- Email: [email protected]
THE BRIDGE – January 2001
Journal of Hepatology 34 (2001) 1
THE BRIDGE ± January 2001 A year has passed since the initial Bridge. I thank Dr Juan RodeÂs and the Editorial team for their support of this page. The view from the Bridge has never been better. Dendritic cells in the liver (see pages 61±67) When presented with foreign antigens, the liver maintains a ®ne balance between an immune response and the development of a tolerant state. Antigen-presenting cells in the liver include sinusoidal, Kuppfer and dendritic cells. In the current issue, Abe et al., (Ehime, Japan) freshly isolated murine dendritic cells. In this condition, no stimulation of allogeneic T cells occurred. When matured after exposure to antigens such as HBsAg, dendritic cells became strong T cell stimulators and induced the proliferation of antigen-speci®c memory lymphocytes. In a well-crafted editorial, Doherty and O'Farrelly (pages 156±160) review the mechanisms of antigen presentation by dendritic cells. The divergent outcome of this interaction, leading to either tolerance or immune reaction, is related to events occurring during activation of this `immunological synapse'. Dissecting these pathways may have profound implications for our understanding of the response to viral antigens, autoimmune liver disease as well as the development of tolerance after transplantation. Encapsulation of hepatocytes (see pages 11±18) Isolated reports of successful outcomes after transplantation of isolated hepatocytes for genetic conditions or in chronic liver failure have intensi®ed the search for viable methods of cell preservation in vitro as well as successful implantation in vivo. Encapsulation of hepatocytes will protect the cells from immune-mediated injury while allowing secretion of synthesized proteins. In this issue, Canaple et al., (Lausanne) present results of primary cultures of murine hepatocytes placed in multicomponent polymer capsules. Biocompatibility was excellent; in addition, the cells could be cryopreserved for up to four months, with intact cellular functions upon thawing. The accompanying editorial by Chang (page 148±149) reviews technical problems of encapsulation and highlights the potential applicability of cryopreserved hepatocytes. Bacterial translocation in cirrhosis (see pages 32±37) In experimental cirrhosis, bacterial translocation (BT) from the gut to mesenteric lymph nodes is frequent in animals with spontaneous bacterial peritonitis. Furthermore, BT has been postulated to trigger subsequent events, such as cytokine release, which may in¯uence the course of chronic liver disease. In a prospective study, Navasa and colleagues (Barcelona) cultured mesenteric lymph nodes in a large cohort of 101 cirrhotic patients undergoing liver transplantation. While the
www.elsevier.com/locate/jhep
AndreÂs T. Blei [email protected] overall incidence of translocation was similar to controls (9%), it was increased in more advanced cirrhosis (31% in Child C); Enterobacteria were not the most common species. In an accompanying editorial, GarcõÂa-Tsao (pages 150±155) examines the experimental evidence supporting a role for BT as a cause of decompensation in cirrhosis as well as results of BT in other clinical conditions where it can be viewed as a consequence of injury. Hepatitis vaccine studies Two reports from Israel examine economic and scienti®c issues surrounding the current use of hepatitis vaccines. In the ®rst, Ginsberg et al. (pages 92±99) add important information surrounding the controversy of cost-effectiveness of hepatitis A immunization. Modelling a population with intermediate endemicity, the authors estimate more than a doubling of health service and societal bene®t over costs resulting from such an effort. In a second report, Shapira et al. (pages 123±127) present results of a human vaccine that includes pre-S1 and S2 antigens. It was associated with a prompter response (60% seroprotection at 4 weeks vs. 13% for currently available S vaccine) and two doses of the vaccine (rather than the standard 3) resulted in 100% seroprotection at 7 months. It will be of interest to examine whether this rapid induction of seroprotection also translates into higher ef®cacy in selected populations. The review article The discovery of the gene for Wilson's disease (ATP7B) has provided new insights into the pathogenesis of this unique disease. Riordan and Williams (London) examine the relation between the different mutations described in ATP7B and the diverse clinical expression of the disease. No de®nite correlations exist between phenotypic diversity and the large (.200) number of mutations described in different populations. The diagnosis of Wilson's disease still challenges the experienced hepatologist. Clinical vignettes Using MR, an increase of azygos blood ¯ow and portal blood ¯ow at midnight in cirrhotics could be prevented with the administration of propranolol during the evening (Sugano, Tokyo, see pages 26±31). The observed cancer rates for a cohort of 174 patients after liver transplantation were signi®cantly increased, especially for skin/lip, colon and renal carcinoma (Haagsma, Groningen, see pages 84± 91). Health-related quality of life and work productivity were increased in patients with chronic hepatitis C who were complete responders to the combination of interferon and ribavarin (McHutchinson, La Jolla, see pages 140±147).
0168-8278/01/$20.00 q 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. PII: S 0168-827 8(00)00103-3
THE BRIDGE ± January 2001 A year has passed since the initial Bridge. I thank Dr Juan RodeÂs and the Editorial team for their support of this page. The view from the Bridge has never been better. Dendritic cells in the liver (see pages 61±67) When presented with foreign antigens, the liver maintains a ®ne balance between an immune response and the development of a tolerant state. Antigen-presenting cells in the liver include sinusoidal, Kuppfer and dendritic cells. In the current issue, Abe et al., (Ehime, Japan) freshly isolated murine dendritic cells. In this condition, no stimulation of allogeneic T cells occurred. When matured after exposure to antigens such as HBsAg, dendritic cells became strong T cell stimulators and induced the proliferation of antigen-speci®c memory lymphocytes. In a well-crafted editorial, Doherty and O'Farrelly (pages 156±160) review the mechanisms of antigen presentation by dendritic cells. The divergent outcome of this interaction, leading to either tolerance or immune reaction, is related to events occurring during activation of this `immunological synapse'. Dissecting these pathways may have profound implications for our understanding of the response to viral antigens, autoimmune liver disease as well as the development of tolerance after transplantation. Encapsulation of hepatocytes (see pages 11±18) Isolated reports of successful outcomes after transplantation of isolated hepatocytes for genetic conditions or in chronic liver failure have intensi®ed the search for viable methods of cell preservation in vitro as well as successful implantation in vivo. Encapsulation of hepatocytes will protect the cells from immune-mediated injury while allowing secretion of synthesized proteins. In this issue, Canaple et al., (Lausanne) present results of primary cultures of murine hepatocytes placed in multicomponent polymer capsules. Biocompatibility was excellent; in addition, the cells could be cryopreserved for up to four months, with intact cellular functions upon thawing. The accompanying editorial by Chang (page 148±149) reviews technical problems of encapsulation and highlights the potential applicability of cryopreserved hepatocytes. Bacterial translocation in cirrhosis (see pages 32±37) In experimental cirrhosis, bacterial translocation (BT) from the gut to mesenteric lymph nodes is frequent in animals with spontaneous bacterial peritonitis. Furthermore, BT has been postulated to trigger subsequent events, such as cytokine release, which may in¯uence the course of chronic liver disease. In a prospective study, Navasa and colleagues (Barcelona) cultured mesenteric lymph nodes in a large cohort of 101 cirrhotic patients undergoing liver transplantation. While the
www.elsevier.com/locate/jhep
AndreÂs T. Blei [email protected] overall incidence of translocation was similar to controls (9%), it was increased in more advanced cirrhosis (31% in Child C); Enterobacteria were not the most common species. In an accompanying editorial, GarcõÂa-Tsao (pages 150±155) examines the experimental evidence supporting a role for BT as a cause of decompensation in cirrhosis as well as results of BT in other clinical conditions where it can be viewed as a consequence of injury. Hepatitis vaccine studies Two reports from Israel examine economic and scienti®c issues surrounding the current use of hepatitis vaccines. In the ®rst, Ginsberg et al. (pages 92±99) add important information surrounding the controversy of cost-effectiveness of hepatitis A immunization. Modelling a population with intermediate endemicity, the authors estimate more than a doubling of health service and societal bene®t over costs resulting from such an effort. In a second report, Shapira et al. (pages 123±127) present results of a human vaccine that includes pre-S1 and S2 antigens. It was associated with a prompter response (60% seroprotection at 4 weeks vs. 13% for currently available S vaccine) and two doses of the vaccine (rather than the standard 3) resulted in 100% seroprotection at 7 months. It will be of interest to examine whether this rapid induction of seroprotection also translates into higher ef®cacy in selected populations. The review article The discovery of the gene for Wilson's disease (ATP7B) has provided new insights into the pathogenesis of this unique disease. Riordan and Williams (London) examine the relation between the different mutations described in ATP7B and the diverse clinical expression of the disease. No de®nite correlations exist between phenotypic diversity and the large (.200) number of mutations described in different populations. The diagnosis of Wilson's disease still challenges the experienced hepatologist. Clinical vignettes Using MR, an increase of azygos blood ¯ow and portal blood ¯ow at midnight in cirrhotics could be prevented with the administration of propranolol during the evening (Sugano, Tokyo, see pages 26±31). The observed cancer rates for a cohort of 174 patients after liver transplantation were signi®cantly increased, especially for skin/lip, colon and renal carcinoma (Haagsma, Groningen, see pages 84± 91). Health-related quality of life and work productivity were increased in patients with chronic hepatitis C who were complete responders to the combination of interferon and ribavarin (McHutchinson, La Jolla, see pages 140±147).
0168-8278/01/$20.00 q 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. PII: S 0168-827 8(00)00103-3