Hepatocellular carcinoma (HCC)
Hepatocellular carcinoma is the commonest primary cancer of the liver — a cancer arising from the liver cells themselves, as distinct from cancer that has spread to the liver from elsewhere. It differs from most other cancers in one important respect: it usually develops in a liver that is already diseased, and treatment must take account of both the tumour and the state of the liver it grows in.
How it forms
HCC is, in the great majority of cases, the end point of long-standing liver injury. Chronic inflammation — from viral hepatitis, alcohol, or fat accumulation — drives repeated cycles of liver cell death and regeneration. Each cycle of division carries a risk of genetic error. Over years, scar tissue accumulates (fibrosis, progressing to cirrhosis), the architecture of the liver is disrupted, and regenerating nodules form. Within those nodules, cells acquire successive mutations, progressing from dysplastic nodule to early carcinoma to established cancer.
The principal underlying causes are:
- Chronic hepatitis B and hepatitis C. Hepatitis B can cause HCC even without cirrhosis, because the virus integrates into the host cell's DNA.
- Alcohol-related liver disease.
- Metabolic dysfunction-associated steatotic liver disease — fatty liver associated with obesity, type 2 diabetes and metabolic syndrome. This is a rising cause worldwide, including in Cyprus.
- Haemochromatosis and other inherited liver conditions.
- Aflatoxin exposure, relevant in some regions.
Two consequences follow from this mechanism. First, HCC is to a significant extent preventable — by hepatitis B vaccination, antiviral treatment of hepatitis B and C, reduction of alcohol, and management of metabolic risk factors. Second, the people at risk are largely identifiable in advance, which is the basis for surveillance.
Surveillance — why it matters
HCC produces no symptoms until it is advanced. By the time it causes pain, weight loss or jaundice, the options are narrower. Patients with cirrhosis, and selected patients with chronic hepatitis B, are therefore offered surveillance with ultrasound, generally at six-monthly intervals, often with alpha-fetoprotein. The purpose is to find tumours small enough to be curable.
This is the single most useful thing that can be said about HCC: attending surveillance changes outcomes, and a great many patients with known cirrhosis are not in a surveillance programme.
Symptoms
Early HCC is silent. When symptoms appear they may include upper abdominal pain or a mass, unexplained weight loss, loss of appetite, or deterioration in a previously stable cirrhosis — new ascites, jaundice or confusion.
How the diagnosis is made
HCC is unusual among cancers in that it can often be diagnosed on imaging alone, without biopsy. In a patient with cirrhosis, a lesion showing the characteristic pattern on contrast-enhanced CT or MRI — arterial enhancement followed by washout in the portal or delayed phase — is diagnostic.
Biopsy is used where imaging is not characteristic, or where the patient does not have underlying liver disease.
Assessment then addresses three questions simultaneously, and all three determine what treatment is possible:
- The tumour — size, number, and whether it has invaded blood vessels or spread beyond the liver.
- The liver — how well the underlying liver functions, assessed by Child-Pugh grade, bilirubin, albumin, clotting and the presence of portal hypertension.
- The patient — general fitness and other medical conditions.
Staging systems give the framework, but they guide rather than dictate. Patients are regularly offered treatment beyond what a strict reading of a staging table would allow, where the tumour's behaviour, the liver's reserve and the patient's fitness justify it — and equally, a patient who fits a category on paper may be better served by a different approach. The recommendation is built for the individual.
Staging systems such as the Barcelona Clinic Liver Cancer classification combine these to guide treatment. Management is decided in a multidisciplinary meeting involving surgeons, hepatologists, radiologists, interventional radiologists and oncologists.
Treatment options
Surgical resection
Removal of the part of the liver containing the tumour, offering the prospect of cure. Best suited to patients with a single tumour and well-preserved liver function without significant portal hypertension. The critical judgement is whether enough functioning liver will remain afterwards — a calculation that is very different in a cirrhotic liver than in a healthy one. Where the future liver remnant is too small, portal vein embolisation may be used beforehand to induce the remaining liver to grow.
Liver transplantation
Treats the cancer and the underlying cirrhosis together, and offers the best long-term outcome for selected patients with tumours within defined criteria and with liver function too poor for resection. Availability and waiting times govern its practicality.
Ablation
Radiofrequency or microwave ablation destroys the tumour with heat delivered through a needle placed under imaging guidance. For small tumours it can achieve results approaching those of resection, and it is well suited to patients whose liver function will not tolerate an operation.
Transarterial therapies
Chemoembolisation (TACE) and radioembolisation deliver treatment directly into the artery feeding the tumour. Used for larger or multiple tumours confined to the liver, and sometimes to control disease while awaiting transplantation.
Systemic therapy
For advanced disease, immunotherapy combinations and targeted agents have changed the outlook considerably in recent years. These are directed by medical oncology.
Recovery after resection
Recovery depends on the extent of resection and on the condition of the underlying liver. A laparoscopic or robotic minor resection may involve three to five days in hospital; a major open resection, longer. Patients with cirrhosis require careful monitoring of liver function afterwards. Return to normal activity typically takes six to eight weeks after a major resection.
Follow-up
Follow-up after curative treatment is intensive, with imaging and tumour markers at regular intervals, because new tumours can arise elsewhere in a liver that remains at risk. Treatment of the underlying liver disease continues in parallel — antiviral therapy, alcohol abstinence, metabolic management — since this influences both recurrence and survival.
When to seek a specialist opinion
Any liver lesion found in a patient with cirrhosis or chronic hepatitis should be assessed without delay by a team experienced in liver cancer. Equally, anyone with cirrhosis who is not currently in a six-monthly surveillance programme should ask to be. A second opinion is reasonable whenever a patient has been told a tumour is inoperable, because assessment of resectability varies with experience and with the availability of techniques such as portal vein embolisation and staged resection.
Common questions
Why did I develop liver cancer?
In the great majority of cases it develops in a liver that has been chronically damaged — by hepatitis B or C, by alcohol, or by fatty liver disease associated with obesity and diabetes. Years of injury, repair and scarring produce genetic changes in the liver cells. It is the underlying liver disease, as much as the tumour, that determines what treatment is possible.
Why do I need scans every six months if I feel well?
Because in people with cirrhosis or chronic hepatitis B, tumours found by surveillance are small and treatable, while those found because they cause symptoms are usually too advanced for cure. Six-monthly ultrasound is one of the clearest examples in medicine of screening changing outcomes, and skipping it is the commonest reason a curable tumour is missed.
Why was no biopsy taken?
Because in a patient with cirrhosis, the pattern of blood flow through a nodule on a CT or MRI scan is diagnostic in itself — the tumour fills rapidly with contrast and then empties faster than the surrounding liver. Biopsy adds a small risk of bleeding and of seeding cells along the needle track, and is reserved for cases where the imaging is not conclusive.
Can it be cured?
Yes, when it is found early. Removing the tumour surgically, destroying it with heat or cold through a needle, or replacing the whole liver by transplantation are all treatments given with the aim of cure. Which is appropriate depends on the size and number of tumours, the function of the rest of your liver, and your general fitness.
Why might a transplant be better than removing the tumour?
Because transplantation treats two problems at once — it removes the tumour and replaces the diseased liver that produced it, so no further tumours can arise. It is the better option for patients whose liver function is poor or who have several small tumours, provided the disease is within accepted limits and a donor organ is available.
My liver function is poor. Does that rule out surgery?
It may rule out removing part of the liver, because the remaining portion has to sustain you, and a cirrhotic liver tolerates resection poorly. It does not rule out treatment. Ablation, treatments delivered through the artery feeding the tumour, and transplantation are all options in that situation.
What are the treatments given through the blood vessels?
The tumour takes its blood supply almost entirely from the hepatic artery, while normal liver tissue is supplied mainly by the portal vein. That difference allows chemotherapy or radioactive beads to be delivered through a catheter directly into the vessels feeding the tumour, concentrating the treatment where it is needed and largely sparing the rest of the liver.
Should my family be tested?
The cancer itself is not inherited, but the conditions that cause it can run in families or households — hepatitis B in particular. Testing family members for hepatitis B and vaccinating those who are not immune is worthwhile, and it prevents the disease rather than detecting it.
Related conditions
Other conditions of the liver covered on this site:
- Liver cysts (simple hepatic cysts)
- Hydatid (echinococcal) cyst of the liver
- Liver haemangioma
- Focal nodular hyperplasia and hepatocellular adenoma
- Liver abscess
- Intrahepatic cholangiocarcinoma
- Liver metastases
This page provides general information and does not replace an individual medical consultation. Assessment and treatment are decided for each patient after review of their history, examination and imaging, and in the setting of a multidisciplinary team.