Future of Liver Disease Treatment: Xenotransplantation and Regenerative Therapies

Jump To Section

• Liver Disease Treatment Evolution
• Xenotransplantation Organ Shortage Solution
• Xenotransplantation Hurdles and Safety
• Liver Regeneration Mystery
• Anti-Fibrotic Therapies Future
• Full Transcript

Liver Disease Treatment Evolution

Dr. Scott Friedman, MD, reflects on the dramatic evolution in liver disease treatment over his career. He notes that in the early 1980s, treatment options were extremely limited. Therapies consisted mainly of diuretics, corticosteroids, and lactulose for hepatic encephalopathy. Dr. Scott Friedman, MD, emphasizes that liver transplantation was not yet a viable option for patients at that time.

The progress in hepatology has been transformative. Dr. Scott Friedman, MD, points to the development of curative therapies for hepatitis C as a landmark achievement. Effective treatments for hepatitis B and improved management of biliary diseases have also significantly advanced patient care. This historical arc, as described by Dr. Friedman to Dr. Anton Titov, MD, demonstrates remarkable medical progress.

Xenotransplantation Organ Shortage Solution

Xenotransplantation represents a potential solution to the critical shortage of donor organs. Dr. Scott Friedman, MD, expresses great excitement about this prospect. He specifically refers to the use of humanized organs from pigs for transplantation into humans.

Dr. Friedman cites the high-profile case of a pig heart transplant performed at the University of Maryland in late 2021. This successful procedure demonstrated the feasibility of cross-species transplantation. The discussion between Dr. Scott Friedman, MD, and Dr. Anton Titov, MD, highlights how xenotransplantation could save countless lives by providing a new organ source.

Xenotransplantation Hurdles and Safety

Several significant hurdles must be overcome before xenotransplantation becomes routine clinical practice. Dr. Scott Friedman, MD, identifies organ rejection as the primary challenge. The human immune system naturally attacks foreign tissue, requiring advanced immunosuppressive strategies.

Another critical safety concern involves endogenous retroviruses present in the pig genome. Dr. Scott Friedman, MD, explains that these viral sequences must be removed using advanced gene editing techniques like CRISPR. This genetic modification is essential to ensure the safety of transplanted organs for human recipients. Dr. Scott Friedman, MD, believes these challenges are surmountable with continued research.

Liver Regeneration Mystery

The liver possesses a unique and remarkable ability to regenerate that fascinates researchers. Dr. Scott Friedman, MD, describes this regenerative capacity as the liver's greatest mystery. He explains that surgeons can remove two-thirds of a healthy liver from a living donor.

The remaining liver segment in the donor will regenerate to full size within weeks. Meanwhile, the resected portion can be transplanted into a recipient where it will also grow. This phenomenon occurs only in healthy liver tissue. Dr. Scott Friedman, MD, tells Dr. Anton Titov, MD, that understanding this process could unlock new therapeutic approaches for liver disease.

Anti-Fibrotic Therapies Future

The future of liver disease treatment includes promising anti-fibrotic and regenerative therapies. Dr. Scott Friedman, MD, expresses confidence that effective anti-fibrotic medications will soon be available. These treatments aim to reverse the scar tissue that develops in chronic liver conditions like NASH.

Dr. Friedman also mentions that pro-regenerative therapies are already entering clinical trials. He envisions a therapeutic approach that combines fibrosis suppression with enhanced regeneration. This dual strategy could fundamentally change how we treat advanced liver disease. The conversation between Dr. Scott Friedman, MD, and Dr. Anton Titov, MD, paints an optimistic picture of hepatology's future.

Full Transcript

Dr. Anton Titov, MD: Professor Friedman, what is the future in liver disease treatment? Fatty liver disease treatment, NASH treatment, and Hepatology in general? You wrote a very thorough review and you are a leading, world-renowned researcher on liver diseases.

Dr. Scott Friedman, MD: It's a very exciting time. It's worth looking at the arc of progress over the course of my career as an example of how far we've come and how far we might still go. When I was a liver Fellow at UCSF in the early 1980s, we basically had no specific treatments for liver disease.

Dr. Anton Titov, MD: What did you have?

Dr. Scott Friedman, MD: We had diuretics or water pills, Lasix, and Aldactone. We had corticosteroids if we thought that there was a lot of inflammation in the liver. We had prednisone. We had a syrup called Lactulose to try to change the risk of altered thinking in patients with very advanced liver disease. And we had no liver transplantation.

So fast forward now to 35 to 40 years. We have liver transplantation, which is life-saving. We have curative therapies for hepatitis C, which wasn't even known about. The Hepatitis C virus wasn't even discovered in the early 80s. Here we went from discovering the virus to curing it.

For Hepatitis B, now we have many effective therapies, and newer drugs are trying to clear the virus, which we haven't succeeded in doing for hepatitis B yet. We have treatments for biliary disease. We have a better understanding of genetics. It's just unrecognizable how far we have come.

But I do believe that the liver has many secrets still to yield. I think among the prospects—not necessarily for NASH, but for liver disease—I'm very excited about the prospects of Xenotransplantation. It is having humanized organ donation from mammals, particularly pigs.

As you know, there was a very high-profile transplant of a pig heart, a humanized pig heart into a man recently at the University of Maryland, I think in late 2021. As far as I know, the patient is still doing okay.

It does speak to the idea that the terrible organ shortage that we confront in patients who need donor organs with advanced liver disease may be somewhat addressed by the availability of Xenotransplantation. Now, there are still lots of hurdles to overcome. The biggest risk, of course, is rejection.

But also, the pig genome has endogenous retroviruses that need to be cleared out of their genome using CRISPR or other gene therapy techniques before that organ can be safe to transplant to humans. But I do think Xenotransplantation could be a major game-changer for the most advanced patients.

At the same time, I'm confident we're going to have anti-fibrotic liver therapies. We will have more effective anti-inflammatory therapies. We can already reduce liver fat. I actually think that the liver's greatest mystery is regeneration. This is not just me.

The liver's greatest mystery is the ability of the liver to regenerate. You can literally surgically resect two-thirds of a healthy human liver. You can take the resected specimen with attached blood vessels and put that into a recipient. And the remaining one-third of the liver that was left behind in the donor will grow back to full size.

Now that only happens if the liver is healthy. But no other organ can regenerate. And so, I believe that liver regeneration and the ability to suppress fibrosis as the liver regenerates holds an array of secrets that could have a profound impact on both understanding and ultimately treating liver disease and perhaps promoting regeneration.

There are already some pro-regenerative therapies that are in clinical trials. So we're not that far off. And I just think about the idea of the Yin-Yang between blocking fibrosis while regenerating.

Dr. Anton Titov, MD: How does the liver know to do that? It harbors a lot of important clues that we need to dig deep to find.