Alan Bonder, MD, on Managing Autoimmune Liver Disease After Transplantation

Dr Bonder discusses the risks of autoimmune liver diseases that present following liver transplantation and how best to manage these conditions.

Alan Bonder, MD, is medical director of liver transplantation at Beth Israel Deaconess Medical Center in Boston, Massachusetts, and an associate professor of medicine at Harvard University Medical School.

TRANSCRIPT:

Alan Bonder:  Hi. Welcome, everyone, to another session of Gastroenterology Learning Network. I am Dr. Alan Bonder. I'm the Medical Director of Liver Transplantation at Beth Israel Deaconess Medical Center from Harvard Medical School in Boston, Massachusetts.

Today, I'm happy to talk to you about our most recent publication about management of autoimmune liver diseases after liver transplantation. When we start talking about managing autoimmune liver disease, we'll talk about three main entities: number 1, autoimmune hepatitis, number 2, primary biliary cholangitis, and number 3, primary sclerosing cholangitis.

Overall, the main objectives when we are treating autoimmune liver diseases are number 1, to make sure that we improve patient survival, number 2, to prevent liver graft failure, and number 3, to decrease the recurrence of the disease.

When we look into specifically each disease, let's talk first about autoimmune hepatitis. Autoimmune hepatitis, it is an autoimmune liver disorder that has a significant risk of recurrence. It is quoted in the literature that it can come within 15% to 25% of patients who have autoimmune hepatitis can recur after liver transplantation.

The treatment of choice for them currently involves calcineurin inhibitors, such as tacrolimus or cyclosporine, and the use of antimetabolite medication, such as mycophenolate mofetil, and also the use of prednisone.

The controversy in the prednisone use is the most important topic in our paper. The pros is a recent publication in 2016 looked at patients who were randomized to either continuous steroids versus withdrawal of the steroids. When we look at survival, patients who withdraw from the steroids had better transplant survival.

When we look at the cons is there has been 2 different papers in the past, looking back at 2006 and 2008, where they looked at the recurrence, graft failure, or even death. In people who at that time were on steroids had improvement of those 3 main objectives.

When they looked at all the data combined in meta-analysis, there was not enough data, but they looked at the side effects. Side effects were more prominent in patients who were taking steroids. AASLD currently recommends to try to withdraw steroids as soon as possible or as the patient allows without having any recurrence or any evidence of rejection.

When we switch the topic to primary biliary cholangitis, PBC accounts for 2% of all transplants in the United States. The therapy that we have available has decreased the transplants significantly in the last couple of years. We have currently more second-line and third-line therapies to improve their outcomes.

Unfortunately, there are still patients who progress and who need the liver transplant. When patients get a liver transplant, the use of ursodeoxycholic acid at the same weight-based dose before transplant has been proven to reduce the recurrence of PBC.

There is 2 landmark studies, one from Aldo Montano from Edmonton, who looked at recurrence of the disease, who was decreased, who looked at survival. It also looked at risk factors that play a role in having recurrence of PBC.

Specifically, risk factors looked at age of transplantation but also the type of immunosuppression that was used. Specifically, he named the tacrolimus as one of the medications that is associated with the recurrence of PBC.

In clinical settings, what we usually do is we will start patients on our standard immunosuppressive therapy post-transplant, which will include a calcineurin inhibitor, specifically tacrolimus. We will start right away ursodeoxycholic acid on a weight-based at 13 to 15 mg divided in 2 doses.

If patients have recurrence of disease, then we will think about and will weigh the risk vs the benefit of recurrence vs rejection, as patients with PBC have a higher rate of rejections overall.

Finally, PSC. PSC is its own entity. Unfortunately, we don't have a therapy that works to treat the condition. Unfortunately, those patients progress to liver cirrhosis or hypertension, and they need a liver transplant.

Most importantly, what we know is that PSC is the disease that has the highest recurrence rates in all liver diseases. We don't have a standard therapy before and even after transplant, but there have been some studies to look at specific risk factors to prevent the recurrence of PSC, specifically colectomy.

We know that PSC is associated with inflammatory bowel disease. In this study, they looked at patients who actually had a colectomy before going to transplant. They found that patients who had a colectomy before transplant had a decreased recurrence of PSC.

What we know about this is patients with PSC with liver disease going for a colectomy is a high-morbid surgery. This also will have to be weighed with the risk and the benefits with the patient.

What we have to say about our paper is that we have specific management of specific diseases, but again we have to make sure that we look at the three 3 objectives. Number 1, patient survival. We've shown that ursodiol improves survival in PSC, we have shown that decreasing steroids increasing survival in autoimmune hepatitis.

Number 2, we prevent liver graft failure. Specifically, in the case of autoimmune hepatitis, the maintenance of immunosuppressive therapy over time leads to preventive of graft failure. We've shown that decreased steroids or withdrawal of steroids will help patients having a longer survival.

Finally, the recurrence of the disease. We have shown that ursodiol decreases recurrence of PBC. Combined withdrawal of steroids improves the survival. There is no benefit about recurrence of the disease.

Finally, for PSC, some patients we will need to discuss with colorectal surgery, transplant surgery if a colectomy is feasible before going into transplantation. Finally, there is certain conditions. They can happen, the 3 of them, specifically, osteoporosis. As we know patients with autoimmune liver disease and after transplant, they are at increased risk for osteoporosis. Number 1, they are malnourished. Number 2, they're immobilized for long periods of time. Number 3, the use of immunosuppression, particularly the use of steroids, will actually have an impact on bone loss and osteoporosis in the long run.

In summary, I would say that we need to make sure that we tailor down the immunosuppression specifically to each disease but also trying to minimizing side effects and actually improving graft survival outcomes. Thank you very much.