NAFLD as a risk factor for HCC: new rules of engagement?

Non-alcoholic fatty liver disease (NAFLD) is increasingly diagnosed worldwide and is the most common cause of abnormal liver function tests and chronic liver disease in clinical practice. Although most patients with simple steatosis will have stable disease, 10–15 % with histologically proven non-alcoholic steatohepatitis (NASH) will progress to cirrhosis and its complications such as liver failure and hepatocellular carcinoma [1–3]. A long-term follow-up study of NAFLD patients showed that patients with NASH have lower survival rates compared to patients with simple steatosis, and most of the patients in the follow-up period developed type 2 diabetes or impaired glucose tolerance [2]. Cirrhosis as a result of NAFLD is predicted to surpass chronic hepatitis C (CHC) as the leading indication for liver transplantation in the USA within the next 5 years, as the incidence of CHC is decreasing whereas that of NAFLD is increasing [4]. Although cirrhosis is a major risk factor for hepatocellular carcinoma (HCC) development, a growing number of case reports and small patient series demonstrate that liver cancers sometimes develop in individuals with NAFLD who do not also have cirrhosis [5]. The studies published in Hepatology International have provided further insight into the natural history of NAFLD and HCC. In this issue, Mohamad and colleagues [6] carefully investigated the characterization of NAFLD-related HCC patients with or without cirrhosis. Thirty-six patients with NAFLD and HCC in NCL (HCC-NCL group) were identified and compared to 47 patients with NAFLD-HCC and liver cirrhosis (HCC-LC group). Liver fibrosis was not present in 55.9 % of patients in the HCC-NCL group (F0), stage 1 was present in 17.6 %, stage 2 in 8.8 % and stage 3 in 17.6 %. Lobular inflammation was present in 63.6 % of non-cirrhotic patients. Patients in the HCC-NCL were older (67.5 ± 12.3 vs. 62.7 ± 8.1 years), and less likely to be obese (52 vs. 83 %) or have type 2 diabetes (38 vs. 83 %), with p values\0.05 for all. More interestingly, compared with the HCC-CL group, those in the HCC-NCL group were more likely to present with a single nodule (80.6 vs. 52.2 %), larger nodule size ([5 cm) (77.8 vs. 10.6 %), and receive hepatic resection as the modality of HCC treatment (66.7 vs. 17 %), and were less likely to receive loco-regional therapy (22.3 vs. 61.7 %) or orthotopic liver transplantation (OLT) (0 vs. 72.3 %), with p values\0.001 for all. These patients presented with larger tumors possibly because they did not receive regular medical check-ups due to their relatively preserved liver function. We have previously reported similar tumor characteristics in elderly HCC patients who also tended to have tumor markers with high DCP and low AFP [7, 8]. These results suggested that there might be a relationship between aging and HCC. Studying differences in tumor markers might be helpful in further understanding the tumor biology. The authors also analyzed the prognosis of patients and found 86 % of patients without cirrhosis had HCC recurrence compared to only 14 % in patients with cirrhosis (p\ 0.001). One possible explanation is that these solitary tumors in the HCC-NCL group might have an aggressive tumor biology, although this result should be interpreted carefully because more cirrhotic patients might have undergone OLT and therefore presented with fewer recurrences than non-cirrhotic patients who might have & Masao Omata [email protected]