Miriam E. Tucker

November 12, 2013

WASHINGTON, DC — Patients with hepatocellular carcinoma account for an increasing proportion of patients infected with hepatitis C on the waiting list for liver transplantation, a retrospective cohort study has found.

"We feel that primary prevention for hepatocellular carcinoma will be key to reversing this trend," Jennifer Flemming, MD, from Queen's University in Kingston, Ontario, told Medscape Medical News.

"In patients with hepatitis C, viral eradication is the most important step in reducing an individual's risk of developing hepatocellular carcinoma," she explained. "As the landscape of antiviral treatment continues to evolve and become easier from both the patient and clinician perspective, we would hope that increased rates of sustained viral response result in a lower incidence of hepatocellular carcinoma and, subsequently, a decrease in the number of individuals listed."

Dr. Flemming presented the findings here at The Liver Meeting 2013. She began the work as a clinical research fellow at the University of California, San Francisco.

Patients with hepatocellular carcinoma are given an exception to the Model for End-Stage Liver Disease (MELD) score, developed by the United Network for Organ Sharing (UNOS) to prioritize patients in most urgent need of liver transplantation. The MELD score, which ranges from 6 to 40, takes into account bilirubin, prothrombin time, and creatinine. Patients with scores of 16 and above are considered to be transplant candidates. Patients with hepatocellular carcinoma are automatically given extra points.

Dr. Flemming's team examined data from the Scientific Registry of Transplant Recipients, which includes all liver transplant waitlist candidates in the United States.

Of the 20,325 patients with liver disease related to hepatitis C infection (about 30% of the total), the indication for listing was end-stage liver disease for 12,724 patients and hepatocellular carcinoma for 7061. Those listed for hepatocellular carcinoma were older (56 vs 52 years; P < .001) and more likely to be male (79% vs 73%; P < .001) than those listed for end-stage liver disease.

More Hepatocellular Carcinoma

After adjustment for age and sex, the overall rate of patients with hepatitis C rose from 6.9 per 100,00 in 2003 to 10.2 per 100,000 in 2010 (P < .001). This was entirely due to the 12% annual increase in patients with hepatocellular carcinoma; the average annual increase in patients with end-stage liver disease was a nonsignificant 1%.

The demand for liver transplantation for hepatocellular carcinoma will likely continue to rise.

"Looking to the future, the demand for liver transplantation for hepatocellular carcinoma will likely continue to rise and further strain the donor pool," Dr. Flemming said. She added that this situation could "push the transplant community to consider nontransplant alternatives for the disease."

The researchers could not account for the plateau in transplant listings for end-stage liver disease in the hepatitis C population, but there are several hypotheses, Dr. Flemming told Medscape Medical News.

The management of patients with cirrhosis in the gastrointestinal and hepatology community could be improving, which might prevent or delay the development of liver decompensation.

"With the publication of clinical guidelines from the American Association for the Study of Liver Diseases [AASLD] on the management of ascites, esophageal varices, portal hypertension, and hepatocellular carcinoma, clinicians may be more educated and feel more comfortable managing complex patients than in the past," Dr. Flemming said.

In addition, increased viral clearance from recently available antiviral therapy for hepatitis C could be reducing the need for liver transplantation, she noted.

Unfair Advantage

There is general agreement within the hepatology community that this exception has become increasingly unfair to non-hepatocellular carcinoma patients with end-stage liver disease, said session moderator Susan Orloff, MD, from Oregon Health & Science University, and chief of the liver transplantation program at the Portland VA Medical Center.

"The issue is that we are overadvantaging patients with hepatocellular carcinoma," she told Medscape Medical News. "Despite the fact that the total number of waitlisted patients with hepatitis C has increased, that increase is solely due to patients with this carcinoma. We have to figure out an allocation system that allows non-hepatocellular carcinoma patients to have equal access to organs," said Dr. Orloff.

There have been attempts within the AASLD and UNOS to come up with a better way of allocating donor livers, she noted.

"We're in the process of trying to sort it out. Should we require a wait time for patients with hepatocellular carcinoma before they can get activated on the list? But how would you choose those patients?"

The key will be to identify genomic biomarkers in tumors that predict the likelihood of progression, Dr. Orloff said.

"I think we have to figure out a scoring system within the hepatocellular carcinoma group to see who has a greater likelihood of progressing, so we don't put them in the hold bucket," she explained. "Those who don't have a high risk of progression could wait 6 or 8 months. But it also depends on individual biology; it's a very difficult situation. There's no hard and fast answer."

Dr. Flemming and Dr. Orloff have disclosed no relevant financial relationships.

The Liver Meeting 2013: American Association for the Study of Liver Diseases (AASLD). Abstract 12. Presented November 3, 2013.


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