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.

Copyright ©2014 Baishideng Publishing Group Co., Limited. All rights reserved.

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.

Correspondence to: Jonathan M Fenkel, MD, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, 132 S. 10th Street, Suite 480, Main Building, Philadelphia, PA 19107, United States. jonathan.fenkel@jefferson.edu

Telephone: +1-215-9558900 Fax: +1-215-5032146

Received October 9, 2013; Revised December 22, 2013; Accepted January 6, 2014;

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.

Keywords: Hepatitis C infection, Natural molecules, Direct acting antivirals, Hepatotoxicity, Herbal 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].

In general, chronic liver diseases such as HCV infection are thought to be associated with an increased incidence of hepatotoxicity induced by several specific drugs. Furthermore, patients with underlying liver disease potentially have worse outcomes than healthy individuals if they do develop DILI[⁹⁶]. For example, the presence of underlying CHC has been shown to increase the risk of DILI caused by the antituberculosis drugs isoniazid and rifampin, as well as ibuprofen and methimazole[^15,97,98]. Due to this, patients with chronic hepatitis C should be counseled and screened by physicians on potential risks associated with herbal medications.

DRUG-CAM INTERACTIONS

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].

Table 1 Herbal supplements to discontinue and/or avoid while taking hepatitis C virus treatment

Herbal Product	Effect
Milk thistle (Silybum marianum)	Concomitant use of milk thistle may result in increased plasma concentrations of simeprevir
St. John’s wort (Hypericum perforatum)	Concomitant use of St. John’s wort may result in decreased plasma concentrations of telaprevir, boceprevir, simeprevir and sofosbuvir

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.

Footnotes

P- Reviewers: De Ponti F, Julie NL, Sunbul M S- Editor: Wen LL L- Editor: A E- Editor: Liu XM

References

Source

Hepatitis C Cure Availability In Developing Countries Hits Snag Over Pricing

Provided by BioNews Texas

Posted by: Mike Nace February 17, 2014

Leading world health organizations agree that the global rise of Hepatitis is an alarming health issue — one that may have already eclipsed AIDS in many parts of the world. It is estimated that at least 150 million people have Hepatitis C worldwide — nearly 5 times the number of people who suffer from HIV. Hepatitis C is a particularly ravaging disease since, if left untreated, it can eventually cause liver damage and lead to cancer. While drug development for a Hepatitis B cure to complement the already-developed vaccine continues to progress, the good news forHepatitis C is that a cure already exists. The issue, however, is not the cure, but its price.

In countries like India, where Hepatitis C is a major health issue, the high cost of the cure is a sticking point between drug developers looking to get value for their product and health officials who see curing the disease as the only consideration in pricing the treatment. According to a recent article in the New York Times by Donald G. McNeil, Jr., the simple pill regimen for curing Hepatitis C — a drug called sofosbuvir developed by Gilead Sciences under the brand name Sovaldi in the U.S. – costs American patients and healthcare companies an estimated $84,000 per treatment.

The price tag for Sovaldi is clearly priced for the hyper-inflated U.S. healthcare market, which often prices high-performance drugs, surgeries, and other specialized medical procedures higher than anyone could ever pay on their own in the U.S., let alone the developing world. In a country like India, however, $84,000 per treatment for Hepatitis C isn’t even a consideration.

For their part, Gilead has suggested a path toward licensing the treatment to Indian drug companies that they believe would get the price of sofosbuvir down to a $2,000-per-treatment version — a mere 2.3% of the U.S. price.

However, worldwide health advocates are lobbying for Gilead to do what it takes to make their Hepatitis C cure widely affordable and available to those who have the disease in the developing world. McNeil’s piece highlights Doctors Without Borders’ efforts to exhort Gilead to craft sofosbuvir-based treatments for $250 or less, and is lobbying the World Health Organization “to put sofosbuvir on its list of drugs the agency tests for countries too poor to have their own drug regulatory agencies.”

Rohit Malpani, a Doctors Without Borders policy advisor, outlines the organization’s position on the pricing issue, and reveals just how far apart the two sides are on getting to a price that satisfies everyone involved: ”We think a $2,000 price tag, although a discount from U.S. prices, is not going to get the job done,” he noted. “It’s a discount from a price we think is absolutely outrageous. The way we look at it is, how much does this drug cost to make and what is patients’ ability to pay?”

Critics of Gilead’s pricing scheme say, that they believe the Hepatitis C treatment could be offered to countries like India for as low as $68 to $136 for a 12-week treatment course.

“We know from our experience treating HIV over the past decade and a half that treatment needs to be simple and affordable,” Malpani says in a Doctors Without Borders statement. “Full hepatitis C treatment needs to be available for no more than $500 per person.”

In recent comments on the issue, Gilead does not appear to be ready to capitulate to these calls for lower prices. Instead, the company has indicated that, once it finalizes licensing for the drug in India, it would be incumbent upon Indian generic producers to offer competitive pricing on Solvadi, not only to make it more affordable, but also to gain a market advantage in India: ”We’ll be working probably with three to five different companies,” Gregg Alton of Gilead told The Hindu Business Line. “We leave it up to the Indian companies to bring the price down, should they choose to do that.”

Source

Researchers look to reduce Hep C infections with "Staying safe intervention" for injecting drug users

February 11, 2014
N-195 2013-14

Despite a number of social/behavioral intervention and educational programs, the spread of hepatitis C (HCV) in people who inject drugs (PWIDs) remains a chronic problem. Now, researchers affiliated with New York University’s Center for Drug Use and HIV Research (CDUHR) are focusing on intervention strategies that highlight the lesser-known dangers of HCV transmission through the sharing of other injection equipment such as cookers, filters, drug-dilution water and water containers.

Their article, “The Staying Safe Intervention: Training People Who Inject Drugs in Strategies to Avoid Injection-Related HCV and HIV Infection,” published in the 2014 March-April issue ofAIDS Education and Prevention, explores the feasibility and efficacy of their “Staying Safe Intervention,” a strengths-based social/behavioral intervention conducted with small groups of PWID, designed to facilitate long-term prevention of HIV and HCV.

“The Staying Safe Intervention seeks to reduce injection risk by intervening upstream in the causal chain of risk behaviors by modeling, training in, and motivating the use of strategies and practices of long-term risk-avoidance,” said Dr. Pedro Mateu-Gelabert, the study’s Principal Investigator, at the NYC-based National Development Research Institutes.

Dr. Mateu-Gelabert and his NDRI-CDUHR team evaluated 68 street-recruited injectors from the Lower East Side of Manhattan. The objective was to reduce participants’ injection risk behaviors, empower and motivate behavioral change, and teach tactics to help reduce drug intake.  The current program was built upon findings of their 2005 study, “Staying Safe,” which looked at the behaviors and strategies of individuals who had injected drugs for long periods of time (8–15 years) but had not contracted HIV or HCV.

“The Staying Safe Intervention does not focus exclusively on the moment of injection,” explains Dr. Mateu-Gelabert, “but on the upstream determinants of risk behavior, such as stigma, risk networks, social support and income, while encouraging injectors to plan ahead in order to better manage the drug-related risk contexts they are likely to face.”

The social/behavioral intervention showed substantial improvement in motivation and planning to avoid injection-related risks, increased use of stigma management strategies, and decreases in drug withdrawal episodes (known to reduce safe injection practices) and number of weekly injections. The research team also noted that participants in the study have been spreading the word on safer drug use within their communities.

The Centers for Disease Control and Prevention estimate that not only do nine percent of new HIV infections originate from drug use, but 18 percent of PWID are HIV positive and up to 70-77 percent of PWIDs have HCV.

“Given the substantial reductions observed among Staying Safe participants in key injection-related risk behaviors associated with HCV transmission, the Staying Safe Intervention may have the potential to contribute to sufficient additional risk reduction to help address the seemingly intractable rates of HCV transmission among PWID,” said Dr. Mateu-Gelabert.

Currently, Dr. Mateu-Gelabert’s team is researching HCV and HIV risk associated with nonmedical prescription opioid use. Future research will evaluate the effectiveness of the Staying Safe Intervention in preventing HIV and hepatitis C infection among young prescription opioid users who have transitioned to heroin injection.  “The goal is to implement the Staying Safe approach with this new generation of young injectors, so they do not get infected with HIV or HCV,” said Dr. Guarino, a Co-investigator in the project.

The project described was supported by Award Numbers R21DA026328, R01DA019383, R01DA031597, and R01DA035146 from the National Institute on Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Drug Abuse or the National Institutes of Health.

The research team members are: P. Mateu-Gelabert, M.V Gwadz, H. Guarino, M. Sandoval, C.M Cleland, A. Jordan, H. Hagan, H. Lune, S.R Friedman. Affiliations: National Development Research Institutes Inc. (PMG,HR,MS,SRF), New York, NY USA; College of Nursing (MVG,CMC,AJ,HH), New York University; Hunter College (SRF), City University of New York, NY USA.

About CDUHR

CDUHR, funded by the National Institute on Drug Abuse, is the first center for the socio-behavioral study of substance use and HIV in the United States. The Center is dedicated to increasing the understanding of the substance use-HIV/AIDS epidemic, particularly among individuals in high-risk contexts. The Center's theme is "Discovery to Implementation & Back: Research Translation for the HIV/Substance Use Epidemic." The Center facilitates the development of timely new research efforts, enhances implementation of funded projects and disseminates information to researchers, service providers and policy makers.

About New York University College of Nursing
NYU College of Nursing is a global leader in nursing education, research, and practice. It offers a Bachelor of Science in Nursing, a Master of Arts and Post-Master’s Certificate Programs, a Doctor of Philosophy in Research Theory and Development, and a Doctor of Nursing Practice degree.  For more information, visit www.nyu.edu/nursing.

This Press Release is in the following Topics:
College of Nursing, NYUToday-feature

Type: Press Release

Press Contact: Christopher James | (212) 998-6876

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Walgreens Expands Access to Pharmacist-Led Hepatitis C Care as Treatments Advance

PRESS RELEASE February 17, 2014, 10:35 a.m. ET

More than 100 Walgreens Pharmacies Designated Hepatitis C-Specialized to Meet Projected Patient Care Management Needs and Improve Medication Adherence

DEERFIELD, Ill.--(BUSINESS WIRE)--February 17, 2014--

With new advances in treatment therapy now available for hepatitis C patients, Walgreens (NYSE:WAG) (Nasdaq:WAG) today announced it is expanding access to Walgreens Connected Care(sm) hepatitis C program through its more than 100 hepatitis C-specialized pharmacies. Walgreens Connected Care is an education and support plan designed to help patients achieve a sustained virologic response (SVR) and improved quality of life through medication adherence.

The expansion comes at a critical time, as the once potentially life-threatening condition affecting more than 3.2 million Americans is now increasingly curable due to recent advances in therapy.(1) Also, a growing number of Americans with hepatitis C infection are expected to have access to health insurance based on the provisions of the Affordable Care Act.

Walgreens now offers more than 100 hepatitis C-specialized pharmacies with new hepatitis C virus (HCV) medications available and pharmacists specially trained on next generation oral therapies. Walgreens hepatitis C specially-trained pharmacists are also qualified to identify HCV-associated health concerns and can provide hepatitis C patient care for those with a HIV co-infection or other comorbid conditions, such as diabetes or high blood pressure. The specialized support has been proven to benefit patients, contributing to 90 percent adherence for patients who completed past treatments(1) .

"While recent hepatitis C therapy advances can be more effective and present fewer side effects, some patients, with high instance of comorbidity, can experience difficulty in managing care and an increased cost of therapy," said Glen Pietrandoni, Walgreens director specialty products and services, virology. "Walgreens Connected Care(sm) hepatitis C program, delivered through our hepatitis C- specialized pharmacies, is designed to meet the holistic needs of people diagnosed with hepatitis C -- before, during and after HCV treatment. This can help patients achieve SVR and an improved quality of life through medication adherence, while continuing to manage other health outcomes."

Patients in Walgreens Connected Care(sm) hepatitis C program receive support services including 24-hour access to specially trained pharmacists, help verifying insurance and identifying financial assistance options, convenient access to or delivery of medication and pharmacist-led regimen check points to monitor response to therapy and encourage medication adherence.

Walgreens hepatitis C specially trained pharmacists work with patients to determine the best method of delivery. HCV medications can be picked up at a Walgreens hepatitis C specialized pharmacy or a designated local Walgreens pharmacy. Delivery is also available through hepatitis C specialized pharmacies or Walgreens Specialty Pharmacy locations.

"As the most common blood transmitted infection in the U.S. largely affecting an aging population with high instance of other health concerns, careful holistic patient pharmaceutical care and supported comprehensive therapy treatment plans are critical to maintain total medication adherence," said Pietrandoni.

About Walgreens

As the nation's largest drugstore chain with fiscal 2013 sales of $72 billion, Walgreens (www.walgreens.com) vision is to be the first choice in health and daily living for everyone in America, and beyond. Each day, Walgreens provides more than 6 million customers the most convenient, multichannel access to consumer goods and services and trusted, cost-effective pharmacy, health and wellness services and advice in communities across America. Walgreens scope of pharmacy services includes retail, specialty, infusion, medical facility and mail service, along with respiratory services. These services improve health outcomes and lower costs for payers including employers, managed care organizations, health systems, pharmacy benefit managers and the public sector. The company operates 8,206 drugstores in all 50 states, the District of Columbia, Puerto Rico and the U.S. Virgin Islands. Take Care Health Systems is a Walgreens subsidiary that is the largest and most comprehensive manager of worksite health and wellness centers, provider practices, and in-store convenient care clinics, with more than 750 locations throughout the country.

(1) Ghany, M. G., Nelson, D. R., Strader, D. B., Thomas, D. L. and Seeff, L. B. (2011), An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology, 54: 1433-1444. doi: 10.1002/hep.24641.

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Exome-Wide Association Study Links Variant, Function to Nonalcoholic Fatty Liver Disease

February 17, 2014

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – Through an exome-wide association study, researchers led by Jonathan Cohen, a professor at the University of Texas Southwestern Medical Center in Dallas, uncovered three variants linked to nonalcoholic fatty liver disease.

As the researchers reported in Nature Genetics yesterday, two of those variants were located in a gene previously linked to disease while one was in the TM6SF2 gene, whose function they traced to the secretion of very-low-density lipoprotein. The variant itself appeared to be associated with higher levels of alanine transaminase, which typically rises in response to liver injury, as well as with lower levels of low-density lipoprotein-cholesterol, triglycerides, and alkaline phosphatase, another marker of liver disease.

"[Our] data indicate that TM6SF2 activity is required for normal VLDL secretion and that impaired TM6SF2 function causally contributes to [nonalcoholic fatty liver disease]," Cohen and his colleagues said.

Nonalcoholic fatty liver disease, or NAFLD, comprises a range of conditions stemming from the accumulation of fat into the liver. The researchers noted that some 30 percent of adults have excess fat in their liver, stored as triglycerides, and that while the condition can be benign, it can also lead to chronic inflammation and cirrhosis. The US National Institute of Diabetes and Digestive and Kidney Diseases reports that NAFLD is becoming more common in the US, possibly due to the increasing number of people with obesity.

Cohen and his colleagues searched for variants associated with hepatic triglyceride content in 2,736 participants from the Dallas Heart Study, sifting through some 138,400 polymorphic sequence variants while adjusting for ancestry, age, body mass index, and gender.

From this, they identified three variants linked to hepatic triglyceride content — two variants in the PNPLA3, which they had previously found to be associated with hepatictriglyceride levels, and one variant in the TM6SF2 gene, whose function was unknown.

The TM6SF2 variant, an adenine-to-guanine substitution leading to lysine replacing glutamate at residue 167, was more common in people of European ancestry than in African Americans or Hispanics, the researchers said. They also noted that the non-substituted form, Glu167, is highly conserved among mammals. People with the variant, though, had elevated hepatic triglyceride content no matter their ancestry.

Additionally, the TM6SF2 variant wasn't linked to other hepatic steatosis risk factors like BMI, insulin resistance, or alcohol consumption. It was also independent from the PNPLA3 variants.

RT-PCR analysis of cDNA from a range of human tissues found that TM6SF2 is highly expressed in the small intestine, liver, and kidneys, though it is found at lower levels in other tissues as well. The TM6SF2 variant is also linked to an increase in serum ALT, a marker of liver injury.

The researchers also confirmed the link between the TM6SF2 variant and NAFLD by drawing two cohorts, one from the Dallas Biobank and one from Copenhagen, including from the Copenhagen City Heart Study and from the Copenhagen General Population Study, with more than 82,000 samples. In both cohorts, the TM6SF2 variant encoding p.Glu167Lys was connected with signifi¬cantly higher activity of ALT in serum.

"These findings further support the hypothesis that the TM6SF2 variant encoding p.Glu167Lys is associ¬ated with NAFLD and are consistent with the notion that the vari¬ant compromises hepatic integrity," Cohen and his colleagues noted.

Further, in all three cohorts, the TM6SF2 variant was linked to lower levelsof triglycerides and LDL-C made in the liver.

By expressing the wild-type and variant forms of the protein in a hepatic cell line, the researchers found that wild-type and variant mRNA levels were comparable, but also that much less — 46 percent less — of the variant protein was expressed. This, the researchers said, suggests that the variant protein is misfolded and quickly degraded within the cell.

To determine how that affects hepatic triglyceride content, Cohen and his colleagues developed recombinant adeno-associated viral vectors that expressed short hairpin RNAs targeting TM6SF2 in mouse livers. Two different shRNAs aimed at TM6SF2 led to a more than 90 percent reduction in TM6SF2 mRNA in mouse livers, but not in other tissues, the researchers said.

Inhibiting TM6SF2 in mouse liver led to a three-fold increase of hepatic triglyceride content while also leading to lower plasma cholesterol levels — LDL, HDL, and the triglyceride content of VLDL were reduced, the researchers reported. ALT levels, though, were unchanged.

This, the researchers said, is consistent with a defect in VLDL secretion. To see just how knocking down TM6SF2 affects VLDL secretion, the researchers inhibited the enzyme — intravascular lipoprotein lipase — that breaks down the triglyceride con¬tent of VLDL and measured how quickly plasma triglycerides built up in plasma. In the knockdown mice, the rate of accumulation was much lower than in the control mice.

"These data indicate that TM6SF2 normally acts to promote VLDL secretion and suggest that the increased HTGC associated with the Glu167Lys TM6SF2 variant in humans results from a reduction in TM6SF2 function," Cohen and his colleagues said.

They noted that diets high in sucrose appear to intensify the effect that knocking down TM6SF2 had on hepatic triglyceride content.

Cohen and his colleagues further hypothesized that TM6SF2 might work in the intestine, where it is also expressed, to influence ALP activity. They said that they are currently exploring whether TM6SF2 is involved in lipoprotein synthesis and ALP activity in the intestine as well as the connection between lower ALP levels and increased hepatic triglyceride content linked to the TM6SF2 variant encoding p.Glu167Lys.

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Determining the Effect of Hepatitis C on Mortality: Sorting the Signal From the Noise - Editorial

Provided by NATAP

Download the PDF here

Clinical Infectious Diseases Advance Access published February 12, 2014 Keith M. Rose Mount Sinai Health System St. Luke's Roosevelt Hospital

Hepatitis C is a major cause of morbidity and mortality estimated to affect over 150 to 200 million people worldwide. 1,2,3 Infection with hepatitis C virus (HCV) carries a large clinical impact and high cost burden to health care systems, and is one of the leading contributing causes of end stage liver disease requiring liver transplantation in the US. 4 Advancements have been made in areas of both diagnosis and treatment, improving our ability to detect and treat the disease earlier. This carries the potential benefit of decreasing the morbidity and mortality caused by this disease.
This month's issue of Clinical infectious Diseases features two articles which address the impact of hepatitis C, highlighting both the significant mortality it brings as well as the potential underreporting of the disease. Both of these studies utilize data collected from death certificates and either disease reporting/ surveillance systems, or electronic medical records.

The study by Pinchoff et al entitled "Death among people with Hepatitis C in New York City, 2000-2011'"examined surveillance data for Hepatitis C reporting, and compared it to cause of death data obtained from death certificates from 2000 to 2011 in New York City (NYC). They evaluated the effect of Hepatitis C on age of death, cause of death (COD), as well as the effect of co-infection with HIV compared to the population without these diseases. This was a well designed study taking advantage of New York City having several robust disease surveillance registries that were able to be cross-matched and then compared to mortality data. By doing the study in NYC, they were able to evaluate a large, well defined, and diverse population with a particularly high incidence of this disease.5 This study adds to the literature as it further helps to delineate the natural history of Hepatitis C in the real world.The authors were able to convincingly demonstrate an increased risk of premature mortality (age <65) in patients infected with hepatitis C, stressing the importance again of early identification and potential treatment of this disease.The study also attempted to further evaluate the cause of death in this population from a review of death certificate data. It is very important to understand when and how people are being diagnosed with the disease and ultimately what they are specifically dying from.

There are however some weaknesses in the study that need to be discussed. Unlike a true cohort, this study only captured people who died in NYC. Patients who were diagnosed and treated in NYC would not be included in the COD analysis if they were to die outside of the city limits. Although the study implies that earlier diagnosis and treatment would likely decrease premature mortality, the study was not able to evaluate the subset of people that were treated for hepatitis C, and with what regimen. Overall the study does an excellent job demonstrating the associated mortality with HCV, but causation is much more difficult to prove. Lastly, the utilization of death certificate data may lead to a classification bias with overrepresentation of certain CODs ie HIV/AIDS and cardiovascular causes. 6,7,8

Also in this issue of Clinical Infectious Diseases, Mahajan et al publish their findings from The Chronic Hepatitis Cohort Study (CHeCS). This large cohort of 11,703 patients was formed from a review of electronic medical records from four large healthcare systems from 2006-2010, extracting demographics and data from patients diagnosed with HCV. They found a significantly higher than expected effect of hepatitis C on mortality, with a mortality rate twelve times higher in their cohort compared to the general population. An interesting finding of this study, was the paucity of HCV being listed on death certificates of these individuals. In fact, the majority of deaths, whether liver or non-liver related, did not have hepatitis C listed as a COD. Although this finding was specifically for hepatitis C, it reiterates the importance of proper death certificate completion and accuracy. It also sheds light on the potential impact on other studies such as the article by Pinchoff et al above that utilize death certificate data, to determine the impact on mortality of a certain disease. Potentially the Pinchoff study may be missing large numbers of patient s that died from both hepatic and non-hepatic causes related to Hepatitis C. Clearly those that had hepatitis C listed on their death certificates tended to died younger with a higher incidence of premature death, but the full impact is uncertain if we don't have an accurate representation of the deaths that HCV may have contributed to.

This paper by Mahajan et al also has some limitations, and opens the door for many further questions. This study was done with data from four large academic centers and may not necessarily be extrapolated to all hospital systems. Furthermore it would be interesting to know who completed the death certificates, ie attending versus resident or intern, how often it was completed by a covering physician who may not have known the patient as well, and what specific training, if any the completing physician had received in proper death certificate completion. Lastly it would be useful to know what percentage of patients were being treated for Hepatitis C and the impact this may have had on this subset of the cohort.

It's important to note that both of the above studies are only able to take into account HCV cases that were picked up by surveillance. HCV is often under diagnosed, so we don't know if the findings from these studies would apply to all subjects infected with HCV. We can only address the mortality risk, and associations in those with an established diagnosis of hepatitis C. Many of these cases may have been detected because of liver function test abnormalities or exam findings consistent with liver disease. It's important to also consider that hepatitis C infection is associated with several social factors and behaviors that can increase the risk of death. This comes back to an important question of whether people are dying with hepatitis C or from hepatitis C. To this point, it is also possible that some of the controls who died in both studies may have had HCV, as not everyone who dies is checked for the disease.

As more studies are done to look at the effect of disease, and ultimately determine what Americans or other populations are dying from, the importance of accurate information on death certificates becomes paramount. Based on their data, Mahajan et al propose that 80,000 Americans died with Hepatitis C in 2010 instead of the reported 16,622 secondary to gross underreporting on death certificates. This huge disparity is unlikely unique to Hepatitis C. Wexelman et al in a survey of residents in NYC found that the majority of residents in NYC felt the death certificate reporting system was inaccurate and often knowingly listed inaccurate CODinformation on death certificates.9 Other studies have also documented the general inaccuracies of death certificates, particularly noting cardiovascular disease being overrepresented. 6,7,8 As less autopsies are being performed, it is becoming more and more important to strive to improve the accuracy and consistency of cause of death reporting.

Increasing education initiatives seem to help, 10 and perhaps with more of these programs we may be moving toward a more reliable system, but this is not the only obstacle. There are system based issues which also need to be further addressed.9 For instance, in the Wexelman et al study, residents reported not being able to enter into the Electronic Death Registration System (EDRS) system what they believed was the true COD for a variety of reasons. These issues seem to be multi-factorial and will ultimately need to be addressed on several levels. However, perhaps it is only when you look at studies like these two well designed, interesting papers on hepatitis C, do you really appreciate the importance of getting this right.

The author has no reported conflicts of interest.

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DAUPHINE: a randomized phase II study of danoprevir/ritonavir plus peginterferon alpha-2a/ribavirin in HCV genotypes 1 or 4

Liver Int. 2014 Jan 19. doi: 10.1111/liv.12471. [Epub ahead of print]

Everson G, Cooper C, Hézode C, Shiffman ML, Yoshida E, Beltran-Jaramillo T, Andreone P, Bruno S, Ferenci P, Zeuzem S, Brunda M, Le Pogam S,Nájera I, Zhou J, Navarro MT, Voulgari A, Shulman NS, Yetzer ES.

Abstract

BACKGROUND & AIMS: Danoprevir is a hepatitis C virus (HCV) protease inhibitor with activity against genotypes (G)1/G4, which is maintained at lower doses by ritonavir-boosting. We report results of a large, randomized, active-controlled phase IIb study of ritonavir-boosted danoprevir (danoprevir/r) plus peginterferon alpha-2a/ribavirin (P/R) in treatment-naive patients with HCV G1/4 infection.

METHODS: Treatment-naive patients with HCV G1/4 infection were randomized to twice-daily danoprevir/r 200/100 mg (A, n = 92); 100/100 mg (B, n = 93); or 50/100 mg (C, n = 94) plus P/R for 24 weeks; twice-daily danoprevir/r 100/100 mg (D, n = 94) plus P/R for 12 or 24 weeks; or P/R alone (E, n = 44) for 48 weeks. Patients in the response-guided therapy arm (D) with an extended rapid virological response (eRVR2: HCV RNA <15 IU/ml during Weeks 2-10) stopped all therapy at Week 12; non-eRVR2 patients continued all treatment to Week 24. The primary efficacy endpoint was sustained the virological response (SVR24: HCV RNA <15 IU/ml after 24 weeks of untreated follow-up).

RESULTS: SVR24 rates in Arms A, B, C, D and E were 89.1%, 78.5%, 66.0%, 69.1% and 36.4%, respectively, in the overall population; 83.6%, 69.6%, 60.3%, 59.2% and 38.5% in G1a-infected patients, 96.6%, 93.1%, 73.1%, 78.4% and 28.6% in G1b-infected patients and 100%, 87.5%, 100%, 100% and 66.7% in G4-infected patients. Danoprevir/r plus P/R was generally well tolerated compared with P/R alone. There was a higher incidence of serious adverse events in danoprevir-treatment arms, but most were associated with P/R.

CONCLUSIONS: The combination of danoprevir/r plus P/R is efficacious in treatment-naïve patients with HCV genotype 1 or 4 infection.

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

KEYWORDS: danoprevir, hepatitis C virus, response-guided therapy, ritonavir-boosting, sustained virological response

PMID: 24517252 [PubMed - as supplied by publisher]

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Interleukin 28B genotype and insulin resistance in chronic hepatitis C patients

Antivir Ther. 2014 Feb 12. doi: 10.3851/IMP2743. [Epub ahead of print]

Degasperi E, Valenti L, Aghemo A, De Francesco R, Rumi M, Soffredini R, Donnici L, Cheroni C, Fargion S, Zanoni V, Orsi E, Colombo M.

Abstract

BACKGROUND: In patients with chronic hepatitis C virus (HCV) infection, an association between IL28B genotype and insulin-resistance (IR), known predictors of sustained virological response (SVR) to PegInterferon (PegIFN) and Ribavirin (Rbv) therapy, has been reported. The aim of this study was to investigate the association of IR and IL28B genotype in two cohorts of well-characterized HCV patients.

METHODS: 480 non-diabetic HCV patients were analyzed: 391 patients who received PegIFN/Rbv in the MIST study, and 89 previously reported patients followed at a Metabolic Liver Diseases center. All were tested for IL28B rs12979860 SNP by RT-PCR and had IR measured by HOMA-IR. Staging of liver disease through liver biopsy was available for all patients.

RESULTS: 164 patients (34%) were IL28B CC. Mean HOMA-IR values did not differ according to IL28B genotype, being respectively 1.14 ± 0.79 in CC vs 1.14 ± 0.78 in CT/TT (p=1.0) in the first, and 2.4 ± 1.0 vs 2.5 ± 1.0 (p=0.7) in the second cohort. HOMA-IR>2 was not associated with IL28B genotype: 16/132 (12%) CC vs 31/259 (12%) CT/TT (p=1.0) in the first cohort, and 16/32 (50%) vs 37/57 (65%) (p=0.18) in the second. This held true also when using different HOMA cut-offs (>2.5, >3.0, >3.5, >4.0). In the MIST cohort, HOMA-IR>2 did not influence treatment outcome, SVR rates being 28/47 (60%) in HOMA-IR>2 vs 214/344 (62%) in HOMA-IR<2 (p= 0.8). IL28B genotype was a strong predictor of SVR: 84% (111/132) in CC vs 51% (131/259) in CT/TT patients (p<0.0001).

CONCLUSIONS: In two cohorts of non-diabetic HCV patients where IL28B genotype predicted treatment outcome, we found no association between IL28B genotype and HOMA-IR.

PMID: 24523350 [PubMed - as supplied by publisher]

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Mental Health Patients up to Four Times More Likely to Be Infected with HIV, Penn Medicine Study Finds

Media Contact:Steve Graff | stephen.graff@uphs.upenn.edu | 215-349-5653

February 14, 2014

People receiving mental health care are up to four times more likely to be infected with HIV than the general population, according to a new study published Feb. 13 in the American Journal of Public Health from researchers at the Perelman School of Medicine at the University of Pennsylvania and other institutions who tested over 1,000 patients in care in Philadelphia and Baltimore. Of that group, several new HIV cases were detected, suggesting that not all patients are getting tested in mental health care settings, despite recommendations to do so from the CDC and the Institute of Medicine.

The study is one of the largest studies to date to estimate HIV prevalence and risk factors among persons receiving treatment in mental health settings and included researchers from the Centers for Disease Control and Prevention (CDC), as well as the University of Maryland and Columbia University Medical Center.

“These findings paint a recent picture of HIV infection rates in the community, and reinforce how important it is to identify patients and get them into appropriate infectious disease care in a timely manner while being treated for mental illness,” said lead author Michael B. Blank, PhD, associate professor in Psychiatry at the Perelman School of Medicine. “With such a high-risk group, it’s imperative to be routinely testing patients to improve care and reduce transmissions to others. Historically, though, HIV testing is often not implemented in mental health care.”

For the study, researchers provided rapid HIV testing to 1,061 individuals (621 men and 436 women) seeking treatment for symptoms, including depression, psychosis, and substance abuse, at university-based inpatient psychiatry units, intensive case-management programs, and community mental health centers from January 2009 to August 2011. About 0.3 percent of the general population is HIV infected, and CDC estimates a much higher prevalence of 1.4 percent in Philadelphia and 1.3 percent in Baltimore, since both cities are HIV epicenters.

The research team found that 4.8 percent of the mental health patients receiving care (51 individuals) were infected with HIV, which is about four times the base rate in each city and about 16 times the base rate for the United States population. Thirteen of the 51 infected patients reported that they did not know they were HIV positive, which represents an important failure in our public health system since they were already receiving ongoing mental health care. These results suggest that even in areas in the U.S. where prevalence is lower those with mental illness may be at substantially higher risk and should be routinely tested.

Results of the study also showed that persons with more severe symptoms of mental illness were at higher risk for being HIV-infected. HIV prevalence was also higher among the groups most likely to be infected in the general population, including African American, gay or bisexual men, and those infected with Hepatitis C, which is often an indicator of past injection drug use.

Previous studies have found that people with serious mental illness are at an increased risk for being infected with HIV, but many were from the 1990s and early 2000s and produced wide variations in risk, most likely because of small sample sizes, differences in sampling frames, and inadequate adjustment for confounding effects of factors associated with the disease. What’s more, the demographics of the HIV epidemic have shifted in the past decade, and the degree to which HIV prevalence among persons with mental illness has changed remains unclear.

Both CDC and the Institute of Medicine recommend routine HIV screening be conducted in all clinical settings, including mental health settings, to increase identification of those infected and strengthen access to care. However, little progress has been made toward integrating HIV testing into mental health care, said Blank.

“There are barriers to testing, be it funding, system-level barriers or access to rapid HIV testing, that need to be addressed in order to have a wider adoption,” said Blank, who also serves as the co-director of the recently-established Penn Mental Health AIDS Research Center, alongside co-author David S. Metzger, PhD, director of the HIV/AIDS Prevention Research Division at Penn Medicine, and chair of Psychiatry Dwight L. Evans, MD.

“The results of this important study highlight the need for research into integrated treatments for people with complex, co-occurring conditions like HIV and mental illness,” said Dr. Evans.

The health care system’s approach to these patients may also play a role in the health disparities that are observed in them. Mental illness and HIV often times go hand in hand; however, today’s system is not fully equipped to treat these co-morbidities in tandem. In order to achieve optimal outcomes, patients would be better served with a more integrated approach, rather than today’s fragmented one.

Click here to view the full release.

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Medicines Made in India Set Off Safety Worries

By GARDINER HARRIS FEB. 14, 2014

NEW DELHI — India, the second-largest exporter of over-the-counter and prescription drugs to the United States, is coming under increased scrutiny by American regulators for safety lapses, falsified drug test results and selling fake medicines.

Dr. Margaret A. Hamburg, the commissioner of the United States Food and Drug Administration, arrived in India this week to express her growing unease with the safety of Indian medicines because of “recent lapses in quality at a handful of pharmaceutical firms.”

India’s pharmaceutical industry supplies 40 percent of over-the-counter and generic prescription drugs consumed in the United States, so the increased scrutiny could have profound implications for American consumers.

F.D.A. investigators are blitzing Indian drug plants, financing the inspections with some of the roughly $300 million in annual fees from generic drug makers collected as part of a 2012 law requiring increased scrutiny of overseas plants. The agency inspected 160 Indian drug plants last year, three times as many as in 2009. The increased scrutiny has led to a flood of new penalties, including half of the warning letters the agency issued last year to drug makers.

Ranbaxy, one of India’s biggest drug manufacturers, pleaded guilty to felony charges and paid a $500 million fine last year. Adnan Abidi/Reuters

Dr. Hamburg was met by Indian officials and executives who, shocked by recent F.D.A. export bans of generic versions of popular medicines — like the acne drug Accutane, the pain drug Neurontin and the antibiotic Cipro — that the F.D.A. determined were adulterated, suspect that she is just protecting a domestic industry from cheaper imports.

“There are some people who take a very sinister view of the F.D.A. inspections,” Keshav Desiraju, India’s health secretary until this week, said in a recent interview.

The F.D.A.'s increased enforcement has already cost Indian companies dearly — Ranbaxy, one of India’s biggest drug manufacturers, pleaded guilty to felony charges and paid a $500 million fine last year, the largest ever levied against a generic company. And many worry that worse is in store.

“If I have to follow U.S. standards in inspecting facilities supplying to the Indian market,” G. N. Singh, India’s top drug regulator, said in a recent interview with an Indian newspaper, “we will have to shut almost all of those.”

The unease culminated Tuesday when a top executive at Ranbaxy — which has repeatedly been caught lying to the F.D.A. and found to have conditions such as flies “too numerous to count” in critical plant areas — pleaded with Dr. Hamburg at a private meeting with other drug executives to allow his products into the United States so that the company could more easily pay for fixes. She politely declined.

India’s drug industry is one of the country’s most important economic engines, exporting $15 billion in products annually, and some of its factories are world-class, virtually undistinguishable from their counterparts in the West. But others suffer from serious quality control problems. The World Health Organization estimated that one in five drugs made in India are fakes. A 2010 survey of New Delhi pharmacies found that 12 percent of sampled drugs were spurious.

In one recent example, counterfeit medicines at a pediatric hospital in Kashmir are now suspected of playing a role in hundreds of infant deaths there in recent years.

One widely used antibiotic was found to contain no active ingredient after being randomly tested in a government lab. The test was kept secret for nearly a year while 100,000 useless pills continued to be dispensed.

More tests of hospital medicines found dozens more that were substandard, including a crucial intravenous antibiotic used in sick infants.

“Some of the fake tablets were used by pregnant women in the post-surgical prevention of infections,” said Dr. M. Ishaq Geer, senior assistant professor of pharmacology at the University of Kashmir. “That’s very serious.”

Investigations of the deaths are continuing, but convictions of drug counterfeiters in India are extremely rare.

Satish Reddy, president of the Indian Pharmaceutical Alliance, said Indian drug manufacturers were better than the F.D.A. now contends. “More rigorous enforcement is needed, for sure, but this impression that India is overrun with counterfeits is unjustified,” Mr. Reddy said.

But Heather Bresch, chief executive of Mylan, which has plants in the United States and India, said regulatory scrutiny outside the United States was long overdue. “If there were no cops around, would everyone drive the speed limit?” Ms. Bresch asked. “You get careless, start taking risks. Our government has enabled this.”

Dr. Margaret A. Hamburg, the head of the Food and Drug Administration, is in India this week to express her concerns. Associated Press

For Dr. Hamburg, the trip is part of a long-running effort to create a global network of drug and food regulators to help scrutinize the growing flood of products coming into the United States, including 80 percent of the seafood consumed in the United States, 50 percent of the fresh fruit, 20 percent of the vegetables and the vast majority of drugs.

She has gone to conclaves of regulators from Europe and elsewhere to coordinate policing, but Indian officials have so far not attended such meetings.

Many of India’s drug manufacturing facilities are of top quality. Cipla, one of the industry’s giants, has 40 plants across the country that together can produce more than 21 billion tablets and capsules annually, and one of its plants in Goa appeared just as sterile, automated and high tech on a recent tour as those in the United States.

Cipla follows F.D.A. guidelines at every plant and on every manufacturing line, and the company exports more than 55 percent of its production, said Yusuf Hamied, the company chairman.

But Benjamin Mwesige, a pharmacist at the Uganda Cancer Institute in Kampala, said in an interview in July that the institute had stopped buying cancer drugs from India in 2011 because it had received shipments of drugs that turned out to be counterfeit and inactive, with Cipla labels that Mr. Mwesige believed were forged.

He became suspicious when doctors began seeing chemotherapy patients whose cancer showed none of the expected responses to the drugs — and who also had none of the usual side effects. The drugs that had been prescribed were among the mainstays of cancer treatment — methotrexate, docetaxel and vincristine. Laboratory tests confirmed that the drugs were bogus, and Mr. Mwesige estimated that in 2011 20 percent of the drugs that the institute bought were counterfeit.

Enforcement of regulations over all is very weak, analysts say, and India’s government does a poor job policing many of its industries. Last month, the United States Federal Aviation Administration downgraded India’s aviation safety ranking because the country’s air safety regulator was understaffed, and a global safety group found that many of India’s best-selling small cars were unsafe.

India’s Central Drugs Standard Control Organization, the country’s drug regulator, has a staff of 323, about 2 percent the size of the F.D.A.'s, and its authority is limited to new drugs. The making of medicines that have been on the market at least four years is overseen by state health departments, many of which are corrupt or lack the expertise to oversee a sophisticated industry. Despite the flood of counterfeit drugs, Mr. Singh, India’s top drug regulator, warned in meetings with the F.D.A. of the risk of overregulation.

This absence of oversight, however, is a central reason India’s pharmaceutical industry has been so profitable. Drug manufacturers estimate that routine F.D.A. inspections add 25 percent to overall costs. In the wake of the 2012 law that requires the F.D.A. for the first time to equalize oversight of domestic and foreign plants, India’s cost advantage could shrink significantly.

Some top manufacturers are already warning that they may leave, tough medicine for an already slowing economy.

“I’m a great nationalist, an Indian first and last,” Dr. Hamied said. “But companies like Cipla are looking to expand their businesses abroad and not in India.”

American businesses and F.D.A. officials are just as concerned about the quality of drugs coming out of China, but the F.D.A.'s efforts to increase inspections there have so far been frustrated by the Chinese government.

“China is the source of some of the largest counterfeit manufacturing operations that we find globally,” said John P. Clark, Pfizer’s chief security officer, who added that Chinese authorities were cooperative.

Using its new revenues, the F.D.A. tried to bolster its staff in China in February 2012. But the Chinese government has so far failed to provide the necessary visas despite an announced agreement in December 2013 during a visit by Vice President Joseph R. Biden Jr., said Erica Jefferson, an F.D.A. spokeswoman.

The United States has become so dependent on Chinese imports, however, that the F.D.A. may not be able to do much about the Chinese refusal. The crucial ingredients for nearly all antibiotics, steroids and many other lifesaving drugs are now made exclusively in China.

Denise Grady contributed reporting from Kampala, Uganda, and Hari Kumar from Srinagar, Kashmir.

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Digital media could work as tool to improve health

BY RONNIE COHEN
NEW YORK Sat Feb 15, 2014 2:58am IST

(Reuters Health) - After a desperate mother in South Wales, UK, posted a video of her baby having a seizure on Facebook, one of her friends provided the diagnosis that had eluded the boy's doctor.

The discovery that Evan Owens suffers from reflex anoxic seizures, a rare but treatable disease, provided a happy ending and is just one example of the public health benefits of digital media, says a new perspective in the Journal of Public Health.

Evan's story, published in the UK's Daily Mail, illustrates how people are turning to the Internet for healthcare advice and how important it is for healthcare professionals to participate in the discussion, the perspective's lead author, Amelia Burke-Garcia, told Reuters Health. (The Daily Mail story is online here:dailym.ai/1eWaEl6.)

"There's always the risk of misinformation or false information floating around on these channels," Burke-Garcia said. "The fact that people are using them demonstrates the need for healthcare professionals to be active and share information in these environments."

Public health professionals are beginning to use digital media as a research tool and to deliver messages about everything from obesity to AIDS, the study says. "But there are many other opportunities that can be explored especially because existing platforms will evolve and new ones will emerge," Burke-Garcia said.

She runs the Center for Digital Strategy and Research at Westat, a research corporation in Rockville, Maryland. She and Dr. Gabriel Scally, from the University of the West of England in Bristol, analyzed academic and online literature to identify future directions for digital media in public health research and communications.

"Digital media is set to revolutionize the way in which health information is communicated and gathered," the researchers write in their perspective. But, they say, despite numerous studies, there has been little "effective and meaningful evaluation."

Digital media is being used to track disease spread and mobilize responses. Healthcare organizations have used it to frame debates and communicate with wide segments of the population.

One future trend the authors identify is what they call "buzz monitoring," listening in on public online conversations about health issues, like smoking or obesity, in an effort to tailor future public health announcements.

Another use of digital media connects healthcare providers and consumers in online meeting places that bring people together for a variety of purposes. As an example, Burke-Garcia said, public health workers might talk to "Mommy and Me" groups about vaccinations.

Recent research found specially created Facebook groups worked to encourage gay men to reach out for information about home HIV/AIDS testing (see Reuters Health story of September 2, 2013 here: reut.rs/1b2pANv.)

Oyinlola Oyebode, a public health researcher at University College London, told Reuters Health in an email that she has seen firsthand the power of digital media in health research. Reports of vomiting on Facebook helped her team identify an additional 80 cases in one disease outbreak, she said.

In addition, she recently ran a study examining text-message reminders and breast cancer screening. Women reminded by text were more likely to attend screening appointments, she said.

Oyebode wrote a commentary published with Burke-Garcia and Scally's perspective.

Social scientist Peter John Aspinall also was not involved in the current study but wrote his own commentary. He told Reuters Health in an email that "the more routine adoption of these technologies may represent something of a slow march given the substantial pressures on already stretched public health resources."

Aspinall, from the UK's University of Kent, warned that web-based disease surveillance "can get the trends wrong because of the lack of contextual information." For example, he said, Google Flu Trends overestimated the number of Americans stricken with flu last year.

"This has led international experts in disease surveillance to conclude that flu-tracking techniques based on the mining of web data should be seen to complement rather than substitute for traditional epidemiological surveillance networks," he said.

Asked about digital media's propensity for fear mongering, Burke-Garcia said new media is no different than old when it comes to whipping up panic.

"I don't think digital media creates fear where other channels don't," she said.

"There are downsides to the speed and the ubiquity of messages in digital. You can say that the channel creates fear. The channel also creates opportunities to combat that fear."

Though Oyebode has embraced digital media, she sees potential drawbacks, particularly if public health announcements keep people in their chairs or on their couches in front of screens.

"It might be an effective way to encourage people to make healthy lifestyle changes or to help them connect and find social support during a difficult time," she said. "And there are some particular instances, for example relating to sexual health, where it might be easier for people to seek information . . . online than face to face," Oyebode added.

"However, those developing online interventions should think about how much sedentary time their intervention will encourage."

SOURCES: bit.ly/1hggf7q, bit.ly/1gzHvcn and bit.ly/1kF3VOz Journal of Public Health, January 2014.

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Are Doctors Screening Their Patients for Hepatitis B?

Provided by Physicians News Digest

Submitted by bin_admin on February 14, 2014 – 4:50 pm

By Curtis T. Miyamoto, MD

I recently met with Chari Cohen, MPH DrPh(c), Director of Public Health, and Kuan-Lung Daniel Chen, MPH, CPH, Program Manager, of the Hepatitis B Foundation about the challenges they are facing working in the area of detection and treatment of the hepatitis B virus. Like many nonprofit organizations, they are having some huge challenges. This particular foundation, however, is unique and special for our area.  You may already know that the hepatitis B virus was discovered in Philadelphia — at the Fox Chase Cancer Center — by Dr. Baruch Blumberg, who created the first vaccine.

The Hepatitis B Foundation, founded in Bucks County, is the only national, nonprofit organization focused on hepatitis B.  It concentrates on hepatitis B research, disease awareness, immunizations and treatment initiatives.

They have a large Philadelphia public health awareness and education campaign, free screening initiative and assist patients with finding care providers. There is also a Hep B United Philadelphia Coalition with over 75 coalition partners and a partnership with the CDC.

Hepatitis B is the most common serious liver infection in the world; 50 to 100 times more infectious than HIV; and affects 1.4 to 2 million Americans. Chronic infections have a one in four chance to develop hepatocellular carcinoma or liver failure and is preventable and treatable.

Asians, especially those new to the United States, are among the highest risk groups for developing hepatitis B. They are the second fastest growing population in Philadelphia behind Hispanics. Nearly one in 10 foreign-born Asian and Pacific Islander Americans have a chronic hepatitis B virus infection. But they are not the only group at risk.

The CDC has specific guidelines for testing. All persons born in regions of high and intermediate HBV endemicity, IV drug users, men with male sexual partners, immunosuppressed patients, people with elevated liver function tests, blood product donors, hemodialysis patients, pregnant women, infants born to HBsAg positive mothers, people living with infected patients, people who engage in needle sharing, individuals with sexual contact with hepatitis B surface antigen positivity and HIV-positive individuals should be tested and treated appropriately. And all US-born citizens not vaccinated as an infant should be tested.

This is an extensive list of individuals who are risk and, therefore, many more individuals should be tested than are currently being tested.  In spite of this, many patients at risk in the Philadelphia region are not being screened for hepatitis B. This means that patients who are chronically infected are not being diagnosed and patients who have been exposed are not being vaccinated, putting them at greater risk. Under the Patient Protection and Affordable Care Act, hepatitis B vaccination is covered. The obvious question is — why aren’t all patients at risk being screened?

The hepatitis B foundation has tirelessly tried to get the word out to both the physician community as well as the patients at risk to increase the amount of screening and improve access to vaccination and treatment. Although there has been some improvement, many patients are still being missed. Of course, funding is also an issue for these efforts. This is a problem for almost every nonprofit organization. In spite of the problems with the economy, there should always be funds for such life-saving and truly altruistic and life saving foundations such as the Hepatitis B foundation, American Cancer Society, etc.

In this particular case, the Hepatitis B Foundation is a local oragnization that is deserving of special attention by our healthcare professionals. The least we can do is to improve our efforts to screen all patients at risk and therefore save lives and encourage the many volunteers in this organization. The Philadelphia County Medical Society strongly supports improved hepatitis B screening, vaccination and treatment, and supports the Hepatitis B foundation.

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Curtis T. Miyamoto, MD is president of the Philadelphia County Medical Society.

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Vitamin D Levels Vary during Antiviral Treatment but Are Unable to Predict Treatment Outcome in HCV Genotype 1 Infected Patients

PLOS ONE

RESEARCH ARTICLE

Georgios Grammatikos, Christian Lange, Simone Susser, Susanne Schwendy, Nektarios Dikopoulos, Peter Buggisch, Jens Encke, Gerlinde Teuber, Tobias Goeser, Robert Thimme, Hartwig Klinker, Wulf O. Boecher, Ewert Schulte-Frohlinde,  Marissa Penna-Martinez, Klaus Badenhoop, Stefan Zeuzem, Thomas Berg, Christoph Sarrazin

Published: February 07, 2014 DOI: 10.1371/journal.pone.0087974

Abstract

Background

Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. Results on the importance of vitamin D levels are conflicting. In the present study, a comprehensive analysis of vitamin D levels before and during therapy together with single nucleotide polymorphisms involved in vitamin D metabolism in the context of other known treatment predictors has been performed.

Methods

In a well characterized prospective cohort of 398 genotype 1 infected patients treated with pegylated interferon-α and ribavirin for 24–72 weeks (INDIV-2 study) 25-OH-vitamin D levels and different single nucleotide polymorphisms were analyzed together with known biochemical parameters for a correlation with virologic treatment outcome.

Results

Fluctuations of more than 5 (10) ng/ml in 25-OH-vitamin D-levels have been observed in 66 (39) % of patients during the course of antiviral therapy and neither pretreatment nor under treatment 25-OH-vitamin D-levels were associated with treatment outcome. The DHCR7-TT-polymorphism within the 7-dehydrocholesterol-reductase showed a significant association (P = 0.031) to sustained viral response in univariate analysis. Among numerous further parameters analyzed we found that age (OR = 1.028, CI = 1.002–1.056, P = 0.035), cholesterol (OR = 0.983, CI = 0.975–0.991, P<0.001), ferritin (OR = 1.002, CI = 1.000–1.004, P = 0.033), gGT (OR = 1.467, CI = 1.073–2.006, P = 0.016) and IL28B-genotype (OR = 2.442, CI = 1.271–4.695, P = 0.007) constituted the strongest predictors of treatment response.

Conclusions

While 25-OH-vitamin D-levels levels show considerable variations during the long-lasting course of antiviral therapy they do not show any significant association to treatment outcome in genotype 1 infected patients.

Citation: Grammatikos G, Lange C, Susser S, Schwendy S, Dikopoulos N, et al. (2014) Vitamin D Levels Vary during Antiviral Treatment but Are Unable to Predict Treatment Outcome in HCV Genotype 1 Infected Patients. PLoS ONE 9(2): e87974. doi:10.1371/journal.pone.0087974

Editor: Kostas Pantopoulos, Lady Davis Institute for Medical Research/McGill University, Canada

Received: October 14, 2013; Accepted: December 31, 2013; Published: February 7, 2014

Copyright: © 2014 Grammatikos et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: KB is supported by the European Union FP7 program NAIMIT, grant agreement 241447. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Almost 3% of the world population is chronically infected with hepatitis c virus (HCV) and thus potentially confronted with life-threatening complications such as liver cirrhosis and liver cancer[1]. During permanent attempts to improve therapeutic strategies, beside the recent approval of two novel direct acting antiviral compounds [2], several predictors of treatment response have been identified [3] with recent studies including gamma-glutamyl-transferase (gGT) [4], cholesterol [5], early viral kinetics [6], interferon-γ-inducible-protein-10 (IP10) [7], ferritin [8] and the interleukin-28B (IL28B) polymorphism [9] as further important predictors of sustained viral response (SVR) as well. However, the pursuit of further surrogate factors able to optimize therapeutic regimes remains challenging.

Beside the above mentioned parameters many studies suggested vitamin D (VitD) as an additional predictor of SVR, whereas low pretreatment levels of 25-OH-Vitamin D₃ (25(OH)D₃) (<20 ng/ml) associated significantly with low responsiveness to antiviral therapy[10]–[14]. However, recent findings also indicate that the pretreatment concentration of VitD is not always capable of predicting treatment outcome in chronic HCV infection [15] as well as in HCV/HIV-coinfected patients [16], [17]. Moreover, serum concentrations of 25(OH)D₃ are getting affected by various factors such as nutrition, comorbidities and seasonal sunlight exposure [18] and since an additional hydroxylation step is needed, 25(OH)D₃-levels just offer an indirect association to the active form of VitD, 1,25(OH)₂D_3. The latter has a half-life of only 4 hours and is detectable in much lower serum concentrations than 25(OH)D₃. 1,25(OH)₂D₃ is additionally strongly affected by the serum levels of calcium, phosphate and parathyroid hormone with clinical guidelines still recommending the routine assessment of 25(OH)D₃ as the appropriate parameter in order to monitor the VitD status of patients [19]. In this context genetic polymorphisms within key enzymes regulating the pathophysiology of VitD have been shown to affect substantially VitD signaling in clinical diseases [20], [21]. In chronic HCV infection genetic polymorphisms within VitD binding proteins [12], the CYP27B1-hydroxylase [22] and the VitD-receptor [23] have been shown to correlate significantly with the outcome of antiviral therapy.

Purpose of the present study is therefore to evaluate the predictive potential of serum VitD levels both prior to as well as during antiviral therapy in a large (n = 398), well characterized cohort of genotype 1 HCV infected patients treated prospectively with pegylated interferon-α (PEG-IFNα) and ribavirin (RBV) for 24–72 weeks (INDIV-2 study) [24]. Since liver histology and genetic data were available in the majority of patients, we additionally evaluated genetic polymorphisms within major enzymes regulating 25(OH)D₃- and 1,25(OH)₂D₃-concentrations,CYP2R1, CYP27B1, DHCR7, CYP24A1 and within VitD binding proteins (DBP). Findings concerning the prediction of treatment outcome were further analyzed in association with several prognostic parameters being available prior to initiation, during and after completion of antiviral therapy in our patient cohort.

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Be an Advocate: Participate in Liver Capitol Hill Day, March 26

By Erika Miller, Cavarocchi – Ruscio – Dennis Associates, Consultants to AASLD

Reports from Washington may be making you question what is in store for your research, your patients, and your practice. The NIH budget may have received a temporary reprieve, but promoting the Institute’s growth is a priority during the continuing debates on the fiscal health of this country. Your patients are providing conflicting reports on what the Affordable Care Act means to them, and at the same time, you may be struggling with meeting the Medicare quality reporting requirements that will impact your reimbursement.

March 26, 2014 marks the Seventh Annual Liver Capitol Hill Day sponsored by the American Association for the Study of Liver Diseases. With the state of affairs in Washington, DC, if there was ever a year in which you need to participate in Liver Capitol Hill Day, 2014 is that year. You will have the opportunity to address these issues and their impact on your patients and your practice directly with the members of Congress and staff.

Any decisions Congress makes will impact the National Institutes of Health, the Centers for Disease Control and Prevention, your patients’ access to health care services, and other programs of importance to you and AASLD. Your expertise is a vital part of these discussions. If you do not educate Congress on how these programs impact the study and treatment of liver disease, no one else will.

AASLD will provide all the tools you need to succeed on Liver Capitol Hill Day. The Public Policy Committee will develop an agenda and meetings with Members of the House and Senate and their staffs will be scheduled for you. You will be supplied with information in advance on process, topics, and who you will be meeting with, so you will be fully briefed on both the issues and the process. AASLD will be creating a Liver Capitol Hill Day website that will include information about the issues you will cover and what to expect during your meetings.

The morning of Liver Capitol Hill Day you will attend a breakfast briefing at which all of the issues you will be bringing to the Hill will be discussed and information to leave behind during your Congressional visits that will summarize the issues will be provided. This information will also be available in advance on the website.

What makes your participation critical is that you know firsthand how liver disease impacts constituents in the member’s state or district. We hope that this visit is the start of an ongoing relationship with the offices, which will require follow up on your part. We will also be providing tips on how to best follow up and remain in contact with those whom you meet.

AASLD members are encouraged to invite a patient to come along if they’d like; the combination of physician and patient is a very powerful one on Capitol Hill. In addition, we have invited patient advocacy groups, including the National Viral Hepatitis Roundtable, the Hepatitis B Foundation, and the American Liver Foundation, to participate in the event.

To make this day work we need to know your plans by February 21. To participate, contact Greg Bologna at AASLD at 703-299-9766 or gbologna@aasld.org.

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