AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma
Open accessAbstract
Singal, Amit G.; Llovet, Josep M.; Yarchoan, Mark; Mehta, Neil; Heimbach, Julie K.; Dawson, Laura A.; Jou, Janice H.; Kulik, Laura M.; Agopian, Vatche G.; Marrero, Jorge A.; Mendiratta-Lala, Mishal; Brown, Daniel B.; Rilling, William S.; Goyal, Lipika; Wei, Alice C.; Taddei, Tamar H. Author Information
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Surgical resection is recognized worldwide as the preferred treatment for early-stage hepatocellular carcinoma, while liver transplantation is indicated when resection is unsuitable.
“Surgical resection is recognized worldwide as the preferred treatment for patients with early stage HCC, whereas liver transplantation is indicated in those with early stage disease who are not deemed suitable for resection7,22.”
From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [7]
The Surgical resection section calls resection the treatment of choice for localized HCC without cirrhosis and recommends it for selected patients with compensated cirrhosis. The Liver transplantation section supports transplantation for early-stage patients ineligible for resection because of liver dysfunction or multifocality. The claim overgeneralizes resection as preferred for all early-stage patients worldwide and omits transplant eligibility; page numbers were not available in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredEligibility criteria for resection vary by location, and European and US guidelines recommend more restrictive criteria than Asian guidelines.
“In general, European and US guidelines recommend more-restrictive criteria for resection than Asian guidelines7,22–27.”
From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [7]
The Surgical resection section says resection is mainly limited to BCLC stage 0/A and advises that extended indications be considered only in high-volume centers after multidisciplinary discussion. It notes that most evidence for resection in patients with portal vein tumor thrombus comes from Asia, but it does not compare the eligibility criteria recommended by European, US, and Asian guidelines. The claimed regional ranking is therefore not established by this source. (LLM, conf=0.79)
Experimental — accuracy not yet measuredRegimens containing immune-checkpoint inhibitors are currently recommended as first-line therapy in clinical guidelines for advanced hepatocellular carcinoma.
“In particular, regimens including immune-checkpoint inhibitors (ICIs) are currently adopted as first-line therapies in clinical guidelines7.”
From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [7]
Current clinical decisions are based on clinical factors including performance status, tumour burden, liver function, and comorbidities.
“Currently, clinical decisions are based on clinical factors including, but not limited to, performance status, tumour burden, liver function and comorbidities7.”
From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [7]
Positive results from IMbrave 050 have led to a revised management algorithm incorporating adjuvant therapies for early-stage HCC.
“Now the positive results of IMbrave 050 (ref. 12) have led to a revised management algorithm for patients with early stage HCC by incorporating adjuvant therapies in this disease setting7 (Fig. 4).”
From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [7]
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Cites
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Acute Abdomen: A Rare Case of Ruptured Hepatocellular Carcinoma
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EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma
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Modified RECIST (mRECIST) Assessment for Hepatocellular Carcinoma
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“[310,311] mRECIST has become the standard tool to assess radiological response after locoregional therapy for patients with early and intermediate stages of HCC, whereas both RECIST 1.1 and mRECIST are recommended for patients with advanced-stage HCC undergoing systemic therapy.”
InfluentialSelf-citationBCLC strategy for prognosis prediction and treatment recommendation: the 2022 update
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“[336] Objective response was achieved in 12% of patients, median OS was 7.6 months, and grade 3/4 treatment-related AEs were observed in 24% of patients, similar to tolerability observed in patients with Child-Turcotte-Pugh A cirrhosis.”
InfluentialAASLD guidelines for the treatment of hepatocellular carcinoma
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“[135,140] Therefore, patients with non-characteristic imaging are advised to undergo biopsy, independent of AFP level.”
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Self-citationBaveno VII – Renewing consensus in portal hypertension
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“[149] It also recognizes the heterogeneity among patients with BCLC Stage B and incorporates concepts of downstaging and stage migration over time.”
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Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma
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“[314] OS was significantly improved versus placebo (10.2 vs. 8.0 mo), as were PFS and ORR.”
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“…≤ 8 cm 81% 5-year survival Total tumor volume < 115 cm [208] Sum of volume for each tumor ≤ 115 cm 3 75% 4-year survival Up-to-seven criteria [209] Diameter or largest tumor (cm) + number of tumors ≤ 7 71% 5-year survival Extended Toronto criteria [210] Biopsy demonstrating well-to-moderate…”
Self-citationProjected U.S. State-Level Prevalence of Adult Obesity and Severe Obesity
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“[15] NAFLD has become a significant public health concern, related to significant increases in the prevalence of obesity and metabolic syndrome, [16] and is currently the fastest growing cause of HCC in liver transplant (LT) candidates.”
Surgery and portal hypertension.
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The International Position on Laparoscopic Liver Surgery
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“…invasive surgical (MIS) approaches, including laparoscopy and robotic assisted hepatectomy, may be appropriate in well-selected patients with HCC. [181] Although many centers commonly perform limited minor resections in anatomically favorable locations (Segments 2, 3, 5, and 6) using MIS…”
Randomized controlled trial of screening for hepatocellular carcinoma
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“[55] Prior attempts at an RCT comparing surveillance with no surveillance in patients with cirrhosis failed given poor enrollment, so there are no similar Level 1 data in patients with cirrhosis.”
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Small Hepatocellular Carcinoma: Treatment with Radio-frequency Ablation versus Ethanol Injection
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“%) and 91% (95% CI, 86% – 94%), respectively, [68] whereas ultrasound plus AFP achieves a sensitivity of 63% for early-stage HCC (95% CI, 48% – 75%).”
Self-citationContemporary Epidemiology of Chronic Liver Disease and Cirrhosis
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“[48,49] Although the target population has been unchanged for years, there are some populations with evolving data informing the value of HCC surveillance: (A) patients with HCV cirrhosis after SVR, (B) patients with noncirrhotic HCV after SVR, and (C) patients with noncirrhotic NAFLD.”
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“[201] The open-label phase III RCT comparing atezolizumab plus bevacizumab versus active surveillance (IMbrave 050) in the adjuvant setting for HCC patients at high-risk of recurrence after resection or local ablation was the first to demonstrate positive results.”
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“[321] Subsequently, the open-label, randomized phase III IMbrave150 trial established the combination of atezo-lizumab, an immunotherapy targeting PD-L1, plus bevacizumab, a monoclonal antibody targeting VEGF, as the preferred first-line treatment option for patients with advanced HCC. [312] The…”
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“[245,246] Both the Metroticket 2.0 [247] and French AFP models [248] demonstrated that a combination of AFP and tumor burden predicts post-LT outcome better than tumor burden alone.”
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Risk of Hepatocellular Cancer in HCV Patients Treated With Direct-Acting Antiviral Agents
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“[37] HBV vaccination has also been shown to significantly reduce HCC risk, so this should be performed in all newborns as well as high-risk adults who failed to undergo vaccination at birth.”
Recurrence of Hepatocellular Cancer After Resection: Patterns, Treatments, and Prognosis
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“[162,194] Factors associated with recurrence include older age; male sex; degree of liver dysfunction; and tumor size, number, and grade/differentiation; microvascular and macrovascular invasion; presence of satellite lesions; and AFP level.”
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“[330] In subgroup analysis, a benefit of ramucirumab for patients with AFP ≥ 400 ng/ml was noted, which was confirmed in the subsequent REACH-2 study evaluating ramucirumab in the subgroup of patients with AFP ≥ 400, although the absolute OS benefit was modest.”
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“[56,58,59] These studies have several potential limitations, including lead time bias, length time bias, risk of overdiagnosis, and residual confounding, although the benefits of surveillance remained in studies that statistically accounted for these biases.”
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Risk of hepatocellular cancer in patients with non-alcoholic fatty liver disease
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“…vitamin K absence/antagonist-II (PIVKA-II), a variant of prothrombin that is also specifically produced at high levels by a proportion of HCCs. [76,77] These biomarkers are currently Food and Drug Administration (FDA) approved for risk stratification but not HCC surveillance in the United States.”
Self-citationLencioni, R. A., de Baère, T., Soulen, M. C., Rilling, W. S., & Geschwind, J. H. (2016) · Hepatology · doi:10.1002/hep.28453 · Cited by 732 · cited 1× · see citing works
“[285] Patients who achieve objective response by modified response evaluation criteria in solid tumors (mRECIST) have prolonged survival compared with those without response (HR, 0.39; 95% CI, 0.26 – 0.619).”
InfluentialSelf-citationYau, T. C. C., Tang, V., Yao, T., Fan, S.-T., Lo, C., & Poon, R. T. P. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.02.032 · Cited by 697 · cited 1× · see citing works
“…with BCLC Stage B. [150] The HKLC system initially had nine stages, which were condensed to five stages to allow more nuanced stratification in intermediate-and advanced-stage HCC. [ 151 ] 147] combination therapies and transitions between types of therapies during follow-up follow-up — related”
Salem, R., Gordon, A. C., Mouli, S. K., Hickey, R., Kallini, J. R., Gabr, A., Mulcahy, M. F., Baker, T., Abecassis, M. M., Miller, F. H., et al. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.08.029 · Cited by 696 · cited 2× · see citing works
“[299] TARE using Y90 was granted FDA approval in 2021 based on results of the LEGACY Trial, [175] a single-arm retrospective analysis of 162 patients with Child-Turcotte-Pugh A cirrhosis and solitary HCC up to 8 cm (median size 2.7 cm).”
InfluentialSelf-citationLencioni, R. A., Llovet, J. M., Han, G., Tak, W. Y., Yang, J., Guglielmi, A., Paik, S. W., Reig, M., Kim, D. Y., Chau, G., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.01.012 · Cited by 692 · see citing works
Self-citationGlobal burden of cancer in 2020 attributable to alcohol consumption: a population-based study
Rumgay, H., Shield, K. D., Charvat, H., Ferrari, P., Sornpaisarn, B., Obot, I. S., Islami, F., Lemmens, V. E. P. P., Rehm, J. T., & Soerjomataram, I. (2021) · The Lancet Oncology · doi:10.1016/s1470-2045(21)00279-5 · Cited by 690 · cited 2× · see citing works
“Lifestyle factors, such as alcohol and tobacco use, increase risk of many cancers, including HCC. [15] Smoking is associated with a 20% – 86% increased risk of HCC, which can return nearly to baseline after 30 years of smoking cessation.”
mRECIST for HCC: Performance and novel refinements
Llovet, J. M., & Lencioni, R. A. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2019.09.026 · Cited by 689 · cited 2× · see citing works
“[310,311] mRECIST has become the standard tool to assess radiological response after locoregional therapy for patients with early and intermediate stages of HCC, whereas both RECIST 1.1 and mRECIST are recommended for patients with advanced-stage HCC undergoing systemic therapy.”
InfluentialSelf-citationMazzaferro, V., Sposito, C., Zhou, J., Pinna, A. D., De Carlis, L., Fan, J., Cescon, M., Di Sandro, S., Yi-feng, H., Lauterio, A., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2017.09.025 · Cited by 655 · cited 1× · see citing works
“[245,246] Both the Metroticket 2.0 [247] and French AFP models [248] demonstrated that a combination of AFP and tumor burden predicts post-LT outcome better than tumor burden alone.”
InfluentialGarin, É., Tselikas, L., Guiu, B., Chalaye, J., Edeline, J., de Baère, T., Assénat, E., Tacher, V., Robert, C., Terroir-Cassou-Mounat, M., et al. (2020) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(20)30290-9 · Cited by 639 · cited 2× · see citing works
“[304] Such decisions should be made in the context of a multidisciplinary tumor board.”
on behalf of the PRECISION ITALIA STUDY GROUP, Golfieri, R., Giampalma, E., Renzulli, M., Cioni, R., Bargellini, I., Bartolozzi, C., Breatta, A. D., Gandini, G., Nani, R., et al. (2014) · British Journal of Cancer · doi:10.1038/bjc.2014.199 · Cited by 606 · see citing works
International trends in hepatocellular carcinoma incidence, 1978–2012
Petrick, J. L., Florio, A. A., Znaor, A., Ruggieri, D., Laversanne, M., Alvarez, C. S., Ferlay, J., Valery, P. C., Bray, F., & McGlynn, K. A. (2020) · International Journal of Cancer · doi:10.1002/ijc.32723 · Cited by 594 · see citing works
Lin, S.-M., Lin, C.-J., Lin, C.-C., Hsu, C.-W., & Chen, Y.-C. (2005) · Gut · doi:10.1136/gut.2004.045203 · Cited by 592 · cited 1× · see citing works
“268] Although there have been no randomized head-to-head studies showing superiority of one thermal ablative modality over another, microwave ablation may be less susceptible to heat sink effects near large vessels.”
Kudo, M., Imanaka, K., Chida, N., Nakachi, K., Tak, W. Y., Takayama, T., Yoon, J., Hori, T., Kumada, H., Hayashi, N., et al. (2011) · European Journal of Cancer · doi:10.1016/j.ejca.2011.05.007 · Cited by 569 · see citing works
Yttrium‐90 Radioembolization for the Treatment of Solitary, Unresectable HCC: The LEGACY Study
Salem, R., Johnson, G. E., Kim, E., Riaz, A., Bishay, V. L., Boucher, É., Fowers, K. D., Lewandowski, R. J., & Padia, S. A. (2021) · Hepatology · doi:10.1002/hep.31819 · Cited by 568 · cited 2× · see citing works
“[299] TARE using Y90 was granted FDA approval in 2021 based on results of the LEGACY Trial, [175] a single-arm retrospective analysis of 162 patients with Child-Turcotte-Pugh A cirrhosis and solitary HCC up to 8 cm (median size 2.7 cm).”
InfluentialPapatheodoridis, G., Dalekos, G. Ν., Sypsa, V., Yurdaydın, C., Buti, M., Goulis, J., Calleja, J. L., Chi, H., Manolakopoulos, S., Mangia, G., et al. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.11.035 · Cited by 561 · see citing works
Yao, F. Y., Xiao, L., Bass, N. M., Kerlan, R. K., Ascher, N. L., & Roberts, J. P. (2007) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2007.01965.x · Cited by 560 · cited 1× · see citing works
“UCSF criteria [207] One tumor ≤ 6.5 cm or 2 – 3 tumors, each ≤ 4.5 cm, with total tumor volume ≤ 8 cm 81% 5-year survival Total tumor volume < 115 cm [208] Sum of volume for each tumor ≤ 115 cm 3 75% 4-year survival Up-to-seven criteria [209] Diameter or largest tumor (cm) + number of tumors ≤ 7…”
InfluentialChan, A. W. H., Zhong, J., Berhane, S., Toyoda, H., Cucchetti, A., Shi, K., Tada, T., Chong, C. C. N., Xiang, B., Li, L., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.08.027 · Cited by 548 · cited 1× · see citing works
“Although risk prediction models to stratify individualized risk of postsurgical resection have been proposed, [195,196] current evidence does not support a survival benefit of more frequent surveillance.”
Silva, M. A., Hegab, B. S., Hyde, C., Guo, B., Buckels, J. A. C., & Mirza, D. F. (2008) · Gut · doi:10.1136/gut.2008.149062 · Cited by 535 · cited 1× · see citing works
“[138] Diagnostic biomarkers AFP, at a threshold of 400 ng/ml, was previously recommended as a diagnostic criterion for HCC, although over 40% of HCC have normal AFP levels, and elevated AFP levels can be observed in other cancers, including intrahepatic cholangiocarcinoma, gastric cancer, and germ…”
Lee, Y. J., Lee, J. M., Lee, J. S., Lee, H. Y., Park, B. H., Kim, Y., Han, J. K., & Choi, B. I. (2015) · Radiology · doi:10.1148/radiol.14140690 · Cited by 524 · cited 1× · see citing works
“[106] Extracellular and hepatobiliary MRI contrast agents are both equally recommended based on current data, [98,107] although prospective head-to-head comparisons are encouraged.”
Meyer, T., Fox, R., Ma, Y. T., Ross, P. J., James, M. W., Sturgess, R. P., Stubbs, C., Stocken, D. D., Wall, L. R., Watkinson, A. F., et al. (2017) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(17)30156-5 · Cited by 500 · cited 1× · see citing works
“[293] – 298] Based on current data, the AASLD advises against combination therapy outside of clinical trials.”
Molecular pathogenesis and systemic therapies for hepatocellular carcinoma
Llovet, J. M., Pinyol, R., Kelley, R. K., El-Khoueiry, A., Reeves, H. L., Wang, X. W., Gores, G. J., & Villanueva, A. (2022) · Nature Cancer · doi:10.1038/s43018-022-00357-2 · Cited by 498 · cited 1× · see citing works
“[331] Noninvasive criteria for the presence of varices (e.g., Baveno VI criteria) have not been validated in patients with HCC.”
Self-citationImaging for the diagnosis of hepatocellular carcinoma: A systematic review and meta‐analysis
Roberts, L. R., Sirlin, C. B., Zaiem, F., Almasri, J., Prokop, L. J., Heimbach, J. K., Murad, M. H., & Mohammed, K. S. (2017) · Hepatology · doi:10.1002/hep.29487 · Cited by 498 · cited 4× · see citing works
“…suboptimal performance of CT or MRI to accurately diagnose HCC in lesions 1 cm, and expected tumor doubling time if the lesion were HCC. [87,97,98] If the liver lesion remains stable on two or more follow-up ultrasound exams, the risk of HCC is likely sufficiently low for the patient to…”
InfluentialSelf-citationAlifakioti, D., Daccord, C., Lachenal, Y., & Fitting, J.-W. (2014) · Respiration · doi:10.1159/000367814 · Cited by 495 · see citing works
Kokudo, T., Hasegawa, K., Matsuyama, Y., Takayama, T., Izumi, N., Kadoya, M., Kudo, M., Ku, Y., Sakamoto, M., Nakashima, O., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.05.044 · Cited by 491 · cited 1× · see citing works
“Although most data for hepatic resection in PVTT comes from Asia, [189,190] limited available data from Western centers support the role of surgical resection in selected patients, [191,192] particularly in subsegmental (Vp1) and segmental (Vp2), in which meaningful long-term survival has been…”
Mazzaferro, V., Battiston, C., Perrone, S., Pulvirenti, A., Regalia, E., Romito, R., Sarli, D., Schiavo, M., Garbagnati, F., Marchianò, A. V., et al. (2004) · Annals of Surgery · doi:10.1097/01.sla.0000143301.56154.95 · Cited by 490 · see citing works
Yao, F. Y., Mehta, N. J., Flemming, J. A., Dodge, J. L., Hameed, B., Fix, O. K., Hirose, R., Fidelman, N. A., Kerlan, R. K., & Roberts, J. P. (2015) · Hepatology · doi:10.1002/hep.27752 · Cited by 485 · see citing works
Self-citationMitchell, D. G., Bruix, J., Sherman, M., & Sirlin, C. B. (2014) · Hepatology · doi:10.1002/hep.27304 · Cited by 483 · cited 2× · see citing works
“[103] diagnosis in patients with cirrhosis and appear to have acceptable accuracy in those with noncirrhotic HBV.”
Peng, Z., Fan, W., Zhu, B., Wang, G., Sun, J., Xiao, C., Huang, F., Tang, R., Cheng, Y., Huang, Z., et al. (2022) · Journal of Clinical Oncology · doi:10.1200/jco.22.00392 · Cited by 462 · cited 1× · see citing works
“…demonstrated superior survival with the combination of camrelizumab and rivoceranib versus sorafenib, [326] TACE plus lenvatinib versus lenvatinib [327] and noninferior survival of tislelizumab versus sorafenib [328] ; however, it is unclear if these therapies apply to patients in the Western…”
Singal, A. G., Zhang, E. D., Narasimman, M., Rich, N. E., Waljee, A. K., Hoshida, Y., Yang, J. D., Reig, M., Cabibbo, G., Nahon, P., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.01.023 · Cited by 455 · see citing works
Self-citationBolondi, L., Gaiani, S., Celli, N., Golfieri, R., Grigioni, W. F., Leoni, S., Venturi, A. M., & Piscaglia, F. (2005) · Hepatology · doi:10.1002/hep.20728 · Cited by 450 · see citing works
Geissler, E. K., Schnitzbauer, A. A., Zülke, C., Lamby, P. E., Proneth, A., Duvoux, C., Burra, P., Jauch, K.-W., Rentsch, M., Ganten, T. M., et al. (2016) · Transplantation · doi:10.1097/tp.0000000000000965 · Cited by 433 · cited 1× · see citing works
“…prospective international phase III SiLVER trial failed to demonstrate an overall benefit of sirolimus in improving long-term recurrence-free survival beyond 5 years after LT, [256] the subgroup within Milan criteria had improved recurrence-free survival with mTOR inhibitor-based immunosuppression.”
Pinato, D. J., Sharma, R., Allara, E., Yen, C., Arizumi, T., Kubota, K., Bettinger, D., Jang, J. W., Smirne, C., Kim, Y. W., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.09.008 · Cited by 416 · cited 1× · see citing works
“Other measures including the MELD score or MELD including sodium (MELD-Na), ALBI score, [171] indocyanine green kinetics, [172] and liver stiffness measurement by transient elastography [173] are associated with risk of postresection hepatic decompensation and may also be used to refine patient…”
Resection Prior to Liver Transplantation for Hepatocellular Carcinoma
Belghiti, J., Cortès, A., Abdalla, E. K., Regimbeau, J., Prakash, K., Durand, F., Sommacale, D., Dondero, F., Lesurtel, M., Sauvanet, A., et al. (2003) · Annals of Surgery · doi:10.1097/01.sla.0000098621.74851.65 · Cited by 415 · cited 1× · see citing works
“Numerous studies have reported equivalent post-LT graft and patient outcomes in patients undergoing salvage LT. [217,218] A large comparative analysis of primary LT ( n = 340) versus resection with intent for salvage LT ( n = 130) revealed superior OS in primary LT versus salvage LT; however, the…”
Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference
Llovet, J. M., Villanueva, A., Marrero, J. A., Schwartz, M., Meyer, T., Galle, P. R., Lencioni, R., Greten, T. F., Kudo, M., Mandrekar, S. J., et al. (2021) · Hepatology · doi:10.1002/hep.31327 · Cited by 413 · cited 1× · see citing works
“[126] Although no biomarker has yet been linked to treatment-related clinical benefit, except for AFP levels ≥ 400 ng/ml and ramucirumab in advanced HCC, [127] systematic collection of histological specimens can facilitate precision treatment initiatives.”
Self-citationSangro, B., Melero, I., Wadhawan, S., Finn, R. S., Abou-Alfa, G. K., Cheng, A.-L., Yau, T., Furuse, J., Park, J.-W., Boyd, Z., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.07.026 · Cited by 407 · cited 1× · see citing works
“[129] Even if in few circumstances, histology can capture mixed HCC-cholangiocarcinoma among LR-5 cases, a feature with significant clinical implications.”
Cucchetti, A., Piscaglia, F., Cescon, M., Colecchia, A., Ercolani, G., Bolondi, L., & Pinna, A. D. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.04.009 · Cited by 404 · cited 2× · see citing works
“263] Eligibility for ablation is determined by tumor size and location and the ability to achieve adequate ablation margins.”
Ioannou, G. N., Beste, L. A., Green, P. K., Singal, A. G., Tapper, E. B., Waljee, A. K., Sterling, R. K., Feld, J. J., Kaplan, D. E., Taddei, T. H., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.07.033 · Cited by 401 · cited 1× · see citing works
“[52] HCC incidence is significantly lower in post-SVR patients without cirrhosis, and surveillance is not cost-effective or recommended in this population.”
Self-citationMehta, N. J., Heimbach, J. K., Harnois, D. M., Sapisochín, G., Dodge, J. L., Lee, D. D., Burns, J. M., Sánchez, W., Greig, P. D., Grant, D. R., et al. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2016.5116 · Cited by 400 · cited 2× · see citing works
“[245,246] Both the Metroticket 2.0 [247] and French AFP models [248] demonstrated that a combination of AFP and tumor burden predicts post-LT outcome better than tumor burden alone.”
InfluentialSelf-citationTrinchet, J., Chaffaut, C., Bourcier, V., Degos, F., Henrion, J., Fontaine, H., Roulot, D. M., Mallat, A., Hillaire, S., Calès, P., et al. (2010) · Hepatology · doi:10.1002/hep.24545 · Cited by 399 · cited 1× · see citing works
“[90] Organized surveillance programs 93] Several models of organized surveillance programs have been proposed to improve surveillance implementation.”
Abou-Alfa, G. K., Chan, S. L., Kudo, M., Lau, G., Kelley, R. K., Furuse, J., Sukeepaisarnjaroen, W., Kang, Y.-K., Dao, T. V., De Toni, E. N., et al. (2022) · Journal of Clinical Oncology · doi:10.1200/jco.2022.40.4_suppl.379 · Cited by 388 · cited 2× · see citing works
“[323] Durvalumab plus tremelimu-mab produced a 36-month survival of 30.7%, compared to 20.2% for sorafenib.”
InfluentialLu, D., Yu, N. C., Raman, S. S., Limanond, P., Lassman, C., Murray, K. A., Tong, M. J., Amado, R. G., & Busuttil, R. W. (2005) · Radiology · doi:10.1148/radiol.2343040153 · Cited by 385 · see citing works
Marrero, J. A., Kudo, M., Venook, A. P., Ye, S.-L., Bronowicki, J., Chen, X., Dagher, L., Furuse, J., Geschwind, J.-F. H., de Guevara, L. L., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.07.020 · Cited by 383 · cited 1× · see citing works
“[335] There are emerging data for safety of other mTKI agents, such as lenvatinib, in patients with Child-Turcotte-Pugh B liver disease as well.”
Self-citationBrown, K. T., Do, R. K., Gönen, M., Covey, A. M., Getrajdman, G. I., Sofocleous, C. T., Jarnagin, W. R., D'Angelica, M. I., Allen, P. J., Erinjeri, J. P., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.64.0821 · Cited by 380 · cited 1× · see citing works
“– 289] Patient selection and vascular selectivity are critical factors to optimize TACE outcomes.”
Sapisochín, G., Goldaracena, N., Laurence, J. M., Dib, M. J., Barbas, A. S., Ghanekar, A., Cleary, S. P., Lilly, L. B., Cattral, M. S., Marquez, M. A., et al. (2016) · Hepatology · doi:10.1002/hep.28643 · Cited by 369 · cited 1× · see citing works
“…75% 4-year survival Up-to-seven criteria [209] Diameter or largest tumor (cm) + number of tumors ≤ 7 71% 5-year survival Extended Toronto criteria [210] Biopsy demonstrating well-to-moderate differentiation for patients beyond Milan criteria and ECOG performance status 0 – 1 68% 5-year survival…”
How Much Remnant Is Enough in Liver Resection?
Guglielmi, A., Ruzzenente, A., Conci, S., Valdegamberi, A., & Iacono, C. (2012) · Digestive Surgery · doi:10.1159/000335713 · Cited by 363 · cited 1× · see citing works
“[168] In these patients, surgical resection affords 5-year survival exceeding 70% and postoperative mortality of 3%.”
Epidemiology and risk-stratification of NAFLD-associated HCC
Ioannou, G. N. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.08.012 · Cited by 361 · see citing works
Ravaioli, M., Grazi, G. L., Piscaglia, F., Trevisani, F., Cescon, M., Ercolani, G., Vivarelli, M., Golfieri, R., D’Errico, A., Panzini, I., et al. (2008) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2008.02409.x · Cited by 361 · see citing works
Loomba, R. S., Lim, J. K., Patton, H. M., & El‐Serag, H. B. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.12.053 · Cited by 360 · see citing works
Ho, W. J., Zhu, Q., Durham, J., Popovic, A., Xavier, S., Leatherman, J., Mohan, A., Mo, G., Zhang, S., Gross, N., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00234-4 · Cited by 360 · see citing works
Self-citationKim, S. Y., An, J., Lim, Y.-S., Han, S., Lee, J.-Y., Byun, J. H., Won, H. J., Lee, S. J., Lee, H. C., & Lee, Y. S. (2017) · JAMA Oncology · doi:10.1001/jamaoncol.2016.3147 · Cited by 356 · cited 1× · see citing works
“[81,82] However, neither have been validated in cohorts of Western patients without HBV.”
Kudo, M., Han, G., Finn, R. S., Poon, R. T. P., Blanc, J., Yan, L., Yang, J., Lu, L., Tak, W. Y., Yu, X., et al. (2014) · Hepatology · doi:10.1002/hep.27290 · Cited by 352 · see citing works
Sieghart, W., Hucke, F., Pinter, M., Graziadei, I. W., Vogel, W., Müller, C., Heinzl, H., Trauner, M. A., & Peck‐Radosavljevic, M. (2013) · Hepatology · doi:10.1002/hep.26256 · Cited by 343 · cited 1× · see citing works
“[305] 308] Response evaluation criteria in solid tumors (RECIST) v1.”
Mazzaferro, V., Citterio, D., Bhoori, S., Bongini, M., Miceli, R., De Carlis, L., Colledan, M., Salizzoni, M., Romagnoli, R., Antonelli, B., et al. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(20)30224-2 · Cited by 341 · cited 1× · see citing works
“[241] Based on these data, patients who are otherwise transplant eligible except with initial tumor burden exceeding the Milan criteria, particularly those within UNOS downstaging (UNOS-DS) criteria, should be considered for LT following successful downstaging to within Milan criteria.”
Stine, J. G., Wentworth, B. J., Zimmet, A., Rinella, M. E., Loomba, R., Caldwell, S. H., & Argo, C. K. (2018) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14937 · Cited by 336 · cited 1× · see citing works
“[157,158] Patients without cirrhosis have lower post-operative liver-related morbidity, lower cumulative HCC recurrence rates, and higher disease-specific survival compared with those with underlying cirrhosis who undergo resection.”
van der Pol, C. B., Lim, C. S., Sirlin, C. B., McGrath, T. A., Salameh, J., Bashir, M. R., Tang, A., Singal, A. G., Costa, A. F., Fowler, K. J., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.11.020 · Cited by 334 · cited 2× · see citing works
“– 120] Conversely, HCC probability is ∼ 75% for LR-4 lesions, so these patients are advised to undergo biopsy or close-interval follow-up imaging at 3 months, depending on the clinical scenario.”
Self-citationWolf, E., Rich, N. E., Marrero, J. A., Parikh, N. D., & Singal, A. G. (2021) · Hepatology · doi:10.1002/hep.31309 · Cited by 333 · cited 1× · see citing works
“[91,94,95] The AASLD recommends use of these evidence-based interventions to increase surveillance utilization in clinical practice.”
Self-citationNg, K. K., Chok, K., Chan, A. C. Y., Cheung, T. T., Wong, T. C.-L., Fung, J., Yuen, J., Poon, R. T. P., Fan, S. T., & Lo, C. M. (2017) · British journal of surgery · doi:10.1002/bjs.10677 · Cited by 331 · see citing works
Projections of primary liver cancer to 2030 in 30 countries worldwide
Valery, P. C., Laversanne, M., Clark, P. J., Petrick, J. L., McGlynn, K. A., & Bray, F. (2017) · Hepatology · doi:10.1002/hep.29498 · Cited by 330 · cited 1× · see citing works
“The strongest risk factor for developing HCC is cirrhosis from any liver disease etiology, which is present in over 80% of patients with HCC. [7] Patients with cirrhosis from any etiology typically have a ∼ 2% annual risk of developing HCC. [8] Chronic hepatitis B virus (HBV) and hepatitis C virus…”
Berhane, S., Toyoda, H., Tada, T., Kumada, T., Kagebayashi, C., Satomura, S., Schweitzer, N., Vogel, A., Manns, M. P., Benckert, J., et al. (2016) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2015.12.042 · Cited by 324 · cited 1× · see citing works
“[78] GALAD was subsequently evaluated in a large Phase III biomarker study, the Hepatocellular carcinoma Early Detection Strategy (HEDS) study, in which it was found to have a sensitivity and specificity of 65% and 82% for HCC, respectively [79] There has also been interest in use of liquid biopsy…”
Tommaso, L. D., Destro, A., Seok, J. Y., Balladore, E., Terracciano, L., Sangiovanni, A., Iavarone, M. A., Colombo, M., Jang, J. J., Yu, E., et al. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2008.11.014 · Cited by 322 · cited 1× · see citing works
“…two of four markers (glypican 3 [GPC3], glutamine synthetase, heat shock protein 70 [HSP70], and clathrin heavy chain) is highly specific for HCC. [131,132] Additional staining can be considered to detect progenitor cell features (K19 and epithelial cellular adhesion molecule) or…”
Tang, A., Bashir, M. R., Corwin, M. T., Cruite, I., Dietrich, C. F., Gian, R. K., Ehman, E. C., Fowler, K. J., Hussain, H. K., Jha, R. C., et al. (2017) · Radiology · doi:10.1148/radiol.2017170554 · Cited by 318 · cited 1× · see citing works
“[103,112] LI-RADS categorizes liver nodules on a scale from LR-1 (benign) to LR-5 (HCC).”
OPTN/SRTR 2019 Annual Data Report: Liver
Kwong, A. J., Kim, W. R., Lake, J. R., Smith, J. M., Schladt, D. P., Skeans, M. A., Noreen, S. M., Foutz, J., Booker, S. E., Cafarella, M., et al. (2021) · American Journal of Transplantation · doi:10.1111/ajt.16494 · Cited by 311 · cited 1× · see citing works
“…is increasing in the United States, with a recent analysis of OPTN data demonstrating excellent post-LT survival in the setting of LDLT for HCC. [ 227,228 ] Use of bridging therapy Given the mandatory 6-month wait time prior to the awarding of MELD exception, neoadjuvant locoregional therapy…”
Kudo, M., Ueshima, K., Chan, S., Minami, T., Chishina, H., Aoki, T., Takita, M., Hagiwara, S., Minami, Y., Ida, H., et al. (2019) · Cancers · doi:10.3390/cancers11081084 · Cited by 309 · cited 1× · see citing works
“[293] – 298] Based on current data, the AASLD advises against combination therapy outside of clinical trials.”
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“[89] A subsequent multicenter RCT demonstrated quarterly surveillance did not improve early HCC detection or survival compared with semiannual surveillance.”
Association of Aspirin with Hepatocellular Carcinoma and Liver-Related Mortality
Simon, T. G., Duberg, A., Aleman, S., Chung, R. T., Chan, A. T., & Ludvigsson, J. F. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1912035 · Cited by 304 · cited 1× · see citing works
“[40,41] Similarly, meta-analyses found statin use may be associated with reduced HCC risk, with a relative risk of 0.54, regardless of underlying disease.”
InfluentialSapisochín, G., Barry, A. S., Doherty, M. K., Fischer, S. E., Goldaracena, N., Rosales, R., Russo, M., Beecroft, R., Ghanekar, A., Bhat, M., et al. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.02.022 · Cited by 302 · cited 1× · see citing works
“[280] The RTOG1112 Trial reported higher survival with SBRT followed by sorafenib compared to sorafenib alone in patients with locally advanced HCC, although this difference did not reach statistical significance (15.8 vs. 12.3 mo; 1-sided p = 0.055).”
InfluentialSelf-citationKulik, L., Heimbach, J. K., Zaiem, F., Almasri, J., Prokop, L. J., Wang, Z., Murad, M. H., & Mohammed, K. S. (2017) · Hepatology · doi:10.1002/hep.29485 · Cited by 297 · cited 1× · see citing works
“[229] Because tumor progression despite LRT is associated with worse post-LT outcome, [230 – 232] observing tumor behavior after LRT may allow for a more refined selection of candidates for LT. [213,233] Although a recent UNOS national analysis suggested ablation or TARE as initial LRT may be…”
Self-citationToso, C., Meeberg, G., Hernandez‐Alejandro, R., Dufour, J., Marotta, P., Majno, P. E., & Kneteman, N. M. (2015) · Hepatology · doi:10.1002/hep.27787 · Cited by 281 · cited 1× · see citing works
“…criteria [207] One tumor ≤ 6.5 cm or 2 – 3 tumors, each ≤ 4.5 cm, with total tumor volume ≤ 8 cm 81% 5-year survival Total tumor volume < 115 cm [208] Sum of volume for each tumor ≤ 115 cm 3 75% 4-year survival Up-to-seven criteria [209] Diameter or largest tumor (cm) + number of tumors ≤ 7 71%…”
InfluentialRecurrence After Liver Transplantation for Hepatocellular Carcinoma: A New MORAL to the Story
Halazun, K. J., Najjar, M., Abdelmessih, R. M., Samstein, B., Griesemer, A. D., Guarrera, J. V., Kato, T., Verna, E. C., Emond, J. C., & Brown, R. S. (2017) · Annals of Surgery · doi:10.1097/sla.0000000000001966 · Cited by 281 · see citing works
Yang, J. D., Mohamed, E. A., Aziz, A. O. A., Shousha, H. I., Hashem, M. B., Nabil, M. M., Abdelmaksoud, A., Elbaz, T. M., Afihene, M., Duduyemi, B. M., et al. (2016) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(16)30161-3 · Cited by 280 · see citing works
Kaseb, A. O., Hasanov, E., Cao, H. S. T., Xiao, L., Vauthey, J.-N., Lee, S. S., Yavuz, B. G., Mohamed, Y. I., Qayyum, A., Jindal, S., et al. (2022) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(21)00427-1 · Cited by 274 · cited 1× · see citing works
“[204] AASLD advises against the use of neo-adjuvant systemic therapies in patients undergoing liver resection outside of a clinical trial setting.”
Fisher, R. A., Kulik, L., Freise, C. E., Lok, A. S.-F., Shearon, T. H., Brown, R. S., Ghobrial, R. M., Fair, J. H., Olthoff, K. M., Kam, I., et al. (2007) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2007.01802.x · Cited by 272 · cited 1× · see citing works
“[222,223] 226] Because of the ongoing critical organ shortage and recent allocation changes, LDLT is increasing in the United States, with a recent analysis of OPTN data demonstrating excellent post-LT survival in the setting of LDLT for HCC. [ 227,228 ] Use of bridging therapy Given the mandatory…”
Self-citationSerper, M., Taddei, T. H., Mehta, R. L., D’Addeo, K., Dai, F., Aytaman, A., Baytarian, M. L., Fox, R. K., Hunt, K. K., Goldberg, D. S., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.02.040 · Cited by 267 · see citing works
Self-citationAtiq, O., Tiro, J., Yopp, A. C., Muffler, A., Marrero, J. A., Parikh, N. D., Murphy, C., McCallister, K., & Singal, A. G. (2017) · Hepatology · doi:10.1002/hep.28895 · Cited by 266 · cited 1× · see citing works
“[62,63] Available data suggest HCC surveillance harms that are due to false positives and indeterminate tests occur in ∼ 10% of patients with cirrhosis and most harms are mild in severity.”
Self-citationNAFLD-driven HCC: Safety and efficacy of current and emerging treatment options.
Foerster, F., Gairing, S., Müller, L., & Galle, P. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.09.007 · Cited by 265 · cited 1× · see citing works
“[159] Although comorbidities associated with NASH may prevent potentially curative therapies in a higher proportion of patients compared with viral-related HCC, outcomes are similar among those who undergo resection.”
Rodríguez‐Perálvarez, M., Tsochatzis, E. A., Naveas, M. C., Pieri, G., García-Caparrós, C., O’Beirne, J. P., Poyato, A., Ferrín, G., Montero-Álvarez, J. L., Patch, D., et al. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.07.012 · Cited by 264 · cited 1× · see citing works
“In terms of immunosuppression, calcineurin inhibitors have been associated with increased HCC recurrence, [255] whereas mTOR inhibitors appear to have antineoplastic properties.”
Terzi, E., Iavarone, M. A., Pompili, M., Veronese, L., Cabibbo, G., Fraquelli, M., Riccardi, L., Bonis, L. D., Sangiovanni, A., Leoni, S., et al. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.11.007 · Cited by 259 · cited 1× · see citing works
“[108,109] However, compared to CT and MRI, CEUS has limitations of operator dependency, impact of patient/tumor factors on visualization (similar to ultrasound), lack of full staging data, and insufficient information for treatment planning.”
Long-term Effects of Hepatitis B Immunization of Infants in Preventing Liver Cancer
Chang, M., You, S., Chen, C., Liu, C., Lai, M., Wu, T., Wu, S., Lee, C., Yang, S., Chu, H.-C., et al. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.05.048 · Cited by 258 · see citing works
Petrick, J. L., Campbell, P. T., Koshiol, J., Thistle, J. E., Andreotti, G., Beane-Freeman, L. E., Buring, J. E., Chan, A. T., Chong, D. Q., Doody, M. M., et al. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0007-z · Cited by 257 · cited 1× · see citing works
“[22] 26 – 28] In the United States, state-level HCC incidence has a moderate correlation with regional obesity and lack of physical activity, suggesting a possible benefit of public policy interventions.”
Inflamed and non-inflamed classes of HCC: a revised immunogenomic classification
Montironi, C., Castet, F., Haber, P. K., Pinyol, R., Torres-Martin, M., Torrens, L., Mesropian, A., Wang, H., Puigvehi, M., Maeda, M., et al. (2023) · Gut · doi:10.1136/gutjnl-2021-325918 · Cited by 253 · cited 1× · see citing works
“Aside from diagnostic purposes, HCC biopsies can be informative of molecular and immune classes of HCC, [9] oncogenic mutations associated with immune excluded phenotypes, [128] and gene signatures predictive of response to immunotherapy.”
Self-citationAgopian, V. G., Harlander‐Locke, M. P., Zarrinpar, A., Kaldas, F. M., Farmer, D. G., Yersiz, H., Finn, R. S., Tong, M. J., Hiatt, J. R., & Busuttil, R. W. (2014) · Journal of the American College of Surgeons · doi:10.1016/j.jamcollsurg.2014.12.025 · Cited by 252 · cited 2× · see citing works
“[251 ,252] Because the two most common sites of posttrans-plant recurrence are the lung ( ∼ 40”
Self-citationHaber, P. K., Puigvehí, M., Castet, F., Lourdusamy, V., Montal, R., Tabrizian, P., Buckstein, M., Kim, E., Villanueva, A., Schwartz, M., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.06.008 · Cited by 248 · cited 1× · see citing works
“[160] Despite higher rates of perioperative complications (post-hepatectomy liver failure, prolonged length of hospitalization) and morbidity, a meta-analysis of nine studies comparing outcomes of curative therapy in NAFLD and non-NAFLD HCC reported improved disease-free and OS after liver…”
Self-citationYopp, A. C., Mansour, J. C., Beg, M. S., Arenas, J. D., Trimmer, C. K., Reddick, M. A., Pedrosa, I., Khatri, G., Yakoo, T., Meyer, J. J., et al. (2013) · Annals of Surgical Oncology · doi:10.1245/s10434-013-3413-8 · Cited by 243 · cited 1× · see citing works
“[155] Radiological assessment of response Patients treated with TACE should undergo multiphase CT or contrast-enhanced MRI approximately 6 weeks after treatment, whereas those treated with TARE or EBRT should undergo imaging to assess response approximately 12 weeks after treatment (Figure 14).”
Self-citationAndersson, K. L., Salomon, J. A., Goldie, S. J., & Chung, R. T. (2008) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2008.08.005 · Cited by 243 · see citing works
Pawlik, T. M., Poon, R. T. P., Abdalla, E. K., Ikai, I., Nagorney, D. M., Belghiti, J., Kianmanesh, R., Ng, I. O., Curley, S. A., Yamaoka, Y., et al. (2005) · Surgery · doi:10.1016/j.surg.2004.12.012 · Cited by 235 · cited 1× · see citing works
“…most data for hepatic resection in PVTT comes from Asia, [189,190] limited available data from Western centers support the role of surgical resection in selected patients, [191,192] particularly in subsegmental (Vp1) and segmental (Vp2), in which meaningful long-term survival has been reported.”
Sun, N., Lee, Y., Zhang, R. Y., Kao, R., Teng, P., Yang, Y., Yang, P., Wang, J. J., Smalley, M. D., Chen, P., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18311-0 · Cited by 233 · cited 1× · see citing works
“[141] Alterations in ctDNA, ctDNA methylation profiles, [142] and extracellular RNA signatures from exosomes [143,144] have been explored in case-control studies for early detection and diagnosis.”
Self-citationKim, T. H., Koh, Y. H., Kim, B. H., Kim, M. J., Lee, J. H., Park, B., & Park, J. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.09.026 · Cited by 232 · cited 1× · see citing works
“[279] EBRT has also been used as a bridge to liver transplantation, with high observed response rates and comparable dropout rates with thermal ablation or TACE.”
AASLD Practice Guidance: Palliative care and symptom‐based management in decompensated cirrhosis
Rogal, S. S., Hansen, L., Patel, A., Ufere, N. N., Verma, M., Woodrell, C. D., & Kanwal, F. (2022) · Hepatology · doi:10.1002/hep.32378 · Cited by 226 · cited 1× · see citing works
“[339] 50.”
Liver Transplantation and Hepatic Resection can Achieve Cure for Hepatocellular Carcinoma
Pinna, A. D., Yang, T., Mazzaferro, V., Carlis, L. G. D., Zhou, J., Roayaie, S., Shen, F., Sposito, C., Cescon, M., Sandro, S. D., et al. (2018) · Annals of Surgery · doi:10.1097/sla.0000000000002889 · Cited by 226 · cited 2× · see citing works
“[162,194] Factors associated with recurrence include older age; male sex; degree of liver dysfunction; and tumor size, number, and grade/differentiation; microvascular and macrovascular invasion; presence of satellite lesions; and AFP level.”
Singal, A. G., Nehra, M. S., ADAMS-HUET, B. A., Yopp, A. C., Tiro, J. A., Marrero, J. A., Lok, A. S.-F., & Lee, W. M. (2013) · The American Journal of Gastroenterology · doi:10.1038/ajg.2012.449 · Cited by 225 · see citing works
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“[104,105] A recent meta-analysis suggests MRI has higher sensitivity (82% vs. 66%), with similar specificity (92% vs. 91”
Hyun, M. H., Lee, Y., Kim, J. H., Lee, C. U., Jung, Y. K., Seo, Y. S., Yim, H. J., Yeon, J. E., & Byun, K. S. (2018) · Hepatology · doi:10.1002/hep.29883 · Cited by 219 · cited 1× · see citing works
“[187] Similarly, a Western multicenter study also reported a 52.8% 5-year survival in multinodular HCC beyond Milan criteria.”
InfluentialOrci, L. A., Sanduzzi-Zamparelli, M., Caballol, B., Sapena, V., Colucci, N., Torres, F., Bruix, J., Reig, M., & Toso, C. (2022) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2021.05.002 · Cited by 218 · cited 1× · see citing works
“[20,54] Patients with HCV and NAFLD without cirrhosis, particularly those with advanced fibrosis, would benefit from risk stratification tools to identify those at highest risk to whom surveillance could be targeted in the future.”
Screening for Hepatocellular Carcinoma in Chronic Liver Disease
Kansagara, D. L., Papak, J., Pasha, A. S., O'Neil, M. E., Freeman, M., Relevo, R., Quiñones, A. R., Motu’apuaka, M. L., & Jou, J. H. (2014) · Annals of Internal Medicine · doi:10.7326/m14-0558 · Cited by 217 · see citing works
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Dhondt, E., Lambert, B., Hermie, L., Huyck, L., Vanlangenhove, P., Geerts, A. M., Verhelst, X., Aerts, M., Vanlander, A., Berrevoet, F. C., et al. (2022) · Radiology · doi:10.1148/radiol.211806 · Cited by 214 · see citing works
Lo, C. M., Fan, S. T., Liu, C. L., Chan, S. C., Ng, I. O., & Wong, J. (2006) · British journal of surgery · doi:10.1002/bjs.5528 · Cited by 213 · cited 1× · see citing works
“[222,223] 226] Because of the ongoing critical organ shortage and recent allocation changes, LDLT is increasing in the United States, with a recent analysis of OPTN data demonstrating excellent post-LT survival in the setting of LDLT for HCC. [ 227,228 ] Use of bridging therapy Given the mandatory…”
Hanna, R. F., Miloushev, V. Z., Tang, A., Finklestone, L. A., Brejt, S. Z., Sandhu, R. S., Santillan, C., Wolfson, T. J., Gamst, A. C., & Sirlin, C. B. (2015) · Abdominal Radiology · doi:10.1007/s00261-015-0592-8 · Cited by 210 · cited 1× · see citing works
“[106] Extracellular and hepatobiliary MRI contrast agents are both equally recommended based on current data, [98,107] although prospective head-to-head comparisons are encouraged.”
Association Between Aspirin Use and Risk of Hepatocellular Carcinoma
Simon, T. G., Ma, Y., Ludvigsson, J. F., Chong, D. Q., Giovannucci, E. L., Fuchs, C. S., Meyerhardt, J. A., Corey, K. E., Chung, R. T., Zhang, X., et al. (2018) · JAMA Oncology · doi:10.1001/jamaoncol.2018.4154 · Cited by 210 · cited 1× · see citing works
“[40,41] Similarly, meta-analyses found statin use may be associated with reduced HCC risk, with a relative risk of 0.54, regardless of underlying disease.”
InfluentialCabibbo, G., Celsa, C., Calvaruso, V., Petta, S., Cacciola, I., Cannavò, M. R., Madonia, S., Rossi, M., Magro, B., Rini, F., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.03.027 · Cited by 207 · see citing works
Choi, J., Kim, G., Han, S., Lee, W., Chun, S., & Lim, Y. (2018) · Hepatology · doi:10.1002/hep.30233 · Cited by 205 · cited 2× · see citing works
“Early detection research network (EDRN) phase of validation Performance characteristics US plus AFP [55] 5 Sensitivity 61% Specificity 92% AFP-L3% [69] 3 Sensitivity 62% Specificity 90% DCP [69] 3 Sensitivity 40% Specificity 81% Multitarget algorithm [70] 2 Sensitivity 82% Specificity 87% GALAD […”
Lü, J., Zhang, X., Zhong, B., Lau, W. Y., Madoff, D. C., Davidson, J. C., Qi, X., Cheng, S., & Teng, G. (2019) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(19)30178-5 · Cited by 204 · cited 1× · see citing works
“[193] With significant improvement in systemic therapy for advanced-stage disease, future studies are necessary to best define which subpopulation of patients with multifocal disease or PVTT may benefit from surgical resection.”
Kudo, M., Cheng, A., Park, J., Park, J. H., Liang, P., Hidaka, H., Izumi, N., Heo, J., Lee, Y. J., Sheen, I., et al. (2017) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(17)30290-x · Cited by 198 · see citing works
Park, J., Kim, Y. J., Kim, D. Y., Bae, S. H., Paik, S. W., Lee, Y. J., Kim, H. Y., Lee, H. C., Han, S. Y., Cheong, J. Y., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.11.029 · Cited by 198 · cited 1× · see citing works
“In addition, the combination of TACE and mTKI therapy failed to improve OS in prior studies of advanced-stage HCC. [329] Therefore, AASLD does not currently recommend the routine addition of TACE to systemic therapy for patients with advanced-stage HCC.”
Singal, A. G., Rich, N. E., Mehta, N. J., Branch, A. D., Pillai, A. A., Hoteit, M. A., Volk, M. L., Odewole, M., Scaglione, S., Guy, J. E., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.07.040 · Cited by 192 · cited 1× · see citing works
“In HCV-associated HCC, two large multicenter studies from North America [198] and Italy [199] confirmed that eradication of HCV with direct-acting antiviral therapy does not increase risk of HCC recurrence and improves survival.”
Self-citationIoannou, G. N., Green, P. K., Kerr, K. F., & Berry, K. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.05.008 · Cited by 191 · cited 1× · see citing works
“33 – 35] There are also several risk stratification models in patients with HBV, although fewer have been validated in Western populations in the setting of antiviral therapy.”
Kennedy, O. J., Roderick, P. J., Buchanan, R. M., Fallowfield, J. A., Hayes, P. C., & Parkes, J. (2017) · BMJ Open · doi:10.1136/bmjopen-2016-013739 · Cited by 190 · see citing works
Rajyaguru, D. J., Borgert, A. J., Smith, A., Thomes, R. M., Conway, P. D., Halfdanarson, T. R., Truty, M. J., Kurup, A. N., & Go, R. S. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.75.3228 · Cited by 189 · cited 1× · see citing works
“[278] A phase III noninferiority RCT comparing PBT and radiofrequency ablation among patients with recurrent/residual HCC demonstrated noninferior 2-year local progression-free survival (PFS: 92.8% vs. 83.2%, respectively) and a lower proportion of patients with increased Child-Turcotte-Pugh score…”
InfluentialOhkuma, T., Peters, S. A. E., & Woodward, M. (2018) · Diabetologia · doi:10.1007/s00125-018-4664-5 · Cited by 188 · cited 1× · see citing works
“[22] 26 – 28] In the United States, state-level HCC incidence has a moderate correlation with regional obesity and lack of physical activity, suggesting a possible benefit of public policy interventions.”
Finn, R. S., Kudo, M., Merle, P., Meyer, T., Qin, S., Ikeda, M., Xu, R., Edeline, J., Ryoo, B.-Y., Ren, Z., et al. (2022) · Annals of Oncology · doi:10.1016/j.annonc.2022.08.031 · Cited by 187 · cited 1× · see citing works
“[324] Interestingly, the median survival for the lenvatinib arm was longer than anticipated at 19.0 months, compared with 21.2 months for the combination of pembrolizumab plus lenvatinib, supporting the role of lenvatinib as a standard of care for patients with advanced HCC who are not candidates…”
InfluentialSelf-citationBodzin, A. S., Lunsford, K. E., Markovic, D., Harlander‐Locke, M. P., Busuttil, R. W., & Agopian, V. G. (2016) · Annals of Surgery · doi:10.1097/sla.0000000000001894 · Cited by 182 · cited 1× · see citing works
“[253] A multicenter analysis has proposed and validated a risk stratification score, Risk Estimation of Tumor Recurrence After Transplant (RETREAT), which incorporates AFP at LT, vascular invasion, the sum of the largest viable tumor diameter, and number of viable tumors on explant.”
Self-citationAbbreviated MRI for hepatocellular carcinoma screening: A systematic review and meta-analysis
Gupta, P. C., Soundararajan, R., Patel, A., Kumar, P. M., Sharma, V., & Kalra, N. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.01.041 · Cited by 178 · cited 1× · see citing works
“[84,85] Early data suggest MRI-based surveillance may have poorer performance in patients with Child-FIGURE Overall value of hepatocellular carcinoma (HCC) surveillance is determined by balance of benefits and harms.”
Pathology of Early Hepatocellular Carcinoma: Conventional and Molecular Diagnosis
Roskams, T., & Kojiro, M. (2010) · Seminars in Liver Disease · doi:10.1055/s-0030-1247129 · Cited by 176 · cited 1× · see citing works
“[ 133,134 ] 137] A negative biopsy does not eliminate the possibility of HCC, and a second biopsy is recommended when findings are inconclusive, particularly if tumor growth or change in enhancement pattern are identified during follow-up but the lesion is still not categorized as LR-5.”
Kaido, T., Ogawa, K., Mori, A., Fujimoto, Y., Ito, T., Tomiyama, K., Takada, Y., & Üemoto, S. (2013) · Surgery · doi:10.1016/j.surg.2013.04.056 · Cited by 175 · cited 2× · see citing works
“[206] 211] The main barrier to LT is a shortage of available liver allografts compared with demand, prompting an allocation system that directs access to deceased donor organs for patients both with and without HCC.”
Berry, K., & Ioannou, G. N. (2013) · Liver Transplantation · doi:10.1002/lt.23652 · Cited by 173 · see citing works
GALAD demonstrates high sensitivity for HCC surveillance in a cohort of patients with cirrhosis
Singal, A. G., Tayob, N., Mehta, A. S., Marrero, J. A., El‐Serag, H. B., Jin, Q., de Viteri, C. S., Fobar, A. J., & Parikh, N. D. (2021) · Hepatology · doi:10.1002/hep.32185 · Cited by 173 · cited 1× · see citing works
“…3 Sensitivity 62% Specificity 90% DCP [69] 3 Sensitivity 40% Specificity 81% Multitarget algorithm [70] 2 Sensitivity 82% Specificity 87% GALAD [ 71 ] 2/3 Sensitivity 54 – 72% Specificity 90% Doylestown plus [72] 2/3 Sensitivity 90% Specificity 95% Turcotte-Pugh B or C cirrhosis, so this may be…”
Self-citationAgopian, V. G., Harlander‐Locke, M. P., Ruiz, R. M., Klintmalm, G. B. G., Senguttuvan, S., Florman, S. S., Haydel, B., Hoteit, M. A., Levine, M. H., Lee, D. D., et al. (2017) · Annals of Surgery · doi:10.1097/sla.0000000000002381 · Cited by 171 · cited 1× · see citing works
“[229] Because tumor progression despite LRT is associated with worse post-LT outcome, [230 – 232] observing tumor behavior after LRT may allow for a more refined selection of candidates for LT. [213,233] Although a recent UNOS national analysis suggested ablation or TARE as initial LRT may be…”
Self-citationKim, E., Sher, A., Abboud, G., Schwartz, M., Facciuto, M. E., Tabrizian, P., Knešaurek, K., Fischman, A. M., Patel, R. S., Nowakowski, S. F., et al. (2022) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(22)00091-7 · Cited by 171 · cited 1× · see citing works
“[301] The choice of intra-arterial therapy has largely been driven by center expertise and availability.”
Self-citationIoannou, G. N., Green, P. K., Beste, L. A., Mun, E. J., Kerr, K. F., & Berry, K. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.07.024 · Cited by 166 · see citing works
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“[238] Therefore, patients in the United States initially exceeding UNOS-DS criteria are considered for MELD exception after successful downstaging on a case-by-case basis by the National Liver Review Board.”
Self-citationCitterio, D., Facciorusso, A., Sposito, C., Rota, R., Bhoori, S., & Mazzaferro, V. (2016) · JAMA Surgery · doi:10.1001/jamasurg.2016.1121 · Cited by 164 · cited 2× · see citing works
“…algorithms incorporating tumor size, extent of resection, and measures of liver dysfunction have been proposed to predict postresection outcomes, [164,167] most data support surgical resection of a single lesion in a patient with compensated cirrhosis without CSPH and an adequate FLR (typically…”
Singal, A. G., Hoshida, Y., Pinato, D. J., Marrero, J. A., Nault, J., Paradis, V., Tayob, N., Sherman, M., Lim, Y., Feng, Z., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.01.233 · Cited by 164 · cited 1× · see citing works
“74] Two well-studied biomarkers include the Lens culinaris lectin binding subfraction of the AFP, or AFP-L3%, which measures a subfraction of AFP, [75] and des gamma carboxy prothrombin (DCP), also called protein induced by vitamin K absence/antagonist-II (PIVKA-II), a variant of prothrombin that…”
Self-citationCost-effectiveness of hepatocellular carcinoma surveillance: an assessment of benefits and harms
Parikh, N. D., Singal, A. G., Hutton, D. W., & Tapper, E. B. (2020) · American Journal of Gastroenterology · doi:10.14309/ajg.0000000000000715 · Cited by 163 · see citing works
Self-citationChalasani, N., Porter, K. M., Bhattacharya, A., Book, A. J., Neis, B. M., Xiong, K., Ramasubramanian, T. S., Edwards, D. K., V, Chen, I., Johnson, S., et al. (2021) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2021.08.010 · Cited by 161 · see citing works
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“[57] Meta-analyses of cohort studies demonstrate surveillance is associated with improved early detection, curative treatment, and improved survival (Figure 3).”
ALPPS Versus Portal Vein Embolization for Hepatitis-related Hepatocellular Carcinoma
Chan, A. C. Y., Zhang, W. Y., Chok, K., Dai, J. W.-C., Ji, R., Kwan, C., Man, N. K., Poon, R. T. P., & Lo, C. M. (2019) · Annals of Surgery · doi:10.1097/sla.0000000000003433 · Cited by 158 · see citing works
PD-1 inhibitor as bridge therapy to liver transplantation?
Tabrizian, P., Florman, S. S., & Schwartz, M. (2020) · American Journal of Transplantation · doi:10.1111/ajt.16448 · Cited by 158 · cited 1× · see citing works
“…we recommend discontinuation of these agents at least 3 months prior to LT, while awaiting further safety data for use closer to the time of LT. [235] Downstaging to liver transplantation Tumor downstaging is defined as a reduction in the size of viable tumor using LRT to meet acceptable LT…”
Gopal, P., Yopp, A. C., Waljee, A. K., Chiang, J., Nehra, M. S., Kandunoori, P., & Singal, A. G. (2013) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2013.09.053 · Cited by 157 · see citing works
Self-citationMehta, N., Frenette, C., Tabrizian, P., Hoteit, M., Guy, J., Parikh, N., Ghaziani, T. T., Dhanasekaran, R., Dodge, J. L., Natarajan, B., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.07.033 · Cited by 154 · cited 2× · see citing works
“[240] Attempts to downstage with a goal of transplantation must be weighted with the probability of success using locoregional therapy.”
InfluentialSelf-citationQu, C., Wang, Y.-T., Wang, P.-P., Chen, K.-T., Wang, M.-J., Zeng, H., Lu, J., Song, Q., Diplas, B., Tan, D., et al. (2019) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1819799116 · Cited by 154 · cited 1× · see citing works
“[141] Alterations in ctDNA, ctDNA methylation profiles, [142] and extracellular RNA signatures from exosomes [143,144] have been explored in case-control studies for early detection and diagnosis.”
Kulik, L., Fisher, R. A., Rodrigo, D. R., Brown, R. S., Freise, C. E., Shaked, A. A., Everhart, J., Everson, G. T., Hong, J. C., Hayashi, P. H., et al. (2012) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2012.04272.x · Cited by 153 · see citing works
Self-citationHepatocellular carcinoma: Ablate and wait versus rapid transplantation
Roberts, J. P., Venook, A. P., Kerlan, R. K., & Yao, F. Y. (2010) · Liver Transplantation · doi:10.1002/lt.22103 · Cited by 151 · cited 1× · see citing works
“…with worse post-LT outcome, [230 – 232] observing tumor behavior after LRT may allow for a more refined selection of candidates for LT. [213,233] Although a recent UNOS national analysis suggested ablation or TARE as initial LRT may be associated with reduced waitlist dropout compared with…”
Vincenzi, B., Maïo, M. D., Silletta, M., D’Onofrio, L., Spoto, C., Piccirillo, M. C., Daniele, G., Comito, F., Maci, E., Bronte, G., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133488 · Cited by 150 · cited 1× · see citing works
“[286] The most common AEs were liver enzyme abnormalities (18.1%), fever (17.2%), bone marrow toxicity (13.5%), pain (11%), and vomiting (6%), although mortality was low at 0.6%.”
InfluentialMehta, N. J., Dodge, J. L., Goel, A., Roberts, J. P., Hirose, R., & Yao, F. Y. (2013) · Liver Transplantation · doi:10.1002/lt.23753 · Cited by 150 · see citing works
Self-citationDoyle, A., Gorgen, A., Muaddi, H., Aravinthan, A. D., Issachar, A., Mironov, O., Zhang, W., Kachura, J., Beecroft, R., Cleary, S. P., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2018.12.027 · Cited by 148 · see citing works
Biomarkers for the Early Detection of Hepatocellular Carcinoma
Parikh, N. D., Mehta, A. S., Singal, A. G., Block, T. M., Marrero, J. A., & Lok, A. S.-F. (2020) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-20-0005 · Cited by 145 · see citing works
Self-citationHepatocellular carcinoma tumour volume doubling time: a systematic review and meta-analysis
Nathani, P., Gopal, P., Rich, N. E., Yopp, A. C., Yokoo, T., John, B. V., Marrero, J. A., Parikh, N. D., & Singal, A. G. (2020) · Gut · doi:10.1136/gutjnl-2020-321040 · Cited by 144 · cited 2× · see citing works
“This recommendation was initially based on HCC tumor doubling time, [87,88] although subsequent analyses demonstrated semiannual surveillance is associated with earlier tumor stage and improved survival compared with annual surveillance after adjusting for lead time bias (40.3 vs. 30 mo, p = 0.03).”
InfluentialSelf-citationDevelopment and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma
Farinati, F., Vitale, A., Spolverato, G., Pawlik, T. M., Huo, T.-L., Lee, Y.-H., Frigo, A. C., Giacomin, A., Giannini, E. G., Ciccarese, F., et al. (2016) · PLoS Medicine · doi:10.1371/journal.pmed.1002006 · Cited by 143 · cited 1× · see citing works
“LI.CA) system subclassifies patients with BCLC Stage B into Stages B1, B2, and B3 to account for heterogeneity within patients with BCLC Stage B. [150] The HKLC system initially had nine stages, which were condensed to five stages to allow more nuanced stratification in intermediate-and…”
Simon, T. G., Duberg, A., Aleman, S., Hagström, H., Nguyen, L. H., Khalili, H., Chung, R. T., & Ludvigsson, J. F. (2019) · Annals of Internal Medicine · doi:10.7326/m18-2753 · Cited by 140 · cited 1× · see citing works
“[44] Lastly, antidiabetic medications, including metformin, have been explored as HCC chemoprevention agents; however, data have been conflicting.”
Schnitzbauer, A. A., Filmann, N., Adam, R. A., Bachellier, P., Bechstein, W. O., Becker, T., Bhoori, S., Bilbao, I., Brockmann, J. G., Burra, P., et al. (2020) · Annals of Surgery · doi:10.1097/sla.0000000000004280 · Cited by 140 · cited 1× · see citing works
“[257 ] Guidance 3-to-6-month period of observation ( Level 2, Strong Recommendation ). a. Patients with AFP > 1000 ng/ml must be downstaged to AFP < 500 ng/ml to be considered downstaged ( Level 2, Strong Recommendation ).”
Leerapun, A., Suravarapu, S. V., Bida, J. P., Clark, R. J., Sanders, E. L., Mettler, T. A., Stadheim, L. M., Aderca, I., Moser, C. D., Nagorney, D. M., et al. (2007) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2006.12.005 · Cited by 138 · cited 1× · see citing works
“74] Two well-studied biomarkers include the Lens culinaris lectin binding subfraction of the AFP, or AFP-L3%, which measures a subfraction of AFP, [75] and des gamma carboxy prothrombin (DCP), also called protein induced by vitamin K absence/antagonist-II (PIVKA-II), a variant of prothrombin that…”
Singal, A. G., Tiro, J. A., Murphy, C. C., Blackwell, J.-M., Kramer, J. R., Khan, A., Liu, Y., Zhang, S., Phillips, J. L., & Hernáez, R. (2020) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2020.06.049 · Cited by 138 · see citing works
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- Marrero JA, Marsh TL, Parikh ND, Roberts LR, Schwartz ME, Nguyen MH, et al. GALAD score improves early detection of HCC prior to the diagnosis of HCC: A phase 3 biomarker validation study. Abstract #138. Hepatology. 2021;74:92A.
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Singal, A. G., Kanwal, F., & Llovet, J. M. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00825-3 · Cited by 1,008 · see citing works
Self-citationEASL Clinical Practice Guidelines on the management of hepatitis B virus infection
Cornberg, M., Sandmann, L., Jaroszewicz, J., Kennedy, P. T. F., Lampertico, P., Lemoine, M., Lens, S., Testoni, B., Wong, G. L., & Russo, F. P. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.03.018 · Cited by 480 · see citing works
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Self-citationAdjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma
Llovet, J. M., Pinyol, R., Yarchoan, M., Singal, A. G., Marron, T. U., Schwartz, M., Pikarsky, E., Kudo, M., & Finn, R. S. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00868-0 · Cited by 391 · see citing works
Self-citationSangro, B., Chan, S. L., Kelley, R. K., Lau, G., Kudo, M., Sukeepaisarnjaroen, W., Yarchoan, M., De Toni, E. N., Furuse, J., Kang, Y. K., et al. (2024) · Annals of Oncology · doi:10.1016/j.annonc.2024.02.005 · Cited by 365 · see citing works
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Self-citationLiver diseases: epidemiology, causes, trends and predictions
Gan, C., Yuan, Y., Shen, H., Gao, J., Kong, X., Che, Z., Guo, Y., Wang, H., Dong, E., & Xiao, J. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02072-z · Cited by 370 · see citing works
Hepatocellular carcinoma: updates on epidemiology, surveillance, diagnosis and treatment
Hwang, S. Y., Danpanichkul, P., Agopian, V. G., Mehta, N., Parikh, N. D., Abou‐Alfa, G. K., Singal, A. G., & Yang, J. D. (2024) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2024.0824 · Cited by 348 · see citing works
Self-citationLiver cancer in 2021: Global Burden of Disease study
Tan, E. Y., Danpanichkul, P., Yong, J. N., Yu, Z., Tan, D. J. H., Lim, W. H., Koh, B., Lim, R. Y. Z., Tham, E. K. J., Mitra, K., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.10.031 · Cited by 238 · see citing works
Self-citationBCLC strategy for prognosis prediction and treatment recommendations: The 2026 update
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Self-citationChan, S. L., Sun, H., Xu, Y., Zeng, H., El‐Serag, H. B., Lee, J. M., Schwartz, M., Finn, R. S., Seong, J., Wang, X. W., et al. (2025) · The Lancet · doi:10.1016/s0140-6736(25)01042-6 · Cited by 247 · see citing works
Self-citationVitale, A., Cabibbo, G., Iavarone, M. A., Viganò, L., Pinato, D. J., Ponziani, F. R., Lai, Q., Gardini, A. C., Celsa, C., Galati, G., et al. (2023) · The Lancet Oncology · doi:10.1016/s1470-2045(23)00186-9 · Cited by 209 · see citing works
Hepatocellular carcinoma surveillance — utilization, barriers and the impact of changing aetiology
Huang, D. Q., Singal, A. G., Kanwal, F., Lampertico, P., Buti, M., Sirlin, C. B., Nguyen, M. H., & Loomba, R. S. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00818-8 · Cited by 199 · see citing works
“…recommends surveillance in people with chronic hepatitis B (men older than 40 years and women older than 50 years) who are from countries where chronic hepatitis B is endemic, and suggests that people from Africa living with chronic hepatitis B start surveillance from the age of 30 years 28,29 .”
BackgroundMethodSelf-citationGe, J., Sun, S., Owens, J., Galvez, V., Gologorskaya, O., Lai, J. C., Pletcher, M. J., & Lai, K. (2024) · Hepatology · doi:10.1097/hep.0000000000000834 · Cited by 182 · see citing works
“[29,30] LiVersa gave the wrong justification for HCC surveillance in this case simply because the 2018 version was not available to it and “ restrictions ” placed by curated RAG data set.”
Rimassa, L., Chan, S. L., Sangro, B., Lau, G. K. K., Kudo, M., Reig, M., Breder, V. V., Ryu, M., Ostapenko, Y., Sukeepaisarnjaroen, W., et al. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.03.033 · Cited by 186 · see citing works
Eslam, M., Fan, J., Yu, M., Wong, V. W., Cua, I. H., Liu, C., Tanwandee, T., Gani, R. A., Seto, W., Alam, S., et al. (2025) · Hepatology International · doi:10.1007/s12072-024-10774-3 · Cited by 186 · see citing works
“Based on cost-effectiveness analyses, when the incidence of HCC is > 1 or 2%/year, it is cost-effective to perform HCC screening/surveillance [295–297].”
InfluentialChanging etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide
Kim, D. Y. (2024) · Journal of Liver Cancer · doi:10.17998/jlc.2024.03.13 · Cited by 167 · see citing works
“71 On the other hand, the European Association for the Study of the Liver (EASL) highlights the importance of categorizing those who should be screened for HCC, thus EASL guidelines state that patients with noncirrhotic stage 3 fibrosis should be included in the surveillance program, although the…”
BackgroundBreakthroughs in Hepatocellular Carcinoma Therapies
Singal, A. G., Kudo, M., & Bruix, J. (2023) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2023.01.039 · Cited by 163 · see citing works
Self-citationCappuyns, S., Corbett, V., Yarchoan, M., Finn, R. S., & Llovet, J. M. (2024) · JAMA Oncology · doi:10.1001/jamaoncol.2023.2677 · Cited by 167 · see citing works
Self-citationFerraioli, G., Barr, R. G., Berzigotti, A., Sporea, I., Wong, V. W., Reiberger, T., Karlas, T., Thiele, M. S., Cardoso, A. C., Ayonrinde, O. T., et al. (2024) · Ultrasound in Medicine & Biology · doi:10.1016/j.ultrasmedbio.2024.03.013 · Cited by 160 · see citing works
“Current guidelines recommend HCC surveillance in patients with cirrhosis and patients with chronic hepatitis B and high-risk features [116,117].”
BackgroundEASL Clinical Practice Guidelines on the management of autoimmune hepatitis
Dalekos, G., Gatselis, N., Drenth, J. P. H., Heneghan, M., Jørgensen, M., Lohse, A. W., Londoño, M., Muratori, L., Papp, M., Samyn, M., et al. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.03.017 · Cited by 163 · see citing works
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ACG Clinical Guideline: Focal Liver Lesions
Frenette, C. T., Mendiratta‐Lala, M., Salgia, R. J., Wong, R. J., Sauer, B. G., & Pillai, A. A. (2024) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000002857 · Cited by 134 · see citing works
“These patients should undergo follow-up imaging as recommended for FLL in the AASLD Hepatocellular Carcinoma Guidance (145).”
MethodSelf-citationKinsey, E. N., & Lee, H. M. (2024) · Cancers · doi:10.3390/cancers16030666 · Cited by 135 · see citing works
“The American Association for the Study of Liver Diseases (AASLD) Practice Guidance recommends that all patients with cirrhosis of any etiology and non-cirrhotic chronic HBV undergo surveillance every 6 months [17].”
BackgroundInfluentialMASLD and the Development of HCC: Pathogenesis and Therapeutic Challenges
Phoolchund, A. G. S., & Khakoo, S. (2024) · Cancers · doi:10.3390/cancers16020259 · Cited by 127 · see citing works
“While there are multiple proposed alternative staging systems, the Barcelona Liver Clinic Cancer (BCLC) (shown in Figure 2) is the most commonly used and is recommended by the AASLD [109] and EASL [77] to help guide treatment.”
MethodImmune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy
Seyhan, D., Allaire, M., Fu, Y., Conti, F., Wang, X. W., Gao, B., & Lafdil, F. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01308-4 · Cited by 131 · see citing works
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Self-citationEASL Clinical Practice Guidelines on TIPS
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AASLD IDSA Practice Guideline on treatment of chronic hepatitis B
Ghany, M. G., Pan, C. Q., Lok, A. S.-F., Feld, J. J., Lim, J. K., Wang, S. H., Kim, A. Y., Tang, A. S., Nguyen, M. H., Naggie, S., et al. (2025) · Hepatology · doi:10.1097/hep.0000000000001549 · Cited by 108 · see citing works
Singal, A. G., Sanduzzi‐Zamparelli, M., Nahon, P., Ronot, M., Hoshida, Y., Rich, N. E., Reig, M., Vilgrain, V., Marrero, J. A., Llovet, J. M., et al. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.02.022 · Cited by 97 · see citing works
Self-citationSellers, Z. M., Assis, D. N., Paranjape, S. M., Sathe, M., Bodewes, F. A. J. A., Bowen, M., Cipolli, M., Debray, D., Green, N., Hughan, K. S., et al. (2023) · Hepatology · doi:10.1097/hep.0000000000000646 · Cited by 100 · see citing works
“[88,89] AFP is considered a biomarker for HCC and has been used in multiple liver diseases to detect HCC once the presence of cirrhosis has been established.”
BackgroundA Phase 3 Biomarker Validation of GALAD for the Detection of Hepatocellular Carcinoma in Cirrhosis
Marsh, T. L., Parikh, N. D., Roberts, L. R., Schwartz, M., Nguyen, M. H., Befeler, A. S., Page-Lester, S., Tayob, N., Srivastava, S., Rinaudo, J. A., et al. (2024) · Gastroenterology · doi:10.1053/j.gastro.2024.09.008 · Cited by 92 · see citing works
Self-citationMultiparametric MRI for characterization of the tumour microenvironment
Hoffmann, E., Masthoff, M., Kunz, W. G., Seidensticker, M., Bobe, S., Gerwing, M., Berdel, W. E., Schliemann, C., Faber, C., & Wildgruber, M. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00891-1 · Cited by 93 · see citing works
“As a result, early stage HCC and HGDN show hypoenhance-ment in the hepatobiliary contrast phase.”
InfluentialHepatocellular carcinoma: Epidemiology, diagnosis and treatment
Mauro, E., de Castro, T., Zeitlhoefler, M., Sung, M. W., Villanueva, A., Mazzaferro, V., & Llovet, J. M. (2025) · JHEP Reports · doi:10.1016/j.jhepr.2025.101571 · Cited by 89 · see citing works
“19,20 In clinical practice, direct HVPG measurement is not always available, so surrogate markers such as platelet counts ( > 100,000/ μ l), absence of splenomegaly, and no portosystemic collaterals, are often used.”
InfluentialSelf-citationLatest advances in hepatocellular carcinoma management and prevention through advanced technologies
Addissouky, T. A., Sayed, I. E. T. E., Ali, M. M. A., Wang, Y., Baz, A. E., Khalil, A. A., & Elarabany, N. (2024) · Egyptian Liver Journal · doi:10.1186/s43066-023-00306-3 · Cited by 89 · see citing works
Alpha-fetoprotein: Past, present, and future
Yeo, Y. H., Lee, Y., Tseng, H., Zhu, Y., You, S., Agopian, V. G., & Yang, J. D. (2024) · Hepatology Communications · doi:10.1097/hc9.0000000000000422 · Cited by 87 · see citing works
“…As such, AFP is currently recommended for HCC surveillance with ultrasound by both the American Association for the Study of Liver Diseases (AASLD) [100] and the Asian Pacific Association for the Study of the Liver (APASL), [74] although the use of AFP is not endorsed by the European Association…”
BackgroundSelf-citationSun, Y., Li, T., Ding, L., Wang, J., Chen, C., Liu, T., Liu, Y., Li, Q., Wang, C., Huo, R., et al. (2024) · Hepatology · doi:10.1097/hep.0000000000000934 · Cited by 87 · see citing works
“[15] Progression-free survival (PFS) was defined as the interval between resection and intrahepatic recurrence or extrahepatic metastasis.”
D'Alessio, A., Stefanini, B., Blanter, J., Adegbite, B., Crowley, F., Yip, V., Slater, S., Fulgenzi, C. A. M., Celsa, C., Manfredi, G. F., et al. (2024) · The Lancet Oncology · doi:10.1016/s1470-2045(24)00457-1 · Cited by 90 · see citing works
Self-citationGenetics of Metabolic Dysfunction-associated Steatotic Liver Disease: The State of the Art Update
Sookoian, S. C., Rotman, Y., & Valenti, L. V. C. (2024) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2024.05.052 · Cited by 81 · see citing works
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Self-citationDigestive cancers: mechanisms, therapeutics and management
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Self-citationComparison of non-contrast abbreviated MRI and ultrasound as surveillance modalities for HCC
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“…the highly heterogeneous nature of HCC. Firstly, non-invasive diagnosis of HCC be established in at-risk patients based on the characteristic “ arterial enhancement and delayed washout ” imaging feature without histological con fi rmation, with a sensitivity of 89% and speci fi city of 95% [83, 84].”
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“3,4 For those with advanced-stage HCC who are not candidates for resection, the 5-year survival rate is fewer than 20%, indicating an extremely poor overall prognosis.”
BackgroundNeoadjuvant and adjuvant systemic therapy in HCC: Current status and the future
Singal, A. G., Yarchoan, M. M., Yopp, A. C., Sapisochín, G., Pinato, D. J., & Pillai, A. A. (2024) · Hepatology Communications · doi:10.1097/hc9.0000000000000430 · Cited by 54 · see citing works
“[3,16,17] Surgical resection in early-stage HCC affords 5-year OS rates approaching 70% [18,19] ; however, recurrence occurs in 50% – 70% of patients at 5 years (Table 1).”
BackgroundResultInfluentialSelf-citationFinancial Burden of Hepatocellular Carcinoma Screening in Patients With Cirrhosis
Narasimman, M., Hernáez, R., Cerda, V., Lee, M., Yekkaluri, S., Khan, A., Sood, A., Gurley, T., Quirk, L., Liu, Y., et al. (2023) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2023.07.018 · Cited by 54 · see citing works
Self-citationAdvances in Locoregional and Systemic Treatments for Hepatocellular Carcinoma
Singal, A. G., Salem, R., Pinato, D. J., & Pillai, A. A. (2025) · Gastroenterology · doi:10.1053/j.gastro.2025.03.047 · Cited by 56 · see citing works
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“Although appropriate treatment might lessen the possibility of disease development, patients with cirrhosis and hepatocellular carcinoma may develop in those with persistently acceptable levels of alanine transaminase [149].”
RetractedPrecision surgery for hepatocellular carcinoma
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Adjuvant and neoadjuvant therapies for hepatocellular carcinoma
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Vitale, A., Romano, P., Cillo, U., Writing Group for the HE.RC.O.LE.S Collaborative Group, Writing Group for the ITA.LI.CA Collaborative Group, Groups, H. R. O. L. S. A. I. L. C. C., Busti, M., Nezi, G., Carlis, R. D., Ratti, F., et al. (2024) · JAMA Surgery · doi:10.1001/jamasurg.2024.1184 · Cited by 47 · see citing works
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“Adjuvant immune checkpoint inhibitor-based systemic therapy was recently recommended by the AASLD guideline for the treatment of HCC in patients at high risk of recurrence after liver resection 9 .”
Kumar, A., Acharya, S. K., Singh, S. P., Duseja, A. K., Madan, K., Shukla, A., Arora, A., Anand, A. C., Bahl, A., Soin, A. S., et al. (2023) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2023.08.005 · Cited by 43 · see citing works
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Non-alcoholic fatty liver disease-related hepatocellular carcinoma
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“[20,22] Major adverse cardiovascular events (MACEs) included death from heart or cerebrovascular events or the occurrence of new and nonfatal cardiovascular and cerebro-vascular episodes (myocardial infarction, unstable angina, heart failure, and stroke).”
The current status and future of targeted-immune combination for hepatocellular carcinoma
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“B and Eastern Cooperative Oncology Group performance status (PS) of 0 [8–10].”
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Non-invasive tests for alcohol-associated liver disease
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“[122,123] Alpha-fetoprotein is a commonly used blood-based marker for HCC surveillance.”
Kao, S. Z., Sangha, K., Fujiwara, N., Hoshida, Y., Parikh, N. D., & Singal, A. G. (2024) · EClinicalMedicine · doi:10.1016/j.eclinm.2024.102755 · Cited by 37 · see citing works
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Self-citationHepatocellular Carcinoma Surveillance Patterns and Outcomes in Patients With Cirrhosis
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Salvage Ipilimumab plus Nivolumab after Anti-PD-1/PD-L1 Therapy in Advanced Hepatocellular Carcinoma
Alden, S. L., Lim, M., Kao, C., Shu, D. H., Singal, A. G., Noonan, A. M., Griffith, P., Baretti, M., Ho, W. J., Kamel, I. R., et al. (2023) · Cancer Research Communications · doi:10.1158/2767-9764.crc-23-0072 · Cited by 35 · see citing works
Self-citationClinical management of intrahepatic cholangiocarcinoma: surgical approaches and systemic therapies
Ruff, S. M., & Pawlik, T. M. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1321683 · Cited by 35 · see citing works
“According to National Comprehensive Cancer Network (NCCN) guidelines and European Association of the Study of Liver (EASL) guidelines, patients with a solitary lesion, anatomically resectable cancer, no severe comorbidities, and adequate future liver remnant (FLR) should be considered candidates for surgery (9, 10).”
BackgroundInfluentialYang, D.-L., Ye, L., Zeng, F.-J., Liu, J., Yao, H., Nong, J.-L., Liu, S., Peng, N., Li, W.-F., Wu, P., et al. (2025) · Hepatology · doi:10.1097/hep.0000000000001229 · Cited by 35 · see citing works
Dawit, H., Lam, E., McInnes, M. D. F., van der Pol, C. B., Bashir, M. R., Salameh, J., Levis, B., Sirlin, C. B., Chernyak, V., Choi, S. H., et al. (2024) · Radiology · doi:10.1148/radiol.231501 · Cited by 35 · see citing works
ESR Essentials: diagnosis of hepatocellular carcinoma—practice recommendations by ESGAR
Cannella, R., Zins, M., & Brancatelli, G. (2024) · European Radiology · doi:10.1007/s00330-024-10606-w · Cited by 34 · see citing works
Oh, J. H., & Sinn, D. H. (2024) · Journal of Liver Cancer · doi:10.17998/jlc.2024.02.27 · Cited by 34 · see citing works
“7,9 Similarly, the European Association for the Study of the Liver (EASL) recommends multidisciplinary discussions, especially in managing smaller lesions and in formulating surgical strategies.”
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Current Treatment Methods in Hepatocellular Carcinoma
Krupa, K., Fudalej, M. M., Cencelewicz-Lesikow, A., Badowska-Kozakiewicz, A. M., Czerw, A. I., & Deptała, A. (2024) · Cancers · doi:10.3390/cancers16234059 · Cited by 34 · see citing works
“Child–Turcotte–Pugh A patients with good performance status have been included to assess the effectiveness of these treatments; however, well-selected patients with Child–Turcotte–Pugh B7 are capable of tolerating those therapies [10].”
Ivancovsky Wajcman, D., Byrne, C. J., Dillon, J. F., Brennan, P. N., Villota-Rivas, M., Younossi, Z. M., Allen, A. M., Crespo, J., Gerber, L. H., & Lazarus, J. V. (2026) · Hepatology · doi:10.1097/hep.0000000000001058 · Cited by 33 · see citing works
“On the contrary, hepatocellular carcinoma management guidelines align in recommending alcohol avoidance for all patients, [127,128] a recommendation that followed a statement by the American Society of Clinical Oncology [129] that alcohol use is related to hepatocellular carcinoma.”
MASLD-related HCC: Multicenter study comparing patients with and without cirrhosis
Vitellius, C., Desjonqueres, E., Lequoy, M., Amaddeo, G., Fouchard, I., Nkontchou, G., Canivet, C. M., Ziol, M., Regnault, H., Lannes, A., et al. (2024) · JHEP Reports · doi:10.1016/j.jhepr.2024.101160 · Cited by 32 · see citing works
“Indeed, biannual screening for HCC is recommended for patients with cirrhosis 18,19 but not for those without it.”
Liu, M., & Wen, Y. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e38444 · Cited by 32 · see citing works
“According to the 2023 guidelines set forth by the American Association for the Study of Liver Diseases (AASLD), the utilization of biomarkers, specifically AFP alone, for diagnosing early-stage HCC is discouraged due to its inadequate detection accuracy [14].”
MethodShin, H., & Yu, S. J. (2025) · Journal of Liver Cancer · doi:10.17998/jlc.2025.02.03 · Cited by 32 · see citing works
Hepatocellular Carcinoma Screening in a Contemporary Cohort of At-Risk Patients
Daher, D., Dahan, K. S. E., Rich, N. E., Tayob, N., Merrill, V., Huang, D. Q., Yang, J. D., Kulkarni, A. V., Kanwal, F., Marrero, J. A., et al. (2024) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.8755 · Cited by 31 · see citing works
Self-citationBrahmania, M., Rogal, S. S., Serper, M., Patel, A., Goldberg, D. S., Mathur, A. K., Wilder, J. M., Vittorio, J., Yeoman, A. D., Rich, N. E., et al. (2024) · Hepatology Communications · doi:10.1097/hc9.0000000000000413 · Cited by 31 · see citing works
“[95] However, SDOH factors negatively influence access to HCC screening and surveillance protocols; therefore, patients from lower SES classes or public insurance have experienced significant rates of late-stage cancer diagnosis and delayed treatment, leading to inferior cancer outcomes.”
- Authors
- Singal, A. G., Llovet, J. M., Yarchoan, M., Mehta, N., Heimbach, J. K., Dawson, L. A., Jou, J. H., Kulik, L. M., Agopian, V. G., Marrero, J. A., Mendiratta-Lala, M., Brown, D. B., Rilling, W. S., Goyal, L., Wei, A. C., & Taddei, T. H.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Johns Hopkins University (US)
- University of California, San Francisco (US)
- Mayo Clinic (US)
- University Health Network (CA)
- Oregon Health & Science University (US)
- Northwestern Medical Faculty Foundation (US)
- University of California, Los Angeles (US)
- University of Pennsylvania (US)
- Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan, USA
- Vanderbilt University Medical Center (US)
- Medical College of Wisconsin (US)
- Stanford Medicine (US)
- Memorial Sloan Kettering Cancer Center (US)
- Yale University (US)
- Corresponding author
- Singal, Amit G.
- ORCID
- Venue
- Hepatology
- Published
- 2023-05-22
- Volume
- 78
- Issue
- 6
- Pages
- 1922-1965
- ISSN
- 0270-9139 (ISSN-L)
- PMC
- PMC10663390
- OpenAlex
- W4377011124
- Cited by
- 2,052
- References
- 341
- Citations by year
- 2026: 760 · 2025: 724 · 2024: 467 · 2023: 97 · 2014: 1 · 2012: 1
- FWCI
- 346.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- AstraZeneca
- American Association for the Study of Liver Diseases
- Gilead Sciences
- Boston Scientific Corporation
- Exelixis
- Incyte
- Cancer Research UK (26813)
- Eisai
- Ipsen
- Sirtex Medical
- National Institutes of Health (UL1TR001863)
- Genentech
- National Cancer Institute (P50CA062924, R01CA285544)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Keywords
- hepatocellular carcinoma, hepatocellular carcinoma prevention, hepatocellular carcinoma diagnosis, hepatocellular carcinoma treatment, liver cancer, clinical guidelines
- MeSH terms
- Contrast Media, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Tomography, X-Ray Computed
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