December 3, 2010

December 2010 B News: HBV Treatment In the News‏

National Strategy for the Prevention and Control of Viral Hepatitis

Dr. Howard Koh, the Assistant Secretary for Health, gave the President’s Choice Lecture at the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston this month, where he spoke about the U.S. administration’s response to the Institute of Medicine (IOM) report on viral hepatitis. Dr. Koh took the initiative to convene the first viral hepatitis interagency work group to look at what is being done across all Health and Human Services (HHS) agencies for this growing epidemic. A “National Strategy for the Control of Viral Hepatitis and Liver Cancer” that builds upon the IOM report is being developed by the HHS working group and is slated for publication in early 2011. Learn more »

HBV Drug Therapy Okay for Pregnant Women

Pregnant women with active hepatitis B infection can be safely and effectively treated with telbivudine (Tyzeka), researchers reported at the 2010 annual AASLD meeting. A study involving more than 80 women found that just over half of the women given telbivudine achieved a complete virologic response right before delivery compared with none of the controls, according to Calvin Pan, MD, of Mount Sinai School of Medicine in Flushing, N.Y., and colleagues. There has been a controversy over whether pregnant women with hepatitis B should be treated, mainly due to concerns over the safety of the fetus. Learn more »

HBV Reactivation and Rituximab:
A Complex Clinical Challenge

HBV reactivation is a serious and often fatal complication of rituximab-based therapy that has led to a black box warning on the package insert. Researchers report, “The importance of HBV reactivation is two-fold. First, symptomatic hepatitis flare carries a high mortality rate, which has ranged from 5 to 40% in various reports. Second, HBV reactivation, if it occurs prior to completion of chemotherapy, will likely result in substantial delays in the delivery of potentially curative chemotherapy for the underlying malignancy…such delay is detrimental to long-term cancer-specific outcome.” Read Full Article »

From Podium to Practice:
Updates in HBV Treatment

Nov. 2 – Capsule Summaries of key oral and poster presentations from the 2010 AASLD Meeting of the American Association for the Study of Liver have been selected by leading experts in the field. Learn more »

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Articles in Press

D.L. Shawcross 1‡, Y. Sharifi 1‡, J.B. Canavan 3, A.D. Yeoman 12, R.D. Abeles 12, N.J. Taylor 1, G. Auzinger 2, W. Bernal 12, J.A. Wendon 12

Received 19 April 2010; received in revised form 23 June 2010; accepted 14 July 2010. published online 01 December 2010.
Uncorrected Proof

Background & Aims
Patients with cirrhosis are prone to infection which is a frequent precipitant of hepatic encephalopathy (HE). Clinical studies have examined the importance of inflammation and infection in modulating the manifestation of symptoms of HE in acute liver failure and patients with cirrhosis and minimal/low grade HE. It would be logical to presume that this relationship persists in patients who develop severe HE in cirrhosis although this has not been examined to date.

Methods
We report the findings of a prospective audit of 100 consecutive patients with cirrhosis admitted between Jan, 2000 and March, 2008 to a liver Intensive Care Unit (ICU) where HE was the primary indication for admission (59% Grade 3; 41% Grade 4). Haematological and microbiological data were collected at ICU admission, and organ scores and outcomes were recorded.

Results
46% of patients had positive cultures taken within ±48h from admission to ICU [25% blood] and a further 22% were culture negative but had evidence of systemic inflammation (SIRS). SIRS score (p=0.03) and SOFA score (p=0.006) were significantly higher in those patients with Grade 4 HE, who were also less likely to survive (p<0.001). HE grade/coma score did not correlate with ammonia, biochemistry or MELD score. Fifty-two percent survived their ICU stay while the remainder developed progressive multiorgan failure and died; 38% survived to discharge, and 16% were transplanted.

Conclusions
These data support an association between infection/SIRS and not ammonia, in patients with cirrhosis that develop severe HE. The presence or absence of infection/SIRS did not determine survival.

Keywords: Hepatic encephalopathy, Cirrhosis, Inflammation, Infection, Outcomes

Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation, CRP, C-reactive protein, GCS, Glasgow Coma Score, HE, hepatic encephalopathy, HDU, High Dependency Unit, ICU, Intensive Care Unit, MELD, Model for End-stage Liver Disease, SIRS, Systemic Inflammatory Response Syndrome, SOFA, Sequential Organ Failure Assessment

1 Institute of Liver Studies, King’s College London School of Medicine at King’s College Hospital, Denmark Hill, London, UK
2 Liver Intensive Therapy Unit, King’s College Hospital, Denmark Hill, London, UK
3 NIHR Comprehensive Biomedical Research Centre at Guy’s & St. Thomas’s NHS Foundation Trust and King’s College London, UK

Corresponding author. Address: Institute of Liver Studies, King’s College Hospital, Denmark Hill, London SE5 9RS, UK. Tel.: +44 20 3299 2316; fax: +44 20 3299 3167.

‡ These authors contributed equally to this paper.

PII: S0168-8278(10)00838-X
doi:10.1016/j.jhep.2010.07.045
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.

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Arizona Cuts Financing for Transplant Patients

By MARC LACEY
Published: December 2, 2010

PHOENIX — Even physicians with decades of experience telling patients that their lives are nearing an end are having difficulty discussing a potentially fatal condition that has arisen in Arizona: Death by budget cut.

Effective at the beginning of October, Arizona stopped financing certain transplant operations under the state’s version of Medicaid. Many doctors say the decision amounts to a death sentence for some low-income patients, who have little chance of survival without transplants and lack the hundreds of thousands of dollars needed to pay for them.

“The most difficult discussions are those that involve patients who had been on the donor list for a year or more and now we have to tell them they’re not on the list anymore,” said Dr. Rainer Gruessner, a transplant specialist at the University of Arizona College of Medicine. “The frustration is tremendous. It’s more than frustration.”

Organ transplants are already the subject of a web of regulations, which do not guarantee that everyone in need of a life-saving organ will receive one. But Arizona’s transplant specialists are alarmed that patients who were in line to receive transplants one day were, after the state’s budget cuts to its Medicaid program, ruled ineligible the next — unless they raised the money themselves.

Francisco Felix, 32, a father of four who has hepatitis C and is in need of a liver, received news a few weeks ago that a family friend was dying and wanted to donate her liver to him. But the budget cuts meant he no longer qualified for a state-financed transplant.

He was prepared anyway at Banner Good Samaritan Medical Center as his relatives scrambled to raise the needed $200,000. When the money did not come through, the liver went to someone else on the transplant list.

“I know times are tight and cuts are needed, but you can’t cut human lives,” said Mr. Felix’s wife, Flor. “You just can’t do that.”

Such high drama is unfolding regularly here as more and more of the roughly 100 people affected by the cuts are becoming known: the father of six who died before receiving a bone marrow transplant, the plumber in need of a new heart and the high school basketball coach who struggles to breathe during games at high altitudes as she awaits a lung transplant.

“I appreciate the need for budget restraints,” said Dr. Andrew M. Yeager, a University of Arizona professor who is director of the Blood and Marrow Transplantation Program at the Arizona Cancer Center. “But when one looks at a potentially lifesaving treatment, admittedly expensive, and we have data to support efficacy, cuts like this are shortsighted and sad.”

State Medicaid officials said they recommended discontinuing some transplants only after assessing the success rates for previous patients. Among the discontinued procedures are lung transplants, liver transplants for hepatitis C patients and some bone marrow and pancreas transplants, which altogether would save the state about $4.5 million a year.

“As an agency, we understand there have been difficult cuts and there will have to be more difficult cuts looking forward,” said Jennifer Carusetta, chief legislative liaison at the state Medicaid agency.

The issue has led to a fierce political battle, with Democrats condemning the reductions as “Brewercare,” after Gov. Jan Brewer.

“We made it very clear at the time of the vote that this was a death sentence,” said State Senator Leah Landrum Taylor, a Democrat. “This is not a luxury item. We’re not talking about cosmetic surgery.”

The Republican governor has in turn blamed “Obamacare,” meaning the federal health care overhaul, for the transplant cuts even though the Arizona vote came in March, before President Obama signed that bill into law.

But a top Republican, State Representative John Kavanagh, has already pledged to reconsider at least some of the state’s cuts for transplants when the Legislature reconvenes in January. Mr. Kavanagh, chairman of the Appropriations Committee, said he does not believe lawmakers had the full picture of the effect of the cuts on patients when they voted.

“It’s difficult to be linked to a situation where people’s lives are jeopardized and turned upside down,” he said in an interview. “Thankfully no one has died as a result of this, and I believe we have time to rectify this.”

Across the country, states have restricted benefits to their Medicaid programs, according to a 50-state survey published in September by the Kaiser Commission on Medicaid and the Uninsured. But none have gone as far as Arizona in eliminating some transplants, which are considered optional services under federal law.

Before the Legislature acted, Arizona’s Medicaid agency had provided an analysis to lawmakers of the transplants that were cut, which many health experts now say was seriously flawed. For instance, the state said that 13 of 14 patients under the state’s health system who received bone marrow transplants from nonrelatives over a two-year period died within six months.

But outside specialists said the success rates were considerably higher, particularly for leukemia patients in their first remission.

“Something needs to be done,” said Dr. Emmanuel Katsanis, a bone marrow transplant expert at the University of Arizona. “There’s no doubt that people aren’t going to make it because of this decision. What do you tell someone? You need a transplant but you have to raise the money?”

Just before the Oct. 1 deadline, Mark Price, a father of six who was fighting leukemia, learned he needed a bone marrow transplant. But his doctor, Jeffrey R. Schriber, found donor matches for his transplant the very day the new rules went into effect, and Mr. Price no longer qualified for coverage by the Arizona Health Care Cost Containment System, the formal name for the state’s Medicaid program.

What happened next was at once inspirational and heart-rending.

Out of the blue, an anonymous financial donor quickly stepped forward and agreed to cover the hundreds of thousands of dollars needed for Mr. Price’s surgery. But Mr. Price died last weekend, after his cancer returned before the operation could be done. He was buried on Thursday, next to his grandfather.

“It’s not correct to say that he died as a result of the cuts,” said Dr. Schriber, who is active in lobbying for the financing to be restored. “Did it prey on his mind? Did it make his last days more difficult? No doubt.”

Elsewhere, the fund-raising is already under way.

Mr. Felix and others are now trying to raise enough for new organs through NTAF, a nonprofit organization based in Pennsylvania formerly known as the National Transplant Assistance Fund that helps transplant patients pay for their medical costs. National coverage of their plight has already led to more than $100,000 in donations for some of the patients affected by the budget cuts. The Felix family is also planning a yard sale this weekend so he does not lose the chance to get another liver.

There has been a flurry of lobbying to persuade the state to reverse the decision. Dr. Gruessner said he and others met with state health officials recently to propose other cuts associated with transplants, like eliminating tests typically conducted before surgery.

If the Legislature does decide to reconsider the cuts, one of the affected people, a plumber and father of three named Randy Shepherd, 36, who has an ailing heart and needs a transplant, plans to attend the debate.

“I’m trying not to take it personally,” he said of being cut out of the program. “None of the politicians had heard of me when they made their decision. They didn’t say, ‘Let’s kill this guy.’ ”

Source
Clinical Gastroenterology and Hepatology
Volume 8, Issue 12 , Pages 1017-1029, December 2010

Ira M. Jacobson , Patrice Cacoub, Luigino Dal Maso, Stephen A. Harrison, Zobair M. Younossi

Abstract

In addition to its effects in the liver, chronic hepatitis C virus (HCV) infection can have serious consequences for other organ systems. Extrahepatic manifestations include mixed cryoglobulinemia (MC) vasculitis, lymphoproliferative disorders, renal disease, insulin resistance, type 2 diabetes, sicca syndrome, rheumatoid arthritis–like polyarthritis, and autoantibody production; reductions in quality of life involve fatigue, depression, and cognitive impairment. MC vasculitis, certain types of lymphoma, insulin resistance, and cognitive function appear to respond to anti-HCV therapy. However, treatments for HCV and other biopsychosocial factors can reduce quality of life and complicate management. HCV treatment has a high overall cost that increases when extrahepatic manifestations are considered. HCV appears to have a role in the pathogenesis of MC vasculitis, certain types of lymphoma, and insulin resistance. Clinicians who treat patients with HCV infections should be aware of potential extrahepatic manifestations and how these can impact and alter management of their patients.

Keywords: Hepatitis C Virus, Burden of Disease, Extrahepatic Comorbidities, Health-Related Quality of Life, Epidemiology

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Transplant International
Volume 24, Issue 1, pages 43–50, January 2011
DOI: 10.1111/j.1432-2277.2010.01141.x

Davide Bitetto 1, Carlo Fabris 1, Ezio Fornasiere 1, Corrado Pipan 2, Elisa Fumolo 1, Annarosa Cussigh 1, Sara Bignulin 1, Sara Cmet 1, Elisabetta Fontanini 1, Edmondo Falleti 1, Romina Martinella 2, Mario Pirisi 3,4, Pierluigi Toniutto 1

Author Information

1 Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
2 Hygiene and Epidemiology, University of Udine, Udine, Italy
3 Department of Clinical and Experimental Medicine, University of Eastern Piedmont “A. Avogadro”, Novara, Italy
4 Interdisciplinary Research Center of Autoimmune Diseases, University of Eastern Piedmont “A. Avogadro”, Novara, Italy

*Correspondence: Pierluigi Toniutto MD, DPMSC, Internal Medicine, Medical Liver Transplantation Unit, University of Udine, 33100 Udine, Italy. Tel.: +390432559801; fax: +39043242097; e-mail: pierluigi.toniutto@uniud.it

Abstract

Keywords: interferon; liver transplantation; recurrent hepatitis C; vitamin D

Summary

In immune-competent patients, higher vitamin D levels predicted sustained viral response (SVR) following interferon (INF) and ribavirin therapy for chronic hepatitis C. This study aimed to verify the influence of vitamin D serum levels and/or vitamin D supplementation in predicting SVR rates for recurrent hepatitis C (RHC). Forty-two consecutive patients were treated for RHC with combination therapy with INF-α and ribavirin for 48 weeks. Vitamin D serum levels were measured in all patients before antiviral therapy. In 15 patients oral vitamin D3 supplementation was administered to avoid further bone loss. SVR was observed in 13 patients; it was achieved in 1/10 severely vitamin D deficient (≤10 ng/ml) patients, in 6/20 deficient (>10 and ≤20 ng/ml) and in 6/12 with near normal (>20 ng/ml) 25-OH vitamin D serum levels (P < 0.05). Cholecalciferol supplementation, in the presence of a normal or near normal baseline vitamin D concentration, (improvement of chi-square P < 0.05, odds ratio 2.22) and possessing a genotype other than 1 (improvement of chi-square P < 0.05, odds ratio 3.383) were the only variables independently associated to SVR. In conclusion, vitamin D deficiency predicts an unfavourable response to antiviral treatment of RHC. Vitamin D supplementation improves the probability of achieving a SVR following antiviral treatment.

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Approval of rapid INSTI[TM] HIV-1 Antibody Test

On November 29, 2010, the Food and Drug Administration (FDA) announced the approval of the INSTI™ HIV-1 Antibody Test, a new, single use rapid test for the detection of antibodies to Human Immunodeficiency Virus Type 1 (HIV-1) in human venipuncture whole blood, fingerstick blood, or plasma specimens. The newly approved test provides results in as little as 60 seconds, in contrast to the six previously approved rapid HIV tests, which typically deliver results in about 10 - 20 minutes.

Rapid HIV tests allow people to learn their HIV status in a single visit to a testing site, instead of returning days later for results, dramatically increasing the number of people who ultimately learn their serostatus after taking an HIV test.

Rapid testing also helps increase access to HIV testing because testing can be performed outside of the traditional laboratory setting. Individuals who undergo testing can be counseled immediately concerning their HIV status and, if they are positive, given the opportunity to enter medical care.

The INSTI™ HIV-1 Antibody Test can be used in clinical laboratories, in public health laboratories and in point-of-care settings. The test is classified as Moderate Complexity under CLIA (Clinical Laboratory Improvements Amendments).

It is highly sensitive [The overall sensitivity for the different sample types: 99.8% (95% CI = 99.3% - 99.9%) in fingerstick whole blood, 99.9% (95% CI = 99.5% - 100%) in venipuncture whole blood, 99.9% (95% CI = 99.5% - 100%) in plasma] and specific [The overall specificity for the different samples types: 99.5% (95% CI = 99.0% - 99.8) in fingerstick whole blood, 100% (95% CI = 99.7% - 100%) in venipuncture whole blood, 100% (95% CI = 99.7% - 100%) in plasma] for the detection of antibodies to HIV-1.

The assay is not intended to be used for screening of blood donors.

The INSTI™ HIV-1 Antibody Test is manufactured by bioLytical Laboratories Inc., Richmond, BC, Canada.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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