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. 

Liver Ecosystem Advancement Project (LEAP) highlights New Zealand’s successful National Hepatitis B Screening Program

Listen to the podcast interview with Prof. Ed Gane on New Zealand’s National Hep B Screening and Surveillance Program

The Challenge of Viral Hepatitis and HCC in New Zealand: A Closer Look

Globally, 240 million people are affected by hepatitis B virus (HBV, Hep B), surpassing deaths from tuberculosis, HIV, and malaria in the WHO Western Pacific Region [1]. HBV is a major cause of hepatocellular carcinoma (HCC), with chronic infections accounting for over half of HCC cases [2]. In response, the United Nations aims to reduce HBV infections and deaths by 2030, with vaccinations from 1990 to 2020 preventing an estimated 310 million infections [3].

In New Zealand, HBV significantly impacts Maori (5.6%), Pacific peoples (7.3%), and Asians (6.2%), who represent over 50% of liver disease mortality, compared to 10% among European New Zealanders [1].

Despite a robust healthcare system, New Zealand faces hurdles in enhancing public awareness, fighting stigma, and increasing testing access, as emphasised by Prof. Ed Gane, Chief Hepatologist, Transplant Physician and Deputy Director of the New Zealand Liver Transplant Unit at Auckland City Hospital, and Professor of Medicine at the University of Auckland, New Zealand.

Nearly half of New Zealand’s chronic HBV infections remain undiagnosed [1], leading to late HCC detection.

Advanced-stage diagnoses leave limited treatment options, with life expectancy post-diagnosis ranging from 7 to 22 months [4]. This underscores the need for better HBV screening, diligent follow-up, and robust HCC surveillance to improve outcomes.

In response, the New Zealand National Hepatitis B Screening Program [5] emphasises early detection, public awareness, and healthcare access, serving as a global model for managing HBV and strengthening HCC surveillance protocols to enhance patient outcomes.

Quick Summary

The recently published Chinese standards for the diagnosis and treatment of primary liver cancer [1] mention various screening strategies, including abdominal ultrasonography (US), serological tests such as alpha-fetoprotein (AFP) and protein induced by vitamin K absence/antagonist-II (PIVKA-II).

However, combined screening strategies may be associated with increased costs. The Chinese guidelines [2] highlight that there is a lack of health economic evaluations and evidence on the cost–effectiveness of different liver cancer screening strategies.

This study aims to compare the cost-effectiveness of seven screening strategies:

1. US
2. AFP
3. PIVKA-II
4. AFP+US
5. AFP+PIVKA-II
6. GAAD
7. GAAD+US

This was done by developing a health economic model from the Chinese healthcare system perspective to identify the most cost-effective strategy for early detection of liver cancer in patients with chronic hepatitis B in China.

Prof MF Yuen & Ronald Lo discuss the liver health ecosystem in Hong Kong, including hepatitis screening and HCC surveillance

Find out more about PIVKA-II in Hepatocellular Carcinoma (HCC) detection, or download our HCC Detection (HD) expert pack by filling in the form below:

Interview transcript:

Ronald Lo:

Hello everyone! Welcome to this video. I’m Ronald, the General Manager of Roche Diagnostics Hong Kong. It’s my honour today to invite Professor Yuen to have a discussion around the topics of hepatitis and hepatocellular carcinoma (HCC). Hello Professor Yuen.

Prof. MF Yuen:

Hi, I am Professor MF Yuen, the Chief of Division of Gastroenterology and Hepatology in the University of Hong Kong.

Ronald Lo:

Again, thank you so much for joining us today. So the first question I would like to get your advice would be, what is the current liver health landscape in Hong Kong; and what are the unmet needs in hepatitis screening and HCC detection in Hong Kong?

Prof. MF Yuen:

At present, Hong Kong still has a high prevalence of 7.8% hepatitis B population, amounting more than 550,000 people. According to the most recent statistics, there were more than 1,700 new cases of liver cancer in 2020. And it is known that more than 80% of Hepatocellular Carcinoma are caused by Hepatitis B infection. Even with this high rate, we do not have population screening program for Hepatitis B infection, and the surveillance for HCC is also suboptimal with respect to the lack of routine regular ultrasound of the liver for Hepatitis B patients. It is mainly due to manpower and financial constraint in the public hospital sector. On top of all these, we do not have a well-organised strategy to deliver disease information to our population. Majority of people do not know the serious disease consequence of Hepatitis B infection which may lead to early death. They also lack of knowledge of early treatment would prevent all these deleterious outcomes.

Ronald Lo:

So I would like to learn from you more, what are the recent advances in the diagnosis of HCC; and how do you see these impacting patient care and the chronic liver disease management in Hong Kong?

Prof. MF Yuen:

From Asian experience, the use of additional biomarkers, such as PIVKA-II, can significantly increase the pick-up rate of HCC at early stage, increase the likelihood for curative treatments, and thus improve the survival. New digital algorithms combining age, gender and biomarkers, such as GAAD and GALAD, have been proposed since 2013, and currently undergoing clinical validations. Recent data presented during APASL 2023 demonstrated that the use of PIVKA-II based algorithm is more cost-effective than current standard of care among Hepatitis B or cirrhotic patients in Hong Kong, which allows an earlier HCC detection and a reduced cost in subsequent HCC treatment.

Ronald Lo:

Let’s switch the gear a bit. So how do you think we can improve the coordination and integration of care among various healthcare providers and systems?

Prof. MF Yuen:

I think the most important step would be the active involvement of different concerned parties, including health care sectors from government, private institutions, policy makers, patient groups, and different NGOs, to establish a core committee which could liaise with different stakeholders to ensure the implementation of different measures to enhance diagnosis rate, screening strategy and treatment.

Ronald Lo:

And to add on, how do you see the future of liver health in Hong Kong, and what steps do you believe need to be taken to improve the patient outcomes?

Prof. MF Yuen:

The future of liver health in Hong Kong depends on whether we could have a statutory body which taking charge of planning, liaising and implementing different measures at different levels.

Ronald Lo:

Thank you Professor. So probably would be my last question. So how do you see the role of the government and the policy in addressing the liver health ecosystem?

Prof. MF Yuen:

Hong Kong government has been working on different policy making processes and decisions by involving different committees. However, the decisiveness should be more enhanced so that policy can be rolled out at a timely manner.

Ronald Lo:

Professor Yuen, thank you so much for your time today and your inspiring insights on the topics of hepatitis and HCC. And I’m sure that there are always many areas that we could further work on together to improve patient outcomes. And thanks a lot for contributing to the “Combating Cancer” educational platform as well. Thank you so much, thank you!

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

Quick Summary

The risk of hepatocellular carcinoma (HCC) is reduced but not eliminated after nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB). This study aimed to investigate the role of serum Prothrombin Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) and alpha-fetoprotein in predicting HCC and mortality in cirrhotic CHB patients at virological remission (VR) following NA therapy. 

Patients with CHB-related cirrhosis undergoing NA therapy from two medical centers in Taiwan were retrospectively included. Serum PIVKA-II were quantified by an automated chemiluminescence assay. Multivariable Cox proportional hazards regression models were used to identify predictors for HCC and death. Serial on-treatment PIVKA-II levels after VR were investigated.

Quick Summary

This study aimed to determine the cutoff values and compare the diagnostic role of alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) in chronic hepatitis B (CHB).

It was found that the optimal cutoff values for PIVKA-II and AFP were 40 mAU/mL and 10 ng/mL, respectively, for the differentiation of hepatocellular carcinoma (HCC) from nonmalignant CHB. Based on the study, when PIVKA-II and AFP were combined, the diagnostic power improved significantly compared to either AFP or PIVKA-II alone for the differentiation of HCC from nonmalignant CHB, especially when cirrhosis was present.

Therefore, serum PIVKA-II might be a better tumor marker than AFP, and its combination with AFP may enhance the early detection of HCC in patients with CHB.

Authors: Seung In Seo, Hyoung Su Kim, Won Jin Kim, Woon Geon Shin, Doo Jin Kim, Kyung Ho Kim, Myoung Kuk Jang, Jin Heon Lee, Joo Seop Kim, Hak Yang Kim, Dong Joon Kim, Myung Seok Lee, Choong Kee Park