AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma

Singal, Amit G.; Llovet, Josep M.; Yarchoan, Mark; Mehta, Neil; Heimbach, Julie K.; Dawson, Laura A.; Jou, Janice H.; Kulik, Laura; Agopian, Vatche G.; Marrero, Jorge A.; Mendiratta‐Lala, Mishal; Brown, Daniel B.; Rilling, William S.; Goyal, Lipika; Wei, Alice C.; Taddei, Tamar H.

doi:10.1097/hep.0000000000000466

Cited by 358 publications

(295 citation statements)

References 335 publications

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“…First-line management of advanced HCC has evolved substantially in the past few years, and updated global guidelines have recognized immunology-oncology–based combinations as the preferred first-line option, retaining tyrosine kinase inhibitors (TKIs) as the alternative in case of contraindications to immunotherapies. After a decade of sorafenib being the only systemic agent associated with an increase in the median OS in patients with advanced HCC (Table 1), in 2017, lenvatinib became another option for patients after demonstrating noninferiority to sorafenib for its primary end point of OS but superiority for its secondary end points of progression-free survival (PFS) and objective response .…”

Section: Overview Of First-line Management Of Advanced Hccmentioning

confidence: 99%

“…As the guidelines show (Figure 1, Table 2), the main recommendations for first-line therapies are as follows. First, for patients without contraindications for immunotherapy, the first option is atezolizumab plus bevacizumab . The AASLD guidance and latest NCCN guidelines published after the HIMALAYA trial proposed the use of tremelimumab plus durvalumab as an alternative to atezolizumab plus bevacizumab in cases with a high risk of gastrointestinal bleeding that might contraindicate the use of bevacizumab .…”

Section: Overview Of First-line Management Of Advanced Hccmentioning

confidence: 99%

“…First, following first-line atezolizumab plus bevacizumab, use of a multitarget TKI is recommended based on expert consensus opinion. The AASLD, ASCO, and EASL guidelines state that sorafenib or lenvatinib are the preferred option, while the ESMO and NCCN guidelines do not provide a distinct recommendation after atezolizumab plus bevacizumab among 5 choices (sorafenib, lenvatinib, cabozantinib, regorafenib, and ramucirumab). Second, following first-line tremelimumab plus durvalumab, there is no clear guidance as this regimen is too new to be incorporated into most of the guidelines.…”

Section: Overview Of Second-line Treatment Of Advanced Hccmentioning

confidence: 99%

“…Given that these patients are naive to any form of anti–vascular endothelial growth factor–targeted therapy, the AASLD guidance recommends the use of sorafenib or lenvatinib in the second-line setting in this population. Third, following first-line sorafenib or lenvatinib, the guidelines do not distinguish second-line recommendations after prior sorafenib or lenvatinib and support use of cabozantinib, regorafenib, or ramucirumab (AFP >400 ng/mL) as the preferred options . The AASLD, ASCO, NCCN, and AGA guidelines also list immunotherapy as an option in the second-line setting despite limited high-level evidence in this context.…”

Section: Overview Of Second-line Treatment Of Advanced Hccmentioning

confidence: 99%

“…A retrospective analysis from the phase 3 CELESTIAL randomized trial demonstrated a similar benefit with cabozantinib over placebo in a subgroup of patients whose liver function declined to Child-Pugh class B at week 8 of therapy as in the overall study population, supporting the continuation of TKI therapy in these patients. Only the AASLD, NCCN and AGA guidelines provide systemic therapy recommendations for patients with Child-Pugh class B HCC (Table 2), while the remaining scientific societies provide no systemic therapy recommendation, instead endorsing a cautious approach and emphasizing shared decision-making with a multidisciplinary team. In this sense, the AASLD guidelines recommend sorafenib, lenvatinib, or single-agent ICI for well-selected candidates with Child-Pugh class B liver disease.…”

Section: Special Populationsmentioning

confidence: 99%

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Critical Appraisal of Guideline Recommendations on Systemic Therapies for Advanced Hepatocellular Carcinoma

et al. 2024

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ImportanceThe combination of immune checkpoint inhibitors with antiangiogenic agents has revolutionized the treatment landscape of advanced hepatocellular carcinoma (HCC). However, due to rapid publication of new studies that attained their predefined primary end points, a lack of robust cross-trial comparison of first-line therapies, and diverging clinical guidelines, no clear-cut treatment flowchart and sequence of therapies are available. This critical analysis of the recommendations for the management of advanced HCC from the main scientific societies in the US and Europe adopted an integrated approach to provide information on the clinical benefit (overall survival and progression-free survival) and safety profile of these therapies using the European Society for Medical Oncology (ESMO)–Magnitude of Clinical Benefit Scale (MCBS) score and an ad hoc network meta-analysis.ObservationsThere is a major consensus among guidelines that atezolizumab plus bevacizumab has a primacy as the recommended first-line treatment of choice in advanced HCC. On progression after immunotherapy-containing regimens and for patients with contraindications for immunotherapies, most guidelines maintain the established treatment hierarchy, recommending lenvatinib or sorafenib as the preferred options, followed by either regorafenib, cabozantinib, or ramucirumab. Thus far, the first-line immune-based regimen of tremelimumab plus durvulumab has been integrated only in the American Association for the Study of Liver Diseases guidance document and the latest National Comprehensive Cancer Network guidelines and is recommended for patients with a high risk of gastrointestinal bleeding. Overall, in the first-line setting, both atezolizumab plus bevacizumab and sintilimab plus IBI305 (a bevacizumab biosimilar) received the highest ESMO-MCBS score of 5, indicating a substantial magnitude of clinical benefit. In a network meta-analysis, no significant differences in overall survival were found among the various combination regimens. However, the newly reported combination of camrelizumab plus rivoceranib was associated with a significantly higher risk of treatment-related adverse events compared with atezolizumab plus bevacizumab (relative risk, 1.59; 95% CI, 1.25-2.03; P &lt; .001).Conclusions and RelevanceThis narrative review found that atezolizumab plus bevacizumab is regarded as the primary standard of care for advanced HCC in the first-line setting. These findings from integrating the recommendations from scientific societies’ guidelines for managing advanced HCC along with new data from cross-trial comparisons may aid clinicians in decision-making and guide them through a rapidly evolving and complex treatment landscape.

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Section: Overview Of First-line Management Of Advanced Hccmentioning

confidence: 99%

Section: Overview Of First-line Management Of Advanced Hccmentioning

confidence: 99%

Section: Overview Of Second-line Treatment Of Advanced Hccmentioning

confidence: 99%

Section: Overview Of Second-line Treatment Of Advanced Hccmentioning

confidence: 99%

Section: Special Populationsmentioning

confidence: 99%

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Critical Appraisal of Guideline Recommendations on Systemic Therapies for Advanced Hepatocellular Carcinoma

et al. 2024

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Prevention, Diagnosis, and Treatment of Hepatocellular Carcinoma

Park,

Davis,

Pillai

2024

JAMA

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Clinician-Level Knowledge and Barriers to Hepatocellular Carcinoma Surveillance

Wong,

Jones,

Niu

et al. 2024

JAMA Netw Open

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ImportanceSurveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is underused. Identifying potentially modifiable factors to address barriers in HCC surveillance is critical to improve patient outcomes.ObjectiveTo evaluate clinician-level factors contributing to underuse of HCC surveillance in patients with cirrhosis.Design, Setting, and ParticipantsThis survey study included primary care clinicians (PCCs) and gastroenterology and hepatology clinicians at 5 safety-net health systems in the US. Clinicians were surveyed from March 15 to September 15, 2023, to assess knowledge, attitudes, beliefs, perceived barriers, and COVID-19–related disruptions in HCC surveillance in patients with cirrhosis. Data were analyzed from October to November 2023.Main Outcome and MeasuresHCC surveillance knowledge was assessed with 6 questions querying the respondent’s ability to correctly identify appropriate use of HCC surveillance. Attitudes, perceived barriers, and beliefs regarding HCC surveillance and perceived impact of the COVID-19 pandemic–related disruptions with HCC surveillance were assessed with a series of statements using a 4-point Likert scale and compared PCCs and gastroenterology and hepatology clinicians.ResultsOverall, 347 of 1362 clinicians responded to the survey (25.5% response rate), among whom 142 of 237 (59.9%) were PCCs, 48 of 237 (20.3%) gastroenterology and hepatology, 190 of 236 (80.5%) were doctors of medicine and doctors of osteopathic medicine, and 46 of 236 (19.5%) were advanced practice clinicians. On HCC knowledge assessment, 144 of 270 (53.3%) scored 5 or more of 6 questions correctly, 37 of 48 (77.1%) among gastroenterology and hepatology vs 65 of 142 (45.8%) among PCCs (P &lt; .001). Those with higher HCC knowledge scores were less likely to report barriers to HCC surveillance. PCCs were more likely to report inadequate time to discuss HCC surveillance (37 of 139 [26.6%] vs 2 of 48 [4.2%]; P = .001), difficulty identifying patients with cirrhosis (82 of 141 [58.2%] vs 5 of 48 [10.4%]; P &lt; .001), and were not up-to-date with HCC surveillance guidelines (87 of 139 [62.6%] vs 5 of 48 [10.4%]; P &lt; .001) compared with gastroenterology and hepatology clinicians. While most acknowledged delays during the COVID-19 pandemic, 62 of 136 PCCs (45.6%) and 27 of 45 gastroenterology and hepatology clinicians (60.0%) reported that patients with cirrhosis could currently complete HCC surveillance without delays.Conclusions and RelevanceIn this survey study, important gaps in knowledge and perceived barriers to HCC surveillance were identified. Effective delivery of HCC education to PCCs and health system–level interventions must be pursued in parallel to address the complex barriers affecting suboptimal HCC surveillance in patients with cirrhosis.

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AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma

Cited by 358 publications

References 335 publications

Critical Appraisal of Guideline Recommendations on Systemic Therapies for Advanced Hepatocellular Carcinoma

Critical Appraisal of Guideline Recommendations on Systemic Therapies for Advanced Hepatocellular Carcinoma

Prevention, Diagnosis, and Treatment of Hepatocellular Carcinoma

Clinician-Level Knowledge and Barriers to Hepatocellular Carcinoma Surveillance

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