Over the years, I have had patients who have had curative surgery for hepatocellular carcinoma (HCC, primary liver cancer) but who then declined to take anti-viral medication to suppress the hepatitis B virus (HBV) within their body. The reasons put forward include: the medicine will not get rid of the virus completely, I don’t like taking unnecessary medicine and it’s inconvenient. 

HCC is a known and dreaded complication for a chronic HBV carrier. HCC usually occurs on a background of liver cirrhosis (hardened liver) but it can occur in a relatively normal liver too. HBV carriers have an increased risk of developing HCC because of the virus itself and also because of the development of liver cirrhosis. Once HCC is diagnosed, the only curative treatment is complete surgical removal of the cancer. Despite a curative liver resection, these patients still have a chance of cancer recurrence because of the underlying HBV infection and / or liver cirrhosis. At present there is no effective treatment to reverse liver cirrhosis. However, we do have drugs to suppress the virus.

A recent study from Hong Kong University examined the impact of anti-viral therapy on the overall and disease-free survival of chronic HBV carriers who had had curative liver resection for HCC (Arch Surg 2011; 146: 675 -681). Between 01/09/2003 and 31/12/2007, 136 patients had major liver resection for HBV-related HCC. Of these, 42 patients received anti-viral therapy (treatment group) and 94 patients did not (control group). The overall and disease-free survival rates of the treatment group were significantly better than those of the control group. The 1-, 3- and 5-year overall survival rates in the treatment group were 88.1%, 79.1% and 71.2% compared to 76.5%, 47.5% and 43.5%, respectively, in the control group (p=0.005). The 1-, 3- and 5-year disease-free survival rates in the treatment group were 66.5%, 51.4% and 51.4% compared to 48.9%, 33.8% and 33.8%, respectively, in the control group (p=0.05). Sub-group analysis showed that anti-viral therapy conferred significant survival benefit in patients with stage I and II HCCs without major venous invasion.

Most HCC patients who have had curative liver surgery die from complications from the underlying liver cirrhosis or from cancer recurrence. There is evidence to suggest that suppressing the virus can reduce the risk of cancer recurrence and may retard the onset or progression of cirrhosis related complications. Some patients like to react to an illness appearing again while others would rather prevent an illness from recurring. Are you the reactionary type or the preventive type? I know what I would rather be. Do you?

Two weeks ago I saw a patient who is known to be a carrier of hepatitis C virus (HCV). He was diagnosed in 2005 but for the last few years had not had regular surveillance of his liver. He had felt bloated for a few months and saw his doctor recently. Subsequent investigations showed he had bilobe liver cancer (hepatocellular carcinoma, HCC) in a cirrhotic liver. Curative surgical resection was not an option as he had lesions in both the right and left lobes of the liver. [The best scenario for any patient with HCC is the presence of a small (< 2cm in diameter) tumour confined to one lobe of the liver (i.e. stage I / II cancer).] Would the situation be different if he had had regular surveillance?

Researchers from Hiroshima Prefectural Hospital reported the results of a study evaluating the usefulness of regular check-ups by ultrasonography and contrast-enhanced imaging for early detection of HCC in patients infected with HCV (J Gastroenterol 2009, Oct 29; epub). From April 2001 to March 2007, 240 consecutive HCV patients with HCC were studied. These patients could be classified into 3 groups:- Group A patients had their HCC diagnosed by regular, imaging surveillance; Group B patients had their HCC detected during scheduled doctor visits for liver disease or other diseases such as diabetes and Group C patients had their HCC detected when they felt a need to visit a doctor. The study found that the prevalence of single tumour at the time of diagnosis was 66% in group A patients. Group B patients had a prevalence of 48% while it was only 24% in group C patients. The percentage of stage I and II patients were 83% for group A, 53% for group B and 24% for group C. The number of patients who underwent curative procedure (surgical resection / ablation) was 99/124 (80%) in group A, 42/79 (53%) in group B and 10/37 (27%) in group C.

At the present moment, we cannot, with one blood or x-ray test, predict the risk of developing HCC in anyone who is a carrier of the hepatitis B (HBV) or C virus. The only way we can help these carriers is to perform regular blood and x-ray screening at 6 monthly intervals. The surveillance / screening is to afford us a chance to detect the liver cancer at an earlier stage. It does not stop the development of the cancer. If the liver cancer can be detected at an earlier stage, the chance of having a curative treatment is much higher.     

To all HBV & HCV carriers and people with liver cirrhosis, please remember to go for regular screening. Please do not wait until you have symptoms. It could be a bit late by then.

Hepatocellular carcinoma (HCC) is the 5^th most common cancer worldwide. Its incidence is very high in Asia and Africa and the incidence in Europe and the US is increasing. HCC can grow to a significant size before becoming symptomatic. Consequently, most HCC are diagnosed late and are not amenable to curative treatments, namely surgical resection and liver transplantation. Surgical treatment for patients with early stage HCC provides good long term survival. In patients with good liver function and a single HCC lesion < 5cm in diameter, the 5-year survival rate following surgical resection is 70%. In patients with HCC meeting the Milan criteria, the 5-year survival rate following liver transplantation is about 74%. The median survival of patients with advanced HCC on supportive care is about 14 – 16 weeks. Thus, early detection of HCC leads to a much better prognosis. At present, the only viable option for early detection of HCC is to undergo regular surveillance with blood tests for the tumour marker, alpha feto-protein (AFP), and ultrasound scan of the liver. However, the number, type and interval of tests can vary among physicians, institutions and countries. So what is the best schedule for the at-risk population?

Researchers from the University of Michigan recently performed a meta-analysis on 13 published studies using ultrasound and AFP for early HCC detection in patients with liver cirrhosis (Aliment Pharmacol Ther 2009; 30: 37 – 47). The study showed that the pooled sensitivity and specificity for ultrasound in detecting HCC at any stage is 94%. For detection of early HCC, the pooled sensitivity is 63%. However, surveillance intervals affected ultrasound sensitivity in detecting early HCC. When the surveillance interval was < 6 months, the pooled sensitivity is 70.1%. The pooled sensitivity drops to 50.1% when the surveillance intervals are between 6 and 12 months. (There is no difference in the sensitivity of ultrasound between European and Asian studies and between studies conducted before and after 1992. This suggests technological advances did not play a major role.) When AFP is added to ultrasound surveillance, the pooled sensitivity for early HCC detection increases to 69%.

The current guidelines from the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of the Liver recommend surveillance of cirrhotic patients with ultrasound with or without AFP every 6 – 12 months. The study above demonstrated a significantly higher sensitivity for early HCC detection when ultrasound scanning is performed at or less than 6 monthly intervals. In Japan, some institutions have a policy of screening the at risk population every 3 months and analysis of their data showed earlier detection of HCC which are also smaller in size at diagnosis. Although the above study only dealt with patients with liver cirrhosis, regular surveillance is recommended for all patients who are carriers of the hepatitis B (HBV) and C (HCV) virus, with or without liver cirrhosis. While it is tempting for an HBV and HCV carrier to think that “It will never happen to me so I don’t need surveillance”, I would certainly not take that chance if I were a carrier.