October 29, 2010

Alnylam Scientists to Present New Data on RNAi Therapeutics at the 61st Annual Meeting of the American Association for the Study of Liver Diseases

-- Research Highlights Include Potential New Therapeutic Applications for RNAi Therapeutics in Liver Fibrosis --

CAMBRIDGE, Mass., Oct 29, 2010 (BUSINESS WIRE) -- Alnylam Pharmaceuticals, Inc. /quotes/comstock/15*!alny/quotes/nls/alny (ALNY 13.14, -0.15, -1.13%) , a leading RNAi therapeutics company, announced today it will present several poster presentations at the 61st Annual Meeting of the American Association for the Study of Liver Diseases ("The Liver Meeting") being held in Boston, Mass from October 29 -- November 2, 2010. At the meeting, new research related to the company's pre-clinical and clinical pipeline efforts will be presented, including new data showing effective delivery of RNAi therapeutics to hepatic stellate cells. Pre-clinical data will also be presented on Alnylam's key development programs, including ALN-TTR01 for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-VSP for the treatment of liver cancers, and ALN-PCS for the treatment of hypercholesterolemia.

"The data we are presenting at this meeting highlight the significant progress we are making in advancing RNAi therapeutics to patients," said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President, Clinical Research. "It is notable that we are now showing effective systemic delivery to stellate cells, creating a potentially new approach for the treatment of liver fibrosis with siRNAs targeting collagen 1a1. We are also pleased with additional updates from some of our key clinical development programs, including ALN-VSP, ALN-TTR01, and ALN-PCS."

In a poster titled "Liposome Mediated Delivery of siRNA to Hepatic Stellate Cells," Alnylam scientists will present new data on the systemic delivery of RNAi therapeutics to hepatic stellate cells (HSCs). HSCs play a key role in the initiation and progression of liver fibrosis, the excessive accumulation of tough, fibrous scar tissue that occurs in most types of chronic liver diseases. These new data show that siRNAs formulated in LNPs comprising the novel cationic lipid "C12-200" result in effective silencing of the HSC-specific gene target, collagen 1a1 (col1a1). These data point to a potential strategy for development of RNAi therapeutics for the treatment of fibrotic diseases.

Other presentations from Alnylam scientists at The Liver Meeting include the following:

a poster titled, "Carbohydrate Conjugation to siRNA for Liver-Specific Delivery" will describe progress made on improving stability and activity of GalNAc-conjugated siRNAs in vitro and their translation to improved in vivo gene silencing efficacy; a poster titled, "RNAi Therapeutics Targeting PCSK9 Result in Significant and Durable LDLc Lowering" will highlight pre-clinical data from the company's PCSK9 program which blocks the production of both intracellular and extracellular PCSK9 and uses a second generation LNP formulation; new data included in the poster will show the ability to utilize siRNA combination approaches to achieve efficient silencing of several genes at one time to achieve improved cholesterol lowering; in addition, new data will also be presented showing that lowering of PCSK9 in an LDLR heterozygous animal model of familial hypercholesterolemia results in a significant lowering of total cholesterol; a poster titled, "ALN-TTR, an RNAi Therapeutic for the Treatment of Transthyretin (TTR) Amyloidosis, Mediates Regression of Peripheral TTR Protein" will highlight pre-clinical data for the company's ALN-TTR01 program, which is currently in a Phase I clinical trial in patients with ATTR; and, a poster titled, "ALN-VSP, an Experimental RNAi Therapeutic, Demonstrates Efficacy in Tumor Model Studies" will review pre-clinical data for Alnylam's ALN-VSP program, which is currently in a Phase I clinical trial in patients with advanced solid tumors with liver involvement. Alnylam plans on providing an additional clinical update on the ALN-VSP program by the end of 2010.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics for the treatment of a wide range of disease areas, including respiratory syncytial virus (RSV), liver cancers, TTR-mediated amyloidosis (ATTR), hypercholesterolemia, and Huntington's disease. In addition, Alnylam formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for application in manufacturing processes for biotherapeutic products, including recombinant proteins and monoclonal antibodies. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. Alnylam and Isis are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit http://www.alnylam.com/.

Alnylam Forward-Looking Statement

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, its expectations regarding the development of effective and efficient delivery approaches for RNAi therapeutics, including through delivery of RNAi therapeutics to hepatic stellate cells, and its expectations regarding the progress of its ongoing research and development programs for its RNAi therapeutic candidates, including ALN-VSP, ALN-TTR01, and ALN-PCS, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including Alnylam's ability to continue advancing its delivery efforts, including its efforts around delivery to hepatic stellate cells, discover and develop novel drug candidates, and successfully demonstrate efficacy and safety of its drug candidates, including ALN-VSP and ALN-TTR01, in human clinical trials, as well as those risks more fully discussed in the "Risk Factors" section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.

SOURCE: Alnylam Pharmaceuticals, Inc.

Alnylam Pharmaceuticals, Inc.
Cynthia Clayton (Investors), 617-551-8207
Amanda Sellers (Media), 202-955-6222 x2597


Spice in Curry Could Prevent Liver Damage

ScienceDaily (Oct. 29, 2010) — Curcumin, a chemical that gives curry its zing, holds promise in preventing or treating liver damage from an advanced form of a condition known as fatty liver disease, new Saint Louis University research suggests.

Curcurmin is contained in turmeric, a plant used by the Chinese to make traditional medicines for thousands of years. SLU's recent study highlights its potential in countering an increasingly common kind of fatty liver disease called non-alcoholic steatohepatitis (NASH). Linked to obesity and weight gain, NASH affects 3 to 4 percent of U.S. adults and can lead to a type of liver damage called liver fibrosis and possibly cirrhosis, liver cancer and death.

"My laboratory studies the molecular mechanism of liver fibrosis and is searching for natural ways to prevent and treat this liver damage," said Anping Chen, Ph.D., corresponding author and director of research in the pathology department of Saint Louis University.

"While research in an animal model and human clinical trials are needed, our study suggests that curcumin may be an effective therapy to treat and prevent liver fibrosis, which is associated with non-alcoholic steatohepatitis (NASH)."

High levels of blood leptin, glucose and insulin are commonly found in human patients with obesity and type 2 diabetes, which might contribute to NASH-associated liver fibrosis.

Chen's most recent work tested the effect of curcumin on the role of high levels of leptin in causing liver fibrosis in vitro, or in a controlled lab setting.

"Leptin plays a critical role in the development of liver fibrosis," he said.

High levels of leptin activate hepatic stellate cells, which are the cells that cause overproduction of the collagen protein, a major feature of liver fibrosis. The researchers found that among other activities, curcumin eliminated the effects of leptin on activating hepatic stellate cells, which short-circuited the development of liver damage.

The findings were published in the September issue of Endocrinology.

Bristol-Myers, Gilead Seek to Match AIDS Cocktail Success in Hepatitis C

Bristol-Myers Squibb Co. and Gilead Sciences Inc., makers of the top-selling combination pills for AIDS, are trying to duplicate their success to combat another evasive virus, hepatitis C.

The companies are among about a dozen that are developing drug cocktails more effective, less toxic and easier to take than current therapy. Hints of which blends may work will emerge next week, in research presented at a Boston meeting of the American Association for the Study of Liver Disease.

The pill combinations are designed to cure the liver- destroying hepatitis C virus without using interferon, a decades-old shot that causes a year of flu-like symptoms and works in only half of patients. While the virus outsmarted new mixtures in preliminary tests, study continues because the first blends to succeed will dominate a market that, according to Decision Resources Inc., may total $8 billion a year by 2014.

“We are trying to duplicate the paradigm that revolutionized HIV therapy well over a decade ago, and apply those lessons learned to hepatitis C,” said Ira Jacobson, medical director of the Center for the Study of Hepatitis C, a New York-based program of Rockefeller University, Weill Cornell Medical College, and New York-Presbyterian Hospital. “My belief is if we suppress it profoundly enough, the virus will eventually wither away and be eradicated in the liver.”

The shares of New York-based Bristol-Myers decreased 16 cents to $26.83 at 11:10 a.m. in New York Stock Exchange composite trading. Gilead, of Foster City, California, fell 2 cents to $39.84 in Nasdaq Stock Market composite trading.

200 Million People

About 200 million people worldwide have hepatitis C, an analysis at Dartmouth Medical School in Hanover, New Hampshire, found. The disease often persists as a chronic condition that causes nausea, weakness and exhaustion as it destroys the liver over the course of years or decades.

Interferon, the standard of care when paired with the generic drug ribavirin to increase potency, works by boosting the immune system. Roche Holding AG of Basel, Switzerland sells a version of interferon under the brand name Pegasys, while Merck & Co. of Whitehouse Station, New Jersey sells a form called PegIntron.

Two new hepatitis C options that may be introduced next year are telaprevir, from Cambridge, Massachusetts-based Vertex Pharmaceuticals Inc. and New Brunswick, New Jersey-based Johnson & Johnson, and boceprevir, from Whitehouse Station, New Jersey- based Merck & Co. The drugs are similar to the family of AIDS medicines called protease inhibitors that prevent viruses from replicating. Both are used with interferon and ribavirin.

$3 Billion

The combinations are expected to generate more than $3 billion in sales annually by 2013, with telaprevir accounting for $2.6 billion, said Howard Liang, an analyst at Leerink Swann & Co. in Boston, in a telephone interview.

The new antiviral combinations are oral drugs, not injections, and may have the potential to cure patients who haven’t benefitted from the older products, Liang said.

“Both clinicians and patients would prefer drugs that lack the side effects of interferon and ribavirin,” said Alexandra Makarova, an analyst at Decision Resources, a research company in Burlington, Massachusetts, in a telephone interview. “If the combination of direct antivirals will allow doctors to exclude interferon and ribavirin, it could spoil the party for those regimens.”

Optimal Combination

Research hasn’t identified the optimal oral combination for hepatitis C. Initial reports show treatment with just one pill or low-dose combinations aren’t enough to keep the virus in check, and investigators are building more, and more-powerful, combinations. The U.S. Food and Drug Administration, which initially rejected efforts to study treatments without interferon and ribavirin, has now let trials begin.

The ability to create liver cells from stem cells, breed mice that are better models for hepatitis C, and isolate cells from human livers infected with the virus are making it easier to identify and pull together the best cocktails before they are tested in humans, said Michael Charlton, director of the liver transplant program at the Mayo Clinic in Rochester, Minnesota.

“The door may be opening to more innovative combinations of oral therapies,” said Charlton, who sees a new patient every 30 minutes, on average, when working in Minneapolis. “There is still a tremendous second and third wave of drug combinations that are being explored,” he said in a telephone interview.

Second-Stage Tests

Bristol-Myers will present results at the Boston meeting from second-stage tests combining an experimental protease inhibitor, similar to those used for AIDS, with a pill from new family of virus-fighting medicines. The two ingredients, called BMS-790052 and BMS-650032 stopped working in as little as three weeks. Adding interferon and ribavirin to the two-drug cocktail suppressed the virus for as long as three months.

Gilead will report outcomes from a monthlong study of its experimental protease inhibitor, GS-9256, with a second new drug, GS-9190, which is in a different family of medicines.

Adding ribavirin alone delayed or reduced the breakthrough virus, the study found. Vertex stopped a low-dose combination of telaprevir and its experimental drug VX-222 after the virus broke through during the first month of treatment. A higher-dose combination is undergoing tests.

The combination approach is being pursued by biotechnology companies, among them Pharmasset Inc. of Princeton, New Jersey; Medivir AB of Huddinge, Sweden; Idenix Pharmaceuticals Inc. of Cambridge, Massachusetts; and Inhibitex Inc. of Alpharetta, Georgia.

Merck Developments

Merck is developing several oral hepatitis C drugs internally, while looking for outsiders to become partners on its compounds, said Lisa Pedicone, global director of scientific affairs for the company’s hepatitis C products.

A combination of two oral drugs from Roche and Pharmasset was able to keep the virus in check during an initial 13-day study. The combination includes a protease inhibitor and another medicine polymerase inhibitor.

“We need to be bringing the people who have all these agents together to sit down at the same table,” Charlton said. “It takes someone with deep resources to develop a multidrug cocktail.”

Preliminary data suggest that a new family of medicines known as nucleoside-based polymerase inhibitors, which block an enzyme the virus needs to thrive, may be a key player in the drug combinations, Leerink’s Liang said. Pharmasset and Idenix are among the few companies working with those drugs, making them desirable partners or potential takeover targets, he said.

‘Early Days’

“This is like the early days of HIV,” said Stuart Ray, director of the infectious-diseases fellowship training program at Johns Hopkins University School of Medicine in Baltimore. “We are trying to weigh the safety of getting these drugs when they are first available, against the risk of waiting when we know liver disease is likely to be progressing in all of our patients.”

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.ne t


Olive Oil Protects Liver

Article Date: 29 Oct 2010 - 1:00 PDT

Extra-virgin olive oil can protect the liver from oxidative stress. Researchers writing in BioMed Central's open access journal Nutrition and Metabolism exposed rats to a moderately toxic herbicide known to deplete antioxidants and cause oxidative stress, finding that those rats fed on a diet containing the olive oil were partially protected from the resulting liver damage.

Mohamed Hammami from the University of Monastir, Tunisia and King Saud University, Riyadh, Saudi Arabia, worked with a team of researchers to carry out the experiments in a group of 80 rats. He said, "Olive oil is an integral ingredient in the Mediterranean diet. There is growing evidence that it may have great health benefits including the reduction in coronary heart disease risk, the prevention of some cancers and the modification of immune and inflammatory responses. Here, we've shown that extra virgin olive oil and its extracts protect against oxidative damage of hepatic tissue".

The researchers separated the rats into a control group, an olive oil group, and 6 groups that were exposed to the herbicide '2,4-Dichlorophenoxyacetic acid' with or without either whole olive oil, or one of two oil extracts the hydrophilic fraction or the lipophilic fraction. All rats given the herbicide showed signs of significant liver damage. However, extra virgin olive oil and hydrophilic fraction intake induced a significant increase in antioxidant enzyme activity and a decrease in markers of liver damage.

Speaking about the results, Hammami said, "The hydrophilic fraction of olive oil seems to be the effective one in reducing toxin-induced oxidative stress, indicating that hydrophilic extract may exert a direct antioxidant effect on hepatic cells. However, more detailed studies about the effect of antioxidant compounds separately and/or their interactions are necessary to substantiate these observations".

Sources: BioMed Central Limited, AlphaGalileo Foundation.


Medivir to Hold Conference Call and Breakfast Meeting to Discuss TMC435 Data Presented at the 61st AASLD Meeting

- Data Includes a Late-breaking Oral Presentation of 24-Week Interim Data of the TMC435 phase 2b PILLAR Study -

HUDDINGE, Sweden, Oct 29, 2010 (BUSINESS WIRE) -- Regulatory News:Medivir AB (omx:MVIR), a research-based specialty pharmaceutical company focused on infectious diseases will hold a conference call for analysts and investors and a breakfast meeting in Boston, USA, for US based investors, analysts and media on Tuesday 2nd November 2010. Both events will discuss Medivir's lead development product TMC435, a once-daily hepatitis C protease inhibitor in phase 2b development, which is being jointly developed by Medivir and Tibotec Pharmaceuticals.

Hosts, Rein Piir (CFO/IR), Bertil Samuelsson, (CSO) and Asa Rosenquist, (Director Medicinal Chemistry) will provide an update on the development of TMC435, which is the subject of four posters and one oral presentation being presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place from 29 October to 2 November 2010 in Boston, USA.

The details are as follows:

Conference Call For Analysts and Investors:

Tuesday, November 2, 2010 at 6.30am EDT / 10.30am GMT / 11.30am CET Please register for the conference call online at: http://invite.taylor-rafferty.com/_Medivir/ConferenceCall

You will receive the dial-in and replay numbers for the conference call following your online registration.

Breakfast Meeting for US based Analysts, Investors and Media

Tuesday November 2, 2010 at 7:00am -- 8.30am EDT (breakfast will be served between 7:00am -- 7.30am EDT) Venue: Colonnade Hotel, Braemore & Kenmore Room 120 Huntington Avenue, Boston Please confirm your participation by registering on-line: http://invite.taylor-rafferty.com/_Medivir/Breakfast/default.htm

For enquiries please contact: Lindsey Neville at M:Communications on +44 (0)20 7920 2333 or Jason Marshall on +1 212 889 4350 or email Neville@mcomgroup.com

Accepted titles for Abstracts to be presented at the 2010 AASLD meeting are as follows:

Late Breaker Oral Presentation for presentation at Monday 1 Nov. 17:45 (EST): LB-5. "Efficacy and safety of TMC435 in combination with peginterferon a-2a and ribavirin in treatment-naive genotype-1 HCV patients: 24-week interim results from the PILLAR study."

Poster Presentations:

278. "In vitro studies investigating the mechanism of interaction between TMC435 and hepatic transporters." To be presented: Saturday 30 Oct, 14:00 (EST)

812. "Virologic analysis of genotype-1-infected patients treated with once-daily TMC435 during the Optimal Protease inhibitor Enhancement of Response to Therapy (OPERA)-1 study." To be presented: Sunday 31 Oct, 08:00 (EST)

895. "A Phase IIa, open-label study to assess the antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2--6." To be presented: Sunday 31 Oct, 08:00 (EST)

1873. "Pharmacokinetic-pharmacodynamic analyses of TMC435 in patients infected with Hepatitis C Virus (HCV) genotypes 2 to 6." To be presented: Tuesday 2 Nov, 07:00 (EST).

About Medivir

Medivir is a 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. Medivir has a strong R&D portfolio and has recently launched its first product Xerese(TM)/Xerclear(R). Medivir's key pipeline asset, TMC435, a protease inhibitor, is in phase 2b clinical development for Hepatitis C and is partnered with Tibotec Pharmaceuticals.

Xerese(TM)/Xerclear(R) is an innovative treatment for cold sores, which has been approved in both the US and Europe. It is partnered with GSK to be sold OTC in Europe and Russia and with Meda in North America. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.

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

About TMC435 clinical trial programs

TMC435 is a once daily protease inhibitor jointly developed by Medivir and Tibotec Pharmaceuticals to treat hepatitis C virus infections. TMC435 is currently being studied in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in genotype 1 (G1) treatment-naive and in G1 patients that failed previous IFN-based treatment. TMC435 is planned to enter phase 3 studies early 2011.

PILLAR Study (TMC435-C205)

TMC435-C205 is an ongoing randomized double-blind global phase 2b study in 386 genotype-1 treatment-naive patients. It evaluates once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.

ASPIRE Study (TMC435-C206)

TMC435-C206 is an ongoing randomized double-blind global phase 2b study in 463 genotype-1 treatment-experienced patients. It evaluates once daily treatment of TMC435 in with different doses of given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.


TMC435-C215 is an ongoing Japanese phase 2b study in 92 genotype-1 treatment-naive patients. It evaluates once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.

Opera-2 (TMC435-C202)

TMC435-C202 is a completed phase 2a study in treatment-naive genotype 2 to 6 HCV patients. It is a once daily treatment of TMC435 during seven days, at 200 mg. Subsequently, patients could continue with Standard of Care treatment consisting of pegylated interferon and ribavirin upon agreement with the study doctor.

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 WHO 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.

This information was brought to you by Cision http://www.cisionwire.com/

SOURCE: Medivir

CFO & VP Investor Relations Office:
Rein Piir, +46 8 546 831 23
Mobile: +46 708 537 292

Mary-Jane Elliott/Emma Thompson/Amber Bielecka, +44(0)20 7920 2330
Jason Marshall, +1 212 897 5497


High hepatitis C mortality and low clearance rates in HIV/HCV-co-infected patients in France

Michael Carter

Published: 29 October 2010

Mortality rates are high among French patients co-infected with HIV and hepatitis C, investigators report in BMC Infectious Diseases. Over 40% of deaths were directly attributable to hepatitis C.

Only a fifth of patients with hepatitis C genotype 1 and 36% of those with genotype 4 treated since 2005 had a successful response to treatment, a finding broadly in line with the results of clinical trials in coinfected people. Only 21% of patients in the French cohort had HCV genotypes 2 or 3, which have proved more likely to respond to treatment.

A low overall success rate was seen in individuals who received a second course of treatment for hepatitis C.

However, treatment for depression not only improved mood but also fatigue and other aspects of health.

Approximately a quarter of HIV-positive patients in France are co-infected with hepatitis C. Investigators wanted to gain a better understanding of these patients, and in 2005 established ANRS CO 13 HEPAVIH cohort.

The investigators describe the cohort as “a unique nation-wide collaboration of HIV treatment, infectious diseases, internal medicine and hepatology centres.”

Between 2006 and 2008 a total of 1175 adults were recruited to the cohort. All were HIV-positive, 1048 had chronic hepatitis C infection and 127 had had a sustained response to hepatitis C therapy.

The patients’ median age was 45 years, 70% were men, their median CD4 cell count was 442 cells/mm3 and 68% had an undetectable HIV viral load.

Most of the patients (71%) were infected with hepatitis C through injecting drug use and the median time since diagnosis of hepatitis C was ten years. The median hepatitis C viral load was 6.2 logUI/ml.

A variety of tests were used to assess the extent of liver damage caused by hepatitis C. The proportion of patients diagnosed with cirrhosis varied according to which test was used.

FibroTest detected cirrhosis in 46% of patients, FibroScan in 30% and a liver biopsy in 27%. Nevertheless, all the tests had a high positive predictive value for cirrhosis diagnosis.

At the time of enrolment to the cohort, 72% of patients were taking antiretroviral therapy. The majority of patients (58%) were taking a combination of drugs based on a ritonavir-boosted protease inhibitor.

Overall, 51% of patients had received hepatitis C therapy. Most (35)% received this treatment before they entered the cohort.

Outcome data were available for 127 patients who had received hepatitis C treatment after entering the cohort.

A total of 32% had a sustained virologic response. The clearance rate was 34% for those taking anti-hepatitis C drugs for the first time, and fell to 27% for individuals taking a second course of therapy.

Outcomes were also analysed according to hepatitis C genotype. Only 20% of patients infected with genotype 1 had a successful response to therapy, and 36% of those with genotype 4 cleared the infection.

By January 2010, a total of 13 new cases of cirrhosis had been diagnosed. All were in patients with chronic hepatitis C. There were nine new cases of liver cancer, three of which were in patients who had had a sustained response to therapy with anti-hepatitis C drugs.

There were 49 deaths, and 41% were attributed to hepatitis C.

The investigators calculated that the rate of severe hepatitis C-related events was 2 per 100 person years of follow-up.

Event rates were notably higher in patients with cirrhosis (7 vs. 0.35 per 100 person years). The investigators note that this was expected, but nevertheless emphasised the importance of accurately diagnosing cirrhosis. All three types of tests detected over 99% of cases of cirrhosis.

A low baseline CD4 cell count (below 200 cells/mm3) also significantly increased the risk of a serious hepatitis C-related outcome (5.5 vs. 1.4 per 100 person years; p = 0.002). Patients co-infected with hepatitis C are especially recommended to start antiretroviral therapy when their CD4 cell count is around 350 cells/mm3.

Using information gathered from questionnaires completed by the patients, the investigators found that treating depression not only improved mood, but also had an impact on fatigue, as well as boosting cognitive, physical and social functioning.

The researchers conclude that cohorts such as theirs “will be critical to address future clinical and public health questions of chronic diseases of infectious origin”.


Loko M-A et al. The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): Early findings, 2006-2010. BMC Infectious Diseases, 10: 303doi:10.1186/1471-2334-10-303, 2010 (click here for access to article text).


Management of Hepatitis B: A longitudinal national survey - impact of the Canadian Hepatitis B Consensus Guidelines

Original Articles

The Canadian Journal of Gastroenterology
September 2010, Volume 24 Issue 9: 537-542
P Marotta, K Lucas

BACKGROUND: The Canadian Association for the Study of the Liver, and The Association of Medical Microbiology and Infectious Diseases Canada, jointly developed the Canadian Chronic Hepatitis B (HBV) Consensus Guidelines to assist practitioners involved in the management of this complex disease. These guidelines were published in The Canadian Journal of Gastroenterology in June 2007 and distributed to all Canadian gastroenterologists and hepatologists.

OBJECTIVE: To assess the degree to which Canadian specialist physicians were able to incorporate the recommendations from the Canadian HBV Consensus Guidelines into their daily practice.

METHODS: A 30 min telephone survey probing the management strategies of 80 key HBV specialists was completed on three occasions, eight months apart, to longitudinally assess the impact of the Canadian HBV Consensus Guidelines on the management of HBV. The questionnaire detailed HBV practice patterns, the impact of the Canadian HBV Consensus Guidelines on clinical practice and HBV management.

RESULTS: The majority of specialists incorporated many of the published recommendations outlined in the Canadian HBV Consensus Guidelines into their daily practice for patients with HBV. However, because public drug coverage is a major hurdle in the management of HBV, patients are provided markedly different HBV treatments depending on whether they have public or private drug insurance coverage.

CONCLUSIONS: The management of HBV is growing in complexity and continues to evolve rapidly. The Canadian HBV Consensus Guidelines have served as a valuable tool for many physicians in the management of HBV. However, effective treatment algorithms continue to be rendered irrelevant by restrictive drug coverage issues. Coverage for effective therapies and, therefore, management of HBV, differs widely across Canada depending on therapy reimbursement criteria rather than patient characteristics.