August 19, 2010

A Cure for HIV Could Be All in the 'Mix'

ScienceDaily (Aug. 18, 2010) — Current HIV treatments do not eradicate HIV from host cells but rather inhibit virus replication and delay the onset of AIDS. However, a new research study published in BioMed Central's open access journal, AIDS Research & Therapy describes an innovative approach to eliminate HIV in host by targeted killing of only HIV infected cells. This approach if successful could lead into an anti-HIV therapy that will eradicate the virus.

On infection, HIV spreads through the human body after the viral DNA is incorporated into the genome of host cells. Highly Active Anti-Retroviral Therapy (HAART) works by blocking HIV replication at various steps but does not eliminate the infected cells.

Professors Abraham Loyter, Assaf Friedler and their colleagues at Hebrew University, Jerusalem, focussed on the elimination of infected cells. Prof. Loyter contends that while HIV integrates its DNA into the human genome, it only inserts enough DNA to replicate yet avoids host genome instability leading to programmed death of the infected cells (apoptosis).

Dr. Loyter and his team sought to induce increased integration of HIV DNA into human genome that could lead to apoptosis. Toward that goal, they developed peptides (called "mix") that can penetrate into infected cells and stimulate the activity of the viral integrase. The stimulation of the viral integrase resulted in an increase in the number of the viral DNA molecules integrated into the infected cells that lead the infected cells into "panic mode," causing self-destruction.

Dr Loyter said: "Whilst this research is promising, a major caveat with these studies is that they are preliminary. So far these experiments have only been shown to 'cure' HIV from small dishes of cultured cells in the authors' laboratory, but the findings are an exciting development in the quest to eradicate this devastating global pandemic."

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August 19, 2010
 
CAMDEN – When kitchens become infiltrated with fruit flies, especially during the dog days of summer, homeowners might wish that the flying pests would just turn to ice.
 
The fruit fly Drosophila melanogaster does boast a powerful genetic system making it an ideal organism to test a cool new discovery: how an enzyme regulates body energy levels. Shutting off this molecular thermostat could result in a newfound cold tolerance that has multiple applications, including extending the 24-hour window donated organs now have for optimum use.

Thanks to a $385,419 grant from the National Institute of Health, a team of Rutgers–Camden biologists is working to engineer cold tolerant fruit flies and ultimately human cells within the next three years.

This research breakthrough can be credited to Daniel Shain, a professor of biology at Rutgers–Camden, who has traveled the globe seeking knowledge on how ice worms don’t just survive in glaciers, but thrive. When Shain identified a key enzyme that helps ice worms do this – AMP phosphatase – he tapped Nir Yakoby, an expert Drosophila geneticist and assistant professor of biology at Rutgers–Camden, to create this cold-tolerant fruit fly.

“The goal is to make human cells survive on ice. Twenty-four hours on ice is pushing it and many people die waiting,” says Shain, who is scheduled to travel to Tibet next year to observe ice worms in the vicinity. “We’re lucky to have an expert Drosophila geneticist on campus to test this genetic switch.”

Not just the ice worm lives on ice; the Rutgers–Camden research team, which includes undergraduate and graduate students, observed how other organisms, like bacteria, fungi, and algae, also are breaking through their internal thermostats.

“Shain accomplished this switch in mono-cell organisms and now we are going further up into the evolutionary tree to a more complex species,” offers Yakoby, who joined the Rutgers­–Camden faculty last year after conducting postdoctoral research at Princeton University’s Lewis Sigler Institute for Integrative Genomics. “If we can get these human cells to survive on ice, we should expect organs to do the same. Organs are just a collection of cells.”

A graduate of the University of New Hampshire, where he earned both his bachelor’s and master’s degrees, Shain earned his doctorate from Colorado State University and held a postdoctoral fellowship through the national Institute of Health at the University of California-Berkeley.

Yakoby, who earned his undergraduate and doctoral degrees from Hebrew University in Israel, teaches genetics at Rutgers–Camden. Both Shain and Yakoby are active members of the Rutgers–Camden Center for Computational and Integrative Biology, which offers doctoral and graduate programs and strives to determine the quantitative organizational principles of complex biological systems, using a combination of theoretical and experimental approaches.

Media Contact: Cathy K. Donovan
(856) 225-6627
E-mail: catkarm@camden.rutgers.edu

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Published on: 2010-08-19

Hyaluronic acid (HA) serum levels correlate with the histological stages of liver fibrosis in hepatitis C virus (HCV) monoinfected patients, and HA alone has shown very good diagnostic accuracy as a non-invasive assessment of fibrosis and cirrhosis. The aim of this study was to evaluate serum HA levels as a simple non-invasive diagnostic test to predict hepatic fibrosis in HIV/HCV-coinfected patients and to compare its diagnostic performance with other previously published simple non-invasive indexes consisting of routine parameters (HGM-1, HGM-2, Forns, APRI, and FIB-4).

Methods: We carried out a cross-sectional study on 201 patients who all underwent liver biopsies and had not previously received interferon therapy.

Liver fibrosis was determined via METAVIR score. The diagnostic accuracy of HA was assessed by are under the receiver operating characteristic curves (AUROCs).

Results: The distribution of liver fibrosis in our cohort was 58.2% with significant fibrosis (F[greater than or equal to]2), 31.8% with advanced fibrosis (F[greater than or equal to]3), and 11.4% with cirrhosis (F4).

Values for the AUROC of HA levels corresponding to significant fibrosis (F[greater than or equal to]2), advanced fibrosis (F[greater than or equal to]3) and cirrhosis (F4) were 0.676, 0.772, and 0.863, respectively. The AUROC values for HA were similar to those for HGM-1, HGM-2, FIB-4, APRI, and Forns indexes.

The best diagnostic accuracy of HA was found for the diagnosis of cirrhosis (F4): the value of HA at the low cut-off (1182 ng/mL) excluded cirrhosis (F4) with a negative predictive value of 99% and at the high cut-off (2400 ng/mL) confirmed cirrhosis (F4) with a positive predictive value of 55%. By utilizing these low and high cut-off points for cirrhosis, biopsies could have theoretically been avoided in 52.2% (111/201) of the patients.

Conclusions: The diagnostic accuracy of serum HA levels increases gradually with the hepatic fibrosis stage.

However, HA is better than other simple non-invasive indexes using parameters easily available in routine clinical practice only for the diagnosing of cirrhosis.

Author: Salvador ResinoJose BellonCristina AsensioDariela MicheloudPilar MirallesAna VargasPilar CatalanJuan LopezEmilio AlvarezJaime CosinRaquel LorenteMaria Munoz-FernandezJuan Berenguer

Credits/Source: BMC Infectious Diseases 2010, 10:244

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Testing for disease with paper the size of a postage stamp

Diagnostics For All device

By Christina Hernandez
Aug 19, 2010

It’s postage stamp-sized technology with global implications for healthcare. With a mission to provide diagnostics for the developing world that are cheap, portable and easy to use, the nonprofit Diagnostics For All has developed a testing technology made from paper.

Founded in 2007 on the work of George Whitesides, a chemistry professor at Harvard University, the Massachusetts-based Diagnostics For All is preparing to begin field testing its device next year. I spoke last week with CEO Una Ryan about the implications of this technology in the developing world — and in the United States.

Your diagnostic tool is made from patterned paper. How does that work?

Instead of trying to re-engineer some of the big, expensive devices we have in the U.S., [we thought] about the problem and what would be the cheapest, most convenient way to address it. The cheapest and most ubiquitous substance that’s available worldwide is paper. We have printed micro-fluidic channels onto the paper. If you take a biological fluid, like blood or urine or tears, it will move down that pathway and interact with chemicals we put in those reservoirs. You get a color reaction that you can easily read by eye. For a more permanent record, you can take a cell phone picture of it. Since everything we do is telemedicine compatible, it gives us the opportunity to make some amazing databases tracking worldwide health trends.

Which medical conditions can the technology detect?

Ultimately we want it to be for everything, so patients can monitor their health and populations can be monitored. You can’t begin to manage healthcare until you know what you’re dealing with. That’s why we started with diagnosis. [But] you need to be able to monitor the course of the disease. If somebody is lucky enough to have medication for that disease, sometimes they cause side effects.

One of the [tests] we started with was liver function. Patients who have HIV or [tuberculosis] and get drugs are at risk of getting liver damage from those drugs. In the U.S., for example, the incidence of liver damage is 2 percent. In the developing world, it’s 25 percent. That’s because people aren’t checked. We wanted tests [with] a very easy, inexpensive action. We wanted tests where it’s just a finger prick or a urine specimen, you get the answer immediately, you could be given the drug and counseling and you’re on your way.

There are many ways our tests can be used. Since they’re paper and the size of a postage stamp, they’re very portable. We could mail them. A healthcare worker in a rural area can carry them in a satchel. Our tests [don't] require electricity. They don’t require water. They don’t require a doctor. It’s game changing.

What’s the status of the liver function test? When will it be put into use?

We have about 10 we’ve tested. Liver function is the most advanced, largely because we have funding from the [Bill and Melinda] Gates Foundation. Now, we’re testing our test with discarded blood from one of the Boston hospitals. We’re finding a nice correlation between our results and [the hospital's]. When we’ve completed that lab-level testing, we want to be in the field. We hope to start field testing at the beginning of 2011. We will probably be testing in Africa.

What are the other conditions you could expand testing to?

Diabetes, cholesterol. We could also [test for] heavy metals in water. We can test for iron imbalances in sweat. We haven’t yet developed them into a product, [but some have been tested at the lab level].

We talked about these tests in the context of the developing world. Do you also see uses for this technology in the U.S.?

Absolutely. We’re already getting an enormous amount of corporate interest from companies here. Medicine is moving more toward the patient. We all want to be empowered to manage our own health. But patients need to be compliant with their drugs. If you have a way of testing yourself, you can very quickly see if you’re not eating well, not taking your medicines. It gives you a sense of control.

Since we take just a small prick of blood, this will be very useful for pediatrics. We think it will be useful on ambulances. We think it will be directly applicable to consumers, [such as] runners in the Boston Marathon who want to check their sweat. We think about this for the military. The uses for the developed world are huge. We can teach the U.S. a thing or two about the cost of healthcare.

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Live organ donation: Lifesaving but risky

Ryan Arnold, 34, who was healthy when he donated 60 percent of his liver to his brother, died four days after the surgery.

By Elizabeth Cohen, CNN Senior Medical Correspondent
August 19, 2010 11:41 a.m. EDT

STORY HIGHLIGHTS

--More than 6,000 living donations take place each year
--Many live donors giving to family, friends, make decisions out of emotion
--Advocates: Make sure you know all risks before donating a kidney or part of liver
 
(CNN) -- Chad Arnold clearly remembers the day he received the call from his older brother, Ryan, telling him they were a perfect match for a liver transplant.

"You feel a lot of things at that point. Relief, gratefulness to God and to Ryan," says Chad, who suffers from an incurable liver disease called primary sclerosing cholangitis.

Chad told his story to Ginger Delgado, a reporter for KDVR in Denver, Colorado.

"After that, you wrestle with a lot of guilt, like I really don't want to bring him through this," Chad added. "But he shut me up pretty fast, and said, 'Well, you would do it for me, wouldn't you?'"

The Arnold family had invited KDVR to be with them the day of the surgery when it took an unexpected and devastating turn. Ryan Arnold, 34, who was completely healthy when he went in to donate 60 percent of his liver to his brother, died four days after the surgery. He is survived by a wife and three young sons.

In a statement, the University of Colorado says, "Despite the risks, Ryan selflessly made the decision to give part of his liver to his brother, Chad. We will learn everything we can from this to keep making the phenomenal gift of transplant safe for donors as well as recipients. We will continue working to improve this vital, life-changing program, which pioneered liver transplants 40 years ago. Ryan's passing will not be in vain."

"This is a story about a man who is deeply convicted by his faith and because of that, what he did for me was just sort of a normal thing that he did for people," Chad, 38, told KDVR after his brother's death. "Ryan is the hero in this."

Advocates for living donors say one should seriously weigh all the risks before deciding to donate a kidney or section of the liver.

Nationally, two out of every 1,000 liver donors die as a result of the surgery , according to OrganDonor.gov, a part of the federal Department of Health and Human Services. From 1996 to 2006, there were 3,016 living liver transplants in the United States.

Between October 1999 and December 2007, 14 people died within a month after donating a kidney, according to a study commissioned by the National Kidney Foundation. During that time, 51,153 people donated a kidney.

Cristy Wright said she didn't do much research before donating a kidney to her sister, Mary Edington.

"Normally I'm a big research hound -- an info junkie," says Wright, 39, a freelance writer who lives in Copley, Ohio. "But with the transplant, I made the decision emotionally. It was pretty impulsive. It was about loyalty. I love my sister and wanted to help her."

Since donating her kidney, Wright started a website, LivingDonor101.com, to help get information to other donors.

Wright says she recovered well physically from losing a kidney but suffered anxiety, anger and depression when the organ failed to function in her sister.

"They had to bring her into surgery and remove the kidney," Wright says. "I was a crying mess. I called up the living donor coordinator at the hospital and she gave me all sorts of platitudes and said she'd call me back, but she never did."

The kidney was removed a week after the donation. A year later, she says, her sister received a kidney from a friend, which did work.

Wright says the consent form she signed at the Cleveland Clinic was "generic" and didn't mention all the specific risks of kidney donation.

"Nobody ever apologized to me," Wright says. "I felt abandoned and betrayed by the surgeons and the transplant center."

Cleveland Clinic offered this response to CNN: "We are committed to ensuring that patients undergoing treatment at our hospitals understand the risks and benefits of procedures. Conversations with patients are thoroughly documented in the patient's medical records. Patients meet with their physician and surgeon, patient educators, donor coordinators, social workers, donor advocates and others if needed for special circumstances. We regret that our patient's experience did not meet her expectations."

"The literature shows most people make the decision to donate without doing research," says Donna Luebke, a nurse practitioner who donated a kidney to her sister in 1994, and a former board member of the Organ Procurement Transplantation Network and the United Network for Organ Sharing.

"You need to be informed about the outcomes for your surgeon and your hospital. Educate yourself."

Luebke says you should ask many questions, including how many transplants of the type you're having the surgeon does per year, and what the short and long-term outcomes have been.

More than 6,000 living donations take place each year, according to HHS, usually among family members or close friends, and the transplants have saved hundreds of thousands of lives. Before becoming a living donor, here are some resources to check:

This sample consent form from the U.S. Department of Health and Human Services includes information on the risks of donating a lobe of your liver.

The National Kidney Foundation has information about the risks of donating a kidney.

The federal government keeps statistics on how many transplants have been done at individual hospitals,, so you can see how experienced a hospital is in a particular procedure.

From livingdonorsonline.org, you can find advice on how to prepare to become a living donor, an online message board to talk to more than 4,000 people who've donated an organ or are considering it and links to read other donors' experiences.

The United Network for Organ Sharing also has information for potential living donors.

The National Living Donor Assistance Center offers videos that feature kidney and liver donors and expert advice on what to expect when donating an organ.

Livingdonor101 has a list of questions you should ask before becoming a living organ donor from someone who herself has donated an organ.

CNN's Sabriya Rice contributed to this report.

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Also See:
Aug. 19, 2010, 9:36 a.m. EDT

ROME, August 19, 2010 /PRNewswire via COMTEX/ -- Radioactive yttrium-90 labelled resin microspheres (SIR-Spheres; Sirtex Medical, Sydney, Australia) appear to be a safe and effective treatment for patients with colorectal cancer liver metastases who have failed available chemotherapy options, according to the final results of a prospective clinical multi-centre phase II trial conducted by the Italian Society of Locoregional Therapies in Oncology (SITILO) and published in the British Journal of Cancer.[1]

The results of the 52-patient study revealed that the liver tumours completely disappeared in one patient (2%), and 11 (22%) patients had a partial response involving at least a 30% reduction in tumour size, which met the pre-determined criteria for significance (P = 0.05). A further 12 (24%) patients had stable disease. The liver tumours shrank sufficiently in two patients (4%) to enable potentially curative surgery to be performed. The median overall survival was 12.6 months for all patients in the trial, with significantly longer survival in the 24 (48%) patients that responded to SIR-Spheres or who had stable disease compared to non-responders (median 16 months versus 8 months; P = 0.0006), and 40% of the responders remaining alive at two years compared to none of the non-responders. Mild-to-moderate side effects consisting mostly of fever and pain were reported in 16% of patients in the first 48 hours and 22% in days 3 to 30.

"These results reveal that radioembolisation using SIR-Spheres is a promising therapy for patients with colorectal cancer liver metastases who have failed chemotherapy," said Prof. Maurizio Cosimelli, Professor of Surgery at the Regina Elena National Cancer Institute in Rome, and co-ordinator of the study. "The prolonged 12.6-month median survival and encouraging tumour response reported in the SITILO study compares favourably with the clinical trial results of second- or third-line chemotherapy, even though three-quarters of our patients had previously received at least four different combinations of chemotherapy drugs and therefore had a poor prognosis with no other treatment options available."

"At a minimum, patients with liver-only or liver-dominant colorectal cancer who are failing chemotherapy and who remain fit should be considered for radioembolisation using SIR-Spheres," said Prof. Cosimelli. "However, SITILO will be conducting a multi-centre randomised trial using SIR-Spheres in combination with chemotherapy at an earlier line of treatment since we believe that this may further improve the prognosis for patients with colorectal liver metastases. Above all, it will be possible to clarify the potential of SIRT together with chemotherapy to increase the rate of surgical resections in patients that were previously unresectable."

Patients in the SITILO study had to have liver metastases from colorectal cancer that could not be removed by surgery and which had progressed despite modern chemotherapy regimens containing oxaliplatin and irinotecan. The presence of metastases outside the liver did not exclude the patients from treatment as long as these were limited in number, size and in the same organ. All patients were heavily pre-treated, having received at least 3 previous chemotherapy regimens: 24% had received 3 different lines or courses of chemotherapy, 50% had received 4 lines and 26% had received 5 lines.

The SITILO study used a single-arm design since this group of patients had no other treatment options available. Patients were reviewed by a multidisciplinary team of cancer specialists prior to recruitment into the study. The median survival of metastatic colorectal cancer treated in clinical studies using modern chemotherapy regimens such as cetuximab plus irinotecan at second-line and panitumumab at third-line treatment has been reported to be 8.6 to 10.7 months[2-5] and 6.3 to 9.3 months[6-9] respectively.

Each year, more than 145,000 Americans and 307,000 Europeans are diagnosed with colorectal cancer. Around half of these patients will develop metastases that have spread from the original site of the disease, predominately to the liver. Up to 90% of these patients ultimately die from liver failure due to the spread of the disease. Selective Internal Radiation Therapy (SIRT) using 90Y microsphere therapy is a novel approach to treating liver metastases. The microspheres are implanted by interventional radiologists to selectively target the tumors with radiation while sparing the much-needed healthy liver tissue.

The SITILO study was conducted by a multidisciplinary team of interventional radiologists, nuclear medicine physicians, medical oncologists, surgeons and other specialists at the Regina Elena National Cancer Institute in Rome, the University of Bologna, the University of Udine and the Cancer Institute of Naples in Italy. SIR-Spheres was developed by, and is manufactured by, Sirtex Medical, and is the only FDA-approved microsphere therapy for colorectal cancer liver metastases.

SITILO is the only Italian multidisciplinary oncology society. Different specialties work together within SITILO to design prospective clinical trials on loco-regional therapies in the field of liver metastases and primary carcinoma, melanoma, soft tissue sarcoma, and other cancers. Each protocol includes a biological component aimed at identifying predictive factors in serum and tissue.

The SITILO trial was conducted at the following hospitals:

- Regina Elena Cancer Institute, Rome, Italy
- University of Bologna, Bologna, Italy
- University of Udine, Udine, Italy
- Fondazione Pascale Cancer Institute, Naples, Italy

References

1. Cosimelli M, Golfieri R, Cagol PP et al. Multi-centre phase II clinical trial of yttrium-90 resin microspheres alone in unresectable, chemotherapy refractory colorectal liver metastases. British Journal of Cancer 2010; 103: 324-331.

2. Sobrero AF et al. EPIC: Phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. Journal of Clinical Oncology 2008; 26: 2311-2319.

3. de Cerqueira Mathias et al. Front cetuximab plus irinotecan in patients (pts) with metastatic colorectal cancer (mCRC) progressing on or after prior irinotecan therapy: final results of the LABEL study. ECCO meeting, European Journal of Cancer Supplements 2007; 5: Abs. P3055.

4. Wilke H et al. Cetuximab plus irinotecan in heavily pretreated metastatic colorectal cancer progressing on irinotecan: MABEL study. Journal of Clinical Oncology 2008; 26: 5335-5343.

5. Cunningham D et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. New England Journal of Medicine 2004; 351: 337-345.

6. Hecht JR et al. Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Cancer 2007; 110: 980-988.

7. Van Cutsem E et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. Journal of Clinical Oncology 2007; 25: 1658-1664.

8. Van Cutsem E et al. An open-label, single-arm study assessing safety and efficacy of panitumumab in patients with metastatic colorectal cancer refractory to standard chemotherapy. Annals of Oncology 2008; 19: 92-98.

9. Yoshino T et al. Phase II study of panitumumab (Pmab) monotherapy in Japanese patients (pts) with metastatic colorectal cancer (mCRC) after the failure of fluoropyrimidine, irinotecan (CPT-11), and oxaliplatin (OHP) chemotherapy. ASCO GI Symposium 2008; Abs. 366.

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Hispanics and Asians less likely to receive liver transplants

Public release date: 19-Aug-2010

Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell

Study links locale to diminished access to organs

Researchers at the University of Michigan and Arbor Research Collaborative for Health, both in Ann Arbor, have identified geographic variation as a key factor accounting for disparities in access to liver transplantation among racial and ethnic groups. Full details appear in the September issue of Liver Transplantation, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases (AASLD).

Organ allocation in the U.S. is designed for equitable distribution of deceased donor organs. Patients are prioritized to receive organs for liver transplantation (LT) based on their Model for End-stage Liver Disease (MELD) score, an objective assessment of their risk of dying on the waitlist. Hence, two candidates with similar MELD scores should have an equal chance of receiving a transplant regardless of race, gender, geography, or economics. However, there are multiple patient-specific as well as healthcare-specific barriers to LT that potentially compromise this system. Some of these variables include inadequate access to healthcare, lack of recognition of the need for transplant, access to a transplant center, and inequities in the transplant evaluation process.

While racial and ethnic disparities are evident throughout this entire process, the researchers found that the locale where candidates seek care for their liver disease modifies the effect of race/ethnicity on access to liver transplantation. Organ availability differs by region, and even within a region, the likelihood of LT varies among donor service areas (DSA). Local organ availability and center specific transplant practices may also play a role.

Amit K. Mathur, M.D., M.S., and colleagues propose that racial/ethnic disparity in access to transplantation at the DSA level must be evaluated because previous studies fail to acknowledge that organ availability is highly variable across DSAs, only evaluate African-Americans as a minority, and fail to account for changes in the severity of liver disease over time while candidates are waitlisted.

The authors conducted a Scientific Registry of Transplant Recipients analysis of data submitted to the Organ Procurement and Transplantation Network (OPTN). They considered 39,114 adult chronic end-stage liver disease candidates on the waitlist between 2002 and 2007. The primary variable of interest was candidate race (74.1% Caucasian, 13.9% Hispanic, 7.3% African-American and 3% Asian) and the primary outcome of interest was transplant rates by race/ethnicity, stratified by DSA and MELD score.

The analysis reveals that without adjustment by DSA, African-Americans appeared to have a 10% lower rate of receipt of LT as compared to Caucasians. After adjustment by DSA the deficit in this rate decreased to 2% and was no longer significant, , suggesting a direct link to DSA as the source of racial disparity and that African Americans are likely over represented in DSAs with organ shortage.

In contrast, Hispanics had an 8% lower LT rate than Caucasians even after adjustment for DSA. Stratified by DSA, this difference was pronounced at a MELD score < 20 (15% lower transplant rate) but the difference was no longer present at higher MELD scores. The persistently lower rates of transplant for Hispanics even after consideration of DSA may indicate Hispanics are over represented at centers that transplant candidates at higher MELD scores. Prior studies also suggest that Hispanics are overrepresented in DSAs with longer median waiting times for LT.

Asians experienced no significant difference in liver transplant rates compared to Caucasians. On analysis of MELD subgroups, however, Asian candidates with lower MELD scores (6-14) had a 24% higher transplant rate relative to Caucasians but a lower transplant rate (15-46%) was observed at MELD scores >15, possibly due to a combination of center effect as well as donor issues such as body size. However, the overall rates of transplant were similar among Caucasians and Asians.

"Geographic variation is being increasingly recognized as a threat to optimizing the use of donated organs, and in our study had a clear effect on the measured differences in transplant rates between minorities and Whites," concluded Dr. Mathur. "We observed significantly lower liver transplant rates for minority candidates compared to their White counterparts, particularly among Hispanic candidates and Asians with high MELD scores. Importantly, these lower relative transplant rates were not accompanied by higher rates of death, removal for non-transplant reasons, and inactivation."

In an editorial also published this month, Patrick Kamath, M.D., from the Mayo Clinic concurred, "Geographic incongruence serves to undermine an organ allocation scheme based on equity and needs to be addressed to make complex path to LT less cumbersome for persons with chronic liver disease, regardless of race, gender, payer or any other status."

###

This study is published in Liver Transplantation. Media wishing to receive a PDF of this article may contact healthnews@wiley.com

Full Citations: "Racial and Ethnic Disparities in Access to Liver Transplantation." Amit K. Mathur, Douglas E. Schaubel, Qi Gong, Mary K. Guidinger, Robert M. Merion. Liver Transplantation; Published Online: May 20, 2010 (DOI: 10.1002/lt.22108); Print Issue Date: September 2010. http://onlinelibrary.wiley.com/doi/10.1002/lt.22108/abstract.

Editorial: "Race and Receipt of Liver Transplantation: Location Matters." Sumeet K. Asrani, W. Ray Kim, Patrick S. Kamath. Liver Transplantation; Published Online: June 30, 2010 (DOI 10.1002/lt.22123); Print Issue Date: September 2010. http://onlinelibrary.wiley.com/doi/10.1002/lt.22123/abstract.

Liver Transplantation is published 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 http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-6473.

Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com/ or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.

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Genes may play a role in liver disease

Updated: 2010-08-18 20:15:28 CST

A family history of liver disease may predict the necessity of liver testing. A new study has found that variations of a particular gene that can be passed from generation to generation may be a contributor to liver conditions such as nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis.

Researchers from the National Institutes of Health Medical Center performed genetic testing on individuals who had one such liver disease or exhibited its early stages. They found that a significant number of patients had a particular gene that is uncommon in healthy individuals.

"Our findings suggest that the 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," said T. Jake Liang, who led the study. "However, once patients develop NASH, the allele predisposes them to more severe injury."

A total of 20 to 30 percent of the population has nonalcoholic fatty liver disease, a precursor to more severe liver conditions. The findings could give physicians a better idea of which patients will benefit from liver testing by including family history as a risk factor.

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Alcohol Use Before Liver Tx Key to Use Afterward



Crystal Phend, Senior Staff Writer, MedPage Today Published: August 19, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

Problem drinking after liver transplantation for alcoholic liver disease can be predicted by looking at just a few factors, a prospective study showed.

Return to alcohol use was predicted by a shorter length of sobriety before transplantation, a positive family history of alcoholism, and a diagnosis of alcohol dependence, Andrea DiMartini, MD, of the University of Pittsburgh Medical Center in Pittsburgh, and colleagues found.

Fully 46% of those in the cohort study started drinking again at some point, with moderate to heavy consumption in 42% of those, the researchers reported online in the American Journal of Transplantation.

The predictors may allow physicians to target their preventive and interventional treatment resources to at-risk individuals at the right time, DiMartini's group suggested.

The study included detailed prospectively-collected data on alcohol consumption from 208 patients who had a liver transplant for a primary or secondary diagnosis of alcoholic liver disease (78% of all such cases treated) at a single center over a six-year period.

Patients were counseled at every follow-up office visit to abstain completely from alcohol. Those who reported drinking got further counseling from the transplant psychiatrist and referral for professional alcohol counseling as needed.

Although therefore not a natural history study, this standard of care is followed at most transplant programs, the researchers noted.

Several patterns emerged for return to alcohol use among the 95 patients who didn't stay on the wagon:

•55 drank low amounts infrequently
•13 started drinking moderate amounts right away but cut down over time
•15 resumed moderate drinking later on and increased the amount over time
•12 immediately started drinking heavy amounts and increased the amount over time

This suggested that problem drinking may not start right away and thus "clinical monitoring should extend well beyond the early years post-liver transplantation," the researchers recommended in the paper.

Early moderate to heavy drinking patterns were predicted by:

•Poorer health after transplantation than in the year prior
•More bodily pain
•More fatigue
•More perceived stress
•A pretransplantation history of other substance use
•Not feeling confident that they would get another liver if needed

One explanation may be that patients felt ineffectual, feeling worse and not sure anything could make it better, the researchers suggested.

Or, alcohol use may have been how they handled stress, including the difficulties of the early post-liver transplantation phase, they added.

"Early identification and treatment of stress especially as it relates to early post-liver transplantation recovery, attention to complaints of pain and fatigue, as well as resumption of addiction counseling may aid in the stabilization of these patients," DiMartini's group wrote in the paper.

By contrast, those who drank minimally and consistently in the early period after transplantation reported better health and more vitality afterward, were less stressed, less likely to be in pain, did not regret their decision, and felt more confident they would get another liver if needed.

A possible explanation for their return to drinking could have been complacency about their overall health and the health of their liver leading to the feeling that occasional drinking early on would not be a problem, the researchers speculated.

They cautioned that the study was limited by the small size of the different trajectory groups and that participation in the study may have affected behavior of those in it.

The authors also noted that they had just begun to collect outcome data, which will be the subject of a later report.

The study was funded by grants from the National Institute of Alcohol Abuse and Alcoholism and the National Institute of Digestive Disorders and Kidney Diseases.

The researchers reported having no conflicts of interest to disclose.

Primary source: American Journal of Transplantation

Source reference:
DiMartini A, et al "Trajectories of alcohol consumption following liver transplantation" Am J Transplant 2010; 10.

Source
India Infoline News Service / 10:07 , Aug 19, 2010

Bristol-Myers Squibb Foundation Delivering Hope Program has committed US$ 2,223,295 to support efforts to combat Hepatitis B and C in India

Liver Foundation, West Bengal is coordinating a first of its kind collaboration among public health facilities to assess the impact of liver disease and in particular hepatitis C on Indian health care system, the organization announced today in New Delhi.

HCV: The Indian Face and Action is a two year operational research project that is first serious attempt to assess the impact of liver disease and hepatitis C in order to be able to advocate for robust viral hepatitis awareness, prevention and educational programs. The project, launched early this year is supported by Bristol-Myers Squibb Foundation (BMSF) Delivering Hope Program through a grant of about Rs19.5mn [US$415857] also aims improve diagnosis skills for 500 blood bank and laboratory technicians while enhancing prevention efforts among high risk groups.

“WHO estimates that it cost between one and three US dollars to prevent Hepatitis B through vaccination but we know it costs about US$5000 to treat a person with hepatitis B infection. For hepatitis C, there is no vaccine but it is curable and therefore awareness and prevention efforts should be paired with early detection, hence our training of laboratory technicians,” says Dr. Abhijit Chowdhury, Secretary-Liver Foundation West Bengal who is leading this consortium.

“Through this initiative we aim to inform public health policy regarding the significance and impact that a liver disease has, HCV in particular, in the general population. Additionally, we would work to foster coordinated HCV prevention and awareness activities through action targeted at key risk populations in awareness or scientific understanding and transmission”, he added.

BMSF Delivering Hope has committed an amount of about Rs105mn [US$2,223,000] to eight non-profit organizations partners across India since 2007. In the year 2010, BMSF would support ‘Americares India Foundation’ in Mumbai, ‘Baptist Christian Hospital’ in Tezpur in addition to HCV: The Indian Face and Action to enhance awareness on Hepatitis in the country. Institute of Development Studies, Kolkata has taken an endeavor to assess the impact of the intervention conducted by Liver foundation, West Bengal which has been also supported by BMSF.

“The Bristol-Myers Squibb Foundation has a long track record of harnessing expert resources and community support to bring measurable advances in the response to public health threats such as Hepatitis and HIV around the world.” said John Damonti, President, Bristol-Myers Squibb Foundation. “Our Delivering Hope Program builds on our expertise and commitment in addressing health disparities to help coordinate the response to hepatitis in countries where the need is the greatest.”

The project aims to determine the footfall in hospitals due to liver diseases and also map the healthcare resource utilization patterns in liver diseases in India. Initiatives will be undertaken to spread awareness on HCV prevention and care through action targeted at key risk populations.

Source

From one arm to another: the journey of donated blood

An ordinary student has the potential to save three lives every two months

By Jessica Neville, Science & Tech Editor

Published: Thursday, August 19, 2010
Updated: Thursday, August 19, 2010

Donated blood goes through many treatments before being distributed to hospitals for patient use. Saving lives isn’t just a job reserved for firefighters and soldiers. In fact, an ordinary University student has the potential to save three lives every two months. How? It’s as easy as giving blood.

This Friday the University, led by the Center for Student Leadership, Ethics and Public Service, has set a goal to collect 500 units of blood, which would be a personal record.

According to Michael Giancola, Director of CSLEPS, 687 people had signed up as of Wednesday at 2 p.m.

“We estimate that we need at least 660 people to sign up to reach the goal of 500, due to the possibility that some people will not come or will not be able to give blood when they arrive,” Giancola said.

Once the goal has been met, what happens to the donated blood? It turns out the blood isn’t shipped directly to a hospital to be transfused into a patient’s arm; there is actually a much longer process blood must go through to make the cut. From collection to treatment to distribution, find out how a blood donation can turn into a saved life.

Step 1: Donation

When a blood donor candidate arrives at a blood drive, the donor registers and completes a health history and mini physical. If everything checks out, about one pint of blood will be collected from the donor along with several small test tubes that can be used for further testing. An identical bar code label is placed on the bag, test tubes and the donor record to keep track of the donation, and the donation is stored in ice coolers until it is transported to a Red Cross processing center.

Kirsten Kruhm, senior blood donor recruiter with the American Red Cross, has worked with the University on multiple blood drives, including Friday’s record-setting drive.

“Last year, N.C. State gave 1,820 pints of blood on campus through 37 unique blood drives,” Kruhm said. “Most people have 10 to 12 pints of blood in their bodies, and donors usually give one pint at blood drives.”

Step 2: Processing

After the blood is donated, the barcode numbers are scanned into a computer database. The blood is sent to a Red Cross processing facility, where the blood is spun in centrifuges to separate it into its sub-components.

Dave Miller, director of testing at the Charlotte Red Cross Treatment Center, said the usable components of blood are the red blood cells, platelets and plasma. According to Miller, red cells are given to patients when their tissues need oxygen, platelets are used for clotting, particularly of capillaries, and plasma is used for clotting, especially for patients with hemophilia.

“The blood is also leuko-reduced, or white-reduced, meaning the blood is filtered to remove the white blood cells,” Miller said.

Primary components can be further manufactured into components such as cryoprecipitate, which is a harvested precipitate of plasma that contains fibrinogen. The test tubes collected from the initial blood donation are sent for testing at this time.

Step 3: Testing

The test tubes donated this Friday will be received at the Charlotte Red Cross National Testing Laboratory, one of five laboratories nationwide. The blood samples then undergo a dozen tests to make sure the blood doesn’t contain any infectious diseases and to establish the blood type. If the blood tests positive for any infectious diseases, the unit is discarded and the donor is notified.

“About one percent of the blood we collect has to be thrown away because it is contaminated,” Miller said. “50 percent of this is due to Hepatitis B, followed by Hepatitis C.”

Miller said blood type refers to the antigens present on the red blood cells. Antigens are substances that can produce an immune response if they are foreign to the body. Blood type A possesses A antigens, blood type B contains B antigens, blood type AB contains AB antigens, and blood type O has no antigens.

There are very specific ways blood types can be matched based on the antigens the patient’s red blood cells possess.

Step 4: Storage

After processing and testing, components of blood that are suitable for transfusion are labeled and stored. Red blood cells are stored in refrigerators at six degrees Celsius for up to 42 days, platelets are stored at room temperature in agitators for up to five days, and plasma and cyroprecipiate are stored in freezers for up to one year.

Miller said platelets are the hardest to maintain blood component because they can only be used for five days and have to stay at room temperature. People undergoing chemotherapy need a constant supply of platelets, according to Miller.

“We constantly need blood donated-not just a large amount at one time,” Miller said.

Step 5: Distribution

The blood is finally available to be distributed! Red Cross blood is available to be shipped to hospitals seven days a week, 24 hours a day.

Kruhm said the Red Cross divides areas of the United States into blood regions. North Carolina, South Carolina and Georgia comprise a common blood region where blood is generally maintained, according to Kruhm.

“In the Carolina blood region we need 1500 pints of blood every day to meet all the local patient needs,” Kruhm said.

Although blood donated in Raleigh will probably stay within the Carolina blood region, Kruhm said there are situations where the blood could be transported to another part of the U.S.

“If there’s a hurricane in another part of the country, we can send blood there to help them if necessary,” Kruhm said. “But we have some of the largest blood-using hospitals in the nation in RDU, such as Duke Medical, WakeMed, and REX, so much of the blood donated on Friday will go to those hospitals.”

Source

Groundsman fully fit to prepare field after receiving a new liver

Thursday, August 19, 2010, 11:00

A groundsman at the University of Bath who had a liver transplant seven years ago will be preparing the site for the British Transplant Games.

Mike Pooley, from Bathwick, was given a new lease of life after his transplant on New Year's Eve in 2003.

Now the 49-year-old is one of the groundsmen who will be preparing the university site for the transplant athletes taking part in the games.

Mr Pooley was first admitted to hospital with pains that were initially put down to gall stones.

But doctors discovered something else was wrong and he spent five weeks in the Royal United Hospital having tests.

The results showed that Mr Pooley had been accidently given hepatitis C in a blood transfusion when he was 14, and as a result his liver was now failing.

Mr Pooley said: "In those days they didn't screen the blood as carefully, and I was given blood with hepatitis C.

"My liver was not able to cope anymore and so I needed a transplant."

After the diagnosis he was sent to the Queen Elizabeth Hospital in Birmingham for assessment, before being put on the transplant list.

Mr Pooley then had to spend the next month waiting for the call, along with his wife Susan.

He said: "It was quite a worrying time, for both me and my family.

"I was told that I had to keep my phone on me at all times in case a suitable liver became available.

"Every time my phone rang my heart was in my mouth as I thought it was the call.

"I had to have a bag packed, as I had to be ready to leave with an hour's notice.

"I tried to keep things as normal as possible but it was hard, as you never know when you will get the call and have to go to hospital.

"It was really hard for Susan as there was nothing she could do to help."

After the operation Mr Pooley faced a long road to recovery.

He spent weeks in bed, with just walking to the toilet being a huge effort, and it took nine months before he was fit enough to go back to work. Now Mr Pooley is fighting fit, and feels like he has been given a second chance.

He said: "I feel brilliant now, and am back to full health.

"It feels like I have been given a second chance of life, and I can now live it to the full.

"Having my transplant on New Year's Eve meant that I started the new year with new hope.

"Organ donation really is the gift of life.

"It is important that people sign up to the organ donor register, as there are so many people who are waiting for transplants.

"Others may not be as lucky as I was."

The British Transplant Games take place during the next four days at various locations throughout the city.

For more information, see our games schedule.

Source

Taiwan, Canada develop new method for hepatitis C detection


2010/08/19 17:05:03
 
Taipei, Aug. 19 (CNA) Researchers from Taiwan and Canada have developed a new microscopy technology that allows for low-cost, portable imaging of the hepatitis C virus, making it more convenient to conduct screenings, a Taiwanese researcher said Thursday.
 
Under the sponsorship of Taiwan's National Science Council, the Industrial Technology Research Institute and National Research Council (NRC) Canada, an international research team recently combined technologies developed in Canada and Taiwan to create a screening device that can be carried in one hand.

Led by Kao Fu-jen, a professor at National Yang-Ming University, and Albert Stolow and John Pezacki from NRC Canada, the team jointly developed the high-sensitivity imaging system by re-engineering a DVD reading and writing head so that it can detect optical signals including fluorescence and tiny vibrations from a technique called coherent anti-Stokes Raman scattering.

The device creates images from cell samples that allow researchers to determine whether the hepatitis C virus is present. The development is expected to help sharply increase the efficiency of the diagnosis of chronic hepatitis C, Kao said in a press release.

The size of the device allows for point-of-care testing, which is diagnostic testing at or near the site of patient care.

According to Kao, the hepatitis C virus is spread through contact with infected blood, and about 170 million worldwide are infected with it. Currently, there is no vaccine against the virus.

How the hepatitis C virus harms the livers of long-term carriers is still unknown, but the risk of people with hepatitis C contracting liver cancer is 10 times higher than for ordinary people, the press release said.

The goal of the collaboration project between Taiwan and Canada is to develop real-time, unobtrusive and efficient biomedical detection methods and instruments for widespread application for hepatitis C and other infectious diseases, it said.

(By Y.L. Kao)

Source
Yen-Chieh Huang MD 1,2,†, Chih-Fang Huang MD 1,3,†, Kuo-Chin Chang MD 4,5, Shu-Fen Hung RN 4, Jing-Houng Wang MD 4,5, Chao-Hung Hung MD 4,5, Chien-Hung Chen MD, PhD 4,5, Po-Lin Tseng MD 4,5, Kwong-Ming Kee MD 4,5, Yi-Hao Yen MD 4,5, Pei-Shan Tsai RN, MPH 6, Chin-Chen Tsai MD 6, Sheng-Nan Lu MD, MPH, PhD 4,5,*

Journal of Gastroenterology and Hepatology
Accepted Article (Accepted, unedited articles published online for future issues)
DOI: 10.1111/j.1440-1746.2010.06476.x
Journal compilation © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd

Author Information
1 Departments of Family Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan;
2 Departments of Family Medicine, Antai Tian-Sheng Memorial Hospital, Tongkang, Pingtung, Taiwan;
3 Graduate Institute of Natural Healing Science, College of Science and Technology, Nanhua University, Chiayi, Taiwan;
4 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan;
5 School of Medicine, Chang Gung University College of Medicine, Taoyuan, Taiwan; and
6 Health Center of Zihguan Township, Kaohsiung, Taiwan.

*Correspondence: Sheng-Nan Lu MD, MPH, PhD,

*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. Tel: +886-7-731-7123 ext. 8301 Fax: +886-7-732-2402 E-mail: juten@ms17.hinet.netc

†* Yen-Chieh Huang, MD and Chih-Fang Huang, MD contributed equally to this study and manuscript

Publication History
Accepted manuscript online: 17 AUG 2010 12:20PM EST
Received date: 08-Jan 2010 Accepted date: 01-Aug-2010

Keywords:
alpha-fetoprotein (AFP);platelet count;community screening;hepatitis C virus (HCV);hepatocellular carcinoma (HCC)

ABSTRACT

Background and Aim: To elucidate a reasonable model and efficacy of hepatocellular carcinoma (HCC) screening on an elderly population.

METHODS: A two-staged HCC screening was conducted in an HCV-endemic area. Firstly, participants underwent blood tests for hepatitis B surface antigen (HBsAg), anti-Hepatitis C (HCV) antibody, serum fetoprotein (AFP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and platelet count, and subjects who were abnormal for any of the 6 markers were enrolled for 2nd stage ultrasonography. Suspected cases were referred for confirmation. HCC cases were followed for 4 years. All subjects were linked to national mortality and cancer register databases to identify newly developed HCC 30 months after screening.

RESULTS: 461 men and 541 women were screened for HCC, with 15.1% of them testing positive for HBsAg and 44.3% positive for anti-HCV. Among them, 619 (61.8%) met the criteria of ultrasonographic screening; 527 (85.1%) responded, and 16 confirmed HCC (M/F = 8/8, 68.8 ± 8.0 years) cases were detected. All tumor diameters were less than 5cm and 6 of them were less than 2cm. AFP and thrombocytopenia were two independent predictive factors of HCC. Overall survival rates of detected cases were 93.8% and 56.3% in years 1, and 4, respectively. The only good prognostic predictor was “underwent curative treatment”. Besides, another 7 developed HCC and 5 of them were with either thrombocytopenia or AFP elevation.

CONCLUSIONS: Under economical consideration, AFP and platelet count should be feasible screening markers of risk identification. Early detection and prompt treatment resulted in good prognosis of an aged population.

Source

Hepatitis Delta: Seek and Ye Shall Find

The Journal of Infectious Diseases 2010;202:822–824
© 2010 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2010/20206-0002$15.00
DOI: 10.1086/655809

EDITORIAL COMMENTARY

Scott D. Holmberg and John W. Ward
Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia

Received 10 June 2010; accepted 10 June 2010; electronically published 11 August 2010.

(See the article by Kucirka et al, on pages 845–852.)

Reprints or correspondence: Dr Scott Holmberg, Division of Viral Hepatitis, Centers for Disease Control and Prevention, MS G‐37, 1600 Clifton Rd NE, Atlanta, GA 30333 (sdh1@cdc.gov).

Hepatitis delta virus (HDV) was discovered in 1977 by Rizzetto and colleagues [1], and—as he expressed it 30 years later—HDV “would have possibly died away as another odd antigenic subtype” of hepatitis B virus (HBV) had it not been for an international collaboration among investigators from Turin, Italy, the National Institutes of Health, and Georgetown University [2]. Chimpanzee experiments demonstrated that the delta antigen, rather than being a component of HBV, was its own defective form that required HBV for its infection and replication, a “virus’s virus.” Dual HBV‐HDV infection was quickly recognized to have worldwide distribution, to be associated with more severe and rapidly progressive hepatitis, and to be especially resistant to treatment.

In the past few decades, remarkable strides in understanding the complex interplay between HBV and HDV at the molecular level have been achieved [3]. But many mysteries remain when these insights are applied to human disease, in which levels of HBV DNA and HDV RNA may fluctuate in relation to each other or not at all in individual patients [4]. Furthermore, some of the groups with HBV‐HDV coinfection, such as injection drug users, also have hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfections. Unrecognized coinfections with these viruses—ie, before the availability of reliable screening tests for HIV (1985) or HCV (1992)—may have confounded early observations of the clinical course of patients with HBV‐HDV coinfections. Indeed, one of the helpful observations of the article by Kucirka and colleagues [5] in the current issue of the Journal is the still very high infection rate found among a sample of injection drug users from 2005 to 2006 when tested for HCV (92%) or HIV (38%).

When first examined in the 1980s, it was clear that there were areas of high endemicity, especially in the Amazon Basin, Eastern Europe, and several regions of Africa and the Middle East, of intermediate endemicity in Southern Europe, and low endemicity in Northern Europe and North America. Over the next 10 years, there was a dramatic decline in HDV infection prevalence in Europe, considered to be the result of declining numbers of hepatitis B surface antigen (HBsAg)–positive injection drug users, vaccination for hepatitis B, and the effects of public health interventions related to the HIV epidemic. However, it has been noted that no additional declines in HDV have been observed in the past decade [6], perhaps because of the influx of immigrants dually infected with HBV‐HDV to the United States from highly endemic areas.

In the United States, several early studies in the late 1970s through the mid‐1980s showed antibodies to delta antigen in HBsAg‐positive blood donors (3.8%) in 1979 [7], persons with acute and chronic hepatitis B infection in Los Angeles (homosexual men, 15%; injection drug users, 22%) [8, 9], and developmentally disabled persons in Illinois state facilities (30%) [10]. Relatively high rates of HDV prevalence were seen in injection drug users in New York City (67%) [11]. Furthermore, a retrospective study of serum collected from 1972 to 1975 from drug‐using HBsAg‐positive patients at several Veterans Administration facilities at US locales showed that 42% had antibodies to delta antigen [12].

Few outbreaks of HDV in the United States (and these among injection drug users) have been detected and examined in the last 25 years. Over a 21‐month period between 1983 and 1985, Lettau and colleagues [13] investigated an outbreak of severe hepatitis among injection drug users in western Massachusetts associated with dual delta and hepatitis B viruses. Another 15 years elapsed before there was detection and investigation of a similar outbreak among injection drug users in Pierce County, Washington, by the Centers for Disease Control and Prevention (CDC) [14]. However, aside from these outbreaks, in recent years only about 6–10 cases of “confirmed” infections with HDV have been reported to the CDC from various states each year. Thus, it is quite difficult to know what is happening with HDV without specific reports such as the one by Kucirka and colleagues [5].

So, where is HDV headed in this country? On the one hand, there has been a gratifying decrease in prevalence of HDV in Asia and Europe, attributed to the expanding rate of hepatitis B vaccination activities over the last 20 years. We should expect a similar decline in HDV in the United States as we progressively remove its “host virus.” Or should we?

Previous outbreaks have shown a high prevalence of HDV coinfection among HBV‐infected injection drug users—54% in Massachusetts and 34.5% in Washington state—whereas HBV‐infected non‐drug users in those outbreaks had much lower HDV coinfection rates (9% in both states) [13, 14]. Indeed, a study of female prostitutes showed that, among those who used intravenous drugs, HBV and HDV coinfection rates were 21%, whereas the HBV‐infected women who were not injection drug users had an HDV coinfection rate of 6% [15]. Similarly, early analyses demonstrated high hepatitis D infection rates among hemophilic men (19%) [16] but not in gay men (0%) [17].

One unifying explanation for these numbers is that HDV, like other bloodborne pathogens, may be more efficiently transmitted parenterally than by sexual contact. If this is the case, perhaps we should not expect the same drop‐off in HDV coinfection rates as seen between 1980 and 2000 in places as diverse as Italy, Japan, Taiwan, and Turkey [6], where proportionately more HBV infection is acquired perinatally, sexually, or horizontally (in households), and proportionately less as the result of injection drug use. This hypothesis would also fit the current observation, albeit from a small sample, that fully 50% of HBV‐infected injection drug users in Baltimore in 2005–2006 had concurrent HDV infection.

Trends in HDV‐HBV coinfection and morbidity are contingent on successes in hepatitis B vaccination and screening. Approximately 15% of persons reported with acute hepatitis B infection in the United States are injection drug users [18]. In 1991, the United States adopted a vaccine‐based strategy to eliminate HBV transmission, with subsequent gains in immunization coverage particularly among children and adolescents [19]. Despite a long‐standing recommendation for hepatitis B vaccination, hepatitis B vaccine coverage among injection drug users remains low. As a result, 20%–70% of injection drug users have evidence of past or current HBV infection, with many lacking serologic evidence of hepatitis B vaccination and thus greater susceptibility to HBV [20]. When barriers to vaccination such as vaccine costs are removed, drug treatment centers successfully integrate hepatitis B vaccination as a routine service and greatly increase the numbers of injection drug users vaccinated [21]. To increase vaccination of injection drug users, the CDC recommends hepatitis B vaccination for all adults in correctional institutions and drug abuse prevention and treatment clinics; the CDC and other federal resources are available to defray the cost of vaccine purchase for these settings [19, 21]. In addition to vaccination, all injection drug users should be screened for HBV [19]. An estimated 3%–11% of injection drug users have chronic HBV infection, and many remain undiagnosed, reflecting inadequate HBV screening services in settings such as drug treatment programs [22]. Management of persons with chronic hepatitis B infection should include interventions to reduce behavioral risks of HBV transmission and referral for medical care. The data from Kucirka et al [5] highlight the importance of HDV testing as a component of clinical management for persons with chronic HBV infection. Unfortunately, few data are available to monitor whether injection drug users are receiving recommended hepatitis B prevention and care services.

Indeed, the study by Kucirka and colleagues [5] is not only useful as a marker of where we are in the US hepatitis D epidemic, but of where we are not. Very few studies such as this can or will be done, simply because there are too few cohorts of injection drug users currently being followed in the United States. The HIV/AIDS epidemic stimulated federal agencies such as the National Institute on Drug Abuse and (then) the CDC to establish studies of HIV and, eventually, of hepatitis virus infections among large populations of injection drug user in several cities. At present, the Baltimore study (ALIVE [AIDS Link to Intravenous Experience]) as reported here is the longest running US cohort study; in fact, its predecessor, “Man ALIVE,” predated the AIDS epidemic but is now one of few such studies left. This stymies our understanding not only of HDV and the “carrier” HBV epidemics in the United States but also of the continuing HCV and, to a lesser extent, HIV epidemics. Thus, we should expect our understanding of the evolution of the HDV epidemic—as well as HBV, HCV, and HIV epidemics—in this country, especially in one of the transmission risk groups most affected, to remain spotty and infrequent. It is a truism to write that “more research is needed,” but there is probably no more fitting comment on the implications of the research of the companion paper in this issue of the Journal.

References

•1.Rizzetto M, Canese MG, Gerin JL, et al. Immunofluorescence detection of new antigen‐antibody system (delta/anti‐delta) associated to hepatitis B virus in liver and serum of HBsAg carriers. Gut 1977;18(12):997–1003.

•2.Rizzetto M. Hepatitis D: thirty years after [review]. J Hepatol 2009;50:1043–1050.

•3.Taylor JM. Hepatitis delta virus. Virology 2006;344:71–76.

•4.Wedemeyer H. Re‐emerging interest in hepatitis delta: new insights into the dynamic interplay between HBV and HDV. J Hepatol 2010;52(5):627–629.

•5.Kucirka LM, Farzadegan H, Field JJ, et al. Prevalence, correlates, and viral dynamics of hepatitis delta among injection drug users. J Infect Dis 2010;202(6):845–852 (in this issue).

•6.Rizzetto M. Hepatitis D: the comeback? Liver Int 2009;29:140–142.

•7.Nath N, Mushawar IK, Fang CT, Berberian H, Dodd RY. Antibodies to delta antigen in asymptomatic hepatitis B surface antigen‐reactive blood donors in the United States and their association with other markers of hepatitis B virus. Am J Epidemiol 1985;122:218–225.

•8.De Cock KM, Niland JC, Lu HP, et al. Experience with human immunodeficiency virus infection in patients with hepatitis B virus and hepatitis delta virus infections in Los Angeles, 1977–1985. Am J Epidemiol 1988;127:1250–1260.

•9.Govindarajan S, Kanel GC, Peters RL. Prevalence of delta‐antibody among chronic hepatitis B virus infected patients in the Los Angeles area: its correlation with liver biopsy diagnosis. Gastroenterology 1983;85:160–162.

•10.Hershow RC, Chomel BB, Graham DR, et al. Hepatitis D virus infection in Illinois state facilities or the developmentally disabled: epidemiology and clinical manifestations. Ann Intern Med 1989;110:779–785.

•11.Novick DM, Farci P, Croxson TS, et al. Hepatitis D virus and human immunodeficiency virus antibodies in parenteral drug abusers who are hepatitis B surface antigen positive. J Infect Dis 1988;158:795–803.

•12.Ponzetto A, Seeff LB, Buskell‐Bales Z, et al. Hepatitis B markers in United States drug addicts with special emphasis on the delta hepatitis virus. Hepatology 1984;4:1111–1115.

•13.Lettau LA, McCarthy JG, Smith MH, et al. Outbreak of severe hepatitis due to delta and hepatitis B viruses in parenteral drug abusers and their contacts. N Engl J Med 1987;317:1256–1262.

•14.Bialek SR, Bower WA, Mottram K, et al. Risk factors for hepatitis B in an outbreak of hepatitis B and D among injection drug users. J Urban Health 2005;82:468–478.

•15.Rosenblum L, Darrow W, Witte J, et al. Sexual practices in the transmission of hepatitis B virus and prevalence of hepatitis delta virus infection in female prostitutes in the United States. JAMA 1992;267:2477–2481.

•16.Troisi CL, Hollinger FB, Hoots WK, et al. A multicenter study of viral hepatitis in a United States hemophilic population. Blood 1993;81:412–418.

•17.Weisfuse IB, Hadler SC, Fields HA, et al. Delta hepatitis in homosexual men in the United States. Hepatology 1989;9:872–874.

•18.Daniels D, Grytdal S, Wasley A. Surveillance for acute hepatitis—United States, 2007. MMWR 2009;58(Suppl 3):1–27.

•19.Centers for Disease Control and Prevention. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). Part II: immunization of adults. MMWR Morb Mortal Wkly Rep 2006;55:1–33.

•20.Centers for Disease Control and Prevention. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Morb Mortal Wkly Rep 2008;57:1–20.

•21.Kresina TF, Hoffman K, Lubran R, Clark HW. Integrating hepatitis services into substance abuse treatment programs: new initiatives from SAMHSA. Public Health Rep 2007;122(Suppl 2):96–98.

•22.Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment. Screening for infectious diseases among substance abusers (Treatment Improvement Protocol [TIP] Series 6; DHHS publication [SMA] 95–3060). Rockville, Maryland: NIH, 1993. http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=hssamhsatip&part=A25461. Accessed 19 April 2010.

Potential conflicts of interest: none reported.

Source
Dong Hyun Sinn 2, Su Rin Shin 3, Jae Sook Kil 1, Jeong Kim 1, Geum-Youn Gwak 1, Moon Seok Choi 1, Joon Hyeok Lee 1, Kwang Cheol Koh 1, Byung Chul Yoo 1, Seung Woon Paik 1,*

Journal of Gastroenterology and Hepatology
Accepted Article (Accepted, unedited articles published online for future issues)
DOI: 10.1111/j.1440-1746.2010.06478.x
Journal compilation © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd

Author Information
1 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
2 Department of Medicine, Armed Forces Capital Hospital, Seongnam, South Korea
3 Department of Medicine, Kangnam Sacred Heart Hospital, Hallym University, Seoul, South Korea

*Correspondence: Seung Woon Paik,

*Correspondence: Seung Woon Paik Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea Tel: +82-2-3410-3409 Fax: +82-2-3410-6983 E-mail: sw.paik@samsung.com

Publication History
Accepted manuscript online: 17 AUG 2010 12:20PM EST
Received date: 16-Apr-2010 Accepted date: 27-Jul-2010

Keywords:
hepatitis C virus;elderly patients;peginterferon;ribavirin;APRI

Abstract

Background and Aim: We evaluated the safety and efficacy of combination therapy with pegylated interferon and ribavirin for treating chronic hepatitis C (CHC) patients aged 60 years and older.

Methods: Three hundred fourteen CHC patients, who were treated with combination therapy, were classified into three groups according to age: younger than 50 years of age (n = 137); 50 to 59 years old (n = 109); and 60 years of age or older (n = 68). The sustained virological response (SVR) rates and discontinuation rates were compared between the three groups.

Results: Discontinuation of therapy due to adverse event was more frequent in the older patient groups: 1%, 5%, and 10% for the <50, 50-59, and ≥60-year-old patients groups, respectively (p = 0.018). However, the older patients group showed a SVR rate that was comparable to the SVR rates of the other age groups; 80%, 73% and 75% for the <50, 50-59, and ≥60-year-old patients groups, respectively (p = 0.420). Multivariate analysis showed the AST to platelet ratio index (APRI) was an independent predictor of a SVR. A SVR was achieved in 95% (19 out of 20) of the elderly patients with an APRI < 0.80.

Conclusion: Although physicians must pay more attention for adverse events in the older patients, combination therapy can be considered for older patients, especially for the patients with a low APRI.

Source
Chen-Hua Liu 1,2,3, Jia-Horng Kao 1,2,3,*

Journal of Gastroenterology and Hepatology
Accepted Article (Accepted, unedited articles published online for future issues)
DOI: 10.1111/j.1440-1746.2010.06488.x
Journal compilation © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd

Author Information

1 Department of Internal Medicine,
2 Hepatitis Research Center, and
3 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan

*Correspondence: Jia-Horng Kao,

*Correspondence: Prof. Jia-Horng Kao Director and Distinguished Professor, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine 1 Chang-Te St., Taipei 10002, Taiwan Tel.: 886-2-23123456 ext 67307 Fax: 886-2-23825962 E-mail: kaojh@ntu.edu.tw

Publication History
Accepted manuscript online: 17 AUG 2010 12:21PM EST
Received date: 1-Aug-2010 Accepted date: 8-Aug-2010


Keywords:
hepatitis C virus;end-stage renal disease;dialysis;interferon;ribavirin

Abstract

Hepatitis C virus (HCV) infection is a major health problem in patients with end-stage renal disease (ESRD). The incidence of acute HCV infection during maintenance dialysis is much higher than that in the general population because of the risk of nosocomial transmission. Following acute HCV infection, most develop chronic HCV infection; a significant proportion develops chronic hepatitis, cirrhosis, and even hepatocellular carcinoma (HCC). Overall, chronic hepatitis C patients on hemodialysis bear an increased risk of liver-related morbidity and mortality, either during dialysis or after renal transplantation. Interferon (IFN) therapy is modestly effective for the treatment of HCV infection in ESRD patients. Conventional or pegylated IFN monotherapy has been used to treat acute hepatitis C in ESRD patients with excellent safety and efficacy. Regarding chronic hepatitis C, about one third of the patients can achieve sustained virologic response (SVR) after conventional or pegylated IFN monotherapy. The combination of low-dose ribavirin and conventional of pegylated IFN has further improved the SVR rate in treatment-naïve or retreated ESRD patients in clinical trials. Similar to treatment of patients with normal renal function, baseline and on-treatment HCV virokinetics are useful to guide optimized therapy in ESRD patients. Of particular note, IFN-based therapy is not recommended at the post-renal transplantation stage because of the low SVR rate and risk of acute graft rejection. In conclusion, ESRD patients with HCV infection should be encouraged to receive antiviral therapy and those who achieve SVR usually have long-term durable virologic, biochemical, and histologic responses.

Source
Hyun Seok Kang 1, Soon Ho Um 1, Yeon Seok Seo 1,*, Hyonggin An 2, Kwang Gyun Lee 1, Jong Jin Hyun1, Eun Sun Kim 1, Sung Chul Park 1, Bora Keum 1, Ji Hoon Kim 1, Hyung Joon Yim 1, Yoon Tae Jeen1, Hong Sik Lee 1, Hoon Jai Chun 1, Chang Duck Kim 1, Ho Sang Ryu 1

Journal of Gastroenterology and Hepatology
Accepted Article (Accepted, unedited articles published online for future issues)
DOI: 10.1111/j.1440-1746.2010.06481.x
Journal compilation © 2010 Journal of Gastroenterology and Hepatology Foundation

Author Information

1 Departments of Internal Medicine and
2 Biostatistics, Korea University College of Medicine, Seoul, Korea

* Correspondence: Yeon Seok Seo,

* Correspondence: Yeon Seok Seo, MD, PhD Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, Korea Tel: 82-2-920-6608, Fax: 82-2-953-1943, E-mail: drseo@korea.ac.kr

Publication History
Accepted manuscript online: 17 AUG 2010 12:20PM EST
Accepted date: 02 August 2010

Keywords:
aminotransferase;metabolic syndrome;insulin resistance;nonalcoholic fatty liver disease

ABSTRACT

Background and Aims: It remains unclear whether the currently used normal range for serum alanine aminotransferase (ALT) levels really reflects a healthy liver. This study was performed to evaluate the healthy range of serum ALT in the Korean adult population and to determine the clinical significance of unhealthy levels.

Methods: We reviewed the medical records, including questionnaires and the results of laboratory and radiologic tests conducted at the Health Promotion Center in Korea University Anam Hospital between March 2005 and February 2007. The records written in questionnaire form included the baseline data, including physical status, social behaviors, medication history, and past and present disease histories.

Results: The mean age of the 7403 enrolled subjects was 48 years, and 49.9% of them were men. A healthy cohort was selected after excluding subjects who showed any abnormalities of the factors that were significantly associated with serum ALT level on multivariate regression analysis. The upper limit of the healthy range of serum ALT level (i.e., 95th percentile) in the healthy population was 31 IU/L for the men and 23 IU/L for the women. The prevalence of metabolic syndrome and insulin resistance were significantly higher in subjects with an “unhealthy” normal ALT level than in subjects with a healthy ALT level.

Conclusion: In our study, the upper limit of the healthy range of serum ALT level was 31 IU/L for the men and 23 IU/L for the women. An unhealthy normal ALT level was associated with higher prevalence of metabolic syndrome and insulin resistance.

Source