HCC is called a silent killer.

The impact is really not on the patient himself; all the families are affected.

Hepatocellular carcinoma (HCC) is a type of liver cancer that affects over 750,000 people globally, with
majority of these cases in Asia.

Over half of all cases of HCC are diagnosed in China.

To further understand the disease Hepatocellular Carcinoma or HCC, it is important for us to review the
main organ that is affected by it.

The liver is the largest organ inside the body. And is located just below the ribs on the right side.

The liver has many functions, it filters waste and other harmful materials from the blood.

It produces enzymes and bile that help with digestion. And it produces chemicals and hormones
necessary for regulating many body functions.

Liver cells are called hepatocytes.

Liver cancer is classified as either primary, starting in the liver, or secondary, spreading to the liver from
cancer in another part of the body.

Hepatocellular carcinoma is the most common form of primary liver cancer. It develops in the liver cells.
And damages other healthy liver cells.

Continuous growth of cancerous hepatocytes can cause malignant or cancerous tumours to form.

In its early stages, liver cancer does not produce many symptoms and is hard to detect.

So what really is Hepatocellular Carcinoma or HCC?

Hepatocellular carcinoma has a very high fatality rate and its incidence is on the rise.

HCC accounts for 90% of liver cancers.

Ranking as the 6th most common cancer globally.

And of all cancers, HCC is the third leading cause of cancer related death.

Further in the United states, between the years 2000 and 2012 we’ve seen a significant increase in the
incidence of this disease.

Its grown from an incidence of 4.4 to 6.7 per 100,000.

That is an increase of over 50% in little more than a decade.

Risk factors for developing HCC include :

Viral hepatitis, specifically Hep B and C. This is the cause of 90% of HCC in developing countries and only
16% in the UK. In the US, infection with hepatitis C is the more common cause of HCC, while in Asia and
developing countries, hepatitis B is more common.

High alcohol intake being another source of inflammation and cirrhosis. Consuming more than a
moderate amount of alcohol daily over many years can lead to irreversible liver damage and increase
your risk of liver cancer.

Smoking. Former smokers have a lower risk than current smokers, but both groups have a higher risk
than those who never smoked.

Advancing age (>70years). Not to mention that Hepatocellular carcinoma is much more common in men
than in women. Much of this is probably because of behaviors affecting some of the risk factors.

Aflatoxin exposure. Which is produced by certain fungi that are abundant in warm and humid regions of
the world. Aflatoxins are poisons produced by molds that grow on crops that are stored poorly. Crops,
such as grains and nuts, can become contaminated with aflatoxins, which can end up in foods made of
these products. Asian and Pacific Islanders have the highest rates of liver cancer.

And lastly, a family history. Inherited Liver diseases that can increase the risk of liver cancer include
hemochromatosis and Wilson's disease. People with hereditary hemochromatosis absorb too much iron
from their food. The iron settles in tissues throughout the body, including the liver. If enough iron builds
up in the liver, it can lead to cirrhosis and liver cancer.

The clinical features for HCC and metastatic liver cancer are largely the same. They include:

Jaundice.

Fatigue.

Fever.

Ascites.

Right upper quadrant pain.

And a hard, and craggy liver border on palpation specially if there is underlying cirrhosis.

Differential Diagnosis other than cancer for somebody presenting with some of these symptoms include:

Infectious Hepatitis which could be confirmed by virology.

Benign hepatocellular adenoma.

Cardiac Failure although they are more likely to have a smooth hepatomegaly due to fluid overload and
portal hypertension.

And liver cirrhosis which has the same risk factors previously mentioned to the HCC.

After taking a history and examining the patient, initial investigations should include laboratory tests.

LFTs give a clear picture of liver function and should therefore be requested.

Clotting abnormalities which is prolonged on and off is important indicator of liver failure

A full blood count should also be requested as “low platelets” possibly indicate a liver dysfunction
leading to a lack of thrombopoietin secretion by the liver.

And finally, alpha fetoprotein has the important biomarker in liver cancer, being raised in 70% of cases.

Ultrasound scans which should be used to investigate palpable masses are often first line.

CT Scans could be done for staging in a more detailed map of the cancer itself.

We may potentially do an MRI.

In the United States, guidelines suggest that for patients who are at high risk of developing liver Cancer
such as those with CIrrhosis, and underlying risk factors for liver disease and liver cancer undergo
screening for HCC.

Current Screening recommendation may include Ultrasound every 6 months.

As Per the TNM Staging system.

All secondary liver cancers are at a significantly advanced stage.

For hepatocellular carcinomas, the main staging system used is the Barcelona Clinic liver cancer staging
system or the BCLC.

This system classifies cancers from A to D.

D being end-stage or terminal.

A separate stage 0 denotes cancers of a very early stage.

Stage A corresponds to early stage HCC.

Stage B corresponds to intermediate or multinodular HCC.

And C is an advanced HCC with portal invasion and extra-hepatic spread.

Stage D cases are terminal and include patients with end-stage liver function.

Still looking specifically at HCC, stages 0 and A can be treated with microwave ablation, liver resections,
or via a total liver transplant.

With microwave ablation being particularly good for surface tumors.

Stage B cancers can be treated with transarterial chemoembolisation or TACE. Which is a minimally
invasive procedure and is often carried out by an interventional radiologist.

Stage C cancer can be treated with systemic therapy. And Stage D is mainly treated with best supportive
care.

The decision of whether to resect or transplant the patient with an HCC can be reached by scoring them
on further criteria.

Such as the Milan Criteria. This looks at tumor size, number of lesions, whether there is any angio
invasion or whether there is any extra hepatic involvement of which they cannot be to qualify for a
transplant.

Another scoring system is the MELD score, standing for Model of End Stage Liver disease. It looks at
serum Bilirubin, INR and Creatinine.

It is used to prioritize patients for liver transplants indicating mortality risk and hence case urgency.

These scoring systems are specific to hepatocellular carcinomas.

With regards to secondary liver malignancy, resection, if possible is the gold standard.

It is important to find liver cancer early because it is in the early stages that it is curable.

For patient’s disease diagnosed early such as Barcelona stage 0, A or B. Curative options include: surgical
resection and ablation or liver transplantation.

In well selected patients, these treatment options yield a 5 year survival rate equal to or greater than
70%.

The initial approach in the management of patients with HCC is to determine if either surgical resection
or transplantation will be an option.

The challenge here is that the majority of patients with HCC have some degree of cirrhosis and
underlying liver disease which makes a simple resection complicated.

Portal hypertension as indicated by thrombocytopenia and a platelet count less than a 100,000 is often
considered a contraindication to resection.

Local ablation such radio frequency ablation or microwave ablation may be appropriate for these
patients.
Post operative complications include:

Bleeding, infection or abscess formation, liver failure or bile leakage.

Along with these are other common post operative complications such as:

Atelectasis, lower respiratory tract infections and DVTs.

One simple way among others to assess liver function is by looking at the serum lactate both intra and
post operatively.

The use of the pringle maneuver can increase lactate due to the reduction in blood supply.

A raised post operative lactate can also indicate that the liver isn’t extracting and metabolizing lactate
effectively as it usually does.

Still the only way to cure patients with early liver cancer and underlying liver disease who cannot
undergo resection would be transplantation.

However donor organs are on short supply and there’s a long wait list.

While resection is the standard of care for non-cirrhotic patients, it has a high recurrence rate.

For patients who undergo resection, currently there is no data to support the use of adjuvant therapy
outside of a clinical trial.

And currently for patients who undergo resection with curative intent, surveillance with regular imaging
would be considered standard of care.

For patients with advanced HCC, considered stage C disease, systemic targeted agents have been proven
to improve survival.

In the frontline setting this include tyrosine kinase inhibitors such as sorafenib and more recently data
from study comparing sorafenib with Lenvatinib has shown that Lenvatinib also is active in improving
survival in advanced liver cancer.

In the secondline setting, regorafenib has shown activity in a phase 3 trial. And more recently there is
exciting data with immuno oncology agent such as monoclonal antibody nivolumab and pembrolizumab.

The general prognosis of HCC depends on the extent of underlying cirrhosis as this plays a large role in
determining how aggressively the cancer can be treated.

Median survival time from diagnosis is around 6 months.

With all these in mind and with the advent of hepatitis B vaccines, it is to be stressed that hepato
cellular carcinoma is still considered a preventable disease.