Hepatocellular Carcinoma (HCC) – Symptoms, Causes, Diagnosis and Treatment

Hepatocellular Carcinoma (HCC) – Symptoms, Causes, Diagnosis and Treatment: The liver is the three pounds weighing, meaty organ, that aligns at the right corner of the belly. It has two main lobes, the right and the left. Lying under it is the gallbladder, pancreas and intestine. The liver’s main function is to absorb, digest and process food. It also metabolizes drugs and detoxifies chemicals along with filtering the coming blood. The blood clotting proteins are also formed by the liver.

Hepatocellular Carcinoma (HCC)

Cancer due to tumour formation by the hepatic cells of the liver is known as hepatocellular carcinoma (HCC). It is the most common adult liver cancer and the third leading cause of death globally.

Chronic liver swelling and severe damage leads to fibrosis and cirrhosis. These ailments cause the development of HCC. Cirrhosis is caused due to some serious infections (hepatitis B, C), and toxin exposure (alcohol, aflatoxin, pyrrolizidine, etc.). Further, the presence of hemochromatosis and AAD (alpha 1-antitrypsin deficiency) elevates the chances of HCC.  Its diagnosis depends upon the histology; the treatments are usually given after identifying the damage, cause and stage of cancer.

Lung Cancer

Stomach Cancer

Cancer Symptoms

Symptoms

The HCC generally has symptoms similar to that of chronic liver disease. During the time of cancer detection, HCC may be present with worsening symptoms or some non-specific symptoms. These include –

• Abdominal pain,
• Nausea and vomiting,
• Weakness, tiredness,
• Loss of appetite, unexplained bruises,
• Jaundice-like symptoms, yellow-green pigmentation of skin due to high bilirubin accumulation,
• Bloating in the stomach,
• Pale, chalky bowel movements,
• Dark-colored urine,
• Unexplained cachexia or obeseness,
• Fluid accumulation, causing inflammation in the abdomen (Ascites),
• Fever and hematemesis (blood vomiting),
• Lump in the abdomen,
• Encephalopathy (impaired brain functions due to viral infections or toxin encounter),
• Hypercalcemia (elevated calcium amount in the body),
• Erythrocytosis (high RBCs in the body), etc.

For Reference:- https://www.cancer.gov/types/liver/what-is-liver-cancer

Causes

• In Ascites, the accumulation of fluid can be from 25 ml to 1 litre of fluid in the abdominal cavity. It leads to shortness of breath, inflammation in the abdomen, increase weight, pain in the abdomen, difficulty breathing, etc.
• Chronic viral hepatitis comprises both hepatitis B and hepatitis C viral infections and can cause both critical and lingering infections. The prevalence of these infections ultimately causes hepatic cell damage and leads to tumour development.
• Cirrhosis can also happen due to too much drinking, which ultimately lead to development of HCC.
• Unknowing consumption of Aflatoxin is a potential carcinogenic and mutagenic compound. This is produced by Aspergillus species, commonly growing in decaying fruits, vegetables, moist soil etc.
• Non-Alcoholic Fatty Liver Disease (NAFLD) is another risk factor for HCC. This ailment is due to the build-up of fat in liver. This leads to NASH (non-alcoholic steatohepatitis) which results in liver inflammation and ultimately to cirrhosis, liver failure, and HCC.

• The A1AT deficiency is a genetic disorder that can lead to the development of cirrhosis and HCC. A1AT is synthesized by hepatic cells and its deficiency is due to a mutation in hepatic cells that ultimately cause HCC.
• Wilson’s disease causes the excess accumulation of copper in the liver and therefore causes HCC, although the research is limited.
• With hepatitis, the body needs repeated blood transfusions, but the accidental coexistence of hepatitis and haemophilia leads to a loss of coagulability, which leads to the development of HCC.
• Some liver disorders such as biliary atresia, cholestasis, glycogen storage disease, cirrhotic diseases, etc. are also risk factors for HCC.
• Low or high level of circulating insulin is also a risk factor for developing hepatocellular carcinoma. This occurs as a result of metabolic disorders.

For Reference:- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047212/

Diagnosis

The diagnosis is a critical step as it helps in detecting the actual scenario and helps in deciding the treatment as well. Over the past years, these techniques have advanced with advancements in research.   Including imaging tests, histological tests, biopsy techniques, etc.

• Ultrasound – doctors recommend ultrasound twice a year in patients with cirrhosis. On ultrasound, HCC often appears as a small hypoechoic lesion with ill-defined thick borders at an irregular interval. As the tumour grows, it can sometimes appear uneven with fibrosis, fatty changes, and calcifications. This heterogeneity may resemble cirrhosis and the surrounding liver parenchyma.
• Blood test – this is done to measure the tumour marker in the blood, i.e., alpha-fetoprotein (AFP). The active HCC is marked by a high level of AFP in the blood.
• CT scan and MRI – in both techniques the HCC gives three distinct patterns of growth, single tumour, multiple tumours and poorly defined tumour with infiltrative growth pattern. CT scan was found with 69% sensitivity and 94% specificity. The MRI scan is advantageous over a CT scan as it gives more clear images with high resolution, with radiations. Therefore, MRI has more sensitivity and specificity than CT scans and ultrasounds.
• Biopsy – in this the doctors take samples from your liver for microscopic examination. They can even numb the area above your liver and then puncture the skin with a needle and put that into the liver directly to take samples.
• Microscopic examination – under a microscope, the tumour appears as a nodule or invasive tumour. These tumour nodules may be round or oval with circumference but not capsulated (in case of bile production). The hepatic cells can exhibit for morphologies under a microscope, fibro lamellar (affects people with healthy liver and is laminated fibrous layers interspersed between the tumour cells), pseudo glandular (mass of tissue, pyramid in shape), pleomorphic (giant cells), and normal healthy cells.

For Reference:- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2023919/

Stages of liver cancer

The stages of liver cancer are useful in the prognosis of the disease as well as the liver function. The classification system should include the tumour size, number of tumours and spread to other organs or surrounding. It should further include liver function, ascites presence, the health status of a patient, and the presence of symptoms. The most accepted staging is ‘The Barcelona Clinic Liver Cancer Staging Classification’ having all the above points considered.

The Barcelona Clinic Liver Cancer Staging Classification –

S.No.	Stage	Description	Child-Pugh class	Survival rate and appropriate  treatment
1	0  (Very Early)	Single tumor nodule, <3 cm	A	>90% for five years (resection)
2	A (Early)	1-3 tumor nodule, all <3 cm	A or B	>50% for five years (curative transplant)
3	B (Intermediate)	Tumour with multiple nodules	A or B	16 months of survival (transcatheter arterial chemoembolization)
4	C (Advance)	Invasive and extra-hepatic spread	A or B	10.5 months (tyrosine kinase inhibitor therapy)
5	D (Terminal)	Severe liver damage	C	6 months  (conservational therapy)

Treatment

There are various treatment options available for hepatocellular carcinoma available –

• Radiation – this uses high radiation energy to kill cancer cells or reduce tumour size.  This can be given internally or externally. In internal radiation therapy, the doctors inject small radio-active particles into the artery, these particles then reach your liver with blood and then block the blood supply to a tumour. Whereas in external radiation therapy, a beam is made to strike your skin surface just above the liver or chest to destroy cancer cells.
• Chemotherapy – this is done via tube. A tube is inserted into the artery that supplies blood to the liver tumour. The chemo drugs are then directly supplied into that artery, blocking blood supply and starving the tumour cells to death. The liver receives blood through other arteries to perform its functions.
• Chemoembolization – in this the chemo drugs are placed directly into the liver for tumour cell death.
• Alcohol injection – Your doctor will inject an alcohol injection directly into the tumor using ultrasound. This is also known as transdermal ethanol injection.
• Targeted therapy – it is the therapy designed to destroy the particular tumour cells directly. Some targeted therapies focus on blocking blood supply while others focus on targeting proteins present in the tumour cells.
• Immunotherapy – in this therapy, certain immune-building or enhancing drugs are used. These drugs called an immune checkpoint, stimulate the immune system and kill cancer cells.
• Cryoablation – in this therapy, a doctor puts a probe in the tumour and passes cold gas that kills cancer cells.
• Radiofrequency ablation – this therapy is the same as that of Cryoablation, the difference is that it uses electric current instead of cold gas to kill cancer cells.
• Partial Hepatectomy – this is the surgical procedure that involves the removal of the infected part of the liver. Then medicines are used to heal after surgery.
• Liver transplant – if the whole liver is infected the liver transplant is the last option. But for this, you have to wait for the donor. New liver will be available for the recently died person, or donor of your sage and the same blood group. As the waiting time can be too long, your doctor might suggest other treatment options until the new liver is available.

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