The Future of the Artificial Liver

It is the current consensus in the field that organ transplantation is the primary treatment for chronic liver disease. Throughout the country, there is a significant shortage of organ donors. Not only are there not enough livers, but the surgery itself is traumatic and these individuals must live on auto immune suppressants for the rest of their lives. Taken as a whole, the present solution is incredibly expensive with a low success rate and only helps a small number of people affected with liver disease. However, recent research into artificial livers shows many promising developments.

Over the past two decades, researchers around the world have made significant progress in the creation of a functioning artificial liver. In particular, there have been many successes in engineering artificially grown liver cells that replicate the liver’s functions with designs functioning both inside and outside of the body. The extracorporeal liver assist device, or ELAD, is one such achievement. Connecting this machine to individuals with liver failure has allowed many individuals to survive long enough until an organ becomes available and has even been successful in treating acute liver failure . It also provides extra support to the liver, giving the organ time to regenerate itself. As ELAD undergoes more clinical trials, an increasing number of hospitals across the United States are beginning to offer it as a therapy for liver disease patients.

At BioEngine, a rising firm in biotechnology, researchers created a similar device designed to function within the human body. This structure would theoretically provide a bioartificial scaffold for human liver cells to grow and function normally. In other aspects of the field, biologists have been able to grow artificial liver cells from embryonic stem cells, human hepatocytes, and porcine hepatocytes. Although these technological advances are large steps towards developing a solution to liver failure, scientists still have a long way to go, as there are many biological, ethical, and economic reasons that are hindering artificial liver development.

The creation of efficient human liver cells requires a large amount of time, money, and resources, which adds to the overall costs of these therapies for a small yield of available cells. As a result, many of these therapies are not economically sound and cannot be available to the general public. Many scientists believe that developing more cost effective designs will be the focus of artificial liver research over the next decade. There is already an ongoing public debate on the ethical issues of using embryonic stem cells for research. This dialogue has restricted research in this area, which hopefully will be lifted under President Obama’s administration. From a biological point of view, there are concerns of porcine cells possibly transferring viruses from pigs to humans. Addressing these concerns in these current technologies will allow for further progress within artificial liver research.

A combination of regenerative medicine and stem cells appear to be the most viable method of creating an artificial liver. Within the next ten years, we believe ELAD will be a more accessible treatment for acute liver failure. Similar to the dialysis for acute kidney failure, the ELAD is the most feasible option in order to provide short-term immediate care for the general public. Healthcare reform will be important in whether or not this technology will be affordable for more people. We think that with the reform offering universal insurance to cover more people, the technology will hopefully not be limited to certain socioeconomic classes. Our long term hope is that an artificial liver may be developed from stem cell research harnessing the body’s natural structure to provide a less invasive and more permanent cure to liver disease.

-John, Robin, Mark, and Andrea (Team Artificial Liver)

BioEngine: One Step Closer to Artificial Liver Device

As the title suggests, this article looks into the developments of BioEngine, a firm focusing upon the development of artificial liver technology. In particular, the company is trying to create support structures that will allow specialized cells to "grow and function outside of an actual organ". Back in 2007, the company hoped to get FDA clearance to perform its first human trials within two years. I did a little bit a research on the company's website, but I did not find any information confirming whether or not BioEngine actually got its approval. However, it appeared as if the website had not been updated in a long time.

The goal of BioEngine is to create "three-dimensional structures that could provide a foothold for human cells" and to then commercialize the technology. The first few prototypes failed, but after completely starting from the scratch, the new designs are starting to show some promise. There are several challenges that engineers must overcome when designing these structures. First off, the cells must be really close to blood vessels in order to exchange nutrients and toxins. As a result, the vessels must branch into ever smaller vessels via a mechanism that does not cause the blood to clot. Researchers originally created channels with flat edges, and this method did not work. BioEngine then teamed up with ExOne, and with their expertise, they created a structure with rounded out grooves, allowing the blood to flow smoothly.



Conceptually, this idea seems to have a lot of promise, but I am not entirely convinced that it will functionally work. The article discusses the challenges of blood clotting, but I think that there are far more serious questions that need to be answered. What kind of cells will they put into the device? Will these cells be able to successfully function within this artificial environment? If an individual's liver is missing a specific function, adding a "simple" one cell type artificial liver seems like a good solution. Given all of the research, I think that this therapy will be incredibly expensive, and it only help a certain sub-population of those with liver disease. Regardless, I found the article very interesting, and I think that it taking a good step towards the production of a truly artificial liver.

-John

Wade Roush, Xconomy, 9/20/07
http://www.xconomy.com/2007/09/20/bioengine-one-step-closer-to-artificial-liver-device/

Researchers Aim To Cut Future Need for Liver Transplants

Several years ago, a group of scientists headed by James Ross at the University of Edinburgh discovered primitive liver cells that have the potential to differentiate and repair a damaged liver. Their hope is that theses cell will be able to provide an alternative treatment to liver transplantation because these cells can mature into different cell types both in and out of the body. Some researchers believe that these cells potentially lie dormant within the liver itself. If found, surgeons could then transfer the undifferentiated cells to locations within the damaged liver in order to repair the organ.

This potential treatment is remarkably similar to the liver's natural healing process. The liver repairs itself through three primary mechanisms. First of all, prior research has shown that mature liver cells inherently divide quickly in response to damage. Secondly, some liver repair results from stems cells circulating in the blood stream. The body recruits these cells from the body, and they differentiate to form new liver cells. The third type of liver repair involves the cell type described in this article. This mechanism only responds when the liver undergoes a significant amount of damage. In response, a specific population of primitive liver cells begins to divide and differentiate. Scientists hope to use this last method in order to develop a new treatment for liver failure. Consequently, the origin and cause of the third mechanism will be play an important role in future research.

So far, there have been several reoccurring themes within the development of artificial livers. It is fact that liver transplants are incredibly expensive, and to complicate matters, there are far too few donors. Researchers are currently looking into several mechanical, extra-corporeal liver alternatives, but none of them are cost effective. As a result, there is strong pressure to develop a new treatment because liver failure is currently a fatal disease. This theoretical technique of harnessing primitive liver cells conceptually overlaps with ideas from regenerative medicine and stem cell technology. In this case, the stem cells can potentially be retrieved from the body itself, and subsequently, doctors will simply be activating the body's natural healing response. My guess is that this method would be substantially cheaper than many of the other artificial liver alternative, and as a result, it has a lot of potential.

-John

No author given, Science Daily, 07/07/06
http://www.sciencedaily.com/releases/2006/07/060706175049.htm

Artificial liver support at present and in the future

This article discusses and summarizes the current as well as future treatments for liver failure. Currently, liver failure is a fatal disease with significantly high mortality rate, and the primary solution involves a liver transplant. This method has numerous complications, and there is a continuous shortage of available organs. The authors suggest that plasma exchange and continuous hemodiafiltration are currently the two most potential treatments for the disease, but they are still a long ways off from the ideal solution. In the best case scenerio, bioartificial liver support, gene therapy and regenerative medicine will lead to the development of a functional artificial liver.

The article takes a different perspective because the authors are from Japan. Since the Japanese health-care insurance program differs from that of the United States and Europe, Japanese researchers approach the treatment of end-stage liver diseases from a different angle. In Japan, it is illegal to run clinical trials with biological artificial livers. As a result, researchers focus on specific aspects of bioartificial liver development that do not use the liver itself.

There are many different techniques being researched to replace the liver's role in detoxification, metabolism, and regulation, but so far, none of the the controlled clinical trials have yielded the expected benefits. The bioartifical livers are both too complex and too expensive to be used as a regular treatment. Some of the blood purification techniques are becoming standard treatments, but they can only do so much. The conclusion of this article is that a significant amount of research still needs to be done before society can benefit from an affordable and functional artificial liver.

-John

Kazuhiko Onodera, Journal of Artificial Organs, 4/14/06
http://www.springerlink.com/content/rk22478g36373872/fulltext.pdf

Artificial Liver May Extend Lives (June 2, 2009)

This article provides an accurate representation of the current progress and uses of the artificial liver, or Extracorporeal Liver Assist Device (ELAD). According to the article, artificial livers have been in trials since the 1960’s, but have had little success. Problems have arisen due to complications such as the difficulty in creating chemicals essential to metabolism and blood clotting. However, with the advances in technology and the ability to grow human cells in culture and then implant these immortalized hepatocytes onto some type of synthetic material, ELADs have overcome many of the earlier issues. Due to this technology and increased success rates, the population eligible to be put on the ELAD has expanded. Now, there are more hospitals around the U.S. that are offering this therapy to acute liver failure patients as part of clinical trials. Thus far, the results of ELAD are very promising and “thirty day transplant survival rates were statistically higher in the ELAD group compared to the control,” which consisted of standard therapy. If clinical trials continue going well, the use of ELAD will expand even more, and may become a standard procedure for acute liver failure patients in a few years.

This progress in liver treatment will most likely prolong life by assisting people who have liver failure until a transplant can be received. While the ELAD itself is not sufficient to sustain life for a long period of time, scientists are hoping that while on ELAD, livers will be able to regenerate and gain back normal function. This would not only save a person’s life, but will also eliminate the need for a transplant.

-Mark

Belinda Mager, Bio-Medicine, 6/2/09

http://www.bio-medicine.org/medicine-news-1/Artificial-liver-may-extend-lives-47650-2/

Doctors test latest attempt at artificial liver (February 2, 2009)

Back in February 1999, a trial was put into place to test the ELAD (an Extracorporeal Liver Assist Device.) As of 2009, ten years later, the ELAD has still not been implemented in our health care system. This article, published ten years after the first testing trial, states that doctors are again experimenting with the device and trying to get hospitals to utilize the machine. The article emphasizes that although this device will not replace a damaged kidney, it could buy enough time for for the damaged liver to recover on its own or sustain itself until a kidney replacement is available.

This experiment is, hopefully, the last quest to implement the use of a device that could temporarily take over some of the liver’s jobs when it is failing or damaged. It’s amazing how this device was designed in 1999 and even after ten years the device is not widely used even though it has proved its efficacy several times. In 2002, a patient named Kevin Fitzmaurice began to emerge from a coma after a day of using the liver assist device. Had Kevin not gotten on the ELAD support, he would have died before the arrival of his donated kidney. Kevin’s case is one of the primary reasons the ELAD has been brought back into testing.

However, now that doctors are trying to get hospitals to use this device, it has been under close scrutiny primarily because of the $30,000 price tag. The FDA is asking for three to 10 days of ELAD liver support to improve the 30-day survival that the similarly ill get with today’s standard supportive care. I think these standards the FDA has placed on the device are extremely reasonable, especially given the current health care situation and debate. There are many illnesses and diseases that plague this world and, of course, acute liver failure is one of them. However, there’s no point in investing large amounts of money and time in a complicated artificial liver device that won’t prove any more effective than the already existent treatments. Considering the large price tag this treatment comes with, this device should prove strong efficacy. Spending thousands upon thousands of dollars on biotechnology that doesn't prove significant efficacy, is, in my opinion, futile when there are other significant health issues that need to be addressed.

-Andrea

No author given, Associated Press (MSNBC), 2/2/09
http://www.msnbc.msn.com/id/28981937/#storyContinued

World’s First Artificial Human Liver Grown in Lab (October 31, 2006)

This article, published three years ago in October 2006, reveals that two British scientists were able to grow the world’s first artificial liver from stem cells. Using blood taken from babies’ umbilical cords just minutes after birth, the scientists were able to create tissue the size of a small coin that replicates the functions of a liver.

This scientific breakthrough can lead to significant benefits for humanity within the next several years. The article states that within two years the mini liver can be used to test new drugs, reducing the number of animal experiments and providing results based on a human rather than an animal liver. Within five years, pieces of the artificial liver could be used to repair livers damaged by injury, disease, and alcohol abuse. And in fifteen years' time, whole functioning livers could be grown in the lab and then be transplanted into the body.

This experiment could be seen as an excellent advancement in the field of tissue engineering. It’s great to see that within the next couple of years, an the artificial liver created in the lab could be used to directly benefits people’s health. Having this work be transferred from the lab to the operating table would result in significant health benefits for those suffering from a failing kidney.

This experiment has also proven groundbreaking proof that stem cell research can be done in a more ethically acceptable manner. It’s great to see an experiment that could be beneficial to the eventual reduction of human suffering without all the politically motivated debates that sometimes hinder great discoveries. If scientists are able to derive stem cells from umbilical cords, then more stem cell research should be conducted using this source. Tissue engineering and stem cell research are amazing scientific and medical breakthroughs. Omitting the constant ethical debate surrounding stem cell research, by utilizing the daily discard of millions of umbilical cords, could result in the implementation of such research in our health care system.

-Andrea

Bill Christensen, Live Science, 10/31/06
http://www.livescience.com/health/061031_artif_liver.html