Screening and interventions to prevent nonalcoholic fatty liver disease/nonalcoholic steatohepatitis-associated hepatocellular carcinoma

Abstract

Liver cancer is the sixth most commonly diagnosed cancer worldwide, with hepatocellular carcinoma (HCC) comprising most cases. Besides hepatitis B and C viral infections, heavy alcohol use, and nonalcoholic steatohepatitis (NASH)-associated advanced fibrosis/cirrhosis, several other risk factors for HCC have been identified ( i.e. old age, obesity, insulin resistance, type 2 diabetes). These might in fact partially explain the occurrence of HCC in non-cirrhotic patients without viral infection. HCC surveillance through effective screening programs is still an unmet need for many nonalcoholic fatty liver disease (NAFLD) patients, and identification of pre-cirrhotic individuals who progress to HCC represents a substantial challenge in clinical practice at the moment. Patients with NASH-cirrhosis should undergo systematic HCC surveillance, while this might be considered in patients with advanced fibrosis based on individual risk assessment. In this context, interventions that potentially prevent NAFLD/ NASH-associated HCC are needed. This paper provided an overview of evidence related to lifestyle changes ( i.e. weight loss, physical exercise, adherence to healthy dietary patterns, intake of certain dietary components, etc. ) and pharmacological interventions that might play a protective role by targeting the underlying causative factors and pathogenetic mechanisms. However, well-designed prospective studies specifically dedicated to NAFLD/NASH patients are still needed to clarify the relationship with HCC risk.

NAFLD Fibrosis Progression and Type 2 Diabetes: The Hepatic–Metabolic Interplay

“…This was also demonstrated in the meta-analysis by Dulai et [4.11-9.95] from F1 to F4) [58]. In addition, the presence of advanced liver fibrosis modifies the clinical management, as it requires periodic surveillance for HCC, and in patients with T2DM it may influence the choices of antihyperglycemic therapeutic agents (mainly in advanced cirrhosis, when insulin might become the only option) [17,59].…”

“…Similarly, the prevalence of advanced fibrosis (F2-4) was reported to be around 5-7% in the general population, and 12-20% in patients with T2DM [10][11][12][13][14][15][16]. Moreover, the risk of HCC is 2.0-2.5 fold higher in subjects with T2DM [17][18][19][20]. A recent individual participant-level data meta-analysis of six retrospective studies (2016 participants with NAFLD) indicated that T2DM was an independent predictor of incident HCC (adjusted hazard ratio (HR): 5.34 [1.67-17.09], p = 0.0048) and of incident hepatic decompensation (adjusted HR: 2.15 [1.39-3.34], p = 0.0006) [21].…”

“…The network meta-analysis conducted by Penissi et al, which evaluated data from 15 phase 2 and 3 RCTs, reported a pooled estimate rate of NASH resolution (without worsening of fibrosis) of 17% ([12-23%], p < 0.01), and of 21% ([13-31%], p < 0.01) for at least one stage of fibrosis improvement without worsening of NASH [52]. Finally, Ampuero and colleagues reported in their meta-analysis of 27 RCTs a pooled efficacy for NASH resolution of 10% [7][8][9][10][11][12], and 18% [15][16][17][18][19][20][21] for improvement in fibrosis in the placebo arms [53].…”

“…Diet and alcohol intake. There are sparce high-quality data evaluating the impact of diet or dietary components on liver fibrosis progression in subjects with NAFLD/NASH [17]. Higher caloric intake was shown to be positively associated with NAFLD, but there is not enough solid evidence regarding the correlations with the progression of NASH-associated fibrosis [99].…”

Role of the HIF-1α/BNIP3 Signaling Pathway in Recurrent Hepatocellular Carcinoma and the Mechanism of Traditional Chinese Medicine

“… 3 Alcohol dependence, smoking, old age, obesity, insulin resistance, and type 2 diabetes are also risk factors for HCC. 4 The invasive potential, metastasis, lower surgical resection rate, higher recurrence rate, and insensitivity to chemotherapy are fundamental causes of the higher mortality rate linked to HCC compared with other types of cancer. 5 The higher recurrence rate of HCC after surgery is the main reason affecting the long-term survival rate of patients.…”