Prof Chan Wah Kheong shares findings from the Malaysian multicentre study on the use of GAAD in HCC detection – Expert Insights from LEAD 2025, the leading APAC Liver Disease Expert Meeting

This is a verbatim transcript of an interview conducted with Prof Chan Wah Kheong in June 2025. The transcript has been lightly edited for clarity.

Introduction

Hello, everyone. I’m Professor Dr Chan Wah Kheong from the University of Malaya Medical Centre and the University of Malaya Specialist Centre in Kuala Lumpur, Malaysia.

What is the current practice in the detection of hepatocellular carcinoma (HCC) in Malaysia?

Hepatocellular carcinoma is the fifth most common cancer in Malaysia, is one of the leading causes of cancer death. And the most common aetiology underlying the liver disease is chronic hepatitis B infection. However, over the years, we are seeing [an] increasing contribution from metabolic dysfunction–associated fatty liver disease (MAFLD).

In the study that we have conducted, metabolic dysfunction–associated fatty liver disease contributed to over two times the proportion of cases of liver cancers in our centre, and the way that we actually look for liver cancer is by performing ultrasound and alpha-fetoprotein (AFP). We do these every 6 months for patients who are at risk of developing liver cancer. This would include patients with cirrhosis as well as patients with chronic hepatitis B infection, for men over the age of 40 years old, for women over the age of 50 years old, as well as for those with a family history of liver cancer.

However, despite the availability of liver cancer surveillance, we still see a lot of our patients presenting at a very late stage. In the study that we have done in our centre, only about 11% of patients present with very early or early disease, where the chance of curative treatment would be much higher. The remaining 89% actually present at later stages, where the chance of curative treatment becomes very low.

So there is certainly a gap that needs to be filled in terms of liver cancer surveillance. And because of that, we actually worked on a scoring system, it’s called GAAD. Basically, it’s an algorithm that uses gender, age, alpha-fetoprotein, and PIVKA-II, and it is a method to actually increase the surveillance for HCC in our at-risk population.

Could you briefly outline the design of this Malaysian multicentre study on GAAD?

So in this study, we actually included 400 patients: 320 of them had increased risk of liver cancer, whereas 80 of them are patients who were diagnosed with early liver cancer.

This is a prospective study. After enrolment into the study, we followed patients for 6 months. So those patients who were in the control group, in case they developed liver cancer within the next 6 months, they would actually be analysed as a case. And we looked at the sensitivity and specificity of the different biomarkers, including AFP, PIVKA-II, and GAAD.

What were the study’s key findings on GAAD’s performance in detecting early-stage HCC?

We found that there was an incremental sensitivity in this order, whereby [with] AFP, we only found a sensitivity of about over 40% and [with] PIVKA-II, over 50%, but with the GAAD score, the sensitivity was over 60%.

So we know that using ultrasound and AFP for liver cancer surveillance has a sensitivity of about 68-over percent for detection of early cancer. And in other words, based on our study, we found that GAAD is at least as good as ultrasound plus AFP for the detection of early cancer.

We know that GAAD is a blood-based scoring system. So our patients with chronic liver disease, as part of their follow-up, would need blood tests anyway, and it’s actually a convenient method for liver cancer surveillance. We just need to add on this additional blood test from the blood sample that we have taken, instead of having the patient go for ultrasonography in another department and sometimes on a different day.

Of course, ultrasound also depends on the operator. And in certain conditions – for example, in a patient with MAFLD, who are often overweight or obese – ultrasound may be inadequate. We know that as many as 20% of patients who go for ultrasound for liver cancer surveillance actually have inadequate examinations. And this is especially so when the underlying liver disease is MAFLD and/or if the person is overweight or obese. So perhaps a blood-based biomarker like GAAD can be useful, especially in this population.

What does GAAD mean for early HCC diagnosis?

I believe patients want convenience during their follow-up with their doctors. So it’s difficult for a patient to come on multiple visits, to have a blood test done, and then to come again another day for ultrasound, and come again another day to see the doctor. It would be good to come in, have the blood taken.

And in that sense, GAAD provides a very good solution, because using the same blood test that has been taken, we already could perform liver cancer surveillance in those at-risk patients. When they come and see their doctor, they can already see the result.

In terms of our laboratory colleague point of view, I think it will be ideal if the system provides the result instantaneously, rather than each of the individual biomarker results and then having to key into a system to get the GAAD score. So if it’s possible to have the GAAD score directly from the computer after the test has been run, that will save a lot of work in the lab, and I feel that this will be a good solution in the liver cancer surveillance program.

What is the key takeaway for APAC clinicians considering GAAD?

Having said that, there’s increasing evidence that ultrasound plus GAAD provides even greater sensitivity for the detection of early liver cancer – up to nearly 90%. So there is a possibility that in the future, with the addition of GAAD to ultrasound, we can diagnose liver cancer at even earlier stages, so that patients have a much higher chance of receiving curative treatment.

The views and opinions expressed by Prof Chan Wah Kheong are his own views and opinions. Roche disclaims all liability in relation to these views and opinions.