Liver cancer is a cancer that begins in the cells of the liver. It has recently become a serious global health concern due to its high mortality and morbidity rates. Its incidence is higher in developing countries than in developed countries. Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, which develops in the hepatocytes (primary liver cells). Hepatoblastoma and intrahepatic cholangiocarcinoma are the other forms of liver cancer that are much less frequent. Liver cancer may develop in the liver (primary cancer) or it may spread from other organs like the breast, and colon (metastatic cancer).

Symptoms

In the early stages, patients with liver cancer do not exhibit any symptoms or signs. Slowly when the disease progresses, the following symptoms will appear:

• Unintentional weight loss

• Loss of hunger

• Pain and swelling in the upper abdomen

• Nausea and vomiting

• General weakness and fatigue

• Defecation of white chalky stools

• Yellowish discoloration of skin and eyeball

Diagnosis

There are several tests to detect liver cancer. Age, general health of the patient, type of liver cancer, signs, and symptoms are the factors that are considered when selecting a diagnostic test. The following is the list of tests for the diagnosis of liver cancer:

1. General history taking and physical examination: A proper medical, family, and occupational history of the patient is taken, and they are questioned about the symptoms experienced. They are also examined for any signs of the disease like the presence of lumps or anything that seems unusual.

2. Liver function tests: They are done to assess the performance of the liver. The levels of proteins and enzymes which help in the body metabolism like bilirubin, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, albumin, lactate dehydrogenase, and gamma-glutamyl transferase are measured in the blood. Measuring the prothrombin time (time taken for the blood to clot) also helps to assess the liver performance. An elevation in these levels may indicate signs of liver damage.

3. Imaging modalities: For the detection and characterization of localized liver lesions in liver cancer, a variety of imaging techniques are currently available. They include positron emission tomography, computed tomography, magnetic resonance imaging, and ultrasonography.

4. Biomarkers: Alpha-fetoprotein (AFP) is the common biomarker that is used in the diagnosis of hepatocellular carcinoma, a common form of liver cancer.  Presence of other biomarkers like β-glutamate and asparagine in blood, pus, and CSF will help to differentiate between HCC and liver cirrhosis.

5. Routine blood investigations: To understand the immune status of the patient and to identify the presence of risk factors, routine lab tests can be performed. Some of these include the complete blood count, tests to measure blood glucose levels, lipid profile, thyroid function tests, and urine analysis.

6. Biopsy: A small portion of liver tissue is removed during a liver biopsy so that it can be studied under a microscope for indications of liver damage. The following types of biopsies are done for liver cancer:

• Percutaneous liver biopsy - taking a small amount of tissue by introducing a thin needle through the belly of the liver.

• Transjugular biopsy - a needle is inserted into a vein in the neck.

• Laproscopic biopsy - inserting instruments through the small abdominal incision.

Treatment

There are numerous treatment options available for liver cancer. When liver cancer is detected early, treatment can be successful, with a survival probability of 70% or greater. The following are the commonly used treatment options for liver cancer:

Surgery

Surgery is performed to control the disease locally (in the liver, lymph nodes, and surrounding tissues). In the past, the only surgical method utilized to treat liver cancer was a partial hepatectomy (removal of part of the liver). For big tumors, a complete hepatectomy can still be necessary. The majority of liver tumors can now be treated with a "lobectomy," a less invasive treatment in which only the tumor is removed from the liver. If the liver is completely removed in hepatectomy, it should be replaced by a liver transplant procedure.

Radiotherapy

Management of liver cancer requires radiotherapy in a critical manner. Additionally, in situations with early-stage liver cancer, radiation therapy can delay the need for hepatectomy. In individuals with advanced malignancies, radiation therapy can reduce the risk of cancer recurrence even after surgery.

Chemotherapy

The majority of chemotherapy treatments may be prescribed as adjuvant (after surgery) or neoadjuvant (before surgery) in liver cancer. Gemcitabine, oxaliplatin, cisplatin, doxorubicin, 5-fluorouracil, capecitabine, and mitoxantrone are the popular chemotherapeutic drugs used in liver cancer.

Immunotherapy and targeted therapy

In order to fight the disease, immunotherapy boosts the immune system’s capacity to attack cancer cells. For the treatment of high-risk, early-stage liver carcinoma, immune checkpoint inhibitors are recommended. Examples are pembrolizumab, nivolumab, ipilimumab, tremelimumab, atezolizumab and durvalumab. Kinase inhibitors are a common class of targeted medications used to treat liver cancer. These medications inhibit several kinase proteins that aid in tumor cell growth, either directly or by encouraging angiogenesis (formation of new blood vessels). Sorafenib, lenvatinib, regorafenib, and cabozantinib are the commonly used targeted therapy drugs for liver cancer.

Other treatments

• Bone-modifying agents, zoledronic acid, and denosumab can be combined with immunotargeted therapy for patients with liver cancer as they prevent bone deterioration and strengthen the bone. They can be used to treat liver cancer that has spread to the bone or to stop it from recurring.

• Radiofrequency ablation, cryoablation, and microwave ablation are the different types of ablation (removal of the tumor) therapies used in liver cancer.

• Embolization is a procedure that injects substances directly into an artery in the liver to block or reduce the blood flow to a tumor in the liver.

Although liver cancer can be somewhat controlled with all these treatment options, it cannot be totally cured. The disease stage affects the overall prognosis. So, in order to improve the survival rate of these patients, early diagnosis and timely treatment is required.