SVR) in IFN-based therapy[71].

One clinical trial demonstrated that the addition of Vit D to the standard IFN plus ribavirin treatment significantly increased SVR in patients with genotype 1 CHC[74]. Regarding the underlying molecular mechanisms, an in vitro study showed that Vit D remarkably inhibits HCV production in Huh7.5 hepatoma cells[75]. These cells express Vit D hydroxylases and can eventually generate calcitriol. Notably, treatment with calcitriol resulted in HCV inhibition through induction of IFN-beta. Overall, 25-OH Vit D levels appear to be an important prognostic marker in helping determine the likelihood of SVR. 25-OH Vit D levels should be checked routinely before HCV treatment and supplementation provided to deficient patients, in an effort to enhance treatment response.

Antioxidants
Antioxidants are one of the most common dietary supplements taken by patients with CHC[14]. The use of these supplements is based on the fact that oxidative stress has been attributed to both host inflammatory processes and induction by viral proteins. By increasing antioxidants, one may be able to decrease oxidative stress and therefore decrease liver injury[76]. Existence of oxidative stress in CHC is well documented, as oxidized protein and nucleic acid markers are increased and antioxidant levels are decreased[77-80]. Studies have shown levels of oxidative stress markers to correlate with disease severity, HCV RNA, iron overload, and insulin sensitivity[78,79]. Oxidative stress has also been shown to be an early event in carcinogenesis and is a risk factor for development of HCC in patients with chronic HCV[81].

Multiple trials have shown antioxidants, such as Vitamin E and N-acetyl cysteine, only lead to small reductions in ALT after chronic administration in some instances[82-93]. Further, the decrease in ALT levels in most studies is marginal and is not sustained after stopping the treatment, raising the question of their clinical significance. No study has shown an improvement in outcome. In addition, no study has shown clear benefit of antioxidants as adjuvant to interferon based therapy of HCV. At the doses studied, these antioxidants appear to be well-tolerated, with no specific adverse events reported in any of the trials. However, very large oral doses of N-acetyl cysteine are commonly associated with nausea and vomiting and intravenous administration of N-acetyl cysteine can result in anaphylactoid reactions, which may be more common in patients with chronic liver disease[94]. Therefore, evidence supporting use of antioxidants as useful therapeutic agents in CHC is lacking.

HERBAL SUPPLEMENTS AND DRUG INDUCED LIVER INJURY IN CHRONIC HCV


Drug-related hepatotoxicity is a serious health problem, with broad implications for patients, healthcare providers, the pharmaceutical industry and governmental regulatory agencies. The Drug Induced Liver Injury Network (DILIN), a federally funded consortium of 12 centers in the United States, recently reported the preliminary results of its prospective study[94]. Dietary supplements were implicated in 9% of reported DILI cases. This may be potentially related to increasing use of herbal or dietary supplements in the US population. The importance of these supplements as a cause of DILI is further underscored by a retrospective Japanese study, in which 10% of 879 cases of single agent DILI from 1997 to 2006 were attributed to dietary supplements and 7% to Chinese herbal drugs[95]. 

DRUG-CAM INTERACTIONS
Telaprevir, Boceprevir, Simeprevir and Sofosbuvir
Another major area of awareness when patients are considering using CAM is whether or not drug-CAM interactions may exist that could impact the medical therapy. This issue is becoming even more complicated with the addition of new medications for the treatment of CHC infection such as simeprevir and sofosbuvir approved for use in the U.S. in December 2013. St. John’s wort (Hypericum perforatum), a common CAM used for the treatment of depression, is an inducer of cytochrome P450 3A4[99].

This cytochrome is also the primary metabolizer of many medications, including the HCV protease inhibitors: telaprevir, boceprevir, and simeprevir. Additionally, St. John’s wort is a potent intestinal P-gp inducer and may lead to a reduced therapeutic effect of the HCV nucleotide polymerase inhibitor sofosbuvir[100]. Concomitant use of St. John’s wort and these HCV treatments is contraindicated and can lead to treatment failure by reducing blood concentrations. Additionally, concomitant use of milk thistle use is contraindicated with simeprevir. This combination may increase levels of simeprevir by milk thistle CYP3A inhibition leading to possible toxicity[101] (Table 1). Garlic extracts, grapefruit juice, and germander also have cytochrome P450 3A4 interactions[102].


CONCLUSION
Many human studies have shown improvements in subjective symptoms and liver biochemistries in HCV patients with CAM, but there is no convincing data to suggest a definite histological and/or virologic improvement with any of the herbal agents currently available. Vit D seems to have the best available data as adjunctive therapy to antiviral medications in patients with Vit D deficiency. Poorly designed studies, heterogeneous patient populations, lack of standardized preparations, and poorly defined nonobjective end points may partly explain the conflicting reports in the literature.

The safety profiles of the interventions discussed within this review are encouraging at the doses studied. However, the long-term safety for use in the treatment of hepatitis C, either alone or in combination with conventional medicines, has not been established. Comparative and placebo-controlled trials suggest that patients experience no more adverse events with these interventions than with placebo or comparative medications, although short-term clinical trials are not designed to detect rare or delayed adverse events. Physicians need to be cognizant of known or occult use of CAM by their patients because hepatotoxicity and drug interactions may occur with many herbal medications, and may occur more frequently in patients with chronic liver disease.

There is an undoubted need for further research into the treatment of hepatitis C, and this review has identified several promising compounds, including Vit D, silymarin, oxymatrine, naringenin, and GTE. Some or all of these may be integral components of future HCV management.

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