Clin Mol Hepatol > Volume 29(2); 2023 > Article
Wang: Clinical practice guidelines and real-world practice for hepatocellular carcinoma in Taiwan: Bridging the gap
Hepatocellular carcinoma (HCC) is highly prevalent in Taiwan, with liver cancer being the second leading cause of cancer-related mortality and a major threat to public health. Many efforts including a nationwide vaccination program against hepatitis B virus, Taiwan Cancer Registry, and National Health Insurance (NHI) program have been developed to improve the prevention and management of HCC. Additionally, the Taiwan Liver Cancer Association (TLCA) and Gastroenterological Society of Taiwan (GEST) collaborated to develop a management consensus for HCC to provide guidance and advice to physicians [1]. However, discrepancies exist between the updated evidence of care for HCC and real-world practice. Taiwan’s NHI program accounts for the majority of health care expenditures in the country, and its policy has significant impacts on real-world practice for HCC by influencing the availability and accessibility of diagnostic tools and treatments. Nevertheless, factors such as patient adherence, comorbidities, attitudes and awareness of physicians, and treatment availability also play an important role in real-world treatment of HCC.
In the current issue of Clinical and Molecular Hepatology, Su et al. [2] reviewed the current status of HCC management in Taiwan and compared clinical guidelines with real-world practice for HCC treatment [2]. Regular surveillance is crucial in HCC management as it improves the outcomes of patients by increasing the likelihood of receiving curative therapy [3,4]. Risk prediction models for HCC stratify patients into risk groups for HCC [5], and surveillance in patients at high risk of HCC has been shown to improve prognosis [3]. The TLCA guideline advocates regular screening for HCC especially in at risk patients; although this screening is reimbursed by the NHI, patient adherence to surveillance is poor. Integration of biomarkers such as serum alpha-fetoprotein (AFP) has been recommended in HCC surveillance in Taiwan. Protein induced by vitamin K absence or antagonist II (PIVKA-II; also known as des-γ-carboxylated prothrombin, DCP), a biomarker useful in the early diagnosis of HCC, has been recently reimbursed in Taiwan [6]. HCC can be diagnosed with characteristic vascular patterns in dynamic imaging methods including computed tomography (CT) or magnetic resonance imaging (MRI) [1,7,8]. Gadoxetic acid is a hepatocyte-specific MRI contrast agent, the combination of which (EOB-MRI) has been shown to be more accurate and sensitive than ultrasound (US) or CT in detecting small HCCs or differentiating HCC from benign focal liver lesions [9]. EOB-MRI was recommended by the TLCA guidelines for early detection and assessment of staging and tumor burden of HCC [1]. Contrast-enhanced US (CEUS) is superior to unenhanced US in the diagnosis of HCC, and CEUS with hepatocyte-specific contrast agents such as Sonazoid can provide Kupffer phase imaging for surveillance of HCC [1]. The TLCA and other international clinical practice guidelines recommend the use of EOB-MRI and CEUS in the management of HCC [1,7,10,11], but neither is covered by the NHI in Taiwan.
Surgical resection remains the major treatment for earlystage HCC in Taiwan. Local ablation with radiofrequency or microwaves is recommended by TLCA guidelines and reimbursed as first-line treatment for early-stage HCC with tumor size less than 5 cm [1]. Trans-arterial chemoembolization (TACE) is the first-line treatment for intermediate-stage HCC in Taiwan. Other treatments such as TACE with drug-eluting beads or radioembolization are not reimbursed. Systemic therapy for HCC has shown significant progress in recent years. Drugs including multi-tyrosine kinase inhibitors, anti-angiogenic agents, and immune checkpoint inhibitors (ICIs) have shown benefits for advanced HCC in randomized controlled trials [12]. Taiwan guidelines recommend either sorafenib, lenvatinib, or a combination of atezolizumab with bevacizumab as firstline systemic therapy for advanced HCC [1]. While other international clinical practice guidelines have recommended the combination of atezolizumab with bevacizumab as first-line therapy for advanced HCC [10,11,13], only sorafenib and lenvatinib are currently covered by NHI as first-line systemic therapy in Taiwan. Regorafenib or ramucirumab (for AFP ≥400 ng/mL) is reimbursed as a second-line therapy for HCC patients who progressed on sorafenib. None of the ICIs are currently covered by the NHI as either first- or second-line systemic therapy for HCC. Systemic therapy has shown to benefit intermediate-stage HCC and has been recommended in patients refractory or unsuitable for TACE [10,14]. A wide range of heterogeneity in the combination of systemic agents has been shown in real-world practice in Taiwan [2]. Analyzing the realworld practice data may be valuable for evaluation of treatment and outcomes of HCC, which may facilitate NHI approval and help the development of practice consensus.
HCC is a highly heterogeneous disease, and management requires a multidisciplinary approach based on the individual characteristics of patients including liver reserve, tumor burden, comorbidities, and underlying liver diseases. Bridging the gap between clinical guidelines and real-world practice for HCC also requires a multidimensional approach. Patient education and physician motivation should be strengthened to improve adherence to surveillance recommendations and early detection of HCC. Academic organizations may provide comprehensive guidance to integrate the use of biomarkers and imaging modalities to guide HCC treatment and may consider updating the recommendations according to recent advances in systemic therapy for HCC. The NHI coverage of diagnostic tools and treatments for HCC should consider embracing the most updated evidence to facilitate real-world practice and improve treatment outcomes for patients with HCC in Taiwan.

FOOTNOTES

Conflicts of Interest
The author has no conflicts to disclose.

Abbreviations

AFP
alpha fetoprotein
CEUS
contrast-enhanced ultrasound
CT
computed tomography
GEST
Gastroenterological Society of Taiwan
HCC
hepatocellular carcinoma
ICI
immune checkpoint inhibitors
MRI
magnetic resonance imaging
NHI
National Health Insurance
PIVKA-II
protein induced by vitamin K absence or antagonist II
TACE
trans-arterial chemoembolization
TLCA
Taiwan Liver Cancer Association

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