Liver cancer is a malignancy that originates in the cells of the liver or the bile ducts within it. Tracing the recognition of this disease involves moving from ancient accounts of severe illness to the precise pathological science of today. Early, descriptive observations of symptoms eventually led to the formal medical definition and accurate classification of the disease.
Early Observational History
Ancient medical practitioners recognized the fatal nature of severe liver dysfunction through observable signs. Texts like the Egyptian Papyrus Ebers, dating to 1550 BCE, described the swelling and hardness of the abdomen, now known as ascites. Greek physicians, including Hippocrates, referred to this fluid accumulation as hydrops or “dropsy,” linking it to severe internal illness.
These early accounts focused on profound jaundice, the yellowing of the skin and eyes, and a palpable, hardened liver. The Roman physician Galen, in the second century CE, also listed a “hardened liver” as a cause of abdominal swelling. These observations were purely symptom-based, grouping complex ailments under broad, non-specific terms that lacked understanding of a specific malignant process.
Formal Pathological Recognition
The understanding of liver disease transformed with the rise of morbid anatomy and systematic autopsies in the 19th century. This discipline correlated clinical symptoms observed during life with physical changes found in organs after death. Austrian pathologist Carl von Rokitansky was a central figure in this shift, performing tens of thousands of autopsies and documenting his findings in his influential Handbuch der pathologischen Anatomie (1842–1846).
Rokitansky’s work established a scientific foundation for classifying diseases based on anatomical changes, moving away from purely symptomatic descriptions. The formal discovery of liver cancer required microscopically differentiating it from other liver conditions, especially common metastatic tumors that spread to the liver from elsewhere. Before this era, any liver mass was likely considered a secondary tumor, as the liver is a frequent site for cancer spread.
Pathologists began recognizing specific features of tumors originating from the liver’s own cells (hepatocytes) or the bile duct cells. This precise differentiation, occurring around the mid-19th century, established the concept of primary liver carcinoma. The ability to distinguish a tumor that started in the liver from one that had merely spread there marked the disease’s formal discovery and classification.
Modern Categorization and Etiology
The 20th century brought a deeper understanding of the types and causes of primary liver cancer. The disease was categorized into two main forms: Hepatocellular Carcinoma (HCC), arising from the main liver cells, and Cholangiocarcinoma (CC), developing from the cells lining the bile ducts. HCC accounts for the vast majority of primary liver cancer cases, typically between 70% and 85%.
A major advance was the identification of the underlying causes, or etiology, of the disease. In 1966, the Hepatitis B virus (HBV) was discovered. By the early 1980s, large studies demonstrated a clear causal link between chronic HBV infection and the development of HCC, establishing a human cancer caused by a virus.
The Hepatitis C virus (HCV) was identified later, and its connection to HCC was established, particularly in the Western world. Both chronic HBV and HCV infections lead to persistent inflammation and scarring of the liver, known as cirrhosis, which is a major precursor to HCC. Cirrhosis resulting from alcohol use and non-alcoholic fatty liver disease (NAFLD) are also recognized as significant risk factors. These discoveries have transformed the medical approach, shifting the focus toward prevention through viral screening and vaccination.