Interview with Prof. Rogers Williams in the APASL 2009

Hepatology Digest: I’m here with Professor Roger Williams at APASL 2009. Welcome Professor. It’s a great honor to have you here today. First, I’d like to ask you about the Mars artificial support device. This device may be used as a bridge for transplantation for ail applications. We would like to know whether artificial liver support technique, represented by Mars, could become a standard therapy for liver failure, no matter whether if there is a need for liver transplant or not?

Pro. Roger Williams: Yes, it is a prototype. There is still great modifications being done in terms of whether you can recirculate the albumin that is being cleansed back to the patient because the binding capacity of albumin may be affected in liver disease and may not be corrected by the Mars device. However, albumin dialysis, some form of albumin dialysis, is going to be the basis of a very efficient and safe form of liver support. It has much more potential than devices based on modules out-functioning liver cells. So, I do think with Mars, that we do have a real advance in the terms of temporary liver support. The latest trial from the French group has shown almost statistically significant survival benefits in paracetamol overdose cases of acute liver failure. The big European multi-central trial of Mars has just been completed, that’s in acute-on-chronic liver failure but it is an advance. You can show that it removes toxins in the blood stream of patients with liver failure and you can show that it corrects that disturbed pathophysiology.

Hepatology Digest: You’ve just mentioned its use in acute-on-chronic liver failure, do you think that it could really be the treatment of choice, or that it could become?

Pro. Roger Williams: At present, it is the treatment of choice because it is relatively inexpensive. It is still expensive, but it is much less expensive than devices where you’ve got components functioning on hepatocytes, which is being tried again in America. However, the albumin dialysis does remove toxins. In acute-on-chronic liver failure the prognosis is going to depend very much on the underlying disease, whether that can recover. You may correct the manifestations of liver failure but there may still be an underlying disease which will not improve. So there is going to be ongoing discussion about its value in acute-on-chronic liver failure.

Hepatology Digest: Are there any other devices that we see on the horizon or are being tested for size, like the Mars device, that you feel optimistic about?

Pro. Roger Williams: The Prometheus device is, again, based on albumin and albumin is taken across a larger core membrane, is then cleansed then put back into the patient. We’re also looking at a device, very similar to Mars but in which the albumin with toxins after transport across the membrane is then lost and we replaced with new albumin. As there is a lot of interest now in the binding capacity of human albumin, whether it is damaged in liver failure and, whether it can be restored by these devices.

Hepatology Digest: So a lot of the work is based on that principle regardless of the device, its looking towards that.

Pro. Roger Williams: That’s actually right. However, we do have a device for the first time ever that has been done, has been confirmed several times to restore the pathophysiology of liver failure.

Hepatology Digest: The assessment of the need of transplantation is mainly based on the King’s or the Clichy’s criteria so could you discuss their relative advantages and disadvantages?

Pro. Roger Williams: I’m not sure that there’s much more to say expect that the King’s criteria has been validated particularly for acetaminophen overdose. They are better than the Clichy’s ones, but now, to the King’s criteria, is being added a number of additional prognostic features, lactic acid levels and so on. The trouble is that in acute liver failure, the negative predicted value is never going to be as high as the positive predicted. In other words, some patients who don’t show these criteria nevertheless progress and become too ill for transplantation. If the criteria are present, it means you do need a transplant but if they are not present then they may still progress and all the efforts are to try and improve the characterization of the cases early on as to whether they are going to need a transplant.

Hepatology Digest: We’ve just listened to the Konia Kudo lecture and there are obviously a lot of interesting questions raised, in regards to transplantation in HCC or in other cases. What do you think about the more inclusive criteria, like the Hangzhou criteria and some of the predictive values?

Pro. Roger Williams: When we started liver transplantation in the UK in 1968, many of our patients had large hepatocellular carcinoma, usually on the base of cirrhosis, but sometimes without the underlying cirrhosis. Some of those patients survived 5 years or more without no tumor recline. In fact, the patients with a very big hepatocellular cancer is still alive. 2-3 of them are still alive at 20 years. I never thought that the Malang criteria should be absolute because there are patients who have large tumors, which are biological not rapidly progressing. The patient may be clinical well and they’re fighting this new works, looking at other predictive criteria, particularly the works that H.T Pan just described detecting cancer cells in the blood is related to the biological nature of the tumor, the identification of stem cells in the blood. These are very important findings because they may enable you to identify the case where there is a chance of recount much more actually than just on the Malang criteria. Malang criteria has been very useful, and continue to be useful but the new knowledge may enable you to concentrate more on the biological nature of the tumor.

Hepatology Digest: I suppose when we have a good criteria for a selection, there really is a shortage of organs at such when we talk about Kadaba organs. Do you think with this increased chance of success that will really help for them to be used efficiently?

Pro. Roger Williams: I don’t know if it’ll help the provision of donor organs. What is does mean is that you get an even better long term survival so every organ is used for maximum overall benefit for the community. However, there is a desperate shortage of Kadaba organs. Certainly in the UK, there is a high refusal rate by relatives and living-donor liver transplantation does carry some risk for the donor and I think it is very sad that the world, as a whole, hasn’t somehow been able to rectify this situation. Expect for Spain where they have a very high Kadaba organ donation rate, none of the other countries have been able to match them.

Hepatology Digest: Hepatocyte transplantation is a promising new treatment for several liver diseases. Could you comment on the current situation of its usage in liver failure?

Pro. Roger Williams: There is no evidence in liver failure, yet, there has been significant clinical benefits. Where hepatocyte transplantation has been proven to be of some benefit is in the inborn errors of metabolism in children where you can restore some of the enzyme defects, either long term or more usually requiring liver transplantation as subsequently. However, most of the promising works with hepatocyte transportation is in the genetic defects in inborn errors of metabolism.

Hepatology Digest: Once again, thank you for joining us today Professor. It was a real honor. Take care

Pro. Roger Williams: Thank you.