August 17, 2010

Richardson Meets With NIH Over Alamogordo Chimps


Meeting Yields Mixed Results

POSTED: 3:41 pm MDT August 17, 2010
UPDATED: 4:04 pm MDT August 17, 2010

BETHESDA, Md. -- Gov. Bill Richardson met with officials at the National Institutes of Health in Maryland on Tuesday to discuss his concerns regarding the agency's plan to transfer the chimpanzees from the Alamogordo Primate Facility to a facility in Texas for medical research.

Richardson reiterated his call to have the chimps permanently retired and to turn the Alamogordo facility into a sanctuary for the primates.

Richardson said the meeting was both a success and a failure.

"They were gracious, they were polite, but they held fast to their position and I'm going to hold fast to mine," said Richardson.

The Alamogordo Primate Facility is operated by Charles River Laboratories and located on Holloman Air Force Base. According to the agreement with Holloman, no research may be conducted on the primates while they are at the facility. The lab's contract with NIH is set to expire in May 2011, at which time NIH plans to transfer the chimps to Texas to continue medical testing on them.

Richardson also stated that he believes the National Academy of Sciences should do an independent review of policies regarding the use of chimps for medical research.

"I think It is important to find solutions to hepatitis C, but there are other ways to do it rather than testing chimpanzees," said Richardson.

Richardson said there was good news to come out the meeting. Once the chimps are transferred to Texas, the 40 jobs that were in jeopardy at the Alamogordo facility will be saved.

"We made some progress," said Richardson. "They agreed to keep the jobs through 2011. They were going to stop the contract on May of 2011, but they assured me there will be full employment."

Richardson said the fight is not over.

"I'm going to keep pressing, there are other congressional ways to deal with this," said Richardson. "I'm going to push that the Alamogordo facility be a permanent retirement facility managed by nonprofit entities."

So far, the federal agency has moved 15 of the chimps from Alamogordo. They plan to move the remaining 185 some time next year.

Previous Stories:
• July 26, 2010: Battle Brews Over Future For Research Chimps
• July 26, 2010: Group Tries To Stop Alamogordo Chimp Transfers

Source 

Maiden study to unravel liver diseases, Hep C infection

Kounteya Sinha, TNN, Aug 18, 2010, 02.14am IST

NEW DELHI: India will find out the actual burden of liver diseases and Hepatitis C infection soon.

In a first-of-its-kind venture, 12 hospitals across the country have joined hands for a two-year-old study that will not only quantify the number of people suffering from liver diseases, but will also look at its economic burden, the possible ways to prevent such infections and train technicians for a better detection of Hep C from blood samples.

BMC Foundation has relased a Rs 2 crore grant for the study, which is expected to be completed by 2011.

Led by the Liver Foundation of West Bengal and the All India Institute of Medical Sciences' biostatistics department, the other hospitals involved in the exercise include Post Graduate Institute (Chandigarh), Christian Medical College (Vellore), Osmania Medical College (Hyderabad), Institute of Post Graduate Medical Education and Research (Kolkata) and Bombay Hospital.

Other institutes like the Bhopal Memorial Hospital, Calicut Medical College (Kerala), Dayanand Medical College (Ludhiana), Catholic Medical Centre (Manipur) and Assam Medical College (Guwahati) are also an integral part of the study.

Speaking to TOI, Dr Abhijit Chowdhury from the Liver Foundation said, "We have been conducting this study since February. It will look at the prevalence of liver diseases in different regions in India, and what's the main cause behind it. For example, in northern states like Delhi alcohol is the primarily causes liver diseases. While in Punjab it is Hep C infection. In north-eastern and eastern states, Hep B and C infection is the main cause."

"This exhaustive study will make the government aware about the causes of liver diseases in the country, and the preventive measures. Whether the prevalence across regions is heterogeneous or homogenous, what's the share on the nation's health care burden, and what percentage of hospital beds is occupied by people with liver disease. Liver patients suffer a long speill of illness, resulting in a major economic burden for the country and respective households," Dr Chowdhury explained.

Hep C infection is becoming a major problem in India, where an estimated 10.9 million have chronic infection. An increasing number of patients, carrying the Hep C virus are developing cirrhosis, or liver failure. Every year, the number of people infected with the Hep C virus increases by three to four million worldwide, adding to the 170 million people already infected.

Experts say 80% of patients with chronic Hep C infection will develop cirrhosis. The Hep C virus is transmitted through direct blood contact with infected blood.

Persons with needle-stick injury, health care workers with exposure to blood/blood products transfusion/blood-product recipients, transplant recipients and persons with tattoos stand a high risk of contracting Hep C. Since 2001, Union health ministry has made it mandatory for blood banks to screen blood for Hep C patients.

Source
By Lois Wingerson
August 17, 2010
 
We cannot escape the realities of biology. Just as children rescued from leukemia and lymphoma live to grow into adults who must confront the adverse effects of their curative treatment, people rescued from AIDS by HAART (highly active antiretroviral therapy) are showing a substantially increased risk of cancers other than the "AIDS-defining" malignancies designated by the Centers for Disease Control in the 1980s: Kaposi sarcoma, non-Hodgkin lymphoma (NHL), and cervical cancer.
 
With increasing numbers of people surviving for long periods whose immune systems have been weakened by HIV, we can expect to witness an increased incidence of this spectrum of "non-AIDS defining" cancers, or NADCs. This is the independent conclusion from unrelated studies in the United States and Switzerland, which show nearly identical increases in the risk of Hodgkin lymphoma and anal cancer many years after the initiation of HAART therapy.

The US-based AIDS Malignancy Consortium has referred to a coming "epidemic" of these cancers. "NADCs are here to stay," remarked immunologist Dirk Dittmer PhD of the Center for AIDS Research at the University of North Carolina, Chapel Hill, in an editorial about the US study.

That study, apparently the largest and longest-term comparison to date matching cancer rates among HIV+ people with those of other cancer patients, used records from a national cancer registry and those of more than 260,000 adults and adolescents diagnosed with AIDS or HIV-positive status between 1980 and 2008. Thus it can speak to the experience of people who have lived as long as 10 years after diagnosis.

The new analysis of data from the NCI-sponsored HIV-AIDS Cancer Match Study appears this month in the Archives of Internal Medicine.

The latest results from the analogous but smaller Swiss HIV Cohort Study were published last month in the British Journal of Cancer. The investigators from the International Agency for Research on Cancer (IARC) matched records from 9,429 persons with HIV or AIDS against data from a Swiss cancer registry.

"By and large, we all agree that several cancers (especially those associated with HPV [human papilloma virus] and HBV/HCV [hepatitis B and hepatitis C virus]) are going to increase in people with HIV and AIDS unless effective screening/treatment of cancer-associated infections are found and implemented," said two of the IARC authors, Silvia Franceschi and Gary Clifford, when asked to compare the two studies.

The NCI researchers found a decline in Kaposi sarcoma (KS) and the AIDS-associated varieties of NHL during the study period, presumably due to the effects of HAART treatment. But there was an overall increase of 20% in non-AIDS defining cancers during the HAART era. The incidence of Hodgkin lymphoma doubled (most commonly the mixed-cellularity type associated with the Epstein-Barr virus). The incidence of anal cancer in this population tripled between the non-HAART and the HAART era, with a relative risk about 30 times that of the general population.

The IARC study also showed a decline in KS and NHL, accompanied by an increase in NADCs to a level approximately double that of the general population.

It is important not to attribute to HAART any "unproven responsibility" for these recent upward trends in NADCs, Franceschi and Clifford remarked. The increase in risk of NADCs can likely be attributed to "age as a proxy of duration of exposure to cancer-causing chronic infections … that are much more common in people with HIV and AIDS than in the general population, and are characterized by long latent phases," they added.

In other words, the oncogenic events that trigger these cancers may happen even before HIV infection is discovered (as the NCI authors also observed). A weakened immune system predisposes to the NADC malignancy, and HAART treatment allows it the time to develop.

Environmental factors implicit in HIV infection—specifically sexual practices and intravenous drug use—might equally play a role, the NCI authors observed, given that most of the NADCs involve the anal and genital regions, the mouth, throat, and tongue, and the blood.

After the advent of HAART, anal cancer became as prevalent as KS and NHL among AIDS/HIV patients. It may be time to add anal cancer to the AIDS-defining malignancies, Dittmer speculated in his editorial. It's also important not to minimize their total impact, he added in an email. "Despite their relative decline, AIDS defining cancers (Kaposi sarcoma and NHL) still account for more diagnosis than any one other cancer," Dittmer wrote. "The AIDS-related cancers are here to stay as well, as new people continue to be infected with HIV."

HAART is not to blame, exactly, but it must be accounted for in using chemotherapy to treat NADCs. Look for results from a collaborative study assessing the effects of HAART on the effects of cancer chemotherapy with the tyrosine kinase inhibitor sutinib maleate. Recruitment is scheduled to close next month. According to a report at this year's annual meeting of the American Society for Clinical Oncology, so far the drug has been well tolerated in this scenario and pharmacokinetic information is being analyzed.

Source
There has been little discussion about the importance of oral management and interferon (IFN) therapy, although management of the side effects of therapy for chronic hepatitis C has been documented.This study determined whether dental problems delayed the initiation of IFN therapy for hepatitis C virus (HCV)-infected patients.

Results: We analyzed 570 HCV-infected patients who were admitted to our hospital from December 2003 to June 2010 for treatment consisting of pegylated IFN (Peg-IFN) monotherapy or Peg-IFN/ribavirin combination therapy. The group comprised 274 men and 296 women with a mean age 57.2 years.

Of the 570 patients, six could not commence Peg-IFN therapy, despite their admission, because of dental problems such as periodontitis, pupitis, and pericoronitis. The ages of six whose dental problems delayed the initiation of Peg-IFN ranged from 25 to 67 years, with a mean age of 47.3 +/- 15.2 years.

IFN therapy was deferred for 61.3 +/- 47.7 days. Among the six subjects for whom IFN treatment was delayed, only one had a salivary flow that was lower than the normal value.

Conclusions: Treatment of dental infections is required before IFN therapy for HCV infection can be started.

To increase the depth of understanding of oral health care, it is hoped that dentists and medical specialists in all areas will hold discussions to generate cooperation.

Author: Yumiko NagaoMichio Sata

Credits/Source: Virology Journal 2010, 7:192

Published on: 2010-08-17
 
Source

Studies Confirm Genetic Link to Advanced Fatty Liver Disease

17 August 2010 Wiley - Blackwell

Genome-Wide Study Identifies an Important Genetic Variant Associated with NAFLD

Researchers at Massachusetts General Hospital found that patients with nonalcoholic fatty liver disease (NAFLD) who carry an allele of the PNPLA3 gene have an increased risk of developing advanced disease, including nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. A second study supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) validates these findings and further concludes that in pediatric patients, the same allele is associated with earlier disease presentation. Both studies are available in the September issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases (AASLD).

NAFLD is the most common cause of chronic liver disease and afflicts an estimated 20%-30% of the general population and 67%-75% of the obese population. The precise mechanism responsible for the development of the NASH phenotype is yet to be clarified. Genome-wide association (GWA) studies are an important initial step in the identification of these genetic factors because they evaluate the genotypic-phenotypic association in large population-based cohorts and have identified susceptibility loci in numerous diseases.

Recently, GWA studies identified an important genetic variant associated with the presence of NAFLD. Whether these genetic variants also determine disease severity is unknown. To find out, researchers at the NIDDK evaluated single nucleotide polymorphism (SNP) genotypes in 894 primarily Caucasian adults, compared with a control group of 336 Caucasians. The patient population was recruited from 1 of 3 National Institutes of Health (NIH) sponsored NASH-Clinical Research Network (NASH-CRN) multicenter studies, as well as a cohort of individuals with NASH at the NIH Clinical Center. Study participants had histological evidence of NAFLD or NASH determined by biopsy obtained prior to enrollment. The focus of the study was the PNPLA3 locus on chromosome 22, and especially the non-synonymous coding SNP rs738409 G.

Results indicate that the rs738409 G allele was significantly associated with increased steatosis, portal inflammation, and lobular inflammation. For all of these parameters, genotypes containing rs738409 G were associated with more severe disease. After adjustment for age, gender, body mass index (BMI), diabetes type 2 and alcohol consumption, all associations remained significant.

“Our findings suggest that the rs738409 G allele may predispose patients to fat accumulation in the liver, but that other factors, environmental or hereditary, may be required for the development of inflammation, cellular injury and fibrosis,” says study leader T. Jake Liang, M.D. “However, once patients develop NASH, the rs738409 G allele predisposes them to more severe injury.”

NAFLD is becoming increasingly prevalent in pediatric patients, prompting the researchers to also search for an association between the PNPLA3 SNPs and disease severity in 223 children enrolled in the same study groups as the adults. While no association was found, the presence of the rs738409 G allele was associated with a younger age at the time of liver biopsy, suggesting a younger age of disease presentation.

Concurrent research at Massachusetts General Hospital also identified the G allele of rs738409 in PNPLA3 as a potential risk factor for NAFLD. The Mass General team examined SNPs at 7 loci associated with steatosis in 592 patients of European ancestry from the CRN and 1,405 ancestry-matched controls from the MIGen study. No association was observed between rs738409 G and BMI, triglyceride levels, and high and low-density lipoprotein levels, or diabetes. None of the variants at the other six other loci were associated with NAFLD.

The results suggest that certain inherited variations in lipid metabolism precede and could lead to the development of liver disease. The analysis indicates that genetic variation at PNPLA3 confers a markedly increased risk of severe histological features of NAFLD, without a strong effect on metabolic syndrome component traits. Given that PNPLA3 appears to be part of a family of enzymes that affect lipid metabolism, this suggests that altering lipid metabolism, particularly within the liver, can affect accumulation of fat and subsequent development of NAFLD.

Study leader Elizabeth Speliotes, M.D., Ph.D., M.Ph., concludes, “Through genetic analyses, we may be able to delineate the causal pathways that lead to specific disease complications of metabolic risk factors such as NAFLD and, in the future, selectively target them for therapeutic intervention.”

Full bibliographic information

Article: “PNPLA3 Variants Specifically Confer Increased Risk for Histologic NAFLD but Not Metabolic Disease.” Elizabeth K. Speliotes, Johannah L. Butler, Cameron Palmer, Benjamin F. Voight, the GIANT Consortium, the MIGen Consortium, the NASH CRN, Joel N. Hirschhorn. Hepatology; Published Online: May 18, 2010 (DOI: 10.1002/hep.23768); Print Issue Date: September 2010. http://onlinelibrary.wiley.com/doi/10.1002/hep.23768/abstract

Article: “The Association of Genetic Variability in PNPLA3 with Histological Severity of Non-Alcoholic Fatty Liver Disease.” Yaron Rotman, Christopher Koh, Joseph M. Zmuda, David E. Kleiner, T. Jake Liang, and the NASH CRN. Hepatology; Published Online: May 14, 2010 (DOI: 10.1002/hep.23759); Print Issue Date: September 2010. http://onlinelibrary.wiley.com/doi/10.1002/hep.23759/abstract
 
Source
Robert Roomer 1, Bettina E. Hansen 1,2, Harry L.A. Janssen 1, Robert J. de Knegt 1,*,†

DOI: 10.1002/hep.23842
Copyright © 2010 American Association for the Study of Liver Diseases

Author Information
1 Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
2 Department of Biostatistics, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands

Email: Robert J. de Knegt (r.roomer@erasmusmc.nl)

*Correspondence: Robert J. de Knegt, Department Gastrenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Room Ca-415's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

Ph: 0031 10 7031617

Publication History
Accepted manuscript online: 29 JUL 2010 12:00AM EST
Manuscript Accepted: 6 JUL 2010
Manuscript Revised: 24 JUN 2010
Manuscript Received: 28 APR 2010

Keywords:
Dose reductions;neutropenia;cirrhosis;HCV;age

Abstract

Neutropenia during treatment with peginterferon alfa and ribavirin for chronic hepatitis C (HCV) is a common cause for dose reductions of peginterferon alfa. These reductions are performed to prevent bacterial and fungal infections, which are common during HCV treatment and attributed to neutropenia. The aims of this study were to investigate the occurrence of infections and their relation to neutropenia and to find potential risk factors for infections during HCV treatment.

In this single center cohort study 2876 visits of 321 patients treated with peginterferon alfa and ribavirin were evaluated for neutropenia, infections, dose reductions and potential risk factors for infection during HCV treatment.

Baseline mean absolute neutrophil count (ANC) was 3420 cells/μL, 16 patients had baseline ANC below 1500 cells/μL. During treatment neutropenia defined as ANC <750 cells/μL was observed in 95 patients (29.7%) and ANC < 375/μL was observed in 16 patients (5%). Ninety-six infections were observed in 70 patients (21.8%). Thirteen infections (13.5%) were defined as severe. Infections were not correlated with neutropenia during treatment. Dose reductions did not lead to a decrease in infection rate. In the multivariate logistic regression analysis age older than 55 (OR 2.06, CI 1.19-3.56, p=0.01) and baseline hyperglycemia (OR 2.17 95% CI 1.15-4.10, p=0.016) were associated with an increased risk of infection during HCV treatment. Cirrhosis and chronic obstructive pulmonary disease (COPD) were no risk factors for infections.

Conclusion:

Bacterial infections during treatment with peginterferon alfa and ribavirin are not associated with neutropenia. Older patients and patients with poorly controlled diabetes mellitus are more at risk to develop infections during HCV treatment. (HEPATOLOGY 2010.)

Source

Beta-blockers in cirrhosis: Friend and foe?†

Florence Wong 1,*,‡, Francesco Salerno 2

DOI: 10.1002/hep.23852
Copyright © 2010 American Association for the Study of Liver Diseases

Author Information
1 Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
2 The Policlinico IRCCS San Donato and Dipartimento di Scienze Medico-Chirurgiche, Università di Milano, Italy

Email: Florence Wong (florence.wong@utoronto.ca)

*Correspondence: Florence Wong, 9N/983, Toronto General Hospital, University of Toronto, 200 Elizabeth Street, Toronto, Ontario M5G2C4, Canada

There is no financial support for this article

‡Ph: 416-340 3834; Fax: 416-340 5019

Publication History
Accepted manuscript online: 29 JUL 2010 12:00AM EST
Manuscript Accepted: 8 JUL 2010
Manuscript Received: 29 JUN 2010

Keywords:
propranolol;non-selective beta-blockers;cirrhosis;refractory ascites;sepsis;variceal bleed

Abstract

Patients with cirrhosis are at risk for developing complications that can negatively impact their survival (1). These complications include the development of hepatocellular carcinoma (HCC), sepsis, renal failure and gastrointestinal bleeding, mainly variceal. The risk of bleeding is mainly related to the development of varices from portal hypertension. Bleeding from varices, whether esophageal or gastric, is associated with a mortality risk of 40% at 1 year (2).

Twenty-nine years ago, a randomized controlled trial (RCT) from France involving 74 patients with cirrhosis with a history of gastrointestinal bleeding showed that propranolol, a non-selective beta-blocker (NSBB), significantly reduced the risk of re-bleeding from esophageal varices (3). Since then, 615 papers have been published in the English literature on the use of propranolol or nadolol (the other NSBB) in cirrhosis, both for primary and secondary prophylaxis. In fact, NSBBs have become one of the most effective preventative therapies in patients with cirrhosis (4). The advantage of using NSBBs, however, must be weighed against the risks associated with their chronic use. NSBBs are contraindicated in patients with refractory asthma, respiratory failure, advanced atrio-ventricular block and severe arterial hypotension. In order to improve the risk/benefit ratio, administration of beta blockers is recommended only in patients with a substantial risk of bleeding such as those patients with medium or large varices or patients with small esophageal varices who are Child-Pugh class C (5,6). If possible, hepatic venous pressure gradient (HVPG) should be measured before and 1-2 months after NSBB administration to identify responders (those with a final HVPG <12mmHg or those who show a decrease of ≥20% in HVPG versus the pre-treatment value) who are most likely to benefit from NSBB prophylaxis. Non-responders should discontinue therapy so to prevent the development of side effects when their chances of any therapeutic benefits are small (7). (HEPATOLOGY 2010.)

Source

Quality of Care in Patients With Chronic Hepatitis C Virus Infection

IMPROVING PATIENT CARE

A Cohort Study

Fasiha Kanwal, MD, MSHS; Mark S. Schnitzler, PhD; Bruce R. Bacon, MD; Tuyen Hoang, PhD; Paula M. Buchanan, PhD; and Steven M. Asch, MD, MPH

+ Author Affiliations

Abstract

Background: Medicare has proposed quality-of-care indicators for chronic hepatitis C virus (HCV) infection. The extent to which these standards are met in practice is largely unknown.

Objective: To evaluate the quality of health care that patients with HCV receive and the factors associated with receipt of quality care.

Design: Retrospective cohort study.

Setting: Nationwide U.S. health insurance company research database.

Participants: 10 385 patients with HCV enrolled in the database between 2003 and 2006. Patients were included if they were eligible for at least 1 quality indicator.

Measurements: Quality of HCV care received by patients, as measured by 7 explicit quality indicators included in Medicare's 2009 Physician Quality Reporting Initiative.

Results: Proportions of patients meeting quality indicators varied, ranging from 21.5% for vaccination to 79% for the HCV genotype testing indicator. Overall, 18.5% of patients (95% CI, 18% to 19%) received all recommended care. Older age and presence of comorbid conditions were associated with lower quality, whereas elevated liver enzyme levels, cirrhosis, and HIV infection were associated with higher quality. Patients who saw both generalists and specialists received the best care (odds ratio of receiving care for which a patient is eligible: specialists alone, 0.79 [CI, 0.66 to 0.95]; primary care physician alone, 0.44 [CI, 0.40 to 0.48]).

Limitations: The study had an observational retrospective design, used a convenience sample, and had no information on patient ethnicity. It may be that the indicators or the reporting of the indicators of HCV care—and not the care itself—is suboptimum.

Conclusion: Health care quality, based on Medicare criteria, is suboptimum for HCV. Care that included both specialists and generalists is associated with the best quality. Our results support the development of specialist and primary care collaboration to improve the quality of HCV care.

Primary Funding Source: Saint Louis University Liver Center.

Article and Author Information

Disclaimer: The opinions and assertions contained herein are the sole views of the authors and are not to be construed as official or as reflecting the views of the Department of Veterans Affairs.

Grant Support: Dr. Kanwal is supported by Veterans Affairs Health Services Research and Development Service Investigator Initiated Research Award IIR-07-111. This study was supported by an intramural grant from the Saint Louis University Liver Center.

Potential Conflicts of Interest: Dr. Kanwal: Grants received: Saint Louis University Liver Center. Dr. Bacon: Consultancies: Merck/Schering-Plough, Valeant. Honoraria: Merck/Schering-Plough, Gilead Sciences, Three Rivers Pharma, Vertex, Human Genome Sciences. Royalties: UpToDate. Dr. Bacon has also received payment for development of educational presentations, including service on speakers' bureaus, and has had his travel/accommodations expenses covered or reimbursed. Dr. Buchanan: Grants received (money to institution): Veterans Affairs Health Services Research and Development Service, Saint Louis University Liver Center. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M09-2380.

Reproducible Research Statement: Study protocol: Available from Dr. Kanwal (e-mail, fasiha.kanwal@va.gov). Statistical code: Available from Dr. Kanwal (e-mail, fasiha.kanwal@va.gov), Dr. Schnitzler (e-mail, schnitm@slu.edu), or Dr. Buchanan (e-mail, pbuchan1@slu.edu). Data set: Not available. These or similar data are available from commercial health insurance companies in the United States.

Requests for Single Reprints: Fasiha Kanwal, MD, MSHS, John Cochran Veterans Affairs Medical Center, 915 North Grand Boulevard, 111 JC/GI, St. Louis, MO 63106; e-mail, fasiha.kanwal@va.gov.

Current Author Addresses: Dr. Kanwal: John Cochran Veterans Affairs Medical Center, 915 North Grand Boulevard, 111 JC/GI, St. Louis, MO 63106.

Drs. Schnitzler and Buchanan: Center for Outcomes Research, Saint Louis University School of Medicine, 3545 Lafayette Avenue, St. Louis, MO 63104.

Dr. Bacon: Saint Louis University School of Medicine, Department of Internal Medicine, Division of Gastroenterology & Hepatology, 3635 Vista Avenue at Grand Boulevard, St. Louis, MO 63110-0250.

Drs. Hoang and Asch: Department of Internal Medicine and Health Services Research, Veterans Affairs Greater Los Angeles Medical Center, 11301 Wilshire Boulevard, Building 500 (111-G), Los Angeles, CA 90073.

Author Contributions: Conception and design: F. Kanwal, M.S. Schnitzler, S.M. Asch.

Analysis and interpretation of the data: F. Kanwal, M.S. Schnitzler, T. Hoang, P.M. Buchanan, S.M. Asch.

Drafting of the article: F. Kanwal, M.S. Schnitzler, P.M. Buchanan, S.M. Asch.

Critical revision of the article for important intellectual content: F. Kanwal, M.S. Schnitzler, B.R. Bacon, S.M. Asch.

Final approval of the article: M.S. Schnitzler, B.R. Bacon, P.M. Buchanan, S.M. Asch.

Provision of study materials or patients: M.S. Schnitzler.

Statistical expertise: M.S. Schnitzler, T. Hoang, P.M. Buchanan.

Obtaining of funding: F. Kanwal, M.S. Schnitzler.

Administrative, technical, or logistic support: F. Kanwal, B.R. Bacon.

Collection and assembly of data: M.S. Schnitzler, P.M. Buchanan.

Source
Salvatore Petta 1,*,‡, Marco Amato 2, Daniela Cabibi 3, Calogero Cammà 1, Vito Di Marco 1, Carla Giordano 2, Aldo Galluzzo 2, Antonio Craxì 1

DOI: 10.1002/hep.23859
Copyright © 2010 American Association for the Study of Liver Diseases

Author Information

1 Cattedra di Gastroenterologia, DiBiMIS, University of Palermo, Italy
2 Dipartimento di Oncologia Sperimentale ed Applicazioni Cliniche (DOSAC), Section of Endocrinology, University of Palermo, Italy
3 Cattedra di Anatomia Patologica, University of Palermo, Italy
Email: Salvatore Petta (petsa@inwind.it)

*Correspondence: Salvatore Petta, Gastroenterologia & Epatologia, Piazza delle Cliniche, 2, 90127 Palermo, Italy

†FINANCIAL SUPPORT No conflict of interest exists.

‡Ph: +39 091 655 2145; Fax +39 091 655 2156

Publication History
Accepted manuscript online: 29 JUL 2010 12:00AM EST
Manuscript Accepted: 13 JUL 2010
Manuscript Revised: 9 JUL 2010
Manuscript Received: 20 MAY 2010

Abstract

Background and Aims:
Metabolic factors have been associated with liver damage in patients with genotype 1 chronic hepatitis C (G1 CHC). We tested visceral adiposity index (VAI), a new marker of adipose dysfunction in G1 CHC patients to assess its association with host and viral factors, and its link to both histological findings and sustained virologic response (SVR).

Materials and Methods:
Two hundred thirty-six consecutive G1 CHC patients were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR, the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and HDL. All biopsies were scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate-severe if ≥30%.

Results:
VAI score was independently associated with higher HOMA score (p=0.009), higher Log10 HCV RNA levels (p=0.01), necroinflammatory activity (p=0.04), and steatosis (p=0.04), by multiple linear regression analysis. IR (OR 3.879,95%CI 1.727–8.713, p=0.001), higher VAI score (OR 1.472,95%CI 1.051–2.062, p=0.02), and fibrosis (OR 2.255,95%CI 1.349–3.768, p=0.002) were linked to steatosis ≥30% by multiple logistic regression analysis. Older age (OR 1.030;95% CI 1.002-1.059; p=0.03), high VAI score (OR 1.618;95%CI 1.001-2.617; p=0.04) and fibrosis (OR 2.608;95%CI 1.565-4.345; p<0.001) were independently associated with moderate-severe necroinflammatory activity by logistic regression analysis. No independent associations were found between VAI score and both fibrosis and SVR.

Conclusion:
In G1 CHC patients, higher VAI score, a new index of adipose dysfunction, is independently associated with both steatosis and necroinflammatory activity, and has a direct correlation with viral load. (HEPATOLOGY 2010.)

Source
JOURNAL OF CLINICAL VIROLOGY
doi:10.1016/j.jcv.2010.07.006
© 2010 Elsevier B.V. All rights reserved.
 
B.A. Payer, T. Reiberger, K. Rutter, S. Beinhardt, A.F. Staettermayer, M. Peck-Radosavljevic, P. Ferenci
Received 12 May 2010; received in revised form 1 July 2010; accepted 6 July 2010. published online 16 August 2010.
Corrected Proof

Abstract

Introduction
The efficacy of antiviral therapy with pegylated interferon (PEGIFN) plus ribavirin (RBV) in patients with HIV and hepatitis C virus (HCV) coinfection is limited. Intravenous silibinin (ivSIL), a milk thistle extract with proven antiviral effects represents a novel therapeutic strategy for virological nonresponders.

Methods
We report a case of an HIV–HCV coinfected patient, who has not responded to a prior course of PEGIFN-α2a (180μg/week/s.c.) and RBV (1000mg/day/p.o.). Testing for IL-28β small nucleotid polymorphism revealed the nonfavourable genotype T/T. Antiretroviral therapy was not prescribed because the patients presented with well-preserved CD4+ cell counts and low HIV-RNA levels. She received retreatment with ivSIL for two weeks followed by PEGIFN/RBV combination therapy starting at week 1.

Results
After 2 weeks of ivSIL therapy both HCV-RNA and HIV-RNA become undetectable. On ivSIL monotherapy we noticed a trend towards an increase of CD4+ cell counts and a decrease of HIV-RNA. After 16 weeks PEGIFN+RBV was discontinued due to patients wish because of adverse events. HCV-RNA was still negative 24 weeks after cessation of therapy, while HIV-RNA returned to baseline levels.

Conclusion
ivSIL may represent a potential treatment option for retreatment of HIV–HCV coinfected patients nonresponding to PEGIFN+RBV combination therapy. Further investigations on the possible beneficial effects of ivSIL on CD4+ cell counts and HIV-RNA levels are necessary.

Keywords: HCV, HIV, Silibinin, Pegylated interferon, Ribavirin, Nonresponse

Source

JBC Thematic Series Explores Hepatitis C Virus

BY NICK ZAGORSKI


The JBC recently unveiled a new thematic minireview series to showcase some of the recent advances in understanding the hepatitis C virus.

Hepatitis C virus is a member of the hepacivirus viral group and the causative agent of hepatitis C, an infectious disease affecting as many as 180 million people worldwide, and a major contributor to chronic liver diseases, including cirrhosis and hepatocellular carcinoma. Although much has been learned about how HCV replicates and how the virus is transmitted, it remains problematic from a therapeutic standpoint. Unlike the related HBV, there is no effective vaccine against HCV, and the present treatment for HCV infection, a regimen of pegylated interferon alpha and the antiviral drug ribavirin, shows varying success rates of 40–80 percent, depending on HCV genotype.

Recently, though, researchers have made significant advances in understanding HCV biochemistry, its life cycle and its interaction with hosts, which may lead to improved treatments and an effective vaccine. To showcase some of these important new findings, the Journal of Biological Chemistry recently presented a thematic review series titled “Hepatitis C Virus-host Interactions.”

This minireview series, coordinated by JBC Associate Editor Charles E. Samuel of the University of California, Santa Barbara, appeared in the May 10 issue of the journal and is collectively available online.

The series consists of five minireviews, two of which appeared in the JBC in previous years but provide an important foundation for the newer studies. The first is a 2006 review by Ralf Bartenschlager and colleagues titled “From Structure to Function: New Insights into Hepatitis C Virus RNA Replication.” The paper describes structural and biochemical insights into HCV RNA replication gained from HCV replicon systems and other methods allowing for efficient propagation of infectious HCV in tissue culture. The subsequent development of a cell-culture system that permitted the complete replication of HCV provided a tool to biochemically delineate the initial processes in infection, namely virion attachment and entry. These advances are described in the 2008 review by Thomas von Hahn and Charles M. Rice entitled “Hepatitis C Viral Entry.”

In the first of the three new minireviews, titled “Hepatitis C Virus Non-structural Protein 3 (HCV NS3): a Multifunctional Antiviral Target,” Craig E. Cameron and colleagues discuss new developments in the biochemistry and structural biology of the bifunctional NS3 protein, which possesses both serine protease activity (in the N-terminal region) and RNA helicase activity (in the C-terminal region). The second new minireview, written by Daniel M Jones and John McLauchlan and titled “Hepatitis C Virus: Assembly and Release of Virus Particles,” summarizes progress in understanding HCV protein trafficking and the various stages of virion assembly and release. The third and final minireview is by Stanley M. Lemon. Titled “Induction and Evasion of Innate Antiviral Responses to Hepatitis C Virus,” this article summarizes the progress in understanding the cellular signaling pathways and antiviral responses antagonized by HCV proteins and the multiple strategies utilized by HCV to evade activated innate antiviral responses.

Together, these five minireviews provide a comprehensive overview of the current state of HCV research and should be a valuable resource to all.

Nick Zagorski (nzagorski@asbmb.org) is a science writer at ASBMB.

Source
International Journal of Cancer
DOI: 10.1002/ijc.25585
Copyright © 2010 UICC

Author Information

Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan
Email: Sheng-Nan Lu M.D., M.P.H., Ph.D. (juten@ms17.hinet.net)

*Correspondence: Sheng-Nan Lu M.D., M.P.H., Ph.D., Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital. 123 Ta Pei Road, Niao Sung 833 Kaohsiung, Taiwan
†Ph: 886-7-7317123 ext. 8301; Fax: 886-7-7322402

Publication History
Accepted manuscript online: 28 JUL 2010 12:00AM EST
Manuscript Accepted: 13 JUL 2010
Manuscript Revised: 22 JUN 2010
Manuscript Received: 30 MAR 2010

Funded by
Chang Gung Memorial Hospital, Taiwan. Grant Number: CMRPG880241
 
Keywords:
hepatitis C virus;diabetes mellitus;interferon;hepatocellular carcinoma;survival

Abstract
There is strong evidence linking chronic hepatitis C virus (HCV) infection and type 2 diabetes mellitus (DM). Recent studies have suggested that DM is associated with increased risk of developing hepatocellular carcinoma (HCC). The aim of this cohort study was to assess whether DM influence the incidence of HCC in chronic hepatitis C patients treated with interferon (IFN)-based antiviral therapy. A total of 1,470 chronic hepatitis C patients treated with IFN or pegylated-IFN plus ribavirin therapy were enrolled. Of them, 253 (17%) patients had DM at entry. Evaluation of HCC incidence was performed by Kaplan-Meier method and Cox proportional hazards analysis. Patients with baseline DM were significantly older and had higher body mass index, serum transaminase levels and fibrosis scores and lower platelet counts compared with non-DM subjects. Sustained virological response (SVR) was achieved in 160 (63%) of DM and 867 (71%) of non-DM patients (P=0.008). During a median follow-up period of 4.3 years, HCC developed in 21 (8.3%) of DM and 66 (5.4%) of non-DM patients (P=0.017). However, DM was not an independent covariate by Cox proportional hazards analysis. In a subgroup analysis, DM (hazard ratio, 4.32; 95% confidence interval, 1.23-15.25; P=0.023) was an independent predictor of HCC in the SVR patients without baseline cirrhosis, despite a low HCC incidence. In conclusion, DM has a selective impact on HCC development among chronic hepatitis C patients after IFN-based therapy. DM may increase the HCC risk in chronic hepatitis C without cirrhosis after eradication of HCV.

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Body composition analysis using phase angle (PA), determined by bioelectrical impedance analysis (BIA), reflects tissue electrical properties and has prognostic value in liver cirrhosis. Objective of this prospective study was to investigate clinical use and prognostic value of BIA-derived phase angle and alterations in body composition for hepatitis C infection (HCV) following antiviral therapy.

Methods: 37 consecutive patients with HCV infection were enrolled, BIA was performed and PA was calculated from each pair of measurements. 22 HCV genotype 3 patients treated for 24 weeks and 15 genotype 1 patients treated for 48 weeks, were examined before and after antiviral treatment and compared to 10 untreated HCV patients at 0, 24, and 48weeks.

Basic laboratory data were correlated to body composition alterations.

Results: Significant reduction in body fat (BF: 24.2+/-6.7kg vs.

19.9+/-6.6kg genotype1; 15.4+/-10.9kg vs. 13.2+/-12.1kg genotype3) and body cell mass (BCM: 27.3+/-6.8kg vs.

24.3+/-7.2kg genotype1; 27.7+/-8.8kg vs. 24.6+/-7.6kg genotype3) was found following treatment.

PA in genotype 3 patients was significantly lowered after antiviral treatment compared to initial measurements (5.9+/-0.7degrees vs. 5.4+/-0.8degrees).

Total body water (TBW) was significantly decreased in treated patients with genotype 1 (41.4+/-7.9l vs. 40.8+/-9.5l).

PA reduction was accompanied by flu-like syndromes, whereas TBW decline was more frequently associated with fatigue and cephalgia. Discussion: BIA offers a sophisticated analysis of body composition including BF, BCM and TBW for HCV patients following antiviral regimens.

PA reduction was associated with increased adverse effects of the antiviral therapy allowing a more dynamic therapy application.

Author: Alisan KahramanJohannes HilsenbeckMonika NygaJudith ErtleAlexander WreeMathias PlauthGuido GerkenAli Canbay

Credits/Source: Virology Journal 2010, 7:191

Published on: 2010-08-16

Source
Carine Jubert, MD; Jean-Michel Pawlotsky, MD; Florence Pouget, MD; Chantal Andre, PhD; Lionel DeForges; Stéphane Bretagne, MD; Jean-Philippe Mavier, MD, PhD; Jean Duval, MD; Jean Revuz, MD; Daniel Dhumeaux, MD; Martine Bagot, MD, PhD

Arch Dermatol. 1994;130(1):73-76.

Abstract

Background and Design
An increased prevalence of chronic liver disease has been reported in patients with lichen planus (LP). We report six cases of LP associated with chronic active hepatitis and actively replicating hepatitis C virus (HCV).

Results
We studied six patients (three men and three women; mean age, 61 years; age range, 47 to 70 years) with various forms (cutaneous and/or mucosal) of LP and abnormal liver test results. Four patients had severe mucosal lesions. Cutaneous and mucosal lesions had a long-term evolution. Liver disease was discovered 2 to 6 years before LP in three cases and was diagnosed at the same time as LP in the three other cases. Liver biopsy performed in five patients showed chronic active hepatitis without cirrhosis in all five cases. Anti—HCV antibodies were detected in all cases by second-generation enzyme-linked immunosorbent assay and confirmed by second-generation recombinant immunoblot assay. Hepatitis C virus RNA was evidenced by means of polymerase chain reaction in the serum samples from the six patients, proving active viral replication.

Conclusions
Lichen planus may be associated with HCV-related chronic active hepatitis. As interferon treatment may induce viral inactivation in some patients with HCV-related chronic liver disease, a search for HCV infection should be systematically performed in patients with chronic LP.

(Arch Dermatol. 1994;130:73-76)

Author Affiliations
From the Departments of Dermatology (Drs Jubert, Pouget, Revuz, and Bagot), Bacteriology and Virology (Drs Pawlotsky, DeForges, Bretagne, and Duval), Immunology (Dr Andre), and Hepatology (Drs Mavier and Dhumeaux), University of Paris XII, Créteil, France.

Source
Fatty acid synthase (FASN) is an enzyme synthesized by the liver and plays an important role in lipogenesis. The present study aimed to investigate whether serum FASN concentration may provide a direct link between HIV and/or HCV viral infections and lipid metabolic disorders commonly observed in HIV/HCV-infected patients.

Methods: We evaluated serum FASN concentration in 191 consecutive HIV-infected patients in the absence or presence of HCV co-infection.

For comparison, 102 uninfected controls were included. Metabolic and inflammatory phenotype was also compared with respect to the presence of HCV co-infection.

Results: Serum FASN concentration was significantly higher in HIV-infected patients than in healthy participants and HCV co-infected patients showed higher levels than those without co-infection.

Levels were also affected by treatment regimen, but marginally influenced by virological variables. Insulin concentration was the sole variable among metabolic parameters that demonstrated a significant correlation with serum FASN concentrations.

Serum alanine aminotransferase (ALT) values correlated significantly with serum FASN concentration and provided the best discrimination with respect to the presence or absence of HCV co-infection. In multivariate analysis, only ALT, monocyte chemoattractant protein-1 (MCP-1) and the presence of antiretroviral treatment regimen significantly contributed to explain serum FASN concentration in HIV/HCV co-infected patients.

Conclusion: Serum FASN concentration is significantly increased in HIV-infected individuals.

The release of FASN into the circulation is further enhanced in patients who are co-infected with HCV. Subsequent studies should explore the usefulness of this indicator to monitor the effect of viral infections on disease progression and survival.

Author: Gerard AragonesCarlos Alonso-VillaverdeCristina Oliveras-FerrarosRaul Beltran-DebonAnna RullFernando Rodriguez-SanabriaJordi CampsAlejandro Vazquez-MartinJavier MenendezJorge Joven

Credits/Source: BMC Gastroenterology 2010, 10:92

Published on: 2010-08-13
 
Source

New stem cell discovery a preliminary step for regenerative medicine

Published: 16 August 2010

A discovery by researchers at UQ's Australian Institute for Bioengineering and Nanotechnology (AIBN) will enable better methods to grow stem cells for use in cancer research and regenerative medicine.

The research team led by AIBN's Associate Professor Ernst Wolvetang found that the inclusion of vitamin C in cell culture media was responsible for chemical modification of DNA which has been known to cause chromosome instability and cancer in laboratory stem cell populations.

According to Dr Wolvetang, this discovery is important for stem cell researchers because they rely on genetically stable, non-cancerous stem cells to develop methods to repair damaged or diseased tissues.

“In order to obtain sufficient cells for regenerative medicine applications, human pluripotent stem cells are grown in the laboratory to increase the number of cells,” Dr Wolvetang said.

“Because vitamin C is essential for human health, we were surprised that it had such a detrimental effect on stem cells in culture.

“We found that it causes widespread yet specific loss of DNA-methylation in stem cells, a chemical modification crucial to normal development and cellular differentiation in mammals.

“With this knowledge we can develop better methods to grow stem cells in the laboratory, which will improve our understanding of them and how we might harness their potential in the fight against disease,” he said.

Stem cells are an attractive tool in treating cancer and many other diseases due to their ability to differentiate into any cell type in the human body.

This work was the subject of two publications in the international journal Stem Cells.

AIBN is a multidisciplinary research institute focused on addressing some of the intricate problems in the areas of health, energy and the environment.

Media contact Associate Professor Wolvetang +61 7 3346 3894

Source
Hepatology International
DOI: 10.1007/s12072-010-9207-1

Venessa Pattullo, E. Jenny Heathcote and David K. H. Wong

Abstract

Purpose
Reported sustained virological response (SVR) rates in Asians with chronic hepatitis C (CHC) exceed those of other ethnic groups, but differences in body weight across races potentially confound this observed superior response. Our aim was to determine whether Asian race independently predicts SVR within a multicultural clinic setting.

Methods
Patients with genotype 1, 2 and 3 CHC prescribed peginterferon and weight-based ribavirin were included in this retrospective study. Logistic regression was performed to identify factors associated with SVR.

Results
Three-hundred ninety-two patients (BMI 26.9 ± 5.0 kg/m2, genotype 1 66%, viral load 5.9 ± 0.66 log10 IU/ml, advanced fibrosis 53%) were included in this study. Caucasians comprised 81%, South Asians 9% and Asians (Non-South) 10%. SVR was achieved by 54% overall, but was highest amongst Asians (Non-South) (79%) compared with South Asians (56%, P = 0.04) and Caucasians (50%, P < 0.001) despite a predominance of genotype 3 infection amongst the South Asians. Asians (Non-South) had the highest SVR rate even amongst those infected with genotype 1 (75%) and those with advanced fibrosis (77%). Independent of viral genotype, Asian (Non-South) race was a strong predictor of SVR (OR 5.10 vs. Caucasians, 95% CI 1.72–17.71, OR 7.84 vs. South Asians, 95% CI 1.62–37.84), as were treatment naïve status (OR 3.85, 95% CI 1.76–8.89), non-diabetic status (OR 3.70, 95% CI 1.30–11.11), non-obesity (OR 2.13, 95% CI 1.06–4.35), peginterferon α2a (2.08 vs. α2b, 95% CI 1.16–3.85), steatosis <10% (OR 2.0, 95% CI 1.05–3.85) and ribavirin exposure (mg/kg/day) (OR 1.13, 95% CI 1.01–1.28).

Conclusion
Asian (Non-South) race is a strong independent predictor of SVR.

Keywords Asian - Sustained virological response - Body mass index - Weight - Obesity - Diabetes - Chronic hepatitis C


Source
NEW YORK (Reuters Health) Aug 13 - In patients being simultaneously treated for HIV and hepatitis C virus (HCV), treating the HCV with interferon and ribavirin doesn't change its protease gene diversity nor make it resistant to protease inhibitors (PI), a new study has shown.
In other words, it looks as if "prior HCV treatment with interferon-ribavirin would not markedly impact the potential efficacy of subsequent HCV protease inhibitors treatment in coinfected patients," the researchers report in an August 3rd online article in the Journal of Infectious Diseases.

A majority of the patients in the study had not responded to interferon-ribavirin, but neither did they develop PI resistance mutations in the crucial HCV non structural protein gene 3 (NS3). This gene codes for an HCV protease with an important role in viral replication, the researchers explain.

The rapid multiplication of HCV RNA polymerase results in many circulating variants of the virus called quasispecies, some of which may carry resistant mutations, lead researcher Dr. Aarthi Chary from the Veterans Affairs Palo Alto Health Care System, California and colleagues write.

As a part of a wider prospective analysis of interferon-ribavirin treatment of HCV, the researchers evaluated the variations in HCV NS3 genes in 26 coinfected patients. All were receiving antiretroviral therapy (ART) for HIV, along with weekly or fortnightly subcutaneous interferon and daily oral ribavirin for HCV.

Eleven patients achieved a sustained viral response to interferon/ribavirin.

Baseline diversity in the NS3 gene prior to starting treatment, measured as the median inter nucleotide distance, was significantly greater in the patients who did not respond or who relapsed, the report says.

However, interferon-ribavirin treatment did not induce any new changes in the gene diversity or HCV protease inhibitor resistant mutations.

Although the study size was small, these results substantiate the potential role of HCV-protease inhibitors in difficult-to-treat HCV infections, the researchers write.

"As HCV protease inhibitors are introduced in clinical practice, further understanding of HCV NS3 diversity in this therapeutically challenging coinfected population is needed," Dr. Chary's team concludes.

J Infect Dis. Posted online August 3, 2010. Abstract

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Out of Grief Sprouts a Life-Saving Legacy

By JANE E. BRODY
Published: August 16, 2010

You don’t have to be rich, famous or even an adult to leave a memorable legacy that can change lives.

Just ask Stacey Oglesby of Lockwood, Mo., whose 15-year-old daughter, Colbey, died in a car accident in 2001. Colbey had told her mother that when she got her driver’s license, she was going to sign up to be an organ donor. So when hospital personnel asked about organ donation, Ms. Oglesby said, “we had no hesitancy.”

Seven people got Colbey’s organs. Her lungs went to Valerie Vandervort, a 29-year-old Oklahoma woman with cystic fibrosis. In the nine years since, Ms. Vandervort has run three 5K races, hiked a mountain, danced at her sister’s wedding, doted on her nieces and nephews, and won medals in swimming at the 2010 National Kidney Foundation United States Transplant Games.

Ms. Oglesby also befriended the recipient of Colbey’s heart, Judy Kaufman of Chesterfield, Mo., who was near death with congestive heart failure. When they met, Ms. Oglesby took a stethoscope to listen to the beat of her daughter’s heart.

Ms. Oglesby, who speaks often about Colbey’s legacy, said she has inspired others to become potential organ donors. If not for donating her daughter’s organs and connecting to the recipients, she said, “it would have been hard to get through the grief.”

A Widespread Need

At any given time in the United States, more than 100,000 people are waiting for donor organs, more than 10 times as many as become available. Some die waiting; others get sicker and sicker, sometimes too ill to survive when a suitable organ finally becomes available.

In addition to kidneys, heart, lungs, liver, pancreas and intestines, donations can include tissues like corneas, skin, heart valves, bone, veins, cartilage, middle ear, tendons and ligaments that can be stored in tissue banks and used when needed.

Most donations come from people who die suddenly, usually from an accident, a gunshot or a brief illness that resulted in brain death. (A small but growing number of donations follow cardiac death.) Some adults indicate their wish to be donors by signing the back of their driver’s license or a donor card or simply telling their next of kin. For minors, hospital personnel often ask the distraught parents if they would consider donating their child’s organs.

But when 6-year-old Katie Coolican died in 1983 from an undiagnosed heart malformation, it was her mother, Maggie, a nurse, who asked about donating the child’s organs — “to make some sense of it all,” Ms. Coolican, of East Hampton, Conn., said in an interview.

“We were willing to donate anything,” she added, “but at the time all they could use were Katie’s corneas and kidneys.”

Likewise for Julie Schlueter of Winsted, Minn., whose daughter, Missy, 10, died of a cerebral hemorrhage in 1992: donating the girl’s organs meant her loss was not in vain.

Missy’s liver and one kidney went to a man who four years later won a silver medal in the Summer Olympics in Atlanta; he sent the medal to the Schlueters to thank them for enabling him to live. Two toddlers, one from Italy and the other from Colorado, got Missy’s heart valves. And an Iowa woman, then 47, got her other kidney and is still doing well 18 years later.

Rose D’Acquisto of St. Paul said that donating all her husband’s usable organs “has led to things I’d never imagined.”

Her husband, Tony, died in 1996 at age 35 when an undiagnosed brain tumor hemorrhaged and left him in an irreversible coma. Ms. D’Acquisto said the recipient of his liver — an Indiana man near death with a rare liver disease — had now been married more than 30 years and has three grown children.

And the Minnesota farmer who got one of Tony’s kidneys got his life back; he had spent three years traveling three hours a day three times a week for dialysis.

Ms. D’Acquisto, now remarried, says she continues to write and speak about organ donation as love’s greatest gift. Along with Ms. Schlueter, she was among more than 7,000 people who attended the Transplant Games last month in Madison, Wis.

When Katie Coolican died, there was no follow-up care for families who donate the organs of their loved ones. After a few years of struggling with grief, her mother wrote about her experience in The American Journal of Nursing and began speaking about organ donation all over the country.

She went back to school, got a master’s degree and wrote a booklet, “For Those Who Give and Grieve,” that was published by the National Kidney Foundation. (The foundation also publishes a quarterly newsletter with that title, edited by Ms. D’Acquisto.)

“Katie’s had a wonderful legacy that continues to this day,” Ms. Coolican said. In 1992 she founded the National Donor Family Council for the kidney foundation to help grieving families that donate loved ones’ organs and tissues. The two-year follow-up program she created for families has become a model for organ donation programs throughout the country.

(To read more “gift of life” stories about organ donation, see the Web site org/gift/index.html.)

Who Is Eligible to Give?

Do not rule yourself out as a potential donor because you think you may be too ill or too old. Only a few circumstances, like pervasive infection or active cancer, absolutely preclude organ donation, and there is no age limit. People in their 80s and 90s have been successful donors of certain tissues, as have newborns. But for anyone under 18, a parent or guardian must approve the donation.

Even if a person dies after an illness that precludes organ donation, or if too much time elapsed after death for organs to be viable, there is still the opportunity of whole-body donation to a medical college, where the body can be used in research or to help students learn anatomy.

While it is best to register one’s interest in whole-body donation with a medical school in advance of death, after death it is up to the next of kin to make it happen. You no longer own your body after you die. If this is something you would want for yourself, discuss it with your spouse and children, who must agree with your wishes.

Most religions support organ donation as a charitable act, although some may not condone whole-body donation. Check the Web site http://www.organdonor.gov/ and click on “Religious Views on Donation” for guidance.

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