A small study from Australia concludes people diagnosed with steatosis, or fatty liver, do not face a higher risk of developing liver cancer in the future.¹

Theories Hinged on Previous Data
Based on animal studies of fatty liver, which can cause an abnormal increase in the growth of liver cells,² it was theorized that steatosis may also lead to hepatocellular carcinoma, the most common form of liver cancer. It's also been suggested that liver cancer can result in people with non-alcoholic steatohepatitis (NASH), an inflammatory form of fatty liver, or obesity.³

"If steatosis increases the risk of hepatocellular carcinoma with chronic HCV infection, this would provide a logical approach to reduce liver cancer risk, by either antiviral treatment or weight reduction," wrote Jacob George, PhD, of the Storr Liver Unit at Westmead Hospital and his colleagues, in describing the basis for their study. "We therefore sought to determine whether the presence of steatosis, per se, is a contributing factor to the subsequent development of hepatocellular carcinoma."

Fat-Driving Engine
Obesity causes steatosis because the former is associated with high insulin levels. This insulin subsequently "drives fat from the diet into tissues including the liver," George explained, in an interview with Priority Healthcare.

"Steatosis in the liver from whatever cause (for example, being obese) can give rise to liver inflammation and damage, which can result in cirrhosis," he said. "Steatosis from obesity gives rise to NASH, which today is the commonest cause of liver damage in the U.S., Australia, and other developed countries."

However, George's team stresses that there is no link between fatty liver and cancer, per se. Other conditions that develop from fatty liver must occur first, they found. "Hence, steatosis is benign, but if it gives rise to liver damage, then this can cause liver disease and/or cancer," George said.

Comparative Prognoses Considered
George and his fellow researchers followed more than 450 people with chronic hepatitis C who had been treated in their liver unit over a 12-year period. Of those, 28 patients eventually developed hepatocellular carcinoma.  Three patients had incomplete information, leaving data on 25 people for the study. These patients' prognoses were compared with 25 patients who had not developed hepatocellular carcinoma during the study period. Each patient in the two groups was matched by age, gender, hepatitis genotype and stage of fibrosis, in order to account for other possible causes of liver cancer.

Each patient had undergone a liver biopsy to confirm the presence or absence of steatosis, or any other liver disease.

Among those with hepatocellular carcinoma in association with hepatitis infection, the majority also had fibrosis. There were similarities between the patients who had liver cancer and those who did not in terms of source of hepatitis infection, level of infection, weight, and alcohol habits. The stage of steatosis was also comparable between liver cancer and non-liver cancer cases.

Fatty Liver Had No Effect on Cancer Risk
The researchers discovered that while 13 patients with liver cancer had a greater extent of fatty liver than matched patients in the group without cancer, in 10 patients also with liver cancer, the opposite was true. This implies that the extent of fatty liver does not play a role in liver cancer development. Two patients with liver cancer and two in the group without liver cancer had had no evidence of fatty liver.

Using statistical analysis, George's group also suggested that the risk of developing hepatocellular carcinoma in those with early or later stages of steatosis was not significantly different from that faced by those without steatosis.

In fact, in this study, only initial levels of liver enzymes predicted whether a person was likely to develop liver cancer eventually or not. (Liver enzymes are released into the bloodstream when it is damaged. Therefore, doctors measure their levels to make assessments about the extent of a particular patient's liver disease). In this study, higher levels of these enzymes tended to increase the risk of developing liver cancer.

Other Factors Should be Considered
Based on their analysis, George and his group determined that other factors besides steatosis are better predictors of liver cancer development. This was true after taking other potential factors associated with liver cancer into account, such as patient age, gender, a patient's hepatitis genotype (a strain of the hepatitis virus—it's been suggested that liver cancer is found more often in those with the genotype 1 strain of the virus⁴), and stage of fibrosis. "Other risk factors, such as the duration of infection, alcohol intake, past HBV infection, and risk factors for nonalcoholic fatty liver disease (particularly diabetes and obesity) were comparable in the two groups," wrote the study team.

George and his associates acknowledge that their study was small, and that larger numbers of patients would have helped to reach their conclusions more solidly. But they explain that following patients from initial liver biopsy to the development of liver cancer "would take years to complete", given the fact that such cancer develops very slowly over time.

While there have been some reports of liver cancer developing in people with fatty liver, it happens rarely, if at all, in the absence of liver fibrosis, the researchers stressed, citing previous research. "Even in these reports, hepatocellular carcinoma occurred in a cirrhotic liver, attesting to the importance of advanced fibrosis rather than to steatosis, per se, being directly [cancer-causing]," they wrote.

It's known that someone with cirrhosis (which may develop following liver fibrosis) faces three to four times the risk of developing liver cancer as someone without it, George told Priority Healthcare.

Their findings seem to be conclusive, the research team wrote, but added that "the jury remains out" on the general role that fatty liver, obesity and insulin resistance play in liver cancer development.

1. Kumar D, Farrell GC, Kench J, George J. Hepatic steatosis and the risk of hepatocellular carcinoma in chronic hepatitis C. J Gastroenterol Hepatol 2005 Sep;20(9):1395-400.
2. Yang S, Lin HZ, Hwang J, Chacko VP, Diehl AM. Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition? Cancer Res 2001 Jul 1;61(13):5016-23.
3. Jansen PL. Nonalcoholic steatohepatitis. Neth J Med 2004 Jul-Aug;62(7):217-24.
4. Benvegnu L, Alberti A. Risk factors and prevention of hepatocellular carcinoma in HCV infection. Dig Dis Sci 1996 Dec;41(12 Suppl):49S-55S.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.