Primary hepatocellular carcinoma and metabolic syndrome: An update

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The incidence of hepatocellular carcinoma has increased dramatically by 80% over the past two decades in the United States. Numerous basic science and clinical studies have documented a strong association between hepatocellular carcinoma and the metabolic syndrome. These studies have documented that, in most patients, non-alcoholic fatty liver disease is the hepatic manifestation of the metabolic syndrome, which may progress to hepatocellular carcinoma through the cirrhotic process. However, minority of patients with non-alcoholic fatty liver disease may progress to hepatocellular carcinoma without cirrhosis. This review summarizes the current literature of the link between hepatocellular carcinoma and metabolic syndrome with special emphasis on various components of the metabolic syndrome including risk of association with obesity, diabetes mellitus, hyperlipidemia, and hypertension. Current understanding of pathophysiology, clinical features, treatments, outcomes, and surveillance of hepatocellular carcinoma in the background of metabolic syndrome and non-alcoholic fatty liver disease is reviewed. With the current epidemic of metabolic syndrome, the number of patients with non-alcoholic fatty liver disease is increasing. Subsequently, it is expected that the incidence and prevalence of HCC will also increase. It is very important for the scientific community to shed more light on the pathogenesis of HCC with metabolic syndrome, both with and without cirrhosis. At the same time it is also important to quantify the risk of hepatocellular carcinoma associated with the metabolic syndrome in a prospective setting and develop surveillance recommendations for detection of hepatocellular carcinoma in patients with metabolic syndrome.

Germline loss of PKM2 promotes metabolic distress and hepatocellular carcinoma

“…6F). Human patients with systemic metabolic disease also exhibit increased systemic inflammation (Rahman et al 2013), and increased circulating Interleukin-6 (IL-6) is associated with this type of obesity-induced inflammation (Mauer et al 2015). Therefore, we characterized the circulating cytokine profile of young and old Pkm2 −/− male mice together with age-and sex-matched wild-type littermate controls.…”

“…Metabolic disease and HCC are also more prevalent in men (El-Serag and Rudolph 2007). The gender disparity observed in human HCC has been attributed in part to the inhibitory action of estrogen on inflammation and, specifically, on the production of IL-6 (Naugler et al 2007;Barros and Gustafsson 2011;Rahman et al 2013). Thus, an influence of inflammation and the immune system may underlie the predisposition for metabolic distress and HCC in Pkm2 −/− mice.…”

“…Pkm2 −/− mice appear to be a model that can be used to further investigate the links between systemic metabolism, the immune system, and HCC progression. As a growing percentage of HCC cases are associated with metabolic syndrome, type 2 diabetes, and NAFLD (Baffy et al 2012;Rahman et al 2013;Byrne and Targher 2015), a better understanding of the mechanistic link between systemic metabolic disease and HCC formation is of crucial importance. An advantage of this mouse model is that HCC arises in the context of systemic metabolic distress, appears to be induced by non-cell-autonomous events, and does not involve the use of chemical tumor promoters.…”

Ultrasound-Guided Intratumoral Delivery of Doxorubicin from in Situ Forming Implants in a Hepatocellular Carcinoma Model

“…Hepatocellular carcinoma (HCC) is the most common primary malignancy that occurs in the liver, with more than 500,000 new cases discovered annually worldwide [1,2]. HCC is the third most common cause of death worldwide [2,3], and the number of reported cases is predicted to increase in developed countries over the course of the next decade [4].…”

“…HCC is the third most common cause of death worldwide [2,3], and the number of reported cases is predicted to increase in developed countries over the course of the next decade [4]. In the USA alone, there has been an 80% increase in the incidence of HCC during the last 20 years, with incidence rates tripling between 1975 and 2005 [2,4,5]. For patients who are diagnosed early, liver transplantation or tumor resection are the most successful treatment options, but because HCC is often asymptomatic, in many cases detection occurs after significant disease progression has already occurred.…”