August 13, 2010

Pioneering hospital halts live liver transplants

By Keith Coffman
Fri Aug 13, 2010 8:41pm EDT

DENVER (Reuters) - A Colorado hospital that pioneered liver transplants using tissue from healthy donors has suspended further surgeries of that type following two recent deaths of U.S. donors.

"We are conducting an internal review and will also have outside experts in the field do an external review," University of Colorado Hospital spokeswoman Erika Matich said on Friday. "We will make any changes or improvements if needed."

Ryan Arnold, 34, died on August 2 at the Colorado hospital days after donating a portion of his liver to his older brother, Chad, 38, who was suffering from liver failure.

Rod Arnold, another brother, told Reuters that Ryan went into cardiac arrest two days after the surgery, was resuscitated by medical personnel and placed on life support. Testing revealed he had no brain activity and he died two days later.

The University of Colorado has long been at the forefront of liver transplants. Surgeons there conducted the world's first successful cadaver transplant in the early 1960s.

The university also conducted the first successful transplant using liver tissue from a healthy donor -- a technique known as a live liver transplant -- in the United States in 1997. It has performed 141 successful live liver transplants since then, Matich said.

Arnold is the fourth donor to die in the United States following a live liver transplant operation and the second this year.

In May, a donor died at the Lahey Clinic in Massachusetts after undergoing the operation.

Rod Arnold said Chad Arnold is still recovering from the transplant, and that the family wanted people to know that it was a "natural decision" by Ryan to try and save his brother's life.

"Ryan took care of people his whole life," Rod Arnold said of his brother, who leaves behind a wife and three young sons.

(Editing by Steve Gorman and Bill Trott)


Histologic outcomes in hepatitis C–infected patients with varying degrees of virologic response to interferon-based treatments

Paul J. Pockros 1,*,‡, Fayez M. Hamzeh 2, Paul Martin 3, Ellen Lentz 2, Xiaolei Zhou 4, Sugantha Govindarajan 5, Anna S. Lok 6

DOI: 10.1002/hep.23809
Copyright © 2010 American Association for the Study of Liver Diseases

Author Information
1 Scripps Clinic, La Jolla, CA
2 Genentech, Inc., South San Francisco, CA
3 Miller School of Medicine, University of Miami, Miami, FL
4 RTI Health Solutions, Research Triangle Park, NC
5 University of Southern California–Keck School of Medicine and Liver Research Laboratory, Downey, CA
6 University of Michigan Medical Center, Ann Arbor, MI

Email: Paul J. Pockros (

*Correspondence: Paul J. Pockros, Division of Gastroenterology/Hepatology, Scripps Clinic, 10666, North Torrey Pines Road, La Jolla, CA 92037

†Potential conflict of interest: Nothing to report.
‡fax: 858-554-8065

Publication History
Article first published online: 23 JUL 2010
Accepted manuscript online: 16 JUN 2010 12:00AM EST
Manuscript Accepted: 7 JUN 2010
Manuscript Received: 25 JAN 2010

Funded by
Roche, Nutley, NJ


Patients with chronic hepatitis C with partial virologic response or nonresponse to interferon-based therapies can experience treatment-related improvements in liver histology. This retrospective analysis assessed the histologic response to treatment in patients with varying degrees of virologic response (sustained virologic response [SVR], breakthrough, relapse, or nonresponse), time to hepatitis C virus (HCV) RNA undetectability, and duration of viral suppression. Patients (HCV genotypes 1-6) with baseline and follow-up liver biopsies from eight phase 2 to phase 4 interferon-based trials were analyzed. Blinded biopsies were evaluated by a single pathologist. Improvements or worsening of METAVIR necroinflammatory activity and fibrosis were defined as increase or decrease of ≥1 grading category from baseline to 24 weeks after end of treatment. A majority of the 1571 patients with paired biopsy data were white, male, with HCV genotype 1/4, baseline HCV RNA levels >800,000 IU/mL, and baseline alanine aminotransferase levels ≤3 × upper limit of the normal range; mean baseline activity and fibrosis scores were 1.8 and 1.7, respectively. Overall, 80% of patients received peginterferon alfa-2a monotherapy or peginterferon alfa-2a/ribavirin combination therapy. Mean treatment duration was 46 weeks. There was a positive correlation between the degree of virologic response and improvements in METAVIR activity and fibrosis, and an inverse correlation with worsening activity and fibrosis (all comparisons, P < 0.0001). Patients with SVR had the greatest histologic benefit. As a combined group, relapsers and patients with breakthrough had significantly greater benefits than nonresponders (activity, P = 0.0001; fibrosis, P = 0.003). Consistent with these results, a better histologic response was correlated with a shorter time to undetectable HCV RNA and a longer duration of viral suppression (all comparisons, P < 0.0001). Conclusion: In patients with chronic hepatitis C who were treated with interferon-based therapies, histologic benefits may be observed even in the absence of an SVR. (HEPATOLOGY 2010;)


Ideal Diet for Hepatitis C

Hepatitis C (HCV), a viral liver disease that leads to the inflammation of the liver, affects about 3.9 million Americans. Hepatitis C is a condition within a class of hepatitis diseases, considered the most serious and life-threatening of them all.

While there is medical treatment available for those with hepatitis that can delay the progress of the disease, diet is an important factor in keeping the person’s immune system strong and healthy.

A diet for a person with HCV is not that much different than a diet that is recommended for anyone who wants to stay fit, strong and maintain a healthy body weight.

Here are nutrition and health guidelines for a person with hepatitis C:

1. Avoid alcohol - Because of alcohol’s known damaging effects on the liver, a person with HCV should avoid alcohol entirely.

2. Eat lots of fresh foods - A healthy diet that is comprised of mostly plant-based foods like vegetables, fruits, legumes, nuts and seeds helps keep the immune system healthy and strong. While anyone is all the more wise (and healthy) to follow such a diet, for a person with HCV, taking the appropriate dietary steps to strengthen the body’s immune system may be a key factor in preventing the progression of liver damage caused by the hepatitis virus.

3. Consider milk thistle - The herb milk thistle has traditionally been used as a healing liver tonic. While current scientific studies yield mixed results in relation to milk thistle and liver health, if you are interested in taking it, talk to your medical practitioner first. Milk thistle can be taken in a capsule, tincture or extract form.

4. Maintain a healthy body weight – Since a person with hepatitis C wants to protect their liver as much as they can, they also want to maintain a healthy body weight, especially if they are prone to carrying weight in their mid-section. Being overweight is linked to a term known as “fatty liver,” where fat deposits around the liver. Having a fatty liver and being hepatitis C positive has been associated with an increased risk for cirrhosis and with a higher viral load, even for those taking antiviral treatments.

5. Avoid excess salt - Following a low-sodium diet is sound dietary advice for anyone, but for a person with any kind of a liver disease, like hepatitis C or cirrhosis, it is a mandatory part of their treatment plan. Salt causes the body to retain water and can incite conditions like extremely low pressure, blood vessel complications, edema and abdominal swelling. Physicians typically advise limiting salt intake to 4-5 grams per day (2,000 mg of sodium) or less.

For hepatitis C-sufferers who are being treated with interferon, nausea, a side effect of the medication, may inhibit the ability to eat a healthy and balanced diet. In addition, individuals with hepatitis C and cirrhosis may also lose their appetite and become too tired and lethargic to eat. In both of these cases, it is important to work with your doctor and a registered dietitian to outline an eating plan that takes into account these additional factors.

Also read:
Foods for a Healthy Liver

August 13th, 2010
Tags: hepatitis, liver, low sodium diet


Fibrosis Progression and the Pros and Cons of Antiviral Therapy for Hepatitis C Virus Recurrence After Liver Transplantation: A Review

Volume 42, Issue 6, Pages 2223-2225 (July 2010)

E. De Martin a, M. Senzolo a, M. Gambato a, G. Germani a, A. Vitale b, F.R. Russo a, P. Burra a


The progression of fibrosis due to hepatitis C virus (HCV) recurrence after liver transplantation (OLT) is faster than in the pretransplant setting, leading to histologically documented cirrhosis within 5 years in 25% to 30% of cases. Whether it is associated with biliary complications or previous alcohol abuse, recurrent HCV is the main cause of graft failure and death after OLT. The most important donor risk factor for HCV recurrence is advanced donor age. The disease's course is even more aggressive if it is associated with anti-HCV positivity or graft steatosis. The type of calcineurin inhibitor does not seem to influence HCV recurrence. Avoiding or slowly tapering steroids has been associated with less disease recurrence, while steroid pulses to treat acute rejection episodes have been associated with a worse progression of fibrosis. Antiviral therapy (AT) is not always recommended in OLT patients, but is of some benefit. Fibrosis has been shown to ameliorate in sustained virological responders to AT and to progress significantly more in nonresponders. Using long-term maintenance, AT has recently been shown to increase the probability of biochemical and histological responses, regardless of the timing of the HCV recurrence. In conclusion, the donor- recipient match should be assessed to limit HCV recurrences and their severity; AT is recommended to reduce or reverse the progression of fibrosis.

a Gastroenterology, Multivisceral Transplant Unit, Department of Surgical and Gastroenterological Sciences, Padua University, Padua, Italy
b Oncological Surgery Unit, IOV (Istituto Oncologico Veneto), Padua University, Padua, Italy

Address reprint requests to Patrizia Burra, MD, PhD, Gastroenterology—Multivisceral Transplant Unit, Department of Surgical and Gastroenterological Sciences, Padua University Hospital, Via Giustiniani 2, 35128 Padova, Italy

PII: S0041-1345(10)00693-7
© 2010 Published by Elsevier Inc.


Role of treatment for depressive symptoms in relieving the impact of fatigue in HIV-HCV co-infected patients: ANRS Co13 Hepavih, France, 2006-2008

Authors: Michel, L.; Villes, V.; Dabis, F.1; Spire, B.; Winnock, M.1; Loko, M.-A.1; Poizot-Martin, I.2; Valantin, M. A.; Bonnard, P.3; Salmon-Céron, D.; Carrieri, M. P.
Source: Journal of Viral Hepatitis, Volume 17, Number 9, September 2010 , pp. 650-660(11)
Publisher: Wiley-Blackwell



Fatigue is a major component of quality of life (QOL) and is associated with depression in HIV-HCV co-infected individuals. We investigated whether treating depressive symptoms (DS) could mitigate the impact of fatigue on daily functioning in co-infected patients, even those at an advanced stage of disease. The analysis was conducted on enrolment data of 328 HIV-HCV co-infected patients recruited in the French nationwide ANRS CO 13 HEPAVIH cohort. Data collection was based on medical records and self-administered questionnaires which included items on socio-behavioural data, the fatigue impact scale (FIS) in three domains (cognitive, physical and social functioning), depressive symptoms (CES-D classification) and use of treatments for depressive symptoms (TDS). After multiple adjustment for gender and unemployment, CD4 cell count <200 per mm3 was associated with a negative impact of fatigue on the physical functioning dimension (P = 0.002). A higher number of symptoms causing discomfort significantly predicted a higher impact of fatigue on all three dimensions (P < 0.001). This was also true for patients with DS receiving TDS when compared with those with no DS but receiving TDS. A significant decreasing linear trend (P < 0.001) of the impact of fatigue was found across the categories `DS/TDS', `DS/no TDS', `no DS/TDS' and `no DS/no TDS'. Despite limitations related to the cross-sectional nature of this study, our results suggest that routine screening and treatment for DS can reduce the impact of fatigue on the daily functioning of HIV-HCV co-infected patients and relieve the burden of their dual infection.

Keywords: ART; depression; fatigue; hepatitis C; quality of life
Document Type: Research article
DOI: 10.1111/j.1365-2893.2009.01223.x
Affiliations: 1: INSERM U897, ISPED, Université Victor Segalen, Bordeaux, France 2: CHU Sainte Marguerite, Marseille, France 3: Hôpital Tenon, Paris, France


A simple, noninvasive test for the diagnosis of liver fibrosis in patients with hepatitis C recurrence after liver transplantation

Authors: Cross, T. J. S.; Calvaruso, V.1; Foxton, M. R.2; Manousou, P.1; Quaglia, A.2; Grillo, F.1; Dhillon, A. P.1; Nolan, J.2; Chang, T. P.1; O'Grady, J.2; Heneghan, M. A.2; O'Beirne, J. P.1; Burroughs, A. K.1; Harrison, P. M.3
Source: Journal of Viral Hepatitis, Volume 17, Number 9, September 2010 , pp. 640-649(10)
Publisher: Wiley-Blackwell



Recurrent hepatitis C is a common cause of graft loss in patients undergoing liver transplantation, and serial protocol liver biopsies have been used to identify patients at risk of graft loss from rapid fibrosis progression. The aim of this study was to derive a simple noninvasive index to predict fibrosis in patients with recurrent hepatitis C post-transplant. A retrospective study was performed assessing serial liver biopsies for post-transplant chronic hepatitis C infection. One hundred eighty-five patients were included in the analysis; median age 53 years (interquartile range 48-59) and 140 (76%) were male. Liver histology showed 53 (29%) had Ishak fibrosis stages F0/F1, 31 (17%) had F2, 29 (16%) had F3, 19 (10%) had F4 and 53 (29%) had F5/F6. The London Transplant Centres' (LTC) score was derived combining aspartate aminotransferase (AST IU/L), time from liver transplant (TFLT months), international normalized ratio and platelets. Diagnostic accuracy of the LTC score was assessed using area under receiver-operating characteristic (ROC) curves. The area under the ROC curve for moderate fibrosis (F ≥ 2) was 0.78 (95% CI, 0.70-0.86; P < 0.0001), for advanced fibrosis (F4-6) was 0.80 (95% CI, 0.72-0.87; P < 0.0001) and for cirrhosis was 0.80 (95% CI, 0.72-0.88; P < 0.0001). An optimal cut-off value of 6.3 distinguished patients with no or mild fibrosis (F ≤ 1) odds ratio 10.8 (95% CI, 5.1-22.9); P < 0.0001), sensitivity 88%, specificity 60%, negative predictive value 67% and positive predictive value 84%. The LTC score can identify patients with Hepatitis C virus recurrence following liver transplant with a low risk of significant fibrosis, thus avoiding the need for protocol biopsy.

Keywords: fibrosis; hepatitis C; liver transplantation; noninvasive marker
Document Type: Research article
DOI: 10.1111/j.1365-2893.2009.01222.x
Affiliations: 1: Department of Hepatology and Liver Transplantation, The Royal Free Hospital, Pond Street, London, UK 2: Institute of Liver Studies, King's College Hospital, Denmark Hill, London, UK 3: Division of Gene and Cell-based Therapy, Department of Liver Studies and Transplantation, King's College London, Denmark Hill Campus, Bessemer Road, London, UK


New Hepatitis Therapy Could Be Vertex's Windfall

August 13, 2010
By Michael Fitzhugh

Vertex Pharmaceutical (VRTX) says a new trial shows that its late-stage hepatitis C therapy, telaprevir, can help some people tackle the virus in half the time the current treatment takes. A quicker cure, one slashing typical treatment times to 24 weeks from 48 weeks, could help millions of infected people stick to their treatment regimens and represent a windfall for Vertex.

Knowing that it’s possible to treat infected patients in less time could “provide important information to motivate people to continue therapy,” says the trial’s principal investigator, Kenneth Sherman, a professor at the University of Cincinnati College of Medicine.

The trial, dubbed ILLUMINATE, was designed to evaluate whether there was any benefit to extending therapy from 24 weeks to 48 weeks in people whose hepatitis C virus was undetectable at weeks 4 and 12 of treatment. Vertex's analysis of the study's results found there was not.

Hepatitis C can lead to liver cancer and scarring and is thought to be carried by more than 4 million people in the United States and 180 million people worldwide, according to the National Institute of Allergy and Infectious Diseases. Between 55 percent and 85 percent of those people will develop chronic infection, and 75 percent of those with chronic infection will develop chronic liver disease, according to the Institute.

Analysts predict telaprevir sales could peak at more than $3 billion annually in the United States, garnering another $1 billion in peak annual sales overseas. Vertex's main competition in becoming the next standard of care for hepatitis C will be Merck's boceprevir. Telaprevir's efficacy has yet to be compared to boceprevir in a scientific study.

Vertex and its partners, Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma, plan to submit the positive trial results to support a new drug application for telaprevir to the U.S. Food and Drug Administration in the form of a rolling submission, a process that could accelerate the agency's review of the drug. A decision is expected in early 2011.


Thai activists call for treatment for hepatitis C for people with HIV

Carole Leach-Lemens
Published: 13 August 2010

Treating co-infection of HIV and hepatitis C (HCV) in Thailand makes sound economic sense, Noah Methany argues in a policy paper published by the Thai AIDS Treatment Action Group (TATAG) on July 28, 2010, in recognition of World Hepatitis Day.

Outlining the public health crisis of HIV and HCV co-infection faced by people who inject drugs in Thailand, the paper makes recommendations to the government to help stop and reverse this dual epidemic.

While Thailand boasts a universal health care system that claims healthcare for all without discrimination, people living with HIV who are co-infected with HCV, notably current or former drug injectors, face unique barriers to effective treatment, notes the author.

Increased access to antiretroviral treatment in low- and middle-income countries has increased life expectancy and improved the quality of life of people living with HIV. But many find they are now dealing with other chronic health problems, of which hepatitis C is one.

Hepatitis C, a blood-borne viral infection, spreads easily through the sharing of injecting equipment, and disproportionately affects injecting drug users (IDUs).

HCV is transmitted when infected blood from one person enters another’s bloodstream through any kind of contact. Unlike HIV it can live outside of the body for a long period of time, making it ten times more infectious than HIV, notes Methany.

HCV is the world’s leading cause of liver disease. It can progress silently from fibrosis (mild scarring of the liver) to cirrhosis (severe scarring). Those with cirrhosis are at increased risk for liver cancer and liver failure. People living with HIV have weakened immune systems so HCV progresses more rapidly than in people who are HIV-negative.

End-stage liver disease is becoming a growing cause of death among people living with HIV. Additionally, Methany notes, “HCV complicates a person living with HIV’s treatment because it can triple the risk of antiretroviral-associated liver toxicity.”

There is a general lack of awareness of the disease amongst the medical community as well as those at risk. Diagnosis, management and treatment are complex and costly and are considered the main barriers to improving access to treatment.

“It is incredibly ironic that we have dramatically altered the prognosis for HIV – a currently incurable disease – only to see co-infected people dying from complications of hepatitis C, a disease that we can cure,” noted Tracy Swan of New York’s Treatment Action Group, the paper’s editor.

IDUs may also have to face other problems when trying to access health care that include denial of, or discriminatory treatment and a lack of confidentiality.

WHO estimates that three percent of the world’s population or 180 million people have been infected with HCV, with an additional three to four million newly infected each year, many of whom remain undiagnosed.

WHO estimates 32.3 million people living in South East Asia are infected with HCV. An estimated two to nine million IDUs are living in the Asia-Pacific region, of which 750,000 are estimated to be living with HIV. While there are few epidemiological studies on the prevalence of HIV and HCV co-infection in Asia, an estimated 60-90% of IDUs are living with HIV.

According to WHO and UNAIDS 610,000 Thais are living with HIV/AIDS; 5 to 10% are estimated to have got it from injecting drugs and at least half of all injecting drug users in Thailand are living with HIV/AIDS.

The International Harm Reduction Association estimates up to 90% of injecting drug users in Thailand have become infected with HCV, notes Methany.

A two-step process is required to determine infection with HCV. The first part-an antibody test shows if a person is or has been infected. A viral load test is then needed to determine whether infection is chronic or not. Liver enzyme levels are needed to monitor people with HCV. Length of treatment is determined by genotypic testing. Methany notes that while there are at least six different genetic versions of hepatitis C virus, genotypes 1,3 and 6 are the most common in Thailand.

A three to twelve month course of treatment with a combination of two drugs – pegylated interferon (PEG-IFN) and ribavirin (RBV) – is the current standard of care. While generally there is a 50% treatment success rate, response varies and is related to genotype.

Ribavirin is available as a generic product, whereas the two versions of pegylated interferon are still under patent. The current costs of treating hepatitis C is approximately US $38,000 for a 48-week course of treatment, prohibitive for many health care systems. In Thailand these drugs are not on the Thai National Essential Drugs List and so are not included in the Thai universal coverage scheme.

Contrary to arguments that treating HCV and HIV co-infection in Thailand is too expensive, the author cites two studies that showed treating people with ribavirin and pegylated interferon to be cost-effective and increased life expectancy.

Researchers showed that treating Thai HCV (genotypes 2 and 3) patients compared to no treatment resulted in a lifetime cost saving of 556,862 baht (US$16,784). Noah Methany argues that not only is it Thailand’s constitutional and moral obligation to provide treatment for Thai HCV patients but it also makes economic sense.

Methany proposes the following policy recommendations to address the challenges faced by Thais, current or former injecting drug users, who are co-infected with HIV and HCV.
  • Immediately scale up of evidence-based harm reduction programmes that promote access to clean injecting equipment/sterile syringes, which prevent new HCV infection.
  • Increase support for Thai civil society involvement in HCV awareness campaigns through promotion of capacity building and education of advocates, patients, healthcare providers and policymakers.
  • Provide universal access to free testing for HCV and offer follow-up diagnostic tests on a routine basis to IDUs who test positive for HIV.
  • Provide national level data collection on HCv incidence and prevalence among Thais living with HIV/AIDS.
  • Include pegylated interferon and ribavirin on WHO and Thai Essential Medicines List.
  • Develop Thai-language national guidelines based on international best practices for HCV treatment and care.
  • Increase political support for the Thai Government Pharmaceutical Organization (GPO) to produce generic versions of pegylated interferon and ribavirin, and
  • Increase political support for Thai government officials to exercise legal, TRIPS flexibilities (such as compulsory licences and parallel importation) to gain access to cheaper HCV treatment.

Methany, N and Swan, T (ed) Illuminating a hidden epidemic: the public health crisis of HIV/HCV co-infection among injecting drug users (IDU) in Thailand. Thai AIDS Treatment Action Group (TTAG) Foundation, July 28, 2010.


Acquisition May Create Headaches for Merck in Foreign Corruption Probe

By Jim Edwards August 13, 2010
EDITOR’S NOTE: This is a revised version of an earlier BNET column. Merck objected to our characterizations of a Department of Justice and the SEC investigation in that article, and BNET regrets any errors or false implications.

Merck (MRK) disclosed in its quarterly 10-Q filing that it is the subject of an investigation by the Department of Justice and the SEC for possible violations of the Foreign Corrupt Practices Act (which prohibits paying bribes to do business in foreign countries). The investigation comes with a bit of unspoken history — and some potential risk created by Merck’s recent acquisition of Schering-Plough.

Merck says “this inquiry is part of a broader review of pharmaceutical industry practice.” That’s true: at least 10 other companies are suspected of doing the same thing, and an 11th — SciClone (SCLN.O) popped up Tuesday.

However, the fuller context is that the letters are more serious than a “review.” A DOJ assistant attorney general warned an assemblage of pharma industry lawyers last year that DOJ “will be intensely focused on rooting out foreign bribery in your industry.” A similar criminal investigation has already led to the imprisonment of one executive at Johnson & Johnson (JNJ) in the U.K., and J&J admitted in its most recent 10-Q that it had violated anti-corruption laws and that investigations are under way in several nations, including the United States.

The U.S. investigation is ongoing, and Merck told BNET it’s cooperating with authorities. While emphasizing that it has an FCPA compliance program in place, Merck’s 10-Q says that the company has not been charged with any FCPA violations:

The company has received letters from the DOJ and the SEC that seek information about activities in a number of countries and reference the Foreign Corrupt Practices Act. The company is cooperating with the agencies in their requests and believes that this inquiry is part of a broader review of pharmaceutical industry practices in foreign countries.

Despite its public assurances and FCPA compliance programs, Merck nevertheless may have significant exposure in the investigation. The biggest source of vulnerability may be Schering-Plough, which Merck acquired in 2009. One ominous sign is that Schering-Plough has already been named in connection with an alleged foreign kickback scheme to promote the Hepatitis C drug PegIntron in Vietnam.

Schering-Plough stands accused of offering Vietnamese doctors a kickback of 10 to 30 percent of the medicine’s price, according to Vietnam’s English-language press. Vietnam’s Health Ministry investigated those reports, and in March 2010, the prime minister demanded penalties be imposed on Schering for paying monthly commissions of $26,300 to doctors who prescribed PegIntron. One doctor at a medical school was rumored, according to the local press, to also be a marketing director at Schering.

As Schering’s new parent, Merck assumes responsibility for any missteps Schering made prior to its acquisition.

While there’s no evidence of wrongdoing at Merck, the company would not have needed to make the disclosure at all if it believed the probe would never become “material” to its financial statements. So what is the potential exposure? As the Vietnam incident suggests, the business practices of Schering-Plough prior to its acquisition by Merck stand out as a potential wildcard.

In response to BNET’s queries about potential liabilities resulting from Schering-Plough’s pre-acquisition business practices, Merck declined to comment beyond the statement contained within its 10-Q filing.

If prosecutors are not singling out Merck, and the letters they sent were just standard forms, then the matter could end with a simple reply to the feds’ letters. On the other hand, companies found guilty of FCPA violations have been forced to disgorge the profits made from any corrupt scheme.

Either way there’s a lesson in this experience for any company that seeks growth through acquisitions: You may get more than you paid for, and that’s not always a welcome thing.


Liver Cancer Kills Legendary Drummer Richie Hayward

Published August 13, 2010 by:
Sylvia Cochran

Famous Musician Succumbs to Deadly Disease
For Little Feat drummer Richie Hayward, cancer became a reality more than a year ago. Diagnosed with liver cancer, the influential musician lost his battle with the disease on Aug. 12, 2010. Would you know how to detect liver cancer symptoms?

Richie Hayward Dead from Liver Cancer

Drum! Magazine reports that Little Feat drummer Richie Hayward died from liver cancer at the age of 64. Even though he was a major powerhouse on the national and international music scene, Hayward did not have health insurance. A currently scheduled benefit concert designed to help defray the drummer's costs associated with healthcare will proceed. It is noteworthy that Hayward fought the illness since last year, when liver cancer symptoms first prompted a diagnosis.

Understanding Liver Cancer

According to the National Cancer Institute, each year liver cancer affects approximately 15,000 men and 6,000 women. The average age of diagnosis is over 64. There are a number of risk factors that heighten a person's susceptibility of contracting liver cancer. A prolonged infection with hepatitis B or C, long-term alcohol abuse, exposure to deadly mold toxins, excessive bodily iron storage and diabetes, as well as obesity, are well-known risk factors.

The fact that the early stages of the disease do not present many noticeable symptoms contributes to the frequently poor liver cancer prognosis. Once the tumor is sufficiently large, liver cancer symptoms include weight loss, upper abdominal pain, bloating, jaundice and fever. Physicians evaluate the stage of the disease by how extensively it is spread; it may reach the lungs, as well as the bones and lymph nodes. A cure is only possible if patient and doctor catch liver cancer before it spreads, and the sufferer is sufficiently well to be a candidate for surgery.

Richie Hayward Joins Long List of Famous Liver Cancer Victims

The Encyclopedia of Jazz Musicians reports that music legend Ray Charles died from liver cancer in 2004 at age 73. Blues celebrity John Jackson succumbed to the disease in 2002 at age 77, All Music reveals.

Liver cancer also claimed the life of Wendy's founder and noted philanthropist Dave Thomas. Back in 2002, CNN revealed that Thomas had battled liver cancer for 10 years before the disease finally won.



Boost for drugs against hepatitis C

Hepatitis virus particles: drugs targeting hepatitis C could make billions of dollars, say analysts.

Published online 13 August 2010
Nature doi:10.1038/news.2010.408

Promising clinical trial results point to the pharmaceutical industry's next blockbuster.

Ewen Callaway

A new generation of drugs with the potential to cure hepatitis C is set to flood the market.

This month, Vertex Pharmaceuticals, based in Cambridge, Massachusetts, and drug behemoth Merck, headquartered in Whitehouse Station, New Jersey, both released promising results from late-stage clinical trials of their leading drugs against hepatitis C virus (HCV).

The two treatments belong to the first wave of what pharmaceutical analysts think will be a profusion of HCV-targeting drugs that could ring up billions of dollars in annual sales. "There certainly is blockbuster potential for new and efficacious drugs in hepatitis C," says Hedwig Kresse, a drug-market analyst at Datamonitor in London.

The virus infects liver cells and can cause cirrhosis and liver cancer. It affects about 3% of the world's population — and new treatments are urgently needed.

"There are a lot of people who don't respond to the current therapies or are unable to tolerate them," says Paul Klenerman, who works on hepatitis C therapies at the University of Oxford, UK. "There's no doubt there's a big unmet need there."

Currently, patients spend about a year taking a combination of interferon-α, a protein that boosts the immune system, and ribavirin, an antiviral drug that does not specifically target HCV. Roughly half of all patients with hepatitis C are cured by this course, but it can also cause serious side effects, such as depression, anaemia, and flu-like illness.

Protease punch

Enter Vertex's drug telaprevir and Merck's boceprevir. Both block HCV's protease enzyme so that it cannot carry out one of its key tasks. All of HCV's proteins are initially produced as one long polyprotein, which needs to be cleaved into its component proteins by the protease. Blocking the protease prevents the virus from producing functional proteins.

The companies will submit their medicines to the US Food and Drug Administration by the end of this year, with an eye towards approval in mid-2011.

Data released this month fulfil the pharmaceutical industry's high expectations for the effectiveness of these drugs. Boceprevir, combined with interferon-α and ribavirin, cured the infections of about two-thirds of the patients who followed a 48-week course, Merck announced on 4 August. Some patients were able to finish the course even sooner, at 28 or 36 weeks.

Telaprevir, also combined with the standard drugs, cured 72% of patients after just 24 weeks of treatment, Vertex said on 10 August. Patients who responded quickly to the drug, within 4 to 12 weeks, were the most likely to be cured by it. Another phase III trial of telaprevir, the results for which Vertex released in May, had already demonstrated the benefits of the 24-week course, but the latest study confirmed that it was just as effective as a 48-week regimen for most patients.

"This is such a huge step forward. You can't call it one step — it's multiple steps with one drug," says Stefan Zeuzem, a professor of medicine who studies hepatitis C at Johann Wolfgang Goethe University Hospital in Frankfurt, Germany.

Analysts are already giving telaprevir the edge, largely because of the shorter course of treatment. Peter Chang, a scientific analyst at Sagient Research Systems in San Diego, California, estimates that sales of telaprevir could reach US$6 billion a year across the United States and Europe by 2014. Vertex is developing the drug in collaboration with the pharmaceutical companies Tibotec Pharmaceuticals, based in Ireland, and Mitsubishi Tanabe Pharma, based in Japan.

Cocktail approach

If approved, telaprevir and boceprevir will take the early lead in an HCV drug field that could grow to be worth $15 billion by 2017, according to Irena Melnikova, a life-sciences analyst at TVM Capital in Boston, Massachusetts. The field is poised to become even more crowded in the coming years. "There are still going to be a number of patients who fail [to be cured by] telaprevir or boceprevir," says Chang. "There's plenty of market to still go after."

Other companies are also developing protease inhibitors, as well as drugs that target other parts of the virus. The main targets apart from the protease are HCV's polymerase enzyme, which copies its RNA genome, and its NS5A protein, which is involved in replication and viral assembly but is not an enzyme. Drugs targeting these proteins are now in phase I and II trials.

Experimental drugs targeting different parts of the virus should also stymie the development of drug-resistant strains of HCV. The approach would be similar to the one taken against HIV, for which patients take a cocktail of drugs.

With vaccines that would prevent HCV infection still in early stages of development, the next-generation drugs will be vital for curing those who are affected. For now, the protease inhibitors being developed will be combined with interferon-α and ribavirin. But Klenerman says that "once we have more agents we will have room to design some interesting therapies".

Pharmaceutical firms are already testing different combinations of drug candidates to see what works best for different patients. "Ultimately, we should have a cocktail allowing viral eradication for every patient," says Zeuzem.