From the Guidelines
A hepatoma, also known as hepatocellular carcinoma (HCC), develops through a multistep process typically occurring in the setting of chronic liver damage, as supported by the most recent evidence from 2021 1. The most common pathway begins with chronic inflammation of the liver, often caused by hepatitis B or C virus infections, alcohol abuse, non-alcoholic fatty liver disease, or exposure to aflatoxins. This persistent inflammation leads to cycles of liver cell damage and regeneration, creating an environment where DNA mutations can accumulate in hepatocytes. Over time, these genetic alterations disrupt normal cellular growth controls, allowing abnormal cells to proliferate unchecked. The liver attempts to repair itself by forming fibrous tissue, leading to cirrhosis in many cases. Within this cirrhotic environment, some hepatocytes undergo malignant transformation, developing into cancerous nodules that can grow, invade surrounding tissues, and potentially metastasize. Key risk factors that accelerate this process include:
- Male gender
- Older age
- Obesity
- Diabetes
- Certain genetic conditions Regular screening with ultrasound and alpha-fetoprotein testing is recommended for high-risk individuals to detect hepatomas at earlier, more treatable stages, as emphasized in recent guidelines 1. It is essential to note that the management of patients with HCC is complicated by the presence of underlying liver disease, and treatment decisions should be made by a multidisciplinary team 1. The rising incidence of HCC worldwide, partly due to the HBV and HCV epidemics and the successful treatment of other complications of cirrhosis, underscores the importance of preventive strategies and early detection 1.
From the Research
Hepatoma Development
The development of hepatoma, also known as hepatocellular carcinoma (HCC), is a complex process involving multiple genetic alterations and risk factors.
- Environmental, infectious, nutritional, metabolic, and endocrine factors contribute directly or indirectly to hepatocarcinogenesis, as stated in the study 2.
- Chronic viral hepatitis B and C, aflatoxin exposure, alcohol consumption, and iron overload are significant risk factors for HCC, and their synchronous occurrence in a single patient or population further increases the risk 2, 3.
- HCC is commonly associated with chronic hepatitis and liver cirrhosis, and different genes have been implicated in its pathogenesis, including those regulating DNA damage response, cell cycle control, growth inhibition, and apoptosis 2, 4.
Genetic Alterations
The development of HCC involves the accumulation of multiple genetic alterations, leading to changes in the genomic landscape.
- Recent studies using genomic technologies have shed new light on the genomic landscape of HCC, uncovering candidate driver genes and providing direction for future personalized treatment approaches 4.
- The pattern of genomic alterations in HCC shows great variability, often between two different HCCs from a single patient, and there is no evidence for an ordered sequence of genomic events leading to hepatocarcinogenesis 2.
Risk Factors and Disease Progression
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging as important risk factors for HCC, particularly in developed countries 3, 5.
- Increased body mass index and diabetes mellitus are associated with developing NAFLD and NASH, which can progress to liver cirrhosis and even HCC 5.
- HCC evolves from precancerous lesions, and well-differentiated HCC further progresses to a less differentiated form, highlighting the need for objective morphological, phenotypic, and genetic markers for disease progression 2.