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. 2023 Dec 1;78(6):1922-1965.
doi: 10.1097/HEP.0000000000000466. Epub 2023 May 22.

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

Amit G Singal  1 , Josep M Llovet  2   3   4 , Mark Yarchoan  5 , Neil Mehta  6 , Julie K Heimbach  7 , Laura A Dawson  8 , Janice H Jou  9 , Laura M Kulik  10 , Vatche G Agopian  11 , Jorge A Marrero  12 , Mishal Mendiratta-Lala  13 , Daniel B Brown  14 , William S Rilling  15 , Lipika Goyal  16 , Alice C Wei  17 , Tamar H Taddei  18   19
Affiliations

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

Amit G Singal et al. Hepatology. .

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Conflict of interest statement

Amit G. Singal consults for Genentech, AstraZeneca, Eisai, Bayer, Boston Scientific, Exelixis, FujiFilm Medical Sciences, Exact Sciences, Glycotest, and Universal Diagnostics. Joseph M. Llovet consults for and received grants from Eisai, Bayer, and Ipsen. He consults for Merck, Bristol-Myers Squibb, Eli Lilly, Roche, Genentech, Glycotest, Boston Scientific, Exelixis, Bluejay, AstraZeneca, Omega Therapeutics, Mina Alpha, and Captor. Mark Yarchoan consults for and received institutional grants from Genentech. He own stock in and has other interests in Adventris Pharmaceuticals. He consults for Exelixis, Eisai, AstraZeneca, Geneos, Replimune, and Hepion. He received institutional grants from Incyte and Bristol-Myers Squibb. Laura A. Dawson received institutional grants from Merck. Janice H. Jou received grants from Gilead. Laura M. Kulik consults for, advises and is on the speakers’ bureau for Eisai. She consults for and advises Eisai, Exelixis, Genetec, and AstraZeneca. She advises and is on the speakers’ bureau for Gilead. She consults for Merck and Bayer. She advises Hepion and Fujifilm. She received grants from HCC Target and Glycotest. Vatche G. Agopian received grants from Early Diagnostics. Jorge A. Marrero consults for Glycotest and AstraZeneca. Daniel B. Brown received institutional grants from Sirtex Medical and Guerbet. William S. Rilling consults for and advises Boston Scientific. He consults for Varian, Terumo, BD Bard, and AstraZeneca. Lipika Goyal advises and or consults for Alentis Therapeutics, Black Diamond, Exelixis, Genentech, H3Biomedicine, Kinnate, Incyte Corporation, QED Therapeutics, Merck, Servier, Sirtex Medical, Surface Oncology, Taiho Oncology, TranstheraBio, and Tyra Biosciences. She is on the DSMC for AstraZeneca. Alice C. Wei is on the speakers’ bureau for AstraZeneca. She consults for Histosonics and Biosapien. The remaining authors have no conflicts to report.

Figures

FIGURE 1
FIGURE 1
Worldwide incidence of HCC and most common risk factors. ASR, age standardized incidence rate; HBV, hepatitis B virus; HCV, hepatitis C virus; NASH, nonalcoholic steatohepatitis; Reprinted with permission from Llovet et al. [9] and the International Agency for Research on Cancer/World Health Organization.
FIGURE 2
FIGURE 2
Proven and emerging primary prevention strategies for hepatocellular carcinoma. Abbreviations: AFP, alpha fetoprotein; GALAD, Gender, Age, AFP-L3%, AFP, and DCP model; HBV, hepatitis B virus; HCV, hepatitis C virus. 1Included in guidance statements given more favorable risk-benefit ratio compared with other potential strategies.
FIGURE 3
FIGURE 3
Data supporting benefits of hepatocellular carcinoma (HCC) surveillance. HCC surveillance has been shown to significantly reduce HCC-related mortality in a randomized controlled trial among patients with chronic HBV infection (left panel) and in several cohort studies among patients with cirrhosis from any etiology (right panel). Reprinted with permission from Zhang et al.[55] and Singal et al.[56]
FIGURE 4
FIGURE 4
Overall value of hepatocellular carcinoma (HCC) surveillance is determined by balance of benefits and harms.
FIGURE 5
FIGURE 5
Recall algorithm for hepatocellular carcinoma (HCC) surveillance. Abbreviations: AFP, alpha fetoprotein; CT, computed tomography; LI-RADS, Liver Imaging Reporting and Data System; MRI, magnetic resonance imaging; PET, positron emission tomography; US, ultrasound; Vis, visualization. 1Increasing AFP represents doubling of AFP, increase on two consecutive tests, or ≥ 20 ng/ml. 2Can return to US q6 months if lesion stable on two exams. 3CT/MRI may be preferred particularly in patients with obesity, alcohol or NASH-related cirrhosis, or Child Pugh class B or C cirrhosis. 4Significantly elevated AFP: although no clear threshold has been established, AFP ≥ 200 ng/ml or ≥ 400 ng/ml may be considered significant elevations depending on clinical context. 5Can perform chest and pelvic imaging in addition to alternative modality. If these are negative, other workup, including PET, can be considered.
FIGURE 6
FIGURE 6
Liver Reporting and Data System (LI-RADS) classification of computed tomography (CT) or magnetic resonance imaging (MRI) liver observations in patients who are at risk. LR, LI-RADS. Reprinted with permission from the American College of Radiology Committee on LI-RADS.[103]
FIGURE 7
FIGURE 7
Applicability of Liver Reporting and Data System (LI-RADS) in surveillance populations. Abbreviations: HBV, hepatitis B virus; HCC, hepatocellular carcinoma; PAGE-B score, platelet, age, and gender-hepatitis B score.
FIGURE 8
FIGURE 8
Risk of hepatocellular carcinoma (HCC) and recommended management strategy. Abbreviations: CT, computed tomography; LR, LI-RADS; MRI, magnetic resonance imaging.
FIGURE 9
FIGURE 9
Updated Barcelona Clinic Liver Cancer Staging System 2022. Abbreviations: AFP, alpha fetoprotein; ALBI, albumin-bilirubin; BSC, best supportive care; ECOG-PS, Eastern Cooperative Oncology Group-performance status; HCC, hepatocellular carcinoma; LT, liver transplant; MELD, Model for End-Stage Liver Disease; TACE, transarterial chemoembolization. Reprinted with permission from Reig et al.[147]
FIGURE 10
FIGURE 10
Algorithm for surgical treatment of early-stage hepatocellular carcinoma (HCC). Abbreviations: CTP, Child-Turcotte-Pugh; UNOS-DS, United Network for Organ Sharing Down-Staging. 1In non-liver transplant (LT) candidate, can consider surgical resection if >1 lesion in the same lobe. 2In non-LT candidate, can consider minor surgical resection if CTP score B7 and/or mild portal hyper-tension. 3E.g., varices, splenomegaly, platelets < 100 × 109/L, hepatic venous pressure gradient >10 mmHg. 4Living donor liver transplant can be considered on a case-by-case basis for patients beyond UNOS-DS criteria. 5Eligible for Model for End-Stage Liver Disease exception without 6-month wait period.
FIGURE 11
FIGURE 11
Management of patients with recurrence during or after adjuvant therapy. 1High-risk features include tumor size > 5 cm, more than 3 tumors, microvascular or macrovascular invasion, and poor tumor differentiation.
FIGURE 12
FIGURE 12
United Network for Organ Sharing (UNOS) hepatocellular carcinoma (HCC) policy timeline. Abbreviations: AFP, alpha feto-protein; MMaT-3, Median MELD at Transplant-3; MELD, Model for End-Stage Liver Disease. *Before completing local-regional therapy, tumor burden meets one of the following criteria: One lesion > 5 cm and ≤ 8 cm; two or three lesions that meet all of the following: at least one lesion > 3 cm, each lesion ≤ 5 cm, and a total diameter of all lesions ≤ 8 cm; or four or five lesions each < 3 cm, and a total diameter of all lesions ≤ 8 cm; AFP levels ≥ 1000 ng/mL are required to show a reduction in AFP level to < 500 ng/mL before liver transplantation. (Boxes shaded in gray denote historical policies; boxes in white reflect current policy.).
FIGURE 13
FIGURE 13
Management algorithm for unresectable T1 lesion/BCLC 0 in patient with cirrhosis. Abbreviations: AFP, alpha fetoprotein; CT, computed tomography; HPS, hepatopulmonary syndrome; LRT, locoregional therapy; MELD, Model for End-Stage Liver Disease; MRI, magnetic resonance imaging; PPHTN, portopulmonary hypertension. 1If lesion not amenable to ablation, alternate options include transarterial chemoembolization (TACE), radiation segmentectomy, or stereotactic body radiation therapy (SBRT). 2Patient has higher risk of rapid tumor progression, defined as > 0.3 cm per month increase in tumor diameter.
FIGURE 14
FIGURE 14
Radiologic assessment of treatment response and recall strategy. Abbreviations: AE, adverse event; BCLC, Barcelona Clinic Liver Cancer; CTP, Child-Turcotte-Pugh; ECOG, Eastern Cooperative Oncology Group; HCC, hepatocellular carcinoma; PS, performance status; TACE, transarterial chemoembolization.
FIGURE 15
FIGURE 15
Timeline of systemic therapies for hepatocellular carcinoma (HCC) and resultant survival. (First line therapies are above the timeline; second line therapies are below the timeline.) 1KEYNOTE 224 was a non-randomized phase 2 trial. Phase 3 studies of pembrolizumab versus sorafenib have had conflicting results, with improved median OS noted in an Asian population.
FIGURE 16
FIGURE 16
Treatment strategy for HCC with systemic therapies. Abbreviations: BCLC, Barcelona Clinic Liver Cancer; ECOG, Eastern Cooperative Oncology Group; HCC, hepatocellular carcinoma. Solid arrows indicate treatments for which there is clear evidence; gray dotted arrows indicate treatments in the second/third line for which further studies are required. 1Treatments that got FDA accelerated approval based on phase II studies. Reprinted with permission from Llovet et al.[331]
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