Paraneoplastic syndromes in hepatocellular carcinoma: a review

ABSTRACT

Introduction

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and a significant proportion (20–40%) of patients with HCC develop paraneoplastic syndromes (PNS). Despite this, there is a paucity of clinical evidence regarding PNS in HCC.

Areas covered

A systematic search was performed to identify relevant case studies regarding PNS in HCC. Another search was conducted to identify studies that evaluated the impact of PNS on survival outcomes in HCC. Since there are currently no international guidelines for PNS in HCC, this review aims to provide comprehensive summaries and recommendations of PNS in HCC, including the pathophysiology, clinical features, diagnostic approach, and management, so that clinicians remain guided in caring for HCC patients with PNS. In general, PNS are associated with poorer survival outcomes and negative prognostic markers of HCC.

Expert opinion

The presence of PNS has a significant influence on survival rates and clinical outcomes of patients with HCC. They contribute to significant morbidity, influencing patients’ quality of life and fitness for curative and palliative therapies. Therefore, it is paramount for PNS to be integrated into routine investigations after diagnosing HCC to guide further management and prognostication of the disease.

KEYWORDS:

• Erythrocytosis
• hepatocellular carcinoma
• hypercalcemia
• hypercholesterolemia
• hypoglycemia
• paraneoplastic syndrome
• thrombocytosis

Article Highlights

• This review provides a comprehensive summary of PNS in HCC, including the pathophysiology, clinical features, and implications on clinical outcomes.

• There is currently no guideline for the diagnosis and management of PNS in HCC. This article provides recommendations for the diagnostic approach and the most effective therapies to manage each syndrome.

• In general, PNS in HCC is associated with poorer survival outcomes and negative prognostic factors such as larger tumor volume, portal vein involvement and metastasis.

• Erythrocytosis is the only PNS that is not consistently associated with poorer survival outcomes. Erythrocytosis may be associated with better survival outcomes in HCC patients undergoing hepatic resection; and poorer survival outcomes in patients undergoing trans-arterial chemoembolization (TACE), and further studies regarding the survival outcomes associated with erythrocytosis are warranted.

• PNS in HCC are manifestations of altered tumor biology and influence the tumor’s responsiveness to conventional therapies. Studying these pathological mechanisms can provide essential insights in developing more efficacious targeted anti-cancer therapies for improving clinical outcomes.

Declaration of interests

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.

Author Contributions

All authors contributed to the writing and editing of the manuscript.