Several recent studies have shown good safety data, but limited benefit of MARS (Saliba et al. Ann Intern Med. 2013;159:522-531; Banares et al. HEPATOLOGY 2013;57:1153-1162).  ELAD was modified from the original design.  We have recently summarized the field (Sussman & Kelly. Clinical Gastroenterology and Hepatology 2014;12:1439–1442).  Vital Therapies has not reported on their most recent study of ELAD - we will all have to wait for them to do so.

Thanks for the quick feedback, both of you. Unfortunately, the patient I am working with has been going down hill quickly. Recently, he acquired aspiration pneumonia, hyperammonemia, pericardial effusion, and bilateral pleural effusion, on top of his ascites. Bit of a mess, frankly.

Is ELAD/MARS adaptable for the pediatric population? And the newborn?

Thanks.

David Lee,

This is the only paper I could find on that question so far. Let me know if you find any additional sources. 

Thanks.

http://www.ncbi.nlm.nih.gov/pubmed/16494508

Liver Transpl. 2015 Mar;21(3):369-80. doi: 10.1002/lt.24037. Epub 2015 Feb 10.

Experience with molecular adsorbent recirculating system treatment in 20 children listed for high-urgency liver transplantation.

The optimally targeted population for ELAD treatment should be investigated. In my opinion, ELAD had limited effect in cirrhotic patients who had organ failure precipitated by bacterial infection and UG bleeding or with unknown acute insults. However, in patients with acute hepatic injury (such as spontaneous HBV flare-up, HBV reactivation, superimposed HEV/HAV infection, hepatotoxic drugs), ELAD may work by adsorbing bilirubin for example (hyperbilirubin is frequent in those patients and may linked to secondary infection). A recent study from China has confirmed the efficacy of ELAD(Artificial liver support system improves short- and long-term outcomes of patients with HBV-associated acute-on-chronic liver failure: a single-center experience. Medicine (Baltimore). 2014 Dec;93(28):e338.PMID: 25526495). As far as I known, another large multi-center prospective study is underway to investigate its efficacy in those patients in China and we expect the encouraging results.

My opinion:

I live in a small country where a livers is available every 15 days aproximately (if we are lucky). The country did a hugh effort to buy a Prometheus and it was only sed 3 times in 7 years. But the 2 fulminant liver falures were alive when a liver apears and a patient with an acute liver failure becaus of a heat shock protein was saved. So, I think it depends onyhe circimstances of each program or country. 

Thanks 

Sounds interesting. I've been researching the way other countries perform their transplants/where they receive their donor organs. In Iran, they can pay kidney donors to give a kidney to a stranger, and the government can partially control the prices set for each transplant.

How does it work in Uruguay?

I think the main problem is high cost and continuous availability. Most trials on liver assist device report how much they improve the biochemical parameters of liver failure rather any clinical improvement which can occur only after liver transplant, so they act only as bridge to transplant. Obviously the time length of this “bridging” depends on availability of donor livers which is uncertain and varies from country to country depending on law, available infrastructure, cost, expertise, donor mindset etc. This escalates the overall cost to such extent that most administrators feel that the cost benefit ratio is not favourable in addition to the high level of effort needed for the coordination between different groups involved in the whole exercise. Moreover all liver assist devices have high recurring cost as the length of its use increase with decrease in effectiveness.

Trials of non-biologic support including two controlled trials published last year have failed to show a survival benefit.  These are very difficult to do because patients are very ill and frail - you may cause as much harm as good.  Biologic devices have suffered from poor design - Vital Therapies changed the original design and cell line, and then seemed surprised that the results were not as good as the animal models and initial studies had suggested.  Adding the complexity and cost of an extracoporeal circulation to a critically ill patient is just more complicated than you think.

It also depends on the scenario of your country. As an example, in Uruguay we have an average of one liver (DD) every 15 days; despite a high rate of donation, our population is only 3 million people. So in the fulminant failures the Prometheus (R) system has been a successful bridge for patients until a liver donor was available. In that cases I think it justifies the cost of the treatment. But if the country has livers every 24 or 48 hurs as in Spain or USA, I don´t think that the treatment is cost-effective.  

So, is the problem really the complexity of the design and application? Would the solution be to build a better artificial liver or find a way to harvest and grow an autologous liver replacement?

Marie Csete,  I have been following vital therapies advances, and am hopeful they will improve.

The design is simple - the complexity comes from getting hepatocytes to function like normal liver on a a man-made matrix.  C3A worked when the device was perfused by blood, but results with plasma perfusion (the current iteration) have been disappointing, presumably because of the poor oxygen carrying capacity of plasma.  The trials are complicated and very expensive. Stem cells are the logical next generation.

An autologous liver is possible, but a complex undertaking.  You need to create a dual blood supply and a biliary drainage system.  You need to figure out how to grow an organ from scratch or repopulated a liver skeleton after dissolving out all the cells.  This is also an expensive undertaking. 

Dr. Norman Sussman,

I learned one of company in California also under developing and have FDA IND approved system "Hepapheresis" for the proposed use for acute liver failure an acute-on-chronic liver faillure patients. The systemm was approved year 2012 and so far no update yet. I think the way of their study and progress looks promissing. How about your perspective about Hepapheresis?

Dk Kang,

Based on my research of the Hepapheresis apparatus, it seems that they use pig liver sections to replace patient liver function, allowing for the patient's own liver to regenerate or recuperate from the cytotoxic insult. 

The problem I see with this is the possibility of porcine viruses being transmitted to the patient. Indeed, this is the reason I have looked into human hepatocytes and stem cells, rather than porcine given the infectious disease concern. 

http://www.koreatimes.co.kr/www/news/include/print.asp?newsIdx=108281

Interesting.

Roland E Winkler

Hello all,

Whatever artificial or bioartificial method is used, it is never going to function exactly like the liver as apart from hepatocytes the liver contains other cells e.g. macrophages, biliary tract cells, mesenchymal cells, endothelial cells, matrix proteins which interplay among each other to give the final output function of liver. The sheer complexity of this makes any artificial approach fall much short of expected results and will continue to be such at least in near future.

Gautam Ray, I'm not disputing that; but perhaps if the more critical functions were at least approximated in an artificial approach, maybe this would increase the survival time to transplant. Again, not saying that we can perfectly approximate all liver functions, but if the most critical were approximated, i.e. glucose homeostasis, clotting proteins, albumin synthesis, etc. maybe we could buy time for more organs to become available.

Agree with Dr. Winkler. Balance between synthesis and metabolism and that also in tune with the body's need from time to time is the key.