HEPATOCELLULAR CARCINOMA

• Hepatocellular carcinoma


  The most common form of liver cancer, where the proliferation of cancer cells primarily happens in the hepatocytes
• Hepatocellular carcinoma


  • It is an aggressive or fast-growing cancer
  • It is most common in people with advanced liver disease, like cirrhosis of the liver
• Cirrhosis


  A severe condition where liver cells are damaged and replaced with scar tissue, making a person more prone to hepatocellular carcinoma
• Metabolic dysfunction-associated steatotic liver disease (MASLD)


  A condition that causes excess fat to build up in the liver, making a person more likely to have it if they have obesity, an inherited metabolic syndrome, or Type 2 diabetes
• Etiology of hepatocellular carcinoma

  • Viruses
  • Inherited diseases
  • Fatty liver disease
  • Metabolic syndrome
  • Carcinogens
• Hepatitis B


  A viral infection caused by hepadnaviridae that can lead to hepatocellular carcinoma even without liver cirrhosis or before cirrhosis occurs
• Hepatitis C


  A viral infection caused by flaviviridae that leads to chronic hepatic inflammation, liver cirrhosis and hepatocellular carcinoma development
• Hepatitis D


  A viral infection caused by viriods that increases the risk of developing hepatocellular carcinoma in patients with chronic hepatitis D compared to those infected with HBV
• Hereditary hemochromatosis


  An autosomal recessive disorder of iron metabolism that leads to progressive liver dysfunction and cirrhosis
• Alpha-1 antitrypsin deficiency


  A condition that leads to an accumulation of polymers of A1AT mutants in the ER of hepatocytes, causing liver disease in childhood and cirrhosis and/or hepatocellular carcinoma in adulthood
• Wilson's disease


  A condition caused by the accumulation of copper in the liver, brain or other organs due to mutation of ATP7B gene, resulting in toxic levels of copper in the hepatocytes
• Hepatic porphyria


  Conditions in which the enzyme deficiency occurs in the liver
• Nonalcoholic fatty liver disease (NAFLD)


  The hepatic manifestation of the metabolic syndrome, closely associated with obesity and diabetes, that can evolve into non-alcoholic steatohepatitis (NASH)
• Alcoholic fatty liver disease


  A condition that induces cirrhosis and promotes hepatocellular carcinoma, with females being more susceptible to the toxic effects of alcohol than males
• Diabetes mellitus


  A component of the metabolic syndrome that has been shown to attribute about 7% of the hepatocellular carcinoma cases worldwide
• Obesity


  A pathological state characterized by insulin resistance, hyperinsulinemia, and inflammation that is also closely associated with hepatocellular carcinoma
• Aflatoxin


  A potent liver carcinogen produced by the Aspergillus fungus that contaminates foodstuffs and induces mutation in the p53 tumor suppressor gene
• Tobacco smoking


  The chemicals in tobacco smoke (4-aminobiphenyl and polycyclic aromatic hydrocarbons) cause hepatotoxicity
• Environmental toxins


  Chemicals such as vinyl chloride, arsenic, cadmium, lead, nickel, toluene, dioxin, xylene, and DDT that have shown to increase the risk of hepatocellular carcinoma via induction of oxidative stress and telomere shortening
• Despite the significance of hepatocellular carcinoma, there is only an elemental understanding of the molecular, cellular and environmental mechanisms that drive disease pathogenesis, and there are only limited therapeutic options, many with negligible clinical benefit
• HBV-induced hepatocarcinogenesis


  1. Host–viral interactions

  2. Sustained cycles of necrosis–inflammation–regeneration

  3. Viral–endoplasmic-reticulum interactions (induction of oxidative stress)

  4. Viral integration into the host genome (and associated host DNA deletions)

  5. Activation of oncogenic pathways by various viral proteins
• HCV-induced hepatocarcinogenesis


  1. Evades the host's immune responses

  2. Promotes cirrhosis
• Alcohol-induced hepatocarcinogenesis


  1. Induction of inflammation

  2. Cycles of hepatocyte necrosis and regeneration

  3. Oxidative stress

  4. Cirrhosis
• Aflatoxin-B1-induced hepatocarcinogenesis


  Carcinogenic mutations
• Genetic events associated with the development of hepatocellular carcinoma

  • Inactivation of the tumour suppressor p53
  • Mutations in β-catenin
  • Overexpression of various ErbB receptor family members
  • Overexpression of the Met receptor
• Macroscopic groups of progressed hepatocellular carcinoma

  • Nodular
  • Massive
  • Diffuse or cirrhotomimetic
• Nodular hepatocellular carcinoma


  • Well-circumscribed neoplasm of spherical or ovoid shape, with well-defined margins and expansive growth pattern, often arising in the context of a cirrhotic liver, and formed by several juxtaposed nodules that can have different colors
• Massive hepatocellular carcinoma


  • Causes a marked increase in liver volume that appears to be mostly replaced by large tumor masses, with a soft consistency and variegated appearance due to the presence of necrosis and hemorrhagic areas
• Diffuse or cirrhotomimetic hepatocellular carcinoma


  • Characterized by the presence of numerous nodules, similar to each other in size and shape, which can reach several hundred and fill the entire liver
• Microscopic architectural changes in hepatocellular carcinoma

  • Trabecular
  • Solid or compact
  • Pseudoglandular or acinar
  • Macrotrabecular (more than 10 cells thick)
• Cytological alterations of neoplastic hepatocytes in hepatocellular carcinoma

  • Well-differentiated: appear very similar to normal hepatocytes, with nuclear crowding and increase in cytoplasmic basophilia
  • Poorly differentiated: characterized by irregular nuclei, cellular pleomorphism and giant cells with highly atypical nuclei
• Signs and symptoms of hepatocellular carcinoma

  • Vary depending on the size of the tumour and whether it has spread to other parts of the body
• The characteristic symptoms of hepatocellular carcinoma usually vary depending on the size of the tumour and whether it has spread to other parts of the body
• Hepatocellular carcinoma (HCC)


  • Absence of portal tracts
  • Presence of aberrant arteries
  • Architectural changes
  • Cytological alterations
• Architectural changes in well-differentiated HCC

  • Trabecular
  • Solid or compact
  • Pseudoglandular or acinar
  • Macrotrabecular (more than 10 cells thick)
• Cytological alterations in well-differentiated HCC

  • Similar to normal hepatocytes
  • Nuclear crowding
  • Increase in cytoplasmic basophilia
• Cytological alterations in poorly differentiated HCC

  • Irregular nuclei
  • Cellular pleomorphism
  • Giant cells with highly atypical nuclei
• Signs and symptoms of hepatocellular carcinoma

  • Swollen abdomen
  • Abdominal pain
  • Painless lump in belly
  • Jaundice
  • Fatigue
  • Nausea
  • Vomiting
  • Loss of hunger
  • Fever
  • Itchy skin
  • Sudden weight loss
  • Dark-coloured urine
  • Pale, chalky bowel movements
• Diagnosis for hepatocellular carcinoma

  1. Complete Blood Count

  2. Comprehensive Metabolic Panel

  3. Imaging Tests

  4. Biopsy
• Alpha-fetoprotein (AFP)


  Elevated in liver damage or cancer