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Review Article| Volume 27, ISSUE 1, P85-102, February 2023

Hepatocellular Carcinoma

New Developments
Published:October 18, 2022DOI:https://doi.org/10.1016/j.cld.2022.08.004

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      References

        • McGlynn K.A.
        • Petrick J.L.
        • El-Serag H.B.
        Epidemiology of hepatocellular carcinoma.
        Hepatology. 2021; 73: 4-13
        • Mittal S.
        • El-Serag H.B.
        • Sada Y.H.
        • et al.
        Hepatocellular carcinoma in the absence of cirrhosis in United States veterans is associated with nonalcoholic fatty liver disease.
        Clin Gastroenterol Hepatol. 2016; 14: 124-131.e1
        • Kanwal F.
        • Singal A.G.
        Surveillance for hepatocellular carcinoma: current best practice and future direction.
        Gastroenterology. 2019; 157: 54-64
        • Tzartzeva K.
        • Obi J.
        • Rich N.E.
        • et al.
        Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis.
        Gastroenterology. 2018; 154: 1706-1718.e1
        • Semmler G.
        • Mandorfer M.
        Reply to: ‘Risk stratification of hepatocellular carcinoma after hepatitis C virus eradication in patients with compensated advanced chronic liver disease in Japan’.
        J Hepatol. 2022; https://doi.org/10.1016/j.jhep.2022.04.031
        • Fujiwara N.
        • Kobayashi M.
        • Fobar A.J.
        • et al.
        A blood-based prognostic liver secretome signature and long-term hepatocellular carcinoma risk in advanced liver fibrosis.
        Med (N Y). 2021; 2: 836-850.e10
        • Wong R.J.
        • Cheung R.
        • Ahmed A.
        Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S.
        Hepatology. 2014; 59: 2188-2195
        • Kanwal F.
        • Kramer J.R.
        • Mapakshi S.
        • et al.
        Risk of hepatocellular cancer in patients with non-alcoholic fatty liver disease.
        Gastroenterology. 2018; 155: 1828-1837.e2
        • Wolf E.
        • Rich N.E.
        • Marrero J.A.
        • et al.
        Use of hepatocellular carcinoma surveillance in patients with cirrhosis: a systematic review and meta-analysis.
        Hepatology. 2021; 73: 713-725
        • Parikh N.D.
        • Singal A.G.
        • Hutton D.W.
        • et al.
        Cost-effectiveness of hepatocellular carcinoma surveillance: an assessment of benefits and harms.
        Am J Gastroenterol. 2020; 115: 1642-1649
        • Simmons O.
        • Fetzer D.T.
        • Yokoo T.
        • et al.
        Predictors of adequate ultrasound quality for hepatocellular carcinoma surveillance in patients with cirrhosis.
        Aliment Pharmacol Ther. 2017; 45: 169-177
        • Roberts L.R.
        • Sirlin C.B.
        • Zaiem F.
        • et al.
        Imaging for the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis.
        Hepatology. 2018; 67: 401-421
        • Kim S.Y.
        • An J.
        • Lim Y.S.
        • et al.
        MRI with liver-specific contrast for surveillance of patients with cirrhosis at high risk of hepatocellular carcinoma.
        JAMA Oncol. 2017; 3: 456-463
      1. Marrero J.A., Parikh N.D., Roberts L.R., et al., GALAD score improves early detection of HCC prior to the diagnosis of HCC: a phase 3 biomarker validation study. American Association for the Study of the Liver. The Liver Meeting 2021.

        • Kotwani P.
        • Chan W.
        • Yao F.
        • et al.
        DCP and AFP-L3 are complementary to AFP in predicting high-risk explant features: results of a prospective study.
        Clin Gastroenterol Hepatol. 2022; 20: 701-703.e2
        • Chaiteerakij R.
        • Zhang X.
        • Addissie B.D.
        • et al.
        Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation.
        Liver Transpl. 2015; 21: 599-606
        • Borel F.
        • Konstantinova P.
        • Jansen P.L.
        Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma.
        J Hepatol. 2012; 56: 1371-1383
        • Kisiel J.B.
        • Dukek B.A.
        • VSRK R.
        • et al.
        Hepatocellular carcinoma detection by plasma methylated DNA: discovery, phase I pilot, and phase II clinical validation.
        Hepatology. 2019; 69: 1180-1192
        • Chen V.L.
        • Xu D.
        • Wicha M.S.
        • et al.
        Utility of liquid biopsy analysis in detection of hepatocellular carcinoma, determination of prognosis, and disease monitoring: a systematic review.
        Clin Gastroenterol Hepatol. 2020; 18: 2879-2902.e9
        • Chen J.
        • Zaidi S.
        • Rao S.
        • et al.
        Analysis of genomes and transcriptomes of hepatocellular carcinomas identifies mutations and gene expression changes in the transforming growth factor-β pathway.
        Gastroenterology. 2018; 154: 195-210
        • Hoshida Y.
        • Villanueva A.
        • Kobayashi M.
        • et al.
        Gene expression in fixed tissues and outcome in hepatocellular carcinoma.
        N Engl J Med. 2008; 359: 1995-2004
        • Reig M.
        • Forner A.
        • Rimola J.
        • et al.
        BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update.
        J Hepatol. 2022; 76: 681-693
        • Bruix J.
        • Fuster J.
        • Llovet J.M.
        Liver transplantation for hepatocellular carcinoma: foucault pendulum versus evidence-based decision.
        Liver Transpl. 2003; 9: 700-702
        • Yao F.Y.
        • Kerlan Jr., R.K.
        • Hirose R.
        • et al.
        Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis.
        Hepatology. 2008; 48: 819-827
        • Sinha J.
        • Mehta N.
        • Dodge J.L.
        • et al.
        Are there upper limits in tumor burden for down-staging of hepatocellular carcinoma to liver transplant? Analysis of the all-comers protocol.
        Hepatology. 2019; 70: 1185-1196
        • Mehta N.
        • Dodge J.L.
        • Grab J.D.
        • et al.
        National experience on down-staging of hepatocellular carcinoma before liver transplant: influence of tumor burden, alpha-fetoprotein, and wait time.
        Hepatology. 2020; 71: 943-954
        • Mazzaferro V.
        • Sposito C.
        • Zhou J.
        • et al.
        Metroticket 2.0 model for analysis of competing risks of death after liver transplantation for hepatocellular carcinoma.
        Gastroenterology. 2018; 154: 128-139
        • Mehta N.
        • Frenette C.
        • Tabrizian P.
        • et al.
        Downstaging outcomes for hepatocellular carcinoma: results from the multicenter evaluation of reduction in tumor size before liver transplantation (MERITS-LT) consortium.
        Gastroenterology. 2021; 161: 1502-1512
        • Mazzaferro V.
        • Citterio D.
        • Bhoori S.
        • et al.
        Liver transplantation in hepatocellular carcinoma after tumour downstaging (XXL): a randomised, controlled, phase 2b/3 trial.
        Lancet Oncol. 2020; 21: 947-956
        • Ferrer-Fàbrega J.
        • Forner A.
        Is downstaging a reliable strategy for expanding criteria for liver transplantation in hepatocellular carcinoma?.
        Lancet Oncol. 2020; 21: 867-869
        • Assalino M.
        • Terraz S.
        • Grat M.
        • et al.
        Liver transplantation for hepatocellular carcinoma after successful treatment of macrovascular invasion – a multi-center retrospective cohort study.
        Transpl Int. 2020; 33: 567-575
        • Serenari M.
        • Cappelli A.
        • Cucchetti A.
        • et al.
        Deceased donor liver transplantation after radioembolization for hepatocellular carcinoma and portal vein tumoral thrombosis: a pilot study.
        Liver Transplant. 2021; 27: 1758-1766
        • Nordness M.F.
        • Hamel S.
        • Godfrey C.M.
        • et al.
        Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: are checkpoint inhibitors safe for the pretransplant patient?.
        Am J Transplant. 2020; 20: 879-883
        • Qiao Z.Y.
        • Zhang Z.J.
        • Lv Z.C.
        • et al.
        Neoadjuvant programmed cell death 1 (PD-1) inhibitor treatment in patients with hepatocellular carcinoma before liver transplant: a cohort study and literature review.
        Front Immunol. 2021; 12: 653437
        • Tabrizian P.
        • Florman S.S.
        • Schwartz M.E.
        PD-1 inhibitor as bridge therapy to liver transplantation?.
        Am J Transplant. 2021; 21: 1979-1980
        • Zhang X.P.
        • Gao Y.Z.
        • Chen Z.H.
        • et al.
        An Eastern Hepatobiliary Surgery Hospital/portal vein tumor thrombus scoring system as an aid to decision making on hepatectomy for hepatocellular carcinoma patients with portal vein tumor thrombus: a multicenter study.
        Hepatology. 2019; 69: 2076-2090
        • Lee K.T.
        • Lu Y.W.
        • Wang S.N.
        • et al.
        The effect of preoperative transarterial chemoembolization of resectable hepatocellular carcinoma on clinical and economic outcomes.
        J Surg Oncol. 2009; 99: 343-350
        • Sasaki A.
        • Iwashita Y.
        • Shibata K.
        • et al.
        Preoperative transcatheter arterial chemoembolization reduces long-term survival rate after hepatic resection for resectable hepatocellular carcinoma.
        Eur J Surg Oncol. 2006; 32: 773-779
        • Labgaa I.
        • Tabrizian P.
        • Titano J.
        • et al.
        Feasibility and safety of liver transplantation or resection after transarterial radioembolization with Yttrium-90 for unresectable hepatocellular carcinoma.
        HPB (Oxford). 2019; 21: 1497-1504
        • Kaseb A.O.
        • Vence L.
        • Blando J.
        • et al.
        Immunologic correlates of pathologic complete response to preoperative immunotherapy in hepatocellular carcinoma.
        Cancer Immunol Res. 2019; 7: 1390-1395
        • Kaseb A.O.
        • Cao H.S.T.
        • Mohamed Y.I.
        • et al.
        Final results of a randomized, open label, perioperative phase II study evaluating nivolumab alone or nivolumab plus ipilimumab in patients with resectable HCC.
        J Clin Oncol. 2020; 38: 4599
        • Pinato D.J.
        • Fessas P.
        • Sapisochin G.
        • et al.
        Perspectives on the neoadjuvant use of immunotherapy in hepatocellular carcinoma.
        Hepatology. 2021; 74: 483-490
        • Li S.
        • Zhong C.
        • Li Q.
        • et al.
        Neoadjuvant transarterial infusion chemotherapy with FOLFOX could improve outcomes of resectable BCLC stage A/B hepatocellular carcinoma patients beyond Milan criteria: an interim analysis of a multi-center, phase 3, randomized, controlled clinical trial.
        J Clin Oncol. 2021; 39: 4008
        • Xu X.-F.
        • Xing H.
        • Han J.
        • et al.
        Risk factors, patterns, and outcomes of late recurrence after liver resection for hepatocellular carcinoma: a multicenter study from China.
        JAMA Surg. 2019; 154: 209-217
        • Han J.
        • Fan Y.C.
        • Wang K.
        Radiofrequency ablation versus microwave ablation for early stage hepatocellular carcinoma: a PRISMA-compliant systematic review and meta-analysis.
        Medicine (Baltimore). 2020; 99: e22703
        • Feng Y.
        • Wang L.
        • Lv H.
        • et al.
        Microwave ablation versus radiofrequency ablation for perivascular hepatocellular carcinoma: a propensity score analysis.
        HPB (Oxford). 2021; 23: 512-519
        • Livraghi T.
        • Meloni F.
        • Di Stasi M.
        • et al.
        Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice?.
        Hepatology. 2008; 47: 82-89
        • Cho Y.K.
        • Kim J.K.
        • Kim M.Y.
        • et al.
        Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies.
        Hepatology. 2009; 49: 453-459
        • Shin S.W.
        • Ahn K.S.
        • Kim S.W.
        • et al.
        Liver resection versus local ablation therapies for hepatocellular carcinoma within the Milan criteria: a systematic review and meta-analysis.
        Ann Surg. 2021; 273: 656-666
        • Llovet J.M.
        • De Baere T.
        • Kulik L.
        • et al.
        Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma.
        Nat Rev Gastroenterol Hepatol. 2021; 18: 293-313
        • Wang C.
        • Wang H.
        • Yang W.
        • et al.
        Multicenter randomized controlled trial of percutaneous cryoablation versus radiofrequency ablation in hepatocellular carcinoma.
        Hepatology. 2015; 61: 1579-1590
        • Kim R.
        • Kang T.W.
        • Cha D.I.
        • et al.
        Percutaneous cryoablation for perivascular hepatocellular carcinoma: therapeutic efficacy and vascular complications.
        Eur Radiol. 2019; 29: 654-662
        • Peng Z.W.
        • Zhang Y.J.
        • Chen M.S.
        • et al.
        Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial.
        J Clin Oncol. 2013; 31: 426-432
        • Chen K.
        • Chen G.
        • Wang H.
        • et al.
        Increased survival in hepatocellular carcinoma with iodine-125 implantation plus radiofrequency ablation: a prospective randomized controlled trial.
        J Hepatol. 2014; 61: 1304-1311
        • Li Q.
        • Chen K.
        • Huang W.
        • et al.
        Minimally invasive photothermal ablation assisted by laparoscopy as an effective preoperative neoadjuvant treatment for orthotopic hepatocellular carcinoma.
        Cancer Lett. 2021; 496: 169-178
        • Qi S.
        • Zhang Y.
        • Liu G.
        • et al.
        Plasmonic-doped melanin-mimic for CXCR4-targeted NIR-II photoacoustic computed tomography-guided photothermal ablation of orthotopic hepatocellular carcinoma.
        Acta Biomater. 2021; 129: 245-257
        • Salem R.
        • Johnson G.E.
        • Kim E.
        • et al.
        Yttrium-90 radioembolization for the treatment of solitary, unresectable HCC: the LEGACY study.
        Hepatology. 2021; 74: 2342-2352
        • Garin E.
        • Tselikas L.
        • Guiu B.
        • et al.
        Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial.
        Lancet Gastroenterol Hepatol. 2021; 6: 17-29
        • Dhondt E.
        • Lambert B.
        • Hermie L.
        • et al.
        (90)Y radioembolization versus drug-eluting bead chemoembolization for unresectable hepatocellular carcinoma: results from the TRACE phase II randomized controlled trial.
        Radiology. 2022; 303: 699-710
        • Lee J.
        • Shin I.S.
        • Yoon W.S.
        • et al.
        Comparisons between radiofrequency ablation and stereotactic body radiotherapy for liver malignancies: meta-analyses and a systematic review.
        Radiother Oncol. 2020; 145: 63-70
        • Yoon S.M.
        • Ryoo B.Y.
        • Lee S.J.
        • et al.
        Efficacy and safety of transarterial chemoembolization plus external beam radiotherapy vs sorafenib in hepatocellular carcinoma with macroscopic vascular invasion: a randomized clinical trial.
        JAMA Oncol. 2018; 4: 661-669
        • Soin A.S.
        • Bhangui P.
        • Kataria T.
        • et al.
        Experience with LDLT in patients with hepatocellular carcinoma and portal vein tumor thrombosis postdownstaging.
        Transplantation. 2020; 104: 2334-2345https://doi.org/10.1097/tp.0000000000003162
        • Kudo M.
        • Ueshima K.
        • Ikeda M.
        • et al.
        TACTICS: final overall survival (OS) data from a randomized, open label, multicenter, phase II trial of transcatheter arterial chemoembolization (TACE) therapy in combination with sorafenib as compared with TACE alone in patients (pts) with hepatocellular carcinoma (HCC).
        J Clin Oncol. 2021; 39: 270
        • Peng Z.
        • Fan W.
        • Zhu B.
        • et al.
        Lenvatinib combined with transarterial chemoembolization as first-line treatment of advanced hepatocellular carcinoma: a phase 3, multicenter, randomized controlled trial.
        J Clin Oncol. 2022; 40: 380
        • Finn R.S.
        • Ikeda M.
        • Zhu A.X.
        • et al.
        Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma.
        J Clin Oncol. 2020; 38: 2960-2970
        • Lee I.-C.
        • Wu C.-J.
        • Chen S.-C.
        • et al.
        Lenvatinib plus pembrolizumab versus lenvatinib in patients with unresectable hepatocellular carcinoma: a real world study.
        J Clin Oncol. 2021; 39: e16138
      2. D’Alessio A, Fulgenzi CAM, Nishida N, et al. Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: a real-world study. Hepatology. n/a(n/a)doi:https://doi.org/10.1002/hep.32468