Non-alcoholic fatty liver disease (NAFLD) has gained attention due to its increasing prevalence worldwide becoming a global epidemic. The increasing incidence of NAFLD and the concurrent increase in the number of hepatocellular carcinoma (HCC) cases at a global level is a matter of concern. HCC has several risk factors, of which NAFLD and its associated metabolic disturbances—type 2 diabetes mellitus, obesity, and dyslipidemia—are of great interest due to their accelerating rise in incidence worldwide. There is a high amount of data derived from basic and clinical studies that reveal the molecular pathways that drive NAFLD-associated HCC. Based on these findings, new prevention, surveillance, and treatment strategies are emerging.
1. Introduction
Over the past few decades, liver cancer incidence and death have both been steadily increasing. With a total of 905,677 new cases reported in 2020, liver cancer constituted the sixth most prevalent cancer globally. Liver cancer still has a poor prognosis despite recent improvements. In terms of cancer-related deaths in 2020, liver cancer came in third with 830,180 fatalities [1]. HCC has several risk factors, of which NAFLD and its associated metabolic disturbances—type 2 diabetes mellitus, obesity, and dyslipidemia—are of great interest due to their accelerating rise in incidence worldwide [2].
The therapeutic management of HCC is complex and, according to the recommendations of current guidelines, it requires a multidisciplinary team consisting of hepatologists, oncologists, and surgeons specialized in liver surgery and transplantation, as well as radiologists. However, data from the literature show that only half of patients diagnosed with HCC are subsequently evaluated by a multidisciplinary team. Currently, the treatment recommendations for HCC are based on the BCLC classification and do not differ from one etiology to another, but do take into consideration the presence of liver cirrhosis and consequently liver function
[3]. Placing patients in a specific therapeutic strategy depends on the BCLC classification, taking into account patient heterogeneity, patient wishes, ongoing clinical trials, and local limitations. There are scarce data regarding both treatment modalities and long-term survival in NAFLD-HCC, taking into consideration that these patients frequently have several comorbidities, such as type 2 diabetes mellitus, cardiovascular disease, and obesity. For instance, Wang et al. demonstrated that cirrhotic patients with type 2 diabetes and HCC have lower overall survival rates after curative hepatectomy compared to those without diabetes
[4]. The authors concluded that diabetes may reduce the OS of HCC patients by exacerbating existing liver fibrosis, resulting in severe liver failure.
2. Hepatic Resection
In patients with HCC without liver cirrhosis and impaired liver function, hepatic resection represents the first option for treatment
[5][6]. However, despite progress having been made in the last years in improving the survival rate in those with liver resection, the recurrence rate has not shown major changes. Research studies that assessed the overall survival (OS) and recurrence-free survival (RFS) in patients with NAFLD-associated HCC showed optimistic results (
Table 1). It appears that OS at 5 years after liver resection for NAFLD-associated HCC ranges from 51.5% to 97%, whereas RFS at 5 years ranges from 36.3% to 66%
[7][8][9][10][11][12][13]. However, there is an ongoing debate regarding the outcomes after resection in patients with NAFLD-associated HCC vs. other liver diseases. It appears that the presence of metabolic and cardiovascular comorbidities, which are often found in patients with NAFLD, has a negative impact on the OS after liver resection for HCC
[14]. A meta-analysis that aimed to evaluate the outcome after hepatic resection for HCC in NAFLD vs. other liver diseases in approximately 7200 patients found a better RFS and OS in those with NAFLD
[15]. Furthermore, a lower RFS was found in a study that compared NAFLD-associated HCC with HCV-related HCC (44.6% vs. 62.5%)
[11]. Still, it is important to acknowledge that the high post-surgical mortality in patients with NAFLD is mainly due to the metabolic comorbidities, which should be carefully diagnosed and managed.
Table 1. Overall survival (OS) and recurrence-free survival (RFS) in patients with NAFLD-associated HCC after liver resection.
Ref. |
Type of Study |
Patients (n) and Characteristics |
Overall Survival Rate * |
Recurrence-Free Survival ** |
Koh et al. [16] |
Retrospective |
N = 996 HCC patients, 844 with non-NAFLD HCC and 152 with NAFLD HCC |
70.1% |
45.4% |
Reddy et al. [17] |
Retrospective |
N = 214 HCC patients, 52 with NASH and 162 with HCV or ALD |
59% |
48% |
Liang et al. [18] |
Retrospective |
N = 177 HCC patients, 75 with NASH and 102 with alcoholic or viral hepatitis |
87% |
51% |
Vigano et al. [19] |
Retrospective |
N = 192 HCC patients, 96 with NASH and 96 with HCV |
65.6% |
37% |
Billeter et al. [20] |
Retrospective |
N = 365 HCC patients, 62 with NASH and 303 with HCV |
71.3% |
36.3% |
Yang et al. [21] |
Retrospective |
N = 1483 HCC patients, 96 with NAFLD HCC and 1387 with HBV HCC |
51.4% |
38.8% |
Wakai et al. [22] |
Retrospective |
N = 225 HCC patients, 17 with NAFLD HCC, 61 with HBV, and 147 with HCV |
59% |
66% |
This entry is adapted from the peer-reviewed paper 10.3390/life13101987