Clinical heterogeneity in patients with non-alcoholic fatty liver disease-associated hepatocellular carcinoma

ABSTRACT

Introduction

The indisputable increase in nonalcoholic Fatty Liver Disease (NAFLD) prevalence (25% of population) has consequently led to an increase in Hepatocellular Carcinoma (HCC) and liver-related mortality worldwide. The characteristics of patients with HCC, secondary to NAFLD, are older age, large tumors due to late diagnosis, often without cirrhosis and high prevalence of the metabolic syndrome components, leading to an increased mortality rate. Although the mechanisms of disease remain partially obscure, insulin resistance, oxidative stress, apoptosis, iron overload, and excessive local and systemic inflammation are identified as culprits for hepatocarcinogenesis in the presence of NAFLD.

Area covered

In this review, the authors report that there are no uniform guidelines for surveillance and early diagnosis in this patient group. Barcelona Clinic Liver Cancer staging is generally applicable to HCC due to NAFLD and management depends on liver function, tumor characteristics, and cardiovascular comorbidity. Evidence suggests that HCC due to NAFLD can be associated with worse survival due to late diagnosis.

Expert opinion

The need for effective early diagnosis and management of NAFLD is urgent, considering the galloping incidence of the obesity and the fact that liver cirrhosis and HCC due to NAFLD will become the first indication for liver transplantation in foreseeable future.

KEYWORDS:

• Liver steatosis
• NAFLD
• hepatocellular carcinoma
• metabolic syndrome
• cirrhosis
• survival

Article highlights

• NAFLD has recently emerged as a global liver health menace and is one of the most important risk factors for HCC worldwide.

• Current guidelines on HCC suggest that surveillance in patients with NAFLD should not be routinely carried out, unless they are at high risk for HCC. Subgroups of NAFLD patients at high risk for HCC are older age patients, suffering from diabetes mellitus and those with high alcohol consumption, and presence of liver fibrosis or cirrhosis.

• Given the expected rise in NAFLD prevalence in the foreseeable future, more trials are needed in order to identify any clinical, laboratory, imaging or genetic-molecular markers for selecting NAFLD patients at high-risk of developing HCC. These patients should then be monitored for the early detection of HCC.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

None declared