HCV Research and News: Hepatocellular carcinoma

February 7, 2012

Hepatocellular carcinoma

Jonathan Manning, Consultant Gastroenterologist, Scottish Borders. Reviewed by Luke Koupparis, general practitioner, Bristol.

Tuesday, 7 February 2012

Key learning points

Hepatocellular carcinoma is a well recognised complication of chronic liver disease.
Viral hepatitis remains the most common cause with alcohol also a significant contributor.
Screening and surveillance is often performed to detect early lesions where possible.
Surgery can be considered in fit patients with early stage disease.
Palliative therapies are now available with lower toxicities and improved patient survival .
Although key, endoscopy is not the only element in managing such patients.

Epidemiology

Hepatocellular carcinoma (HCC) refers to a liver tumour originating from within the liver tissue. Liver metastases are approximately 30 times more common than primary tumours and making this differentiation is imperative to further investigations and management. It ranks as the 5^thmost prevalent cancer in the world (7% male cancers and 3% female cancers – approximately ½ million cases per year).

Symptoms

Patients may in fact be asymptomatic and have their tumour picked up on routine scanning for other reasons. Others may present with one or a combination of fatigue, abdominal pain, ascites, weight loss, jaundice or abnormal liver blood tests. Any of these should lead to further investigations by the primary care physician, referral to a Gastroenterologist and/or other Specialist.

Aetiology

Cirrhosis is known to be the greatest risk factor for the development of HCC. Significant geographical differences are apparent in relation to this risk factor. HCC rates of 30% are reported in South Africa but lower rates of 20% in Great Britain and North America. This is likely to be related to the larger cohort of chronic Hepatitis B virus (HBV) infection seen in those countries compared to the developed world.

Figure 1: Severe liver cirrhosis with gross ascites.

In cirrhotic alcoholics there is a four-fold increase in HCC compared to the general non-cirrhotic population. Chronic viral carriage of HBV can increase the HCC risk even in the absence of cirrhosis. The same applies to chronic hepatitis C virus (HCV) infection as well, with a four-fold increase in HCC in HCV patients compared to HBV when cirrhosis is present.

The mechanism of HCC is thought to reflect disorganised DNA during cellular repair or nodule regeneration in the presence of cirrhosis or chronic inflammation. Addressing some of the other chronic liver conditions, iron overload, as seen in genetic haemochromatosis, is also high risk for HCC when cirrhosis is present.

Other high risk cirrhotic patients include alpha₁-antitrypsin deficiency, type 1 glycogen storage disease and porphyria cutanea tarda. Primary biliary cirrhosis and chronic active auto-immune hepatitis with cirrhosis are both considered lower risk scenarios than those stated above. However, cirrhotic hepatitis B or C patients co-infected with HIV are possibly at the greatest risk.

Figure 2: Histology showing chronic hepatitis with ground glass hepatocytes.

Diagnosis

Small lesions can be hard to see in a nodular cirrhotic liver and may simply represent a regenerative nodule. Once a liver lesion has been identified, often by ultrasound, several factors, including it’s likely aetiology, need to be considered. Multi-phase CT scanning, or MRI, may be required to define a lesion further and follow-up interval scanning performed as appropriate, if deemed low risk.
The current evidence suggests that the standard initial imaging interval should be 6-monthly. Higher risk patients do not warrant more intensive screening. In addition to appropriate imaging the serum α-fetoprotein level is often monitored as it can be elevated in HCC. However, it may not increase in 20-40% or so. It may also be elevated in the absence of HCC but in the presence of other cancers, such as cholangiocarcinoma. It is also raised in pregnancy.

Liver biopsy is avoided if at all possible due to the high incidence of tumour seeding, particularly if a potentially curative outcome is predicted.

Treatments

This depends on the location, size and number of the tumours and also on the fitness of the patient. Small tumours (<2-3cm) will have a 1-year survival close to 85% but only a 50% 2-year survival. Surgical resection or liver transplantation both offer the only real chance of cure. Tumours that are invading the portal vein or breaching the liver capsule would be considered unresectable and perhaps only amenable to palliative therapies. A size of 5cm is the usual cut off for suitability of a single lesion resection.

Resection offers a greater than 50% 5-year survival with a 70% likelihood of recurrence. Patients with advanced cirrhosis are poor candidates for resection with an increased mortality and risk of liver failure post-operatively. Therefore, a liver transplant offers the best alternative. A shortage of donor organs has lead to live-donor right lobe transplants, with improving results.

Radiofrequency ablation (RFA) is a palliative therapy which can induce tumour necrosis. An electrode is passed via the peripheral vasculature into the liver. Heat can be delivered directly into the lesion and therapy repeated. It can be offered in patients with lesions >2cm, with a procedure-related mortality of 0.3%. Studies have shown upto a 70% 5-year survival with this treatment.

Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) are two other alternatives for palliation. Gelofoam or small metal coils can be inserted into the feeding vessels by interventional radiologists. TACE is the same as TAE but with prior injection of a chemotherapeutic agent into the lesion with improved results but higher associated toxicity.

TACE is considered the first line therapy for non-surgical patients with HCC that has no vascular invasion. However, it is much higher risk in those with Child-Pugh B or C due to the possibility of post-treatment liver failure.

Sorafenib, is a multikinase inhibitor, which has shown a survival benefit in palliative patients. Median survival is increased from 7.9 to 10.7 months. It is offered to those patients with preserved liver function who are not suitable for other treatment modalities.

References