Telaprevir Effective in Hard-to-Treat Cirrhotic HCV

Neil Canavan

December 6, 2011 (San Francisco, California) — Adding the recently approved protease inhibitor telaprevir to pegylated interferon (peginterferon) plus ribavirin therapy achieved a 47% sustained viral response (SVR) in hard-to-treat patients with hepatitis C virus (HCV) infection and cirrhosis who had previously failed the standard 2-drug regimen. This finding comes from a subset analysis of the phase 3 REALIZE trial, presented here at The Liver Meeting 2011: American Association for the Study of Liver Diseases 62nd Annual Meeting.

The REALIZE investigators originally looked at telaprevir in combination with peginterferon plus ribavirin in patients with HCV genotype 1 who had had a previous null or partial response, or who had relapsed after treatment with the 2-drug regimen. REALIZE had 3 treatment groups — 2 with different schedules of triple therapy and a third with placebo plus the 2-drug regimen.

Stanislas Pol, MD, PhD, from the Université Paris Descartes, Institut National de la Santé et de la Recherche Médicale, and Assistance Publique-Hôpitaux de Paris, Cochin Hospital, France, and colleagues performed the subanalysis of the REALIZE trial to gauge the effect of triple therapy on a subset of patients with Child class A cirrhosis who had responded poorly to the 2-drug regimen. "For this analysis, we pooled the 2 telaprevir arms since there was no difference in safety and efficacy" between the 2, he explained.

The REALIZE study population consisted of 169 patients with cirrhosis (stage F4) and 493 patients without cirrhosis (stages F0 to F3). For the entire cohort, median age was 52 years, 93% was white, 88% had an HCV RNA level of at least 800,000 IU/mL, and median body mass index was 28 kg/m². Just more than half of the patients were infected with HCV genotype 1a.

There were more null responders in the group with cirrhosis (36% vs 25%), but fewer relapsers (43% vs 57%).

Results showed that in patients with no, minimal, or portal fibrosis (F0 to F2), SVR was achieved in 75% of patients receiving telaprevir and in 22% of those receiving placebo.

"If we consider SVR according to fibrosis stage and prior response, we see no clear impact of fibrosis stage on the overall SVR rate of around 85%. For prior partial responders, there was a significant impact by fibrosis stage, with a decrease in SVR rate from 77% to 56% in patients with mild fibrosis, declining to 34% in those patients with cirrhosis," Dr. Pol told Medscape Medical News.

In previous null responders, the SVR rate after triple therapy was 41% in the patients without cirrhosis, 42% in those with mild fibrosis, and 14% in those with cirrhosis.

More than half (53%) of these previously treated patients with cirrhosis did not achieve an SVR with the addition of telaprevir, compared with 27% of patients without cirrhosis.

Regarding safety, the prevalence of rash was higher in patients with than without cirrhosis (67% vs 53%), but other rates for common adverse events were similar. For hematologic events, anemia was more frequent in patients with cirrhosis (42% vs 34%). In addition, neutropenia was higher (25% vs 17%) and, "as might be expected, platelet counts were lower in the cirrhotic subset," Dr. Pol noted.

Can Early Responders Stop Treatment?

The relatively high response rate in patients with cirrhosis and HCV who had failed previous treatment with peginterferon and ribavirin raises the question of whether treatment can be stopped early with triple therapy.

Michael Bernstein, MD, director of the hepatitis clinic at the Coney Island Hospital, Brooklyn, New York, asked: "If they had an extended RVR [rapid virologic response], if they were negative for virus at week 4 and again at week 12, for which there was evidence in REALIZE, then perhaps they could get just 24 weeks of treatment. That's called response-guided therapy."

Dr. Bernstein's reasoning is that in patients without cirrhosis, an extended RVR is indicative of a greater than 90% SVR rate.

"The current recommendation is to treat these patients for 48 weeks, whether they have an extended RVR or not. In this study, this is a special subgroup of patients — even a sub-subgroup — because it is not just cirrhotics, but cirrhotics who have not responded previously to treatment.... It may be feasible to stop [treatment] at 24 weeks if they have this very favorable RVR," he told Medscape Medical News. As phase 4 data accrue, evidence might support doing so.

Dr. Pol reports being a consultant for Bristol-Myers Squibb, Boehringer Ingelheim, Tibotec, Novartis, and Gilead; and receiving grants for research from Bristol-Meyers Squibb, Gilead, Roche, and Schering-Plough/Merck. Dr. Bernstein has disclosed no relevant financial relationships.

The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 31. Presented November 6, 2011.

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Telaprevir Not Cost Effective in All Patients With HCV

Neil Canavan

December 6, 2011 (San Francisco, California) — The recently approved and highly effective hepatitis C virus (HCV) protease inhibitor telaprevir was shown not to be cost effective for the treatment of patients with HCV genotype 1 and the (CC) interleukin (IL)-28B polymorphism, a genetic variant that predicts a favorable response to treatment with the standard dual regimen of pegylated interferon (peginterferon) and ribavirin.

This cost analysis was reported here at The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting.

"IL-28B is the strongest pretreatment predictor of sustained virologic response in genotype 1 patients," said study presenter Ziad Gellad, MD, MPH, from the Department of Medicine–Gastroenterology, Duke University Medical Center, Durham, North Carolina. "In genotype 1 patients with the favorable (CC) IL-28B polymorphism, dual therapy with peginterferon and ribavirin is effective in the majority of patients."

That said, telaprevir in combination with peginterferon plus ribavirin has demonstrated significantly increased sustained viral response rates, compared with peginterferon plus ribavirin alone in phase 3 studies of treatment-naive and treatment-experienced genotype 1 patients with HCV.

Dr. Gellad asked: Is the addition of telaprevir cost effective in the subpopulation of patients with IL-28B (CC)? The answer, he said, is no.

"One of the potential benefits of tailoring therapy is decreasing cost," Dr. Gellad said. The current wholesale cost of the 2-drug regimen is $18,336 at 24 weeks and $36,672 at 48 weeks; for the 3-drug regimen, the cost is $67,536 at 12 weeks and $85,872 at 36 weeks.

Because the addition of telaprevir more than doubles the cost of treatment, Dr. Gellad designed a cost-effectiveness model to determine whether the added expense is really worth it for a patient with the favorable genotype 1 (CC) IL-28B profile.

The model is based on a number of assumptions: that societal perspective is limited, that no patients would have a coinfection with other viruses that accelerate liver-related death or prevent treatment, "and importantly, that nonresponders or relapsers after dual therapy are retreated with a 48-week course of telaprevir."

The researchers developed a decision model that evaluated 3 treatment strategies:

• peginterferon plus ribavirin for 48 weeks, with a 12-week stopping rule for nonresponse; patients who did not respond or who relapsed would be treated with telaprevir
• a response-guided treatment approach with peginterferon plus ribavirin, in which those who achieved a rapid viral response (undetectable at week 4) would receive 24 weeks of dual therapy alone, and those with still-detectable viral loads at week 4 were treated for 48 weeks; nonresponsive or relapsed patients received telaprevir.
• 12 weeks of telaprevir in combination with 24 or 48 weeks of peginterferon plus ribavirin based on the extended rapid virologic response.

Treatment outcomes generated by the model were based on outcomes data derived from the IDEAL, REALIZE, and ADVANCE clinical trials.

A theoretical cohort of patients with 10,000 iterations was performed. The end point assumed 1 of 2 health states: sustained virologic response (cure) or fibrosis progression. Dr. Gellad's team assessed the cost of each. "As patients progressed through the model, they accumulated costs, which were expressed in [quality-adjusted life-years]," Dr. Gellad explained.

"The key point is that the efficacy of all 3 strategies is similar, but when you consider point estimates, telaprevir is dominated by the interferon/ribavirin strategies, and this preference is driven by the cost of therapy," Dr. Gellad told Medscape Medical News.

Costs generated by the model were $46,785 for peginterferon plus ribavirin given as response-guided therapy, $54,931 for peginterferon plus ribavirin (not response-guided), and $68,788 for telaprevir plus peginterferon plus ribavirin.

"We then investigated the impact of the cost of telaprevir on the probability of cost effectiveness, and assumed a weekly cost of $3321 [the current cost of the drug].... If the cost dropped below $1433, a triplet with telaprevir became the preferred strategy," he reported.

Dr. Gellad concluded that in treatment-naïve patients with HCV genotype 1 and the (CC) IL-28B polymorphism, initial therapy with a telaprevir-based regimen is unlikely to be cost effective under current cost and efficacy conditions.

Comparison Shopping

"What this group from Duke did is very important because, with resources dwindling, we need to figure out whether a particular treatment is more cost effective than another," said AASLD president T. Jake Liang, MD, tenured senior investigator and chief of the Liver Diseases Branch at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. "This is somewhat related to so-called personalized medicine because it uses a genetic marker to identify patients who will respond well to a certain treatment."

Major genetic studies conducted over the past several years have indicated that (CC) IL-28B is a genetic marker highly associated with treatment response to interferon-based therapy. "This is a great marker — probably the best genetic marker we have so far — to gauge how a person will respond to treatment," Dr. Liang said.

The analysis by Dr. Gellad's team "suggests that this could be a way to save some money for patients with the favorable IL-28B genotype," he noted. Certainly, there is excitement about the recent availability of direct-acting antivirals, such as telaprevir, which greatly enhance treatment response, "but then again, maybe not one size fits all. In the spirit of personalized medicine, this may be one way we can reduce costs and, at the same time, retain the same success rate treating patients with HCV."

Dr. Gellad reports consulting for Merck & Co and receiving grants or research support from Merck & Co and PENTAX Medical. Dr. Liang has disclosed no relevant financial relationships.

The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 118. Presented November 7, 2011.

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OraSure Technologies Receives CLIA Waiver for OraQuick(R) HCV Rapid Test

Nov. 29, 2011, 6:00 a.m. EST

BETHLEHEM, Pa., Nov 29, 2011 (GlobeNewswire via COMTEX) -- OraSure Technologies, Inc. announced today that the U.S. Food and Drug Administration ("FDA") has granted a waiver under the Clinical Laboratory Improvement Amendments of 1988 ("CLIA") for its OraQuick(R) HCV Rapid Antibody Test for use with fingerstick whole blood and venous whole blood specimens.

The OraQuick(R) HCV Rapid Antibody Test is the first and only FDA-approved rapid test for the detection of antibodies to the hepatitis C virus ("HCV"). The test, which utilizes the OraQuick(R) technology platform, provides results in 20 minutes. With this waiver, the OraQuick(R) HCV test now can be used by more than 180,000 sites in the United States to test persons who are at risk for hepatitis C or have signs or symptoms of hepatitis. These sites now extend to facilities that can perform CLIA-waived tests, such as outreach clinics, community-based organizations and physician offices.

"Today, more than 4 million Americans are infected with hepatitis C and the vast majority do not know it," said Dr. Willis C. Maddrey, President of the Chronic Liver Disease Foundation. "Hepatitis C is a leading cause of chronic liver disease, cirrhosis and liver cancer. However, new therapies are now available that can effectively treat a high percentage of people with HCV infection, making expanded and accessible testing for HCV a critical step in fighting this epidemic."

"A CLIA waiver for our OraQuick(R) HCV test represents a critical milestone in our quest to make the test available to the widest possible range of at risk individuals in the U.S.," said Douglas A. Michels, President and Chief Executive Officer of OraSure Technologies. "The CLIA waiver will enable healthcare providers, those on the front lines of fighting this devastating disease, to use this simple and accurate test in physician offices and outreach settings so more individuals infected with hepatitis C can be diagnosed and treated."

As previously announced, OraSure has entered into agreements with Merck & Co. to collaborate on the development and promotion of the OraQuick(R) HCV test. Under these agreements, Merck will provide detailing and other promotional support for the test in the physicians' office markets in the United States and internationally. The approval of the CLIA waiver will now enable physicians to utilize the test in their office settings.

About OraSure Technologies

OraSure Technologies is a leader in the development, manufacture and distribution of oral fluid diagnostic and collection devices and other technologies designed to detect or diagnose critical medical conditions. Its innovative products include rapid tests for the detection of antibodies to HIV and HCV at the point of care and testing solutions for detecting various drugs of abuse. In addition, through its wholly-owned subsidiary, DNA Genotek Inc., the Company also is a leading provider of oral fluid sample collection, stabilization and preparation products for molecular diagnostic applications. OraSure's portfolio of products is sold globally to various clinical laboratories, hospitals, clinics, community-based organizations and other public health organizations, research and academic institutions, distributors, government agencies, physicians' offices, and commercial and industrial entities. The Company's products enable healthcare providers to deliver critical information to patients, empowering them to make decisions to improve and protect their health. For more information on OraSure Technologies, please visit www.orasure.com.

The OraSure Technologies, Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=6440 

This news release was distributed by GlobeNewswire, www.globenewswire.com 

SOURCE: OraSure Technologies, Inc.

CONTACT:

Investor Contact:

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610-882-1820
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Boceprevir Often Successful as Rescue Treatment in HCV

Neil Canavan

November 30, 2011 (San Francisco, California) — Patients with hepatitis C virus (HCV) infection who previously failed combination treatment with pegylated interferon alfa-2a (peginterferon) and ribavirin achieved up to a 50% sustained viral response (SVR) with the recently approved protease inhibitor boceprevir. This finding, from the preliminary results of the ongoing PROVIDE study, was reported here at The Liver Meeting 2011: American Association for the Study of Liver Diseases 62nd Annual Meeting.

"This study was designed to give boceprevir treatment to patients who were null responders in the control arms of our previous pivotal trials," said Michelle Treitel, PhD, from Merck Research Laboratories in Kenilworth, New Jersey.

Patients were rolled over from the SPRINT-1, SPRINT-2, RESPOND-2, and PEG 2a/BOC studies into PROVIDE. "These are patients who had either met the futility rule or who had relapsed after the end of treatment with peginterferon and ribavirin. After failure, they were immediately started on 44 weeks of boceprevir/peginterferon/ribavirin triple therapy." The aim of the study was to assess SVR after boceprevir, peginterferon, and ribavirin treatment in nonresponders.

Overall, 168 patients from the 4 studies were enrolled in PROVIDE. Patients were eligible if they received 12 or more weeks of peginterferon plus ribavirin treatment and failed to achieve a SVR (HCV RNA levels below the lower limit of detection of +9.3 IU/mL at treatment week 12 in treatment-experienced patients or at treatment week 24 in treatment-naïve patients), had a virologic breakthrough, or relapsed after the end of treatment (undetectable HCV RNA at the end of treatment but no SVR).

The subanalysis presented by Dr. Treitel involved 48 patients from the SPRINT-2 and RESPOND trials.

Patients were treated with boceprevir 800 mg orally twice daily, peginterferon 1.5 µg/kg subcutaneously once daily, and ribavirin 600 to 1400 mg/day (based on weight) orally in 2 divided doses. All patients received 4 weeks of peginterferon plus ribavirin induction therapy prior to receiving boceprevir. Patients received the boceprevir, peginterferon, ribavirin combination for up to 44 weeks, and were followed for an additional 24 weeks to determine SVR.

The PROVIDE cohort was 64.6% male, 68.8% white, had mean age of 51.0 years, and had a mean body mass index of 26.8 kg/m². Among the patients, 87.5% had a baseline viral load greater than 800,000 IU/mL, 64.6% were infected with HCV genotype 1a, and 4.2% had detectable cirrhosis.

The primary end point of PROVIDE was undetectable HCV RNA 24 weeks after therapy.

In this nonresponder subpopulation, 38% of patients treated with the triple combination achieved a SVR. The achievement of SVR differed by race (27% of black subjects and 42% of nonblack subjects), age (50% of those younger than 50 years and 29% of those older than 50 years), alanine transaminase levels (50% of those with normal levels and 34% of those with elevated levels), and genotype (41% of those infected with genotype 1a and 33% of those with genotype 1b).

"The difference by genotype is the reverse of what you would expect," said Dr. Treitel. "That most likely has to do with the small sample size."

The magnitude of decline in HCV RNA after 4 weeks of peginterferon plus ribavirin induction therapy was positively related to the rate of SVR. Dr. Treitel reported a 50% SVR for patients who experienced a reduction of at least 1 log in HCV RNA, compared with 34% SVR for patients who experienced a reduction of less than 1 log.

"This null group has not been specifically studied for boceprevir before, and these patients are really poor interferon responders," said Dr. Treitel. "In these traditionally very hard-to-treat subjects, we're still showing that you can get a 38% SVR."

Taking It to the Street

"I was very interested to see the rate of response to triple therapy in patients who have previously failed treatment or who were nonresponders," said Abu Hamour, MBBS, MSc, FRCP, from the University Hospital of Northern British Columbia in Prince George, Canada.

The lack of patients with cirrhosis in the study was a sticking point for Dr. Hamour. Although this does not reflect the population of patients he sees in his practice, the conclusions give him something valuable to take home.

"I have this information that I can give to my patients — a prognosis," he said. After treatment with this triple therapy, I can tell patients "who failed treatment with peginterferon/ribavirin or who were nonresponders...[that] if you have a more than a 1 log drop, you have a 50% chance of response; if you have less than a 1 log drop, then your response is much lower, around 35%. Patients can then make choices based on that information."

Dr. Treitel is an employee of Merck Research Laboratory. Dr. Hamour has disclosed no relevant financial relationships.

The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 931. Presented November 7, 2011.

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Novel Hep C Treatment Excludes Peginterferon Alfa

By: DENISE NAPOLI, Internal Medicine News Digital Network

Therapy with a novel nonnucleoside polymerase inhibitor, in combination with a protease inhibitor and ribavirin, achieved a 100% virologic response rate at 29 days among patients with hepatitis C genotype 1, Dr. Stefan Zeuzem and colleagues reported in the December issue of Gastroenterology.

Moreover, this novel alternative to the standard peginterferon alfa regimen was safe, with no serious adverse events, and was highly tolerable, the investigators said.

"This indicates that HCV [hepatitis C virus] can be eradicated in chronically infected patients with a PegIFN-free DAA [direct-acting antiviral agent] combination regimen," the authors wrote.

Dr. Zeuzem, of the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany, and colleagues studied 34 adult patients (mean age 51 years) who were naive to interferon, PegIFN, ribavirin, or any DAA for acute or chronic hepatitis C infection.

All patients had plasma HCV RNA levels of at least 100,000 IU/mL at screening and did not have cirrhosis.

Patients with hepatitis B virus, human immunodeficiency virus, previous or ongoing rash or photosensitivity, decompensated liver disease, or hyperbilirubinemia greater than 1.5 times the upper limit of normal were excluded.

Participants were randomized in a 1:1 fashion to receive a thrice-daily 400-mg or 600-mg dose of BI 207127, "an orally bioavailable, reversible, thumb pocket 1 nonnucleoside inhibitor (NNI) of the HCV NS5B polymerase with potent and specific antiviral activity in vitro," according to the authors (Gastroenterology 2011 [doi:10.1053/j.gastro.2011.08.051]).

All participants also received BI 201335, "a second-generation HCV NS3/4A protease inhibitor with highly potent in vitro activity against GT-1a/1b subtypes," wrote the authors, at a dose of 120 mg per day, as well as daily weight-dosed ribavirin, all taken with food, for 4 weeks.

"Drug-resistance studies in cell culture demonstrate that BI 201335 and BI 207127 have different resistance profiles, and previous observations using NS3/4A protease inhibitors and NS5B thumb pocket 1 NNI compounds demonstrate that 2-drug combinations profoundly reduce the selection of drug-resistant variants," explained Dr. Zeuzem.

The researchers found that in the cohort taking the larger, 600-mg doses of the polymerase inhibitor BI 207127, virologic response rates (defined as plasma HCV RNA levels of less than 25 IU/mL) were 18%, 82%, 100%, and 100% at days 8, 15, 22, and 29, respectively.

Slightly less impressive results were seen in the 400-mg group, with rates of 27%, 47%, 67%, and 73% at days 8, 15, 22, and 29 respectively.

Also in the 400-mg cohort, "higher response rates were observed in genotype 1b infected patients, compared with genotype 1a infected patients," wrote the authors, whereas results in the 600 mg group were not contingent on sub-genotypes.

"Most patients in the 600 mg TID [three times a day] dose group even had undetectable HCV RNA at days 22 and 29 (53% and 71%, respectively), while these rates did not exceed 20% in the 400 mg TID dose group," added the investigators.

Looking at safety and tolerability, Dr. Zeuzem and colleagues noted that most patients in both dosing cohorts complained of mild diarrhea, nausea, and vomiting.

Additionally, at the 600-mg dose, 42% developed mild rashes or photosensitivities, they said, and four patients developed "transient and very mild paresthesias of very different localizations."

"However, there were no severe AEs [adverse events], serious AEs or AE-related premature treatment discontinuations within the 4-week study period."

The "crucial next step," according to the investigators, will be achievement of longer-term SVR on the novel peginterferon-free regimen.

"Moreover, eliminating not only PegIFN but also RBV [ribavirin] from future HCV treatment would undoubtedly improve tolerability and would potentially allow for the treatment of patients with RBV contraindications," they added.

Indeed, at the time of this study’s publication, a phase 2b study was ongoing.

Dr. Zeuzem, along with several of his coinvestigators, disclosed financial and consulting relationships with multiple pharmaceutical companies, including the makers of the novel drugs used in this study, Boehringer Ingelheim. Boehringer Ingelheim also funded editorial assistance provided for this article.

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WHO: HIV Progress Includes 15% Drop in New Infections

Emma Hitt, PhD

November 30, 2011 — Increased access to HIV services has resulted in a 15% reduction of new infections during the past decade and a 22% decline in AIDS-related deaths in the last 5 years, according to a report released today by the World Health Organization (WHO).

The new report, "Report on the Global HIV/AIDS Response," emphasizes the benefits of sustaining investment in HIV/AIDS for the longer term, according to a press release from WHO. The report represents the joint effort of WHO, United Nations Children's Fund (UNICEF), and the Joint United Nations Programme on HIV/AIDS (UNAIDS) in collaboration with national and international partners.

"It has taken the world 10 years to achieve this level of momentum," noted Gottfried Hirnschall, MD, MPH, director of WHO's HIV Department, in the release. "There is now a very real possibility of getting ahead of the epidemic. But this can only be achieved by both sustaining and accelerating this momentum over the next decade and beyond."

According to new data presented in the report, improved access to HIV testing services have enabled 61% of pregnant women in eastern and southern Africa to receive testing and counseling for HIV, representing an increase from only 14% in 2005.

In addition, in 2010, 48% of pregnant women in need received antiretroviral therapy (ART), thereby decreasing the risk for mother-to-child transmission of HIV. The report also found that ART is now available for 6.65 million people in low- and middle-income countries, or 47% of the 14.2 million people eligible to receive it.

Investment in HIV services could lead to total gains of up to $34 billion by 2020 in increased economic activity and productivity, the report indicates, and this would more than offset the cost of providing ART to people who need it.

Although great strides have been made, the report also indicates areas for improvement. "More than half of the people who need antiretroviral therapy in low- and middle-income countries are still unable to access it," the WHO news release states. "Many of them do not even know that they have HIV."

In addition, some programs around the world are not effectively tailored for those in need. "In many cases, groups including adolescent girls, people who inject drugs, men who have sex with men, transgender people, sex workers, prisoners and migrants remain unable to access HIV prevention and treatment services," WHO notes.

Women are now disproportionately affected with HIV: Nearly two thirds of those aged 15 to 24 years living with HIV today are women, and in sub-Saharan Africa, women make up 71% of all young people living with HIV, "essentially because prevention strategies are not reaching them," according to the news release. In addition, only about 25% of children in low- and middle-income countries received ART in 2010 compared with about half of adults.

The report also discusses specific data pertaining to various regions around the world, including sub-Saharan Africa, Asia, Eastern Europe and Central Asia, the Middle East and North Africa, and Latin America and the Caribbean.

According to WHO, several initiatives are underway to sustain the global HIV response through the next 10 years. For example, a WHO, UNICEF, and UNAIDS "elimination initiative" aims to eliminate new HIV infections among children by 2015 and keep their mothers alive. In addition, WHO is developing new guidance on the strategic use of antiretroviral drugs for both prevention and treatment.

The full report is available on the WHO Web site.

Source

Low-Dose IL-2 Induced HCV Vasculitis Remission

By: MARY ANN MOON, Internal Medicine News Digital Network

Low-dose interleukin-2 induced remission of the main symptoms of hepatitis C virus–related vasculitis in 8 of 10 patients participating in a phase I/phase II clinical trial, according to results reported in the Dec. 1 issue of the New England Journal of Medicine.

The remission of purpura, arthralgia, and nephropathy was accompanied by a 420% increase in the potently suppressive regulatory T cells known as Tregs, which are abnormally decreased in patients who have mixed cryoglobulinemic vasculitis induced by chronic infection with hepatitis C virus, said Dr. David Saadoun of the Université Pierre et Marie Curie, Paris, and his associates (N. Engl. J. Med. 2011;365:2067-77).

The interleukin-2 immunotherapy did not activate other T cells and did not cause any adverse events related to immune activation. The treatment appeared to reduce HCV viral load modestly.

"Further studies are needed to determine whether this intervention could be further modified and whether it would also be effective in the treatment of other inflammatory and autoimmune diseases, such as atherosclerosis or type 1 diabetes," the authors noted.

Dr. Saadoun and his colleagues recently found "a quantitative defect in Tregs" among patients with HCV-induced mixed cryoglobulinemia vasculitis, which was reversed when the vasculitis in those patients was cured.

"We therefore reasoned that induction of Tregs could have beneficial effects for patients with HCV-induced vasculitis that is resistant to HCV therapy," the researchers noted. That prompted them to conduct an open-label phase I/ IIa trial to assess the safety as well as the immunologic and clinical effects of repeated administration of low-dose interleukin-2 in HCV-infected patients who had associated autoimmunity, they added.

The prospective, single-center study included five men and five women with a median age of 58.5 years and a mean duration of HCV infection of 30 years. Eight patients had purpura, eight had neuropathy, six had asthenia, three had arthralgia, and one had kidney involvement. The vasculitis had been refractory to conventional antiviral therapy, rituximab therapy, or both.

The patients underwent an initial 5-day course of subcutaneous interleukin-2 injections (1.5 million IU per day, or half the target dose) with safety monitoring. "This dose led to a significant increase of Treg percentages in all patients; adverse events were minor and transient," the researchers said.

After a washout period, all the subjects received three more 5-day courses at the target dose of 3 million IU per day, separated by washout periods. During each treatment period, the percentage of Tregs increased. "We do not know whether this increase was consequent to the increased dosage, to the repetition of treatment, or both," the investigators noted.

The researchers selected the primary end point – an absolute increase of 4 percentage points in the proportion of circulating Tregs at the end of treatment – because it was the mean increase seen in earlier patients whose vasculitis was cured by standard HCV treatment. All 10 patients reached that end point.

"Notably, Treg proportions had increased by approximately a factor of 2 after the first 5-day course of 1.5 million IU of interleukin-2 per day, continued to increase during the washout period between courses, and were further boosted after the administration of subsequent courses," Dr. Saadoun and his associates said.

The median peak value corresponded to a 420% increase in Tregs. The proportion of Tregs remained significantly elevated for 130-150 days of follow-up, at twice the baseline value. That level is within the normal range for healthy adults.

Tests of the functionality of the Tregs induced by the interleukin-2 therapy demonstrated that they were "highly suppressive," the study authors said.

Serum levels of cryoglobulin decreased during treatment, and the HCV viral load decreased modestly but significantly, even though patients were not receiving antiviral therapy.

Concomitantly with those biologic improvements, the HCV-induced mixed cryoglobulinemic vasculitis also improved in 8 of 10 patients. Purpura resolved in all eight patients who had had it at baseline, and arthralgia resolved in all three patients who had had it at baseline. Neuropathy remitted in all but two patients. Measures of kidney function normalized in the one patient who had had nephropathy.

Clinical improvement was noted after the first or second course of treatment, simultaneously with the peak increases in Tregs.

Only the two patients who had presented with neuropathy as their sole vasculitis symptom failed to show clinical improvement, the investigators said.

The French Agency for Research on AIDS and Viral Hepatitis funded the study, with additional support from the authors’ institutions. Dr. Saadoun had no disclosures but his associates reported ties to numerous industry sources.

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Longer Follow-Up Is Critical

"The concern that suppressing T-cell immunity by up-regulating Treg cells would put the patient with HCV at risk for a worsened viral load appears groundless in this small series," said Jeffrey A. Bluestone, Ph.D.

"However, the possible long-term effects of interleukin-2 treatment are uncertain, since these patients were followed for only 3-4 months. A sustained increase in Treg cells may be problematic in patients with ongoing acute or chronic infections," he noted.

Jeffrey A. Bluestone, Ph.D., is at the University of California, San Francisco. He reported no financial conflicts of interest. These remarks were taken from his editorial accompanying the report (N. Engl. J. Med. 2011;365:2129-31).

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Studies of patients with cirrhosis uncover limitations in liver cancer screening

Public release date: 1-Dec-2011

Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell

Two studies available in the December issue of Hepatology, a journal of the American Association for the Study of Liver Diseases, have uncovered limitations in screening for primary liver cancer, also known as hepatocellular carcinoma (HCC). The first study found that, if given the choice during a clinical trial, most patients with cirrhosis prefer surveillance over the possibility of non-screening, therefore making a randomized study of HCC screening not feasible. A second study determined that ultrasonographic screening at three monthly versus six monthly intervals did not improve the detection of small liver cancers.

Medical evidence reports HCC to be the sixth most common cancer and the third most common cause of cancer death worldwide, with 90% of all cases in western countries attributed to chronic liver diseases, typically at the cirrhosis stage. The National Cancer Institute estimates that more than 26,000 cases and close to 20,000 deaths from liver and bile duct cancer occurred in the U.S. in 2011. Clinical guidelines recommend routine screening for HCC, but the efficacy and optimal intervals for testing are strongly debated by experts.

In the first study, researchers led by Professor Jacob George from the University of Sydney and Westmead Hospital in Australia, examined the feasibility of undertaking a randomized controlled trial of HCC surveillance in patients with cirrhosis. The screening program included ultrasonography every six months and alpha-fetoprotein testing every three months. Of the 205 participants with cirrhosis who received information outlining the risks and benefits of surveillance for liver cancer, 99.5% declined randomization, with 88% electing for a non-randomized screening program.

"While a randomized controlled trial is ideal to assess the success of a cancer surveillance program, we found that patients with cirrhosis declined randomization due to possible allocation to a non-screening group," explains Professor George. "Since HCC screening in cirrhotic patients is routine practice for a majority of clinicians, it is impossible to assign patients to a genuine control group. However, further prospective studies that compare individual screening strategies are warranted." In a survey of 40 gastroenterologists of the Sydney Liver Group, the authors found that 74% routinely screen cirrhotic patients despite believing that screening did not increase patient survival (37%) or that the surveillance was cost-effective (66%).

One such liver cancer screening strategy was investigated by a team of French and Belgian researchers led by Professor Jean-Claude Trinchet with the Hôpital Jean Verdier in Bondy, France. The team conducted a multicentre trial with 1278 cirrhotic patients who received ultrasonographic screening at either three-month or six-month intervals. Their results indicated that cirrhosis resulted from excessive alcohol use in 39% of participants, 44% from hepatitis C virus (HCV), and 13% from hepatitis B virus (HBV). During the study period from July 2000 to July 2009, researchers detected at least one focal lesion in 28% of patients, but confirmed small HCC (less than 30 mm) in only 10% of participants.

Dr. Trinchet said, "Our study found that ultrasonographic surveillance performed every three months detects more small focal lesions than screening at six-month intervals. However, more frequent screening did not improve the detection of liver cancer at an earlier stage." The authors note that detection of small tumors were more likely missed in patients with HCV or who abuse alcohol and suggest the limitations of current diagnostic procedures may explain their negative findings. Again, further investigations of screening methods and diagnostic procedures are needed to improve the outcomes in those at risk for developing liver cancer.

###

Full Citations: "Feasibility of Conducting a Randomized Control Trial for Liver Cancer Screening: Is a Randomized Controlled Trial for Liver Cancer Screening Feasible or Still Needed?" H. Poustchi, GC Farrell, SI Strasser, AU Lee, GW McCaughan and J George.Hepatology; August 24, 2011 (DOI: 10.1002/hep.24581); Print Issue Date: December 2011. http://onlinelibrary.wiley.com/doi/10.1002/hep.24581/abstract.

"Ultrasonographic Surveillance of Hepatocellular Carcinoma in Cirrhosis: A Randomized Trial Comparing 3- and 6-month Periodicities." Jean-Claude Trinchet, Cendrine Chaffaut, Valérie Bourcier, Françoise Degos, Jean Henrion, Hélène Fontaine, Dominique Roulot, Ariane Mallat, Sophie Hillaire, Paul Cales, Isabelle Ollivier, Jean-Pierre Vinel, Philippe Mathurin, Jean-Pierre Bronowicki, Valérie Vilgrain, Gisèle N'kontchou, Michel Beaugrand and Sylvie Chevret. Hepatology; September 6, 2011 (DOI: 10.1002/hep.24545); Print Issue Date: December 2011. http://onlinelibrary.wiley.com/doi/10.1002/hep.24545/abstract.

Author Contact: To arrange an interview with Professor George, please contact Ellie Martel with the University of Sydney at ellie.martel@sydney.edu.au.

These studies are published in Hepatology. Media wishing to receive a PDF of the articles may contact healthnews@wiley.com.

About the Journal

Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Hepatology's current impact factor is 10.885.Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350 .

About Wiley-Blackwell

Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit www.wileyblackwell.com or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.

Source

Green tea flavonoid may prevent reinfection with hepatitis C virus following liver transplantation

Public release date: 1-Dec-2011

Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell

German researchers have determined that epigallocatechin-3-gallate (EGCG)—a flavonoid found in green tea—inhibits the hepatitis C virus (HCV) from entering liver cells. Study findings available in the December issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases, suggest that EGCG may offer an antiviral strategy to prevent HCV reinfection following liver transplantation.

HCV infection can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) or primary liver cancer. HCV is one of the most common causes of chronic liver disease and a primary indication for liver transplantation, affecting up to 170 million individuals worldwide according to estimates from the World Health Organization (WHO). Prior studies report that nearly 2% of the world population is infected with chronic HCV and up to 20% of the population in some countries.

While standard treatment with interferon with ribavirin and newer protease inhibitors may clear infection in some individuals, a substantial number of patients still may not respond to these therapies. For individuals receiving liver transplants due to complications from HCV, reinfection of the healthy donor liver remains a significant concern. Antiviral strategies that target HCV in its early stages are urgently needed to prevent graft reinfection and improve long-term outcomes for patients.

To address this critical issue, Dr. Sandra Ciesek and Dr. Eike Steinmann from the Hannover Medical School in Germany investigated the effect of the EGCG molecule, which is a major component of green tea, in preventing HCV from attaching to liver cells. "Green tea catechins such as EGCG and its derivatives epigallocatechin (EGC), epicatechingallate (ECG), and epicatechin (EC) have been shown to exhibit antiviral and anti-oncogenic properties," explains Dr. Ciesek. "Our study further explores the potential effect these flavonoids have in preventing HCV reinfection following liver transplantation."

Results showed that unlike its derivatives, EGCG inhibits entry of HCV into liver cells. The authors suggest that EGCG may impede HCV cell entry by acting on the host cell as the green tea catechin was not found to alter the density of virus particles. Pretreatment of cells with EGCG before HCV inoculation did not reduce the infection; however application during inoculation inhibited the rapid spread of the HCV. Lastly, researchers showed that EGCG inhibits viral attachment—the initial step in the HCV infection process. "The green tea antioxidant EGCG inhibits HCV cell entry by blocking viral attachment and may offer a new approach to prevent HCV infection, particularly reinfection following liver transplantation." concludes Dr. Ciesek.

###

Full Citation: The Green Tea Polyphenol Epigallocatechin-3-Gallate (EGCG) Inhibits Hepatitis C Virus (HCV) Entry." Sandra Ciesek, Thomas von Hahn, Che C. Colpitts, Luis M Schang,Martina Friesland, Jörg Steinmann, Michael P. Manns, Michael Ott, Heiner Wedemeyer, Philip Meuleman, Thomas Pietschmann and Eike Steinmann. Hepatology; Published Online: November 30, 2011 (DOI: 10.1002/hep.24610); Print Issue Date: December 2011. http://onlinelibrary.wiley.com/doi/10.1002/hep.24610/abstract.

Author Contact: To arrange an interview with Dr. Sandra Ciesek or Dr. Eike Steinmann, please contact Jo Schilling at jo.schilling@twincore.de.

This study is published in Hepatology. Media wishing to receive a PDF of the article may contact healthnews@wiley.com.

About the Journal

Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Hepatology's current impact factor is 10.885.Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350 .

About Wiley-Blackwell

Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit www.wileyblackwell.com or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.

Source

Medivir - TMC435 Will Be Evaluated in a Phase II Combination Study With daclatasvir (BMS 790052) for HCV Genotype-1 Patients

Dec. 2, 2011, 7:30 a.m. EST

HUDDINGE, Sweden, December 2, 2011 /PRNewswire via COMTEX/ -- Medivir AB (omx:MVIR), the research-based speciality pharmaceutical company focused on the development of high-value treatments for infectious diseases, announces that its development partner, Tibotec Pharmaceuticals, has entered into an agreement with Bristol-Myers Squibb Company.

TMC435, a once daily NS3/4A protease inhibitor (PI) for the treatment of genotype-1 chronic hepatitis C virus (HCV) infection will be investigated in combination with Bristol-Myers Squibb's investigational NS5A replication complex inhibitor, daclatasvir.

Charlotte Edenius, Executive VP Research & Development, of Medivir, commented, "We are very excited to work with Bristol-Myers Squibb to investigate our protease inhibitor, TMC435, in combination with an NS5A replication complex inhibitor to enable the advancement of novel treatment options for people chronically infected with HCV. We believe that an all oral, treatment regimen for HCV would represent a major step towards improved HCV treatments."

Bristol-Myers Squibb released the following statement on 2nd December 2011:

Bristol-Myers Squibb Enters Clinical Collaboration Agreement with Tibotec Pharmaceuticals for Phase II Combination Study in Patients Chronically Infected with Hepatitis C

(NEW YORK, December 2, 2011) - Bristol-Myers Squibb Company /quotes/zigman/220498/quotes/nls/bmy BMY +0.18% announced today that it has entered into a clinical collaboration agreement with Tibotec Pharmaceuticals, one of the Janssen Pharmaceutical Companies, to evaluate the utility of daclatasvir (BMS-790052), Bristol-Myers Squibb's investigational NS5A replication complex inhibitor, in combination with Tibotec Pharmaceuticals' investigational NS3 protease inhibitor, TMC435, for the treatment of chronic hepatitis C virus (HCV).

Under the agreement the companies will evaluate the potential to achieve sustained viral response 12 and 24 weeks post treatment in patients with HCV genotype 1 in a study with three treatment regimens: an oral, once-daily treatment regimen of daclatasvir and TMC435 with pegylated-interferon alpha plus ribavirin; an oral, once-daily treatment regimen of daclatasvir and TMC435 with ribavirin and an oral, once-daily treatment regimen of daclatasvir and TMC435 alone. The study is planned to start in the first half of 2012.

"Bristol-Myers Squibb is dedicated to developing innovative treatment options for patients with serious diseases like HCV," said Brian Daniels, senior vice president, Development. "We are pleased to work with Tibotec to advance the scientific understanding for the potential for an all-oral regimen of direct acting antivirals, which would be an important advancement for patients with HCV. This is a continuation of our leadership in forging partnerships to advance combination antiviral therapy."

About TMC435

TMC435 is a highly potent and selective once-daily (q.d.) investigational drug that is being jointly developed by Tibotec Pharmaceuticals and Medivir to treat chronic hepatitis C virus infections in genotype 1 patients.

TMC435 has received "Fast Track" designation by the U.S. Food and Drug Administration ("FDA") for the treatment of chronic hepatitis C (CHC) genotype-1 infection. TMC435 is currently being developed in three global phase III studies, QUEST-1 and QUEST-2 in treatment-naïve patients and PROMISE in patients who have relapsed after prior interferon-based treatment. In parallel with these trials, phase III studies for TMC435 in Japan, in both treatment naive and treatment experienced hepatitis C genotype-1 infected patients, are ongoing. These phase III studies are fully recruited.

For additional information from these studies, please see http://www.medivir.com and http://www.clinicaltrials.gov

About Hepatitis C

Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The World Health Organization estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.

About Medivir

Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a novel protease inhibitor is in phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.

In June 2011, Medivir acquired the specialty pharmaceutical company BioPhausia to ensure timely commercialization of TMC435 in the Nordic markets, once approved.

Medivir's first product, the unique cold sore product Xerese®/Xerclear®, was launched on the US market in February 2011. Xerese®/Xerclear®, which has been approved in both the US and Europe is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia. Rights in North America, Canada and Mexico were sold to Meda AB in June 2011. Medivir has retained the Rx rights for Xerclear® in Sweden and Finland.

For more information about Medivir, please visit the Company's website: http://www.medivir.com

For more information about Medivir, please contact:

Medivir ( http://www.medivir.com ): Rein Piir, CFO & VP Investor Relations Mobile: +46-708-537-292 M:Communications Europe: Peter Laing, Amber Bielecka, Hollie Vile Medivir@mcomgroup.com +44(0)20-7920-2330 USA: Roland Tomforde +1-212-232-2356

SOURCE Medivir

Copyright (C) 2011 PR Newswire. All rights reserved

Source

Also See: Bristol-Myers, J&J form hepatitis C partnership

Hepatitis A, B Susceptibility High in Patients on Methadone

Nancy A. Melville

December 2, 2011 (Washington, DC) — Patients in methadone maintenance treatment facilities, known to be at higher risk for hepatitis C virus (HCV) infection than the general population, might also have higher rates of vaccine-preventable hepatitis A (HAV) and B (HBV) infection, according to research presented here at the American Public Health Association 139th Annual Meeting.

HCV, which is often asymptomatic, can be particularly dangerous when patients are coinfected with HAV or HBV, potentially causing more acute liver disease, fulminant hepatitis, hepatocellular carcinoma, and/or death, investigators from the Beth Israel Medical Center in New York City told meeting attendees.

In an effort to determine the prevalence of the diseases at a methadone maintenance treatment program at Beth Israel, the researchers evaluated 8060 patients who were screened from June 2007 to July 2009.

They found that 35% of patients were susceptible to HBV, 15% had isolated HBV core antibody (cAb), 1% were positive for HBV surface antigen, 27% were immune to HBV because of natural disease, 23% were immune to HBV because of vaccination, and 35% were susceptible to HAV.

"Overall, 50% were susceptible to HAV, HBV, or both," the authors write.

In addition, of the 56% of patients who were positive for the HCV antibody, 17% were susceptible to HBV and 22% were susceptible to HAV, representing a very high-risk population.

Overall, 31% who were positive for the HCV antibody were susceptible to HAV and/or HBV.

Of the 1029 patients positive for HBV cAb who were also screened for the HCV antibody, 954 (93%) were positive for the HCV antibody, and 24% of the HCV-positive patients had isolated HBV cAb positivity (24% vs 2%; P < .0001; odds ratio, 12.5; 95% confidence interval, 9.8 to 16.0).

The findings highlight a heightened susceptibility of the substance-abusing generation born before hepatitis A and B vaccines became standard for newborns, said Catherine L. Troisi, PhD, who moderated the session.

"The average age was around 50. What this shows is they were likely not vaccinated at birth and, because of their drug use, there is a heightened risk," said Dr. Troisi, who is from the division of management, policy, and community health at the University of Texas School of Public Health in Houston.

"The fact that so many were hepatitis C–positive, which you cannot vaccinate against, indicates that they should be vaccinated against A and B, because those diseases can place additional assaults on the liver."

Dr. Troisi added that one of the more unusual findings is that 15% were positive for isolated HBV cAb. "It's unclear what that means," she said. "It's higher than you would find normally. It may be that these people had occult hepatitis B [with undetectable hepatitis B antigen]."

Vaccinating populations at methadone maintenance clinics has always been a challenge, but Dr. Troisi noted she had success in one study with an accelerated vaccination schedule, in which patients were vaccinated at 0, 1, and 2 months, instead of the typical 0, 1, and 6 months.

"Using an accelerated schedule is easier because you don't have to find people 6 months later," she said. "But it's hard, especially with hepatitis C, because if they're using needles, they can become positive pretty quickly, and you'd like to vaccinate them against hepatitis A and B before they are infected with C."

The authors and Dr. Troisi have disclosed no relevant financial relationships.

American Public Health Association (APHA) 139th Annual Meeting: Abstract 237717. Presented October 31, 2011.

Source

Babyboomers Most at Risk for Hepatitis C Virus

Dec. 2, 2011, 8:25 p.m. EST

NEW YORK, Dec. 2, 2011 /PRNewswire via COMTEX/ -- Montefiore Liver Specialists Urge Population to be Tested for This Potentially Deadly Virus

"Twitter Chat" Hosted by @MontefioreNews on December 8, noon, #MonteHepC

Experts at Montefiore Medical Center urge the general public to be tested for the Hepatitis C virus, especially baby boomers, adults born between 1946-1964, who could be most at risk for this disease. Baby boomers are more likely to have been exposed to dangerous risk factors decades ago, such as sharing a drug needle, being tattooed or pierced with unsterilized tools or receiving a tainted blood transfusion. The disease often has no symptoms, and if untreated, can lead to chronic infection that can scar the liver, cause liver failure or cancer and potentially lead to liver transplantation.

Hepatitis C virus (HCV) is the most common chronic blood borne infection in the United States, with 35,000 to 185,000 new cases diagnosed per year. Worldwide, 180 million people are chronically infected with Hepatitis C, with an estimated 3-4 million new cases reported each year. The disease particularly affects minorities, Hispanics, Asian-Americans and African-Americans.

"This disease has grown to epidemic proportions, with 350,000 people around the world dying from Hepatitis C-related liver disease," said Milan Kinkhabwala, MD, Chief, Division of Transplantation at the Montefiore Einstein Center for Transplantation. "But it is called the 'silent killer' because many people don't even know they have it. This condition can be asymptomatic for decades and then present itself when it has already severely damaged the liver."

Individuals at risk can get a simple blood test to detect the virus before chronic infection leads to permanent liver damage. The Montefiore Medical Center Comprehensive Liver Disease Program offers simple and effective screenings. It is recommended that individuals talk to their primary care physician or contact 888-RX-LIVER (888-795-4837) for more information or to set up an appointment for a screening.

"This is a revolutionary time in the treatment of the disease and there is more hope than ever before," said Dr. Kinkhabwala. "The blood test is essential to detecting Hepatitis C, because now there are ways to treat the condition, and even reverse damage to the liver."

Two new anti-viral oral medications, boceprevir and teleprevir, received FDA approval in May 2011. Both drugs work by blocking an enzyme that helps the virus reproduce. The drugs are intended to improve on standard treatments using the injected drug pegylated interferon alpha and the pill rivavrin.

"So far, the new drugs have shown promise in clearing the virus from the body and almost doubling the cure rate of the disease," said Allan Wolkoff, MD, Professor of Medicine and of Anatomy and Structural Biology at Albert Einstein College of Medicine of Yeshiva University and Chief of the Division of Gastroenterology and Liver Diseases at Montefiore and Einstein. "Another key benefit is that they cut treatment time in half, thus reducing the time the patient has to endure the severe side effects, which include anemia, depression and flu-like symptoms like fatigue, fever and headache."

When symptoms do occur after the disease has progressed, they're generally mild and flu-like and may include fatigue, fever, nausea or poor appetite, muscle and joint pain, bruising, abdominal pain, jaundice and itching. At that point, chronic infection can lead to scarring of the liver (fibrosis) and then advanced scarring (cirrhosis). Scarring of the liver makes it difficult for the liver to function properly and can be devastating to the rest of the body, often causing liver failure or liver cancer.

If the liver disease progresses too far and the medications are not effective, then transplantation is the last resort. However, more than 16,000 people in the United States are currently waiting for a liver donor, and in New York State, there are 1,700 patients on the waiting list.

Factors that have been reported to accelerate the rate of HCV disease progression include age, gender (males have more rapid disease progression than females), alcohol consumption, HIV coinfection (approximately 35% of patients) and fatty liver (the presence of fat in liver cells caused by obesity).

Unlike Hepatitis B, there is no vaccine to prevent this disease. While the symptoms are similar, distinct differences exist between the two viruses. Hepatitis B is primarily transmitted through sexual intercourse and is less severe.

Dr. Kinkhabwala will be available for a live twitter chat to answer questions about Hepatitis C and liver disease on December 8, 2011 at noon. Follow @MontefioreNews to discuss #MonteHepC.

About Montefiore Medical CenterAs the University Hospital for Albert Einstein College of Medicine, Montefiore is a premier academic medical center nationally renowned for its clinical excellence, scientific discovery and commitment to its community. Recognized among the top hospitals nationally and ranked sixth out of 184 in the New York metropolitan area by U.S. News & World Report, Montefiore provides compassionate, patient- and family-centered care and educates the healthcare professionals of tomorrow. The Children's Hospital at Montefiore is consistently named in U.S. News' "America's Best Children's Hospitals," and is second among those in the New York metro area. With four hospitals, 1,491 beds and 93,000 annual hospital discharges, Montefiore is an integrated health system seamlessly linked by advanced technology. State-of-the-art primary and specialty care is provided through a network of nearly 100 locations across the region, including the largest school health program in the nation and a home health program. Montefiore's partnership with Einstein advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. The medical center derives its inspiration for excellence from its patients and community, and continues to be on the frontlines of developing innovative approaches to care. For more information please visit www.montefiore.org and www.montekids.org and follow us on Twitter @MontefioreNews.

SOURCE Montefiore Medical Center

Source

Bristol-Myers, J&J form hepatitis C partnership

The Associated Press December 2, 2011, 11:32AM ET

NEW YORK

Bristol-Myers Squibb Co. said Friday it will collaborate with a unit of Johnson & Johnson to study a potential combination therapy for chronic hepatitis C.

The companies will study a regimen that combines Johnson & Johnson's drug TMC435 with Bristol-Myers Squibb's daclatasvir. The clinical trial of the drug cocktail will begin in the first half of 2012. It will include a combination of the two drugs, the drugs plus pegylated interferon and ribavirin, and the drugs plus ribavirin.

Pegylated interferon and ribavirin have been staples of hepatitis C treatment for decades. Several drugmakers are studying potential treatments that could work without interferon, which is given by IV and is associated with particularly severe side effects. That could allow patients to treat their hepatitis C infections using only pills. Some studies are testing experimental drugs alone and without ribavirin.

Bristol-Myers of New York and Johnson & Johnson, based in New Brunswick, N.J., did not disclose the terms of their partnership.

Tibotec Pharmaceuticals is part of J&J's Janssen Pharmaceuticals business. In July the company announced a partnership with Pharmasset Inc. that will combine TMC435 with Pharmasset's PSI-7977, which is considered one of the most promising of all the current experimental therapies for hepatitis C in part because it's an oral treatment. Bristol-Myers is conducting late-stage trials of daclatasvir.

Shares of Johnson & Johnson fell 36 cents to $64.08 in morning trading, while Bristol-Myers Squibb stock rose 24 cents to $33.14.

Source

New Book About Hepatitis C and Other Liver Conditions Just Released by Dr. Tuesdae Stainbrook

Dr. Tuesdae Stainbrook is pleased to announce her new book, Hepatitis C: What You Need To Know. From diagnosis to treatment, the book contains important information people need to know about hepatitis C.

Philadelphia, PA, December 04, 2011 --(PR.com)-- "Hepatitis C: What You Need To Know" contains questions and answers about hepatitis C. From diagnosis to treatment and other important information people need to know about hepatitis C.

The book is very straight forward and easy to understand and is intended to help patients and families understand the causes, effects, and health risks of Hepatitus C and other liver conditions.

Facts: Hepatitus C can be cured.

Most people with hepatitis C do not have any symptoms. The two most common symptoms are right upper quadrant pain and fatigue.
Only about 80-85% of individuals exposed to hepatitis C will go on to have chronic hepatitis C. Learn about the new treatments available and their side effects.

Want To Know More? Check Out The New Book, "Hepatitis C: What You Need To Know" By Dr. Tuesdae Stainbrook.

Book Information:
"Hepatitis C: What You Need To Know"
Author: Dr. Tuesdae Stainbrook
Publisher: AuthorHouse
ISBN: 978-1-4634-2854-9
Pages: 37
Published: September 2011

About The Author
Dr. Tuesdae Stainbrook is an infectious disease physician in central Pennsylvania. She is board certified in internal medicine, infectious disease, and HIV. She has also a master's degree in public health. Dr. Stainbrook has a large hepatitis C treatment population and is considered to be one of the largest hepatitis C providers in Pennsylvania.

Dr. Stainbrook has been crucial in bringing community and physician awareness along with free hepatitis C testing in her area. In 2007, she was honored with the Viral Hepatitis Award of Excellence given by the Commonwealth of PA Health Department. Dr. Stainbrook in 2011 received the Outstanding Community Service Award for her exceptional support and dedication to the field of Substance Abuse by the Clearfield-Jefferson Drug and Alcohol Commission.

For more information, review copies, or interviews please contact the author at:

Dr. Tuesdae Stainbrook
Email: trrod203@pol.net
Website: http://www.hepcinfo.com

"Hepatitis C: What You Need To Know" is available for purchase through the author’s website, from the publisher, from Amazon.com, BN.com and other online retailers. Bookstores should contact Ingram for wholesale orders.

###

Contact Information

Dr. Tuesdae Stainbrook
419-791-8004
Contact
www.hepcinfo.com

Source

Achillion Announces Preliminary Phase 1b Proof-of-Concept Data With ACH-2928 NS5A Inhibitor for the Treatment of Hepatitis C

Dec. 5, 2011, 7:00 a.m. EST

Achieves 3.68 Log10 Reduction in HCV RNA After Three Days of Treatment

NEW HAVEN, Conn., Dec 5, 2011 (GlobeNewswire via COMTEX) -- Achillion Pharmaceuticals, Inc. /quotes/zigman/100395/quotes/nls/achn ACHN +1.61% , a leader in the discovery and development of small molecule drugs to combat the most challenging infectious diseases, today reported proof-of-concept data from its Phase 1b clinical trial of ACH-2928, a first-generation NS5A inhibitor, demonstrating that patients treated with ACH-2928 achieved a mean maximum 3.68 log10 reduction in HCV RNA after three-day monotherapy of 60 mg once daily. The compound also demonstrated good safety and tolerability both in healthy volunteers and in patients with chronic hepatitis C (HCV).

ACH-2928, Achillion's first generation inhibitor of the NS5A protein, was discovered through the Company's NS5A inhibitor program. Achillion also recently nominated a second-generation NS5A inhibitor, ACH-3102, which is currently undergoing IND-enabling studies and is expected to be advanced into clinical trials during the first half of 2012.

"We believe NS5A inhibitors have emerged as an important component for an all-oral, direct acting antiviral (DAA) regimen," commented Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "Furthermore, NS5A inhibitors, when combined with a protease inhibitor, have achieved sustained viral responses in clinical trials in tough to treat genotype 1 HCV populations. We believe this highlights the potential to form a proprietary interferon-free DAA combination regimen for the treatment of HCV within Achillion's pipeline."

ACH-2928 Phase 1 Program

In July 2011, Achillion initiated dosing in a randomized, double-blind, placebo-controlled phase 1a/1b clinical trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity of ACH-2928. The trial consists of three segments: assessment of single ascending oral doses (SAD) in healthy volunteers, evaluation of 3 days of oral repeat doses in subjects with genotype 1a or 1b HCV, and a 5-day multiple ascending doses segment in healthy volunteers.

During the oral repeat doses segment in subjects infected with HCV, a total of 10 patients were enrolled with 2 patients (genotype 1a) receiving placebo and 8 patients (7 genotype 1a and 1 genotype 1b) treated with 3 doses of 60 mg ACH-2928 administered once daily. No serious adverse events (SAE) were reported and there were no patient discontinuations during treatment. The mean maximum HCV RNA decline during therapy was 3.68 log10 compared to a 0.54 log10 decline for patients receiving placebo. There were no viral breakthroughs observed during ACH-2928 monotherapy.

Preliminary data from the SAD trial segment demonstrated ACH-2928 was well tolerated at all doses evaluated up to and including the maximum dose of 500 mg. There were no serious adverse events, no clinically significant changes in vital signs, electrocardiograms (ECGs), or laboratory evaluations.

All reported adverse events were classified as mild or moderate, and were transient in nature.

Based upon these preliminary results, the ongoing Phase 1 study will continue to evaluate the pharmacokinetic, pharmacodynamic, and antiviral profile of ACH-2928. These Phase 1 results have been submitted for presentation at a medical meeting being held during the second quarter of 2012.

In parallel, Achillion is advancing its second generation NS5A inhibitor ACH-3102 through IND-enabling studies and the Company expects to initiate clinical development during the first half of 2012.

"As we continue to evaluate ACH-2928 in this Phase 1 study, we are also working rapidly to advance ACH-3102, which has shown in preclinical studies to possess the same potent activity against genotype 1a HCV as ACH-2928, as well as enhanced activity against resistant HCV mutants that have been observed in this patient population," stated Milind Deshpande, PhD, President of Research and Development and Chief Scientific Officer. "We believe these results validate our NS5A development program, and look forward to developing an all-oral combination for clinical evaluation that includes one of our protease inhibitors and an NS5A inhibitor next year."

About NS5A Inhibitors

The NS5A protein is a clinically validated target that serves multiple functions at various stages of the HCV life cycle including involvement in virion production, interaction with host proteins and association with interferon-resistance. Achillion's NS5A inhibitors, including ACH-2928 and ACH-3102, possess potent in vitro activity against all HCV genotypes and demonstrate, in preclinical studies, additive to synergistic activity when combined with NS3 protease inhibitors, NS5B polymerase inhibitors, and ribavirin. In preclinical studies, ACH-2928 and ACH-3102 have demonstrated excellent potency, in the pico-molar range, against HCV RNA replication, including potent activity against genotype 1a while ACH-3102 has been shown to possess enhanced activity against recognized genotype 1 resistant variants.

About HCV

The hepatitis C virus infects the liver and is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide and The American Association of Liver Disease estimates that up to 80 percent of individuals become chronically infected following exposure to the virus. If left untreated, chronic hepatitis can lead to permanent liver damage, which can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease including hepatitis C and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors, including statements with respect to the potency, safety and other characteristics of Achillion's NS5A inhibitors, which may not be duplicated in clinical studies, and Achillion's expectations regarding results, timing and duration of clinical trials and reporting of results from clinical trials of Achillion's NS5A inhibitors. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to: Achillion's ability to advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; to obtain patent protection for its drug candidates, and the freedom to operate under third party intellectual property; to establish commercial manufacturing arrangements and to identify, enter into and maintain collaboration agreements with appropriate third-parties; and to raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2010 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any obligation to update any forward-looking statement, except as required by applicable law.

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Achillion Pharmaceuticals, Inc.

CONTACT:
 Glenn Schulman Achillion Pharmaceuticals, Inc.
Tel. (203) 752-5510
gschulman@achillion.com

Investors: Mary Kay Fenton
Achillion Pharmaceuticals, Inc.
Tel. (203) 624-7000
mfenton@achillion.com

Media: Christin Culotta Miller
Ogilvy PR
Tel. (212) 880-5264        
christin.miller@ogilvy.com

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Poor Liver Transplant Outcomes for HIV/HCV Coinfected Patients

Neil Canavan

December 5, 2011 (San Francisco, California) — Patients coinfected with hepatitis C virus (HCV) and HIV have only a 55% chance of survival 5 years after liver transplantation, according to results from a study performed at a French transplant center and reported here at The Liver Meeting 2011: American Association for the Study of Liver Diseases 62nd Annual Meeting. The study authors concede that improvements in care might depend on the near-term availability of new HCV therapies.

Liver disease progression to cirrhosis is rapid in HIV-infected patients, and liver transplantation is now an accepted therapeutic option for those with end-stage liver disease. "However, everyone knows that the mortality in HIV/HCV coinfected patients is very high," said principal investigator Jean-Charles Duclos-Vallée, MD, Centre Hépato-Biliaire, Hôpital Paul-Brousse, Villejuif, France. "A paper from 2005 puts the figure at just 25% 5 years after the first episode of decompensation, compared with 44% for HCV patients without HIV."

This reference aside, there are limited data overall regarding the survival of coinfected patients who undergo liver transplantation, he said. However, the increasing frequency of HIV-positive patients undergoing transplantation and the severity of recurrence of HCV infection in the liver grafts in transplanted patients is of growing concern.

Dr. Duclos-Valle and colleagues looked at survival rates and the degree of recurrence of HCV infection in 105 transplant patients at their center. The patient cohort was 83% male, 61% had HCV genotype 1, median MELD score was 16.0, and waiting time to transplantation was 4.9 months. All patients were using highly active antiretroviral therapy (HAART) at the time of transplantation. Reasons for transplant included HCV-related cirrhosis (56%), hepatocellular carcinoma (HCC; 19%), hepatitis B virus (HBV)-related cirrhosis (7.6%), HBV/HCV-related cirrhosis (4.7%), and other (14%).

"The overall survival rate for the entire cohort was 55% at 5 years posttransplant," said Dr. Duclos-Valle.

The 5-year survival rate for patients with HCV-related cirrhosis was 45%, with HCC was 49%, and with HBV-related cirrhosis was 100%. Nine patients have undergone retransplantation. Of the 40 deaths, 20 were due to HCV recurrence, 5 were due to HCC, 5 were due to sepsis, and 2 were due to myocardial infarction; the remaining patients died for other reasons.

After transplantation, anti-HCV therapy (pegylated interferon alfa-2a plus ribavirin) was given to 36 of 58 patients who had a recurrence of HCV infection in the new liver graft. The response rates were as follows: no response in 24 patients, partial response in 6, and sustained viral response in 6.

"For response to treatment after recurrence, we had [a sustained viral response] of 16.6%, with 64% nonresponders and 1 relapse," said Dr. Duclos-Valle. Given the dismal survival outcomes 5 years after transplantation and the less-than-optimal response rates to retreatment after HCV recurrence, Dr. Duclos-Valle said he is doubly concerned. Transplant organ resources are already strained, and with the success of HAART treatment, the number of HIV-infected individuals that will require transplantation in the future will only increase.

Race Against Demographics

"We are going to be seeing more of these patients," noted Jay H. Hoofnagle, MD, director of the Liver Disease Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, in Bethesda, Maryland. "They're living longer so they're going to have other health issues."

Dr. Hoofnagle said he is seeing an increase in complications from chronic conditions such as heart disease. "As HAART therapy extends lives, you're going to see these complications. That is particularly true with hepatitis C because of the common modes of transmission."

Dr. Hoofnagle is optimistic, however, about the overall prognosis for the situation. "The treatments for hepatitis C are improving so fast that what looks bad now is just going to improve with new drugs. This will be particularly helpful for the coinfected group, when you get the chance to get these patients away from interferon, which is very hard to take." Dr. Hoofnagle expects to see critical improvements in HCV treatment within the next 5 years.

Dr. Duclos-Valle and Dr. Hoofnagle have disclosed no relevant financial relationships.

The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 4. Presented November 6, 2011.

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Largest Ever Genetic Study of Liver Function Could Point the Way to New Treatments

Published: October 16, 2011. Imperial College London

Researchers have identified a large number of areas in the human genetic code that are involved in regulating the way in which the liver functions, in a new study of over 61,000 people, published today in the journal Nature Genetics.

The work is an international collaboration led by Imperial College London and it identifies 42 genetic regions associated with liver function, 32 of which had not been linked to liver function before. The work should lead to a better understanding of precisely what goes wrong when the liver ceases to work normally. Ultimately, it could point the way to new treatments that can improve the function of the liver and help to prevent liver damage.

The liver is the body's largest internal organ and the British Liver Trust estimates that around two million people in the UK have a liver problem at any one time. The liver carries out hundreds of different tasks, including making proteins and blood clotting factors, and helping with digestion and energy release. It also purifies the blood of bacteria, and of the by-products of digestion, alcohol and drugs.

In the new genome-wide association study, the researchers compared the genetic makeup of over 61,000 people, in order to identify areas of the genetic code that were associated with liver function.

The team assessed the function of the volunteers' livers by looking at the concentrations of liver enzymes in their blood. People who have liver damage have high concentrations of these enzymes, which are associated with an increased risk of conditions such as cirrhosis, type 2 diabetes and cardiovascular disease.

Dr John Chambers, the lead author of the study from the School of Public Health at Imperial College London, said: "The liver is a central hub in the body and because it has so many diverse functions, it is linked to a large number of conditions. Our new study is a big step towards understanding the role that different genes play in keeping the liver working normally, and towards identifying targets for drugs that can help prevent the liver from functioning abnormally or becoming susceptible to disease."

The researchers identified 42 areas on the genetic code associated with liver function and they then went on to pinpoint 69 associated genes within these areas. Some of the genes are known to play a part in other functions in the body, including inflammation and immunity, and metabolising glucose and carbohydrates.

Professor Jaspal S Kooner, the senior author of the study from the National Heart and Lung Institute at Imperial College London, said: "This massive international research effort provides in-depth new knowledge about the genes regulating the liver. We are particularly excited about the genes whose precise role we don't yet know. Investigating these further should help us to fill in the gaps in our understanding about what happens when the liver ceases to function normally and how we might be able to tackle this."

Professor Paul Elliott, also a senior author of the study, from the School of Public Health at Imperial College London, said: "Liver problems affect a huge number of people and they can have a devastating effect on a person's quality of life. This study represents a vast discovery that opens up multiple new avenues for research."

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Predicting clinical outcomes using baseline and follow-up laboratory data from the hepatitis C long-term treatment against cirrhosis trial

HepatologyVolume 54, Issue 5, pages 1527–1537, November 2011

Marc G. Ghany^1,*,§, Hae-Young Kim², Anne Stoddard², Elizabeth C. Wright³, Leonard B. Seeff⁴, Anna S.F. Lok⁵, the HALT-C Trial Group

Article first published online: 28 OCT 2011
DOI: 10.1002/hep.24550
Copyright © 2011 American Association for the Study of Liver Diseases

Abstract

Predicting clinical outcomes in patients with chronic hepatitis C is challenging. We used the hepatitis C long-term treatment against cirrhosis (HALT-C) trial database to develop two models, using baseline values of routinely available laboratory tests together with changes in these values during follow-up to predict clinical decompensation and liver-related death/liver transplant in patients with advanced hepatitis C. Patients randomized to no treatment and who had ≥2-year follow-up without a clinical outcome were included in the analysis. Four variables (platelet count, aspartate aminotransferase [AST]/alanine aminotransferase [ALT] ratio, total bilirubin, and albumin) with three categories of change (stable, mild, or severe) over 2 years were analyzed. Cumulative incidence of clinical outcome was determined by Kaplan-Meier analysis and Cox regression was used to evaluate predictors of clinical outcome. In all, 470 patients with 60 events were used to develop models to predict clinical decompensation. Baseline values of all four variables were predictive of decompensation. There was a general trend of increasing outcomes with more marked worsening of laboratory values over 2 years, particularly for patients with abnormal baseline values. A model that included baseline platelet count, AST/ALT ratio, bilirubin, and severe worsening of platelet count, bilirubin, and albumin was the best predictor of clinical decompensation. A total of 483 patients with 79 events were used to evaluate predictors of liver-related death or liver transplant. A model that included baseline platelet count and albumin as well as severe worsening of AST/ALT ratio and albumin was the best predictor of liver-related outcomes. Conclusion: Both the baseline value and the rapidity in change of the value of routine laboratory variables were shown to be important in predicting clinical outcomes in patients with advanced chronic hepatitis C. (HEPATOLOGY 2011;)

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Living with chronic illness during the holiday season

by Toni Bernhard, JD
Posted on KevinMD.com

In the U.S., we’re getting ready to celebrate Thanksgiving. Soon, people around the world will turn their attention to the holiday season. Chronic health problems can take a toll on relationships any time of the year. Most people have to experience unrelenting pain or illness themselves before they understand how debilitating it is, physically and mentally. Loved-ones (by whom I mean family and close friends) may be in some form of denial about what’s happened to you, or they may be scared and worried about the future. Bottom line, suffering from a chronic condition can be an ongoing crisis—for you and for those you’re close to.

That crisis can come to a head during the holidays when people’s expectations of one another are high and when stress levels for everyone are likely to be off the charts for any number of reasons—health, financial, relationship issues. If you’re like me, during the rest of the year, you carefully limit interactions with others in order to manage your symptoms; on a typical day, your most complex decision may be to choose between showering and shopping! But when the holidays arrive, you’re suddenly thrust into the middle of a lively and chaotic social scene where you’re expected to participate in a range of activities, often for days in a row. A bit of advance warning to loved-ones can go a long way toward minimizing stress levels over unrealistic expectations.

I know that this piece won’t apply to everyone. One of the heartbreaking consequences of living with chronic pain and illness is that some people are unable to be with loved-ones at all during the holidays, either because people are too disabled by their pain or illness to be able to gather with others, or because family and close friends having drifted out of their lives. I know the pain of that isolation; I’ll be writing about it in my next piece.

For those of you who are able to gather with others, the holidays can be a recipe for double disaster—the increase in activity exacerbates your physical symptoms, while coping with sadness, frustration, and maybe even guilt about your physical limitations gives rise to emotional pain. No wonder many people with health problems dread the approaching holidays.

If you’re one of the many people with chronic health problems who don’t look sick, the initiative is with you to make your condition visible. Here are some suggestions for helping loved-ones understand what your life is like and for giving them a heads-up on what to expect from you during the holidays.

Share information with them from the Internet or from books

Often the best way to educate loved-ones about chronic pain and illness is to use a neutral source because it takes the emotional impact out of the communication. A quick web search will yield a host of organizations devoted to every conceivable medical problem. Print out select pages or forward a few links to family and close friends. Alternatively, if you have a book about your condition, photocopy the pages that cover what you’d like them to know about you. In your accompanying note, keep it “light”—you could joke that “there won’t be a test.” But also make it clear that this favor you’re asking is important to you.

Write a letter

Many years ago, two friends of mine were in couples therapy. They weren’t able to speak to each other about their marital problems without one of them shutting down emotionally and the other reacting by shouting recriminations. Their therapist told them to write letters to each other expressing their feelings and their concerns about the marriage. It turned out to be a major first step in healing their relationship.

If you decide to write a letter, be sure it’s not accusatory. In composing it, use the word “I” more than the word “you.” Without complaining, express how difficult it’s been for you to adjust to this unexpected change in your life and how you wish you could be as active as you once were during the holidays.

You could briefly describe what your day-to-day life is like, including how unpredictable your condition is which means that you can’t know for sure how you’ll feel on the day of the actual gathering no matter how much you rest in advance. (This is the hardest concept for most loved-ones to comprehend—that we can spend weeks before a big event in full “rest mode,” but still feel very sick when the day arrives.)

I would end by telling them what to expect from you during the holidays—that you may have to skip some events, that you may have to excuse yourself right after eating to go lie down, that you may have to come late and leave early. In my experience, spelling out my limitations ahead of time is helpful not just to others, but to me, because I find it much easier to exercise the self-discipline it takes to excuse myself from a room full of people if I know that at least some of them are already expecting it.

P.S. It will be tempting to send an email, and if you have a lot of people you want to communicate with, it may be the most feasible way to reach everyone. But one thing’s for sure: people will read a handwritten letter, antiquated document that it’s become!

Find that ONE ally and enlist his or her help

If you have just one close friend or family member who understands what you’re going through, enlist his or her help in explaining your condition and your limitations. Before the holidays start, you could ask your ally to talk to loved-ones on your behalf or to be present when you talk to them. Ask your ally to be supportive if you have to excuse yourself in the middle of a gathering, or even to let you know if you’re wilting (as we call it in my household). It’s so helpful for me to be “prompted” by my ally because, when I start to overdo things, adrenaline kicks in which fools me into thinking I’m doing fine. But using adrenaline to get by just sets me up for a bad crash later on.

Your ally may be a close friend or family member who’s just waiting for you to enlist his or her help. Think long and hard before you decide there’s no such person in your life.

In the end, you may have to recognize that some loved-ones may never accept your limitations

Some family and close friends may refuse to accept that you’re disabled by pain or illness. I know this from personal experience and it hurts. Try to recognize that this inability is about them, not you. Don’t let their doubt make you doubt yourself. Your medical condition may trigger their own fears about illness and mortality, or they may be so caught up in problems in their own lives that they’re not able to see their way clear to empathize with you.

Just as you can’t force people to love you, you can’t force people to accept you. But getting angry at them just exacerbates your own symptoms. That’s why it’s important to protect yourself from allowing their lack of understanding to continually upset you. Think of it as protecting yourself from another chronic condition: chronic anger.

The physical suffering that accompanies chronic pain and illness is hard enough to endure without adding emotional suffering to it. When I feel let down family or close friends, the first thing I do is acknowledge how much it hurts. Then I reflect on the many possible reasons for their behavior. Finally, I work on genuinely wishing them well. These three steps immediately lessen my emotional suffering.

As you experiment with these suggestions, treat yourself kindly. Don’t blame yourself if one of them doesn’t work out. Instead, give yourself credit for having had the courage to try! My heartfelt wish is that your loved-ones come to understand and accept your limitations, but that if they don’t, you’ll be able to accept them as they are without bitterness.

Toni Bernhard was a law professor at the University of California—Davis, serving six years as the law school’s dean of students. She is the author of How to Be Sick: A Buddhist-Inspired Guide for the Chronically Ill and Their Caregivers and can be found online at HowToBeSick.com.

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