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

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 Tawesak Tanwandee and Asst Prof Sansnee Senawong demonstrates how digital algorithms are used in Siriraj Hospital for the early detection of HCC

Interview transcript:

TT: Prof. Tawesak Tanwandee

SS: Asst. Prof. Sansnee Senawong

Introduction

TT: My name is Tawesak Tanwandee, Professor of Medicine, Head of Division of Gastroenterology, Faculty of Medicine, Siriraj Hospital.

SS: Hello, I am the Assistant Professor of Medicine, Sansanee Senawong, Chief of the Immunology Department, Faculty of Medicine, Siriraj Hospital, Mahidol University.

TT: Siriraj Hospital is the largest and the oldest hospital in Thailand. As it is a large and highly advanced hospital, a large number of patients come to Siriraj Hospital annually.

SS: The laboratory of the Department of Immunology was certified by the international standard ISO 15189 since May 2006. It has passed the continuous evaluation and inspection for the ISO 15189:2012 standards to date.

TT: As we are a large hospital, we receive patients from other hospitals. The patients who are referred to our hospital are mostly terminally ill. They are already in the terminal stage of cancer.

What is the unmet need in HCC surveillance and diagnosis in Siriraj Hospital?

SS: In Thailand, liver cancer is one of the most common and leading causes of death in cancer patients in the country. We find that over 70% of patients who die of liver cancer are not admitted to the surveillance program, resulting in delayed diagnosis at the terminal stage and they pass away soon after.

TT: For patients at risk of liver cancer, we don’t always have the chance to screen them sufficiently at an early stage. Moreover, an early stage of liver cancer has no visible symptoms. Therefore, the patient does not realize they need to be tested.

SS: In terms of liver cancer, there are still challenges regarding the effectiveness of liver cancer surveillance.

TT: The standard practice for liver cancer surveillance today is composed of ultrasound scans and blood (biomarker) tests to check alpha fetoprotein (AFP) levels every 6 months.

SS: However, we find that the sensitivity rate is as low as 63%.

TT: Due to ultrasound capacity limitations, patients may have to wait for months or even a year for a scan. Ultrasound also relies heavily on the doctor conducting the scan and how meticulous they are. Patients who are obese or have been diagnosed with liver cirrhosis, may be difficult to detect liver cancer by ultrasound.

SS: As a laboratory, when choosing a test or a platform for our services, we must take into account the challenge of reporting laboratory results quickly and efficiently to keep up with the increasing laboratory workloads. Also, it has to minimize human errors as much as possible. We need to find an appropriate system that can support various biomarker testing and is reliable.

What is your clinical experience with PIVKA-II? How has it brought value to HCC diagnosis?

TT: The data from studies show that PIVKA-II was quicker to detect early stages of liver cancer in patients. Checking the levels of AFP and PIVKA-II at the same time is much more convenient to doctors. Therefore, a single blood test from the patient allows both tests to be run. When testing both, we see for some patients, that the level of AFP is normal but the PIVKA-II level is abnormal. This helps to alert the doctor to abnormalities in the patient.

SS: Providing PIVKA-II to use in our laboratory will help improve the efficiency of early liver cancer surveillance in the future.

What is your experience using digital algorithms? How does the digital algorithm bring value to enable early HCC diagnosis?

TT: There are about 50-60 patients who have used the digital algorithm. And it has been very beneficial to some patients.

SS: But due to the limitations of ultrasound access combined with the sensitivity performance of AFP, considering to add new biomarkers such as PIVKA-II and  the digital algorithm will play a very important role.

TT: When applying the digital algorithm, in practice, we have to add two other factors, age and gender. Sometimes, abnormalities in the AFP level or PIVKA-II level is detected. But the digital algorithm shows it as normal. The algorithm makes surveillance more accurate.

SS: According to many studies and the reports from the doctors who directly treat the patients, it was found that using PIVKA-II and the digital algorithm, compared to the results of AFP and ultrasound, which is considered standard/conventional practice, helps detect liver cancer at an early stage more efficiently.

What does your workflow using the digital algorithm look like?

TT: The digital algorithm has simplified the workflow. Every time a patient has a health check, it’s standard practice to run a blood test to check the liver health. With the blood sample, we can run the digital algorithm at the same time. This means the patient only needs to give one blood sample. Everything is done in one visit.

SS: After collecting the samples, the laboratory performs AFP, PIVKA-II, and digital algorithm tests. After the AFP and PIVKA-II test results are reported, the laboratory results will be combined with gender and age to automatically calculate the score. The result will be sent to the LIS or HIS system of the hospital, allowing the doctors to see the test results quickly. This makes the laboratory workflow more convenient and reporting of results faster.

TT: It’s very easy to interpret the result because there is only ‘positive’ or ‘negative’ (score). The doctors don’t need to interpret complicated numbers. When an abnormality in the digital algorithm is found, the doctor should conduct further (confirmatory) testing, especially using medical imaging techniques such as X-ray, CT or MRI scans.

What’s your expectation for the digital algorithm in the future?

TT: If we use the digital algorithm or PIVKA-II in addition to AFP, the liver cancer surveillance will likely be more accurate because this test already shares the same platform as their regular blood tests. And this will help us to decide if the patient is at risk of cancer, or need further surveillance tests. We might be able to detect the liver cancer at an earlier stage in more patients and provide successful treatment.

What is Siriraj  Hospital’s vision for the liver disease and HCC management?

TT: In patients who have been screened and found to have liver cancer, over 90% of them live longer than 5 years. In this case, it changes the patient’s life. If we can use other surveillance methods such as PIVKA-II or the digital algorithm, it might help to improve surveillance effectiveness.

SS: The department is very pleased to have been a part of an important step in using digital diagnostic tools which are helping liver cancer patients have a better quality of life and increase the survival rate.

TT: At Siriraj Hospital, we provide knowledge and raise awareness for everyone, which includes both patients and healthcare workers. So, the patients who are at risk of liver cancer, can receive surveillance regularly. We hope that in the future, every patient who is at risk of liver cancer, everyone in Siriraj Hospital, will receive the surveillance process regularly.

The views and opinions expressed by Prof. Tawesak Tanwandee and Asst. Prof. Sansnee Senawong are their own views and opinions. Roche disclaims all liability in relation to these views and opinions.

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.

Performance review of Phase II liver cancer tumor markers & biomarker panels for the early detection of HCC

Quick Summary

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and the cancer with the fastest increase in mortality in the United States, with more than 39,000 cases and 29,000 deaths in 2018. As with many cancers, survival is significantly improved by early detection. The median survival of patients with early HCC is >60 months but <15 months when detected at an advanced stage. Surveillance of at-risk patients improves outcome, but fewer than 20% of those at risk for HCC receive surveillance, and current surveillance strategies have limited sensitivity and specificity.

Ideally, blood-based biomarkers with adequate sensitivity or specificity would be available for early detection of HCC; however, the most commonly used biomarker for HCC, alpha-fetoprotein (AFP), has inadequate performance characteristics. There are several candidate serum proteomic, glycomic, and genetic markers that have gone through early stages of biomarker validation and have shown promise for the early detection of HCC, but these markers require validation in well-curated cohorts. Ongoing prospective cohort studies will permit retrospective longitudinal (phase III biomarker study) validation of biomarkers. In this review, the authors highlight promising candidate biomarkers and biomarker panels that have completed phase II evaluation but require further validation prior to clinical use.