Hepatocellular cancer (HCC)
Discuss the risk of HCC in cirrhosis?
HCC occur mostly (90-95%) in a cirrhotic liver. There is a considerable variation in the risk of HCC development in cirrhosis of different aetiologies.
- Cirrhosis due to hepatitis B or C carries a higher risk (3-5% per year).
- Patients with cirrhosis due to genetic haemochromatosis who were iron loaded at presentation had a very high risk of HCC development (7–9% per year). The risk falls with venesection but not to baseline levels (1–3% per year).
- In contrast, patients with cirrhosis of autoimmune hepatitis have a very low risk of HCC development.
- Alcoholic cirrhosis carries an increased risk of HCC development (1-4% per year for males).
- The rate of HCC development in women with alcohol related cirrhosis seems significantly lower.
- Primary biliary cirrhosis has a low risk in females but males have a similar risk to patients with alcohol related cirrhosis.
- HCC in Wilson’s disease is well described despite adequate copper chelating therapy, although the true incidence is difficult to establish.
What are the clinical features of HCC?
- Usually have no symptoms. Some patients may present with upper abdominal pain, weight loss or a palpable mass
- HCC should be suspected in patients with compensated chronic liver disease who decompensate.
What investigations are needed to establish the diagnosis?
- Cirrhotic patient presenting with a focal liver lesion
- If AFP is raised, this confirms the diagnosis and further investigation is only required to establish the most appropriate therapy.
- If AFP is normal, further radiological imaging (CT/MRI) will usually allow a confident diagnosis to be made and proceed to assessment of treatment without the need for biopsy. In the few cases where real diagnostic doubt persists, biopsy may be indicated.
- Non cirrhotic patient presents with a liver mass
- If AFP is raised in the absence of a testicular primary, this confirms the diagnosis. If the lesion is potentially operable, then biopsy of the non- tumour liver may be required to determine the best treatment option.
- If AFP is normal, a search for other causes (non-liver primary) and further radiological assessment of the mass are required. Radiological imaging can exclude benign liver lesions with a high degree of sensitivity and specificity. Only in situations where considerable doubt exists will biopsy of the lesion be required.
- Initial assessment should be by spiral computed tomography (CT) of the liver (local spread) and thorax (metastases).
- Biopsy is rarely required for diagnosis, and seeding of tumour in the needle tract occurs in 1–3%. Biopsy of potentially operable lesions should be avoided where possible
Discuss screening tests for HCC?
- AFP, a normal serum protein synthesised by fetal liver cells and yolk sac cells, is the most widely studied screening test used as a tumour marker for HCC. The normal range for AFP is 10–20 ng/ml and a level >400 ng/ml is usually regarded as diagnostic. Up to 20% of HCC do not produce AFP, even when very large. False positive AFP is frequently seen in regenerating nodules in viral cirrhosis. A rising AFP over time, even if the level does not reach 400 ng/ml, is virtually diagnostic of HCC.
- Ultrasound can detect large HCCs with high sensitivity and specificity. In the UK at present, detection of lesions below 2 cm by ultrasound is uncommon. Combining AFP and ultrasound improves detection rates.
Discuss treatment options for HCC?
I. Surgery
- The only proven potentially curative therapy for HCC remains surgical, either hepatic resection or liver transplantation, and patients with single small HCC (<5 cm) or up to three lesions <3 cm should be referred for assessment for these treatment modalities.
- Liver transplantation should be considered in any patient with cirrhosis and HCC.
- Resection can be carried out in highly selected patients with hepatic cirrhosis and well preserved hepatic function (Child-Pugh A) who are unsuitable for liver transplantation. Perioperative mortality in experienced centres remains between 6% and 20% depending on the extent of the resection and the severity of preoperative liver impairment. The majority of this early mortality is due to liver failure. The residual liver after resection continues to have a malignant potential.
- Hepatic resection should be considered as primary therapy in any patient with HCC and a non-cirrhotic liver (including fibrolamellar variant).
- Fibrolamellar HCC has a very different biology and arises in non-cirrhotic liver. Survival rates following resection vary from 65% to 12.5%. Survival overall tends to be longer than with tumours arising in cirrhosis, and five year survival after surgical resection is approximately 25%. Liver transplantation has been undertaken for tumours which are too extensive for resection but the results are poor and thus transplantation is rarely offered for this indication.
- It is well established that patients with single lesions of 5 cm diameter or up to three lesions of less than 3 cm in the absence of vascular invasion, as defined by imaging, have an almost zero recurrence rate for HCC and the prognosis after transplantation is the same as for a similar underlying liver disease without HCC.
II. Chemotherapy has a very limited role in the treatment of HCC. Any chemotherapy used in HCC should be given in the context of clinical trials.
III. Non-surgical management
Non-surgical therapy should only be used where surgical therapy is not possible.
- Percutaneous ethanol injection (PEI) – is best suited to peripheral lesions, less than 3 cm in diameter
- Radiofrequency ablation- RFA induces temperature changes using high-frequency alternating current applied via an electrode or electrodes placed within the tissue to generate ionic agitation. RFA can be done using percutaneous ultrasound guidance.
- Chemoembolisation has been shown to affect survival in highly selected patients with good liver reserve. Chemoembolisation using lipoidal is effective therapy for pain or bleeding from HCC.
- Systemic chemotherapy has a poor response rate and should only be offered in the context of clinical trials only.
- Hormonal therapy with tamoxifen has shown no survival benefit in controlled trials and is not recommended.
Discuss surveillance for HCC?
I. Surveillance for HCC should be considered in the following high risk groups:
- Males and females with established cirrhosis due to hepatitis B or C
- Males and females with established cirrhosis due to genetic haemochromatosis
- Males with alcohol related cirrhosis who are abstinent from alcohol or likely to comply with treatment.
- Males with cirrhosis due to PBC
The risk of HCC development in cirrhosis due to autoimmune hepatitis, primary sclerosing cholangitis in both sexes, and alcoholic and primary biliary cirrhosis in women is generally low. Non-cirrhotic HCCs do occur in viral cirrhosis but the absolute risk is low.
II. If surveillance is offered, it should be six monthly abdominal ultrasound assessments in combination with serum AFP estimation. This is based on estimated median doubling time of 6 months for HCC. Patients with a negative ultrasound and an elevated but not diagnostic level of AFP appear to be at high risk and more frequent ultrasound examination in this group, probably three monthly, may have a higher yield.
III. If surveillance is offered, patients should be aware of the implications of early diagnosis and the lack of proven survival benefit.
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