Outcomes of curative treatment for hepatocellular cancer in nonalcoholic steatohepatitis versus hepatitis C and alcoholic liver disease

Abstract

Concomitant increasing incidences of hepatocellular carcinoma (HCC) and nonalcoholic steatohepatitis (NASH) suggest that a substantial proportion of HCC arises as a result of hepatocellular injury from NASH. The aim of this study was to determine differences in severity of liver dysfunction at HCC diagnosis and long-term survival outcomes between patients undergoing curative therapy for HCC in the background of NASH compared to hepatitis C virus (HCV) and/or alcoholic liver disease (ALD). Patient demographics and comorbidities, clinicopathologic data, and long-term outcomes among patients who underwent liver transplantation, hepatic resection, or radiofrequency ablation for HCC were reviewed. From 2000 to 2010, 303 patients underwent curative treatment of HCC; 52 (17.2%) and 162 (53.5%) patients had NASH and HCV and/or alcoholic liver disease. At HCC diagnosis, NASH patients were older (median age 65 versus 58 years), were more often female (48.1% versus 16.7%), more often had the metabolic syndrome (45.1% versus 14.8%), and had lower model for end-stage liver disease scores (median 9 versus 10) (all P < 0.05). NASH patients were less likely to have hepatic bridging fibrosis or cirrhosis (73.1% versus 93.8%; P < 0.001). After a median follow-up of 50 months after curative treatment, the most frequent cause of death was liver failure. Though there were no differences in recurrence-free survival after curative therapy (median, 60 versus 56 months; P 5 0.303), NASH patients had longer overall survival (OS) (median not reached versus 52 months; P 5 0.009) independent of other clinicopathologic factors and type of curative treatment. Conclusion: Patients with HCC in the setting of NASH have less severe liver dysfunction at HCC diagnosis and better OS after curative treatment compared to counterparts with HCV and/or alcoholic liver disease. (HEPATOLOGY 2012;55:1809-1819 C oncomitant increases in the incidence of hepatocellular carcinoma (HCC) and prevalence of nonalcoholic fatty liver disease (NAFLD) suggest that a substantial proportion of HCC arises as a result of hepatocellular injury from nonalcoholic steatohepatitis (NASH). As a result, HCC is the most rapidly increasing cause of cancer death in the United States.

Nonalcoholic Fatty Liver Disease (NAFLD) and Hepatocellular Carcinoma: How Common?

“…In a study from Germany, only 58 % of 36 NAFLD-related HCC had cirrhosis at time of HCC diagnosis [33]. A single-center study among HCC patients undergoing curative resection evaluated explant specimens and found significantly lower prevalence of cirrhosis among NASH-HCC than HCV-or alcohol-related HCC (73 vs. 94 %) [42]. We conducted a study using a national cohort of 1500 veterans diagnosed with HCC and found that 35 % of NAFL D-related HCC and 19 % of HCC with metabolic syndrome did not have evidence of cirrhosis at the time of HCC diagnosis compared with 10 % of those with alcohol abuse or HCV-related HCC [76].…”

“…Another limitation is the potential for reverse causality, by which some of the risk factors (e.g., diabetes or BMI) are affected by the development of HCC or the preceding cirrhosis. Our search found at least 9 studies performed in Asia (n=7 in Japan), 6 in Europe, and 7 in the USA [8,23,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]44•, 45•] (Table 1C). All compared a case group with HCC attributed to NASH/NAFLD or to CC presumptively NAFLD related, with at least 1 control group, typically with HCC attributed to another cause of liver disease (n=19); though 2 had only NASHrelated cirrhosis controls without HCC as their sole comparison or control group.…”

Non-Alcoholic Steatohepatitis-Related Hepatocellular Carcinoma: A Growing Epidemic?

“…A similar mix of therapies was seen in the comparison group of 162 patients, with 51% undergoing liver transplantation, 32% surgical resection and 20% ablation. Three-year overall survival was significantly better in the NASH group (60.9%) than in the HCV-alcohol group (36.2%), with no difference in recurrence-free survival (60 vs. 50 months, median survival) [20]. Given similar tumor characteristics and recurrence-free survival rates, overall survival is most likely predicated not by tumor presentation but by the poorer liver function associated with the HCV-alcohol group.…”

“…Currently, there are no published series examining the outcome of either locoregional therapies, including transarterial chemoembolization and Yttrium-90 therapy, or systemic therapies. Reddy et al [20] have recently published the largest series of patients with NASH-related HCC who have undergone curative-intent therapy (surgical resection, liver transplantation or tumor ablation). They compared outcomes to a cohort of patients with HCV- or alcohol-related HCC who were presented over the same 11-year time period.…”

“…Reddy et al [20], in a report detailing the University of Pittsburgh experience, compared a cohort of HCV- and NASH-related HCC patients presenting for curative-intent therapy. This study confirmed the findings seen in NASH-related cirrhosis.…”