Question 1

How is immunosuppression managed in recipients after the surgery, and will it be lifelong, or is there a point at which these medications can be discontinued?

Dr. Dheeraj Manchanda · Accepted Answer

Immunomodulation is a natural property of the liver; we do not do anything from our side. Our usual regimen starts with a higher dose of steroid during the operation: 1 mg per kg of methylprednisolone during implantation, which we taper slowly after surgery. For about the last six months to a year, in patients whose surgery we finish early in the day, by the afternoon or evening, we have started low-dose tacrolimus on the night of surgery, and we start mycophenolate the next day. The first thing we taper is the steroid, because steroids have metabolic complications of their own. The liver's immunomodulatory property is what allows us to taper immunosuppression, which matters because sepsis is the first problem patients encounter with immunosuppression in the immediate post-operative period, and it becomes even more evident in patients who develop rejection, because their immunosuppression has to be increased immediately to counter it. We keep the tacrolimus level at around 8 to 10 during the first month, and we can manage stable liver function tests with a level of 5 to 8 for the first six months after surgery. After that, we can reduce it to around 5, or even less than 5, about a year after surgery. That is what allows us to stop mycophenolate a year after surgery, which also allows female patients to conceive.

Question 2

When the right lobe is taken from a donor, is there documented evidence of the liver regenerating in the donor over the years?

Dr. Dheeraj Manchanda · Accepted Answer

Yes. As part of a study, our centre started doing a non-contrast CT scan of the abdomen on the sixth post-operative day in donors as a protocol. It did two things. It gave us documented evidence of any collection in the donor after surgery, which was rare. And it showed us the dimensions of the liver on day 6. This data is under review and we are planning to publish it: we have documented growth of the liver on CT scan as early as day 6 after surgery.

Question 3

When minimally invasive surgery is used for the donor, how do you take out a liver graft large enough to transplant into the recipient?

Dr. Dheeraj Manchanda · Accepted Answer

Performing the surgery is not the major challenge: operating through the robot, you have about ten-times magnified vision on the console. The real challenge is taking the graft out of the donor safely without damaging it. For that we use a Pfannenstiel incision. Although it is a large incision, it is covered under the belt and hardly visible, and we close the skin with absorbable monofilament subcuticular sutures, so cosmesis is not much of an issue. We keep a liberal length of incision so that the graft can be taken out safely, while keeping the first warm ischaemia time to a minimum. That time, measured from clamping the graft's portal vein in the donor, is usually around 5 to 6 minutes. Initially it was about 7 minutes; we have progressed to taking the graft out in about 5 minutes. It seems a marginal improvement, but minimising the warm ischaemia time and taking the graft out safely is a priority.

Question 4

Liver transplant recipients normally need immunosuppressants for life. What is your outlook on immunosuppression withdrawal or new drug molecules: will liver transplant reach a point, as in bone marrow transplant, where recipients need immunosuppression for only a year or so?

Dr. Dheeraj Manchanda · Accepted Answer

It does happen. In my career I can easily recall at least three patients who were free of immunosuppression about five years after liver transplantation, and it is the liver itself that allows this. Current research is focused on exactly this, because the Achilles heel of all organ transplantation is the immunosuppression patients have to take lifelong, as in kidney and liver transplantation, which keeps them at risk of sepsis. Hopefully in some time we will have a breakthrough.

Question 5

Is liver transplant offered to patients who are HIV positive?

Dr. Dheeraj Manchanda · Accepted Answer

Yes, we have done liver transplantation in HIV-positive patients. They need to have some immunity of their own, as measured by their CD4 count, since HIV affects the immune system. We monitor the CD4 cell count in the post-operative period. We have successfully transplanted HIV-positive patients who remain on long-term follow-up with us and are doing well.

Question 6

Immunosuppressants lower immunity, and a patient with HIV already has low immunity. How does that work out, and how do mortality rates compare?

Dr. Dheeraj Manchanda · Accepted Answer

We keep the overall dose of immunosuppression lower in these patients, which allows them to do well, and it does not create much of a problem. In our experience, their mortality and long-term morbidity rates are the same.

Question 7

Are the donor and the recipient in the operating theatre at the same time, so that the liver portion removed from the donor goes immediately into the recipient?

Dr. Dheeraj Manchanda · Accepted Answer

Yes, both operations are done simultaneously, but we follow a protocol on which starts first. In non-malignant cases, we start the donor surgery first, because there have been discrepancies between the donor liver quality and volume seen on pre-operative imaging and what we actually encounter during surgery. We look at the donor's liver directly, and if there is any apparent steatosis or any irregularity of the surface, we take a biopsy and send it for frozen section. If the report shows no fibrosis and no significant steatosis, we proceed with the recipient surgery. In malignant cases, we start the patient's surgery first with an inspection laparotomy, and once we are sure there is no peritoneal metastasis and no deposits on the diaphragm, the spleen or the surface of the gut, we start the donor surgery.

Question 8

How does the kidney get affected after liver transplant surgery?

Dr. Dheeraj Manchanda · Accepted Answer

After surgery there are two things. The first is surgical stress: I always tell my patients that undergoing a liver transplant is equivalent to running a marathon. In about 5% of patients this shows immediately as a rise in creatinine and a drop in urine output. We support them with albumin infusions after surgery and we avoid giving them tacrolimus immediately. Instead, we give basiliximab as part of the induction regimen, two doses four days apart, and start tacrolimus once the creatinine begins to settle. The later effect on the kidney comes from the nephrotoxicity of tacrolimus itself. For this we stick to the therapeutic window: a tacrolimus level of about 8 to 10 in the first month, reduced to 5 to 8 for the first six months, and around 5 or even less after the first year. If the creatinine still rises, we switch to the extended-release preparation of tacrolimus, which is given once daily. Nephrotoxicity relates to the peak tacrolimus level; with the extended-release preparation the peak level decreases, but the effect remains the same.

Question 9

Around 30,000 liver transplants are needed each year but only about 3,000 are done, so only 10% of patients who need one receive it. What explains the gap: transplant centre capacity, organ donation or affordability?

Dr. Dheeraj Manchanda · Accepted Answer

It is multifactorial. One problem is awareness among the general population: it is very commonly seen in clinical practice that when you tell patients they need a liver transplant, they go to another doctor, because they do not believe a liver transplant is actually possible. Another is the cost of the surgery, which keeps people from undergoing a transplant. Yet if you compare the long-term cost of continuing medical management with the cost of a liver transplant, I would say a transplant is the much cheaper option, which people do not realise. The other factor is finding a suitable donor in the family. At our centre, about 35% of donors are rejected, sometimes for being overweight, sometimes because the anatomy is not suitable, and sometimes because the donor is diagnosed with comorbidities during evaluation. Capacity is not the challenge. Our centre does 20 to 25 transplants a month, some centres do only around five, and as a unit we have the capacity to do more. Finance, donor availability and patients' understanding are what keep the numbers where they are.

Question 10

Most liver transplant recipients are men. Does that mean women develop liver failure less often, or is something else going on?

Dr. Dheeraj Manchanda · Accepted Answer

There is something else as well. There is a cultural factor: in our society, men are usually the breadwinners of the family. The other factor is the prevalence of alcohol intake, which is higher in men than in women. I would not say women do not consume alcohol at all, but they consume less, and not in quantities that affect the liver as much as in men. So I would say cultural differences contribute more to this than physiology.

Question 11

Given the shortage of suitable donors, what is the future of xenotransplantation, using livers from other animals?

Dr. Dheeraj Manchanda · Accepted Answer

It has been attempted in the past, but there has not been much success. The grafts initially do well, but the long-term results of xenotransplantation have not been very encouraging.

Question 12

In the long term, which would you bet on: xenotransplantation, or artificial livers created through biotechnology research, or a mix of both?

Dr. Dheeraj Manchanda · Accepted Answer

I would bet more on lab-grown livers than on xenotransplants.

Live Discussion with Dr. Dheeraj Manchanda