Liver is the largest glandular organ in human body weighing about 1.4 kilograms in a healthy adult. It sits below the diaphragm and beneath the right ribs in the abdominal cavity. It is divided into two lobes by the falciform ligament, with right lobe being larger than the left one. Major functional cells of the liver are known as hepatocytes (specialized epithelial cells).
It receives blood from two main sources – oxygenated blood from the hepatic artery and deoxygenated blood containing absorbed nutrients (and other substances) from the hepatic portal vein. It performs many functions that include: secretion of bile (that help in digestion of fat); metabolism of carbohydrate, lipid, protein, and many drugs; excretion of bilirubin; storage of vitamins and minerals; phagocytosis; removal of worn out WBCs and RBCs; and activation of vitamin D.
The overall incidence and mortality rate of liver cancer has been increasing during the last few decades, which is postulated to be due to the increasing incidence of hepatitis B and hepatitis C infections during this time. It is more common among men than women and mostly occur at an age of 55 to 64 years.
- Hepatocellular carcinoma (HCC) (affecting hepatocytes) is the most commonly encountered (about 90% of the cases) liver cancer.
- Intrahepatic cholangiocarcinoma (bile duct cancer) is also generally grouped with liver cancer, which affects cells lining the bile ducts (tubes that carry bile secreted by hepatocytes to the gallbladder and to the intestine) within the liver.
- Angiosarcoma, hemangiosarcoma (affecting cells lining the blood vessels of the liver), and
- Hepatoblastoma (that usually occur at younger age wherein cells resemble fetal liver cells) are some less common type of liver cancers. The liver is a vascular organ, and thus, is a common site of secondary cancers. However, in case of secondary cancers (cancers that originated somewhere else in the body and have spread to the liver), liver cancer is viewed as a part of primary cancer and treated in the way primary cancer is treated.
Risk Factors for Liver Cancer
Hepatitis B or C infection
Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is the well-recognized major risk factor for the liver cancer development. HBV is responsible for high incidences of liver cancer in Asia and Africa, while HCV is responsible for the high incidences of the disease in Europe, Japan, and North America.
Alcohol intake may act synergistically with these infections and can further increase the risk of developing liver cancer. Population at high risk of hepatitis induced liver cancer is males, family history of disease, age more than 45 years and patients with cirrhosis.
Hepatitis B has relative risk of 12.7,100 fold increased risk than non-carriers. Lifetime risk of liver cancer among HBV carriers in population where infection occurs early in life is 27% for males and 4% for females. Virus integrates into the hepatocyte genome causing microdeletions that can target cancer relevant genes.
Also, HBx can cause transcriptional activation altering the expression of growth-control genes. HCV is more likely to lead to chronic infections (10 % vs 60% to 80%) and cirrhosis ( 20-fold increase).
The average age of HBV-associated HCC is around 52 yr compared with 62 yrs for HCV is only about 30 yr ( compared with 40 to 50 yr for HBV ). HCV-associated HCC patients tend to have more frequent and advanced cirrhosis
Patients with liver cirrhosis remain at high risk of developing liver cancer. The cirrhosis may result from any of the following cause:
- excessive alcohol intake,
- chronic liver injury,
- inherited error of metabolism (for example, hemochromatosis – a condition characterized by increased absorption of iron due to mutation in HFE gene),
- Wilson’s disease,
- schistosomiasis (infection caused by a blood fluke), or
- alpha-1 anti-trypsin deficiency.
All these disorders have been reported to be the independent risk factor for liver cancer development.
Metabolic disorders and Obesity
Many studies have suggested that the presence of certain metabolic disorders like obesity, diabetes, impaired glucose metabolism, and non-alcoholic fatty liver is associated with increased risk of developing liver cancer.
Exposure to aflatoxin (produced by Aspergillus fungus that commonly contaminates peanuts, wheat, soybeans, groundnuts, corn, and rice), arsenic or microcystin in drinking water, vinyl chloride, and thorium dioxide have also been reported to increase the risk of liver cancer development.
Individuals with prolonged use of anabolic steroids are generally at higher risk of developing liver cancer.
Male gender and Ethnicity
Liver cancer is about 2 to 3 times more common in men compared to women, worldwide. This disparity is postulated to be related to the differential effect of androgen on the hepatocytes. According to different epidemiological studies, incidences of liver cancer are highest in Asians followed by African Americans and then Caucasians.
Chronic cigarette/tobacco smoking and prolonged use of oral contraceptives are less common risk factors for the development of liver cancer.
How can you Reduce the Risk?
Some of the risk factors of liver cancer are modifiable and other are non-modifiable. By making some lifestyle changes, liver cancer risk may be reduced.
- Regular exercise
- Weight control
- Eating a healthy diet
- Taking Alcohol in moderation
- Avoiding infection with Hepatitis B and C virus (avoid high risk sexual behaviour, vaccination)
Signs and Symptoms
One or more of the following symptoms may raise the suspicion of liver cancer-
- Fever or malaise
- Unexplained weight loss
- Abdominal pain
- Loss of appetite or early satiety
- Nausea and vomiting
- Liver or spleen enlargement
- Abdominal distension (due to ascitis)
- Jaundice and/or itching
- Hypoglycemia (related to IGF-I)
- Erythrocytosis (3 to 12%)
- Hypercholesterolemia (10 to 40%)
- Carcinoid syndrome
- Increased TBG
- Sexual changes And PCT
Stages of Liver Cancer
It includes the cases with T1a N0 M0 disease.
A solitary tumor in the liver that measures </=2 cm in largest dimension and has not invaded any blood vessel. No spread of disease to nearby lymph nodes or distant body parts.
It includes the cases with T1b N0 M0 disease.
A solitary tumor in the liver that measures >2 cm and has not invaded any blood vessel. No spread of disease to nearby lymph nodes or distant body parts.
It includes the cases with T2 N0 M0 disease.
A solitary tumor in the liver that measures >2 cm and has invaded a blood vessel OR multiple tumors but none measuring >5 cm. No spread of disease to nearby lymph nodes or distant body parts.
It includes the cases with T3 N0 M0 disease.
Multiple tumors in the liver with at least one measuring >5 cm. No spread of disease to nearby lymph nodes or distant body parts
It includes the cases with T4 N0 M0 disease.
A solitary tumor or multiple tumors in the liver of any size with at least one tumor invading a large blood vessel (for example, portal or hepatic vein) or any adjacent organ except gallbladder or perforation of visceral peritoneum. No spread of disease to nearby lymph nodes or distant body parts.
It includes the cases with anyT N1 M0 disease.
A solitary tumor or multiple tumors of any size in the liver with or without invasion into a large blood vessel but with the spread of disease to nearby lymph nodes. No spread of disease to distant body parts.
It includes the cases with anyT anyN M1 disease.
A solitary tumor or multiple tumors in the liver of any size with or without invasion into a large blood vessel and the disease might or might not has spread to nearby lymph nodes. The disease has spread to distant body parts such as lungs or bones.
Child-Pugh Score is used to assess liver function (or liver cirrhosis) in liver cancer patients. Most patients with liver cancer have accompanying liver cirrhosis or other liver disorder due to which liver function is generally diminished in such patients. An assessment of liver function help in selecting an appropriate treatment approach for liver cancer. The Child-Pugh scoring system is most commonly used for this purpose, which takes into consideration following 5 parameters:
- bilirubin level in blood,
- albumin level in blood,
- prothrombin time,
- presence or absence of ascites, and
- whether the liver disease is affecting brain function.
Based on the status of the above parameters liver cirrhosis/functioning is divided into 3 classes, that is, Class A, B, and C, where C represents the worse liver function. However, this system does not take into consideration any parameter of liver cancer itself. Thus, this system is used along with the TNM staging system for the assessment of overall disease.
It was the first validated system used for staging of liver cancer, which takes into consideration both cancer parameters and liver function parameters.
Many other staging systems have been developed and used for staging of liver cancer that accommodated different parameters related to liver cancer and liver function. Examples for such systems include Cancer of the Liver Italian Program (CLIP) scoring system, Barcelona Clinic Liver Cancer (BCLC) system, Chinese University Prognostic Index (CUPI) scoring system, the Groupe d’Etude et de Traitement du Carcinoma Hepatocellulaire (GETCH) staging system, and the Japan Integrated Staging (JIS) system. These staging systems have their own advantages and disadvantages and are used in different geographical regions as per physician’s preference and local practice.
What are the final Stages of Liver Cancer?
Final stages of liver cancer include cases in which cancer has spread to lymph nodes and/or distant organs. Most common sites of distant spread of liver cancer are lungs and bones.
Most common symptoms of final stages of liver cancer include-
- Abdominal discomfort or pain
- Abdominal distention or ascitis
- Generalized body weakness, decreased appetite
- Yellowish discoloration of eyes and/or urine (jaundice)
- Breathlessness, cough and/or chest pain
- Pain at one or more bony sites
- Blood in vomitus or stools
One or more of the above symptoms may suggest advanced liver cancer. These symptoms may be caused due to extensive liver function derangement due to cancer, or due to spread to one or more distant sites.
5 year survival in metastatic liver cancer is approximataely 11%.
Curative treatment is not possible in advanced liver cancer in most cases. Some treatment options include targeted therapy, immunotherapy or chemotherapy. Other supportive modalities may be used for palliation or relief of symptoms.
Stage I and II Liver Cancer Treatment
Potentially resectable or transplantable
This category includes TNM stage I and II liver cancer that can be completely removed with surgery or treated with liver transplant and patient is healthy enough (sufficient liver function) to tolerate the surgical treatment. The decision to go for local therapy or liver transplant is taken based on many parameters like size and number of tumors (UNOS criterion for liver transplant), liver functional status (child pugh grade and functional liver residue), availability of donor, fitness for transplant, etc. Local therapy may be done with surgical resection or ablation of liver tumor depending on size and location of tumor, along with other factors.
In patients with potentially resectable liver cancer and adequate liver function, Surgery (partial hepatectomy) is considered the preferred treatment approach. For patients who are the candidates for liver transplantation, treatments like ablation or embolization may be employed until as a bridge for transplantation.
Inoperable with only local disease
This category includes TNM stage I and II liver cancer that has not invaded important structures but the patient is not healthy enough (liver function is significantly compromised or poor performance status) to tolerate surgery.
In some cases, the tumor is limited to a part of the liver (which can be removed with surgery) but patients cannot have surgery due to poor liver function or performance status. Thus, treatments like ablation or embolization are usually employed in such cases. Targeted therapy or chemotherapy may also be considered.
Stage III Liver Cancer Treatment
This category includes TNM stage III liver cancer that cannot be completely removed with surgery as it has invaded important blood vessels or other structures. The patient may or may not have sufficient liver function.
In patients with some advanced stage cancer that are considered unresectable due to invasion into blood vessels or large tumor size, treatments like ablation and/or embolization are generally preferred, depending on the location and the extent of invasion. Targeted therapy or chemotherapy may also be employed.
Stage IV Liver Cancer Treatment
This category includes TNM stage IV liver cancers that has spread to distant body parts and cannot be surgically removed. The patient may or may not have sufficient liver function. The liver cancer treatment options depends on many factors including but not limited to the type of liver cancer, stage of the disease, liver function, performance status of the patient, along with other factors.
For patients with advanced liver cancer that has spread to distant body parts, targeted therapy or chemotherapy are generally considered.
Surgical Treatment of Liver Cancer
Surgery provides significantly longer survival and is considered as the treatment of choice for most early-stage liver cancers. Sometimes, surgery is employed to relieve symptoms of advanced stage disease like bleeding and pain. The following types of surgery may be used for the treatment of Liver cancer:
In this surgery, only the liver tissue containing cancer and some of the nearby tissue is removed leaving the rest of the liver in place. This is generally preferred in case of early-stage disease where the tumor is limited to a part of the liver (not affecting major blood vessels) and when liver function is adequate.
In this surgical procedure, the entire liver is removed and replaced by a liver donated by some other individual. This is generally used to treat patients with small tumors (either 1 tumor smaller than 5 cm across or 2 to 3 tumors no larger than 3 cm) that have not invaded nearby major blood vessels, with poor liver function. However, a patient who is a good candidate for transplantation may have to wait until availability of the donated liver, which may take too long. Thus, these patients generally receive other treatment(s) during this time to keep the liver cancer in check.
Non-Surgical Treatment of Liver Cancer
Ablation is a technique in which tumors are destroyed without actual removal from the body. This technique is generally used for patients with small tumors (usually <3 cm) when surgery is not an option due to location of the tumor, poor performance status of the patient, etc. Ablation can destroy cancer cells along with some of the nearby tissue, and hence, it is not used for the treatment of tumors invading blood vessel or important structures. High-energy radio waves are utilized in radiofrequency ablation (RFA), microwaves are used in microwave ablation (MWA) technique, while very cold gases are used in cryoablation to destroy tumors. Imaging techniques are utilized along with these ablation techniques to accurately locate the target tumors.
in this technique liver cancer is destroyed by blocking the blood supply to the cancer cells with the help of some inert tiny particles (particles are loaded with drugs in chemo-embolization and with a radioactive substance in radio-embolization) that are injected directly in the artery supplying blood to cancer cells. This technique is generally employed in patients who cannot undergo surgery and in those waiting for liver transplantation. Embolization can be employed for large tumors (>5 cm) and can also be used in conjunction with ablation.
Targeted therapy has been found very effective in treatment of Hepatocellular Carcinoma. This is mainly indicated for unresectable and/or metastatic disease. Sorafenib is preferred targeted drug in cases of Child Pugh A liver cancer, unresecatble or metastatic disease.
Chemotherapy means treatment with anti-cancer drugs that kill or decrease the growth of rapidly growing cancer cells. It is not very effective in treating liver cancer and is not commonly employed for its treatment.
Best Liver Cancer (Hepatocellular Carcinoma) Specialist in Delhi
Dr Sunny Garg is a renowned Medical Oncologist in New Delhi with an experience of around 10 years of treating liver cancer patients. He has treated hepatocellular carcinoma patients with Chemotherapy, Targeted Therapy and Immunotherapy. He is currently practicing at Manipal Hospital, Dwarka.
Diagnostic modalities available at our hospital include Alpha Fetoprotein, Triple Phase CT Scan, Whole Body PET CT Scan, CT or ultrasound Guided Biopsy, etc. Other treatment facilities for Liver Cancer available are Partial Hepatectomy, Liver Transplant, Radiation Therapy, etc.
Call +91 9686813020 for appointment.