Hepatocellular carcinoma
Sections
OneLiver Science Hub
OneLiver
Burden of disease
Screening and early detection
HCC prognosis & treatment
MDT approach to HCC care
Resources
Sections
OneLiver Science Hub
OneLiver
Burden of disease
Screening and early detection
HCC prognosis & treatment
MDT approach to HCC care
Resources
OneLiver Science Hub

OneLiver Science hub is a repository of information on chronic liver disease and liver cancer, including disease burden, early detection and treatment, and the benefits of multidisciplinary management.

OneLiver
Welcome to OneLiver Science Hub
Together, let’s stop chronic liver disease and, one day, cure HCC

Around one in five people globally suffer from chronic liver disease (CLD),1 despite 90% of cases being preventable.2 This usually undetected disease silently progresses to hepatocellular carcinoma (HCC), the third leading cause of cancer death.3,4

If something doesn’t change, it is predicted that deaths from liver cancer will increase by more than 50% by 2040.3

OneLiver Science hub is a repository of information on chronic liver disease and hepatocellular carcinoma, examining the increasing burden of global disease, discussing the unmet clinical need for screening of patients at risk of HCC and the benefits of early detection, through patient prognosis by disease stage and available treatments between early and advanced disease, and finally the benefits of managing patients with a dedicated HCC MDT and the barriers and avenues to building a successful clinical team.

Our OneLiver mission is to help stop, or even reverse the disease, and our ambition is to one day cure it. Our core expertise will continue to focus on cutting-edge diagnostics and treatment. To enable greater impact, partnerships are key. We want to work together with liver specialists, researchers and patient organisations on ambitious programmes across the disease continuum to prevent progression and ultimately save lives.

References

  1. Cheemerla S. and Balakrishnan M. Clin Liver Dis (Hoboken) 2021;17:365–370.
  2. Macpherson I, et al. Frontline Gastroenterol 2022;13:367–73.
  3. Rumgay H, et al. J. Hepatol. 2022;77:1598–1606.
  4. Sung H, et al. CA Cancer J Clin 2021;71:209–49.
  5. Vogel A, et al. Ann Oncol. 2021;32(6):801–5.
  6. Reig M, et al. Journal of Hepatology 2022;76:681–93
  7. Ginès P, et al. Hepatology. 2022;75(1):219–22.
  8. Zhu XD, et al. Genes & Diseases 2020;7:359–69.
  9. Yopp AC, et al. Ann Surg Oncol 2014;21(4):1287–95.

Burden of disease
Global burden of Chronic Liver Disease
Globally, approximately one in five people suffer from chronic liver disease,1 despite 90% of cases being preventable.2

CLD was related to over 1.3 million deaths in 2017, mainly among men, and associated with an increasing incidence of obesity and alcohol consumption.1 The absolute number of CLD cases is estimated at 1.5 billion worldwide, with the most common causes of disease including non-alcoholic fatty liver disease (NAFLD) (59%), infection with viral Hepatitis (HBV or HCV) (38%), and alcohol-related liver disease (ALD) (2%).1
  • Challenging diagnosis: Signs and symptoms of CLD can be nonspecific, such as fatigue, anorexia, weight loss, or depend upon the complication that the patient has developed.4 It is estimated that <2% of potential CLD patients have been diagnosed.3 The three ‘classical’ complications are associated with the progression of fibrosis to liver cirrhosis and comprise portal hypertension (esophageal varices, ascites), hepatocellular insufficiency (e.g., jaundice, hepatic encephalopathy), and hepatocellular carcinoma.4
  • Social stigma and poor prognosis: Perceived stigma is common among CLD patients, regardless of disease aetiology. CLD stigma is associated with impaired quality of life5,6 and contributes to a delay or failure in seeking help, and risks delaying the ‘cascade of care’ (screening, referral, treatment) resulting in negative health outcomes.5,7,8
  • Need for early screening: Identifying liver disease in ‘healthy’ at-risk populations is challenging within health care systems already struggling to provide high standards of care to patients with established disease. Historically, the primary method of identifying patients with CLD has been liver function tests (LFTs). However, most people with abnormal LFTs do not have liver disease.2 CLD is usually diagnosed late in the disease process. Earlier diagnosis would permit interventions (e.g., alcohol interventions, antiviral therapies, weight loss) before the onset of irreversible disease or progression to liver cancer.2
  • Preventing progression from CLD to HCC: The epidemiology of CLD is shifting from viral etiologies to reflect the rising prevalence of metabolic syndrome and alcohol misuse.6 A key goal of disease management is to disrupt the CLD continuum and prevent progression to liver cancer.6 Patients with CLD who are at risk of developing liver cancer require surveillance and regular monitoring,4 with a broadening of prevention and treatment strategies.6
Undiagnosed CLD can progress to Liver Cancer

People with undiagnosed CLD can silently progress to liver cirrhosis, placing them at high risk of developing hepatocellular carcinoma (HCC); up to 10% of people with liver cirrhosis may progress to HCC.2,9 Cirrhosis and liver cancer account for 3.5% of all deaths worldwide.6
Global burden of HCC
Liver cancer is the sixth most common cancer worldwide12 and is a complex, deadly disease.9 Potential curative options exist for patients in early settings;13 however, early HCC remains an area of high unmet need.9,14

Liver cancer is the sixth most common cancer worldwide12 and is a complex, deadly disease.9 Potential curative options exist for patients in early settings;13 however, early HCC remains an area of high unmet need.9,14

Third leading cause of cancer death: HCC comprises approximately 90% of all liver cancers and is the third leading cause of cancer death worldwide.9 In 2020, there were an estimated 900,000 new liver cancer cases (75% increase from 1990) and 830,000 cancer-related deaths worldwide.12 The most significant increases in liver cancer-related mortality were in North America, Europe, and Australia.6

Rising Global incidence: Despite advances in treatment options,13 the global incidence and mortality of HCC continue to rise6 and constitute a worldwide health challenge.9 By 2025, over 1 million patients per year will receive an HCC diagnosis compared with 840,000 in 2018 – a relative increase of almost 20%.9,12 Global deaths from liver cancer are predicted to increase by more than 50% by 2040.12
Screening & Early detection

Early stage disease is difficult to detect and diagnose,15,16 but improved diagnostic open the possibility of earlier detection.17
See more

References

  1. Cheemerla S. and Balakrishnan M. Clin Liver Dis (Hoboken) 2021;17:365–70.
  2. Macpherson I, et al. Frontline Gastroenterol 2022;13:367–73.
  3. American Liver Foundation. How Many People Have Liver Disease?Available at: https://liverfoundation.org/about-your-liver/facts-about-liver-disease/how- many-people-have-liver-disease/ [accessed August 2023].
  4. Sharma A, et al. Chronic Liver Disease. [Updated 2022 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554597/
  5. Carol M, et al. PLoS ONE 2022;17(4):e0265153.
  6. Moon AM, et al. Clin Gastroenterol Hepatol 2020;18:2650–66.
  7. Schomerus G, et al. J Hepatol 2022;77:516–24.
  8. Vaughn-Sandler V, et al. Dig Dis Sci 2014;59(3):681–6.
  9. Llovet JM, et al. Nat Rev Dis Primers. 2021;7(1):6.
  10. Marquardt JU, et al. Nat Rev Cancer 2015;15(11):653–67.
  11. Pinter M, et al. ESMO Open 2016;1:e000042.
  12. Rumgay H, et al. J Hepatol 2022;77:1598–1606.
  13. Zhu X-D, et al. Genes & Diseases 2020;7:359–69.
  14. Minami Y, et al. Hepatobiliary Surg Nutr. 2019;8(4):414–6.
  15. Vogel A, et al. Ann Oncol 2021;32(6):801–5.
  16. Reig M, et al. J Hepatol 2022;76:681–93.
  17. Ginès P, et al. Hepatology 2022;75(1):219–22.

Screening and early detection
Improved surveillance and diagnostics open the possibility of earlier detection and curative therapies for HCC1
More than 50% of patients are diagnosed late or incidentally, removing the chance for curative therapies2,3

Delayed hepatocellular carcinoma (HCC) diagnosis is due to lack of symptoms, lack of awareness and screening, and limited sensitivity or access to diagnostic approaches1,4 – dramatically worsening prognosis and limiting curative options.2,3
HCC the silent killer

HCC has few specific symptoms, especially in the early stages. Combined with a general lack of awareness, a wide range of etiologies, and paucity of screening programs, diagnosis in the early stages of disease is understandably complex.2,5
Signs and symptoms

Early stage disease is difficult to detect and diagnose, as symptoms are rare6,7 and conventional liver tests have poor sensitivity.1

In advanced disease, approximately half of patients are identified incidentally following development of abdominal pain, weight loss, or worsening liver dysfunction.2

Abdominal pain/enlarged abdomen

Unexplained weight loss

Easy bleeding or bruising

Jaundice
Risk factors for developing HCC

The risk of developing HCC increases with older age, and is greater among males than females.8,9 In addition, HCC risk can vary depending on different etiologies of origin: viral or metabolic. There has been a recent shift of HCC causes towards metabolic liver diseases, which has significantly increased the potential patient population and the need for a stepwise approach to risk stratification models to optimize healthcare resources.10

Viral etiologies

HBV or HCV infection8,9

The most important additional risk factors for developing HCC are the presence of HBV or HCV infections.8,9

Metabolic dysfunction-associated fatty liver disease (MAFLD)

Obesity, type 2 diabetes, non-alcoholic fatty liver disease2,8,9

Metabolic syndrome, type 2 diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD) have also become prominent causes of HCC. 2,8,9

Environmental exposures

Alcohol, aflatoxin, smoking2,8,9

Environmental factors including excessive alcohol consumption, aflatoxin-contaminated foods (especially in the presence of HBV), and tobacco exposure significantly increase the risk of HCC2,8,9
Prevention of HCC risk factors

Hepatitis B (HBV) is a virus that induces chronic liver inflammation leading to an increased risk of developing HCC. HBV vaccination programs are a key HCC prevention strategy, with many countries implementing programmes in the 1980s. Antiviral treatment of HBV infection can also improve liver function.9

Chronic hepatitis C virus (HCV) infection is a firmly established risk factor for HCC. There is no vaccine available to prevent HCV infection. Currently, antiviral treatment (Direct Acting Antiviral: DAA) of HCV infection decreases the risk of HCC developing in these patients.9

The changing trends in HCC etiology from viral towards metabolic suggest that more effort needs to be focused on combating obesity and diabetes to decrease the incidence of NAFLD, with more effective strategies required to identify and control alcohol misuse.9
HCC surveillance is associated with improved early detection, use of curative treatment, and prolonged survival times11-15
Early diagnosis enables initiation of treatment or behavioural changes to prevent disease progression and improve survival1

Patients with risk factors for HCC should undergo surveillance and regular monitoring when curative treatments are feasible.5,11 Identification of tumors at an early stage is critical, as curative treatments exist and provide the best opportunity for a positive prognosis.16 While it is recognised that an estimated 90% of HCC cases are associated with liver cirrhosis, there is still a need for reliable and effective HCC risk prediction models based on routinely available patient factors.17,18

Currently, HCC diagnosis is often delayed due to lack of symptoms and awareness, with advanced stage associated with significantly worse prognosis2,3 as curative treatment becomes unavailable and systemic management options are limited.2,16 International guidance for HCC recommends that surveillance in at-risk patients should consist of a program of measures, including standardized screening tests (including ultrasound screening every 6 months), recall procedures, and quality control procedures.19
Although recommended by several guidelines, HCC surveillance is limited and underutilised in real-world practice

Despite the guideline recommendations, real-life implementation of surveillance programs is far from optimal, with ≤50% of the high-risk population estimated to not receive routine screening, even in countries with surveillance programmes.20,21 Thus, over 60% of HCC cases are diagnosed at an intermediate or advanced stages11 – limiting patient eligibility for curative options, and reducing survival outcomes.2 In patients undergoing surveillance, HCC-related mortality decreases by over a third compared with those not screened for HCC.2

This can contribute to the many barriers that HCPs and patients face:

  • Screening activities are de-prioritised due to time, capacity, and healthcare funding constraints22
  • Some patients struggle to attend appointments due to scheduling and living distances from treatment centers23
  • Low awareness of early diagnosis and need to screen high-risk patients13
  • Stigmatisation of patients may result in non-attendance at scheduled hospital24-26
  • Recommended screening/diagnostic imaging is not reimbursed in all countries4
  • As HCC is rarely identified in Primary care, patients may experience delays in referrals22
Less than 50% of patients are identified with early disease11
Early identification of people at risk of developing HCC should rely on multimodal information: clinical, imaging and molecular

Currently, screening biomarkers for HCC are lacking and rarely implemented in clinical practice.10 The sensitivity of AFP testing, even when combined with ultrasound screening, remains suboptimal in detecting early-stage HCC.27

Early detection of HCC is essential to improve patient outcomes, and current guidelines recommend surveillance programs to screen at-risk patients, including ultrasound scans every 6 months with or without alpha-fetoprotein (AFP) testing.28

Ultrasound is the standard screening test used in clinical practice, although its sensitivity is approximately 50%.27,29

In combination with ultrasound, the sensitivity of AFP testing is still <63% for detecting early-stage HCC,27,30 and up to 50% of HCCs do not have elevated levels of AFP.30

Numerous clinical scores and molecular biomarkers for HCC have been proposed;10 none has been adopted into clinical practice guidelines.
Opportunity for improved HCC detection via GAAD or GALAD algorithms

Serum biomarkers, such as AFP, protein induced by vitamin K absence-II (PIVKA-II) and Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), have been proposed to improve the detection of HCC28 but do not provide adequate specificity or sensitivity alone and inclusion in guidelines has been inconsistent.29,31 Both the GAAD and GALAD algorithms* are in vitro diagnostic multivariate index assays combining patient data points to provide a semi-quantitative result.31

The GAAD algorithm combines gender (sex) and age with two biomarkers (AFP and PIVKA-II), while the GALAD algorithm combines gender and age with three-serum biomarkers (AFP-L3, AFP and PIVKA-II).31 Both GAAD and GALAD algorithmic scores demonstrate equivalent clinical performance for HCC surveillance in prospective, multicenter, case-control studies,28 irrespective of etiology and disease stage.31

GAAD and GALAD algorithms demonstrate good and similar performance for the clinical detection of early-stage and all-stage HCC.28,31-34

The GAAD algorithm* offers 92% specificity† and 73% sensitivity† for detection of early-stage HCC – superior to individual biomarkers alone.32

When combined with ultrasound, the GAAD algorithm* offers a sensitivity of approximately 90% in early-stage HCC,35 demonstrating its utility as a complementary tool in early-stage HCC detection.33

GAAD* also demonstrates cost-effectiveness (gain of 0.01 QALYs) compared with US+AFP for HCC, and could lead to better outcomes for HCC patients and save healthcare resources.36
HCC prognosis & treatment

Curative treatments exist for early stage HCC and provide the best opportunity for long-term survival.16
See more

*based on use with Elecsys® assays‡

† Sensitivity is the probability of a positive test result truly being positive; specificity is the probability of a negative test result truly being negative

‡ Assay results from other manufacturers have not been validated for the use of the Elecsys® GAAD test. The Elecsys® GAAD test should not be used without an independent clinical/radiological evaluation for the diagnosis of Hepatocellular Carcinoma (HCC). For each Elecsys® GAAD determination the measurement of the Elecsys® AFP and Elecsys® PIVKA-II assays must be determined from the same sample and measurement performed on the same analyzer type (either on cobas e 402, cobas e 411, cobas e 601, cobas e 602, or cobas e 801 analyzers).

References

  1. Ginès P, et al. Hepatology. 2022;75(1):219–22.
  2. Llovet JM, et al. Nat Rev Dis Primers. 2021;7(1):6. 
  3. Yang JD, et al. Nat Rev Gastroenterol Hepatol 2019;16(10):589–604.
  4. Kardashian A, et al. Hepatology. 2023;77:1382–1403.
  5. Sharma A, et al. Chronic Liver Disease. [Updated 2022 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Disponible en: https://www.ncbi.nlm.nih.gov/books/NBK554597/ 
  6. Vogel A, et al. Ann Oncol. 2021;32(6):801–5.
  7. Reig M, et al. Journal of Hepatology 2022;76:681–93.
  8. Rumgay H, et al. J. Hepatol. 2022;77:1598–1606.
  9. McGlynn KA, et al. Hepatology 2021;73(suppl1):4–13.
  10. Lee Y-T, et al. Hepatology 2023;78(1):31–62.
  11. Del Poggio P, et al. World J Gastroenterol 2021;27(37):6180–90.
  12. Singal AG, et al. PLoS Med 2014;11:e1001624.
  13. Singal AG, et al. Am J Med 2017; 130:1099–106.
  14. Cadier B, et al. Hepatology 2017;65:1237–48.
  15. Mourad A, et al. Hepatology 2014;59:1471–81.
  16. Zhu XD, et al. Genes & Diseases 2020;7:359–69.
  17. Liu Y, et al. Front. Public Health 2022;10:955287.
  18. Fattovich G, et al. Gastroenterology 2004;127:S35–S50.
  19. NCCN Clinical Practice Guidelines in Oncology. Hepatocellular Carcinoma V1.2023.
  20. Xu K, et al. Ann Glob Health 2017;83:281–92.
  21. Singal AG. Clin Gastroenterol Hepatol. 2015;13(12):2140–51.
  22. Beal EW. et al. Provider- and system-level barriers to surveillance for hepatocellular carcinoma among patients with chronic liver disease. ASCO GI 2022 (Abstract 404).
  23. Farvardin S, et al. Hepatology. 2017;65(3):875–84.
  24. Carol M, et al. PLoS ONE 2022;17(4):e0265153.
  25. Schomerus G, et al. J Hepatol 2022;77:516–24.
  26. Vaughn-Sandler V, et al. Dig Dis Sci 2014;59(3):681–6.
  27. Singal AG, et al. Hepatology Communications. 2022;6:2925–36.
  28. Hou J, Berg T, Vogel A, et al. GAAD and GALAD algorithmic scores demonstrate equivalent clinical performance for hepatocellular carcinoma (HCC) surveillance in prospective, multicenter, case-control studies. Presentado en EuroMedLab 2023: 21-25 de mayo, Roma, Italia. Poster P2089.
  29. Piratvisuth T, et al. Hepatol Commun. 2022;6(4):679–91.
  30. Parikh ND, et al. Cancer Epidemiol Biomarkers Prev. 2020;29(12):2495–2503.
  31. Chan HLY, et al. J Hepatol. 2022;77:S937.
  32. Teerha Piratvisuth ET AL. Hepatol Commun. 2023 Nov 8;7(11):e0317. doi: 10.1097/HC9.0000000000000317. eCollection 2023 Nov 1. Disponible en: https://pubmed.ncbi.nlm.nih.gov/37938100/ 
  33. Huang CF; Kroeniger K; Wang CW, et al. Clinical Performance of GAAD and GALAD Algorithmic Scores for Hepatocellular Carcinoma Surveillance in Patients with Chronic Hepatitis. Presentado en congreso de la Asociación Internacional de Cáncer Hepático (ILCA) 2023: 7–9 de septiembre, Ámsterdam. Poster P-72.
  34. Chan HLY, Vogel A, Berg T, et al. Performance Evaluation of the Elecsys® GAAD Assay for the Detection of Hepatocellular Carcinoma Across Different Disease Stages and Etiologies. Presentado en la Cumbre Global de Hepatitis ISHVLD 2021: 18–20 de junio, Taipéi, Taiwán [Virtual].
  35. Huang CF, Sharna A, Yu ML. The clinical utility of Elecsys GAAD score in the diagnosis of hepatocellular carcinoma. Presentado en el congreso de la Asociación de Asia Pacífico para el Estudio del Hígado (APASL) 2022: 23-25 de junio, Taipéi, Taiwán. Poster P161.
  36. Garay OU, Ambühl LE, Bird T, et al. Cost-utility analysis of the Elecsys GAAD algorithm versus ultrasound plus α-fetoprotein for HCC surveillance in patients with compensated liver cirrhosis in the United Kingdom. Presentado en ISPOR Europa 2022: 6-9 de noviembre, Viena. Poster EE37.

HCC prognosis & treatment
Early diagnosis provides the best outcomes1-4
Curative therapies for HCC present the best choice for long term survival, but are only available for early disease stages4

The prognosis of patients with hepatocellular carcinoma (HCC) is associated strongly with disease staging.2 Identification of tumors at an early stage is critical, as curative treatments exist and provide the best opportunity for long-term survival.4 

However, HCC diagnosis is often delayed due to lack of symptoms and awareness,5,6 significantly worsening prognosis, limiting available treatment options,1,3 and reducing patient survival outcomes.1-4
Early stages

Very early stage (0)

Patients with very early stage disease may not have any cancer-related symptoms.2,7 If identified and treated at this stage, survival is expected to extend beyond 5 years.2

Management of very early stage disease should consider liver transplantation as a standard of care due to the high risk of disease recurrence.2 If liver transplantation is not feasible, the other treatment approaches may include resection or thermal ablation,2,7 which is associated with similar survival outcomes to resection.2

Early stage (A)

Patients with early stage disease have a similar initial presentation as those with very early disease and without any cancer-related symptoms.2,7 Survival is expected to extend beyond 5 years with early treatment and no high-risk tumor features.2

Treatment recommendations are defined by the presence of either a single cancer, or the presence of several small cancers (≤3 nodules each ≤3 cm), without extrahepatic spread.2 If transplantation is not feasible, patients should be evaluated for ablation or resection with curative intent.2
There is an urgent need of adjuvant treatment options to address the high recurrence risk1,8,9

Currently, there is no recognised consensus on ‘high risk’ criteria for HCC recurrence, and MDTs/HCPs must use their own clinical judgment to identify such patients. Some suggested ‘high risk’ criteria for HCC recurrence have included:

Up to three tumors, with the largest >5 cm (following resection) 9

Multifocal disease (≥3 nodules)2,4,9,12

Poor tumor differentiation (defined as Grade 3 or 4) 9

Vascular invasion4,9,12
Adjuvant therapy could help reduce the risk of recurrence after curative surgery or ablation

The availability of adjuvant treatment options following curative interventions are urgently needed to reduce the recurrence risk and improve opportunities for long-term cure, especially for patients at high risk of early HCC recurrence.9 Although several phase III trials with newer immunotherapy agents in the adjuvant setting are ongoing,1 there are no approved adjuvant treatment options available and HCC recurrence remains an area of unmet need.9

Currently active global trials in adjuvant HCC

*Optional round of TACE after curative intervention allowed;
†Estimated enrolment
Information based on clinicaltrials.gov
(accessed February 2023)

Currently active Chinese trials in adjuvant HCC

†Estimated enrolment
Information based on clinicaltrials.gov (accessed February 2023)
Intermediate stages

Intermediate HCC presents in patients without any cancer-related symptoms2,7 and comprises multiple nodules without vascular invasion or extrahepatic spread. At this disease stage, tumor burden may be quite heterogeneous and influences available management options.2

Patients with well-defined HCC nodules may be candidates for liver transplantation or locoregional therapy (such as transarterial chemoembolization). Patients with diffuse, infiltrative, and extensive HCC liver involvement do not benefit from TACE, and systemic therapy should be the recommended option.2

Expected survival is dependent on available treatment options, ranging from >5 years with transplantation, >2.5 years following TACE, or >2 years with systemic treatment.2

Currently active global trials in 1L unresectable HCC (Intermediate stage)

Information based on clinicaltrials.gov (accessed September 2023)
*: Time to Failure of treatment strategy
†: Time to TACE Progression
†: Patients criteria: Beyond Up to 7 criteria
Advanced stages

Patients with advanced HCC tend to be relatively fit with preserved liver function.2 Symptoms tend to be vague and can include fatigue, unexplained weight loss, nausea, disturbed sleep, altered bowel function, and jaundice.13,14 HCC is an aggressive cancer and, when diagnosed at an advanced stage, curative treatment become unavailable and systemic management options are limited 1,4
Progress has been made in 1L systemic treatment of HCC in recent years

* Optional round of TACE after curative intervention allowed.
† Estimated enrolment.
‡ The use of this product has EMA authorisation and funding conditions from the HNS.
§The atezolizumab indication in combination with bevacizumab is funded by the HNS for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma who have not received prior systemic therapy, with liver function (Child-Pugh stage A), an ECOG score of 0 or 1, in the absence of untreated or undertreated esophagogastric varices and in the absence of autoimmune diseases.
‖The reflected information refers to the bevacizumab data sheet; in case of administering another bevacizumab, the corresponding data sheet should be consulted.
¶In China only.
**The use of this product has EMA authorisation but is pending for obtaining funding conditions from HNS.
††Does not currently have EMA authorisation. This figure contains research data from products without EMA authorisation, with the only purpose of medical education. SEARCH study: sorafenib + erlotinib vs sorafenib + placebo. Trials in bold supported an approval.

Since 2017, new systemic therapies for advanced HCC have become available, resulting in a major paradigm shift in the treatment pathway.29 Patient survival following systemic treatment is expected at >2 years.2

Currently active global trials in 1L Unresectable HCC (Advanced stage)

Information based on clinicaltrials.gov (accessed September 2023)
Terminal stages

Patients with terminal stage HCC have major cancer-related symptoms, usually with impaired liver function. Due to the HCC burden associated with terminal stage disease, liver transplantation is not feasible, and additional non-HCC-related factors combine to provide poor short-term survival.2

Treatment of terminal stage HCC does not change expected survival and is of limited benefit. In such instances, management of symptoms and best supportive care (including palliative care) are mandatory.2 Patients with terminal stage HCC may be expected to survive approximately 3 months with best supportive care.2
MDT approach to HCC care

Establishment of an HCC MDT is associated with improved time to diagnosis and treatment.30
See more

OS, overall survival; RFS, recurrence-free survival

References

  1. Llovet JM, et al. Nat Rev Dis Primers. 2021;7(1):6.
  2. Reig M, et al. Journal of Hepatology 2022;76:681–93.
  3. Yang JD, et al. Nat Rev Gastroenterol Hepatol 2019;16(10):589–604.
  4. Zhu X-D, et al. Genes & Diseases 2020;7:359–69.
  5. Kardashian A, et al. Hepatology. 2023;77:1382–1403.
  6. Ginès P, et al. Hepatology. 2022;75(1):219–22.
  7. Vogel A, et al. Ann Oncol. 2021;32(6):801–5.
  8. Roayaie S, et al. Hepatology 2013;57(4):1426–35.
  9. Hack SP, et al. Future Oncol 2020;16(15):975–89.
  10. Imamura H, et al. J Hepatol 2003;38:200–7.
  11. Jung S-M, et al. J Gastrointest. Surg 2019;23(2):304–11.
  12. NCCN Clinical Practice Guidelines in Oncology. Hepatocellular Carcinoma V1.2023. 
  13. Norman EML, et al. Eur J Cancer Care. 2022;31:e13672.
  14. Singal AG, et al. PLoS Med 2014;11:e1001624.
  15. Llovet JM, et al. N Engl J Med 2008;359:378–90.
  16. Cheng AL, et al. J Clin Oncol 2013;31:4067–75.
  17. Zhu AX, et al. J Clin Oncol 2015;33:559–66.
  18. Cainap C, et al. J Clin Oncol 2015;33:172–9.
  19. Kudo M, et al. Lancet 2018;391:1163–73.
  20. Yau C, et al. Lancet Oncol 2022;23:149–60.
  21. Finn RS, et al. N Engl J Med 2020;382:1894–905.
  22. Ren Z, et al. Lancet Oncol 2021;22:977–90.
  23. Qin S, et al. J Clin Oncol 2021;39:3002–11.
  24. Kelley RK, et al. Lancet Oncol 2022;23:995–1008.
  25. Abou-Alfa GK, et al. N Engl J Med Evidence 2022;1:EVIDoa2100070.
  26. Finn RS, et al. Ann Oncol 2022;33(Suppl 7):S808–69.
  27. Kudo M, et al. Ann Oncol 2022;33(Suppl 7):S808–69.
  28. Qin S, et al. Ann Oncol 2022;33(Suppl 7):S808–69.
  29. Su T-H, et al. Liver International. 2022;42:2067–79.
  30. Yopp AC, et al. Ann Surg Oncol 2014;21(4):128–95. 

MDT approach to HCC care
Utilization of a multidisciplinary team (MDT) in HCC
A holistic, multidisciplinary approach significantly improves outcomes in patients with HCC through early diagnosis and intervention

The MDT is an alliance of medical and healthcare professionals dedicated to managing a specific tumor disease, with a focus on evidence-based clinical decisions and coordination of care delivery across all stages of the management and treatment.1 As the clinical features of hepatocellular carcinoma (HCC) are often subtle and nonspecific, management by MDT permits care providers with different roles, expertise and functions to provide optimum patient care.1,2

The core members of an HCC MDT include liver surgeons, hepatologists/gastroenterologists, oncologists, interventional radiologists, pathologists, and primary care physicians, with additional consultative experts included based on the individual needs of the patient.2,3
Value of an MDT in HCC
A multidisciplinary holistic approach to HCC care improves diagnosis rates, referral pathways, access to treatment, and ultimately, patient survival4

MDTs reduce the waiting time from referral to treatment and accelerate the diagnostic process of HCC, mainly due to a reduction in time from referral to the first visit and time from first visit to MDT treatment decision.5

When an MDT approach is applied, HCC patients have a significantly increased rate of receiving an appropriate, individualised treatment plan with associated increases in improved survival.6

Limited access to an MDT may hinder time to HCC diagnosis, with patients presenting later at a more advanced disease stage.4 Establishment of an MDT HCC clinic is associated with improved diagnoses at an earlier disease stage, with reduced time to diagnosis and treatment potentially resulting from having all providers (e.g., surgeons, interventional radiologists, and medical oncologists) present in the clinic setting – eliminating untimely delays from scheduling multiple physician visits on different days in varying clinic settings.4

An MDT holistic approach improves diagnosis rates, referral pathways, and access to treatment. Ultimately, HCC MDTs are associated with improved overall survival, independent of tumor stage.4
Barriers to establishing an MDT in HCC
Patients perceive the MDT setting as superior to the more traditional care ‘serial’ clinic model.8 However, there can be significant barriers to accessing MDT-based care.1,9

There are several obstacles to creating and managing a successful HCC MDT. A highly complex and variable decision-making process4,10 can be further compounded by local policies and funding restrictions,1,9 inequalities in patient access,9 and weak communication and collaboration across the MDT team.3

HCC is a complex disease: As the complexity and cost of HCC management increases, the need to collect and provide evidence on the cost benefits of an MDT becomes more important for obtaining buy-in from hospital administrations.9

Healthcare policies: Despite clinical evidence supporting the functionality of MDTs, healthcare policies to support MDT management of HCC are often lacking due to limited resources, team capacities, and cost issues.1

Funding: Lack of funding often means that the healthcare team must donate the extra time and effort to make the MDT a reality – hospitals may need to allocate funds to reimburse the MDT service.9

Patient access: Equal access to speciality care remains a challenge in areas where communications among providers and streamlined processes are lacking. In under-served populations, access to speciality care remains a particular challenge.9

Integrated working: HCC management requires the involvement of multiple specialists to provide individualised treatment strategies. These specialists must find ways to coordinate and communicate treatment recommendations and collaborate on patient management within the confines of local procedures and resources.9
Overcoming MDT barriers

Administration: Administrative support is key to the success of an MDT programme, and a nurse specialist in HCC or a hepatobiliary oncology is critical for administering and coordinating the programme. In addition, an acknowledged leader of the consensus group is important for both clinical decisions, quality control, as well as providing direct outreach to the local community.9

Telemedicine: Many MDTs utilise telemedicine or teleconferencing to permit virtual participation of other non-local providers using real-time videoconferencing to share knowledge. Such technology is especially relevant for centers that lack full resources or necessary local specialists.9

Different MDT models: Depending on local needs and available resources, different models of MDT care may be considered, ranging from a multidisciplinary tumor board to a fluid referral system between specialties to a co-located clinic.3

Regular meetings: Regular MDT meetings provide many benefits, such as enabling input from all MDT members, providing time to develop comprehensive treatment plans, minimising communication errors and delays in treatment, and increasing member awareness of new research in related fields.9
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References

  1. Sinn DH, et al. PLoS One 2019;14:e0210730.
  2. Siddique O, et al. Journal of Multidisciplinary Healthcare 2017;10:95–100. 
  3. Byrd K, et al. Semin Liver Dis 2021;41:1–8.
  4. Yopp AC, et al. Ann Surg Oncol 2014;21(4):1287–95.
  5. Villadsen GE, et al. J Gastrointestin Liver Dis 2019;28(1): 83–8.
  6. Duininck G, et al. J Surg Oncol 2019;120(8):1365–70.
  7. Agarwal PD, et al. J Clin Gastroenterol 2017;51(9):845–9.
  8. Soares KC, et al. Ann Surg Oncol 2014; 21:1059–61.
  9. Naugler WE, et al. Clin Gastroenterol Hepatol 2015;13:827–835.
  10. Reig M, et al. Journal of Hepatology 2022;76:681–93.

Resources
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