Two new studies examine non-invasive ways to determine liver fibrosis and cirrhosis. An enhanced version of the Original European Liver Fibrosis panel was found to have good diagnostic accuracy for fibrosis in patients with non-alcoholic fatty liver disease. Conversely, transient elastography was unreliable for detecting cirrhosis in patients with acute liver damage. The studies are published in the February issue of Hepatology, a journal by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). The articles are also available online at Wiley Interscience.

Liver biopsy is the undisputed best way to assess liver fibrosis or cirrhosis; however, it is an invasive procedure that can cause rare, but potentially life threatening complications. Researchers have been seeking less invasive ways to diagnose liver disease, developing and testing clinical tools, like the Original European Liver Fibrosis Panel and transient elastography.

Researchers led by William Rosenberg in the United Kingdom, sought to validate the Original European Liver Fibrosis panel and consider a simplification that removed age as a factor yielding the Enhanced Liver Panel. They also tested the diagnostic performance of the ELF panel with the addition of the following simple markers: age, BMI, presence of diabetes/impaired fasting glucose, AST/ALT ratio, platelets, and albumin.

They recruited 196 patients with non-alcoholic fatty liver disease from two separate centers and tested the diagnostic accuracy of the new panels. They found that the Enhanced Liver Fibrosis panel detected severe fibrosis, moderate fibrosis and no fibrosis at AUCs of .90, .82, and .76 respectively. The diagnostic accuracy of the ELF panel plus simple markers was .98, .93 and .84 respectively. They report that using either panel could eliminate the need for liver biopsy in diagnosing severe fibrosis in more than 80 percent of cases.

“The ELF panel has good diagnostic accuracy in an independent validation cohort of patients with NAFLD,” the authors conclude. “The addition of established simple markers augments the diagnostic performance across different stages of fibrosis, which will potentially allow superior stratification of patients with NAFLD for emerging therapeutic strategies.”

Meanwhile, researchers in Germany led by Abdurrahman Sagir used transient elastography - Fibroscan (FS) - to measure liver stiffness in 20 patients presenting with acute hepatitis. In 15 (75 percent) of the patients, the test showed liver stiffness values that suggested cirrhosis. However, none of these patients showed any signs of cirrhosis in a physical exam, on ultrasound, or in liver histology.

“Liver stiffness measurement by FS in patients with acute liver damage overestimate the real stage of fibrosis and may erroneously suggest the presence of liver cirrhosis,” the authors report. The stiffness may relate to hepatocyte swelling, cholestasis, or infiltrates of inflammatory cells in the inflamed liver, they suggest.

“FS results need to be interpreted with caution in patients with acute liver damage and high values of liver stiffness do not predict the simultaneous presence of cirrhosis in these patients,” they conclude.

Both studies offer new information on the ability of non-invasive methods to diagnose liver disease, though further studies are needed to advance our understanding of these diagnostic tools.

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Article: “Non-invasive markers of fibrosis in non-alcoholic fatty liver disease: validating the European Liver Fibrosis panel and exploring simple markers.” Guha, Indra Neil; Parkes, Julie; Roderick, Paul; Chattopadhyay, Dipanker; Cross, Richard; Harris, Scott; Kaye, Philip; Burt, Alastair; Ryder, Steve; Aithal, Guruprasad; Day, Christopher; Rosenberg, William. Hepatology; February 2008.

Article: “Transient elastography is unreliable for detection of cirrhosis in patients with acute liver damage.” Sagir, Abdurrahman; Erhardt, Andreas; Schmitt, Marcus; Haussinger, Dieter. Hepatology; February 2008.

Source: Amy Molnar
Wiley-Blackwell

Tiny molecules that help cells regulate which proteins they make might one day help doctors predict which liver-cancer patients are likely to live longer than others, new research suggests.

Researchers compared levels of molecules called microRNA in tumor cells and adjacent nontumor cells from liver-cancer patients, most of whom also had hepatitis and cirrhosis.

The study found that patients with poor disease-free survival had low overall levels of 19 particular microRNAs compared with those showing better survival after 16 years of follow-up.

The work was led by researchers at the Ohio State University Comprehensive Cancer Center in collaboration with investigators at the Mayo Clinic and the University of Oklahoma Health Sciences Center.

The study is published in the journal Clinical Cancer Research.

“The findings must be verified in larger groups of patients, but they suggest that we might improve survival in some liver-cancer cases by adding back those microRNAs as a drug,” says principal investigator Thomas D. Schmittgen, associate professor of pharmacy and a researcher with Ohio State’s Comprehensive Cancer Center.

But that possibility will require years of additional laboratory and preclinical research, Schmittgen says.

Liver cancer, or hepatocellular carcinoma, is the third most common cause of cancer death worldwide, killing some 662,000 people in 2007, according to the World Health Organization. The disease is more common in men and is usually caused by hepatitis infection or cirrhosis of the liver.

For this study, Schmittgen and his collaborators examined specimens from 43 liver tumors, 28 of which were paired with nearby nontumor tissue, and specimens from six normal livers. Two-thirds of the cancerous livers also had hepatitis and cirrhosis.

The researchers examined the levels of 196 different microRNAs in liver-cancer cells vs. nearby noncancer cells, and in liver cells with hepatitis and cirrhosis vs. healthy cells.

Both comparisons showed interesting differences in microRNA levels, but the most important finding came when the researchers looked for a correlation between cancer-cell microRNA levels and disease-free survival times in 25 patients for whom disease-free survival data was available.

The analysis showed that patients with poor survival had generally lower levels of 19 particular microRNAs than did patients with significantly better survival.

“This may also be a good clue as to which microRNAs are most important in liver cancer,” Schmittgen says.

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Funding from the National Cancer Institute, the Richard M. Schulze Family Foundation and the Miles and Shirley Fiterman Center for Digestive Diseases at the Mayo Clinic supported this research.

Source: Darrell E. Ward
Ohio State University Medical Center

MIGENIX Inc. (TSX: MGI, OTC: MGIFF), a clinical-stage developer of drugs for infectious diseases, will add a 600mg celgosivir combination therapy arm to its currently enrolling Phase II viral kinetics study in hepatitis C virus (”HCV”) treatment-naive patients. The protocol amendment to this study has received Health Canada and Institutional Review Board (IRB) approvals. The purpose of this new treatment arm is to assess 600mg celgosivir (an oral alpha glucosidase I inhibitor) for tolerability, pharmacokinetics and viral kinetics when combined with the standard of care drugs, pegylated interferon plus ribavirin, as compared to the standard of care drugs alone and to 400mg celgosivir plus the standard of care for up to 12 weeks of therapy.

AnnKatrin Petersen, M.D., VP Clinical Development for MIGENIX commented, “The favorable tolerability experienced to date with 400mg per day of celgosivir in triple combination with pegylated interferon plus ribavirin, along with the clinically significant benefit demonstrated in our previous non-responder study, gives us confidence that increasing the dose to 600mg per day in combination therapy is an important development step for the optimization and advancement of celgosivir.”

The currently enrolling Phase II viral kinetics study is a 12-week randomized, active-controlled study initially planned to enroll up to 20 patients in two treatment arms: (i) celgosivir (400mg once daily) plus peginterferon alfa-2b plus ribavirin (”PRC”); and (ii) peginterferon alfa-2b plus ribavirin (”PR”). Tolerability, pharmacokinetics and viral kinetics are being evaluated in the trial. The approved protocol amendment allows for the addition of a 600mg once daily dosing arm and the flexibility to increase the total number of patients in the study up to 50. With 15 patients enrolled to date, it is planned that approximately six additional patients will be enrolled, all in the new 600 mg arm. Results from the study are expected to be reported in the third calendar quarter 2008.

Jim DeMesa, M.D., President and CEO of MIGENIX added, “With results from this study expected in the third quarter 2008, we now have another near-term clinical milestone. Additional key clinical milestones include Omigard Phase III results for preventing catheter-related infections (CLIRS study) expected by our partner, Cadence Pharmaceuticals, in the second half of 2008 (enrollment to be completed in the second quarter) and Cutanea Life Sciences, our partner in the CLS001 rosecea product, planning to advance CLS001 to Phase III.”

About Celgosivir (MX-3253)

Celgosivir, an oral inhibitor of alpha-glucosidase I, is currently the only anti-HCV drug in clinical development which acts on host-directed glycosylation. In preclinical studies, celgosivir has shown in vitro synergy with various interferons on the market or in development including Pegasys, PEG-Intron, Infergen, Alferon and IFN-omega (with or without ribavirin) and other drugs in development for the treatment of HCV (e.g. polymerase inhibitors) and therefore could have the potential to be included as part of many combination therapeutic approaches to improve efficacy in future anti-HCV therapies.

Results announced in April 2007 from a Phase II study demonstrated a clinically significant benefit when celgosivir was added to the standard of care in non-responder patients. Interim results from the first 10 patients in the current viral kinetics study who had completed 4-weeks of therapy were reported in December 2007. Detailed analysis of data from these two studies, and an extension protocol designed to provide expanded access to the non-responder patients, provided the rationale for increasing the dose of celgosivir from 400mg per day to 600mg per day in combination therapy as the next step for the optimization and advancement of celgosivir.

About HCV

HCV, the most common chronic blood-borne infection in the United States, causes inflammation of the liver and may progress to more serious complications such as cirrhosis of the liver, liver cancer and death. Approximately 2.7 million people in the United States are chronically infected with HCV, and the Centers for Disease Control and Prevention (CDC) estimates that by the year 2010, the number of deaths attributed annually to HCV could surpass that due to HIV/AIDS in the US. Worldwide, the World Health Organization estimates that 170 million individuals have chronic HCV infection, with 3 to 4 million new infections each year.

Therapy for HCV currently employs a drug combination approach, which is anticipated to continue in the future. The current standard of care for treatment-naive chronic hepatitis C is pegylated interferon combined with ribavirin (PR), which fails to provide a satisfactory outcome for approximately 50% of patients infected with HCV genotype 1 (the most prevalent genotype in North America).

About MIGENIX

MIGENIX is committed to advancing therapy, improving health, and enriching life by developing and commercializing drugs primarily in the area of infectious diseases. The Company’s clinical programs include drug candidates for the treatment of chronic hepatitis C infections (Phase II and preclinical), the prevention of catheter-related infections (Phase III) and the treatment of dermatological diseases (Phase II). MIGENIX is headquartered in Vancouver, British Columbia, Canada with US operations in San Diego, California. Additional information can be found at http://www.migenix.com.

FORWARD-LOOKING STATEMENTS

This news release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995, and forward-looking information within the meaning of applicable securities laws in Canada, (collectively referred to as “forward-looking statements”). Statements, other than statements of historical fact, are forward-looking statements and include, without limitation, statements regarding our strategy, future operations, timing and completion of clinical trials, prospects, plans and objectives of management. The words “anticipates”, “believes”, “budgets”, “could”, “estimates”, “expects”, “forecasts”, “intends”, “may”, “might”, “plans”, “projects”, “schedule”, “should”, “will”, “would” and similar expressions are often intended to identify forward-looking statements, which include underlying assumptions, although not all forward-looking statements contain these identifying words. By their nature, forward-looking statements involve numerous assumptions, known and unknown risks and uncertainties, both general and specific, that contribute to the possibility that the predictions, forecasts, projections and other things contemplated by the forward-looking statements will not occur.

Although our management believes that the expectations represented by such forward-looking statements are reasonable, there is significant risk that the forward-looking statements may not be achieved, and the underlying assumptions thereto will not prove to be accurate. Forward-looking statements in this news release include, but are not limited to, statements concerning our expectations for: increasing the celgosivir dose to 600mg being an important development step for the optimization and advancement of celgosivir; our plans to add approximately six patients at 600mg dose in the celgosivir Phase II viral kinetics study and having results from the study in the third quarter 2008; Cadence Pharmaceuticals completing enrollment in the CLIRS trial in the second quarter of 2008, with results available in the second half of 2008; and Cutanea Life Sciences’ plans to advance omiganan for the treatment of rosacea to Phase III clinical development.

With respect to the forward-looking statements contained in this news release, we have made numerous assumptions regarding, among other things: our ability to enroll approximately six patients at the 600mg dose in the celgosivir Phase II viral kinetics study and having results from the study in the third quarter of 2008; Cadence’s ability to enroll sufficient patients to complete the Omigard CLIRS trial; the adequacy of the CLIRS trial design to generate data that are deemed sufficient by regulatory authorities to support potential regulatory filings, including an NDA, for Omigard; Cutanea’s ability to manage, fund and advance omiganan for dermatological applications into Phase III, the adequacy of Cutanea’s Phase II results for regulatory authorities to support advancing to Phase III; our ability to manage licensing opportunities; and our ability to initiate, fund and complete non-clinical studies, clinical studies, manufacturing and all ancillary activities within our expected timelines.

Actual results or events could differ materially from the plans, intentions and expectations expressed or implied in any forward-looking statements, including the underlying assumptions thereto, as a result of numerous risks, uncertainties and other factors including: dependence on corporate collaborations; potential delays; uncertainties related to early stage of technology and product development; uncertainties as to the requirement that a drug be found to be safe and effective after extensive clinical trials and the possibility that the results of such trials, if completed, will not establish the safety or efficacy of our products; uncertainties as to future expense levels and the possibility of unanticipated costs or expenses or cost overruns; the possibility that opportunities will arise that require more cash than presently anticipated and other uncertainties related to predictions of future cash requirements; and other risks and uncertainties which may not be described herein. Certain of these factors and other factors are described in detail in the Company’s Annual Information Form and Annual Report on Form 20-F for and other filings with the Canadian securities regulatory authorities and the U.S. Securities & Exchange Commission.

Forward-looking statements are based on our current expectations and MIGENIX assumes no obligations to update such information to reflect later events or developments.

MIGENIX Inc.
http://www.migenix.com

Patients with chronic hepatitis C (HCV) infection should not use marijuana (cannabis) daily, according to a study published in Clinical Gastroenterology and Hepatology, the official journal of the American Gastroenterological Association (AGA) Institute. Researchers found that HCV patients who used cannabis daily were at significantly higher risk of moderate to severe liver fibrosis, or tissue scarring. Additionally, patients with moderate to heavy alcohol use combined with regular cannabis use experienced an even greater risk of liver fibrosis. The recommendation to avoid cannabis is especially important in patients who are coinfected with HCV/HIV since the progression of fibrosis is already greater in these patients.

“Hepatitis C is a major public health concern and the number of patients developing complications of chronic disease is on the rise,” according to Norah Terrault, MD, MPH, from the University of California, San Francisco and lead investigator of the study. “It is essential that we identify risk factors that can be modified to prevent and/or lessen the progression of HCV to fibrosis, cirrhosis and even liver cancer. These complications of chronic HCV infection will significantly contribute to the overall burden of liver disease in the U.S. and will continue to increase in the next decade.”

This is the first study that evaluates the relationship between alcohol and cannabis use in patients with HCV and those coinfected with HCV/HIV. It is of great importance to disease management that physicians understand the factors influencing HCV disease severity, especially those that are potentially modifiable. The use and abuse of both alcohol and marijuana together is not an uncommon behavior. Also, individuals who are moderate and heavy users of alcohol may use cannabis as a substitute to reduce their alcohol intake, especially after receiving a diagnosis like HCV, which affects their liver.

Researchers found a significant association between daily versus non-daily cannabis use and moderate to severe fibrosis when reviewing this factor alone. Other factors contributing to increased fibrosis included age at enrollment, lifetime duration of alcohol use, lifetime duration of moderate to heavy alcohol use and necroinflammatory score (stage of fibrosis). In reviewing combined factors, there was a strong (nearly 7-fold higher risk) and independent relationship between daily cannabis use and moderate to severe fibrosis. Gender, race, body mass index, HCV viral load and genotype, HIV coinfection, source of HCV infection, and biopsy length were not significantly associated with moderate to severe fibrosis.

Of the 328 patients screened for the study, 204 patients were included in the analysis. The baseline characteristics of those included in the study were similar to those excluded with the exception of daily cannabis use (13.7 percent of those studied used cannabis daily versus 6.45 percent of those not included). Patients who used cannabis daily had a significantly lower body mass index than non-daily users (25.2 versus 26.4), were more likely to be using medically prescribed cannabis (57.1 percent versus 8.79 percent), and more likely to have HIV coinfection (39.3 percent versus 18.2 percent).

The prevalence of cannabis use amongst adults in the U.S. is estimated to be almost 4 percent. Regular use has increased in certain population subgroups, including those aged 18 to 29.

Hepatitis is an inflammation of the liver. Hepatitis C is the most common form of hepatitis and infects nearly 4 million people in the U.S., with an estimated 150,000 new cases diagnosed each year. While it can be spread through blood transfusions and contaminated needles, for a substantial number of patients, the cause is unknown. This form of viral hepatitis may lead to cirrhosis, or scarring, of the liver. Coinfection of hepatitis C in patients who are HIV positive is common; about one quarter of patients infected with HIV are infected with hepatitis C. The majority of these patients, 50 to 90 percent, were infected through injection drug use. Hepatitis C ranks with alcohol abuse as the most common cause of chronic liver disease and leads to about 1,000 liver transplants yearly in the U.S.

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About the AGA Institute

The American Gastroenterological Association (AGA) is dedicated to the mission of advancing the science and practice of gastroenterology. Founded in 1897, the AGA is one of the oldest medical-specialty societies in the United States. Comprised of two non-profit organizations - the AGA and the AGA Institute - our more than 16,000 members include physicians and scientists who research, diagnose and treat disorders of the gastrointestinal tract and liver. The AGA, a 501(c6) organization, administers all membership and public policy activities, while the AGA Institute, a 501(c3) organization, runs the organization’s practice, research and educational programs. On a monthly basis, the AGA Institute publishes two highly respected journals, Gastroenterology and Clinical Gastroenterology and Hepatology. The organization’s annual meeting is Digestive Disease Week®, which is held each May and is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. For more information, please visit http://www.gastro.org/.

About Clinical Gastroenterology and Hepatology

The mission of Clinical Gastroenterology and Hepatology is to provide readers with a broad spectrum of themes in clinical gastroenterology and hepatology. This monthly peer-reviewed journal includes original articles as well as scholarly reviews, with the goal that all articles published will be immediately relevant to the practice of gastroenterology and hepatology. For more information, visit http://www.cghjournal.org/.

Source: Aimee Frank
American Gastroenterological Association

Human Genome Sciences Inc. (Nasdaq: HGSI) announced that it will modify the dosing in one arm of each of its ACHIEVE clinical trials of Albuferon(R) (albinterferon alfa-2b) for chronic hepatitis C. Patients in the Phase 3 trials who have been receiving the 1200-mcg dose will now receive a 900-mcg dose. The change is based on recommendations made by the studies’ independent Data Monitoring Committee (DMC). HGS continues to expect to have all Phase 3 data available by spring 2009 to support the filing of global marketing authorization applications by fall 2009.

“For some time we have viewed the 900-mcg dose administered every two weeks as the most likely marketed dose of Albuferon,” said H. Thomas Watkins, President and Chief Executive Officer, HGS. “The 900-mcg dose demonstrated comparable efficacy and safety to Pegasys in Phase 2 - with half the injections, improvements in quality of life and fewer missed days of work during treatment. We continue to believe that Albuferon could become the market-leading interferon for the treatment of hepatitis C if Phase 2 900-mcg results are confirmed in Phase 3.”

Consistent with its charter, the DMC routinely reviews all adverse events for each treatment group. Serious pulmonary adverse events, while expected and rare during interferon therapy, were higher in the treatment group receiving 1200-mcg Albuferon administered every two weeks. The DMC did not express any safety concerns about the 900-mcg dose of Albuferon. Based on the DMC’s review and conclusions, the patients receiving a 1200-mcg dose of Albuferon will be moved to the 900-mcg dose.

“The independent Data Monitoring Committee for these trials assessed risk/benefit based on review of unblinded safety and efficacy data for all doses, to which HGS remains blinded, and concluded that dosing should be modified for patients receiving the 1200-mcg dose of Albuferon every two weeks,” said David C. Stump, M.D., Executive Vice President, Research and Development, HGS. “HGS and Novartis have chosen to accept the Data Monitoring Committee’s recommendation to modify dosing in the 1200-mcg arms in these studies. We are pleased that after careful review by the Data Monitoring Committee, the safety and continued dosing of 900-mcg Albuferon was affirmed. Thus, all Albuferon patients will now receive 900-mcg every two weeks.”

About Albuferon

Albuferon is a novel, longer-acting form of interferon alpha that was created using the proprietary HGS albumin-fusion technology. Recombinant interferon alpha is approved for the treatment of hepatitis C, hepatitis B and a broad range of cancers. HGS is currently conducting two pivotal Phase 3 clinical trials of Albuferon in combination with ribavirin: ACHIEVE 1 in treatment-naive patients with genotype 1 chronic hepatitis C, and ACHIEVE 2/3 in treatment-naive patients with genotype 2 or 3 chronic hepatitis C.

Albuferon requires half as many injections as Pegasys, and Phase 2 clinical results suggest that Albuferon could offer efficacy and safety comparable to Pegasys, in addition to the potential for improved quality of life and fewer lost days of work on treatment. Based on these data, HGS believes that Albuferon could become the market-leading interferon for the treatment of hepatitis C if Phase 2 results are confirmed in Phase 3 trials.

Albuferon is being developed by HGS and Novartis under a worldwide co- development and commercialization agreement entered into in June 2007. ACHIEVE 1 and ACHIEVE 2/3, assuming that they are successful, will provide the pivotal data to support global marketing authorization applications for Albuferon, which HGS and Novartis expect to file by fall 2009.

About Human Genome Sciences

The mission of HGS is to apply great science and great medicine to bring innovative drugs to patients with unmet medical needs.

The HGS clinical development pipeline includes novel drugs to treat hepatitis C, lupus, anthrax disease, cancer and other immune-mediated diseases. The Company’s primary focus is rapid progress toward the commercialization of its two key lead drugs, Albuferon for hepatitis C and LymphoStat-B(R) (belimumab) for lupus. Phase 3 clinical trials of both drugs are ongoing.

ABthrax(TM) (raxibacumab) is in late-stage development for the treatment of anthrax disease, and the Company is on track to begin the delivery in 2008 of 20,000 doses of ABthrax to the Strategic National Stockpile under a contract entered into with the U.S. Government in June 2007. Other HGS drugs in clinical development include two TRAIL receptor antibodies for the treatment of cancer. AEG40826, a small-molecule antagonist of IAP (inhibitor of apoptosis) proteins, is expected to enter Phase 1 clinical trials for the treatment of cancer in early 2008.

For more information about HGS, please visit the Company’s web site at http://www.hgsi.com. Health professionals or patients interested in Albuferon clinical trials or other studies involving HGS products may inquire via the “Contact Us” section of the Company’s web site, http://www.hgsi.com/products/request.html

HGS, Human Genome Sciences, ABthrax, Albuferon and LymphoStat-B are trademarks of Human Genome Sciences, Inc.

Safe Harbor Statement

This announcement contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements are based on Human Genome Sciences’ current intent, belief and expectations. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Actual results may differ materially from these forward-looking statements because of the Company’s unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials, the Company’s ability to develop and commercialize products, its dependence on collaborators for services and revenue, its substantial indebtedness and lease obligations, its changing requirements and costs associated with facilities, intense competition, the uncertainty of patent and intellectual property protection, the Company’s dependence on key management and key suppliers, the uncertainty of regulation of products, the impact of future alliances or transactions and other risks described in the Company’s filings with the Securities and Exchange Commission. In addition, the Company will continue to face risks related to animal and human testing, to the manufacture of ABthrax and to FDA concurrence that ABthrax meets the requirements of the ABthrax contract. If the Company is unable to meet the product requirements associated with the ABthrax contract, the U.S. government will not be required to reimburse the Company for the costs incurred or to purchase any ABthrax doses. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today’s date. Human Genome Sciences undertakes no obligation to update or revise the information contained in this announcement whether as a result of new information, future events or circumstances or otherwise.

Human Genome Sciences, Inc.
http://www.hgsi.com

For the first time, a 3D animation has been used to inform patients about complex scientific information as part of the informed consent procedure for a Phase 1 clinical trial. Arkitek Studios, specialists in the development of visual content for science, technology and education, created the animation to help patients understand the scientific rationale behind the experimental gene silencing therapy for Hepatitis B being developed by Nucleonics, Inc.

Nucleonics announced on January 11, 2008 that the company had begun treating patients in a Phase 1 human safety study of its experimental RNA interference (RNAi), NUC B1000, a treatment for chronic Hepatitis B virus (HBV) infection. The experimental therapy uses a technology known as expressed interfering RNA to simultaneously target four different sequences of the HBV genome, resulting in a potent antiviral effect designed for efficacy against all HBV genotypes, including drug resistant strains. Additionally, unlike currently available HBV therapeutics, NUC B1000 is designed to specifically reduce viral antigen load in addition to viral titer, thereby reducing the destructive effects of hepatitis and increasing the potential for resolution of viral infection.

In preparing for the clinical study, an Institutional Review Board at one trial site had specifically suggested that Nucleonics use computer animation to explain the product and its method of action to patients, rather than relying on physicians to explain the relatively complex science underlying the treatment. The use of a computer animation would help to ensure that the technology was presented to each patient in a consistent manner throughout the conduct of the clinical trial.

“Informed consent has evolved of necessity in recent years - patients expect targeted information and feel they deserve to understand the technology surrounding the particular therapy they’re being asked to test.” explains Beth Anderson, CEO of Arkitek. “Most physicians haven’t been exposed to this information either, therefore the burden of explanation falls on the company. With time and resources at a premium, this method offers the best way to address questions or concerns patients may have.”

Arkitek Studios, located in Seattle, Washington, specializes in visual content for science, technology and education. For more information, please visit http://www.arkitek.com or http://www.arkitek.com/nucleonics.html.

Liver cancer is the fifth most common cancer in the world with a poor prognosis. About three quarters of the cases of liver cancer are found in Southeast Asia, including China, Hong Kong, Taiwan, Korea, India, and Japan. The frequency of liver cancer in Southeast Asia and sub-Saharan Africa is greater than 20 cases per 100,000 population. Moreover, recent data show the frequency of liver cancer in the U.S. overall is rising.

With the increasing trend in the incidence of cancers in our country, biomedical research directed at early detection and diagnosis, prognosis and survival, as well as prevention of progression of malignancy, is of prime importance. The aim of cancer chemoprevention is to circumvent the development and progression of malignant cells through the use of non-cytotoxic nutrients, herbal preparations/natural plant products, and/or pharmacological agents. Encouraging dietary intake with herbal supplements may therefore be an effective strategy to limit DNA lesions and organic injuries leading to cancers and other chronic degenerative diseases.

A research article published in the World Journal of Gastroenterology (volume 13, issue 48) addresses this problem. The research team led by Prof. Malay Chatterjee from Jadavpur University investigated the primary chemopreventive mechanisms of Acanthus ilicifolius in an in vivo tumor-transplanted murine model. A. ilicifolius, popularly known as ‘Harkach Kanta’ is distributed widely throughout the mangroves of India, including Sunderbans in West Bengal, west coasts, and the Andamans, and in other Asian countries like Singhal, Burma, China, Thailand etc.

The results showed the aqueous leaf extract (ALE) of the plant was substantially effective in preventing hepatic DNA alterations and sister-chromatid exchanges (a type of chromosomal damage) in tumor-bearing mice. The study further demonstrated that ALE treatment was able to limit liver metallothionein expression, a potential marker for cell proliferation, and lengthen the mean survival of animals to a significant extent. The findings suggest that A. ilicifolius may be used as a potential chemoprotector against hepatic neoplasia.

This research from Prof. Chatterjee’s laboratory opens up a promising avenue in cancer chemoprevention with the use of indigenous plants. The results obtained from this in vivo study seem interesting and encouraging. Lack of toxicity favors further preclinical evaluation of A. ilicifolius in a defined chemical carcinogenesis model. Elucidation of its anticarcinogenic mechanisms of action at the intricate molecular circuits, and isolation and characterization of its active principles, will provide a better understanding of the anti-cancer/chemoprevention strategy of A. ilicifolius. If these studies are found to be really functional, we will have the beginning of a new chemoprevention program with herbal supplements that could have the broadest implications for the well-being of society.

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Reference: Chakraborty T, Bhuniya D, Chatterjee M, Rahaman M, Singha D, Chatterjee BN, Datta S, Rana A, Samanta K, Srivastawa S, Maitra SK, Chatterjee M. Acanthus ilicifolius plant extract prevents DNA alterations in a transplantable Ehrlich ascites carcinoma-bearing murine model. World J Gastroenterol 2007; 13(48): 6538-6548http://www.wjgnet.com/1007-9327/13/6538.asp

Correspondence to: Professor Malay Chatterjee, Ph.D. D.Sc., Chemical Carcinogenesis and Chemoprevention Laboratory, Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, P.O. Box-17028, Calcutta 700032, India.

About World Journal of Gastroenterology

World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.

About The WJG Press

The WJG Press mainly publishes World Journal of Gastroenterology.

Source: Jing Zhu
World Journal of Gastroenterology

Lamivudine is an effective antiviral agent for treatment of patients with chronic hepatitis B and advanced liver diseases. However, long-term lamivudine monotherapy leads to the emergence of lamivudine-resistant hepatitis B virus (HBV) mutants in some patients chronically infected with HBV. Sensitive methods for early detection of lamivudine-resistant mutants will help physicians make clinical decisions in treating patients with HBV infection.

To date, many assays have been used for detection of lamivudine-resistant mutants in patients with Hepatitis B. Differences in sensitivity, specificity, cost, and time required, exist in these methods. Real-time PCR is able to quantitatively detect a small portion of resistant mutants in HBV populations and ligase detection reaction (LDR) is a newly developed method for detection of low abundant mutants in the background of wild-type HBV. However, there are no studies which have compared the clinical performance of the two methods.

A research article published in the World Journal of Gastroenterology (volume 14, issue 1) addresses this question. It compared LDR and real-time PCR for detection of low abundant YMDD mutations in mixed plasmids and serum samples from 52 lamivudine treated patients. Time required and reagent cost for both assays were evaluated. The research was conducted carefully by an experienced team of investigators.

The article suggested both methods are sensitive and inexpensive for detection of YMDD mutation; but LDR is more sensitive than real-time PCR. The results obtained with both methods were completely concordant in all serum samples. LDR was able to detect as low as 0.01% (100 copies/mL) of YIDD plasmid, while real-time PCR only detected 0.1% (1000 copies/mL) of YIDD plasmid in the background of YMDD plasmid. In addition, the cost of LDR is slightly lower than that of real-time PCR.

However, real-time PCR is much more rapid and requires less manual work than LDR. The total assay time for LDR and real-time PCR was 4.5 and 2.5 h, respectively. Another advantage of the real-time PCR method is it is able to calculate the ratio of mutants to total virus in samples. This will be useful in clinical studies on the dynamics of resistant mutants during lamivudine therapy.

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Reference: Wang XL, Xie SG, Zhang L, Yang WX, Wang X, Jin HZ. Comparison of ligase detection reaction and real-time PCR for detection of low abundant YMDD mutants in patients with chronic hepatitis B. World J Gastroenterol 2008; 14(1): 120-124http://www.wjgnet.com/1007-9327/14/120.asp

Correspondence to: Xiao-Ling Wang, 98 West Nantong Road, Subei People’s Hospital, Yangzhou 225001, Jiangsu Province, China.

About World Journal of Gastroenterology

World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.

About The WJG Press

The WJG Press mainly publishes World Journal of Gastroenterology.

Source: Jing Zhu
World Journal of Gastroenterology

In 1994, the team of Tchernev and Petrova from Alexandrovska Hospital in Sofia examined a female patient with liver cirrhosis caused by chronic Hepatitis C virus (HCV). They were intrigued by the patient’s many extra-hepatic manifestations — vascular lesions on the lower limbs, acute pain in the joints, intense tingling of the fingers, and extreme labor-impairing fatigue. They were also intrigued by the presence of cryoglobulins in the patient’s blood. Two years later, the patient developed enlarged lymph nodes on the neck. When one of the nodes was histologically tested, the patient was found to have lymphoma.

This case spurred the interest of the investigators in the extra-hepatic manifestations and complications of HCV infection, and for over a decade they studied the links between HCV infection, cryoglobulinemia, and lymphoma.

A research article published in the World Journal of Gastroenterology addresses this problem. In a study of 136 Bulgarian patients with HCV, the team of Tchernev and Petrova found 76.5% of the patients had extra-hepatic manifestations. Common manifestations were fatigue (59.6%), renal impairment (25%), type 2 diabetes (22.8%), paresthesia (19.9%), arthralgia (18.4%), and purpura predominantly of the lower limbs (17.6%). Over 37% of the patients had cryoglobulins, and 8.8% had B-cell lymphoma.

The study found positive links between the presence of extra-hepatic manifestations and age, female gender, duration of the infection, infection by transfusion of blood and blood products, and extensive liver fibrosis. Therefore, elderly women with chronic HCV and advanced liver fibrosis, who were infected by transfusion during childbirth, are at the highest risk of developing extra-hepatic manifestations of HCV infection.

The study also showed most extra-hepatic manifestations of HCV infection are associated with the presence of cryoglobulins. In particular, the risks of developing B-cell non-Hodgkin lymphoma are much higher in cryoglobulin-positive than in cryoglobulin-negative patients. In the study, 17.6% of cryoglobulin-positive patients had lymphoma, whereas only 3.5% of cryoglobulin-negative patients did.

Given the prevalence of HCV around the world, it is important for physicians to recognize the extra-hepatic signs and symptoms of HCV infection. Patients who exhibit such manifestations should be tested for HCV infection. This can lead to prompt diagnosis and effective treatment of the infection before the development of cryoglobulinemia, when treatment gives poor results or is ineffective.

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6.1 Reference: Stefanova-Petrova DV, Tzvetanska AH, Naumova EJ, Mihailova AP, Hadjiev EA, Dikova RP, Vukov MI, Tchernev KG. Chronic hepatitis C virus infection: Prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients. World J Gastroenterol 2007; 13(48): 6518-6528http://www.wjgnet.com/1007-9327/13/6518.asp

6.2 Correspondence to: Dr. Diana Vasileva Stefanova-Petrova, Department of Gastroenterology, Alexandrovska Hospital, 1 Georgi Sofiiski St, Sofia 1431, Bulgaria.

6.3 About World Journal of Gastroenterology

World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.

6.4 About The WJG Press

The WJG Press mainly publishes World Journal of Gastroenterology.

Source: Jing Zhu
World Journal of Gastroenterology

Many hepatocellular carcinoma (HCC) patients in China may be treated with Traditional Chinese medicine (TCM). Some say it works, others doubt its effectiveness. These stated that a research group in China had found TCM can down-regulate the expression of PTEN in HCC, which may suppress tumor cell growth and regulate tumor cell invasion and metastasis.

A research article published on January 7, 2008 in the World Journal of Gastroenterology (volume 14, issue 1) addresses this problem. The research group imbedded hepatoma carcinoma tissue in the livers of 48 male athymic mice. The mice were distributed randomly into two groups: The chemotherapy group was treated by intragastric administration with FT207 (Tegafur). The TCM group was treated by intragastric administration with FZJDT (complex prescription of Chinese crude drug) that had been deliquated into 3 kinds of density as the low, middle, and high.

Four weeks later, the researchers found the TCM group had distinct superiority in their survival rate compared with the chemotherapy group. There was less tumor metastasis in the livers of the TCM group than in the chemotherapy group. Particularly the results of immunohistochemistry showed the intensity of PTEN (Phosphatase and Tensin Homolog deleted on Chromosome 10) in the TCM group was higher than in the chemotherapy group.

PTEN was recently identified as a tumor suppressor gene by three American research teams. They found PTEN may suppress tumor cell growth and regulate tumor cell invasion and metastasis through inhibiting many signal pathways of cell proliferation.

FZJDT has been widely used to treat HCC for years in The First Affiliated Hospital of Sun Yat-Sen University. Just what is the mechanism of the Chinese herbs that strengthens the body’s resistance and removes toxic substances? Our research showed TCM could markedly increase expression of PTEN in the athymic mice, compared with the chemotherapy group treated with FT207, indicating the anticancer mechanism of the TCM used in this study.

Mechanisms of TCM healing HCC may partially be explained by the enhancing of the expression of PTEN in the liver. The results of this study suggest a promising future for TCM as a combined therapy to treat HCC in China .

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6.1 Reference: Yin LR, Chen ZX, Zhang SJ, Sun BG, Liu YD, Huang HZ. Expression of chromosome ten in liver of athymic mice with hepatocellular carcinoma and the effect of Fuzheng Jiedu Decoction. World J Gastroenterol 2008; 14(1): 108-113http://www.wjgnet.com/1007-9327/14/108.asp

6.2 Correspondence to: Dr. Ze-Xiong Chen, Department of TCM, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.

6.3 About World Journal of Gastroenterology

World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.

6.4 About The WJG Press

The WJG Press mainly publishes World Journal of Gastroenterology.

Source: Jing Zhu
World Journal of Gastroenterology