Arun B. Jesudian, MD: When we talk about refractory patients, we’re all transplant professionals so I think we have to discuss liver transplantation as a treatment for very severe HE [hepatic encephalopathy]. Can you give us an overview of: is it effective, does it cure this condition, does it come back?
Steven L. Flamm, MD: Well, certainly when patients develop hepatic encephalopathy, that is considered a decompensation, even if they don’t yet have ascites or variceal bleeding or other complications, and it’s been shown in multiple studies that within a few years these patients have a high mortality. So they should, in my opinion, be referred for liver transplantation evaluation when they get encephalopathy. And this one’s also a little tricky because in between episodes of encephalopathy the patients are normal, or they appear normal. So you might think when they’re better that, well, it’s not so bad right now. But usually it’s a harbinger of bad things to come. So they should be evaluated for transplant. Now certainly if they continue to do poorly from an encephalopathy standpoint or develop other complications of end-stage liver disease, or a poor synthetic function for liver testing, those are reasons you would proceed with liver transplant. And when you do liver transplant, one of the dogmas always has been that the encephalopathy has no long-lasting consequences, that it’s reversible. It was a toxic metabolic event only, without structural changes in the brain, and therefore, when the new liver is put in and a toxic metabolic insult is removed, that you don’t have any consequences.
There have been some studies more recently that have called that into question. For instance, some patients after liver transplant who have had encephalopathy before transplant have learning issues. They don’t learn as well when given computerized testing or pen and paper tests, pencil and paper tests. So there may be some consequences in a fraction of patients that have encephalopathy, after liver transplant. I’m not aware of any major cognition issues, but Elliot may have something different to comment on this, but [no] major issues after transplant. But certainly it’s a transplant indication and certainly you should proceed with transplantation if you really can’t get the patient’s liver status under control. Do you have any comments on post-transplant changes?
Elliot B. Tapper, MD: I agree with you, and that’s what you experience in your own clinical practice, in our own clinical practice. But I think the data suggest that over time repeated episodes of encephalopathy are neurotoxic, and we have the basic science to back that up. But when you transplant somebody, you are creating such a dramatic improvement in their life, more often than not, that those changes are really minor in the grand scheme of things. And I think, although there’s caveats and asterisks, it is a cure for hepatic encephalopathy.
Arun B. Jesudian, MD: And a common question that we get, just to put to rest, if you have encephalopathy do you get any added priority for transplantation on the waiting list?
Elliot B. Tapper, MD: We prioritize patients based on a relatively objective algorithm called the MELD [model for end-stage liver disease] score, which is based exclusively on renal function, sodium, the INR [international normalized ratio], and bilirubin. And unfortunately, the suffering of some patients who don’t have high MELD scores continues in the MELD-based calculation. It just does not give you any priority, unfortunately.
Steven L. Flamm, MD: Yes, the MELD score, the model for end-stage liver disease, is solely based on objective criteria—[laboratory test results], as Elliot said. There’s no accommodation for encephalopathy. And some patients have a low MELD score and yet have terrible recurrent encephalopathy. And sadly for them, they will not get a liver through the regular channels. What does that mean? If a program does living liver donation, liver transplantation, which we do at Northwestern [University Feinberg School of Medicine], they can get a liver because it’s not based on a MELD score allocation system. But if they’re in the regular allocation system, [there’s] no accommodation for it. It’s very sad. These patients really are not dealt with well with the current system.