|Publishing time||No.||Drafted by (Guidelines)||Abbreviations|
European Association for the Study of the Liver
(Clinical management of hepatocellular carcinoma. Conclusions of Barcelona-2000 European Association for the Study of the Liver Conference)
British Society of Gastroenterology
(Guidelines for the diagnosis and treatment of hepatocellular carcinoma in adults)
Korean Liver Cancer Study Group and National Cancer Center
(Practice guideline for diagnosis and treatment of hepatocellular carcinoma)
Belgian Association for the Study of the Liver
(BASL guidelines for the surveillance, diagnosis and treatment of hepatocellular carcinoma)
National Comprehensive Cancer Network
(NCCN clinical practice guidelines in oncology - Hepatocellular carcinoma)
American Association for the Study of Liver Disease
(Management of hepatocellular carcinoma)
Japanese Ministry of Health, Labor and Welfare
(Clinical practice guidelines for hepatocellular carcinoma)
Saudi Gastroenterology Association
(Saudi Gastroenterology Association guidelines for the diagnosis and management of hepatocellular carcinoma: Summary of recommendations)
American College of Surgeons
(Consensus and controversy in the management of hepatocellular carcinoma)
Japan Society of Hepatology
(Expert panel of Japan Society of Hepatology: Clinical practice manual for hepatocellular carcinoma)
European Society for Medical Oncology
(Hepatocellular carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up)
Italian Southern Oncological Group
(Highlights of regional meeting of Italian Southern Oncological Group (GOIM): focus on hepatocellular carcinoma: biological and clinical background, therapeutic guidelines and perspectives)
Asian Pacific Association for the Study of the Liver
(Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma)
|2009||1||Chinese Society of Liver Cancer||Chinese Guideline|
|Chinese Society of Clinical Oncology|
Chinese Society of Hepatology Liver Cancer Study Group
(The expert consensus on the treatment standards for hepatocellular carcinoma)
Asian Oncology Summit 2009 organized by Elsevier under the auspices of the Lancet Oncology and Singapore Society of Oncology
(Management of hepatocellular carcinoma in Asia: Consensus statement from the Asian Oncology Summit 2009)
World Gastroenterology Organisation
(Hepatocellular carcinoma: A global perspective)
United States National Cancer Institute
(Hepatocellular carcinoma: Consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting)
|NCI (USA) Guideline|
Classification of guidelines for hepatocellular carcinoma
The 17 current guidelines were categorized according to the following criteria (Table 2): (i) Organizations or bodies drafting the guideline. Guidelines were classified into ‘Government-financed guidelines’ (1 guideline) and ‘Guidelines drafted by academic/medical societies’ (16 guidelines). Usually, guidelines were drafted by an expert panel that consisted mainly of hepatologists. In particular, the guideline drafted with the support of the Japanese Ministry of Health, Labor and Welfare (J-HCC Guideline) and the guideline drafted with the support of the Asian Pacific Association for the Study of the Liver (APASL Guideline) specified an expert panel consisting of radiologists, statisticians and other experts besides hepatologists. (ii) Approach. Guidelines were devised by ‘Literature Analysis’ (providing data-supported recommendations) (5 guidelines) or an ‘Expert panel’ (providing experience-supported recommendations) (12 guidelines). Guidelines drafted by an expert panel were classified as those that were ‘conclusions of a society conference’ (4 guidelines) and those drafted by an ‘expert panel commissioned by an academic/medical society’ (8 guidelines). (iii) Applicability. Fifteen of the 17 guidelines applied to HCC. The British Society of Gastroenterology Guideline (BSG Guideline)  applied to adult HCC and the National Comprehensive Cancer Network Guideline (NCCN Guideline)  applied to hepatobiliary cancers although the management of HCC was part of the NCCN Guideline. (iv) Content. All 17 guidelines dealt with diagnosis and treatment. Ten guidelines mentioned epidemiology, 8 mentioned prevention, 11 mentioned surveillance and 1 mentioned follow-ups. None of the 17 guidelines were published in a version for patients or the public, so the content was primarily technical and appropriate for use by clinicians with professional knowledge. v) Evaluation measures. The 17 guidelines featured three major types of evaluation measures: 8 guidelines had evidence categories and recommendation grades, 3 had dissemination evaluation and 2 had resource-based recommendations. (vi) Recent updates. Six of the 17 guidelines have been revised after publication. The other 11 guidelines may not have been revised because the guidelines were only recently published or a system for updates had not been established.
|Areas||Guidelines||Approach||Content||Evaluation measures||Recent updates|
|America||NCCN Guidelinee||expert panelc||D&T + E + S||consensus categories||2010|
|AASLD Guideline||literature analysis||D&T + S||evidence categories and recommendation grades; dissemination evaluation||2010|
|ACS Guideline||expert panelc||D&T||—||—|
|WGO Guideline||expert panelc||D&T + E + P + S||resource-based recommendations||—|
|NCI (USA) Guideline||expert panelb||D&T + E||—||—|
|Asia||Korean Guideline||literature analysis||D&T||evidence categories and recommendation grades||2009|
|J-HCC Guidelinea||literature analysis||D&T + P + S||evidence categories and recommendation grades; dissemination evaluation draft; evaluation prior to publication||2009|
|SGA Guideline||literature analysis||D&T + E + P||evidence categories and recommendation grades||—|
|JSH Guideline||expert panelc||D&T + S||question and answer analyser system||2009|
|APASL Guideline||expert panelc||D&T + E + P + S||evidence categories and consensus grade||—|
|Chinese Guideline||expert panelc||D&T||—||—|
|AOS Guideline||expert panelb||D&T + P + S||evidence categories and recommendation grades; resource-based recommendations||—|
|Europe||EASL Guideline||expert panelb||D&T + E + P + S||—||—|
|BSG Guidelined||literature analysis||D&T + E + S||evidence categories and recommendation grades||—|
|BASL Guideline||expert panelc||D&T + E + P + S||—||—|
|ESMO Guideline||expert panelc||D&T + E + P + S + F||dissemination evaluation||2010|
|GOIM Guideline|| |
|D&T + E||—|| |
Summary of diagnostic algorithms in current guidelines for hepatocellular carcinoma
Early diagnosis of HCC remains a key goal in improving the prognosis of patients . Characteristic diagnostic algorithms in the 17 guidelines are described herein (Fig. 1) and these algorithms have been assessed from different viewpoints according to current studies.
Figure 1. The diagnostic algorithm in current guidelines for HCC.
There are three types of diagnostic algorithms in the 17 guidelines: (i) Size-based diagnostic algorithms. When a nodule is detected, definitive diagnosis will be achieved with a nodule diameter of <1 cm, 1–2 cm and >2 cm, was recommended by 8 of the 17 guidelines. Definitive diagnostic approaches include imaging [ultrasonography (US)/computed tomography (CT)/magnetic resonance imaging (MRI)], a combined approach [US/CT/MRI + biopsy or α-fetoprotein (AFP)], and a histological approach (biopsy). (ii) Non size-based diagnostic algorithms. HCC can be diagnosed with characteristic features on dynamic CT or dynamic MRI (i.e. a nodule is hypervascular in the arterial phase with washout in the portal venous or delayed phase) regardless of tumour size, as recommended by 4 of the 17 guidelines. (iii) Diagnostic algorithms with no criteria. These algorithms only provide a diagnostic tool and do not describe a detailed diagnostic algorithm, which was true for 5 of the 17 guidelines.
In general, the tests used to diagnose HCC around the world include imaging diagnosis, serological diagnosis and histological diagnosis. Imaging diagnosis tools in wide use are US, CT and MRI, with a respective sensitivity of 60% (95% CI 44–76%), 68% (95% CI 55–80%) and 81% (95% CI 70–91%) and a respective specificity of 97% (95% CI 95–98%), 93% (95% CI 89–96%) and 85% (95%CI 77–93%) . The sensitivity and specificity of AFP, which has been widely used in serological diagnosis, vary widely and total AFP is not always specific for HCC [17, 18]. A biopsy (also known as fine needle aspiration cytology, FNAC) has overall sensitivity and specificity of 95.2% and 100% , but biopsy tests should be avoided if curative surgery is planned because the chance of needle track tumour seeding following a biopsy is 2.7% unless such a biopsy might change management of the patient or the major diagnostic doubt persists that cannot be resolved with imaging techniques or AFP .
Assessment of the 17 guidelines indicated that they had similar diagnostic approaches and agreed with current studies, but the 17 guidelines did differ in terms of detailed diagnostic algorithms: (i) Imaging diagnosis. HCC can be diagnosed by two instances of characteristic features on US/CT/MRI with a nodule of 1–2 cm according to the NCCN/European Society for Medical Oncology (ESMO) Guideline [15, 21] or with a nodule >2 cm according to the EASL/BSG/Belgian Association for the Study of the Liver (BASL)/Saudi Gastroenterology Association (SGA) Guideline [11, 14, 22, 23]. In contrast, the American Association for the Study of Liver Disease (AASLD)/Korean Guideline recommended that HCC be diagnosed by an instance of characteristic features on dynamic CT/MRI with a nodule >2 cm [24, 25]; the J-HCC/Japan Society of Hepatology (JSH)/APASL/Asian Oncology Summit (AOS) Guideline recommended that HCC be diagnosed by an instance of characteristic features on dynamic CT or dynamic MRI regardless of tumour size [12, 13, 26, 27]. The AASLD/Korean/APASL Guideline recommended that US be used as a screening test and not as a test for confirmation because US may reveal a nodule but US cannot characterize nodules and has little ability to detect the microflow in nodules [13, 24, 25]. (ii) Serological diagnosis. AFP was considered to be a useful and feasible screening tool in China, but it serves as an adjunctive diagnostic tool in the EASL/BSG/Korean/BASL/SGA/ESMO Guideline [11, 14, 21, 22, 23, 25] and AFP alone is not recommended. The combined testing of des-γ-carboxyprothrombin (DCP) and AFP or lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) could help to increase the sensitivity of HCC diagnosis [28, 29] but is used in only a few countries. Testing of DCP (also known as prothrombin induced by vitamin K absence-II, PIVKA-II), for example, is currently approved in Japan, South Korea and Indonesia [30, 31]. (iii) Histological diagnosis. A biopsy is recommended by all 17 guidelines if imaging diagnosis or serological diagnosis does not reveal characteristic features of HCC, but the EASL Guideline  recommends that a biopsy, rather than imaging techniques or AFP, be performed for definitive diagnosis when the nodular diameter is 1–2 cm since imaging techniques do not have sufficient accuracy to distinguish HCC from other benign or malignant conditions and AFP will usually remain at normal levels or be slightly elevated.
Summary of treatment algorithms in current guidelines for hepatocellular carcinoma
The choice of treatment approaches for HCC depends greatly on the extent of disease . The treatment algorithms for HCC in the 17 guidelines were comparatively assessed in line with current studies on treatment approaches, with an emphasis on treatment criteria and new advances in treatment.
In general, a liver resection should be the first approach for non-cirrhotic patients with local lesions, a liver transplant should be the first approach for patients with decompensated cirrhosis (Child–Pugh C), and advances in the utilization of nonsurgical invasive therapies, such as PEI, RFA and TACE, should also be incorporated in the management of HCC [33, 34, 35]. These points were cited by all 17 guidelines and agree with current studies. The 17 guidelines do differ regarding appropriate candidates for surgery. For example, according to the EASL/NCCN/World Gastroenterology Organisation (WGO) Guideline, appropriate candidates for a liver resection are patients with a single tumour ≤5 cm and up to three tumours ≤3 cm each with good liver functional reserve [11, 15, 36]. In contrast, the J-HCC/JSH Guideline recommends that a liver resection be performed for patients with Child–Pugh A/B and 3 tumours or less regardless of tumour size [37, 38]. A liver resection has been found to be most beneficial for solitary tumours in patients without cirrhosis, with post-resection 5-year survival rates of 41–74% [39, 40, 41]. For cirrhosis patients with local lesions and good liver function (Child–Pugh A), the choice of a resection or transplant is a subject of discussion. European guidelines such as the EASL Guideline  recommend a liver transplant as the first approach because resections are performed a second time more often than transplants. A resection may have to be performed again in 50% of cases at 3 years and 70% at 5 years [42, 43]; a transplant may have to be performed again for patients meeting the Milan criteria (a solitary tumour ≤5 cm or up to three tumours ≤3 cm each) in approximately 10% of cases and the 5-year survival rate for such patients is 70–80% [44, 45]. In contrast, the J-HCC/JSH Guideline recommends a liver resection as the first approach in these cases. Local ablation therapy is another choice for patients with a single tumour or up to three tumours ≤3 cm each and good liver function (Child–Pugh A/B) whereas a liver transplant is recommended for patients age 65 years or younger with Child–Pugh C and a single tumour ≤5 cm or up to three tumours ≤3 cm [37, 38]. Besides, AOS Guideline recommends antiviral therapy with a nucleoside or nucleotide analogue for patients with hepatitis B virus (HBV) and combination peginterferon alfa 2a plus ribavirin for patients with hepatitis C virus (HCV) could delay progression of liver cirrhosis and reduce HCC occurrence .
In recent years, research on biotherapy and molecular targeted therapy has attracted a great deal of attention [46, 47, 48]. Sorafenib has been approved for the treatment of patients with unresectable HCC by the European Medicines Evaluation Agency and the U.S. Food and Drug Administration in 2007 and by the State Food and Drug Administration of China in 2008 . The efficacy of sorafenib in advanced HCC has resulted in an overall decrease in mortality of 31%, with a median survival of 10.7 months for patients taking sorafenib versus 7.9 months for those taking a placebo [50, 51]. Sorafenib was recommended for the treatment of advanced patients by 11 guidelines, but the WGO Guideline  noted that sorafenib may be unavailable in poorer regions and moderately equipped regions because it is too expensive for patients in these regions.
Challenges and prospects
The current guidelines have both similarities as well as differences in terms of what organizations or bodies drafted the guidelines and the approach, applicability, content and recent updates of the guidelines as well as in terms of diagnostic and treatment algorithms. The differences could be attributed to various aetiological factors, high-risk patients, health systems, health resources, medical technology, treatment choices and income levels in different countries. For example, infection with HBV or HCV is the main aetiological factor for HCC development globally, HCV infection is the primary aetiological factor in Western countries but HBV infection is the primary aetiological factor in Asian countries except Japan. The optimal interval for surveillance and the targeted populations are also defined differently. The AASLD Guideline recommends the optimal interval for surveillance is 6 months and it does not need to be shortened for patients with higher risks of HCC including in the setting of cirrhosis; the targeted populations are Asian HBV carriers who are men and ≥40 years of age and carriers who are women and ≥50 years of age, as well as African HBV carriers who are ≥20 years of age and for patients with HCV or any form of cirrhosis [24, 52]. In contrast, Korean/J-HCC/JSH/AOS Guideline recommends the interval for surveillance could be shortened for patients with super-high risk. For example, the J-HCC Guideline and JSH Guideline recommend surveillance could be taken with the interval of 3–4 months for patients with cirrhosis type B or C, and 6 months for patients with HBV, HCV or cirrhosis [26, 27, 37, 53]. With regard to diagnostic algorithms, US is the most widely used modality for HCC screening and diagnosis largely because of its relatively low cost and ready accessibility ; CT and MRI can have a higher diagnostic accuracy than US but are more costly . With the continued development of imaging techniques, dynamic CT, dynamic MRI and contrast-enhanced ultrasound (CEUS) are featured in guidelines from some high-income countries with advanced medical techniques, such as the USA, Japan and South Korea [37, 38, 52, 55]. In the AASLD Guideline (2010 update), dynamic CT and dynamic MRI are recommended to be applied for diagnosis of HCC with both the nodule diameter of 1–2 cm and larger than 2 cm; but CEUS is not recommended to be applied owing to its less discriminative ability to differentiate HCC from intra-hepatic cholangiocarcinoma as well as its less availability . With regard to treatment algorithms, research on biotherapy and molecular targeted therapy has attracted a great deal of attention, but molecular targeted therapy as recommended by NCCN/AASLD/JSH/ESMO Guideline is expensive, with an average cost around US$6 000 per month , so it can only be performed in countries with extensive financial resources for healthcare services [15, 21, 38, 52].
Projected goals and implementation of guidelines for hepatocellular carcinoma
According to the projected goals of guidelines, the full implementation of guidelines could benefit clinicians, patients and authorities. Many guidelines for cancer have been published around the world, but few studies have been published regarding the implementation of those guidelines, and little is known about how these guidelines are influencing decision-making by clinicians or whether the guidelines are of use to individual patients and authorities . Only two countries have published studies on the awareness of guidelines for HCC and how influential these guidelines are. One is from Japan , which surveyed 2,279 members of the Liver Cancer Study Group of Japan and 689 primary care physicians in Osaka and Hyogo prefectures. After the introduction of J-HCC, 19–21% of hepatologists or liver surgeons changed their practices and 50–52% did not change but were convinced that their choice of treatment was similar to that recommended in the guidelines; 43% of primary care physicians changed their practices to follow the recommendations in the guidelines or paid closer attention to patient preferences. The other country publishing studies on the awareness of guidelines for HCC and how influential these guidelines are, is the USA , which found that most gastroenterologists correctly identified common high-risk scenarios, methods and intervals for HCC screening as recommended by AASLD. Gastroenterologists who knew the HCC guidelines applied them in their own practice, but approximately one quarter did not know how to appropriately deal with a positive result, likely hampering the overall effectiveness of screening. No other supporting data were found with regard to implementation improving outcomes for patients and influencing regional or national authorities when allocating resources. Therefore, goal (i) has been achieved in a few countries, but there are still gaps in the achievement of goals (ii) and (iii).
Factors potentially influencing the implementation of guidelines for hepatocellular carcinoma
What organizations or bodies are drafting guidelines
Of 17 guidelines studied, only the J-HCC Guideline was established with governmental support, which came from the Japanese Ministry of Health, Labor and Welfare . The remaining 16 guidelines were established by academic/medical societies through academic research or conclusions of an expert panel, particularly one of hepatologists. The absence of governmental support and lack of public health experts may lead to gaps in information on the management of HCC, especially with regard to appropriate prevention and surveillance measures, domestic health systems, health resources, income levels, and similar topics. This may lead to health resources not being optimally allocated. Of the 17 guidelines, only the J-HCC Guideline incorporated public comments – prior to publication, the 2005 version was evaluated by an external review board and the 2009 revision was available on the web for comments from the public . Failing to include the public, and especially patients with HCC, might lead to a lack of public awareness and influence patient adherence to guidelines.
Content and emphasis of guidelines
All 17 guidelines dealt with diagnosis and treatment, but only 5 guidelines mentioned epidemiology, prevention, or surveillance and only 1 guideline mentioned follow-ups. The absence of some content, and especially that dealing with epidemiology, prevention and surveillance, may mean that patients lack adequate information about prevention and early detection and authorities may lack adequate information on the optimal distribution of health resources to efforts like measures to prevent HBV/HCV and establish nationwide screening and surveillance programmes. Unlike the ‘Guidelines for patients’ of the NCCN in the USA  and the National Institute for Health and Clinical Excellence in the UK , none of the 17 guidelines are available in a version for patients or the public. The content is primarily technical and hard for patients and the public to understand. In the course of diagnosis and treatment, patients usually receive information from clinicians, so this lack of information could influence patient awareness of and adherence to guidelines.
Modification of guidelines
The NCCN clinical practice guidelines for oncology have set the standard for cancer care in the USA. To promote standardized treatment practices around the world, NCCN committees reviewed NCCN Guidelines for seven types of cancers to identify any modifications required for those guidelines to apply to the Middle East and North Africa based on available evidence and regional experience . Of the 17 guidelines, only the AOS Guideline and WGO Guideline suggested providing different recommendations for countries with minimal resources, moderate resources, or extensive resources [27, 36]. Another serious issue is how to implement guidelines in different regions of a country once domestic guidelines are established. Thus, the lack of information on the status of local resources could influence guideline implementation.
Consistency of patient management
A serious issue is how to implement guidelines that clinicians should follow. Although many therapies for the treatment of HCC are available and these therapies are effective for select patient groups, the therapy chosen by clinicians does not always coincide with that recommended by guidelines, and this is especially true in non-specialized centres . Only two countries had studies on the awareness and influence of published guidelines, indicating that not all clinicians change their practices to follow guidelines. To promote guidelines for use by clinicians nationwide, the more appropriate approach might be to establish guidelines for the domestic health system and implement those guidelines at pilot medical institutions and then adopt those guidelines nationwide.
Factors that warrant attention when establishing and implementing guidelines
Basis in user
Owing to the specificity and depth of medical knowledge, different versions of guidelines should be created for clinicians, patients and authorities: (i) Guidelines for clinicians – emphasizing technical aspects and particularly advanced diagnostic and treatment techniques. Clinicians should include not only hepatologists but also clinicians in internal medicine, imaging, pathology and similar fields. (ii) Guidelines for patients – emphasizing basic medical knowledge about the prevention of HBV/HCV and other risk factors for HCC and encouraging patient adherence to guidelines. (iii) Guidelines for authorities – emphasizing public health policies and health resources with an eye towards aspects such as HBV vaccine programmes, HCC surveillance programmes, essential drug lists and health insurance.
Although different versions of guidelines target different populations, participants in drafting those guidelines should include clinicians, patients and authorities as well as experts in health policy, health economics, health statistics, and epidemiology.
Basis in evidence
According to levels of evidence (from level 1 to level 5, from high to low) from the Oxford Center for Evidence-Based Medicine (EBM) , guidelines drafted based on a literature analysis have a different level of evidence (level 1–level 3) than do guidelines drafted by an expert panel (level 5), but both are still in accordance with EBM. There are two guidelines in Japan. Published in 2005, the J-HCC Guideline is a systematic review of the medical literature on HCC in English; a total of 7192 publications were selected, with most coming from MEDLINE (1966–2002). After the second selection, 334 articles were adopted in the guidelines to form 58 pairs of research questions and recommendations . Although the J-HCC Guideline have been acknowledged by many Japanese clinicians and have contributed greatly to clinical practice, 45% of the research questions are grade C recommendations and the guidelines lack the most up-to-date articles . The JSH summarized HCC treatment as performed in Japan based on a consensus of opinions from many experts even though clear evidence was not available and published the JSH Guideline in 2007. The two guidelines do not contradict since they play different roles in Japan. In fact, the JSH Guideline provides additional information for the J-HCC Guideline based on the experience of experts, and this is especially helpful for up-to-date information lacking supporting data . Assessment of guidelines established by Literature Analysis or Expert Panel in the current study found that both have advantages and disadvantages. Thus, the best move is to establish guidelines for HCC by combining a systematic literature review with experience from experts. In January 2012, an international consensus on liver transplantation for HCC was published based on a novel format which combines the topic identification from Organizing committee, the evidence-based reviews and discussion from Expert groups, and the recommendations revision from Jury together . This may be a helpful exploration and could benefit people involved in designing new guidelines in the future.
Basis in resources
Evidence-based guidelines that outline optimal approaches to the management of HCC have been established and adopted in affluent countries, but many of the current methods of HCC control and intervention cannot be implemented in low-income and middle-income countries (LMCs) . This could be owing to the failure of recommendations to consider inconsistent resource distribution in LMCs with high overall standards of living and failure to address deficits in infrastructure and resources. Recommendations also fail to consider implementation costs or provide guidance on how a suboptimal system can be incrementally improved to become an optimum system.
As noted by the WHO, guidelines defining optimal care and services have limited use in resource-constrained countries , so local resources in terms of health systems, medical technology, income levels and other resources must be fully considered when establishing domestic guidelines.
The collection and analysis of epidemiological HCC data will play a critical role in guiding future disease prevention strategies and optimizing patient management . There are many geographical variations in the prevalence of HBV-related and HCV-related HCC. The major aetiological factor is HBV infection in northeast and southeast Asia as well as HCV in Europe and in the USA . There are also geographical variations in other cancerogenic factors such as aflatoxin B, which is found more frequently in developing nations where food is less well preserved . From the perspective of cost-effectiveness analysis, epidemiological information, measures for domestic prevention, screening and surveillance and appropriate selection of treatment candidates should all be taken into account.
The 17 guidelines studied feature many evaluation measures such as evidence categories and recommendation grades. In particular, the management of HCC in Japan has achieved remarkable results, which are attributed to a combination of quantitative and qualitative forms of evaluation incorporated in the guidelines .
Assessment of the 17 guidelines indicated that systematic evaluation must be performed when establishing and implementing guidelines. Assessment included disease progression, prognosis, and responses to treatment as well as recommendations from other studies and assessment of the implementation and adoption of guidelines. Systematic evaluation should be done before evaluation, during evaluation and after evaluation: (i) Before evaluation. A multidisciplinary team to treat malignant tumours has been found to improve patient quality of life . The participation of a multidisciplinary team including hepatologists, pathologists, radiologists, surgeons and oncologists is recommended by the AASLD/SGA/WGO Guideline [23, 36, 52]. An expert panel should consist of experts from multiple departments, including clinicians as well as experts in health policy, health economics, health statistics, and epidemiology. (ii) During evaluation. When establishing guidelines, steps that should be performed include a systematic examination and analysis of the literature, soliciting the experiences and knowledge of experts, evaluating draft guidelines both internal and externally prior to publication. (iii) After evaluation. Studies should examine guideline implementation, including acknowledgement of the guideline, outcomes of adhering to the guideline, updates to the guideline every 3–4 years to incorporate new evidence.
In the past 10 years, many countries and areas have published guidelines for HCC. Seventeen current guidelines examined in this study have both similarities as well as differences, and differences are attributed to varying aetiological factors, high-risk patients, health systems, health resources, medical technology, treatment choices and income levels in different countries. Although the full implementation of guidelines could benefit clinicians, patients and authorities, there is still a gap in achieving projected goals. The factors potentially influencing guideline implementation are what organizations or bodies are drafting guidelines and guideline content and emphasis, modification, and consistency of patient management.
Comparative assessment of 17 guidelines indicated that different versions of guidelines should be established for target audiences of clinicians, patients and authorities. When such guidelines are established, participants should include clinicians, patients, and authorities as well as experts in health policy, health economics, health statistics and epidemiology. To promote standard care for HCC, countries should establish and implement domestic guidelines combining a basis in evidence, a basis in available resources, applicable patients and systematic evaluation.
Conflict of interest: No conflicts of interest to disclose.
Funding: This work was supported by Grants-in-Aid from Japan Society for the Promotion of Science and the Ministry of Education, Culture, Sports, Science and Technology of Japan and supported by Japan-China Medical Association.