HCC CONNECT review paper published in Mayo Clinic Proceedings: Innovations, Quality & Outcomes

Sammy Saab, MD is a Professor in the Departments of Internal Medicine and Surgery at the David Geffen School of Medicine in Los Angeles, California, USA. He is also Head of Outcomes Research in Hepatology at the Pfleger Liver Institute. Dr Saab received his BS, MD, and MPH from University of California Los Angeles (UCLA). He completed his residency in internal medicine at University of California at San Diego Medical Center and a fellowship in gastroenterology/hepatology at UCLA Center for Health Sciences. Dr Saab is board certified in gastroenterology and transplant hepatology. He has received honorary fellowships from the American Gastroenterology Association (AGAF), American College of Gastroenterology (FACG) and the American Association for the Study of Liver Diseases (FAASLD). Relevant publications Saab S, Hunt D, Stone MA, McClune A, Tong MJ. Timing of Hepatitis C Antiviral Therapy Pre and Post Liver Transplantation: A Decision Analysis Model. Liver Transpl 2010: 16: 748-59. With accompanying editorial. Duffy JP, Kao K, Ko CY, Farmer DG, McDiarmid SV, Hong JC, Venick RS, Feist S, Goldstein L, Saab S, Hiatt JR, Busuttil RW. Long-term patient outcome and quality of life after liver transplantation: analysis of 20-year survivors. Ann Surg. 2010; 252: 652-61 Saab S, McTigue M, Finn R, Busuttil RW. Sorafenib as adjuvant therapy for high risk Hepatocellular Carcinoma in Liver Transplant Recipients: Feasibility and Efficacy. Exp Clinl Transplant 2010; 8: 307-13. Saab S, Bownick H, Ayoub N, Younossi Z, Durazo F, Han SH, Farmer D, Hong J, Busuttil RW. Differences in Health Related Quality of Life Scores after Orthotopic Liver Transplant with Respect to Selected Socioeconomic Factors. Liver Transpl 2011;17:580-90. Chak E, Talal AH, Sherman KE, Schiff ER, Saab S. Hepatitis C Virus Infection in the United States: An Estimated of the True Prevalence. Liv Intern 2011; 31: 1090-101. Wertheim J, Kupiec-Weglinski J, Petrowsky H, Saab S, Busuttil, RW. Major challenges limiting liver transplantation in the United States. Am J Transplant 2011; 11: 1773-84. Hong JC, Jones CM, Duffy JP, Petrowsky H, Farmer DG, French S, Finn R, Durazo FA, Saab S, Tong MJ, Hiatt JR, Busuttil RW. Comparative analysis of resection and liver transplantation for intrahepatic and hilar cholangiocarcinoma: a 24-year experience in a single center. Arch Surg 2011; 146: 683-9. Everson GT, Terrault NA, Lok AS, Rodrigo DR, Brown RS Jr, Saab S, Shiffman ML, Al-Osaimi AM, Kulik LM, Gillespie BW, Everhart JE; and the A2ALL Study Group. A Randomized Controlled Trial of Pretransplant Antiviral Therapy to Prevent Recurrence of Hepatitis C after Liver Transplantation. Hepatology 2013; 57: 1752-62. Rubin J, Ayoub N, Kaldas F, Saab S. Management of Recurrent Hepatocellular Carcinoma in Liver Transplant Recipients: A Systematic Review. Exp Clinl Transplant 2012; 10(6):531-43. Sood A, Cox GA, McWilliams JP, Wang HL, Saab S. Patients with Nodular Regenerative Hyperplasia Should be Considered for Hepatocellular Carcinoma Screening. Hepatology Research 2014; 44: 689-93. Matsuda T, Tonnu-Mihara I, Yuan Y, Hines P, Saab S, Italien GJ, McCombs J. External validation of the risk-prediction model for hepatocellular carcinoma [hcc] from the reveal HCV study. Value in Health. 2013; 16: A12. Campsen J, Zimmerman M, Trotter J, Hong J, Freise C, Brown R, Cameron A, Ghobrial M, Kam I, Busuttil R, Saab S, Holt C, Emond J, Stiles J, Lukose T, Chang M, Klintmalm G. Liver transplantation for hepatitis B liver disease and concomitant hepatocellular carcinoma in the United States with hepatitis B immunoglobulin and nucleoside/nucleotide analogues. Liver Transpl 2013; 19: 1020-9. Agopian VG, Petrowsky H, Kaldas FM, Zarrinpar A, Farmer DG, Yersiz H, Holt Cm Harlander-Locke M, Hon JC, Rana AR, Venick R, McDiarmid SV, Goldstein LI, Durazo F, Saab S, Han S, Xia V, Hiatt JR, Busuttil RW. The Evolution of Liver Transplantation During 3 Decades. Analysis of 5347 Consecutive Liver Transplants at a Single Center. Annals of Surgery 2013; 258: 409-21. Saab S, Manne V Akhtar E. Cirrhosis Regression in Hepatitis C Patients with Sustained Virologic Response after Anti-Viral therapy: A Meta-analysis. Liver International 2015; 35: 30-36. Saab S, Manne V, Bui V, Sundaram. Cumulative Radiation Exposure in Liver Transplant Candidates and Patients Transplanted with Hepatocellular Carcinoma. J Liv Dis Transplant 2014; 3 (1). Stepanova M, Wai H, Saab S, Mishra A, Venkatesan C, Younossi ZM. The Portrait of an Adult Liver Transplant Recipient in the United States From 1987 to 2013. JAMA Intern Med 2014; 174: 1407-9. Stepanova M, Wai H, Saab S, Mishra A, Venkatesan C, Younossi Z. The outcomes of adult liver transplants in the united states from 1987 to 2013. Liver Int 2015; 358: 2036-41. Al-hamoudi W, Elsiesy H, Bendahmash A, Al-masri N, Ali S, Allam N, Al Sofayan M, Al Bahili H, Al Sebayel, Dieter Broering M, Saab S, Abaalkhail F. Liver transplantation for hepatitis B virus: Decreasing indication and changing trends. W J Gastroenterol 2015; 21: 8140-7. Saab S, Jimenez M, Fong T, Wu C, El Kabany M, Tong MJ. Timing of Antiviral Therapy in Liver Transplant Candidates listed for Hepatitis C and Hepatocellular Carcinoma. Exp Clin Transpl 2016; 14: 66-71. Al-Hamoudi W, Elsiesy H, Bendahmash A, Al-Masri N, Ali S, Allam N, Al Sofayan M, Al Bahili H, Al Sebayel M, Broering D, Saab S, Abaalkhail F. Liver transplantation for hepatitis B virus: Decreasing indication and changing trends. World J Gastroenterol. 2015; 21:8140-7 Kuei A, Saab S, Cho SK, Kee ST, Lee EW. Effects of Yttrium-90 selective internal radiation therapy on non-conventional liver tumors. World J Gastroenterol. 2015;21:8271-83. Nguyen K, Jimenez M, Moghadam N, Wu C, Farid A, Grotts J, Elashoff D, Choi G, Durazo FA, El-Kabany MM, Han SHB, Saab S. Decrease of Alpha-Fetoprotein in Patients with Cirrhosis Treated with Direct Acting Agents. J Clin Transl Hepatol 2017; 5(1): 43-49. Ahmed A, Gonzalez SA, Cholankeril G, Perumpail RB, McGinnis J, Saab S, Beckerman R, Younossi ZM. Treatment of Patients Waitlisted for Liver Transplant with an All-Oral DAAs is a Cost-Effective Treatment Strategy in the United States. Hepatology 2017; 66(1): 46-56.

Dr Singal is an expert in hepatocellular carcinoma (HCC), particularly in early tumor detection and screening process failures, and serves as Medical Director of the Liver Tumor Program at UT Southwestern Medical Center, USA. He has research training in Patient Centered Outcomes Research, with a Masters in Health and Healthcare Research from the University of Michigan. He currently is leading several federal and state funded projects to evaluate interventions to improve the effectiveness of early tumor detection efforts among patients with cirrhosis in the USA. Dr Singal has published over 100 scientific papers and has established collaborations with experts throughout the USA over the past several years. He has been active in many academic professional societies including American Association for Study of Liver Diseases (AASLD), International Liver Cancer Association (ILCA), American College of Gastroenterology (ACG), and American Gastroenterological Association (AGA). He was selected as Chair of the ICLA Surveillance and Biomarkers Special Interest Group and is a member of the AGA Liver Disease Measures workgroup. He has editorial experience including an Academic Editor for PLOS Medicine and an Associate Editor for Clinical Gastroenterology and Hepatology and Seminars in Liver Disease. Selected Recent Publications: Singal A, Volk ML, Waljee AK, Salgia R, Higgins P, Rogers M, Marrero JA. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther 2009; 30(1): 37-47. Singal AG, Yopp A, Skinner CS, Packer M, Lee WM, Tiro JA. Utilization of hepatocellular carcinoma surveillance among American patients: a systematic review. J Gen Intern Med 2012; 27(7): 861-867. Singal AG, Conjeevaram H, Fu S, Volk ML, Fontana RJ, Askari F, Su GL, Lok AS, Marrero JA. Effectiveness of hepatocellular carcinoma surveillance in patients with cirrhosis. Cancer Epidemiol Biomarkers Preven 2012; 21(5): 793-9. Singal AG, Nehra M, Adams-Huet B, Yopp AC, Tiro JA, Marrero JA, Lok AS, Lee WM. Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: Where did surveillance fail? Am J Gastroenterol 2013; 108(3): 425-32. Singal AG, Pillai A, Tiro JA. Early detection, curative treatment, and survival rates for HCC surveillance in patients with cirrhosis: a meta-analysis. PLOS Medicine 2014; 11(4): e1001624. Singal AG, Li X, Tiro JA, Kandunoori P, Huet B, Nehra M, Yopp AC. Racial, social, and clinical determinants of hepatocellular carcinoma surveillance. Am J Med 2015; 128(1): 90e1 – 90e7. Dalton-Fitzgerald E, Tiro J, Kandunoori P, Halm E, Yopp A, Singal AG. Practice patterns and attitudes of primary care providers and barriers to surveillance of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol 2015;13(4):791-8. Patel N, Yopp AC, Singal AG. Diagnostic delays are common among patients with hepatocellular carcinoma. J Natl Compr Canc Netw 2015; 13(5): 543-9. Mokdad A, Zhu H, Marrero JA, Mansour JC, Yopp AC, Singal AG. Hospital volume and survival after hepatocellular carcinoma diagnosis. Am J Gastroenterol 2016; 111(7): 967-75. Parikh ND, Marshall VD, Singal AG, Nathan H, Lok AS, Balkrishnan R, Shahinian V. Survival and cost-effectiveness of sorafenib therapy in advanced hepatocellular carcinoma: An analysis of the SEER-Medicare Database. Hepatology 2017; 56(1): 122-33. Simmons O, Fetzer DT, Yokoo T, Marrero JA, Yopp A, Kono Y, Parikh N, Browning T, Singal AG. Predictors of adequate ultrasound quality for HCC surveillance in patients with cirrhosis. Aliment Pharmacol Ther 2017; 45(1): 169-77. Farvardin S, Patel J, Khambaty M, Yerokun O, Mok H, Tiro JA, Yopp AC, Parikh ND, Marrero JA, Singal AG. Patient-reported barriers are associated with lower HCC surveillance rates in patients with cirrhosis. Hepatology 2017; 65(3): 875-84. Singal AG, Tiro JA, Marrero JA, McCallister K, Mejias C, Sanders J, Bishop WP, Santini NO, Halm EA. Mailed outreach program increases ultrasound screening of patients with cirrhosis for hepatocellular carcinoma. Gastroenterology 2017; 152(3): 608-15. Atiq O, Tiro J, Yopp AC, Muffler A, Marrero JA, Parikh ND, Murphy C, McCallister K, Singal AG. An assessment of benefits and harms of hepatocellular carcinoma surveillance in patients with cirrhosis. Hepatology 2017; 65(4): 1196-1205. Singal AG, Mittal S, Yerokun OA, Ahn C, Marrero J, Yopp A, Parikh ND, Scaglione SJ. Hepatocellular carcinoma screening associated with early tumor detection and improved survival among patients with hepatocellular carcinoma in the United States. Am J Medicine (epub ahead of print)

Dr Irene Bargellini completed her medical degree and post-graduate course in Radiology at the University of Pisa in Italy. Since then, she has been working in the Department of Interventional Radiology and has become Supervisor of the Interventional Oncology Program of Pisa University Hospital. She is specifically interested in diagnosis and management of patients with hepatocellular carcinoma (HCC), particularly with regards to outcomes of transarterial therapies. Relevant publications Crocetti L, Bargellini I, Cioni R. Loco-regional treatment of HCC: current status. Clin Radiol 2017 Feb 28. pii: S0009-9260(17)30041-7. doi: 10.1016/j.crad.2017.01.013. [Epub ahead of print] Bargellini I. How does selective internal radiation therapy compare with and/or complement other liver-directed therapies. Future Oncol 2014 Nov;10(15 Suppl):105-9. doi: 10.2217/fon.14.236. Golfieri R, Giampalma E, Renzulli M, Cioni R, Bargellini I, Bartolozzi C, Breatta AD, Gandini G, Nani R, Gasparini D, Cucchetti A, Bolondi L, Trevisani F; PRECISION ITALIA STUDY GROUP. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer 2014 Jul 15;111(2):255-64. doi: 10.1038/bjc.2014.199. Bargellini I, Scionti A, Mismas V, Masi G, Vivaldi C, Bartolozzi C, Sacco R. Identification of responders to sorafenib in hepatocellular carcinoma: is tumor volume measurement the way forward? Oncology 2014; 86(4):191-8. doi: 10.1159/000358599. Dufour JF, Bargellini I, De Maria N, De Simone P, Goulis I, Marinho RT. Intermediate hepatocellular carcinoma: current treatments and future perspectives. Ann Oncol 2013 Apr; 24 Suppl 2:ii24-9. doi: 10.1093/annonc/mdt054. Bargellini I, Florio F, Golfieri R, Grosso M, Lauretti DL, Cioni R. Trends in utilization of transarterial treatments for hepatocellular carcinoma: results of a survey by the Italian Society of Interventional Radiology. Cardiovasc Intervent Radiol 2014 Apr; 37(2): 438-44. doi: 10.1007/s00270-013-0656-5. Bargellini I, Bozzi E, Campani D, Carrai P, De Simone P, Pollina L, Cioni R, Filipponi F, Bartolozzi C. Modified RECIST to assess tumor response after transarterial chemoembolization of hepatocellular carcinoma: CT-pathologic correlation in 178 liver explants. Eur J Radiol 2013 May; 82(5): e212-8. doi: 10.1016/j.ejrad.2012.12.009. Sacco R, Bargellini I, Bertini M, Bozzi E, Romano A, Petruzzi P, Tumino E, Ginanni B, Federici G, Cioni R, Metrangolo S, Bertoni M, Bresci G, Parisi G, Altomare E, Capria A, Bartolozzi C. Conventional versus doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol 2011 Nov; 22(11): 1545-52. doi: 10.1016/j.jvir.2011.07.002. Bargellini I, Sacco R, Bozzi E, Bertini M, Ginanni B, Romano A, Cicorelli A, Tumino E, Federici G, Cioni R, Metrangolo S, Bertoni M, Bresci G, Parisi G, Altomare E, Capria A, Bartolozzi C. Transarterial chemoembolization in very early and early-stage hepatocellular carcinoma patients excluded from curative treatment: a prospective cohort study. Eur J Radiol 2012 Jun; 81(6): 1173-8. doi: 10.1016/j.ejrad.2011.03.046. Bargellini I, Vignali C, Cioni R, Petruzzi P, Cicorelli A, Campani D, De Simone P, Filipponi F, Bartolozzi C. Hepatocellular carcinoma: CT for tumor response after transarterial chemoembolization in patients exceeding Milan criteria--selection parameter for liver transplantation. Radiology 2010 Apr; 255(1): 289-300. doi: 10.1148/radiol.09090927. Grosso M, Vignali C, Quaretti P, Nicolini A, Melchiorre F, Gallarato G, Bargellini I, Petruzzi P, Massa Saluzzo C, Crespi S, Sarti I. Transarterial chemoembolization for hepatocellular carcinoma with drug-eluting microspheres: preliminary results from an Italian multicentre study. Cardiovasc Intervent Radiol 2008 Nov-Dec; 31(6):1141-9. doi: 10.1007/s00270-008-9409-2. Lencioni R, Crocetti L, Petruzzi P, Vignali C, Bozzi E, Della Pina C, Bargellini I, Cioni D, Oliveri F, De Simone P, Bartolozzi C, Brunetto M, Filipponi F. Doxorubicin-eluting bead-enhanced radiofrequency ablation of hepatocellular carcinoma: a pilot clinical study. J Hepatol 2008 Aug; 49(2): 217-22. doi: 10.1016/j.jhep.2008.03.021. Vignali C, Bargellini I, Grosso M, Passalacqua G, Maglione F, Pedrazzini F, Filauri P, Niola R, Cioni R, Petruzzi P. TIPS with expanded polytetrafluoroethylene-covered stent: results of an Italian multicenter study. AJR Am J Roentgenol 2005 Aug; 185(2): 472-80.

Catherine Frenette, MD underwent medical training at Rush Medical College in Chicago, IL. She then completed internal medicine training at Scripps Mercy Hospital in San Diego, CA, and subsequently underwent training in gastroenterology with a focus on transplant hepatology at Scripps Clinic in La Jolla, CA. Dr Frenette currently works at the Scripps Clinic Center for Organ and Cell Transplantation where she is the Medical Director of Liver Transplantation. She is also the Medical Director of the Hepatocellular Carcinoma Program. Dr Frenette has several active research trials as well as serving in a teaching capacity for the residents and fellows at Scripps Clinic. Dr Frenette holds special clinical interest and expertise in liver transplantation to treat cirrhosis, hepatocellular carcinoma, autoimmune hepatitis, viral hepatitis, acute liver failure and end stage liver disease. She is a world-renowned expert in the treatment of all stages of hepatocellular carcinoma, and has done multiple national and international educational sessions on this topic. She has been awarded Fellow Status of the American Society of Transplantation, and has recently also been awarded Fellow of the American Gastroenterology Association. Relevant publications Abou-Alfa G, Yen C-J, Hsu C-H, O’Donoghue J, Beylergil V, Ruan S, Pandit-Taskar N, Gansukh B, Lyashchenko S, Ma J, Wan P, Shao Y-Y, Lin Z-Z, Frenette CT, O’Neil B, Schwartz L, Smith-Jones P, Ohtomo T, Tanaka T, Morikawa H, Maki Y, Ohishi N, Chen Y-C, Agajanov T, Boisserie F, De Laurenzio L, Lee R, Larson S, Cheng A, Carrasquilo J. Phase Ib study of codrituzumab in combination with sorafenib in patients with non-curable advanced hepatocellular carcinoma. Cancer Chemother Pharmacol 2017 Feb; 79(2): 421-429. doi: 10.1007/s00280-017-3241-9. Nhu QM, Knowles HJ, Pockros PJ, Frenette CT. Pulmonary complications of transcatheter arterial chemoembolization for hepatocellular carcinoma. World J Respirol 2016 Nov; 6(3): 69-75. PMID 27035078 Yan M, Ha J, Aguilar M, Liu B, Frenette CT, Bhuket T, Wong RJ. Older patients with hepatocellular carcinoma more advanced disease, lower rates of treatment, and lower survival. J Clin Gastroenterol 2016; in press. PMID 27380460 Frenette CT. Surveillance for hepatocellular carcinoma. Gastroenterol Hepatol (N Y) 2016 Jun; 12(6): 394-6. PMID 27493599 Frenette CT. Surveillance for hepatocellular carcinoma. Clin Adv Hematol Oncol 2016 Jun; 14(6): 407-9. PMID 27379808 Ahn J, Bhuket T, Mosadeghi S, Frenette CT, Liu B, Wong RJ. End stage liver disease patients with MELD > 40 have higher waitlist mortality compared to status 1A patients. Hepatol Int Sep 2016; 10(5): 838-46. doi: 10.1007/s12072-016-9735-4. Curry MP, O’Leary JG, Bzowej N, Muir AL, Korenblat KM, Fenkel JM, Reddy KR, Lawitz E, Flamm SL, Schiano T, Teperman L, Fontana R, Schiff E, Fried M, Doehle B, An D, McNally J, Osinusi A, Brainard DM, McHutchinson JG, Brown RS Jr, Charlton Ml, ASTRAL-4 Investigators. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med 2015 Dec 31; 373(27): 2618-28. PMID 26569658 Nhu QM, Knowles HJ, Pockros PJ, Frenette CT. An unexpected pulmonary complication following transcatheter arterial chemoembolization of a small hepatocellular carcinoma. J Clin Gastroenterol 2016; 50(6): 524-5. PMID 27035078 Brown RS, O’Leary JG, Reddy KR, Kuo A, Morelli GJ, Burton JR, Stravitz RT, Durand C, Di Bisceglie AM, Kwo P, Frenette CT, Stewart TG, Nelson DR, Friend MW, Terrault NA, HCV-TARGET Study Group. Inteferon-free therapy for genotype 1 hepatitis C in liver transplant recipients: real world experience from HCV-TARGET. Liver Transpl 2016 Jan; 22(1): 24-33. PMID 26519873 Ha J, Yan M, Aguilar M, Tana M, Liu B, Frenette CT, Bhuket T, Wong R. Race/ethnicity-specific disparities in hepatocellular carcinoma stage at diagnosis and its impact on receipt of curative therapies. J Clin Gastroenterol 2016; 50 (5): 423-430. PMID 26583267 Bhangoo MS, Karnani DR, Hein PN, Giap H, Knowles H, Issa C, Steuterman S, Pockros P, Frenette CT. Radioembolization with Yttrium-90 microspheres for patients with unresectable hepatocellular carcinoma. J Gastrointest Oncol 2015; 6(5): 469-478. PMID 26487939 Au J, Frenette CT. Management of hepatocellular carcinoma: current status and future directions. Gut Liver 2015; 9(4): 437-448. PMID 26087860 Chiao H, Frenette CT. Solid organ transplantation: little research, big need for patients with HCV. HCV Next 2014 May/June; 1(3): 15-20. Scherschel A, Minteer WB, Frenette CT. An interesting case of inclusion body myositis after 48-week interferon treatment for hepatitis C. HCV Next 2014 Mar/Apr; 1(2): 8-10. Crissien AM, Frenette CT. Current management of hepatocellular carcinoma. Gastroenterol Hepatol 2014 Mar; 10(3): 153-61. PMID 24829542. Torres HA, Kaseb A, Mahale P, Miller E, Frenette CT. Telaprevir-containing regimen for treatment of hepatitis C virus infection in patients with hepatocellular carcinoma awaiting liver transplantation: a case series. J Hepatocell Carcinoma 2014; 1: 109-14. Naugler WE, Alsina AE, Frenette CT, Rossaro L, Sellers MT. Building the multidisciplinary team for management of patients with hepatocellular carcinoma. Clin Gastroenterol Hepatol 2014; doi:10.1016/j.cgh.2014.03.038. PMID 24909910 Brose MS, Frenette CT, Keefe SM, Stein SM. Management of sorafenib-related adverse events: a clinician’s perspective. Semin Oncol 2014; 41(S2): S1-S16. PMID 24576654