Dr Bing Liu discusses the outcomes of Project Pearl, an end-to-end liver disease management project, at Zhuhai People’s Hospital

Interview transcript:

Introduction

Hi everyone. My name is Bing Liu. I’m an interventional radiologist. I got my PhD at Heidelburg University Germany, and then finished my training as postdoc at Yale University. And then I work at Zhuhai People’s Hospital, also as a member of Zhuhai Project Pearl until April this year. And now I’m working at Guangzhou First People’s Hospital.

About Project Pearl

Project Pearl is a collaboration between Zhuhai Hospital and Roche to transform liver disease care in China through holistic, end-to-end management.

By integrating advanced diagnostics, streamlined workflows, and digital tools, it addresses challenges in hepatocellular carcinoma (HCC) care. The project focuses on early detection, personalized risk stratification, and continuous follow-up, improving patient outcomes and empowering clinicians with data-driven insights.

To date, thousands of patients are enrolled and the program shows high rates of early-stage HCC detection.

What is the current liver disease landscape in China and what is Zhuhai doing to improve HCC screening?

We all know that China has a huge burden of liver cancer accounting for over 40% of the new cases and death cases around the world. As we have already accumulated a lot of experience in our Project Pearl, we know clearly what improvements we can make in the future. We are now trying to upgrade our screening modalities, especially the patient follow-up module.

What were the key outcomes of Project Pearl?

Up to now, we have finished screening and risk assessments in 5,122 patients and 41 of them were diagnosed with HCC; the percentage was 0.8%. And besides the early diagnosis rate of HCC was reported as 30% in our country, while, in our Zhuhai project, 39 of the 41 HCC patients were diagnosed with early-stage HCC and the early diagnosis rate of HCC was 95%, which means our project has greatly improved the early diagnosis rate of HCC. For the patients diagnosed with HCC, after our MDT discussion, all of them finally received optimal treatments in Zhuhai People’s Hospital.

How has the implementation of digital solutions influenced your overall clinical workflow?

Digital solutions are great assistants to our clinicians, especially inpatient registration, data collection, data analysis, and risk assessment, it’s indeed increased the efficiency of screening and decision-making.

Based on the project outcomes, what recommendations do you have for other APAC clinicians regarding the implementation of digital solutions in their institute?

It is an artificial intelligence century now, and we have to admit that many high-techs are changing our lifestyle. Therefore, I recommend our clinicians to embrace digital solutions to grow with them. And trust me, they will finally become excellent assistants to us.

The views and opinions expressed by Dr. Bing Liu are his own views and opinions. Roche disclaims all liability in relation to these views and opinions.

Prof Jacob George discusses the shifting trends in liver fibrosis etiology and the new innovations in fibrosis detection

Interview transcript:

What is the current liver disease landscape in APAC?

So firstly, we know that the largest burden of liver disease across the world is in the APAC or the Asia Pacific region. We know that traditionally the APAC region had a high proportion of patients with viral hepatitis, and while the numbers have decreased, they are still an enormous burden in APAC.

However, the etiology of liver diseases, the main four liver diseases have significantly changed. One of the consequences of our current modern western lifestyle with overnutrition and lack of physical activity, is that the incidence and the prevalence of fatty liver disease, which I like to call metabolic associated fatty liver disease or MAFLD, has increased. And even in patients with viral hepatitis, whether it be hepatitis B or C, the concomitant association of fatty liver disease in these patients has increased. And the last group of patients is with alcohol-related liver disease. And across our region, we are seeing an increasing burden of alcohol-related liver disease in combination with MAFLD or fatty liver disease. So the epidemiology has changed and probably the commonest liver disease in APAC now is MAFLD or fatty liver disease, followed by various combinations of alcohol, hepatitis C or hepatitis B with fatty liver disease occurring concomitantly.

We know that the major clinical manifestation of end stage liver disease occurs in patients with advanced liver fibrosis or cirrhosis. These are the patients that die from liver cancer or liver failure. But the very interesting thing about liver disease as opposed to for example myocardial infarction or heart attacks, is that when you get cardiac disease, you develop symptoms. Liver disease is very asymptomatic until you have the development of cirrhosis, liver failure or liver cancer. So we’ve got this silent disease in our community affecting about 1 in 3 individuals. And we really need to be able to identify these individuals because for many of these diseases we have got good effective treatments. We can cure hepatitis C, we can control hepatitis B virus replication, we can reduce the risk of liver cancer, and even for fatty liver disease, there are treatments on the horizon and lifestyle intervention and treating the target of cardiovascular risk factors can be very, very beneficial for these patients.

So case finding becomes very, very critical in this large group of asymptomatic patients. And we need now to focus on biomarkers and biomarker algorithms to case find and diagnose disease starting from primary care but also in specialist care. When I talk about specialist care, I’m talking about the non-liver community, endocrinologists, cardiovascular physicians, kidney physicians. And we need to identify those patients with advanced fibrosis using some of the biomarkers in algorithms so that the hepatologist or the gastroenterologist can give them appropriate care so that we can detect liver cancer early and we can either treat or prevent liver failure before it occurs.

What are the current gaps in the diagnosis of liver fibrosis? What are some up-and-coming innovations for liver fibrosis detection?

Diagnosing liver fibrosis, the fundamental problem is the patient is asymptomatic, so you need to be able to use some sort of test to be able to diagnose it. The traditional tests that we all use are liver function tests: an AST, an ALT, but they’re very, very insensitive and not even very specific. And indeed you can have cirrhosis or even require a liver transplant with a normal AST and ALT. So we need to be able to look for tests or algorithms that diagnose fibrosis in an asymptomatic individual.

And over the last 3 to 4 years, there’s been a consilience of opinion and there’ve been guidelines from across the world, including from APAC, talking about algorithms to diagnose these patients. And the most simple algorithm is the FIB-4 test, which basically uses elements of the AST, ALT, and platelet count in an individual to calculate a score that predicts and stratifies patients according to the risk of fibrosis. There is also imaging-based techniques such as FibroScan and various transient elastography techniques. And there are new emerging biomarkers and biomarker combinations, such as the ADAPT score which is based on PRO-C3, that we developed a few years ago that has the potential, in combination, when used appropriately by appropriately educated individuals, to stratify patients and refer patients appropriately for therapy in specialist care.

How might the adoption of new diagnostic tools into clinical practice across healthcare systems be accelerated?

So I think for some of the simple tools such as the FIB-4 or elastography techniques, we have quite a lot of data, but we really need to do several things.

At the patient level, we need to be able to talk to patients. We need to increase awareness of two simple facts: that we do have liver disease treatments and that liver disease is asymptomatic. So the message really is we’ve got good treatments, please get your liver health assessed. That’s what we need to do for patients.

For the care groups, including the medical profession and allied health groups, we need to be able to have appropriate use and cascading use of these tests, so that it’s in a cost-effective manner; we need to be able to identify these patients.

But the other aspect that needs to happen is we need to work at a policy level, at government level, again to emphasize the importance of being able to diagnose asymptomatic disease and risk stratify individuals so that we can take care of them earlier, link them to appropriate care. So we need policy decisions at the big picture level from government, and we also need to interact with hospital and pathology systems to implement some of these algorithm-based tests. What we need to do is we need to be talking to the pathologists that run the machines, but we also need at the backend to link it to the IT services, and then integrating all that information from a pathology test, to IT development, to putting it into the electronic health records.

So a lot of work from patient level, to health professional level, to pathology laboratories, to policy has to happen. But I think we’ve now got a very good set of tests that are available. What we need now is to actually begin to implement. So we need to implement to improve patient outcomes.

What recommendations do you have for other APAC clinicians who are looking to improve their fibrosis detection and diagnosis strategy?

I think the simple message that I would give is we should be talking about liver health and we should be encouraging this concept of assessing liver health in all our patients. 70% of the world’s population today dies of cardiometabolic diseases, non-communicable diseases and liver disease is one of them. So just as you manage diabetes, chronic kidney disease, cardiac disease, we should be screening and stratifying patients for their liver disease. And many of these are very simple tests that can be easily ordered and we can also easily stratify these patients. And based on the risk stratification, patients should be appropriately referred for care.

The views and opinions expressed by Prof. Jacob George are his own views and opinions. Roche disclaims all liability in relation to these views and opinions.

Prof Grace Wong shares recommendations from the recent HKASLD Consensus on the use of PIVKA-II for HCC surveillance and detection.

Interview transcript:

What is the current liver disease landscape in Hong Kong?

In Hong Kong, the commonest chronic liver disease is chronic hepatitis B and metabolic associated steatotic liver disease, or in short MAFLD. So these two diseases affect in total more than a million out of 7.5 million population in Hong Kong. Because of the heavy disease burden, the HCC (Hepatocellular Carcinoma) surveillance for patients with chronic liver disease has been suboptimal, because of the very long waiting time for surveillance ultrasound. 

Based on the recent HKASLD consensus recommendations, how can Hong Kong clinicians use PIVKA-II in their HCC surveillance practice?

We find that our current practice using alpha fetoprotein (AFP) will be helpful in HCC surveillance. But we also noticed that roughly around a third of the patients who have HCC diagnosed will have normal AFP (levels). So in a recent pilot study in Hong Kong, organized by the Hong Kong Association for the Study of Liver Diseases (HKASLD), we found PIVKA-II would be helpful to further increase the sensitivity of detecting early HCC. So we will advise clinicians to consider using both tumor markers, AFP and PIVKA-II, together in patients who need HCC surveillance. 

How can clinicians overcome the current challenges highlighted in the consensus when incorporating PIVKA-II testing into HCC surveillance practice in Hong Kong?

At this moment, we find that using both tumor markers for HCC surveillance probably is only limited to some high risk populations. In fact, our association has been discussing with the government to prioritize patients who are at high risk of HCC, namely those with liver cirrhosis to have both AFP and PIVKA-II tumor markers as part of the screening. But we also advocate for patients who can afford paying for the tumor markers themselves, they can also consider to use PIVKA-II together with AFP in a private setting.

What advice would you give clinicians who are looking to improve their HCC surveillance strategy?

I think good communications with patients and their family is important. They have to understand the importance to adhere to regular HCC surveillance as well as to use the very sensitive tools. So, apart from the current standards: ultrasound together with AFP, we will strongly recommend to also use PIVKA-II in patients who are at high risk.

The views and opinions expressed by Prof. Grace Wong are her own views and opinions. Roche disclaims all liability in relation to these views and opinions.

Every year, liver cancer claims 740,000 lives worldwide, with 42% of these deaths occurring in China. In China, the 5-year survival for hepatocellular carcinoma (HCC) patients is just 14.4%, and over 80% of liver cancer patients diagnosed are those with Hepatitis B. Despite this alarming statistic, early screening and comprehensive, end-to-end disease management approaches remained limited in China. This created a critical gap in care, one that Zhuhai People’s Hospital in collaboration with Roche, aimed to address with the initiation of Project Pearl in 2022.

Project Pearl is a pioneering multi-stakeholder initiative designed to provide holistic care to patients with chronic liver disease by enabling end-to-end chronic disease management involving healthcare professionals, hospital administration, and payors. At its core, the project leverages on the Liver Integrated Solution, comprising of two key digital solutions:

• Liver Disease Pathway (LDP), a digital platform streamlining HCC screening workflow and offering a patient portal for better care management
• Oncology Hub (OH), a clinical workflow for multidisciplinary team meetings and decision support system

This integrated solution empowers clinicians with the right information at the right time, ensuring informed, precise decision-making throughout the patient’s journey.

Let’s explore how the patient’s journey has evolved under this new framework. Upon their first hospital visit, patients with chronic liver disease are registered on the digital solution, and are evaluated with abdominal ultrasound, AFP, PIVKA-II, and GAAD, aimed at early detection of HCC. The patients’ data and reports are synchronized for physicians to view in real time. Meanwhile, risk stratification scores provide physicians with a clearer understanding of each patient’s likelihood of developing liver cancer, allowing for more personalized, periodic surveillance plans. Physicians are able to easily arrange follow-ups with the patients and track their disease progression over time. Beyond the hospital, an interoperable mobile platform extends support with follow-up reminders, report interpretation, patient education, and 1 on 1 consultation. This empowers patients to better understand their condition and also ensures they receive continuous, standardized care, essential for early detection and intervention. For physicians, the new patient journey not only streamlines operations but also enhances clinical effectiveness by enabling early detection, offering curative treatment options, and improving patient outcomes.

The entire clinical and operational workflow from screening and diagnosis and follow-up is now automated, making it easier to manage every step of care delivery. Once patients are diagnosed with HCC, they are seamlessly transitioned into a comprehensive treatment management system. This integrated approach addresses the following challenges that are commonly observed in MDT care delivery. Lack of standardized MDT clinical protocol, absence of robust post-treatment follow-up system, and limited capabilities to analyse and gain insights from treatment data. Upon transition, a patient’s 360 report is automatically generated to show their entire patient history. This empowers them with data-driven insights to deliver clinical, operational and economic outcomes to manage HCC treatment more effectively and confidently.

Ultimately, Project Pearl enables a win for all stakeholders. For patients, early detection and personalized care plans lead to better outcomes. For physicians, streamlines, standardized workflows and digitally-enabled decision-making support clinical practice in a timely and effective manner. For the health system, the project accelerates the goals of “Healthy China 2030”, improving outcomes at reduced costs. By improving both patient outcomes and healthcare efficiency, we are taking significant steps toward a future where liver cancer can be detected early and treated effectively, creating hope for thousands of lives.

Since its launch, Project Pearl has seem promising results. Till date, 4,972 patients had been screened, and 40 cases of HCC had been diagnosed. Remarkably, 39 of those cases were detected at an early stage, offering significantly better chances for curative treatment. These outcomes demonstrate the project’s real-world impact in transforming liver cancer care and improving patient outcomes.

Quick Summary

In this article, Lab Insights summarises the key takeaways from AOGIN 2024. The bi-annual conference was held in Seoul, South Korea, this year, with the theme “Empowering Women, Together against Cervical Cancer”.

Prof Young-Tak Kim, President of AOGIN, discusses AOGIN’s recently released 2024 Position Statement to improve cervical cancer screening in the region.

Interview transcript:

Introduction

My name is Young-Tak Kim, a gynecologic oncologist and president of AOGIN. Also, the CEO of CHA Global and Women’s Hospital.

What is AOGIN’s goals for cervical cancer screening?

AOGIN, the Asia Oceania Research Organization in Genital Infection and Neoplasia was founded 20 years ago with 22 member countries, focuses on improving cervical cancer screening and prevention in the Asia-Oceania region.
Their goals include increasing awareness, enhancing screening programs, improving assess, and developing new guidelines.

The 2024 AOGIN Position Statement for Cervical cancer screening was announced at the recent AOGIN 2024. Please briefly introduce the AOGIN Position Statement.

The AOGIN Position Statement outlines key recommendations from 14 countries for enhancing cervical cancer screening in the Asia-Oceania region.
The statement aims to guide countries in improving screening programs, increasing access for underserved populations, and integrating HPV vaccination efforts.

Why is it important to use clinically validated HPV tests, especially for primary screening?

The 2024 AOGIN Position Statement emphasizes the importance of clinically validated HPV tests for primary cervical cancer screening, aligned with the WHO goals for effective cancer prevention and control.

Clinically validated HPV tests have a higher sensitivity compared to traditional Pap smears, meaning they are more effective at detecting cervical pre-cancerous lesions and cancer.
Also, HPV testing allows for longer intervals between screening, typically every 5 years, reducing the frequency of unnecessary exams and associated healthcare costs while still maintain high safety standards.
Lastly, HPV testing provides better stratification of risk of progression. Positive result can lead to immediate follow-up and management, while negative results offer reassurance for longer periods.

Why is it important for those 25-65 years to undergo testing?

It’s important for individuals aged 25 to 65 to undergo cervical cancer screening not only for early detection, but for effective prevention and risk stratification. By ensuring regular screenings, individuals can significantly contribute to their health and well-being while helping to lower the overall incidence of cervical cancer in the community.

What are AOGIN’s upcoming plans for HPV testing and cervical cancer elimination in the APAC region?

AOGIN has several upcoming plans focused on HPV testing and cervical cancer elimination in the APAC region.
First, AOGIN plans to advocate for the widespread adoption of clinically validated HPV testing as the primary screening method, emphasizing its effectiveness in early detection.
Also, AOGIN aims to work closely with government health departments to integrate HPV testing into national screening programs and align policies with international guidelines.
Lastly, ongoing research to gather data on HPV prevalence and cervical cancer incidence in the region will support evidence-based decision-making and policy formulation.

What countries does AOGIN plan to work with and why?

AOGIN plans to focus on several countries in the Asia-Pacific region, particularly those with high disease burden.

Countries like India, Indonesia, and Vietnam have high cervical cancer incidence and mortality rates, making targeted interventions vital. Also, countries such as Bangladesh, Pakistan, and the Philippines exhibit substantial gaps in achieving the WHO’s screening and vaccination targets, necessitating focused efforts to improve access and awareness.

How has HPV self-sampling helped to improve screening rates?

HPV self-sampling has shown promising results in improving cervical cancer screen rates. Studies have found that self-sampling can increase screening participation rates by 20 to 50% compared to traditional clinician-collected samples. Women often prefer the convenience and privacy of self-sampling.

Also, self-sampling helps to eliminate some barriers to screening, such as fear of the clinical environment, discomfort during examinations, and stigma, leading to more women engaging in regular screening.

Based on the Position Statement and AOGIN’s upcoming plans, how can clinicians work together with AOGIN to implement cervical cancer screening into their clinical practice?

Clinicians can collaborate with AOGIN to effectively implement cervical cancer screening in several ways. They can integrate the recommendations from AOGIN’s Position Statement into clinical practice, ensuring that screening protocols align with the latest evidence and WHO guidelines. Lastly, clinicians can join AOGIN’s networks and forums to exchange knowledge, share their best practices, and collaborate with other clinicians in the region to strengthen cervical cancer prevention efforts.

The views and opinions expressed by Prof. Young-Tak Kim are his own views and opinions. Roche disclaims all liability in relation to these views and opinions.

Dr. Huey-En Tzeng shares her experience setting up a Molecular Tumour Board (MTB) at Taichung Veterans General Hospital (VGH), and the advantages of using digital solutions to faciliate the MTB meetings

Introduction

My name is Dr. Huey-En Tzeng and I am a medical oncologist at Taichung Veterans General Hospital. I also serve as the CEO of the Precision Medicine Center, where I oversee precision oncology and lead the MTB. My journey with the MTB started in 2017 at Taipei Medical University Hospital, where Professor Yen Yun established Taiwan’s first MTB, and I was a key member. In 2022, I moved to Taichung Veterans General Hospital. With the support of the superintendent Professor Shih-Ann Chen, I established the MTB at this hospital as well.

What is the vision of cancer care at Taichung VGH?

Taichung Veterans General Hospital is the National Medical Center in Taiwan, treating five to six thousand newly diagnosed cancer patients each year. In 2019, the hospital established the Precision Medicine Center, which integrates clinical practice, tumor biology and bioinformatics to offer the latest in cancer NGS testing. In 2022, we joined the National Health Research Institutes’ Precision Oncology Demonstration Project, providing comprehensive genomic profiling (CGP) testing for 2,000 cancers patients across Taiwan. As of April 2024, we have already enrolled 440 cases. We have also assembled a team of molecule experts and hold MTB meetings every two weeks to explore and discuss the optimal treatment plan which can benefit the most to our patients. Additionally, we aim to build a robust database to accumulate real-world data and establish a large-scale precision medicine repository.

What are the challenges encountered in precision oncology diagnosis, treatment decision making and progression monitoring in your country/your institution?

Starting in May this year, the government began to reimburse NGS testing, including CGP. Additionally, hospitals are now required to establish MTB and have to submit relevant data reports to national health insurance database. CGP provides a comprehensive analysis of cancer genes, but it brings significant challenges because of the large and complicated number of the mutation variants. These different mutation variants need input from multidisciplinary experts. However, for hospitals without experts, this is a new and difficult area. Especially in terms of data management, there is an urgent need to use standard data formats and build systems that can effectively use cancer database for clinical decisions and patient outcome monitoring.

Why were MTBs important in your institution? What were the challenges you encountered in conducting oncology MTBs in your institution?

There are four objectives to set up MTB in our hospital. First, it provides consultations, including testing options, hereditary cancer tests, and report interpretation. Second, it discusses the treatment plans. Third, it refers patients to clinical trials. Lastly, the MTB plays an educational role. However, traditional MTBs rely heavily on manual effort to collect data from various sources. When we review cases, we need to look at both the genetic test mutation variants and the patient’s clinical data. This data is stored in different HIS systems, making it difficult to keep everyone on the same page. As a result, we spend a lot of time organizing discussion materials, and the conclusions from these discussions are hard to store in the HIS for the attending physicians to refer at any time. In addition, we follow up with patients every six months, so managing the MTB patient list is also very important to us.

How have digital MTBs been implemented into your institution for cancer management?

After adopting MTB digital platforms, both genetic and clinical data can be stored in the same platform. In terms of workflow, physicians just simply need to fill in the patient’s medical record number and submit it, and I will receive the submission. At the same time, the platform will initiate automated data entry. Therefore, I can quickly review the cases that need to be discussed in the MTB on the digital platform and further schedule dates for MTB discussion. Even if the MTB members are in different locations, they can edit discussion data on the platform at any time before the MTB. In the discussions of the MTB clinical trials are important information. The platform integrates external clinical trial information and can match possible clinical trials and the latest journal literature based on the patient’s genomic profiling. In addition, the decision-making process of the discussions can also be stored completely on the platform, assisting us in cancer patients management and follow up.

What is your experience using digital MTB platforms? How have digital MTB platforms streamline your process?

Using a digital MTB platform, the biggest benefit is that it automates the collection of genetic and clinical data. MTB members can look at patient level data simultaneously, making preparation faster. It also improves patient management and follow –up across specialties. In the past, the information for each step, from physicians requesting case discussions, to reviewing cases, to preparing slides, and writing discussion records – was scattered. The digital MTB platform not only helps us digitize the process but also streamlines it. I can say it saves us a lot of time and workload.

What advice would you give your fellow colleagues to incorporate digital MTB platforms into their clinical or institutional practice?

Implementing the digital MTB platform requires effective change management and the ability to endure initial challenges. I would say it requires top-down decision support to sustain it. Once we overcome this phase, we can fully appreciate the value the MTB platform brings. Additionally, during the implementation phase, integrating clinical and IT capabilities is crucial. While IT skills are fundamental, understanding clinical processes and needs is indispensable. Last but not the least, automating data integration isn’t something that happens overnight; it should align with clinical milestones and be completed by phases.

Dr. Ming-Ling Chang and Dr. Chung-Guei Huang talk about their experience using PIVKA-II, and their expectations for digital algorithms in HCC surveillance

Interview transcript:

MLC: Ming-Ling Chang

CGH: Chung-Guei Huang

Introduction

MLC: Hi, everyone, I am Dr. Ming-Ling Chang. Currently, I am the Director of the Department of Hepatology and the Gastroenterology of the Chang Gung Memorial Hospital at the Lin-Kou.

CGH: Hello everyone, I am Dr. Chung-Guei Huang. Currently, I am the Director of Department of Medical Laboratory at Lin-Kou Chang Gung Memorial Hospital.

MLC: Chang Gung Memorial Hospital is the biggest chain hospital in
Taiwan with 10 branches and more than 11,000 beds. Chang Gung Memorial Hospital at Lin-Kou is the headquarter among this healthcare system.

CGH: Our laboratory has been CAP accredited since 2003, which means every report from our laboratory meet international standards requirements; we’ve been maintaining CAP accreditation for over 20 years. Beyond CAP accreditation, we also got National Golden Quality Award several times in the past 10 years. Over 1 million tests were reported from our laboratory every month.

What are the challenges in HCC surveillance & diagnosis and testing capacity in your institution?

MLC: In Chang Gung Memorial Hospital, for patients with liver disease, we usually recommend patients with hepatitis to visit our outpatient departments every six months; while those with cirrhosis might have to come every three months. We also conduct liver cancer surveillance by using ultrasound and the alpha fetoprotein, which is AFP. However, not all patients with liver cancer can be diagnosed early despite these measures. The main reason is that the detection rate of tumor by ultrasound is affected by factors such as tumor size, the presence of fatty liver and the liver fibrosis. Moreover, the traditional serum tumor marker AFP only rises in the serum of less than half of the patients with early liver cancer, and can be affected by hepatitis flare leading to false positive results. So, patients with early-stage liver cancer can’t receive timely treatment, and this crucially affects their survival.

CGH: Because of the robust national health insurance system, there are lots of medical behaviors such as blood testing. And the increasing testing loads prompting laboratories to integrate and optimized workflows continuously. Our team had been putting many efforts on streamlining processes for over one decade, making our lab smarter and more efficient, including the application of Artificial Intelligence, business intelligence system, HIMSS 7 close loop system, which helps us successfully release additional testing capacity.

What are the important factors for your lab to consider when selecting a tumor marker?

CGH: As a certificated laboratory, a well-validated assay with official registration approval like CE or FDA is definitely our first priority.

Please share your experience implementing PIVKA-II.

MLC: Currently, in Taiwan, under the National Health Insurance, patients with liver cirrhosis and hepatocellular carcinoma, which is HCC, are entitled to undergo PIVKA-II testing twice a year. This can be complemented with ultrasound and AFP testing. Given the complementary roles of PIVKA-II and AFP in HCC surveillance, their combined use enhances the sensitivity of HCC surveillance, especially for the detection of early-stage HCC. Within hospitals, there have been numerous cases of liver cancer without elevations in AFP levels that were identified through PIVKA-II testing. These patients may exhibit either significant or insignificant ultrasound findings, providing clinicians with greater confidence to proceed with further computer tomography, which is CT, or magnetic resonance imaging, which is MRI, to confirm the diagnosis of liver cancer.

What are your expectations for digital algorithms for HCC surveillance and how is your experience with the new HCC digital algorithm so far?
CGMH is evaluating a new HCC digital algorithm in a clinical study.

MLC: To assess the severity of liver disease, we commonly rely on some algorithms or scores such as fibrosis-4, which is FIB-4, or Child-Pugh score for clinical or decision making. So, there is considerable anticipation for scores like GAAD, which integrates high-risk factors for liver cancer including G for gender, A for age, A for AFP, and the D for DCP, which is PIVKA-II. This integration is expected to serve as an early liver cancer surveillance tool, enhancing efficacy of surveillance, facilitating treatment improvement, and improving patient survival rates. We are still on the road to accumulate the research data on GAAD. If the performance meets expectations, surely, we would like to enroll all patients with high risk for HCC to undergo regular surveillance with GAAD.

CGH: The implementation and calculation framework of GAAD is a brand new trying for laboratories. However, with the rapid development of digitization, AI, and personalized medicine, laboratories are not only dealing with specimens and instruments but also digital algorithms. Facing the trends, laboratories have also strengthened efforts in digital medical talent and ensuring information security.

What advice would you give to other healthcare institutions or professionals looking to improve their HCC management?

MLC: To enhance screening efficacies for early liver cancer in Taiwan, which is a viral hepatitis endemic country, in addition to reinforcing public awareness of liver disease and encouraging regular surveillance among high-risk groups, the surveillance tools should be enhanced. It is important to follow health insurance coverage guidelines when incorporating PIVKA-II. Hopefully, in the future, digital algorithms like GAAD can be applied to further enhance early liver cancer detection rates.

CGH: The values of the testing data offers clinicians as evidence on clinical decisions. In recent years, we focused on the collaboration and communication with clinicians, which contributed to get a better understanding of their perspectives. This allowed us to integrate resources into what clinicians really need and enhancing the value of testing.

What is CGMH’s vision for liver disease and HCC management for the future?

MLC: Hopefully, through collaborative efforts across different units within the healthcare system, the caring for liver diseases, including hepatitis cirrhosis, and HCC, could be enhanced through effective screening, diagnosis, and treatment. In the future, the patients’ quality of life and the survival rates could be improved ultimately.

CGH: Delivering fast and accurate reports is a fundamental requirement for any laboratory. Additionally, we are actively introducing cutting-edge technologies to provide more valuable insights, thereby enhancing early diagnosis rates and patient survival rates.

The views and opinions expressed by Dr. Ming-Ling Chang and Dr. Chung-Guei Huang are their own views and opinions. Roche disclaims all liability in relation to these views and opinions.

Prof Pisit shares recent health economic data from Thailand, revealing that the GAAD score is cost-effective for HCC surveillance among Thai population

Interview transcript:

Introduction

Hello everyone. I am Dr. Pisit Tangkijvanich from the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Nice to meet all of you.

Could you provide an overview of the HECON study?

Hepatocellular Carcinoma, or HCC is one of the most common cancers in Thailand. From Global Cancer Statistic 2020, liver cancers, especially HCC, is the number 1 of cancer in Thailand with its highest incident in men and the fourth highest incidence in women. HCC is also a leading cause of cancer mortality in Thailand, like other countries in Southeast Asia. Together, these data highlight the importance of HCC as a major public health problem in our country.

The majority of HCC occurs in patients with chronic viral hepatitis, including hepatitis B and hepatitis C, fatty liver disease, and heavy alcohol consumption. It is generally accepted that the screening or regular surveillance for HCC should be performed in patients known to be at risk of this cancer, because the surveillance could identify HCC at an early stage and can improve the overall survival of the patients receiving curative treatment, such as surgical resection or liver transplantation.

Most professional society guidelines recommend using ultrasound and serum alpha fetoprotein, or AFP every 6 months for HCC detection in at-risk patients, such as those with cirrhosis. However, ultrasound (US) is operator dependent and its sensitivity is variable between centre to centre. Moreover, the US may have lower sensitivity in patients with obesity or fatty liver disease. As a result of US limitation, more accurate and accessible (surveillance) programs that could improve HCC early detection are required.

Currently, there are several emerging strategies for HCC detection. Among them, GAAD score which is derived from Gender, Age, and the combination of double tumour markers including AFP, and DCP (or PIVKA-II), is a promising tool for early detection of HCC. The available data show that GAAD score is superior to US for HCC diagnosis with a high sensitivity and specificity.

So the aim of our HECON study was to compare cost-effectiveness analysis between GAAD score with the standard-of-care using US plus AFP for HCC surveillance in Thai patients with compensated cirrhosis and chronic hepatitis B.

Could you walk us through the methodology employed in the HECON study and discuss key findings or results?

We selected cirrhotic patients in our study because these patients are at-risk of developing HCC as the incidence rate is more than 1.5% per year. For non-cirrhotic hepatitis B, we included this group of patients because the infection is highly prevalent in Thailand and also the subgroup of patients that at-risk of HCC, especially among males older than 40 years, and females older than 50 year, or those with family history of HCC.

So, we performed an economic model with Markov micro-simulation to simulate disease progression for individual patients, based on Thai population data. Literature review and interviews with Thai clinical experts were also used to identify model inputs that reflect current Thai clinical practice. Health states within the model were based on the patient’s underlying liver disease, such as cirrhosis or non-cirrhotic hepatitis B, HCC staging, such as early or late stage and treatment outcome according to the cancer stage.

Our results showed that GAAD score was cost-effective for Thai populations at the willingness to pay threshold of 160,000 THB (or approximately 4,400 USD). In fact, GAAD yielded lower cost and a better health outcome compared to US plus AFP. In addition, sensitivity analysis confirmed that routine surveillance using GAAD score had at least 55% probability of being cost-effective compared to no surveillance.

Together, our data indicate that GAAD score is suitable for use as a screening tool in Thailand.

In your opinion, what makes the HECON data important in the context of changing healthcare policies and decision-making in Thailand?

As the burden of liver cancer is high, HCC surveillance and control must be considered a public health priority. However, in Thailand, national efforts are focused on the control of viral hepatitis, which is primary prevention for HCC rather than the cancer surveillance.

So our data show that the new method using GAAD score is cost-effective, and importantly more feasible than US plus AFP testing, because GAAD score can be done the same day in the clinics. That will help in reducing several patient barriers such as transportation or logistical concerns.

Our data could play an important part in supporting the policymakers for making the best decision within limited resource in our country, to accelerate the reimbursement program for HCC surveillance in the future.

Are there any challenges or considerations that healthcare professional should be aware of when interpreting or applying the results of the HECON study in clinical practice?

Although our study provides promising results, there might be some concerns about the role of GAAD score as a screening tool for HCC detection. For example, in countries where there are inadequate facility for cancer therapy, the benefit of early detection might be reduced as limited number of patients could achieve curative treatment. In contrast, GAAD score is more suitable in community hospital or rural areas where access to US is limited, such as some areas in Thailand and many countries in the APAC region.

How do you foresee the results of the HECON study will help to inform clinicians’ HCC surveillance and clinical practice in the APAC region?

I think the results of HECON study can be used not only in Thailand but also can be applied to other country as well, which had a similar situation as Thailand, for example, the Philippines or Vietnam. Thank you.

The views and opinions expressed by Prof. Pisit Tankijvanich are his own views and opinions. Roche disclaims all liability in relation to these views and opinions.

Results of the Liver Ecosystem Advancement Project (LEAP) initiatives in Thailand

Listen to the podcast discussion with Dr. Passakorn Wanchaijiraboon on the EZ Liver Clinic

Introduction

Hepatitis B (HBV) and Hepatitis C (HCV) viruses significantly impact public health in Thailand, affecting about 5% (2-3 million people) and 0.4% (300,000 people) of the population, respectively. [1] Chronic HBV infections account for 49.8%  [2] of hepatocellular carcinoma (HCC) cases.

Despite a decline in viral hepatitis due to effective vaccinations and treatments, HCC related to metabolic dysfunction–associated steatotic liver disease (MASLD) is on the rise.[3]

Liver cancer remains the leading cause of cancer-related deaths in Thailand, accounting for over 10,000 deaths annually as of 2008, with a mortality rate of 87% and a survival rate of only 13% post-diagnosis. It is the most common cancer among men and the third most common among women.[1] Challenges in treatment include a lack of healthcare staff and resources, particularly in rural areas, and insufficient nationwide epidemiological data for tracking infected patients.[3] Managing these diseases in a diverse and uneven healthcare landscape requires innovative approaches.

In response, integrated health initiatives such as the Liver Ecosystem Advancement Program (LEAP)  were developed to bridge these gaps. They focus on improving the patient pathway, from screening and diagnosis to treatment and surveillance, using multi-disciplinary approaches and leveraging digital health platforms to enhance patient education and healthcare provider training. [1,3] 

The LEAP Program: Bridging Gaps in Hepatitis Management

LEAP represents a strategic initiative to address the comprehensive needs of hepatitis management in the APAC region. In Thailand, it is a collaborative effort involving healthcare professionals (HCPs), experts, and policymakers from the National Health Security Office. It combines functions into a cohesive system that enhances the management and surveillance of hepatitis and its progression to HCC.

1. Efficacy of the HBV Screening Pilot

“The patient pathway should include screening for viral hepatitis (HBV, HCV) in the general population. Infected persons will then be linked to antiviral treatment and care by general practitioners and/or medical specialists. Subsequently, high-risk groups will require further tests for HCC surveillance, or referrals for HCC treatment if indicated,” says  Prof. Pisit Tangkijvanich. [3]

One of the critical programs launched under LEAP was the nationwide HBV screening pilot. It evaluated people born before 1992, targeting a demographic that was largely unvaccinated and at higher risk for HBV. Approximately 100,000 Hepatitis B Rapid Test Kits (HBsAg strip tests) were distributed across 100 primary healthcare settings and district hospitals in more than 30 provinces across 5 regions. Under LEAP,10,000 fingertip blood tests for hepatitis B were provided at Sub-district Health Promoting Hospitals (SHPH) to benefit residents of other districts in Chanthaburi.[3]

The HBV screening pilot involved nearly 100,000 tests on a demographic of 40% males and 60% females, with average ages of 49.6 and 52.5, respectively. It found a 3.1% total HBV prevalence, down from 4.5% nationwide [4] in 2014, providing crucial data for governmental planning and resource allocation. [3]

Amplifying the Impact of HBV Screening with Digital Health Platforms and Education Campaigns

“Digital health platforms have the potential to increase awareness and knowledge, as well as facilitate HBV care that leads to the prevention and early detection of HCC,” continues Prof. Pisit Tangkijvanich. [5]

To boost the efforts of the HBV screening pilot, HBV-infected patients and healthcare professionals were engaged through various digital interventions. These included a self-administered questionnaire and e-learning modules to help patients better understand the disease and empower them to take charge of their liver health. Additionally, an online training program was developed for healthcare professionals to enhance their capacity in managing HBV. 

Even in remote areas, significant public engagement was achieved through the World Hepatitis Day Campaign 2023, using videos, infographics, and texts across multiple digital platforms like Facebook, YouTube, and TikTok. This campaign alone garnered almost 9,000,000 views. [3]

2. The EZ Liver Clinic: A Comprehensive Care Model

The EZ Liver Clinic at the Phrapokklao Cancer Center of Excellence, the first in Thailand, represents a pioneering model in the integrated care for hepatitis and HCC, in the eastern provinces. Led by medical oncologist Dr. Passakorn Wanchaijiraboon, operator of the Chantaburi EZ liver network, this clinic was developed to address the region’s high prevalence of liver diseases by streamlining the process from screening to treatment.

It offered four key elements: proactive high-risk HCC group identification, digital health for HCC surveillance, new biomarkers for surveillance, and health information exchange. [1,5]

The clinic focused on comprehensive liver function testing, ultrasound diagnostics within six weeks, and swift connection to treatment options such as microwave ablation or liver transplantation, if necessary. 

The program’s success was evident as it: 

• Revealed an HBV prevalence of 5.5% over three years in the Chanthaburi province.
• Reduced waiting time for treatment from 6 months to less than two months.
• Ensured collaboration among GI physicians, radiologists, interventionists, hepatobiliary surgeons, and medical oncologists to streamline patient care.

Over the past two years, 30,000 at-risk individuals were screened, identifying new Hep B patients; 50% required no treatment due to normal liver inflammation levels, while the other 50% were referred to Siriraj Hospital for treatment.[1] 

Early-stage liver cancer was detected in some, leading to referrals for potential curative surgeries or microwave ablation, supported by 2.5 million baht donations to purchase necessary equipment. 

After the clinic’s success, the Ministry of Public Health (MoPH) announced the “Cancer Warrior” project to prevent, screen and provide effective treatment for various cancers, including liver cancer. The goal is to screen 1,000,000 at-risk individuals above 35 years old for HBV. [1]

EZ Liver Clinic Supporting Initiatives

As Dr. Passakorn Wanchaijiraboon emphasises, “Resolving breaks in the ecosystem cannot always be tackled by more resources, but we can look towards technology to connect the resources we do have.” [5]

Digital platforms for education and screening have expanded access and engagement, proving essential for the widespread dissemination of health information. Examples include:

• Health Link is a cloud platform under development intended to store and share patient health information digitally and connect community labs with referral hospitals to streamline the diagnostic and treatment processes.
• SurviLiver is an app with educational materials, a patient diary, an appointment booking system, and features allowing physicians to monitor their patient’s health between visits. [1]

These solutions are still undergoing development to allow the full integration of appointment scheduling and teleconsultation with the hospital systems. [1]

To further these initiatives, the partnership between the Ministry of Public Health (MoPH) and the Ministry of Digital Economy and Society (MDES) is necessary. While MDES handles the development of the Health Link project, it is the medical personnel from MoPH who are in charge of direct care for HCC and HBV patients.[5]

Future Directions for Scaling Up: Shaping reimbursement policies, education and partnership

Updating national guidelines to include the latest diagnostic tools and treatments would ensure advanced care is available uniformly across all regions.[3]

In Thailand, AFP testing costs approximately USD 8, and PIVKA-II costs about USD 10.  Ultrasound is significantly more expensive at around USD 100 per session, with long waiting times. [5] 

To advocate for improved surveillance strategies – such as blood-based biomarkers, compared to traditional methods like ultrasound – the HECON study evaluated the cost-effectiveness of HCC surveillance in Thailand. 

The results showed that GAAD (Gender, Age, AFP, DCP/PIVKA-II) was cost-effective in Thailand at ICER <160,000 THB compared to no surveillance. GAAD also yielded lower costs and better health outcomes than US + AFP. [6] These data are invaluable in shaping local reimbursement policies to include blood-based biomarkers in HCC surveillance strategies. 

Additionally, broadening insurance coverage for critical diagnostics and treatments is recommended to address gaps in hepatitis management and enhance access and affordability. Investing in Health Information Exchanges, patient management apps, and provider training would also streamline monitoring and data management. 

As seen from the HBV Screening promotion efforts, educational campaigns can be effective in reaching even those in remote areas. Educational campaigns should be continued to boost hepatitis awareness and screening rates. [3]

Leveraging partnerships with the diagnostic and pharmaceutical industry can boost resource availability and technology transfer. This was exemplified by collaborations with Roche that catalysed efforts in the EZ Liver Clinic. [1] Collaboration and partnership are critical for these next steps, wherein HCPs, patients, government and industry partners will need to work closely with each other in order to effectively manage liver disease.

Conclusion

The LEAP program has enhanced patient pathways and healthcare access in Thailand through the synergy between the HBV Screening Pilot and the EZ Liver Clinic. By combining the strengths of both initiatives of wide-scale screening and education with an integrated care model, there has been a comprehensive enhancement in managing liver diseases from prevention to treatment.

Listen to our podcast episode with Dr Passakorn Wanchaijiraboon to find out more about the EZ Liver Clinic.