A host of potential complications could explain Apple CEO Steve Jobs's newly announced medical leave of absence. The health of the 55-year-old tech executive has seemed tenuous to many observers since his previous liver transplant and bout with pancreatic cancer, and some doctors are speculating that medications could be contributing to his ailments.

Jobs's liver transplant, reportedly completed in March 2009 at a Memphis, Tenn., hospital, seemed at the time to be successful. Liver transplants, although relatively common, come with a host of potential long-term health risks and complications, including troubles caused by the immunosuppressant drugs that patients often have to take to prevent their bodies from rejecting the organ.

Liver transplants can be used to help combat islet cell neuroendocrine tumors—the rare but often treatable form of pancreatic cancer that Jobs was diagnosed with—if the cancer has spread only to the liver. Because the number of pancreatic cancer patients who fit the liver transplant profile is so small, data have been scant on the success of this procedure in fending off recurrence. A 2010 review paper reported that with a liver transplant five-year survival rates in neuroendocrine tumors range from 36 percent to 80 percent depending on the study. But a small 2007 study found that only 20 percent of patients who had had a liver and multivisceral transplantation were still disease-free after five years.

Jobs's tumor was surgically removed in July 2004. On January 5, 2009, he announced that he was being treated for a hormone imbalance, and starting January 14 of that year he took a medical leave of absence. He returned to work in June 2009.

During Jobs's current absence he will remain "involved in major strategic decisions," but his day-to-day duties will be handled by the company's chief operating officer, Tim Cook, according to a release from the company. The leave's duration is unspecified, and spokespeople for Apple declined to provide additional information about its length or the reasons for it. "I love Apple so much and hope to be back as soon as I can," Jobs wrote in Monday's message. Apple stock has dropped slightly in the wake of the announcement.

Is Steve Jobs likely to be able to get back on the job soon? Scientific American spoke with the director of University of Chicago Medical Center Transplant Center, J. Michael Millis about the ways Jobs's liver surgery and cancer diagnosis might currently be affecting the Apple executive's health.


[An edited transcript of the interview follows.]


Given what has been reported about Steve Jobs's previous liver transplant and his treatment for pancreatic cancer, what might explain why he has taken another medical leave from Apple?
Of course we know nothing about his current health—so it could be absolutely fine. We really don't have much information.

What are some of the more common complications for a liver transplant patient?
I can only speak in general about what a liver transplant patient may experience. They can develop any number of complications after their transplant: a narrowing of the bile duct where it connects the liver to the recipient, and that can cause problems. Any of the blood vessels can get a narrowing, or stenosis, that can cause problems, so those are the anatomic potential complications.

And there are metabolic complications; with the immunosuppressants, the recipients can develop hypertension, hypoglycemia and hyperlipidemia. There are the physiologic complications, such as renal dysfunction. Then there are the immunologic complications that could be over-immunosuppression or under-immunosuppression. Under-immunosuppression can lead to organ rejection, which is almost always treatable. If it's over-immunosuppression, viral infection would be the most common result.

There are also malignant complications, which in his case could be a recurrence of his tumor that he was treated for. It could also be a new tumor. Patients under immunosuppression have a tendency to develop more tumors. There's a specific type of tumor from post-transplant lymphoproliferative disorder, or PTLD, and the first treatment for that is a decrease or limitation of immunosuppressants.

Those are 90 percent of possible complications of a liver transplant. I have no clue if Steve Jobs has any of these.

Judging from what we see of Jobs in the media and other reports about his physical appearance—especially those emphasizing his "gaunt" appearance in the past few years—help us glean anything about what current health challenges he might be facing?
He's always looked very thin to me. He's a lot more gaunt than I am.

Some people are suggesting that as part of his 2004 cancer treatment he had a so-called Whipple operation (in which parts of the bile duct, pancreas, stomach and small intestine are removed). Would that procedure explain some of the possible complications he might be facing now?
I only know from what I've read, but my understanding is that his pancreatic cancer resection was not a Whipple. Now it doesn't really matter, and the bottom line is that it shouldn't have any affect on his transplant. If he had had a Whipple it would have made the initial transplant more difficult, but it shouldn't be making a difference now.

Are there other ways Jobs' liver health might have been affected by his bout with pancreatic cancer?
First, when health care providers say "pancreatic cancer," they generally refer to adenocarcinoma—which is not what he had. We don't do liver transplants for metastatic adenocarcinoma of the pancreas. There are thousands of people every year who have metastatic adenocarcinoma. Because of the high-profile cases, people think they can have a transplant for that, and that the reason centers are turning them down is because they are not Steve Jobs. That is not the situation at all. He had what is called a neuroendocrine tumor, more specifically an insulinoma. And based on the biology and presentation—those that are metastatic only to the liver—only those are suitable for transplantation. He developed metastasis in his liver—and only in his liver—and that was able to justify transplantation.

Given what we know about liver transplants and their success rate in neuroendocrine pancreatic cancer patients, is there any way to speculate about what we might expect to see for Jobs's health in the near future?
It's impossible to know what we're going to see down the road when we don't know what the issue is. Some of the potential complications won't affect your ability to work, and some of them will.