New Liver Cancer Marker Promises Earlier Diagnosis and Better Outcomes

Australian researchers have found a way to predict the risk of liver cancer in people with chronic hepatitis B, promising earlier diagnosis, better management and potentially better prevention of hepatitis B- related liver cancer.

For some time now scientists have known that when the hepatitis B virus (HBV) replicates it leaves behind bits of its DNA in string form, different to its original circular shape. They refer to this as “splicing”. They also noticed that higher viral load results in more splicing; and retrospective examination of blood samples showed that splicing increased each year prior to the development of liver cancer.

It has been noted that Asians with chronic hepatitis B are more likely to develop liver cancer. Serum samples have revealed that hepatitis B genotypes more commonly found in Asia (B and C) have significantly greater levels of splicing than those common in European genotypes (A and D)1.

Presenting these findings at the recent Viral Hepatitis 2018 conference, Associate Professor Peter Revill from the Doherty Institute said one explanation of how the hepatitis B virus causes cancer in the liver is that the double stranded linear DNAs resulting from HBV splicing are more easily integrated into the similarly shaped human DNA.

Researchers compared the levels of spliced HBV by looking at blood samples from over 150 patients with liver cancer and 370 patients who have chronic hepatitis B but had not developed liver cancer.

Results showed that people with more than 10 per cent spliced HBV were at least three times more likely to develop liver cancer than those with lower levels of spliced HBV. For people with over 20 per cent spliced HBV, the likelihood of developing liver cancer rose to over 23 times more.

It may be possible to predict the development of hepatitis-B mediated liver cancer as far as five years ahead

Furthermore, it may be possible to predict the development of hepatitis-B mediated liver cancer as far as five years ahead. Examination of the blood samples found that  in people with liver cancer who have elevated levels of spliced HBV, the levels of these spliced variants started increasing five years before their liver cancer was diagnosed.

Assoc. Prof Revill said based scientists have thus validated the association between splice HBV variants and hepatitis-B related liver cancer. These “striking findings”, he said, meant that researchers have identified a new bio-marker for hepatitis-B related liver cancer.

Liver cancer is among the leading causes of cancer death worldwide and in 2015 hepatitis B virus was the leading cause of new cases of liver cancer and deathsand it is, undoubtedly, the outcome most dreaded by people living with chronic hepatitis B.

Almost 240,000 Australians live with hepatitis B with an estimated 420 deaths in 20153. Globally, 880,000 people die each year from hepatitis B related cirrhosis or cancer.

The current approach to dealing with that risk is regular monitoring with blood tests and ultrasound scans. The identification of these new markers in the blood means that by checking spliced HBV levels in the blood, doctors can identify those who need to be checked further, especially if they also have other risk factors.


  1. Other Virological Mechanisms – Prof. Stephen Locarnini, VIDRL, Doherty Institute at HBV Cure Workshop 2017, Toronto (http://regist2.virology-education.com/2017/4HBV/14_Locarnini.pdf)
  2. Global Burden of Disease Study Focuses on Liver Cancer – JAMA Network (https://media.jamanetwork.com/news-item/global-burden-disease-study-focuses-liver-cancer/)
  3. https://kirby.unsw.edu.au/sites/default/files/kirby/report/SERP_HepBandC-Annual-Surveillance-Report-Supp-2016.pdf

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