The Bioartificial Liver

There is reason for optimism that the bioartificial liver can eliminate the need for a transplanted liver in other patients with fulminant liver failure. Ironically, nobody knows what toxins accumulate in the brain, or how the liver operates to relieve intracranial pressure. "We are treating a disease we do not understand with a treatment we do not understand," according to Demetriou. Acute liver failure is usually due to a temporary event, like Tylenol overdose (a common means of attempted suicide) or hypersensitivity to other drugs. The liver is a fairly robust organ and could possibly regain function in many instances--if the patient doesn't go brain-dead first. This is an important point, one he hopes to impress on health maintenance organizations (HMOs) and insurance companies. Traditionally, these companies have been slow to adopt payment schedules for new technologies. Demetriou's bioartificial liver treatments require constant monitoring in expensive intensive care units. Worse yet, from the financial side, the treatments allow a patient who might have died access to a liver transplant, which costs in excess of half a million dollars. If Demetriou can show recovery of patients, in some cases, without a liver transplant, he stands a far better chance of having the bioartificial liver accepted by HMOs, Medicare and private insurance companies as standard medical practice in the U.S. For every 7 hours of treatment with the bioartificial liver, Demetriou figures he gains another 24 hours of life for his patients. Although the experiment hasn't really been tried yet, most in the field expect that using pig liver cells instead of human limits the amount of time that the device could be used on a human patient. In addition to its detoxification function, the liver supplies most of the non-cellular protein found in the blood. It is expected that eventually the patient will develop an immune response to the pig proteins secreted by the pig liver cells-- and Demetriou concedes he has detected porcine proteins in the blood of his patients.

Long term treatment of patients with chronic liver disease in a manner analogous to the hemodialysis treatment of kidney patients would probably require a bioartificial liver which used human cells. But where to get the cells? As it stands now, technology is not the limiting factor in treating liver patients; it is the number of human livers available. Every year, 30-50,000 people die of liver failure, while only about 3000 transplants are available. Geoffrey Block may have an answer to the human liver shortage. Recently, he and his co-workers at the University of Pittsburgh stimulated liver cells to divide and grow in laboratory culture, using a chemically defined culture medium. The secret? A few hormones--some of which are proprietary, and 75 different nutrients. Surprisingly, fully differentiated, functioning hepatocytes divide and grow, according to Block. It had been widely believed by many cell biologists and embryologists that these fully differentiated cells will not reproduce. Differentiated cells are replaced, it is thought, by the division of immature "committed progenitor" cells. While the latter can be cultured in the laboratory, they lack the liver cell functions that would be needed in a bioartificial liver. Block believes that his group has "dedifferentiated" the liver into growing, immature cells. He also claims that he can manipulate the cultures to develop again into functioning mature hepatocytes, which would be necessary for his work to be medically significant. Lola Reid of the University of North Carolina, who has done careful work on the developmental biology of liver, urges caution in interpreting Block's results. The "de-differentiation" of hepatocytes runs contrary to her own experience, which suggests that the liver cells mature in an ordered fashion in the body, starting with the division of immature stem cells. Demetriou, for his part, is skeptical that Block's laboratory cultured cells will ultimately provide the detoxification function necessary for use in the bioartificial liver, citing many previous claims in the literature of laboratory cultured, functioning hepatocytes that turned out to be premature. If Block is correct, however, "I'll buy the cells from him," says Demetriou.