Large Analysis Looks at Characteristics of Subset of Patients With Liver Cancer

In the population of patients with nonalcoholic steatohepatitis (NASH)-associated hepatocellular carcinoma (HCC), about a quarter of patients do not have cirrhosis at diagnosis. This is suggesting an important subset of patients for research regarding the implications for HCC screening and surveillance, according to Ju Dong Yang, M.D., M.Sc., at the 10th Annual Conference of the International Liver Cancer Association (ILCA), a meeting of hundreds of oncologists and other liver cancer experts in Vancouver, Canada.

In a multivariate analysis of retrospective data for 4,734 patients, hypertension and cigarette smoking were independently associated with non-cirrhotic NASH-related HCC. The odds ratio (OR) for non-cirrhotic NASH HCC was 2.52 for those with hypertension and 2.27 for those who smoked. Diabetes was inversely related with having non-cirrhotic NASH.

“We identified potential risk factors for the development of HCC in the absence of cirrhotic liver disease in patients with NASH,” said Yang, an associate faculty member, Division of Gastroenterology and Hematology, Mayo Clinic College of Medicine in Rochester, Minnesota, in an interview with CURE. “Our data proposed that potentially we can put liver cancer surveillance, for example, [in place] for a patient who has smoked in the past or is currently smoking because they may be at high risk of developing liver cancer, even in the absence of cirrhotic liver disease.”

NASH, a form of non-alcoholic fatty liver disease, is one of the major causes of HCC in Western countries. In the United States, NASH is the most rapidly growing etiology of HCC and second leading cause of liver transplantation.

The idea that cirrhosis is not present in all patients with NASH-associated HCC has been shown previously; however, Yang and his colleagues set out to confirm these findings in a larger analysis. For this study, researchers looked at data from 4,734 patients who were part of the longitudinal BRIDGE study.

This study found that males had a 1.61-fold increased risk of non-cirrhotic HCC, while Hepatitis B was associated with a 3.15-fold increased risk and hypertension was associated with a 1.60-fold increased risk. Most importantly, Yang pointed out, NASH was associated with a 3.57-fold increased risk of non-cirrhotic HCC.

“Our study confirmed that patients with NASH, which is a common cause of liver disease in the US, may develop liver cancer in the absence of cirrhosis,” Yang said, noting that previous studies were performed in a small number of patients.

To identify risk factors associated with non-cirrhotic HCC in patients with NASH, the retrospective study also looked at data from just over 312 patients from the BRIDGE study with NASH—82 did not have cirrhosis while 230 did. A number of factors were significantly different between arms, namely male gender (78 percent non-cirrhotic vs 65 percent cirrhotic), diabetes (65 percent vs 83 percent, respectively), hypertension (78 percent vs 65 percent), smoking (67 percent vs 50 percent), albumin (4.0 vs 3.6), platelets (248 vs 132) and tumor size in centimeters (6.5 vs 4.0).

There were some differences between the groups in regard to treatment: patients with non-cirrhotic NASH HCC more commonly received surgical resection compared with their cirrhotic NASH HCC counterparts (36 percent vs 9 percent), though they were less likely to receive liver transplantation (0 percent vs 18 percent). The groups were treated with curative intent at the same rate (49 percent for non-cirrhotic patients vs 45 percent for cirrhotic patients) and overall survival was similar (HR, 0.8; 0.6-1.2; P = .25).

With the increasing prevalence of NASH in the general population, NASH-associated HCC will increase too, Yang noted, so researchers should have some sense of urgency—though there is still important work to be done.

“The associations seen in the current study between cigarette smoking, hypertension, and non-cirrhotic HCC may help to guide HCC risk stratification, but they should be further validated in a future study,” Yang concluded.