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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 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]
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“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]
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“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]
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“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]
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“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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Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21660 · Cited by 108,699
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534 · cited 1×
“[309] mRECIST criteria has been proposed to adapt RECIST criteria to particularities of HCC, enabling capture of antitumoral response without observed shrinkage after local and systemic therapies.”
Sorafenib in advanced hepatocellular carcinoma
Llovet, J. M., Ricci, S., Mazzaferro, V., Hilgard, P., Gane, E., Blanc, J.-F., de Oliveira, A. C., Santoro, A., Raoul, J.-L., Forner, A., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0708857 · Cited by 13,097
Self-citationErdogan, D., Heijnen, B. H. M., Bennink, R. J., Kok, M., Dinant, S., Straatsburg, I. H., Gouma, D. J., & van Gulik, T. M. (2004) · Liver International · doi:10.1111/j.1478-3231.2004.00901.x · Cited by 11,656
Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma
Finn, R. S., Qin, S., Ikeda, M., Galle, P. R., Ducreux, M., Kim, T.-Y., Kudo, M., Breder, V., Merle, P., Kaseb, A. O., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1915745 · Cited by 7,470 · cited 2×
“…PD-L1, plus bevacizumab, a monoclonal antibody targeting VEGF, as the preferred first-line treatment option for patients with advanced HCC. [312] The median OS of 19.2 months with atezolizumab plus bevacizumab is the longest median OS of any first-line treatment for advanced-stage HCC to…”
InfluentialMazzaferro, V., Regalia, E., Doci, R., Andreola, S. A., Pulvirenti, A., Bozzetti, F., Montalto, F., Ammatuna, M., Morabito, A., & Gennari, L. (1996) · New England Journal of Medicine · doi:10.1056/nejm199603143341104 · Cited by 7,173 · cited 1×
“[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.”
Llovet, J. M., Kelley, R. K., Villanueva, A., Singal, A. G., Pikarsky, E., Roayaie, S., Lencioni, R., Koike, K., Zucman-Rossi, J., & Finn, R. S. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-00240-3 · Cited by 7,055
Self-citationCancer statistics for the year 2020: An overview
Ferlay, J., Colombet, M., Soerjomataram, I., Parkin, D. M., Piñeros, M., Znaor, A., & Bray, F. (2021) · International Journal of Cancer · doi:10.1002/ijc.33588 · Cited by 6,308
A New Era of Systemic Therapy for Hepatocellular Carcinoma with Regorafenib and Lenvatinib
Kudo, M. (2017) · Liver Cancer · doi:10.1159/000462153 · Cited by 5,974
Cheng, A.-L., Kang, Y.-K., Chen, Z., Tsao, C.-J., Qin, S., Kim, J. S., Luo, R., Feng, J., Ye, S., Yang, T.-S., et al. (2009) · The Lancet Oncology · doi:10.1016/s1470-2045(08)70285-7 · Cited by 5,832 · cited 1×
“[320] In 2018, lenvatinib (an oral mTKI targeting vascular endothelial growth factor [VEGF]2 and other kinases) met its primary endpoint of noninferiority versus sorafenib in a global phase III randomized study, REFLECT.”
Kudo, M., Finn, R. S., Qin, S., Han, K.-H., Ikeda, K., Piscaglia, F., Baron, A., Park, J.-W., Han, G., Jassem, J., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)30207-1 · Cited by 5,497 · cited 2×
“IMbrave150 [312] HIMALAYA [323] REFLECT [313] Study TABLE 8 Summary efficacy data for selected second line studies after prior sorafenib therapy Aspect CELESTIAL [314] RESORCE [315] REACH-2 [127] KEYNOTE-240 [316] KEYNOTE-394 [317] CheckMate 040 [318] Study”
Acute Abdomen: A Rare Case of Ruptured Hepatocellular Carcinoma
Gloor, S., Jensen, K. O., Breitenstein, S., Binkert, C. A., Angst, E., & Hetzer, F. H. (2017) · Case Reports in Gastroenterology · doi:10.1159/000463378 · Cited by 5,370
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma
European Association for the Study of the Liver, & European Organisation for Research and Treatment of Cancer (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2011.12.001 · Cited by 5,218
Marrero, J. A., Kulik, L., Sirlin, C. B., Zhu, A. X., Finn, R. S., Abecassis, M. M., Roberts, L. R., & Heimbach, J. K. (2018) · Hepatology · doi:10.1002/hep.29913 · Cited by 4,597
Self-citationVillanueva, A. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1713263 · Cited by 4,508
Modified RECIST (mRECIST) Assessment for Hepatocellular Carcinoma
Lencioni, R. A., & Llovet, J. M. (2010) · Seminars in Liver Disease · doi:10.1055/s-0030-1247132 · Cited by 4,354 · cited 1×
“[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
Reig, M., Forner, A., Rimola, J., Ferrer-Fàbrega, J., Burrel, M., Garcia-Criado, Á., Kelley, R. K., Galle, P. R., Mazzaferro, V., Salem, R., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2021.11.018 · Cited by 4,319
Self-citationEl-Khoueiry, A. B., Sangro, B., Yau, T., Crocenzi, T. S., Kudo, M., Hsu, C., Kim, T.-Y., Choo, S.-P., Trojan, J., Welling, T. H., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31046-2 · Cited by 4,280 · cited 1×
“[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
Heimbach, J. K., Kulik, L., Finn, R. S., Sirlin, C. B., Abecassis, M. M., Roberts, L. R., Zhu, A. X., Murad, M. H., & Marrero, J. A. (2017) · Hepatology · doi:10.1002/hep.29086 · Cited by 4,107 · cited 1×
“[135,140] Therefore, patients with non-characteristic imaging are advised to undergo biopsy, independent of AFP level.”
Self-citationPrognosis of Hepatocellular Carcinoma: The BCLC Staging Classification
Llovet, J., Brú, C., & Bruix, J. (1999) · Seminars in Liver Disease · doi:10.1055/s-2007-1007122 · Cited by 3,805 · cited 1×
“[148] The BCLC system classifies tumors as very early stage (Stage 0) followed by Stages A –”
Self-citationBruix, J., Qin, S., Merle, P., Granito, A., Huang, Y., Bodoky, G., Pracht, M., Yokosuka, O., Rosmorduc, O., Breder, V. V., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)32453-9 · Cited by 3,725 · cited 2×
“IMbrave150 [312] HIMALAYA [323] REFLECT [313] Study TABLE 8 Summary efficacy data for selected second line studies after prior sorafenib therapy Aspect CELESTIAL [314] RESORCE [315] REACH-2 [127] KEYNOTE-240 [316] KEYNOTE-394 [317] CheckMate 040 [318] Study”
Self-citationLlovet, J. M., Real, M. I., Montañá, X., Planas, R., Coll, S., Aponte, J. Á. N., Ayuso, C., Sala, M., Muchart, J., Sola, R. L., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08649-x · Cited by 3,490 · cited 1×
“Transarterial therapies TACE TACE is the primary treatment option for patients with BCLC Stage B HCC. [282,283] TACE leverages the arterial blood supply of HCC, compared with portal venous blood flow to the background liver, and can be performed with lipiodol (conventional TACE) or drug-eluting…”
Self-citationLlovet, J. M., & Bruix, J. (2003) · Hepatology · doi:10.1053/jhep.2003.50047 · Cited by 3,041 · cited 1×
“Meta-analyses of RCTs comparing TACE and best supportive care demonstrate significant improvements in OS among patients with BCLC Stage B HCC, [ 284 ] leading to adoption of TACE in management guidelines.”
Self-citationBaveno VII – Renewing consensus in portal hypertension
de Franchis, R., Bosch, J., Garcia-Tsao, G., Reiberger, T., Ripoll, C., Abraldes, J. G., Albillos, A., Baiges, A., Bajaj, J., Bañares, R., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2021.12.022 · Cited by 2,930 · cited 1×
“[322] The optimal time to wait between band ligation and initiation of atezolizumab plus bevacizumab to minimize risk of bleeding from banding ulcers is unknown, although 2 weeks is likely reasonable given risk of post-banding ulcers.”
Johnson, P. J., Berhane, S., Kagebayashi, C., Satomura, S., Teng, M. J., Reeves, H. L., O’Beirne, J. P., Fox, R., Skowrońska, A., Palmer, D. H., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.57.9151 · Cited by 2,865 · cited 1×
“[149] It also recognizes the heterogeneity among patients with BCLC Stage B and incorporates concepts of downstaging and stage migration over time.”
Lo, C., Ngan, H., Tso, W., Liu, C., Lam, C., Poon, R. T. P., Fan, S.-T., & Wong, J. (2002) · Hepatology · doi:10.1053/jhep.2002.33156 · Cited by 2,609
Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma
Abou‐Alfa, G. K., Meyer, T., Cheng, A., El-Khoueiry, A. B., Rimassa, L., Ryoo, B., Çiçin, İ., Merle, P., Chen, Y.-H., Park, J., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1717002 · Cited by 2,347 · cited 2×
“[314] OS was significantly improved versus placebo (10.2 vs. 8.0 mo), as were PFS and ORR.”
InfluentialEpidemiology of Hepatocellular Carcinoma
McGlynn, K. A., Petrick, J. L., & El‐Serag, H. B. (2020) · Hepatology · doi:10.1002/hep.31288 · Cited by 2,200
Mazzaferro, V., Llovet, J. M., Miceli, R., Bhoori, S., Schiavo, M., Mariani, L., Camerini, T., Roayaie, S., Schwartz, M., Grazi, G. L., et al. (2008) · The Lancet Oncology · doi:10.1016/s1470-2045(08)70284-5 · Cited by 2,048 · cited 1×
“…≤ 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
Ward, Z. J., Bleich, S. N., Cradock, A. L., Barrett, J. L., Giles, C. M., Flax, C., Long, M. W., & Gortmaker, S. L. (2019) · New England Journal of Medicine · doi:10.1056/nejmsa1909301 · Cited by 2,009 · cited 1×
“[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.
Child, C. G., & Turcotte, J. (1964) · PubMed · Cited by 1,933
Finn, R. S., Ryoo, B.-Y., Merle, P., Kudo, M., Bouattour, M., Lim, H. Y., Breder, V., Edeline, J., Chao, Y., Ogasawara, S., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.19.01307 · Cited by 1,789 · cited 2×
“IMbrave150 [312] HIMALAYA [323] REFLECT [313] Study TABLE 8 Summary efficacy data for selected second line studies after prior sorafenib therapy Aspect CELESTIAL [314] RESORCE [315] REACH-2 [127] KEYNOTE-240 [316] KEYNOTE-394 [317] CheckMate 040 [318] Study”
Zhu, A. X., Kang, Y., Yen, C., Finn, R. S., Galle, P. R., Llovet, J. M., Assénat, E., Brandi, G., Pracht, M., Lim, H. Y., et al. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30937-9 · Cited by 1,702 · cited 3×
“IMbrave150 [312] HIMALAYA [323] REFLECT [313] Study TABLE 8 Summary efficacy data for selected second line studies after prior sorafenib therapy Aspect CELESTIAL [314] RESORCE [315] REACH-2 [127] KEYNOTE-240 [316] KEYNOTE-394 [317] CheckMate 040 [318] Study”
Self-citationLämmer, J., Malagari, K., Vogl, T. J., Pilleul, F., Denys, A. L., Watkinson, A. F., Pitton, M. B., Sergent, G., Pfammatter, T., Terraz, S., et al. (2009) · CardioVascular and Interventional Radiology · doi:10.1007/s00270-009-9711-7 · Cited by 1,553
The International Position on Laparoscopic Liver Surgery
Buell, J. F., Cherqui, D., Geller, D. A., O’Rourke, N., Iannitti, D. A., Dagher, I., Koffron, A. J., Thomas, M., Gayet, B., Han, H., et al. (2009) · Annals of Surgery · doi:10.1097/sla.0b013e3181b3b2d8 · Cited by 1,524 · cited 1×
“…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
Zhang, B.-H., Yang, B.-H., & Tang, Z.-Y. (2004) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-004-0552-0 · Cited by 1,496 · cited 2×
“[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.”
Chen, M.-S., Li, J. Q., Zheng, Y., Guo, R., Liang, H.-H., Zhang, Y.-Q., Lin, X.-J., & Lau, W. Y. (2006) · Annals of Surgery · doi:10.1097/01.sla.0000201480.65519.b8 · Cited by 1,430
Small Hepatocellular Carcinoma: Treatment with Radio-frequency Ablation versus Ethanol Injection
Livraghi, T., Goldberg, S. N., Lazzaroni, S., Meloni, M. F., Solbiati, L., & Gazelle, G. S. (1999) · Radiology · doi:10.1148/radiology.210.3.r99fe40655 · Cited by 1,282
Yau, T., Kang, Y.-K., Kim, T.-Y., El-Khoueiry, A. B., Santoro, A., Sangro, B., Melero, I., Kudo, M., Hou, M.-M., Matilla, A., et al. (2020) · JAMA Oncology · doi:10.1001/jamaoncol.2020.4564 · Cited by 1,273
Tzartzeva, K., Obi, J., Rich, N. E., Parikh, N. D., Marrero, J. A., Yopp, A., Waljee, A. K., & Singal, A. G. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.01.064 · Cited by 1,207 · cited 1×
“%) 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
Moon, A. M., Singal, A. G., & Tapper, E. B. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2019.07.060 · Cited by 1,200 · cited 2×
“[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.”
InfluentialSelf-citationBruix, J., Takayama, T., Mazzaferro, V., Chau, G.-Y., Yang, J., Kudo, M., Cai, J., Poon, R. T., Han, K.-H., Tak, W. Y., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00198-9 · Cited by 1,120 · cited 1×
“[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.”
Self-citationYau, T., Park, J.-W., Finn, R. S., Cheng, A.-L., Mathurin, P., Edeline, J., Kudo, M., Harding, J. J., Merle, P., Rosmorduc, O., et al. (2022) · The Lancet Oncology · doi:10.1016/s1470-2045(21)00604-5 · Cited by 1,106 · cited 1×
“[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…”
Lencioni, R. A., Allgaier, H.-P., Cioni, D., Olschewski, M., Deibert, P., Crocetti, L., Frings, H., LAUBENBERGER, J., Zuber, I., Blum, H. E., et al. (2003) · Radiology · doi:10.1148/radiol.2281020718 · Cited by 995
Duvoux, C., Roudot‐Thoraval, F., Decaens, T., Pessione, F., Badran, H. M., Piardi, T., Francoz, C., Compagnon, P., Vanlemmens, C., Dumortier, J., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.05.052 · Cited by 953 · cited 1×
“[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.”
InfluentialYau, T. (., Park, J. W. (.-W., Finn, R. S. (. S. )., Cheng, A. L. (.-L., Mathurin, P., Edeline, J., Kudo, M. (., Harding, J. J., Merle, P., Rosmorduc, O., et al. (2022) · Deposito Adademico Digital Universidad De Navarra (University of Navarra) · Cited by 934
Risk of Hepatocellular Cancer in HCV Patients Treated With Direct-Acting Antiviral Agents
Kanwal, F., Kramer, J. R., Asch, S. M., Chayanupatkul, M., Cao, Y., & El‐Serag, H. B. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.06.012 · Cited by 931 · cited 1×
“[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
Tabrizian, P., Jibara, G., Shrager, B., Schwartz, M., & Roayaie, S. (2015) · Annals of Surgery · doi:10.1097/sla.0000000000000710 · Cited by 903 · cited 1×
“[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.”
Shiina, S., Teratani, T., Obi, S., Sato, S., Tateishi, R., Fujishima, T., Ishikawa, T., Koike, Y., Yoshida, H., Kawabe, T., et al. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.04.009 · Cited by 875
International Consensus Group for Hepatocellular Neoplasia (2008) · Hepatology · doi:10.1002/hep.22709 · Cited by 862
Zhu, A. X., Park, J. O., Ryoo, B., Yen, C.-J., Poon, R. T. P., Pastorelli, D., Blanc, J., Chung, H. C., Baron, A. D., Pfiffer, T., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00050-9 · Cited by 845 · cited 1×
“[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.”
Kudo, M., Izumi, N., Kokudo, N., Matsui, O., Sakamoto, M., Nakashima, O., Kojiro, M., Makuuchi, M., & for the HCC Expert Panel of Japan Society of Hepatology (2011) · Digestive Diseases · doi:10.1159/000327577 · Cited by 822
Singal, A. G., Pillai, A., & Tiro, J. (2014) · PLoS Medicine · doi:10.1371/journal.pmed.1001624 · Cited by 817 · cited 1×
“[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.”
Self-citationRisk of hepatocellular cancer in patients with non-alcoholic fatty liver disease
Kanwal, F., Kramer, J. R., Mapakshi, S., Natarajan, Y., Chayanupatkul, M., Richardson, P. A., Li, L., Desiderio, R., Thrift, A. P., Asch, S. M., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.08.024 · Cited by 795
Feng, K., Yan, J., Li, X., Xia, F., Ma, K., Wang, S., Bie, P., & Dong, J. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.05.007 · Cited by 764
Marrero, J. A., Feng, Z., Wang, Y., Nguyen, M. H., Befeler, A. S., Roberts, L. R., Reddy, K. R., Harnois, D. M., Llovet, J. M., Normolle, D. P., et al. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.04.005 · Cited by 745 · cited 2×
“…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×
“[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-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 728 · cited 2×
“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.”
Younossi, Z., Stepanova, M., Ong, J., Jacobson, I., Bugianesi, E., Duseja, A., Eguchi, Y., Wong, V., Negro, F., Yılmaz, Y., et al. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.05.057 · Cited by 702
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“…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×
“[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
Self-citationmRECIST 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×
“[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×
“[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×
“[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
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
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“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
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×
“[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
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×
“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 553 · cited 1×
“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×
“[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 533 · cited 1×
“[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.”
Imaging 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 524 · cited 4×
“…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-citationMeyer, 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 504 · cited 1×
“[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×
“[331] Noninvasive criteria for the presence of varices (e.g., Baveno VI criteria) have not been validated in patients with HCC.”
Self-citationAlifakioti, D., Daccord, C., Lachenal, Y., & Fitting, J.-W. (2014) · Respiration · doi:10.1159/000367814 · Cited by 495
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×
“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
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
Self-citationMitchell, D. G., Bruix, J., Sherman, M., & Sirlin, C. B. (2014) · Hepatology · doi:10.1002/hep.27304 · Cited by 483 · cited 2×
“[103] diagnosis in patients with cirrhosis and appear to have acceptable accuracy in those with noncirrhotic HBV.”
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 467
Self-citationPeng, 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×
“…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…”
Bolondi, 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
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×
“…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×
“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×
“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×
“[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×
“[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×
“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×
“[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×
“[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×
“[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×
“[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
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×
“[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×
“– 289] Patient selection and vascular selectivity are critical factors to optimize TACE outcomes.”
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 372 · cited 1×
“[168] In these patients, surgical resection affords 5-year survival exceeding 70% and postoperative mortality of 3%.”
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×
“…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…”
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
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
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
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
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×
“[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
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×
“[305] 308] Response evaluation criteria in solid tumors (RECIST) v1.”
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 342 · cited 2×
“– 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-citationMazzaferro, 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×
“[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×
“[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.”
Wolf, 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×
“[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
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×
“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×
“[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×
“…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×
“[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×
“…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×
“[293] – 298] Based on current data, the AASLD advises against combination therapy outside of clinical trials.”
Tan, D. J. H., Ng, C. H., Lin, S. Y., Pan, X. H., Tay, P., Lim, W. H., Teng, M., Syn, N., Lim, G., Yong, J. N., et al. (2022) · The Lancet Oncology · doi:10.1016/s1470-2045(22)00078-x · Cited by 307
Santi, V., Trevisani, F., Gramenzi, A., Grignaschi, A., Cappa, F. M., Poggio, P. D., Nolfo, M. A. D., Benvegnù, L., Farinati, F., Zoli, M., et al. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.03.010 · Cited by 304 · cited 1×
“[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×
“[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×
“[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×
“[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-citationNAFLD-driven HCC: Safety and efficacy of current and emerging treatment options
Foerster, F., Gairing, S. J., Müller, L., & Galle, P. R. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.09.007 · Cited by 285 · cited 1×
“[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.”
Toso, 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×
“…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
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“[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×
“[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
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×
“[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-citationRodríguez‐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×
“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×
“[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
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×
“[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×
“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×
“[251 ,252] Because the two most common sites of posttrans-plant recurrence are the lung ( ∼ 40”
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“[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×
“[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
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“…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.”
Kim, 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×
“[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×
“[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×
“[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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Self-citationScreening 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 220
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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×
“[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×
“[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.”
Sun, N., Lee, Y.-T., Zhang, R. Y., Kao, R., Teng, P.-C., Yang, Y., Yang, P., Wang, J. J., Smalley, M. D., Chen, P.-J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18311-0 · Cited by 217 · cited 1×
“[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.”
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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 214 · cited 1×
“[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.”
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
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“[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…”
Aggressive cutaneous malignancies following cardiothoracic transplantation
Veness, M., Quinn, D. I., Ong, C. S., KEOGH, A. M., Macdonald, P. S., Cooper, S. G., & Morgan, G. W. (1999) · Cancer · doi:10.1002/(sici)1097-0142(19990415)85:8 · Cited by 213
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×
“[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 210
Choi, J., Kim, G., Han, S., Lee, W., Chun, S., & Lim, Y. (2018) · Hepatology · doi:10.1002/hep.30233 · Cited by 209 · cited 2×
“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×
“[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
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“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 198 · cited 1×
“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×
“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
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×
“[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×
“[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×
“[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-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 185 · cited 1×
“[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.”
Bodzin, 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×
“[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-citationPathology 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×
“[ 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×
“[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.”
Qu, C., Wang, Y., Wang, P., Chen, K., Wang, M., Zeng, H., Lu, J., Song, Q., Diplas, B. H., Tan, D., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1819799116 · Cited by 174 · cited 1×
“[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.”
Berry, K., & Ioannou, G. N. (2013) · Liver Transplantation · doi:10.1002/lt.23652 · Cited by 173
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×
“…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×
“[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×
“[301] The choice of intra-arterial therapy has largely been driven by center expertise and availability.”
Self-citationSingal, 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 170 · cited 1×
“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-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
Chalasani, 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 166
Self-citationMehta, N. J., Dodge, J. L., Grab, J. D., & Yao, F. Y. (2019) · Hepatology · doi:10.1002/hep.30879 · Cited by 165 · cited 1×
“[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×
“…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…”
Cost-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
Self-citationPoustchi, H., Farrell, G. C., Strasser, S. I., Lee, A. U., McCaughan, G. W., & George, J. (2010) · Hepatology · doi:10.1002/hep.24581 · Cited by 158 · cited 1×
“[57] Meta-analyses of cohort studies demonstrate surveillance is associated with improved early detection, curative treatment, and improved survival (Figure 3).”
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 158
Self-citationALPPS 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
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×
“…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…”
Mehta, 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×
“[240] Attempts to downstage with a goal of transplantation must be weighted with the probability of success using locoregional therapy.”
InfluentialSelf-citationKulik, 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
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×
“…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×
“[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
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
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 148
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 147 · cited 2×
“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-citationPrevention of NAFLD-associated HCC: Role of lifestyle and chemoprevention
Lange, N. F., Radu, P., & Dufour, J. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.07.025 · Cited by 144
Development 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×
“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 142 · cited 1×
“[44] Lastly, antidiabetic medications, including metformin, have been explored as HCC chemoprevention agents; however, data have been conflicting.”
Rich, N. E., John, B. V., Parikh, N. D., Rowe, I. A. C., Mehta, N. J., Khatri, G., Thomas, S., Anis, M., Mendiratta‐Lala, M., Hernandez, C., et al. (2020) · Hepatology · doi:10.1002/hep.31159 · Cited by 141 · cited 4×
“[88] RETREAT stratifies 5-year recurrence risk from 3% in patients without viable tumor on explant or microvascular invasion and AFP 20 ng/ml (i.e., RETREAT 0) up to 75% in the highest-risk patients (RETREAT Z 5).”
InfluentialSelf-citation
Research works printed but not linked: 2
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- Dawson, 2022, ORAL SCIENTIFIC SESSIONS LBA 01: NRG/RTOG 1112: Randomized Phase III Study of Sorafenib vs. Stereotactic Body Radiation Therapy (SBRT) Followed by Sorafenib in Hepatocellular Carcinoma (HCC) (NCT01730937). Int J Radiation Oncol, Biol, Physics, 114, P1057
Cited by
Sorted by citations
Singal, A. G., Kanwal, F., & Llovet, J. M. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00825-3 · Cited by 1,029
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
Llovet, J. M., Kudo, M., Merle, P., Meyer, T., Qin, S., Ikeda, M., Xu, R., Edeline, J., Ryoo, B.-Y., Ren, Z., et al. (2023) · The Lancet Oncology · doi:10.1016/s1470-2045(23)00469-2 · Cited by 469
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
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
Self-citation
Metadata
- 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
- 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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