Liver cancer or hepatoma is either primary or secondary. Primary is the type of cancer that originates in the liver from native liver cells and tissues, while secondary is the type of cancer that originates elsewhere in the body and spreads to the liver; since the liver is a highly vascular organ getting its blood from two main sources: the portal vein and the hepatic artery, making it the most common organ for cancer metastases and makes secondaries in the liver 20 times more common in comparison to primary cancers. Metastases mostly come from the gastrointestinal tract, most commonly from colorectal adenocarcinoma (colon cancer).
Primary liver cancer or hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver with hepatocellular differentiation (80%) followed by intrahepatic cholangiocarcinoma (20%) originating from the ducts of the biliary system, and lastly,hepatoblastoma in infants and children within 2 years of life, which is mostly seen in males in association with some syndromes like Beckwith Wiedemann syndrome, familial adenomatous polyposis, progressive familial intrahepatic cholestasis and trisomy 18. There is a rare form of HCC calledthe fibrolamellar type that originates in young adults but with a better prognosis than other variants of HCC along with better resectability.
Clinical features
Symptoms of hepatic dysfunction:
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- Painless mass in the right upper abdomen(hypochondrium). On palpation, the liver feels hard and maybe nodular with sharp edges from the cirrhosis and fibrosis.
- Dull aching abdominal pain
- nausea andvomiting
- general Fatigue
- Loss of appetite
- unintentional loss of weight
- Sometimes,when the tumor undergoes sudden necrosis and hemorrhage, it presents with acute severe abdominal pain and symptoms of shock due to the life-threatening spontaneous hemoperitoneum which means accumulation of blood within the peritoneal cavity.
Signs of hepatic dysfunction:
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- Jaundice,which is yellowing of skin and mucous membranes that happen due to failure of conjugation of bilirubin or due to compression on biliary tracts by the mass leading to failure of excretion.
- Ascites,which can be a massive fluid collection within the abdominal cavity due to portal hypertension.
- Splenomegaly due to portal hypertension
- Esophageal and gastric varices due to portal hypertension
- Easy bruising due to clotting factor abnormalities
- Palmar erythema
- Spider nevi
- Gynecomastia
- Testicular atrophy due to excessive estrogen
- Hepatic encephalopathy due to excessive ammonia levels in the blood
- Para neoplastic syndrome in 1% of cases, with hypercalcemia, hypoglycemia, hyperlipidemia, hyperthyroidism and erythrocytosis.
- Symptoms of the main malignant source of metastasis
- Acute Liver failure.
Diagnosis
As many of the cases present with atypical features and the majority are asymptomatic, the main modality for proper diagnosis is imaging studies with a wide variety of methods available including:
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- Ultrasound: Avery useful first imaging study used for screening mainly which helps indicate the presence of a mass or not, and it is also very helpful in determining the amount of fluid within the abdomen in people suffering from ascites, but it isn’t reliable enough on its own for diagnosis, as it cannot accurately estimate the extent of spread or differentiate between the different types of masses within the liver.
- Triphasic abdominal CT scan: These scans are more reliable than ultrasound in revealing the size, location, extent, vascularity, portal vein invasion, and lymph node metastasis and differentiates between the different types of masses within the liver showing rapid arterial enhancement and rapid venous washout in hepatocellular carcinoma.
- CT angiography: Another type of CT scans that shows the vascularity of the tumor and portal vein invasion or thrombosis more accurately and is mostly used in treatment planning.
- Dynamic MRI scans: They are the most sensitive and specific for HCC identification, especially smaller onesappearing as hyperechoic mass in T2 weighted images and hypoechoic mass inT1 weighted images.
To confirm the diagnosis:
The American association for the study of liver diseases recommends screening people with chronic liver cirrhosis with an ultrasound every 6 months and measurement of the tumor marker AFP to help identify the disease in its early curable stages as well as to decrease the rates of morbidity and mortality associated with HCC.
Spread :
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- Lymphatic spread to other parts of the liver:to porta hepatis or to other abdominal lymph nodes.
- Blood spread to the lung, bone,or adrenals.
- Direct infiltration of the diaphragm and surrounding structures.
Risk factors
- Hepatocellular carcinoma is mostly attributable to cirrhosis with its wide magnitude of causes in sub-Saharan Africa and Asia the leading causes of cirrhosis are: chronic hepatitis B and chronic hepatitis C infections,with the latter being more common than the former, and in the Western community, alcohol use disorders are the leading cause of cirrhosis.
- Aflatoxin,which is a product of aspergillus fungus, a very powerful carcinogen which can be found on cereals and peanuts.
- Hemochromatosis (iron overload)
- Non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD)
- Alpha-1 antitrypsin deficiency
- Smoking
- High grade dysplastic nodules in the liver like adenoma
- Obesity and metabolic syndrome
- Diabetes mellitus
- Cholangiocarcinoma is related to liver fluke infestations, primary sclerosing cholangitis, ulcerative colitis, choledochal cysts with its aggressive form (Caroli disease), congenital liver disorders like biliary atresia, infantile cholestasis, and glycogen storage disease
Staging
There are plenty of staging systems for hepatocellular carcinoma, but the most commonly used one to assess the condition of the patient and determine the appropriate treatment regimen is the Barcelona Clinic Liver Cancer classification.
It classifies the tumor according to size and number of lesions and presence of vascular invasion or extra hepatic metastasis along with the child Pugh classification that indicates the residual function of the liver by checking liver function tests as bilirubin, albumin, coagulation profile, the presence or absence of ascites and hepatic encephalopathy, along with a performance score to assess the general health status of the patient, combining all these gives an accurate picture of the severity of the cancer and helps set a suitable treatment plan.
Treatment
There are plenty of treatment options that have been developing over the years with the constant introduction of new modifications and using of less invasive methods to achieve better results in some cases even reaching total cure. All of that is definitely dependent on the stage of the disease and the condition of the liver and the general health of the patient at diagnosis.
Curative options
1. Surgical resection:
It is the best option for cure in a very early diagnosed tumor that is respectable with enough margins to leave behind a good amount of liver tissue capable of taking over the functions of the liver in the body without compromising the state of the patient any further; so it is best used in cirrhotic patients with Child Pugh class A or non-cirrhotics, as they would have some residual functioning capacity but it is associated a high recurrence rate.
In order to choose the right candidates doctors use what is known as a MELD score (Model for End-stage Liver Disease) using creatinine, bilirubin, PT, and INR to assess the condition of the patient because there is no regenerative capacity in patients with poor coagulation status, portal hypertension, varices, or ascites.
2. Liver transplantation:
Total hepatectomy with orthotopic liver transplant which means taking out the diseased liver and replacing it by a new one from a healthy living donor or a cadaveric donor. This is best reserved for patients with cirrhosis in whom resection isn’t an option for cure. there are certain criteria called the MILAN criteria that are used to select the patients in whom transplant would be a great option with higher chances of recovery, and it includes:
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- Not being a candidate for resection
- One massthat is <5cm
- Less than three masses each of them not exceeding 3 cm
- Tumor without portal or hepatic vein invasion
- Tumor without extra hepatic metastasis
These criteria, if fulfilled, puts the patient on a waiting list for liver transplant until a donor is found. If the case is critical, the patient can use a bridging treatment modality like radiofrequency ablation or trans arterial chemoembolization (TACE) to make sure the condition doesn’t deteriorate any further.
It is a great option but many people can’t afford the transplant fees or may live in an area with no big centers that perform this type of surgery that requires a specialized center with extensive expertise in doing this operation another obstacle is that the transplant isn’t the end of treatment the patient must live on immunosuppressants which have a ton of effects on the body, but are necessary for the overall survival of the patient to avoid getting host graft rejection, so it is definitely not suitable solution for all types of patients.
3. Radiofrequency ablation:
A new method that is way less invasive than resection and transplant. It is a thermal ablation technique that uses a probe that passes to the middle of the tumor percutaneously under ultrasound or CT guidance or through laparoscopy and passes an electric current of 500 KHZ and this heat leads to a zone of necrosis within the tumor. It is a simple procedure that can be done in less than half an hour with fewer complications and better end results, but it has limitations in that the maximum zone of necrosis created by the ablation doesn’t exceed 7 cm, which makes it only suitable for lesions that are 5 cm or less and preferably deep tumors within the liver parenchyma away from the helium of the liver that contains important structures like the hepatic artery, hepatic vein, portal vein, and porta hepatis, which could be accidentally injured if it is close to the helium. As a result, the smaller the lesion the better the outcome and it can be repeated more than once to achieve the best results.
Another ablation technique is cryoablation that does the opposite by using cold temperatures – 190 c to cause tumor necrosis without affecting the surrounding structures.
An old method that is similar to ablation but cheaper is percutaneous ethanol or acetic acid injections which requires that the mass to be less than 3 cm and mainly less than 3 in number, but it has a high recurrence rate and doesn’t provide good results as ablation nowadays.
4. Transarterial chemoembolization (TACE):
This method uses the concept of injecting the chemotherapeutic agent intralesionally mostly cisplatin or adriamycin through the feeding artery of the tumor along with the addition of radio opaque contrast lipiodol and an embolic agent gel foam to trap the agent within the tumor for a longer period of time concentrating its effect on the lesion only.
It is mainly used for patients not suitable for resection and the tumor is larger than the extent of ablation and as a bridge in some candidates of liver transplant and the extent of tumor regression is followed monthly by CT scans to assess the successes of the procedure and detect any recurrence. It can also be done more than once like ablation till it gives the required effect.
5. Selective internal radiation therapy (SIRT):
It is a method similar in concept to TACE, and is sometimes called TARE transarterial radiofrequency embolization. It is done in the same manner by injecting the feeding artery with a radioactive beads or microspheres made out of yttrium 90 or theraspheres that are subjected to direct high dose radiation >100 Gy that causes tumor necrosis without affecting the surrounding structures and this technique has been mostly used in treating metastatic lesions from a primary colorectal cancer with good outcomes.
6. Adjuvant chemotherapy:
In cases where there is extensive affection of the liver by the lesions or if there is vascular invasion or extra hepatic metastasis, systemic chemotherapy is used as the main line of treatment with sorafenib, an oral multikinase inhibitor being the first line of treatment of advanced HCC. It acts mainly by blocking the tumors ability to make new blood vessels leading to its shrinkage to smaller sizes.
Prevention
One of the most beneficial methods of primary prevention is immunization, and luckily there is a hepatitis B vaccine that everyone should take to decrease their risk of getting the virus, especially those at increased risk like health care workers and people living in endemic areas of hepatitis B.
Unfortunately, there is no hepatitis C vaccine available at the moment, but there are plenty of antiviral drugs available for patients with hepatitis C that can drastically decrease their risk of getting cancer, especially if treatment starts in the early stages before progressing to cirrhosis and end-stage liver disease.
Other forms of prevention include: using safe injection methods with proper sterilization techniques, proper handling of waste products that were in contact with blood, and screening blood products before supplying patients with them.
Reducing alcohol consumption and healthy eating habits with proper exercise to avoid obesity and diabetes with its related problems especially in the western hemisphere are also important methods for reducing the risk of getting liver cancer.
Prognosis
The prognosis is related to the tumor stage and treatment modality used with curative options reaching up to 70% 5-year survival rates compared to 1 to 2 year median survival for advanced stages treated with systemic chemotherapy.