Nonalcoholic Fatty Liver Disease Raises Liver Cancer Risk

Daniel M. Keller, PhD

April 25, 2012

April 25, 2012 (Barcelona, Spain) — A study with a large multicenter cohort has shown that nonalcoholic fatty liver disease (NAFLD) is a predisposing factor for hepatocellular carcinoma (HCC) in the absence of other liver diseases, and frequently without cirrhosis.

Here at the International Liver Congress 2012, Helen Reeves, BMedSci, BM, PhD, senior lecturer and honorary consultant gastroenterologist at Newcastle Hospitals in the United Kingdom, presented evidence that obesity is a worldwide problem and, as a result, the prevalence of NAFLD is rising.

Dr. Reeves spoke on behalf of the Fatty Liver Inhibition of Progression consortium, which was formed in January 2010 to address the problem. A central goal of the consortium is to create an "observatory" of HCC, NAFLD, and metabolic syndrome to characterize the diseases with high-quality data and sample collection.

The consortium has been collecting data for 3 years on patients with HCC and no other liver disease and who imbibe less than 50 g/day of alcohol. Unless the features of metabolic syndrome or NAFLD were present on liver histology or ultrasound, cases were considered cryptogenic.

A Minority of Cases Are Cryptogenic

"The fact is that only very few of these patients develop their hepatocellular cancer in the absence of metabolic syndrome, so just 20 of 221, which is 9%, had no metabolic risk factor," Dr. Reeves reported. Of the 201 remaining cases, 187 had metabolic syndrome risk factors, 66 had fatty liver diagnosed on ultrasonography, and 37 had fatty liver diagnosed on liver biopsy.

Alcohol consumption appeared to play a minor role at most. Fifty-five percent of participants rarely or never drank alcohol, 33% drank moderately in the past but no longer drink, and only 12% consume alcohol now but not more than 50 g/day.

Mean age at HCC diagnosis was 69 years, almost 4 times as many men as women were diagnosed, and fatty liver was previously diagnosed in 50% of the cohort. HCC was detected with scheduled monitoring in 48%; for most of the rest, it was detected with ultrasound for other reasons or from symptoms.

A single liver nodule was detected in 58% of the cohort, and 75% had preserved liver function (Child-Pugh grade A). Dr. Reeves said that despite the high prevalence of preserved liver function, 55% of the participants were graded as Barcelona Clinic Liver Cancer stage C or D, indicating symptomatic disease at the time of presentation.

"Forty-three percent developed their cancer in the absence of cirrhosis," Dr. Reeves told the delegates. The ratio of men to women was similar in those with and without cirrhosis, as was body mass index and the prevalence of diabetes. Still under analysis are the alcohol and smoking history of the cohort.

"What was significantly different was the size of the largest nodule.... [It] was significantly greater in those who did not have cirrhosis," she explained (30 vs 48 mm; P < .001). Patients with cirrhosis were more likely to have encephalopathy at the time of diagnosis than patients without cirrhosis (12% vs 3%; P = .04), and trended toward more ascites (33% vs 18%, P = .062).

Only about 10% of the patients received no definitive treatment for their liver cancer and were referred for best supportive palliative care. For the rest, only a few received liver transplants, but many received radiofrequency ablation, transarterial chemoembolization, medical therapy with sorafenib, or other treatment.

Dr. Reeves concluded that NAFLD is a predisposing condition for HCC in the absence of other liver diseases, and that NAFLD-associated HCC often occurs in the absence of cirrhosis. She said many of the patients were eligible for potentially curative therapies, and the consortium will continue to follow this cohort to observe outcomes.

Mark Thursz, MBBS, MD, secretary general of the European Association for the Study of the Liver and professor of hepatology in the Department of Medicine at Imperial College, London, United Kingdom, told Medscape Medical News that, ironically, there is good news for patients with hepatitis C, in that several new drugs are coming along. "You can see cures just around the corner for high proportions of patients. Nonalcoholic fatty liver is much more difficult to deal with. It's quite difficult to change people's lifestyles."

He noted that NAFLD is now the leading cause of liver disease in North America, and will be in Europe before too long. "The fact that people are developing cancer before they develop cirrhosis — that's a concern because our current guidelines tell us we should be instituting surveillance programs for cancer in cirrhotic patients," Dr. Thursz said. "Extending that into precirrhotic patients is going to be quite challenging to resources, and the selection of patients is then going to be really critical."

He said the risk factors for NAFLD are well known and include abdominal fat, diabetes (or at least insulin resistance), low high-density-lipoprotein cholesterol, and high low-density-lipoprotein cholesterol.

"We can't predict with any accuracy which individual patient has progressive disease, as opposed to pure fat in the liver," he said.

There is no noninvasive way to tell if a patient has pure steatosis, has fat and inflammation, or has fat, inflammation, and fibrosis. "It's the latter group that is at risk" for HCC, he warned.

Dr. Thursz and Dr. Reeves have disclosed no relevant financial relationships.

The International Liver Congress 2012: Abstract 5. Presented April 19, 2012.


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