Miriam E. Tucker

April 25, 2015

VIENNA — Nonalcoholic fatty liver disease is emerging as a major cause of hepatocellular carcinoma in the United States, a new study shows.

In fact, from 2004 to 2009, the annual increase in hepatocellular carcinoma in fatty liver disease patients was approximately 5%.

Survival is shorter for patients with fatty liver who develop cancer than it is for patients with hepatitis B or hepatitis C who develop hepatocellular carcinoma, said Zobair Younossi, MD, from the Inova Health System in Falls Church, Virginia.

Tumor stage is also more advanced at diagnosis in patients with fatty-liver-associated carcinoma, and liver transplantation is less common, he reported.

"Given the epidemic of nonalcoholic fatty liver, the burden of disease-related complications is expected to rise," Dr Younossi said here at the Liver Congress 2015.

Fatty liver disease affects about 25% of the population in the United States. About 2% to 3% of the population has the progressive form of the disease — nonalcoholic steatohepatitis.

"I suspect it is the nonalcoholic steatohepatitis patients who are primarily at risk for adverse outcomes," Dr Younossi told Medscape Medical News. "In 2015, the only way to confidently establish the diagnosis of steatohepatitis is by a liver biopsy. Because biopsy is invasive, it is done in the small minority of patients. Therefore, a large number of patients with nonalcoholic steatohepatitis are undiagnosed," he explained.

"And there may not be a recognition that patients with advanced fibrosis are at risk for hepatocellular carcinoma," he added.

His recommendation is to "determine if a patient with fatty liver has steatohepatitis-related advanced fibrosis or cirrhosis. If so, they should be screened for hepatocellular carcinoma every 6 months."

More Deaths

From 2004 to 2009, Dr Younossi and colleagues identified 5748 hepatocellular carcinoma patients and 17,244 control subjects without cancer from the Surveillance, Epidemiology, and End Results (SEER)–Medicare database.

The liver cancer was related to hepatitis C in 48% of the cases, to fatty liver in 26%, to alcoholic liver disease in 14%, to hepatitis B in 8%, and to autoimmune hepatitis or biliary cirrhosis in 4%.

This is a very important study because of the very large number of patients.

The number of cases of hepatocellular carcinoma increased each year during the study period. Annual increases in fatty-related cancers were proportionate to increases in hepatocellular carcinoma related to other causes.

Patients with fatty-liver-related cancer were older at diagnosis than patients with cancer related to hepatitis B or C (72 vs 66 years), were more likely to be white, and were more likely to have unstaged or advanced tumors. In addition, average survival was 4 months shorter in patients with fatty-liver-related cancer (P < .05).

On multivariate analysis, being male and being of a nonwhite or nonblack race were independently associated with cancer, as were having a high Charlson Comorbidity Index score and the presence of hepatitis B, hepatitis C, or fatty liver.

More patients with hepatocellular carcinoma related to fatty liver than related to hepatitis B or C died within 1 year of diagnosis (62% vs 50%; P < .05). The most common cause of death was cancer or liver disease (96.3%), followed by cardiac death (3.7%).

For patients with cancer, factors associated with 1-year mortality were being older, having a lower income, having an unstaged tumor, being eligible for Medicare, having end-stage renal disease, and having fatty liver. Factors protective against 1-year mortality were having undergone liver transplantation and having a localized tumor.

"This is a very important study because of the very large number of patients," said session moderator Helena Cortez-Pinto, MD, from the University Hospital of Lisbon in Portugal.

Fatty-liver-associated cancer is particularly challenging to detect because it can occur in the absence of cirrhosis. "You can't do surveillance of all patients with fatty liver; that would be a very high burden," she told Medscape Medical News.

But the possibility should be kept in mind, particularly with obese patients. "We have to recognize that there is the possibility of patients with fatty liver developing cancer even in the absence of cirrhosis. We don't know exactly how frequent this is, but it exists," Dr Cortez-Pinto explained. "If there is any kind of suspicion, refer patients for further investigation."

The mortality rate for fatty-liver-associated cancer is rather surprising, and hasn't been seen in all studies, said Dr Cortez-Pinto. The finding is likely the result of the poor cancer surveillance in fatty liver patients. "If a tumor is discovered during cirrhosis surveillance, it is more likely to be monitored," she pointed out.

Dr Younossi said he agrees with that. "Fatty liver is associated with shorter survival because by the time these patients present clinically, they have advanced cancer. The reason may be that they don't undergo screening or that screening ultrasound fails to detect small cancers with fatty liver visceral obesity."

And, he added, "because of their comorbidities, they don't undergo liver transplant."

Dr Younossi is a consultant to Gilead, BMS, Intercept, GSK, AbbVie, and Salix. Dr Cortez-Pinto reports receiving consulting fees from Intercept and Janssen.

European Association for the Study of the Liver (EASL) International Liver Congress 2015. Presented April 24, 2015.


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