Wednesday, August 1, 2012

Disparities Affect Inpatient Mortality in Liver Cancer

By: MITCHEL L. ZOLER, Oncology Report Digital Network

SAN DIEGO – African Americans and Asian Americans with hepatocellular carcinoma had significantly worse inpatient mortality than did white patients, and the data suggest that socioeconomic disparities in availability of health services may at least partially explain the difference.

In a multivariate analysis that also applied propensity-score matching, African American inpatients with hepatocellular carcinoma (HCC) were 30% more likely to die, compared with their white counterparts, and Asian Americans had a 60% higher inpatient mortality, compared with white Americans who had HCC.

The findings were based on data collected from 27,741 patients during 2002-2011 by the University Health Consortium, Dr. Sabeen F. Medvedev said at the the annual Digestive Disease Week.

The data analyzed by Dr. Medvedev and her associates showed a broad range of disparities by racial and ethnic groups for type of medical coverage, disease severity at the time of hospitalization, presence of metastatic disease, and whether patients received invasive treatment or liver transplantation.

"Despite increased survival due to advances in surveillance and surgical interventions for HCC, we found racial disparities exist in prognosis and disease presentation," said Dr. Medvedev of the division of gastroenterology and liver diseases at the George Washington University in Washington.

After propensity scores to mimic randomization of treatment options were used, a 60% excess mortality in African Americans, compared with whites, was reduced to a 30% excess, "indicating that the observed disparity in deaths might extend beyond disproportionate treatment allocation. The take home message is, due to their insurance and economic status and lack of access to care, African Americans did not have as many treatment options," Dr. Medvedev said. "We think that this is a delivery-of-care issue," she added in an interview.

The University Health Consortium includes 116 U.S. academic medical centers and 272 of their affiliated hospitals – about 90% of America’s nonprofit academic medical centers. HCC patients who were treated during the 9 years studied had a median age of 61 years; 54% of them were white, 16% were African American, 11% Asian, 9% Hispanic, and 10% were from other ethnic groups.

The white subgroup had the highest percentage of patients with private medical insurance (41%) and the lowest rate of Medicaid or uninsured status (15%). In contrast, among African Americans, 30% had private insurance, and 37% received Medicaid or were uninsured. Among Asian Americans, 38% had private insurance, and 30% had Medicaid or were uninsured.

An analysis of disease presentation and treatments applied showed that the African American and Asian American subgroups each had a 20% higher rate of HCC metastasis at the time of hospitalization, compared with the white subgroup.

African Americans also received significantly fewer liver transplants, resections, ablations, and transarterial chemoembolizations, compared with the white subgroup. Asian Americans received significantly fewer transarterial chemoembolizations, compared with whites, but their rates for other types of treatments were similar to the rates seen in the white subgroup. The only treatment received significantly less often by Hispanic patients, compared with whites, was resection.

FDA Hepatitis Update - Victrelis (boceprevir) label updated for drug-drug interactions

FDA Hepatitis Update - Victrelis (boceprevir) label updated for drug-drug interactions

On July 31, 2012, FDA updated the Victrelis (boceprevir) label to include drug-drug interactions between Victrelis and cyclosporine, tacrolimus, escitalopram, atorvastatin and pravastatin. The main changes to the label are highlighted below.

Changes were also made to the Medication Guide to reflect the new interaction data.
Section 7: Drug Interactions was updated to include information regarding the following drug-drug interactions:

  • Atorvastatin: Exposure to atorvastatin was increased when administered with VICTRELIS. Use the lowest effective dose of atorvastatin, but do not exceed a daily dose of 40 mg when coadministered with VICTRELIS
  • Cyclosporine: Dose adjustments of cyclosporine should be anticipated when administered with VICTRELIS and should be guided by close monitoring of cyclosporine blood concentrations, and frequent assessments of renal function and cyclosporine-related side effects.
  • Escitalopram: Exposure of escitalopram was slightly decreased when coadministered with VICTRELIS. Selective serotonin reuptake inhibitors such as escitalopram have a wide therapeutic index, but doses may need to be adjusted when combined with VICTRELIS
  • Pravastatin: Concomitant administration of pravastatin with VICTRELIS increased exposure to pravastatin. Treatment with pravastatin can be initiated at the recommended dose when coadministered with VICTRELIS. Close clinical monitoring is warranted
  • Tacrolimus: Concomitant administration of VICTRELIS with tacrolimus requires significant dose reduction and prolongation of the dosing interval for tacrolimus, with close monitoring of tacrolimus blood concentrations and frequent assessments of renal function and tacrolimus-related side effects.
Section 12: Clinical Pharmacology was updated to include the magnitude of interaction between boceprevir and these medications.

Victrelis is a protease inhibitor for the treatment of HCV infection and manufactured by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co.

The complete, revised label and Medication Guide can be viewed at Drugs@FDA.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

Drug-Drug Interactions Added to Hepatitis C Drug Label

By: ELIZABETH MECHCATIE, Family Practice News Digital Network

New information about interactions between boceprevir and several other drugs has been added to the prescribing information for the antiviral drug, the Food and Drug Administration announced Aug. 1.
Boceprevir (Victrelis), a protease inhibitor approved for treating hepatitis C in 2011, interacts with cyclosporine, tacrolimus (Prograf), escitalopram (Lexapro), atorvastatin (Lipitor), and pravastatin (Pravachol), according to the FDA statement.

The new information states that, when administered with boceprevir, exposure to atorvastatin increases. When the two drugs are used together, the lowest effective dose of atorvastatin should be used, not to exceed a daily dose of 40 mg, according to the FDA.
Dose adjustments of cyclosporine should be anticipated when it is given with boceprevir, and "should be guided by close monitoring of cyclosporine blood concentrations, and frequent assessments of renal function and cyclosporine-related side effects."

When administered with boceprevir, exposure of escitalopram "was slightly decreased," the statement said. Although selective serotonin reuptake inhibitors (SSRIs) such as escitalopram have a wide therapeutic index, it may be necessary to adjust the dosage when it is administered with boceprevir.
Coadministration of boceprevir with pravastatin increases exposure to pravastatin, but pravastatin can be started at the recommended dosage when coadministered with boceprevir. "Close clinical monitoring is warranted," the statement said.

Giving tacrolimus and boceprevir together "requires significant dose reduction and prolongation of the dosing interval for tacrolimus, with close monitoring of tacrolimus blood concentrations and frequent assessments of renal function and tacrolimus-related side effects," the statement said.
Boceprevir is manufactured in a capsule formulation by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., and is taken by mouth three times a day.

The drug-drug interaction data are from in vivo drug interaction trials, which the company conducted as part of its postmarketing commitments.

At a meeting in April 2011, an FDA advisory panel enthusiastically supported the approval of boceprevir for treating hepatitis C infection because of the antiviral’s efficacy but emphasized that postmarketing studies on interactions with other drugs, including antidepressants, were needed.
Serious adverse events associated with boceprevir should be reported to MedWatch or by phone at 800-332-1088.

Related June 28

Polymorphisms influences sustained virological response in HCV-2 and -3 in patients

Polymorphisms influences sustained virological response in HCV-2 and -3 in patients
The most recent issue of the Alimentary Pharmacology & Therapeutics investigates the impact of IL28B polymorphisms on rapid and sustained virological response in HCV-2 and -3 patients.
Recent studies suggested that IL28B polymorphisms may affect rapid and sustained virological response rates in HCV patients infected with genotype 2 or 3.

Dr Deltenre and colleagues from Belgium assessed the role of IL28B polymorphisms on the virological response in HCV-2 and -3 patients.

The researchers performed a meta-analysis of studies evaluating the impact of rs12979860 and rs8099917 polymorphisms on rapid and sustained virological response in HCV-2 or -3 patients.
The team included 23 studies involving 3042 patients.

The first meta-analysis evaluated the impact of rs12979860 polymorphism and included 1963 patients.

When compared with rs12979860 CT/TT patients, CC patients had a higher rapid virological response rate, and a higher sustained virological response rate.

The second meta-analysis evaluated the impact of rs8099917 polymorphism and included 2246 patients.

When compared with rs8099917 TG/GG patients, the team found that TT patients had a higher rapid virological response rate and a higher sustained virological response rate.

The team noted that when considering only patients treated for 24 weeks, results were unchanged.
The researchers identified no potential sources of between-study heterogeneity.

Dr Deltenre's team commented, "Favorable IL28B polymorphisms are associated with higher rapid and sustained virological response rates in HCV-2 and -3 patients."

"However, as the impact on a sustained response is very limited, it is unlikely that IL28B polymorphisms provide additional predictive value when considering other predictors of a sustained response."

Aliment Pharmacol Ther 2012: 36(4): 353–362
27 July 2012

Obese donors increase risk of death for pediatric liver transplant recipients

Obese donors increase risk of death for pediatric liver transplant recipients

Children undergoing liver transplantation are at greater risk of graft loss and death from adult organ donors who are severely obese according to research published in the August issue of Liver Transplantation, a journal of the American Association for the Study of Liver Diseases. The study, funded in part by a grant from the National Institutes of Health (NIH), found that pediatric donor body mass index (BMI) did not increase mortality risk in this pediatric population.

Obesity is a global health concern. A 2008 report from the World Health Organization (WHO) estimates that 1.4 billion adults were overweight, and of these 200 million men and 300 million women were classified as obese. WHO also reports that more than 40 million children under the age of five were overweight in 2010. In the U.S., rates of being overweight or obese have risen in children and now exceed 30% say experts.

Prior research shows the prevalence of overweight and obese donors to adult liver transplant recipients has increased during the last two decades. "Donor BMI is associated with post-transplant obesity, but not survival rates of adult liver recipients," explains lead author Dr. Philip Rosenthal, from the University of California, San Francisco's Benioff Children's Hospital. "Our study is the first to evaluate the impact of donor BMI on pediatric liver transplant recipients."

Using data from the United Network for Organ Sharing (UNOS), researchers identified 3788 pediatric liver transplants between 2004 and 2010. Analysis indicates that adult donor BMI 25-35 kg/m2 was not associated with graft loss or mortality in pediatric liver recipients. However, adult donors with a BMI greater than 35 kg/m2 increased the risk of graft loss and death in children receiving livers, after adjusting for other recipient, donor, and transplant risk factors. The authors found that pediatric donor BMI was not associated with graft or patient survival.
"While we found it common for adult donors to be overweight or obese, our analysis suggests that BMI in the 25 to 35 range should not deter liver donation," concludes Dr. Rosenthal. The authors note that causes of graft loss, death, and donor steatosis could not be determined due to lack of donor biopsies. Rosenthal added, "Further research is needed to understand the impact of obesity on donor acceptability and how this affects pediatric liver transplant patients."
This study is published in Liver Transplantation. Media wishing to receive a PDF of this article may contact

Full citation: "An Evaluation of the Impact of Donor BMI on Survival and Post-Transplant Obesity in Pediatric Liver Transplant Recipients." Emily Rothbaum Perito, Sue Rhee, Dave Glidden, John Paul Roberts, Philip Rosenthal. Liver Transplantation; Published Online: July 24, 2012 (DOI: 10.1002/lt.23438) Print Issue Date: August, 2012. URL:

About the Author: Dr. Philip Rosenthal is with the University of California, San Francisco's Benioff Children's Hospital. To arrange an interview with Dr. Rosenthal, please contact Juliana Bunim with UCSF at or at 415-476-8810.

About the Journal:Liver Transplantation is published by Wiley on behalf of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Since the first application of liver transplantation in a clinical situation was reported more than twenty years ago, there has been a great deal of growth in this field and more is anticipated. As an official publication of the AASLD and the ILTS, Liver Transplantation delivers current, peer-reviewed articles on surgical techniques, clinical investigations and drug research — the information necessary to keep abreast of this evolving specialty. For more information, please visit Liver Transplantation.

About WileyFounded in 1807, John Wiley & Sons, Inc. has been a valued source of information and understanding for more than 200 years, helping people around the world meet their needs and fulfill their aspirations. Wiley and its acquired companies have published the works of more than 450 Nobel laureates in all categories: Literature, Economics, Physiology or Medicine, Physics, Chemistry, and Peace.

Our core businesses publish scientific, technical, medical, and scholarly journals, encyclopedias, books, and online products and services; professional/trade books, subscription products, training materials, and online applications and Web sites; and educational materials for undergraduate and graduate students and lifelong learners. Wiley's global headquarters are located in Hoboken, New Jersey, with operations in the U.S., Europe, Asia, Canada, and Australia. The Company's Web site can be accessed at The Company is listed on the New York Stock Exchange under the symbols JWa and JWb.

Colo. dentist may have infected 3 patients

DENVER (AP) -- State health officials say three people may have been infected by a Colorado dentist accused of reusing syringes and needles to administer drugs to some of his patients over more than a decade, but it's impossible to say for sure.

The Colorado Department of Public Health and Environment said Wednesday three people tested positive after the department mailed letters to at least 8,000 patients advising them to be tested for HIV, hepatitis B and hepatitis C if they received intravenous drugs under the dentist's care
The department said no specific infections have been linked to the offices of the dentist, identified as Stephen Stein. The dentist operated Stein Oral and Facial Surgery from September 1999 until June 2011, first in Highlands Ranch, a subdivision south of Denver, then in Denver.


Scotland- NHS hepatitis helpline

NHS hepatitis helpline will help and inform you
NHS inform, Scotland’s national health information service, is providing a new helpline for people with questions and concerns about viral hepatitis (B and C).

The service has been developed in partnership with Hepatitis Scotland, the charity dedicated to helping improve responses to viral hepatitis’ prevention, treatment and support and was officially launched on World Hepatitis Day - July 28.

The helpline, which can be accessed via 0800 22 44 88 from 8am to 10pm seven days a week, will provide a single point of health information about viral hepatitis for patients, the public and professionals involved in providing care and support for people affected by the condition. The helpline, which is supported by the Scottish Government, will improve access to information by aligning all the services previously available and be a cost effective resource for both patients and professionals.

Lynne Huckerby, Head of Health Information Services at NHS 24, said: “The more people know about viral hepatitis the greater the chance of beating it, whether that be through better prevention, testing or treatment.

“Getting information out there is key.

“The new telephone helpine will have an important part to play in raising the profile and knowledge regarding viral hepatitis.”

Hepatitis C -The word “cure” or “viral eradication” has always been hotly debated

August 2012 HCV Advocate Newsletter

In This Issue:

Cure: Really?
Alan Franciscus, Editor-in-Chief

HCV Snapshots
Lucinda K. Porter, RN

Disability & Benefits: What Happens When COBRA Ends
Jacques Chambers, CLU

HealthWise: Medically-Acquired Hepatitis C
Lucinda K. Porter, RN

HCV Increases the Risk of Non-Liver Deaths
Alan Franciscus, Editor-in-Chief

Curing Fatigue with Treatment
Alan Franciscus, Editor-in-Chief

HCV Advocate Eblast
Stay informed on the latest news here to register for email alerts

Mice With Humanized Livers For Drug Screening

Research funded by NIBIB at the Massachusetts Institute of Technology has resulted in the ability to provide both mouse liver function and human liver function in the same mouse. This capability enables researchers to investigate how human livers metabolize drugs, to test susceptibility to toxicity, and to demonstrate species-specific responses that typically do not show up until clinical trials.

Human Livers in Mice Aid Therapeutics