Patología Hepática y Carcinoma Hepatocelular

Pathophysiology

• Hepatocellular carcinoma (HCC) originates from hepatocytes, the main functional cells of the liver.
• Chronic liver damage and inflammation, often resulting from cirrhosis, are crucial factors driving HCC development.
• Genetic mutations and epigenetic alterations play a significant role in the transformation of normal hepatocytes to cancerous cells.
• These changes activate oncogenes or inactivate tumor suppressor genes, leading to uncontrolled cell growth and division.
• Mechanisms involved include altered DNA repair, cell cycle regulation, and angiogenesis (formation of new blood vessels).
• Inflammation and oxidative stress create a microenvironment conducive to carcinogenesis.
• Viral hepatitis (B and C) and alcohol use disorder are major chronic liver diseases implicated in HCC development.
• Hepatocyte damage and regeneration contribute to the accumulation of genetic mutations in these cells.

Risk Factors

• Chronic hepatitis B virus (HBV) infection is a significant risk factor globally, especially in endemic areas.
• Chronic hepatitis C virus (HCV) infection is another critical risk factor increasing HCC risk substantially.
• Alcohol-related liver disease (ALD) is a substantial risk factor, with a higher risk of HCC associated with increased alcohol consumption over time, particularly excessive alcohol intake.
• Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH), is becoming a growing concern correlating with a rise in obesity.
• Genetic predisposition, such as familial adenomatous polyposis (FAP) or hereditary hemochromatosis, can increase the risk of liver cancer.
• Exposure to aflatoxins, particularly in food crops in some regions, is an environmental risk factor.
• Cirrhosis, a late stage of various liver diseases, substantially increases HCC risk.
• Dietary factors, including specific dietary habits and insufficient consumption of certain essential nutrients and/or vitamins, might play a role.

Diagnostic Methods

• Imaging techniques are vital in detecting HCC.
• Ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) are used to identify liver masses and assess their characteristics.
• Contrast-enhanced imaging helps distinguish between benign and malignant lesions.
• Liver biopsy remains a crucial method for confirming the diagnosis, although its invasiveness and potential complications should be considered.
• Serum biomarkers, such as alpha-fetoprotein (AFP), are used as screening markers, but their sensitivity and specificity are not always high enough for definitive diagnosis.
• Advanced techniques like elastography and molecular imaging add specificity to diagnostic methods.
• Liver biopsy (tissue sample taken from the liver) is usually necessary for a definitive diagnosis, but it is usually used as a last resort.

Treatment Options

• Treatment options for HCC depend on the stage of the disease, patient's general health, and other factors.
• Surgical resection (removal of the tumor and surrounding tissue) is a potentially curative option for early-stage HCC, but it is not always feasible.
• Liver transplantation is an option for patients with HCC and end-stage liver disease when a suitable donor organ is available.
• Radiofrequency ablation (RFA) and microwave ablation (MWA) are minimally invasive techniques to destroy the tumor.
• Transarterial chemoembolization (TACE) delivers chemotherapy directly to the tumor through the hepatic artery.
• Systemic therapies, such as chemotherapy, targeted therapies, and immunotherapy are considered for advanced cases.

Prognosis

• The prognosis for HCC varies considerably, often depending on disease stage and the patient’s response to treatment at the time of diagnosis.
• Early-stage HCC with localized disease can be cured with surgery or other localized therapies, but as the disease progresses, survival rates decrease.
• Liver transplantation can provide a chance for long-term survival when appropriate, especially in early-stage liver cancer cases.
• Complications of the disease and treatments, such as liver failure, liver decompensation and side effects from treatments, can also affect prognosis.
• The patient's general health, age, and presence of co-morbidities significantly influence survival rates.