EASL Recognition Awardee 2013: Professor Yun-Fan Liaw

Abstract

Professor Yun-Fan Liaw received the EASL international recognition award during the latest International Liver Conference in Amsterdam on April 26, 2013.Yun-Fan Liaw graduated in 1967 at the College of Medicine, National Taiwan University, Taipei, Taiwan. Then, he became resident in internal medicine at the National Taiwan University Hospital. After being a Clinical Assistant Professor at the National Defense Medical Center in Taipei, he became Professor of Medicine at the Chang Gung University Medical College in 1987; since 2012, he has been Distinguished Chair Professor. After being attending physician, he became Director of the Department of Hepato-Gastroenterology as well as Director of the Liver Research Unit at the Chang Gung Memorial Hospital in 1976.Among his many professional activities, Professor Liaw has been a Member of the Hepatitis Control Committee, Department of Health of Taiwan (1982–1992); President of the Taiwan Association for the Study of the Liver (1994–1995); and President of the Asian Pacific Association for the Study of the Liver (2000–2002).He has also contributed to editorial activities of internationally renowned Hepatology journals; as examples, he has been editor of Journal of Gastroenterology & Hepatology (1993–2001) and Hepatology International (2007–2008), as well as Associate Editor of the Journal of Hepatology (2010–2012). As recognition of his work in the field of hepatitis B research, he received several national and international awards.During his training, he became rapidly interested in Hepatology. Professor Juei-Low Sung, his mentor, who guided and supported him during his career, asked him to work on liver cancer, but he was frightened by the high mortality rate. He then chose to work on hepatitis B virus infections, which represent a major public health problem in this region of the world. He established a liver research unit with outstanding collaborators involved in viral hepatitis clinical research. Thanks to this research group, his work led to a major publication record in viral hepatitis, with 459 publications referenced in PubMed, 18,958 citations and an H index of 70.His main contribution to the field of hepatitis B clinical research was the characterization of the natural history of the infection in the ‘80s. This included the definition of the clinicopathological events associated with the so called «chronic active hepatitis», the events preceding HBe seroconversion, and the clinical features of HBV reactivation [1Liaw Y.F. Chu C.M. Chen T.J. Lin D.Y. Chang-Chien C.S. Wu C.S. Chronic lobular hepatitis: a clinicopathological and prognostic study.Hepatology. 1982; 2: 258-262Crossref PubMed Scopus (21) Google Scholar, 2Liaw Y.F. Chu C.M. Su I.J. Huang M.J. Lin D.Y. Chang-Chien C.S. Clinical and histological events preceding hepatitis B e antigen seroconversion in chronic type B hepatitis.Gastroenterology. 1983; 84: 216-219Abstract Full Text PDF PubMed Scopus (312) Google Scholar].A landmark paper was published in 1985, in collaboration with the team of Professor Howard Thomas in London, on the characterization of the different phases of the disease, i.e., the immune tolerant phase, the immunoactive phase, and the residual phase, now called inactive carrier state [[3]Chu C.M. Karayiannis P. Fowler M.J. Monjardino J. Liaw Y.F. Thomas H.C. Natural history of chronic hepatitis B virus infection in Taiwan: studies of hepatitis B virus DNA in serum.Hepatology. 1985; 5: 431-434Crossref PubMed Scopus (304) Google Scholar]. These phases reflect the immunopathological mechanism of chronic HBV infections and are now classically recognized by all clinicians managing hepatitis B patients. The new molecular diagnostic assays allowed to confirm these phases and to delineate the current indications for antiviral therapy [[4]EASL clinical practice guidelines Management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185Abstract Full Text Full Text PDF PubMed Scopus (2658) Google Scholar]. His group was also interested in the study of the effect of HCV infection on the natural course of hepatitis B and demonstrated the suppressive effect of HCV super infection on HBV replication in chronic HBV carriers [5Liaw Y.F. Chen Y.C. Sheen I.S. Chien R.N. Yeh C.T. Chu C.M. Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection.Gastroenterology. 2004; 126: 1024-1029Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar, 6Liaw Y.F. Tsai S.L. Chang J.J. Sheen I.S. Chien R.N. Lin D.Y. et al.Displacement of hepatitis B virus by hepatitis C virus as the cause of continuing chronic hepatitis.Gastroenterology. 1994; 106: 1048-1053Abstract Full Text PDF PubMed Google Scholar].As a logical continuation of his work on the natural history of the disease, he was then interested in improving the health of chronically infected patients. His dedication to clinical studies of new antivirals and predictors of treatment outcome was tremendous and led to outstanding knowledge, which was used by international liver societies to write treatment recommendations and guidelines as well as by all hepatitis B treating physicians. Professor Liaw and his colleagues studied the effect of standard and then pegylated interferon alpha in Asian patients and demonstrated its benefit in inducing HBe seroconversion [[7]Liaw Y.F. Jia J.D. Chan H.L. Han K.H. Tanwandee T. Chuang W.L. et al.Shorter durations and lower doses of peginterferon alfa-2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C.Hepatology. 2011; 54: 1591-1599Crossref PubMed Scopus (165) Google Scholar]. He was also involved in the early phases of development of nucleos(t)ide analogs including lamivudine, telbivudine, and entecavir [8Liaw Y.F. Leung N.W. Chang T.T. Guan R. Tai D.I. Ng K.Y. et al.Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.Gastroenterology. 2000; 119: 172-180Abstract Full Text Full Text PDF PubMed Scopus (710) Google Scholar, 9Lai C.L. Gane E. Liaw Y.F. Hsu C.W. Thongsawat S. Wang Y. et al.Telbivudine versus lamivudine in patients with chronic hepatitis B.N Engl J Med. 2007; 357: 2576-2588Crossref PubMed Scopus (697) Google Scholar, 10Sherman M. Yurdaydin C. Simsek H. Silva M. Liaw Y.F. Rustgi V.K. et al.Entecavir therapy for lamivudine-refractory chronic hepatitis B: improved virologic, biochemical, and serology outcomes through 96 weeks.Hepatology. 2008; 48: 99-108Crossref PubMed Scopus (140) Google Scholar]. His studies showed the long-term impact of antiviral therapy on the improvement of chronic hepatitis B [[8]Liaw Y.F. Leung N.W. Chang T.T. Guan R. Tai D.I. Ng K.Y. et al.Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.Gastroenterology. 2000; 119: 172-180Abstract Full Text Full Text PDF PubMed Scopus (710) Google Scholar]. He also showed that nucleos(t)ide analogue based therapy with the drugs exhibiting a high barrier to resistance (tenofovir or entecavir), can rescue patients with decompensated cirrhosis [11Liaw Y.F. Raptopoulou-Gigi M. Cheinquer H. Sarin S.K. Tanwandee T. Leung N. et al.Efficacy and safety of entecavir versus adefovir in chronic hepatitis B patients with hepatic decompensation: a randomized open-label study.Hepatology. 2011; 54: 91-100Crossref PubMed Scopus (174) Google Scholar, 12Liaw Y.F. Sheen I.S. Lee C.M. Akarca U.S. Papatheodoridis G.V. Suet-Hing Wong F. et al.Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease.Hepatology. 2011; 53: 62-72Crossref PubMed Scopus (267) Google Scholar]. Another major finding was that, in patients with advanced liver fibrosis, efficient antiviral therapy with lamivudine, leading to maintained control of viral replication, can prevent the development of decompensation and hepatocellular carcinoma [[13]Liaw Y.F. Sung J.J. Chow W.C. Farrell G. Lee C.Z. Yuen H. et al.Lamivudine for patients with chronic hepatitis B and advanced liver disease.N Engl J Med. 2004; 351: 1521-1531Crossref PubMed Scopus (1972) Google Scholar]. This pioneering work paved the way to new studies, which demonstrated that not only disease progression could be slowed down, but also that liver fibrosis could regress during efficient therapy [14Marcellin P. Gane E. Buti M. Afdhal N. Sievert W. Jacobson I.M. et al.Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study.Lancet. 2013; 381: 468-475Abstract Full Text Full Text PDF PubMed Scopus (1187) Google Scholar, 15Chang T.T. Liaw Y.F. Wu S.S. Schiff E. Han K.H. Lai C.L. et al.Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B.Hepatology. 2010; 52: 886-893Crossref PubMed Scopus (746) Google Scholar]. This outstanding work now opens new questions toward a cure of the infection and early treatment intervention to prevent the development of hepatocellular carcinoma [16Zoulim F. Mason W.S. Reasons to consider earlier treatment of chronic HBV infections.Gut. 2012; 61: 333-336Crossref PubMed Scopus (83) Google Scholar, 17Lampertico P. Liaw Y.F. New perspectives in the therapy of chronic hepatitis B.Gut. 2012; 61: i18-i24Crossref PubMed Scopus (50) Google Scholar].On a more personal note, Professor Liaw is recognized to be an open person, always willing to share is enormous clinical experience with his colleagues and has always been considered to be one of the major «hepatologist gentlemen».For all these reasons, and Professor Liaw’s outstanding scientific achievements and dedication to the development and progress of liver research, EASL is proud to award him this international recognition. Professor Yun-Fan Liaw received the EASL international recognition award during the latest International Liver Conference in Amsterdam on April 26, 2013. Yun-Fan Liaw graduated in 1967 at the College of Medicine, National Taiwan University, Taipei, Taiwan. Then, he became resident in internal medicine at the National Taiwan University Hospital. After being a Clinical Assistant Professor at the National Defense Medical Center in Taipei, he became Professor of Medicine at the Chang Gung University Medical College in 1987; since 2012, he has been Distinguished Chair Professor. After being attending physician, he became Director of the Department of Hepato-Gastroenterology as well as Director of the Liver Research Unit at the Chang Gung Memorial Hospital in 1976. Among his many professional activities, Professor Liaw has been a Member of the Hepatitis Control Committee, Department of Health of Taiwan (1982–1992); President of the Taiwan Association for the Study of the Liver (1994–1995); and President of the Asian Pacific Association for the Study of the Liver (2000–2002). He has also contributed to editorial activities of internationally renowned Hepatology journals; as examples, he has been editor of Journal of Gastroenterology & Hepatology (1993–2001) and Hepatology International (2007–2008), as well as Associate Editor of the Journal of Hepatology (2010–2012). As recognition of his work in the field of hepatitis B research, he received several national and international awards. During his training, he became rapidly interested in Hepatology. Professor Juei-Low Sung, his mentor, who guided and supported him during his career, asked him to work on liver cancer, but he was frightened by the high mortality rate. He then chose to work on hepatitis B virus infections, which represent a major public health problem in this region of the world. He established a liver research unit with outstanding collaborators involved in viral hepatitis clinical research. Thanks to this research group, his work led to a major publication record in viral hepatitis, with 459 publications referenced in PubMed, 18,958 citations and an H index of 70. His main contribution to the field of hepatitis B clinical research was the characterization of the natural history of the infection in the ‘80s. This included the definition of the clinicopathological events associated with the so called «chronic active hepatitis», the events preceding HBe seroconversion, and the clinical features of HBV reactivation [1Liaw Y.F. Chu C.M. Chen T.J. Lin D.Y. Chang-Chien C.S. Wu C.S. Chronic lobular hepatitis: a clinicopathological and prognostic study.Hepatology. 1982; 2: 258-262Crossref PubMed Scopus (21) Google Scholar, 2Liaw Y.F. Chu C.M. Su I.J. Huang M.J. Lin D.Y. Chang-Chien C.S. Clinical and histological events preceding hepatitis B e antigen seroconversion in chronic type B hepatitis.Gastroenterology. 1983; 84: 216-219Abstract Full Text PDF PubMed Scopus (312) Google Scholar]. A landmark paper was published in 1985, in collaboration with the team of Professor Howard Thomas in London, on the characterization of the different phases of the disease, i.e., the immune tolerant phase, the immunoactive phase, and the residual phase, now called inactive carrier state [[3]Chu C.M. Karayiannis P. Fowler M.J. Monjardino J. Liaw Y.F. Thomas H.C. Natural history of chronic hepatitis B virus infection in Taiwan: studies of hepatitis B virus DNA in serum.Hepatology. 1985; 5: 431-434Crossref PubMed Scopus (304) Google Scholar]. These phases reflect the immunopathological mechanism of chronic HBV infections and are now classically recognized by all clinicians managing hepatitis B patients. The new molecular diagnostic assays allowed to confirm these phases and to delineate the current indications for antiviral therapy [[4]EASL clinical practice guidelines Management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185Abstract Full Text Full Text PDF PubMed Scopus (2658) Google Scholar]. His group was also interested in the study of the effect of HCV infection on the natural course of hepatitis B and demonstrated the suppressive effect of HCV super infection on HBV replication in chronic HBV carriers [5Liaw Y.F. Chen Y.C. Sheen I.S. Chien R.N. Yeh C.T. Chu C.M. Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection.Gastroenterology. 2004; 126: 1024-1029Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar, 6Liaw Y.F. Tsai S.L. Chang J.J. Sheen I.S. Chien R.N. Lin D.Y. et al.Displacement of hepatitis B virus by hepatitis C virus as the cause of continuing chronic hepatitis.Gastroenterology. 1994; 106: 1048-1053Abstract Full Text PDF PubMed Google Scholar]. As a logical continuation of his work on the natural history of the disease, he was then interested in improving the health of chronically infected patients. His dedication to clinical studies of new antivirals and predictors of treatment outcome was tremendous and led to outstanding knowledge, which was used by international liver societies to write treatment recommendations and guidelines as well as by all hepatitis B treating physicians. Professor Liaw and his colleagues studied the effect of standard and then pegylated interferon alpha in Asian patients and demonstrated its benefit in inducing HBe seroconversion [[7]Liaw Y.F. Jia J.D. Chan H.L. Han K.H. Tanwandee T. Chuang W.L. et al.Shorter durations and lower doses of peginterferon alfa-2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C.Hepatology. 2011; 54: 1591-1599Crossref PubMed Scopus (165) Google Scholar]. He was also involved in the early phases of development of nucleos(t)ide analogs including lamivudine, telbivudine, and entecavir [8Liaw Y.F. Leung N.W. Chang T.T. Guan R. Tai D.I. Ng K.Y. et al.Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.Gastroenterology. 2000; 119: 172-180Abstract Full Text Full Text PDF PubMed Scopus (710) Google Scholar, 9Lai C.L. Gane E. Liaw Y.F. Hsu C.W. Thongsawat S. Wang Y. et al.Telbivudine versus lamivudine in patients with chronic hepatitis B.N Engl J Med. 2007; 357: 2576-2588Crossref PubMed Scopus (697) Google Scholar, 10Sherman M. Yurdaydin C. Simsek H. Silva M. Liaw Y.F. Rustgi V.K. et al.Entecavir therapy for lamivudine-refractory chronic hepatitis B: improved virologic, biochemical, and serology outcomes through 96 weeks.Hepatology. 2008; 48: 99-108Crossref PubMed Scopus (140) Google Scholar]. His studies showed the long-term impact of antiviral therapy on the improvement of chronic hepatitis B [[8]Liaw Y.F. Leung N.W. Chang T.T. Guan R. Tai D.I. Ng K.Y. et al.Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.Gastroenterology. 2000; 119: 172-180Abstract Full Text Full Text PDF PubMed Scopus (710) Google Scholar]. He also showed that nucleos(t)ide analogue based therapy with the drugs exhibiting a high barrier to resistance (tenofovir or entecavir), can rescue patients with decompensated cirrhosis [11Liaw Y.F. Raptopoulou-Gigi M. Cheinquer H. Sarin S.K. Tanwandee T. Leung N. et al.Efficacy and safety of entecavir versus adefovir in chronic hepatitis B patients with hepatic decompensation: a randomized open-label study.Hepatology. 2011; 54: 91-100Crossref PubMed Scopus (174) Google Scholar, 12Liaw Y.F. Sheen I.S. Lee C.M. Akarca U.S. Papatheodoridis G.V. Suet-Hing Wong F. et al.Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease.Hepatology. 2011; 53: 62-72Crossref PubMed Scopus (267) Google Scholar]. Another major finding was that, in patients with advanced liver fibrosis, efficient antiviral therapy with lamivudine, leading to maintained control of viral replication, can prevent the development of decompensation and hepatocellular carcinoma [[13]Liaw Y.F. Sung J.J. Chow W.C. Farrell G. Lee C.Z. Yuen H. et al.Lamivudine for patients with chronic hepatitis B and advanced liver disease.N Engl J Med. 2004; 351: 1521-1531Crossref PubMed Scopus (1972) Google Scholar]. This pioneering work paved the way to new studies, which demonstrated that not only disease progression could be slowed down, but also that liver fibrosis could regress during efficient therapy [14Marcellin P. Gane E. Buti M. Afdhal N. Sievert W. Jacobson I.M. et al.Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study.Lancet. 2013; 381: 468-475Abstract Full Text Full Text PDF PubMed Scopus (1187) Google Scholar, 15Chang T.T. Liaw Y.F. Wu S.S. Schiff E. Han K.H. Lai C.L. et al.Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B.Hepatology. 2010; 52: 886-893Crossref PubMed Scopus (746) Google Scholar]. This outstanding work now opens new questions toward a cure of the infection and early treatment intervention to prevent the development of hepatocellular carcinoma [16Zoulim F. Mason W.S. Reasons to consider earlier treatment of chronic HBV infections.Gut. 2012; 61: 333-336Crossref PubMed Scopus (83) Google Scholar, 17Lampertico P. Liaw Y.F. New perspectives in the therapy of chronic hepatitis B.Gut. 2012; 61: i18-i24Crossref PubMed Scopus (50) Google Scholar]. On a more personal note, Professor Liaw is recognized to be an open person, always willing to share is enormous clinical experience with his colleagues and has always been considered to be one of the major «hepatologist gentlemen». For all these reasons, and Professor Liaw’s outstanding scientific achievements and dedication to the development and progress of liver research, EASL is proud to award him this international recognition.