Journal of Clinical & Experimental Pathology
Open Access

Hepatocellular Carcinoma (HCC) is the most common form of primary liver cancer, causing approximately 75% of all cases. It develops from hepatocytes, the primary liver cells, and is a main cause of cancer-related deaths globally, particularly in areas with a high prevalence of chronic liver illness. Knowing about HCC is important not only for clinical implications, but also for pathological reasons, as it provides illumination on carcinogenesis, liver disease development, and diagnostic advancements. HCC is a major health problem worldwide, with a higher frequency in Asia and Africa due to the prevalence of Hepatitis B Virus/ Hepatitis C Virus (HBV/HCV) infections. In recent years, the incidence of HCC in Western countries has increased due to Non-Alcoholic Fatty Liver Disease (NAFLD) and metabolic syndrome, both of which are associated with obesity and diabetes. HBV and HCV infection are the leading causes of HCC. Chronic inflammation induced by these viruses leads to liver cirrhosis, a key factor to HCC. Irrespective of its cause Cirrhosis, is the most significant risk factor for the development of HCC. Chronic viral hepatitis, alcohol abuse, NAFLD, and autoimmune liver disorders can all cause liver cirrhosis.

Obesity and type 2 diabetes have caused an increase in Non- Alcoholic Fatty Liver Disease (NAFLD) instances, which may lead to NASH, cirrhosis, and ultimately, HCC. Chronic high alcohol consumption causes alcoholic liver disease, cirrhosis, and raises the risk of HCC. Aflatoxin, a carcinogen produced by Aspergillus fungi in contaminated food, has been associated to a high rate of HCC in underdeveloped nations. HCC is caused by complex genetic and epigenetic changes in hepatocytes, resulting in uncontrolled cell proliferation and tumor growth. Persistent liver inflammation, as observed in chronic HBV or HCV infections, causes hepatocyte damage and regeneration growth. Over time, this increases the risk of genetic alterations, which promote transformation into cancer. Liver fibrosis, caused by chronic liver injury, affects normal liver architecture and produces a pro-tumorigenic milieu by activating hepatic stellate cells and releasing fibrogenic proteins. Changes in tumor suppressor genes and oncogenes cause HCC development. Epigenetic changes, such as DNA methylation and histone modifications, also contribute to liver carcinogenesis. HCC cells frequently undergo metabolic alterations that promote rapid growth and survival in a hostile microenvironment. Cancer cells, particularly HCC, have altered glucose metabolism (the Warburg effect), accelerated lipid production, and higher tolerance to oxidative stress.

HCC is frequently asymptomatic in its early stages, making early detection difficult. Jaundice, weight loss, stomach pain, and ascites are common symptoms in the later stages of the disease. Patients with underlying liver cirrhosis or viral hepatitis are routinely monitored through surveillance programs, which often involve imaging techniques such as ultrasonography and biomarker testing. The diagnosis of HCC is based on a combination of imaging modalities (ultrasound, CT scan, MRI) and, in some situations, biopsies. Noninvasive imaging techniques, such as multiphase contrast-enhanced CT or MRI, can detect HCC-specific characteristics such arterial phase hyperenhancement and venous phase washout. Imaging is essential for identifying and staging HCC. Although imaging is usually sufficient for diagnosis in cirrhotic patients, liver biopsy is occasionally required, especially for unusual lesions. Histopathological investigation remains the accepted level for determining HCC and its subtypes. Pathologists evaluate cellular architecture, tumor differentiation, and the presence of vascular invasion, which is essential for prognosis. Treatment for HCC is determined by the disease's stage, liver function, and patient performance status. Liver resection may be a cure for those with earlystage HCC and preserved liver function. However, it is only possible in a small percentage of individuals due to underlying cirrhosis or multifocal illness. For individuals with early HCC with cirrhosis, liver transplantation is an excellent curative option since it treats both the cancer and the underlying liver disease.

The outlook for patients of HCC varies greatly depending on the stage of disease, liver function, and therapy response. Early-stage HCC, particularly when treated with surgery or transplantation, has a rather good prognosis, with 5-year survival rates exceeding 70% in some instances. However, advanced-stage HCC has a significantly reduced outcome, with median survival times estimated in months. Pathologists are involved in the identification and validation of biomarkers that can be utilized for early detection of HCC, therapy response assessment, and prognostic prediction. For example, AFP is commonly utilized, although other biomarkers such as Des-Gamma- Carboxy Prothrombin (DCP) and circulating Tumor DNA (ctDNA) are being studied. Hepatocellular carcinoma is a major public health issue, causing significant illness and death worldwide. While the risk factors for HCC, such as viral hepatitis, cirrhosis, and metabolic problems, are well understood, ongoing clinical and experimental pathology research is still addressing the molecular mechanisms which cause this disease. This knowledge is essential for increasing early detection, improving diagnostic techniques, and developing targeted medicines that provide hope for better results.