Showing posts with label transplant. Show all posts
Showing posts with label transplant. Show all posts

Saturday, November 10, 2018

The Liver Meeting® African-Americans Face Significant Delays in Liver Transplantation Despite High Priority Scores

African-Americans Face Significant Delays in Liver Transplantation Despite High Priority Scores
November 9, 2018
Data from a new study presented this week at The Liver Meeting® found that African-American patients on waitlists for liver transplantation, despite severe disease and high scores for prioritization, persistently face significant disparities and delays in referral. 

SAN FRANCISCO – Preliminary data from a new study presented this week at The Liver Meeting® – held by the American Association for the Study of Liver Diseases – found that African-American patients on waitlists for liver transplantation, despite severe disease and high scores for prioritization, persistently face significant disparities and delays in referral.

To prioritize liver transplantation recipients, the Model for End Stage Liver Disease, or MELD, scoring system is widely used. However, disparities in timely referral for liver transplantation persist. This study by researchers in the Alameda Health System in Oakland, Calif., evaluated race- and ethnicity-specific disparities in the severity of liver disease of patients at the time of waitlist registration and the time of liver transplantation across the United Network for Organ Sharing, or UNOS, regions in the United States.

“Prior studies had conflicting data on how the adoption of the MELD scoring system for liver allocation had affected racial disparities in liver transplantation. In particular, ethnic minorities − specifically African-Americans − consistently had lower rates of receiving liver transplantation and higher rates of death while awaiting liver transplantation,” says Ann Robinson, MD, an internist at Highland Hospital in Oakland, Calif., and the study’s co-author. “We aimed to specifically evaluate whether these disparately worse outcomes among African-Americans also extended to differences in liver disease severity at [the] time of waitlist registration. The finding of more severe liver disease, as manifested by higher MELD scores, suggests potential delays in referral for liver transplantation among African-Americans. This is critical information to understand, as delays in timely referral may ultimately affect survival outcomes.”

The researchers retrospectively evaluated UNOS liver transplantation data from 2005 to 2016 to compare race- and ethnicity-specific MELD scores at the time of waitlist registration and at the time of liver transplantation among U.S. adults without hepatocellular carcinoma, a type of liver cancer. They compared MELD scores between the groups, and adjusted race- and ethnicity-specific comparisons of these scores for factors like age, sex, year, liver disease etiology, body mass index, ascites and hepatic encephalopathy.

Among 88,542 waitlist registrants for liver transplantation, the researchers found the overall average MELD at the time of registration was 17.4 ± 8.6. African-American patients had a significantly higher average MELD score at waitlist registration than all other race/ethnic groups across all years and regions. All non-white racial and ethnic minorities were significantly more likely to have a higher MELD scores at time of waitlist registration compared to non-Hispanic white patients, with African-American patients having the greatest disparity, the study shows. Similar trends were seen at the time of liver transplantation, with African-American and Hispanic patients having significantly higher MELD scores compared to non-Hispanic whites.

“African-Americans had significantly higher MELD scores at time of liver transplantation waitlist registration, which was observed even after correcting for potential geographic variations. This is particularly important, given that prior data suggested that ethnic disparities may be a direct result of geographic differences,” explains Dr. Robinson of the study’s findings. “While the process of liver transplantation referral is complex and affected by multiple factors, our observations raise serious concerns about persisting race/ethnicity-specific disparities in liver transplantation in the U.S. that need to be studied further so that targeted interventions may be developed to mitigate these disparities.”

Editor’s note: This study was sponsored by AASLD Foundation (link is external) through its Clinical and Translational Research Award in Liver Diseases.

Dr. Robinson will present these findings at AASLD’s press conference in Room 312-314 at the George R. Moscone Convention Center in San Francisco on Saturday, November 10 from 4:00 PM – 5:30 PM. The study entitled “African Americans Have Significantly Higher Model for End Stage Lier Disease Scores at Time of Liver Transplant Waitlist Registration across All Liver Transplant Regions” will be presented on Sunday, November 11 at 4:30 PM in Room 153/155. The corresponding abstract (number 0164) can be found in the journal, HEPATOLOGY (link is external).
About AASLD

AASLD is the leading organization of clinicians and researchers committed to preventing and curing liver disease. The work of our members has laid the foundation for the development of drugs used to treat patients with viral hepatitis. Access to care and support of liver disease research are at the center of AASLD’s advocacy efforts.

Press releases and additional information about AASLD are available online at www.aasld.org.
Read the press release.

The Liver Meeting® Under-Immunization Still a Major Problem in Pediatric Liver Transplant Patient Population

Under-Immunization Still a Major Problem in Pediatric Liver Transplant Patient Population

SAN FRANCISCO – Data from a new study presented this week at The Liver Meeting® – held by the American Association for the Study of Liver Diseases – found that more than half of pediatric liver transplant recipients are under-immunized at the time of their transplant and are at increased risk for vaccine-preventable infections.

Vaccine-preventable infections are a serious complication for pediatric patients following a liver transplantation. These infections can lead to significant co-existing diseases and conditions, graft rejection, death and increased medical costs. In a prior study published in The Journal of Pediatrics, researchers at Children’s Hospital Colorado demonstrated that one in six pediatric liver transplant recipients is hospitalized with a vaccine-preventable infection in the first two years following transplantation.

Immunizations are a minimally invasive and cost-effective way to reduce such infections. The research team has continued their work in this project to learn more about the reasons behind the high number of under-immunized pediatric patients.

“Our study, which used the Pediatric Health Information System database, demonstrated that one in six liver transplant recipients was being hospitalized in the first two years post-transplant with an infection that was potentially vaccine preventable,” says Amy Feldman, MD, MSCS, program director, Liver Transplant Fellowship at Children’s Hospital Colorado, and the study’s co-author. “Therefore, we became interested in investigating whether immunizations were an actionable gap in practice that could lead to significantly improved transplant outcomes.”

The researchers collected immunization records at the time of liver transplantation for patients undergoing transplant at one of 39 North American centers in the Studies of Pediatric Liver Transplantation Consortium, or SPLIT, from August 2017 through May 2018. Immunization records were available for 106 of 119 potential subjects (89 percent) from 27 centers.

Using the CDC’s Immunization Schedule, 51 percent of the patients who received their transplant before the age of two, and 40 percent of patients who received their transplant at age two or older, were completely up to date for their age on immunizations. Using an accelerated schedule of immunizations allowed for children awaiting transplantation (published by the American Society of Transplantation and the Infectious Diseases Society of America) only four percent of patients were fully up to date on age-appropriate immunizations at the time of transplant. Out of all 106 patients in the study, five percent had delayed transplant listing to allow time for them to become up to date on their immunizations.

The immunizations most frequently missed were DTaP (diphtheria, tetanus, pertussis) and PCV13 (the pneumococcal conjugate vaccine). The study found that out of 23 children who were six to 11 months old at transplant, who would have been eligible for accelerated live immunizations, only 13 percent had received the MMR (measles, mumps, rubella) vaccine and only nine percent were immunized against varicella prior to surgery. The study also found that out of 79 patients one year or older at transplant, only 80 percent were immunized against hepatitis A despite eligibility. Of 20 children age 11 or older at the time of transplant, only 70 percent had received the DTaP booster and 65 percent had received the HPV (human papilloma virus) vaccine. The researchers found that age, gender, race, ethnicity; and underlying diagnosis were not associated with under-immunization.

The study’s data show that 56 percent of pediatric liver transplant patients are under-immunized at the time of their transplant, leaving a significant portion of transplant recipients at increased risk for vaccine-preventable infections.

“Our study highlights under-immunization as a problem in the transplant population. In future studies, we plan to investigate what are the specific barriers faced by parents, primary care providers and hepatologists that prevent transplant candidates from being fully immunized at the time of transplant,” explains Dr. Feldman. “We then hope to develop tools within the healthcare system that can overcome these barriers and improve immunization delivery to transplant candidates and recipients, ultimately leading to improved post-transplant outcomes.”

Editor’s note: This press release contains updated data that is not reflected in the published abstract, but will be presented at The Liver Meeting®.

Dr. Feldman will present the study entitled “Immunization Rates at the Time of Pediatric Liver Transplant: A Prospective Multicenter Study through the Studies of Pediatric Liver Transplantation (SPLIT)” on Monday, November 12 at 10:30 AM in Room 312/314. The corresponding abstract (number 0240) can be found in the journal, HEPATOLOGY (link is external).

About AASLD
AASLD is the leading organization of clinicians and researchers committed to preventing and curing liver disease. The work of our members has laid the foundation for the development of drugs used to treat patients with viral hepatitis. Access to care and support of liver disease research are at the center of AASLD’s advocacy efforts.

Press releases and additional information about AASLD are available online at www.aasld.org.

Liver Meeting® 2018 - AASLD Poster Roundup: Gender, Insurance, Weight and Waitlists

Meeting Coverage > AASLD

AASLD Poster Roundup: Gender, Insurance, Weight and Waitlists
Selections from poster sessions at the annual Liver Meeting

  • by Staff Writer, MedPage Today

SAN FRANCISCO -- Women and liver transplant waitlists, the impact of insurance on waitlist outcomes, and the tie between obesity and waitlist representation were highlighted in a group of poster presentations at the annual Liver Meeting, sponsored by the American Association for the Study of Liver Diseases (AASLD).

Rubin said it has been well-established that women waiting for a liver transplant may have worse outcomes than men, but the mechanisms for this disparity remain unclear. She told MedPage Today her group hypothesized that hospitalization would be a sufficient surrogate marker for disease severity, and that "if there were differences in hospitalization, maybe that could explain how the disease trajectory is different in women compared with men."


Meeting Coverage
Liver Meeting to Focus on Practice Matters Along with Science
Topics range from 'day in the life' of a hepatology consultant to novel NASH therapies 
View all coverage at MedPage Today

Thursday, October 4, 2018

Would you rather die of liver failure or live with HIV?

Would you rather die of liver failure or live with HIV? 
4 October 2018 - Wits University 

Living donor liver transplantation from an HIV positive mother to her HIV negative child in South Africa 

This was the ethical dilemma faced by doctors at Wits Donald Gordon Medical Centre to save a child's life.

In 2017, doctors from the Transplant Unit at the Wits Donald Gordon Medical Centre performed what is believed to be the world's first intentional liver transplant from a mother living with HIV to her critically ill HIV negative child, who had end-stage liver disease.

Now, more than a year later, the mother and child have fully recovered, however, doctors are unsure the HIV-status of the child.

In South Africa, a country with the largest anti-retroviral therapy (ART) programme in the world, people with HIV live long and healthy lives.

The success of this world-first operation thus presents a potential new pool of living donors that could save additional lives.

Leveraging "living positive" to save more lives
In a paper published in prestigious, peer-reviewed journal AIDS on October 4, 2018, scientists in surgery, ethics, and HIV from the University of Witwatersrand, Johannesburg (Wits) explain how a chronic shortage of organs compromise their efforts to save lives, and how the decision they made to perform a world-first operation could advance transplantation.

Jean Botha, principal investigator and transplant surgeon is Professor of Surgery in the Department of Surgery in the School of Clinical Medicine, Faculty of Health Sciences at Wits University.

"Two aspects of this case are unique. Firstly, it involved intentional donation of an organ from a living HIV positive individual. Secondly, pre-exposure prophylaxis [medication to protect at-risk individuals from contracting the HI virus] in the child who received the organ may have prevented the transmission of HIV. However, we will only know this conclusively over time," says Botha, who is also Director of Transplantation at the Transplant Unit at the Wits Donald Gordon Medical Centre.

Currently, the Wits Donald Gordon Medical Centre is the only Transplant Programme doing living donor liver transplantation in southern Africa. It is also the first privately administered teaching hospital in Johannesburg and, as a Wits hospital, advances specialist training and research.

Stringent adherence to ethical guidelines
In this case of transplanting a liver from an HIV positive donor to a non-infected recipient, the transplant team had to unpack the potential risks and benefits to both. The Human Research Ethics Committee (Medical) at Wits University approved the liver transplantation from the mother living with HIV to her HIV negative child. Their personal details remain confidential.

The child - on the waiting list for a deceased donor for 180 days (the average is 45 days) - was frequently admitted for life-threatening complications of end-stage liver disease. Without transplant, the child would certainly have died. However, saving the child's life needed to be balanced against harm to the donor and the risk of almost certainly transmitting HIV if the mother was the donor.

Dr Harriet Etheredge is a medical bioethicist who holds an honorary position in the Department of Internal Medicine, School of Clinical Medicine at Wits, and oversees Ethics and Regulatory Issues at the Wits Donald Gordon Medical Centre.

"Extensive efforts were made to identify either a deceased liver donor or an HIV negative living donor for the child before considering an HIV positive parent donor. Transplanting HIV positive organs is not illegal in South Africa; however, it is not considered best practice internationally because of the risk of HIV transmission to the recipient. To minimise risk to donors and recipients, this operation is offered only under exceptional circumstances. Full consent is required from the parents who must be able to care for a child infected with HIV," says Etheredge, whose PhD is in the field of medical ethics and organ transplantation.

In this transplantation case, the mother asked a number of times for the opportunity to save her child's life by donating a segment of her liver. For this mother, quantifying the risk was simpler for the transplant team. Dr Francesca Conradie, HIV clinician, notes, "When considering an HIV positive parent, it is important that they have an undetectable viral load. This means that they know they are HIV positive and that they have been taking their antiretroviral medication properly for at least six months".

This made the risk of donation equivalent to that of an HIV negative living donor. However, living liver donation is never a risk-free procedure, and the team took care to ensure that the mother understood the full ambit of the risk she was undertaking.

"Our Independent Donor Advocate helps the parents understand the risks, makes representations to the transplant team on behalf of the donor if necessary, and provides emotional support throughout the process," says Etheredge.

Intentional transmission of HIV to save a life
The transplant team faced the dilemma of saving the child's life whilst at the same time knowing that the child might end up HIV positive because of this decision. However, because this intentional HIV positive living donor liver transplant is likely a world first, the actual chance of transmitting HIV was unknown.

The team decided to work on the basis that the child would contract HIV, and provide management accordingly. But in the time since the transplant, there have been some surprises when it comes to the child's HIV status.

"In the weeks after the transplant, we thought that the child was HIV positive, because we detected HIV antibodies," says Botha.

The transplant team then accessed specialised testing by HIV experts at the National Institute of Communicable Diseases (NICD) who subsequently could not find any active HIV infection in the blood stream of the child, meaning there is a chance that the child is HIV negative.

Caroline Tiemessen is Research Professor in the School of Pathology at Wits and head of Cell Biology within the Centre for HIV and STIs.

"At the moment, we are developing new methods for testing the child, and we hope to be able to have a definitive answer to the question of seroconversion in future. For now the child will remain on ART until we have a more comprehensive picture," says Tiemessen who, in 2017, led the laboratory investigations in the case where of a South African child living with HIV had remained in remission without ART since 2008.

Seroconversion is the period of time during which a specific antibody develops and becomes detectable in the blood. After seroconversion has occurred, HIV can be detected in blood tests for the antibody.

Expanded organ donor pool to advance transplantation in Africa

More than a year since the intentional liver transplantation from a mother living with HIV to her HIV negative child, both donor and recipient have recovered and are well.

Dr June Fabian, a nephrologist and Research Director at Wits Donald Gordon Medical Centre says, "We have formalised this procedure as a research programme. As we offer this type of transplantation to more children, we hope to be able to draw more definitive conclusions."

Organ transplantation at the Wits Donald Gordon Medical Centre is offered to any person irrespective of income or demographic according to "sickest first" criterion. This is possible through an existing partnership between the Wits Donald Gordon Medical Centre and the Gauteng Department of Health.

"We hope that this ground-breaking operation will be the first of many like it and will contribute towards promoting justice and equity in liver transplantation in South Africa," says Fabian. 

University of the Witwatersrand

Friday, September 28, 2018

Hepatitis C Infection May Be a Blessing for Patients in Need of a Transplant

Hepatitis C Infection May Be a Blessing for Patients in Need of a Transplant
Lara C. Pullen PHD
First published: 27 September 2018
https://doi.org/10.1111/ajt.15091

This month's installment of “The AJT Report” looks at how transplanting HCV‐positive organs can reduce risks for patients awaiting organs. We also report on Bristol Myers Squibb's recent easement of restrictions in prescribing belatacept (Nulojix).

“We are very proactive about our hepatitis C patients,” says Uttam Reddy, MD, medical director of the kidney transplant program at the University of California, Irvine (UCI) Medical Center. This is because in Southern California, the average wait time for a hepatitis C virus (HCV)‐negative organ is 8 to 10 years. If, however, a patient with HCV is willing to receive an HCV‐positive organ, the typical wait time is less than two years, a difference that Dr. Reddy describes as a “notably significant benefit.” In fact, he adds, “Before treating HCV in patients with advanced kidney disease, we recommend that they be evaluated at UCI first to assess the degree of their liver disease. If their liver disease is not advanced, we recommend proceeding with transplant and then treating their HCV after transplantation.”

Key Points
• Hepatitis C virus (HCV)-positive patients who elect to receive HCV-positive organs may cut years off their wait time.
• While the risk from an HCV-positive organ is difficult to quantify, it needs to be weighed against known risk from years on dialysis.
• Direct-acting antivirals (DAAs) lower risks associated with receiving HCV-positive organs.
• More frequent HCV diagnoses, greater use of DAAs and a potential ebbing of the opioid epidemic mean that fewer HCV-positive organs will be available in the future.

Read online: https://onlinelibrary.wiley.com/doi/full/10.1111/ajt.15091

Download PDF: https://onlinelibrary.wiley.com/doi/epdf/10.1111/ajt.15091

Monday, September 17, 2018

HCV Next October Issue - Research continues to invalidate link between DAA treatment, liver cancer

HCV NEXT September/October Issue
Greetings, the following articles appeared in this months issue of HCV NEXT, published online over at Healio.

Table of Contents
HCV vaccine could reduce transmission in people who inject drugs

AASLD invests $4.06 million in liver disease research, development

Cover Story
HCV-Positive Organs: A Viable Option for Uninfected Transplant Patients

In the Journals
Research continues to invalidate link between DAA treatment, liver cancer

Novel ‘genotype 8’ surfaces among four patients with HCV

Treating HCV in prison ‘microenvironment’ reduces transmission

Heart transplant with HCV-positive organs successful, virus cleared

In the Journals Plus

Children lose out on liver transplants, study finds

“Children with chronic liver disease who are in need of transplant may be at a disadvantage compared with adults in a similar situation,” they wrote in their report, published in the journal JAMA Pediatrics.

Children lose out on liver transplants, study finds
by Maggie Fox / Sep.17.2018
The system for allocating liver transplants is stacked against kids, a new study finds.

Children who need lifesaving liver transplants are losing out to adults, according to a new study released Monday.

A system used to determine who is most in need of a transplant significantly underestimates the risk of death for younger children with liver disease, the team at the University of Pittsburgh found
Continue reading....

Thursday, June 14, 2018

Canadian team reports success in transplanting hepatitis C organs

Toronto doctors safely transplant lungs from hepatitis C-infected donors
by Sheryl Ubelacker, The Canadian Press
Last Updated Jun 14, 2018 at 8:24 am EDT

Toronto doctors have successfully transplanted lungs from deceased donors with hepatitis C into patients in need of the lifesaving organs, followed by treatment to prevent them from becoming infected with the potentially liver-destroying virus.

Since October, surgeons at Toronto General Hospital have performed the transplants in 11 patients as part of a pilot study to evaluate the safety of using lungs from hepatitis C-infected donors — a previously untenable idea.

That’s because antiviral drugs can now cure the disease in 98 per cent of people infected with hepatitis C, which affects an estimated 250,000 Canadians, about 40 to 70 per cent of them unaware they harbour the blood-borne virus.

“With the opioid crisis and persistent high rates of intravenous drug use, we have a great number of potential lung donors who are hepatitis C-positive, many of whom didn’t even know they were sick when they were alive,” said Dr. Marcelo Cypel, a thoracic surgeon at TGH and principal investigator of the study.

Canadian team reports success in transplanting hepatitis C organs
WASHINGTON: A long-running shortage in donor organs has pushed doctors to find ways to use those with hepatitis C, an infection that is increasingly common in the United States due to the opioid crisis, and which can be cured with medicine.

Some US hospitals, particularly in Boston, have already transplanted infected donor organs into people without hepatitis C. These patients are swiftly treated with drugs to eliminate the virus.

In Toronto, Canada, another team of doctors on Thursday announced early results from a trial using a different technique, involving 10 people who received lung transplants from donors with hepatitis C.

Continue reading: 

Friday, June 8, 2018

HCV/HIV-coinfection - Successful direct acting antiviral (DAA) treatment before and after liver transplantation

PLOS ONESuccessful direct acting antiviral (DAA) treatment of HCV/HIV-coinfected patients before and after liver transplantation
Julia M. Grottenthaler, Christoph R. Werner, Martina Steurer, Ulrich Spengler, Thomas Berg, Cornelius Engelmann, Heiner Wedemeyer, Thomas von Hahn, Wolfgang Stremmel, Anita Pathil, Ulrich Seybold, Eckart Schott, Usha Blessin, Christoph P. Berg

Published: June 6, 2018 https://doi.org/10.1371/journal.pone.0197544 

Links

Abstract
Objectives
The aim of this multicenter retrospective study was to investigate safety and efficacy of direct acting antiviral (DAA) treatment in the rare subgroup of patients with HCV/HIV-coinfection and advanced liver cirrhosis on the liver transplant waiting list or after liver transplantation, respectively.

Methods
When contacting 54 German liver centers (including all 23 German liver transplant centers), 12 HCV/HIV-coinfected patients on antiretroviral combination therapy were reported having received additional DAA therapy while being on the waiting list for liver transplantation (patient characteristics: Child-Pugh A (n = 6), B (n = 5), C (n = 1); MELD range 7–21; HCC (n = 2); HCV genotype 1a (n = 8), 1b (n = 2), 4 (n = 2)). Furthermore, 2 HCV/HIV-coinfected patients were denoted having received DAA therapy after liver transplantation (characteristics: HCV genotype 1a (n = 1), 4 (n = 1)).

Results
Applied DAA regimens were SOF/DAC (n = 7), SOF/LDV/RBV (n = 3), SOF/RBV (n = 3), PTV/r/OBV/DSV (n = 1), or PTV/r/OBV/DSV/RBV (n = 1), respectively. All patients achieved SVR 12, in the end. In one patient, HCV relapse occurred after 24 weeks of SOF/DAC therapy; subsequent treatment with 12 weeks PTV/r/OBV/DSV achieved SVR 12. One patient underwent liver transplantation while on DAA treatment. Analysis of liver function revealed either stable parameters or even significant improvement during DAA therapy and in follow-up. MELD scores were found to improve in 9/13 therapies in patients on the waiting list for liver transplantation; in only 2 patients a moderate increase of MELD scores persisted at the end of follow-up.

Conclusion
DAA treatment was safe and highly effective in this nation-wide cohort of patients with HCV/HIV-coinfection awaiting liver transplantation or being transplanted.

Tuesday, June 5, 2018

Editorial - If Hepatitis C therapy is so great, why isn’t everyone doing it?

Editorial
If Hepatitis C therapy is so great, why isn’t everyone doing it? 
Robert S. Brown, Jr., M.D., M.P.H
Am J Transplant. [Epub ahead of print]
First published: 04 June 2018
https://doi.org/10.1111/ajt.14960
In this issue of the journal, Drs. Axelrod et al. aimed to investigate the impact of direct-acting antiviral agents for Hepatitis C (HCV) on liver and kidney transplant outcomes and cost for HCV positive patients.

Link
Download PDF Article 
Given that hepatitis C therapy is recommended for all patients who do not have a short life expectancy, certainly all transplant recipients should be treated for hepatitis C in the early post-transplant period prior to developing any significant liver disease in the liver allograft or progressive disease in the renal transplant recipient. Early therapy would also prevent any cases of cholestatic hepatitis. Given that hepatitis C therapy is likely cost-effective in the non-transplant setting, it would certainly be cost-effective in the transplant setting. One would hope that we are doing better with pangenotypic lower cost DAA options with fewer drug-drug interactions now available. Given the WHO's recommendation for HCV elimination by 2030, the fact that the transplant community has not been able to eliminate HCV in our transplant recipients remains a concern. Better education of our providers, advocacy for our patients, and better access to medications are the only solution to this problem. I certainly hope we get there soon.
Continue reading: Download PDF Article 

Tuesday, May 22, 2018

More patients with severe alcoholic hepatitis receiving liver transplants

More patients with severe alcoholic hepatitis receiving liver transplants
Medical centers willing to perform transplants without mandated six-month wait

Washington, DC (May 22, 2018) -- Increasingly, liver transplant centers are changing a long-standing practice of delaying potentially life-saving liver transplantation for patients with severe alcoholic hepatitis until after they stopped drinking alcohol for six months, according to a new study scheduled for presentation at Digestive Disease Week® (DDW) 2018.

Study implications
"Liver transplant for severe alcoholic hepatitis is being increasingly accepted, with positive outcomes, and the hope is that more and more patients will be evaluated for transplants," said Saroja Bangaru, MD, chief resident in internal medicine at the University of Texas Southwestern Medical Center, Dallas, and co-author of the study. "The hope is that survival rates are encouraging enough for centers, so that even more of them will reverse past practices."

Severe alcoholic hepatitis has an extremely high mortality rate. The primary treatment option has been the use of steroids, predominantly prednisolone. But, many patients do not respond to steroids, and a significant percentage of them will die within three months.

Historically, centers would not perform transplants until patients had stopped drinking for six months due to concerns about a return to drinking after transplant. Additionally, there was a perceived high risk that patient's continued drinking would cause them to miss medical appointments and failure to take their immunosuppressant medications, which prevent organ rejection, all of which could contribute to transplant failure.

Only in recent years have limited studies begun to show greater success for transplants for severe alcoholic hepatitis, Bangaru said. These studies have also shown that a variety of other factors -- aside from recent drinking -- influence whether a patient relapses. These include whether the patient has good social support, suffers from psychiatric ailments and accepts that they have an alcohol problem. "These studies suggest that predicting risk of relapse is much more complicated than just duration of abstinence," Bangaru said.

Study design and results
Researchers gathered data from 45 transplant centers, of which 23 said they were now performing such transplants. Among those, 17 centers reported that patients had a one-year survival rate of more than 90 percent, which is higher than that reported in several previous studies.

The survey found that centers have become more willing to perform transplants, as long as patients are carefully screened. Researchers reported that centers use highly selective criteria in approving candidates for transplant, assessing their medical history, social support system and whether they have additional health problems, particularly psychiatric disorders.

"If patients are selected well, according to these criteria, it allows for the excellent survival that we are seeing post-transplant," Bangaru said. Past policy has done a disservice to those patients who were previously unaware that they had liver disease. "Some patients come in for the first time with severe alcoholic hepatitis, and no one has ever told them to stop drinking. Because they are not eligible for transplant, they have a really high mortality rate."

The survey also concluded that most transplant centers had "inadequate" post-transplant support for patients. While most offered the services of social workers, only a limited number provided psychiatric or group therapy support that could be very important in helping patients avoid relapse and further medical problems.

Next steps
Dr. Bangaru said further study is needed to encourage more transplants, in particular a controlled clinical trial that follows survival rates over one, three and five years, along with an assessment of rates of alcoholic relapse.

DDW presentation details
Dr. Saroja Bangaru will present data from the study, "Increased use of liver transplantation as therapeutic option for severe alcoholic hepatitis," abstract Sa1457, on Saturday, June 2, at noon EDT. For more information about featured studies, as well as a schedule of availability for featured researchers, please visit http://www.ddw.org/press.

Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place June 2-5 at the Walter E. Washington Convention Center in Washington, DC. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. 
More information can be found at http://www.ddw.org.
https://www.eurekalert.org/pub_releases/2018-05/ddw-mpw051818.php

Thursday, April 19, 2018

Life of a liver awaiting transplantation - Machine that preserves livers might offer a way forward


NEWS AND VIEWS
18 April 2018

Life of a liver awaiting transplantation
Stefan Schneeberger
People waiting for a liver transplant can die before an organ is found, or, if one is available but of poor quality, there is a risk of transplant failure. A machine that preserves livers might offer a way forward.

The concept of machine perfusion of an organ awaiting transplantation is not new. Indeed, machine-assisted perfusion was in use before cold storage became the method of choice owing to its simplicity and reproducibility2. However, interest in revisiting perfusion as a transplant approach has been gaining momentum.

The main outcome monitored in the latest trial was the post-transplantation level of the enzyme aspartate transaminase in patients’ blood. This measurement is commonly used to assess liver damage and to estimate the risk of transplant failure. The authors found that the use of NMP was associated with less liver damage than that found in livers preserved on ice. Moreover, preservation by NMP reduced the number of organs that were discarded as unsuitable for transplantation compared with livers preserved on ice, and was associated with a better blood-flow profile in the recipient.

Tuesday, April 17, 2018

Every Cloud Has a Silver Lining: Overdose-Death Donors in Organ Transplantation

HIV and ID Observations
Hepatitis C Positive Organ Donors — Coming Soon to a Transplant Center Near You
There’s one immutable fact in solid organ transplantation — the number of patients awaiting transplant exceeds the number of available organs.
Continue reading...

Reuters Health
Organs from overdose-death donors a viable option for transplant
Last Updated: 2018-04-16
By Marilynn Larkin
NEW YORK (Reuters Health) - Transplantation with overdose-death donor (ODD) organs has increased dramatically in the U.S., with equivalent outcomes to non-ODD organs, and therefore these organs should not be routinely discarded, researchers in Maryland say.

"Most Americans know that the U.S. faces an epidemic of deaths due to drug overdose, and many are also aware that there is a critical shortage of organs available for transplant," Dr. Christine Durand of Johns Hopkins University School of Medicine in Baltimore told Reuters Health.

"Perhaps less widely known is that today, more than one in every 10 deceased organ donors died from a drug overdose," she said by email.

"Patients who received transplants from these donors had excellent outcomes; patient survival and organ function were similar to cases when donors died due to trauma, and similar or better than cases when the donor died due to medical causes of death like heart attack or stroke," she added.

Dr. Durand and colleagues examined data from January 2000 to September 2017 on 138,565 deceased donors and 337,934 transplant recipients at 297 transplant centers in the U.S.

Ann Intern Med 2018
Editorial |17 April 2018
Nearly 115 000 candidates currently await organ transplantation in the United States (mostly kidneys [81%] and livers [12%]) (1). Because of the profound organ shortage, many candidates awaiting transplant experience significant morbidity and mortality each year. In this issue, Durand and colleagues (2) review the use of overdose-death donor (ODD) organ transplants involving 138 565 deceased donors and 337 934 solid organ transplant recipients from 2000 to 2017. The study used the Scientific Registry of Transplant Recipients, which includes U.S. national data collected by the Organ Procurement and Transplantation Network (OPTN). The authors found that ODD transplants increased 24-fold, from 149 in 2000 (1.1% of donors) to 3533 in 2016 (12.7% of donors). For the most part, outcomes with ODD organs were noninferior to those with organs from trauma-death donors (TDDs) and medical-death donors (MDDs). Compared with MDDs, ODDs were less likely to have hypertension, diabetes, or prior myocardial infarction but had slightly higher creatinine levels and were more likely to donate after circulatory death. Cold ischemic time of transplanted kidneys was similar across all donor types. In an adjusted analysis, recipients of ODD kidneys and livers had a lower risk for death than recipients of MDD organs and a similar risk for death and graft loss compared with recipients of TDD organs.

Monday, April 16, 2018

Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?

World J Gastroenterol. Apr 14, 2018; 24(14): 1491-1506
Published online Apr 14, 2018. doi: 10.3748/wjg.v24.i14.1491

Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?
Ivana Mikolasevic, Tajana Filipec-Kanizaj, Maja Mijic, Ivan Jakopcic, Sandra Milic, Irena Hrstic, Nikola Sobocan, Davor Stimac, Patrizia Burra

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a primary cause of macrovesicular steatosis and has several impacts on liver transplantation (LT), which is transmitted to transplant recipients and organ donors. Current data indicate a new trend in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome (MetS) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT.

Wednesday, April 11, 2018

#ILC2018 Alcoholic liver disease replaces hepatitis C infection as leading cause of liver transplantation in patients without hepatocellular carcinoma in the USA

Alcoholic liver disease replaces hepatitis C infection as the leading cause of liver transplantation in patients without hepatocellular carcinoma in the USA

European Association for the Study of the Liver
11 April 2018, Paris, France: Two independent studies have today reported that alcoholic liver disease has now replaced hepatitis C virus (HCV) infection as the leading cause of liver transplantation in the USA in patients without HCC. Non-alcoholic steatohepatitis (NASH) is also on the increase, now ranking second as a cause of liver transplantation due to chronic liver disease.

Chronic HCV infection has remained the leading indication for liver transplantation in the USA for the last two decades.1 However, the availability of second-generation direct-acting antiviral agents (DAAs) in late 2013 led to a decline in the number of HCV-related liver transplant waiting list registrations and surgeries from 2015 onwards.2,3 Alcohol consumption began to increase markedly in the US during the 1990s and early 2000s, with data highlighting dramatic rises in alcohol use and high-risk drinking in recent years.4

The two studies presented this week at The International Liver Congress™ 2018 in Paris, France, were conducted to evaluate recent trends in the aetiology of liver disease among liver transplant recipients in the USA in view of the changing landscape of potential risk factors. In the first study, data from the United Network for Organ Sharing (UNOS) between 2005-2016 were analyzed, looking at four indications for chronic liver disease: alcoholic liver disease (ALD), NASH, HCV infection, and HCV/ALD combined. According to the results of the study, the number of liver transplant recipients with HCV peaked in 2014 (1,905 individuals) and has been declining ever since. In contrast, the number of liver transplants due to ALD and NASH has been steadily increasing and, in 2016, there were 1,624 liver transplants performed as a result of ALD, compared with 1,535 due to HCV, 1,334 due to NASH, and 424 due to HCV/ALD.

'Although we found that, overall, alcoholic liver disease became the leading indication for liver transplantation in the US in 2016, NASH was not far behind', said Dr Jennifer Wang from the California Pacific Medical Center in San Francisco, USA, who presented the study findings. 'Importantly, NASH is now the leading cause of liver transplantation in women, which is not entirely surprising given the higher rates of metabolic syndrome in women and the resultant increased risk of non-alcoholic fatty liver disease'.

'In African Americans and those with hepatocellular carcinoma, HCV remains the leading cause of transplantation and a major burden'.

The second study presented today also evaluated data from the UNOS registry, looking at first liver transplants performed in individuals without HCC between January 2012 and October 2017. As in the first study, HCV infection remained the leading aetiology for liver transplant recipients until 2016, when ALD surpassed it, accounting for 24% of liver transplants performed compared with 19% for NASH and 18% for HCV. In 2017, ALD, NASH, and HCV were responsible for 24%, 18%, and 17% of liver transplants, respectively, according to the results of this study.

'One of our most worrying findings was that patients with ALD are being listed for liver transplantation at a much younger age and with more severe disease than patients with either HCV infection or NASH', said investigator, Dr George Cholankeril from Stanford University Medical Center, California, USA. 'These are very ominous trends and we need to take aggressive action to address these rising rates of liver transplantation in patients with alcoholic liver disease'.

'So far, alcoholic liver disease has received much less attention with regards to clinical and basic research than either hepatitis B or C',5 said Prof. Helena Cortez-Pinto from the University Hospital of Santa Maria, Lisbon, Portugal, and EASL Governing Board Member. 'It is time to change and turn our attention to ALD, both in research and of course in policies that have been shown to reduce consumption, such as increases in taxation, in order to decrease affordability'.

About The International Liver Congress™
This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Attending specialists present, share, debate and conclude on the latest science and research in hepatology, working to enhance the treatment and management of liver disease in clinical practice. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. The International Liver Congress™ 2018 will take place from 11¬-15 April 2018 at the Paris Convention Centre, Paris, France.

About The European Association for the Study of the Liver (EASL)
Since its foundation in 1966, this not-for-profit organization has grown to over 4,000 members from all over the world, including many of the leading hepatologists in Europe and beyond. EASL is the leading liver association in Europe, having evolved into a major European association with international influence, and with an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

Onsite location reference
Session title: Poster presentations Time, date and location of session: Poster area (Hall 7.2) Presenters: Jennifer Wang and George Cholankeril, USA Abstracts: Alcoholic liver disease surpasses hepatitis C virus in 2016 to become the leading indication for liver transplantation among adults without hepatocellular carcinoma in the United States (13 April 2018 9:00-17:00) and Alcoholic liver disease replaces HCV infection as the leading indication for liver transplantation in the United States (14 April 09:00-17:00)

Author disclosures
Jennifer Wang: None reported
Robert Gish: Dr. Gish has received Grants/Research Support from AbbVie, Benitec Biopharma, Gilead Sciences, and Merck & Co. Dr. Gish has performed as Consultant and/or Advisor to AbbVie, Akshaya Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Genentech, Gilead Sciences, Hoffman-LaRoche, Ltd., Ionis Pharmaceuticals, Janssen, Merck & Co., Nanogen Biopharmaceutical, and Presidio Pharmaceuticals. Dr. Gish has current activity with the scientific or clinical advisory boards of AbbVie, AstraZeneca, Genentech, Gilead Sciences, Janssen, Merck & Co., and Nanogen Biopharmaceutical. Dr. Gish is a member of the Speakers Bureau for AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Merck. Dr. Gish is a minor stock shareholder of Cocrystal Pharma.

Benny Liu: None reported Taft Bhuket: None reported
Robert Wong: Dr Wong receives research funding from Gilead Sciences and AbbVie, has served as a consultant and member of the advisory board for Gilead Sciences, and serves on the speaker's bureau for Gilead Sciences, Salix, and Bayer. Dr Wong is also funded by an AASLD Foundational Clinical and Translational Research Award in Liver Diseases.

George Cholankeril and co-authors: None reported
References 1. Cholankeril G, Ahmed A. Alcoholic liver disease replaces hepatitis C virus infection as the leading indication for liver transplantation in the United States. Clin Gastroenterol Hepatol. 2017; doi: 10.1016/j.cgh.2017.11.045 [Epub ahead of print].

2. Goldberg D, et al. Changes in the prevalence of hepatitis C virus infection, nonalcoholic steatohepatitis, and alcoholic liver disease among patients with cirrhosis or liver failure on the waitlist for liver transplantation. Gastroenterology. 2017;152(5):1090-9.e1.

3. Flemming JA, et al. Reduction in liver transplant wait-listing in the era of direct-acting antiviral therapy. Hepatology. 2017;65(3):804-12.

4. Grant BF, et al. Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the United States, 2001-2002 to 2012-2013: results from the National Epidemiologic Survey on Alcohol and Related Conditions. JAMA Psychiatry. 2017;74(9):911-23.

5. Ndugga, N, et al. Disparities between research attention and burden in liver diseases: implications on uneven advances in pharmacological therapies in Europe and the USA. BMJ Open. 2017;7(3):e013620; doi: 10.1136/bmjopen-2016-013620 [Epub ahead of print].

Monday, March 19, 2018

March 2018 Webinar: Overview of living-donor liver transplants

Webinar: Living-Donor Organ Transplant
On Thursday, March 8th ALF offered a webinar focused on living-donor liver transplants. Swaytha Ganesh, M.D., medical director of the University of Pittsburg Medical Center (UPMC) Living Donor Transplant Program, provided an overview of living-donor liver donation, including the process and considerations for donors and recipients. A parent advocate also shared her daughter’s story and strategies she used to find a living donor, and a patient who provided a living organ donation to his brother shared their story.

To watch a recording of the informative presentation, click here.

Monday, March 5, 2018

One year posttransplant, recipients of hepatitis C kidneys disease-free

One year posttransplant, recipients of hepatitis C kidneys disease-free
Johns Hopkins Medicine

Study: Published in Annals of Internal Medicine

In a small study, doctors at Johns Hopkins have successfully transplanted 10 hepatitis C-infected kidneys into patients without hepatitis C and prevented the patients from becoming infected by hepatitis C. The success of these transplants could mean more organs being available for the nearly 100,000 people in the U.S. currently waiting for a kidney transplant.

"Right now, most of the usable organs from donors with hepatitis C are discarded because there are very few hepatitis C-positive recipients on the waiting list," says Niraj Desai, M.D., an assistant professor of surgery at Johns Hopkins University School of Medicine and senior author of the new paper, published in Annals of Internal Medicine. "Figuring out how to use these kidneys is a way to do more transplants and save more lives."

Until recently, treating hepatitis C was difficult; treatment regiments often included weekly injections, led to serious side effects that not all patients could tolerate and didn't cure all cases of the viral infection. That meant that organs -- including kidneys -- from hepatitis C-positive people were considered too high-risk to transplant into patients without the virus.

Around 500 hepatitis C-positive kidneys are discarded from organ donors in the U.S. every year, Desai says. And hundreds more may never make it to a recipient because some organ procurement organizations don't procure the kidneys in the first place due to the lack of a suitable recipient.

In the past seven years, however, a handful of new direct-acting antivirals have hit the market; the drugs cure more than 95 percent of all hepatitis C cases and carry few side effects. Desai and his colleagues thought it was time to try taking advantage of the new drugs to pave the way for using hepatitis C-positive kidneys for transplants.

"In this era of organ shortages, it's difficult to watch good organs get discarded," says Christine Durand, M.D., an assistant professor of medicine at Johns Hopkins University School of Medicine. "This was a great opportunity to take a neglected public health resource and put it to good use."

Desai, Durand and their colleagues approached patients over age 50 who were awaiting kidney transplants, had no previous transplants and no available living donors, and were negative for hepatitis C as well as HIV and hepatitis B. Ten patients agreed to receive hepatitis C-positive kidneys. Their average age was 71 and they had been on the transplant waiting list an average of four months. All donor kidneys were recovered from donors aged 13 through 50, tested positive for hepatitis C and showed no evidence of kidney disease. The donors' blood was tested for strain and quantity of hepatitis C virus.

Each recipient received a dose of grazoprevir/elbasvir, an oral combination pill, while they were waiting to go into the operating room for their transplant. Each recipient then continued taking a daily pill of grazoprevir/elbasvir for 12 weeks after transplantation. Three patients also took a daily dose of sofosbuvir due to the strain of hepatitis found in their donor organ.

In five of the kidney recipients, there was never any hepatitis C RNA detected in their blood. In the other patients, low levels of the virus were detected shortly after transplant but then became undetectable within days or a week. No recipients ever developed any clinical signs of chronic hepatitis C infection. In addition, the kidneys themselves functioned well. At the time of the study's publication, all patients are at least a year out from their transplant and doing well, says Desai.

"This was an overwhelmingly positive study," adds Durand.

The researchers would next like to see their results replicated in a larger, multicenter trial. They say if the success of the transplants continues, it could pave the way for other hepatitis C-positive organs, including hearts and livers, to be transplanted as well.

"We're always trying to expand what we consider acceptable for an organ donor," says Durand.

Due to the opioid epidemic and deaths from drug overdoses -- many of which occur in hepatitis C-positive individuals -- there are an increasing number of hepatitis C-positive organs available. Being able to use these organs for transplants could mean many hundreds of lives saved each year.

"These 10 kidneys we used are 10 kidneys that would not have been transplanted outside of this study," says Desai. "They would have been discarded."

Other authors of the study are Mary Grace Bowring, Diane Brown, Michael Chattergoon, Guido Massaccesi, Nichole Bair, Russell Wesson, Ashraf Reyad, Fizza Naqvi, Darin Ostrander, Jeremy Sugarman, Dorry Segev and Mark Sulkowski, all from Johns Hopkins.

Funding for the study and support for the researchers involved was provided by Merck Sharp & Dohme Corp, the National Cancer Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Allergy and Infectious Disease.

COI: Christine Durand has received research grants from Bristol Meyers Squibb, Gilead Sciences, Merck Pharmaceuticals and Viiv Healthcare, and she has served as a scientific adviser for Bristol Meyers Squibb, Gilead Sciences and Merck Pharmaceuticals. Jeremy Sugarman serves on Merck KGaA's Bioethics Advisory Panel and Stem Cell Research Oversight Committee, and Quintile's Ethics Advisory Panel. Mark Sulkowski served as scientific adviser for AbbVie, Gilead Sciences, Cocrystal, Janssen, Merck Pharmaceuticals and Trek and also received research grants from AbbVie, Gilead Sciences and Merck Pharmaceuticals. Niraj Desai has served as a scientific adviser for Merck Pharmaceuticals.

https://www.eurekalert.org/pub_releases/2018-03/jhm-oyp022818.php

Norah A. Terrault, MD - Managing HBV Infection Following Liver Transplant: Expert Q&A

Jasenka Piljac Žegarac, PhD
March 05, 2018

Managing HBV Infection Following Liver Transplant: Expert Q&A
In an interview with Infectious Disease Advisor, Norah A. Terrault, MD, MPH, professor of medicine and director of the Viral Hepatitis Center at the University of California, San Francisco (UCSF), discussed the recent advances and remaining challenges in managing HBV infection in patients undergoing liver transplantation.

Infectious Disease Advisor: What is the primary indication for liver transplantation in patients with HBV infection?

Norah A. Terrault, MD, MPH: In our transplant center at UCSF, as in others throughout the United States, the majority of patients with HBV have liver cancer as the primary indication for liver transplantation.7 The other group of patients in whom we perform liver transplants are patients with acute liver failure due to hepatitis B and those with decompensated cirrhosis. For those with decompensated cirrhosis, these are frequently patients with HBV who present very late to care and who have been undiagnosed and untreated for a very long time. However, anyone who is engaged in care and having their hepatitis B appropriately managed is generally at low risk of getting decompensated cirrhosis, because current guidelines recommend that patients who have cirrhosis and HBV continue with antiviral therapy for life. Long-term suppressive antiviral therapy would be expected to prevent progression of cirrhosis and decompensated liver disease.

Continue reading.......

Of Interest
Developing a New Combination Treatment for HBV Infection
NVR3–778, a capsid assembly modulator, reduces serum levels of hepatitis B virus (HBV) DNA and HBV RNA in mice with humanized livers and stable HBV infection, researchers report in the February issue of Gastroenterology. The combination of NVR3–778 and interferon prevented viral replication and HBV RNA particle production to a greater extent than either compound alone or entecavir.

Read more

Friday, March 2, 2018

Friday, February 9, 2018

People on liver transplant waitlist may be no worse off if they have used marijuana

People on liver transplant waitlist may be no worse off if they have used marijuana
Last Updated: 2018-02-08
By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Candidates on the liver transplant (LT) waitlist who have used marijuana have no worse outcomes than their counterparts on the list who have not used it, a single-center study suggests.

"Unlike illicit drug use, marijuana use was not associated with worse outcomes on the LT waitlist. . . We found a high prevalence of historical marijuana use that did not have clear adverse effects on LT waitlist outcomes," lead author Prashant Kotwani of the University of California San Francisco School of Medicine and colleagues write in Transplantation, online January 10.

Continue reading: http://www.chronicliverdisease.org/reuters/article.cfm?article=20180208Other1065659537