Association between hereditary hemochromatosis and hepatocellular carcinoma: a comprehensive review

Abstract

Hepatocellular carcinoma (HCC) is a significant global health problem with high morbidity and mortality. Its incidence is increasing exponentially worldwide with a close overlap between annual incidence and death rates. Even though significant advances have been made in HCC treatment, fewer than 20% of patients with HCC are suitable for potentially curative treatment. Hereditary hemochromatosis (HH) is an important genetic risk factor for HCC. HH is an autosomal recessive disorder of iron metabolism, characterised by elevated iron deposition in most organs including the liver, leading to progressive organ dysfunction. HCC is a complication of HH, nearly always occurring in patients with cirrhosis and contributes to increased mortality rates. Identifying the susceptibility of development of HCC in HH patients has gained much traction. This review summarises the current knowledge with regard to the association of HH and HCC in order to encourage further research. In this review, we focus particularly on HFE gene-related HH. Herein, we highlight and discuss emerging clinical research which addresses the prevalence of HCC in HH patients and the coincidence of HH with other risk factors for HCC development. We also focus on the therapeutic tools in the management of HCC associated with HH.

Pre-Clinical Insights into the Iron and Breast Cancer Hypothesis

“…However, the modest trend toward an increase in urinary 8-isoprostane F-2 alpha (a useful index of overall in vivo lipid peroxidation) with increasing dietary iron is consistent with the possibility that in vivo, iron may mediate oxidative events in only a limited number of organ sites. It is of interest that iron-associated liver carcinogenesis is an active area of investigation [ 65 , 66 ].…”

Imaging of the Liver and Pancreas: The Added Value of MRI

“…The liver is the first organ that shows iron overload because one of its functions is to store iron within hepatocytes and Kupffer cells. Calculating the amount of iron deposition can lead to a better management of patients that suffer from this disease as an untreated high iron overload may lead to a cirrhosis with a risk to develop an HCC 20-fold higher than in the general population [3].…”

Immunometabolic factors contributing to obesity-linked hepatocellular carcinoma

“…Most commonly is chronic viral hepatitis, driven by hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Other factors include alcoholic liver disease, metabolic liver diseases such as hereditary hemochromatosis and Wilson’s disease ( Gunjan et al, 2017 ; Jayachandran et al, 2020 ), and exposure to toxins such as aflatoxin B1 ( Cao et al, 2022 ). Of rising concern is the impact of non-alcoholic fatty liver disease (NAFLD), which is expected to become the most common cause ( Ascha et al, 2010 ; Karagozian et al, 2014 ; Estes et al, 2018a ; Estes et al, 2018b ; Younossi et al, 2018 ; Ioannou, 2021a ).…”