Domino Transplant

Provided by Science Daily

Sep. 18, 2013 — Tiffany Schwantes was going to die without a new liver. The 31-year old mother of two suffered from an aggressive form of liver cancer and, because of organ allocation rules, she could not be placed high enough on the liver transplant list to receive a new liver in a timely manner. Surgeons at Houston Methodist Hospital and her oncologist at the University of Texas MD Anderson Cancer Center determined that the only way to save her life was a domino transplant.

This is a rarely performed and complicated procedure that would allow her to receive a new liver from a living donor,” said R. Mark Ghobrial, M.D., director of the Center for Liver Disease and Transplantation at Houston Methodist Hospital.

The majority of patients with her type of cancer, cholangiocarcinoma, never receive a transplant, but Schwantes’ case was different.

“She was young and her tumor was responding to chemotherapy for a sustained duration,” said Milind Javle, M.D., an MD Anderson GI oncologist. “Because of her positive response to treatment I was able to refer her to the Houston Methodist liver transplant team.”

Tiffany was on what is called the ‘out-of-criteria’ list. Her liver was not sick enough for her to receive one from the normal donor pool where recipients are chosen by their degree of illness, said Howard Monsour, M.D., chief of hepatology at Houston Methodist Hospital. “If we would have waited for her liver to deteriorate, her cancer would have spread and she would have never made it.”

Meanwhile, 60-year old Vernon Roberson was suffering from amyloidosis, a genetic blood disease that attacks and destroys organs such as the heart, liver, kidneys, etc. He was progressively getting worse and was in need of a heart and liver transplant. When the organs became available this past July, surgeons asked him if he would be okay with donating his liver to Schwantes.

“I told them if I can save someone’s life, I am all for it,” Roberson said.

“While the diseased liver was not working for Mr. Roberson, we determined it was a viable organ for Tiffany,” Ghobrial said. “It will take her 20 to 30 years to develop amyloidosis, if at all, and if that occurs she can get another liver transplant. This was really the only option for saving her life.”

Ghobrial says more precision is necessary for this surgery than a standard liver transplant because blood flow to the organ must be preserved to keep it viable for the recipient. During a normal procedure, the liver is removed and discarded.

The 12-hour plus procedure involved a large transplant team that included four liver surgeons, two cardiac surgeons, two anesthesia teams, a perfusion team, transplant coordinators and at least 10 nurses.

“This is the first domino transplant we have ever done at Houston Methodist Hospital. It’s a very rare procedure, but I think the shortage of organs will cause us to look at doing more in the future,” Ghobrial said.

“There’s been a national push to use more of these so-called ‘marginal’ organs,” Monsour said. “We have a great joint program with MD Anderson where they are referring more of these patients like Tiffany to us for evaluation. I think if we can catch these cancers early, I believe we can save many more lives by performing domino transplants.”

Roberson is on the road to recovery in Houston and Schwantes is back home in Alabama enjoying life with her husband and children.

“This is a wonderful example of collaboration between different institutions to provide innovative approaches to betterment of human life,” Ghobrial said. “Thinking outside the box, we all helped prolong the life of a young wife and mother. That’s what makes this job so great.”

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Patient Profile: Living With Childhood Hepatitis C

Provided by EverydayHealth.com

A Texas couple shares the story of their child with hepatitis C. Learn about precautions they take as well as treatment that holds the promise of a cure.

By Karen Appold

Medically reviewed by Pat F. Bass III, MD, MPH

When Frances and Terry Perryman, of Spring, Texas, adopted their son Austin, they knew his mother had tested positive for hepatitis C. However, "because only a small percent of children get hepatitis C from their mother, we thought the odds were in our favor," says Frances.

According to the American Liver Foundation, mothers infected with hepatitis C have just a 5 percent chance of infecting their child. What’s more, up to 40 percent of children born with hepatitis C clear the virus on their own before they turn 2.

The couple had Austin tested as a precaution at age 2 and were surprised that their child had the hepatitis C infection. "Although we knew that the possibility existed, our beautiful baby was a picture of health," Terry says.

Hepatitis C, a chronic viral infection of the liver, affects about 0.15 percent of children ages 6 to 11 and 0.4 percent of children ages 12 to 19. An estimated 23,000 to 46,000 children in the United States are living with hepatitis C. Austin is typical — most kids living with hepatitis C were infected at birth.

Austin didn’t have any signs of hepatitis C, which is also typical. Most children living with hepatitis C have no symptoms. "That's what is so scary about this disease," Frances says. "You don't see symptoms until there's significant damage to the liver."

The Perrymans were devastated by the diagnosis. "It's hard to look at a child that you love so much and know that there's something inside him that's making him a little sicker every day," Terry says.

Precautions for Kids Living With Hepatitis C

Children with hepatitis C should take special precautions. If an injury occurs, parents need to make sure that their child’s blood and other bodily fluids don’t come into contact with anyone else. This contact could spread disease, says Austin’s doctor, Daniel Leung, MD, an assistant professor of pediatrics at Baylor College of Medicine and medical director of the Viral Hepatitis Clinic at Texas Children’s Hospital in Houston.

This means that caregivers — even parents — who are helping an injured child who has hepatitis C should wear gloves to prevent exposure.

In addition, Dr. Leung says that a teen or child with hepatitis C should not share toothbrushes, needles, or razors, which can spread hepatitis C. There are no concerns related to living in the same household such as kissing, hugging, or sharing cups or utensils, however.

After learning that their child had hepatitis C, the Perrymans told Austin, now 12, about his diagnosis. "He's fully aware of the precautions that he has to take if he bleeds for any reason," Frances says. "We make sure that we have gloves on hand."

Children living with hepatitis C can participate in any activities they choose. The couple told Austin's baseball coaches about his condition so they can wear protective gloves in case he gets injured on the field.

Success of Treatment for Hepatitis C in Children

Treatment options depend upon the genotype of the child with hepatitis C. In Austin's case, only one type of treatment was available. The first round of Austin's treatment, ribavirin (in liquid form) twice a day and a weekly injection of peginterferon alfa-2b, failed. However, after consulting with his doctor at Texas Children's Hospital, Austin and his parents agreed to try a second round of treatment, using the same drug combination.

Austin has the same side effects adults often experience: He’s fatigued and feverish for 24 to 48 hours after getting the injection, Frances says.

"We've also seen a change in his personality and ability to focus," says Terry, who notes that although Austin is in many advanced school classes, he's had some struggles because of the drugs’ side effects. He's also changed from a chatterbox to a quieter child at school. Three to four times a week, he goes to the school nurse's office to nap.

Austin's blood counts also have to be monitored. His dosage of medication had to be reduced twice because of low white and red blood counts.

"We considered the side effects before starting the second round of treatment," Frances says. "Ultimately, we decided to move forward with the treatment, hoping that the side effects would be more tolerable now than when he gets older."

The choice seems to be working. Austin’s most recent tests found that the hepatitis C virus is undetectable in his blood. He'll remain on treatment for another six months and will be considered cured six months after treatment stops if the virus is still undetectable. "Based on his genotype, we are very optimistic," Terry says.

Last Updated: 09/20/2013

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Patient, Heal Thyself: Solution To Personalised Treatment For Chronic Infections Could Lie In The Patient's Own Blood

Provided by MarketWatch

Sept. 21, 2013, 12:10 a.m. EDT

Singapore, Sept 21, 2013 (ACN Newswire via COMTEX) -- A recent discovery by scientists at A*STAR's Singapore Institute for Clinical Sciences (SICS), in close collaboration with researchers at the Singapore Immunology Network (SIgN), provides hope for a new personalised treatment strategy that could use a patient's own blood to treat the infection. This could help treat millions of people living with chronic infections such as HIV, Hepatitis B or Hepatitis C. These findings were published in the August 2013 issue of The Journal of Clinical Investigation.

Patients suffering from chronic infections often have to undergo long periods of anti-viral drug therapy to control the virus. Anti-viral drugs are not fully effective against viruses such as Hepatitis B and Hepatitis C, which have chronically-infected about 400 million worldwide with more than 1,000,000 people dying from Hepatitis-related diseases every year.[1]

Vaccines are a potentially effective means to treat chronic viral infections such as this because they can eliminate the virus naturally. However, vaccines for patients with chronic infections are often difficult to produce since these patients already have weak immune responses or the vaccine is not effective due to genetic diversity amongst viruses.

The team at SICS led by Prof Antonio Bertoletti has discovered that monocytes, a type of white blood cell that can activate an immune response, are able to capture the virus in chronically-infected patients and use the captured virus to boost the patient's own immune response.

By using the viral antigen already present in the blood of the patient suffering from a chronic illness, this strategy redefines therapeutic vaccines by cutting down on time and resources as there is no need to specially isolate the viral proteins from patients, purify it, and then inactivate it to create a vaccine.

All the proteins present within the virus can be used to create a personalised vaccine for each individual. This also means that many of the complex issues associated with current vaccine therapy against chronic infections can be overcome, such as that of genetic diversity of viruses.

One of the greatest beneficiaries of this discovery would be chronically-infected patient populations in lower socio-economic strata. By tailoring vaccines to be more specific to each virus and each patient, vaccine production can be simplified and thus less costly. Vaccines produced via this discovery could improve the accessibility of such treatments.

Prof Bertoletti said, "Mobilizing the immune system to use the virus within the patient for a vaccine is a simple idea that could lead to a personalised, yet widely applicable, vaccine for chronic infections."

Prof Judith Swain, Executive Director of SICS said, "This excellent collaborative discovery between SICS and SIgN is a milestone in vaccine therapy for chronic infections. I believe that these findings will go a long way in improving future therapeutic treatments for chronic infections."

[1] WHO (ed). WHO | Hepatitis B Fact sheet No 204. WHO. July, 2013.

Notes:

The research findings described in this media release can be found in the August 2013 online issue of The Journal of Clinical Investigation under the title, "Mobilizing monocytes to cross-present circulating viral antigen in chronic infection" by Adam J. Gehring,1, Muzlifah Haniffa,2,3, Patrick Kennedy,4, Zi Zong Ho,1, Carolina Boni,5, Amanda Shin,3, Nasirah Banu,1, Adeline Chia,1, Seng Gee Lim,6, Carlo Ferrari,5, Florent Ginhoux,3, and Antonio Bertoletti,1,7,8.

1. Infection and Immunity Programme, Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore.

2. Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom.

3. Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Singapore.

4. Center for Digestive Disease, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, United Kingdom.

5. Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.

6. Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

7. Program Emerging Viral Diseases, Duke-NUS Graduate Medical School, Singapore.

8. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

About the Singapore Institute for Clinical Sciences (SICS)

Established in 2007, the Singapore Institute for Clinical Sciences (SICS) is a research institute within the Agency for Science, Technology and Research (A*STAR), and its mission is to develop disease-oriented clinical and translational research programmes in key disease areas.

SICS is distinguished by its focus on clinical sciences and the use of innovative approaches and technologies that enable the efficient and effective study of human health and diseases. The clinical scientists in SICS conduct the full spectrum of "bench to bedside" research activities in metabolic diseases (including diabetes, obesity and insulin resistance), pathways to normal growth and development (including cognitive and behavioural development), nutritional sciences as well as in certain viral infectious diseases such as chronic viral diseases.

The institute aims to attract, train and nurture clinician-scientists and to develop joint programs with universities, academic medical centres, government hospitals and research institutes. For more information on SICS, please visit: www.sics.a-star.edu.sg.

About A*STAR

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that fosters world-class scientific research and talent to drive economic growth and transform Singapore into a vibrant knowledge-based and innovation driven economy. In line with its mission-oriented mandate, A*STAR spearheads research and development in fields that are essential to growing Singapore's manufacturing sector and catalysing new growth industries. A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry. A*STAR oversees 20 biomedical sciences and physical sciences and engineering research entities, located in Biopolis and Fusionopolis as well as their vicinity. These two R&D hubs house a bustling and diverse community of local and international research scientists and engineers from A*STAR's research entities as well as a growing number of corporate laboratories. For more information about A*STAR, please visit www.a-star.edu.sg.

Source: A*STAR

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Understanding the liver can help keep it healthy

Published: Thursday, September 19, 2013

(Metro) -- The human liver performs an array of functions. In addition to detoxification and protein synthesis, the liver also produces chemicals necessary for digestion. Understanding the role of the liver can help people make smart choices about keeping their livers healthy and avoiding disease.

Understanding the liver

The largest glandular organ of the body, the liver weighs about three pounds and is divided into four lobes of unequal size and shape. The liver can be found in the right side of the abdominal cavity. A healthy liver will be a reddish-brown color.

One of the main functions of the liver is to eliminate harmful biochemical waste products. Much like the kidneys, the liver acts a filter for the body, helping to detoxify alcohol and certain drugs. It also helps clear the body of environmental toxins that may have been ingested.

The liver also produces substances that break down fats. The liver turns glucose to glycogen, which serves as a secondary energy storage in the body. The liver produces urea, the primary compound in urine, and makes certain amino acids, which are the building blocks of proteins.

The liver also produces bile, which aids in the digestion and intestinal absorption of the fat-soluble vitamins A, D, E, and K. Bilirubin is the main bile pigment that is formed from the breakdown of waste substances in red blood cells.

Diseases of the liver

The Centers for Disease Control and Prevention indicate chronic liver disease and cirrhosis is diagnosed in roughly 100,000 patients who visit hospitals each year.

Jaundice is one of the most recognizable warning signs that the liver may not be functioning properly. Jaundice is the yellow coloring of the skin, the sclera in the eyes as well as other mucous membranes. It is caused by hyperbilirubinaemia. If the liver isn't functioning at full capacity, it cannot maintain the correct amount of bilirubin in the blood.

Several behaviors can negatively affect the liver. Drinking too much alcohol can damage liver function over time, and certain drugs -- both pharmaceutical and recreational drugs -- can compromise the liver. Some drugs that treat cancer and diabetes can be harsh on the liver.

Drugs that treat cholesterol can also affect liver function because the liver is also responsible for producing a good amount of the cholesterol in the body. The cholesterol that the liver produces is vital to strengthening the membranes of cells in the body.

Hepatitis is an inflammatory disease of the liver that is caused by a number of different viruses. Hepatitis comes in many forms and is even named A through G, depending on the virus responsible for the infection.

Cirrhosis is scarring that appears on the walls of the liver.

While alcohol consumption is largely blamed for liver disease, it is only one of the many causes. Cancer also can occur in the liver, and liver cancers typically spread through the bloodstream from other areas of the body.

Keeping the liver healthy

Maintaining a healthy liver involves eating a well-balanced diet and drinking plenty of water, which helps to flush toxins out of the body. Foods that are high in fat or sugar can be harder on the liver, and should be consumed in moderation.

People should avoid overconsumption of alcohol and only use drugs as prescribed by a doctor. According to the University of Maryland Medical Center, drinking 10 or more cups of green tea per day was associated with less liver disease in men.

The liver is vital to human health, performing so many functions in the body. So it pays to keep the liver healthy by eating well and avoiding drugs and alcohol.

New test enables early diagnosis of liver cancer

Provided by MedicalXpress

September 19, 2013

by Toni Baker

Drs. Ravindra Kolhe, pathologist and Medical Director of the Georgia Esoteric, Molecular Labs, LLC, at the Medical College of Georgia at Georgia Regents University; Amyn Rojiani, Chairman of MCG's Department of Pathology; Andy Rahardja and Puneeta Vasa, pathology residents. Credit: Phil Jones

Researchers have found a way to make early liver cancer show its true colors. They have developed a test that will help pathologists clearly distinguish early liver cancer cells from nearly identical normal liver cells by giving them a distinctive red-brown hue.

The inability to definitively tell the difference often means the disease is detected late when treatment options are less effective, said Dr. Ravindra Kolhe, pathologist and Medical Director of the Georgia Esoteric, Molecular Labs, LLC, at the Medical College of Georgia at Georgia Regents University.

"There is no definitive test for early diagnosis of liver cancer," said Kolhe, lead author of the study being presented at the American Society of Clinical Pathology 2013 Annual Meeting in Chicago, Sept. 18-21. "Our test adds a level of comfort for making the diagnosis."

"The deadly liver cancer cells seek to recapitulate the appearance of normal liver cells," said Dr. Amyn M. Rojiani, Chairman of MCG's Department of Pathology. And they are very good at that, the pathologists agree, which is the frustration they have when trying to give patients definitive answers from looking at the tiny core biopsies of their liver under the microscope.

"As pathologists, we often find ourselves wanting to know more," said Dr. Andy Rahardja, a pathology resident who worked on the project. "Our test helps us differentiate between the two."

Unfortunately early liver cancer also is mostly silent. By the time it's large enough to cause classic symptoms such as abdominal pain and weight loss, the cancer cells look distinctive but the liver is failing. The myriad of treatment options - from removing the diseased portion of the liver to liver transplants to freezing or heating cancer cells - have a high chance of failing as well, Kolhe said.

"You want to make the correct diagnosis as early in the game as you can," Kolhe said. He began collaborating with BioGenex laboratories, a California company with expertise in cell and tissue testing, to develop a probe that gives cancer cells the distinctive red-brown hue. The probe detects and stains a microRNA called mir-21, which is found in liver cancer but not healthy liver cells, Kolhe said.

Unlike RNA, microRNA doesn't make proteins rather helps control proteins that are expressed by RNA. That means it's more stable and can survive harsh chemicals normally used to prepare the biopsy for microscopic evaluation. This includes using formaldehyde and replacing natural fluids with paraffin so the tissue can be easily cut and stained with different reagents to help pathologists try to pinpoint a patient's problem.

For the study, they used their probe on biopsies of 10 healthy livers and 10 livers with early cancers. In every case of liver cancer, the biopsy took on the red-brown hue. The probe was not detected in normal cells. The studies were done retrospectively, so they already knew which patients ultimately were diagnosed with cancer. They are now using the test on 200 similar cases of liver cancer.

The group also is exploring this approach in other hard-to-detect-early cancers. Kolhe worked with pathology resident Dr. Puneeta Vasa to identify microRNAs selectively expressed in melanoma. Under the microscope, the potentially deadly skin cancer cells look a lot like common mole cells. These findings also will be presented at the American Society of Clinical Pathology meeting and the researchers are working with BioGenex to develop probes to make melanoma-relevant microRNA stand out as well.

In the case of diagnosing early liver cancer, the physicians note that cirrhosis, a massive scarring of the liver resulting from chronic infection with hepatitis B and C viruses, further muddies the current diagnostic waters by essentially giving cancer cells cover. These common viruses are the most common cause of liver cancer worldwide, according to the American Cancer Society. Alcohol abuse, a leading cause of cirrhosis in the United States, also is a risk factor for liver cancer. The new probe fortunately does not interact with cirrhosed cells, Kolhe said.

Explore further: Liver cancer due to chronic inflammation: Tumour growth follows programmed cell death (apoptosis)

Provided by Medical College of Georgia 

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