ABSTRACT
Introduction 3 Molecular mechanisms controlling collagen synthesis 5 Mediators influencing collagen expression in HSCs 10 Posttranscriptional regulation of type I collagen expression 13
2. CYP2E1-Biochemical and Toxicological Aspects and Role in Alcohol-induced Liver Injury A rthur I. Cederbaum (U SA )
27-44
Introduction 27 CYP2E1 29 CYP2E1 and alcohol-induced liver injury 35 Biochemical and toxicological properties of CYP2E1 in HEPG2 cells 35 Future perspectives 38
3. Alcohol and Methyl Transfer. Implications for Alcohol-related Hepatocarcinogenesis Felix Stickel (Switzerland), Christoph Herold, H elm ut K. Seitz and D etlef Schuppan (Germany)
45-58
Introduction 45 Alcohol-related hepatocarcinogenesis: A multi-step process 46 Mechanisms of alcohol toxicity 47 Lipotropes as a target of alcohol toxicity 47 SAMe for chemoprevention in hepatocarcinogenesis 54 Conclusion 54
4. Methionine Adenosyltransferase and S-adenosylmethionine in Liver Health and Disease Shelly C. Lu and Jose M. M ato (U SA )
59-78
Introduction 59 Historical perspective 60 Hepatic methionine metabolism 61 MAT genes and enzyme isoforms 61 Abnormalities of MAT in liver disease 62 Mechanisms of altered MAT gene expression in liver cirrhosis and cancer 65 SAMe as control switch in maintaining normal liver function 66 Importance of MAT and SAMe in liver disease-lessons learned from the MAT1A null mice 68 Concluding remarks 72
5. Acetone Metabolism in the Liver: Two Approaches to the Same Phenomenon Med. Habil. Miklos Peter Kalapos (Hungary)
79-92
Introduction and history 79 Metabolic pathways for acetone and role of liver 80 Effects of acetone on biotransformation of xenobiotics 82 Summary of clinical implications 84 Possible pathophysiological role(s) of acetone biodegradation: two approaches to the same phenomenon 86 Conclusion, perspectives and unanswered questions 87
6. Oxidative Stress and Liver Fibrosis: From Liver Irtjury to Modulation of Cell Signalling and Response Elena Zamara, Erica Novo and Maurizio Parola (Italy)
93-114
Introduction 94 Oxidative stress, liver fibrosis, and chronic liver diseases: major concepts 96 Major consequences of oxidative stress generation in relation to liver fibrosis and its progression 101 Antioxidants: a possible tool to support conventional therapy for CLDs to reduce fibrosis progression? 107 Concluding remarks 108
7. Role of Nitric Oxide in Liver Disorders Pablo Muriel (Mexico)
115-132
Introduction 115 Nitric oxide and hepatic fibrosis 116 Nitric oxide and hyperdynamic circulation 117 Nitric oxide and paracetamol-induced liver injury 119 Nitric oxide, and liver inflammation and septic shock 120 Nitric oxide and hepatic ischemia-reperfusion injury 122 Role of nitric oxide in hepatocellular carcinoma 123 Nitric oxide effects on mitochondria and other organelles 124 Concluding remarks 125
8. Renin-Angiotensin System and Liver Fibrosis Hitoshi Yoshiji, Shigeki Kuriyama and Hiroshi Fukui (Japan)
133-140
Introduction 133 Angiotensin II and liver fibrosis 135 Angiotensin II and angiogenesis 135 Angiotensin II and TIMP-1 136 Conclusions 138
Simon C. Afford and Patricia F. Lalor (UK) 143-158
Introduction 143 Triggering hepatic inflammation 145 Trafficking and retention of inflammatory cells in the liver and role of hepatic endothelium 146 Role of cholangiocytes and hepatocytes during Inflammation 149 Regulation of hepatic stellate cell function and survival 153 Potential targets for therapeutic intervention 154
10. Role of Activated Macrophages in Liver Disease Ion V. Deaciuc and Craig /. McClain (USA)
159-178
Introduction 159 Markers of macrophage activation 160 Mechanisms of monocyte and Kupffer cell activation 162 Liver injury by MC-and KC-secreted mediators 165 Conclusions and future directions 171
11. Basis for Immune Recognition of Cellular Targets in Primary Biliary Cirrhosis Ruth Joplin (UK)
179-196
Introduction 179 Cellular targets in PBC 180 Antigenic targets in PBC 184 Models of PBC 187 Infectious agent as basis of immune recognition of cellular targets in PBC? 190
12. Cross Talk of Hepatocytes and Nonparenchymal Liver Cells in Physiology and Pathology: Monoxides and Eicosanoids 197-216 Zbigniew Kmiec (Poland) Nitric oxide in normal and diseased liver 197 Role of heme oxygenase and carbon monoxide in liver function 202 Eicosanoids in liver physiology and pathobiology 204
13. Activity of Cytokines in Chronic HCV Infection and Influence of Antiviral Drugs Tadeusz Wojciech Lapinski (Poland)
217-226
Introduction 217 Role of IL-1 in HCV infection 217 Implication of IL-12 in HCV infection 219 Role of IL-18 in HCV infection 219 Synergy of cytokines in activation of apoptosis 219 Significance of Thl and Th2 lymphocytes in HCV infection 220 Role of IL-2 in HCV infection 220 Significance of IL-15 in hepatitis C infection 220 IFN-y activity in HCV infection 222 Role of IL-4 in HCV infection 222 Influence of HCV infection on IL-6 concentration 222 Activity of other cytokines in HCV infected patients 223
14. Role of Chemokines in Liver Pathophysiology Fabio Marra (Italy)
227-242
Introduction 228 Alcoholic liver disease 230 Ischemia-reperfusion injury 230 Transplant rejection 231 Viral hepatitis 232 Other causes of liver inflammation 233 Liver cancer 234 Angiogenesis 234 Liver regeneration 234 Chemokines and the biliary system 235 Liver fibrosis 235 Conclusions 237
15. Nonalcoholic Fatty Liver Diseases: Clinical and Pathophysiological Features Frank A. Anania (USA)
245-272
Introduction 245 Primary and secondary causes of hepatic steatosis-macrosteatosis 246 Epidemiology of NAFLD and NASH 248 Pathogenesis of nonalcoholic fatty liver disease and steatohepatitis: current concepts 251 Rodent models of NAFL and NASH-in vivo tools to study NAFLD 255
Status of the utility of animal models 257 How is the diagnosis of NAFLD made? 259 Medical therapy for human fatty liver disease 261 Weight reduction for NAFLD: a multidisciplinary approach 262 Novel therapies specifically for NAFLD 265 Surgical therapy for NAFLD 266
16. Genetic Basis of Hepatocellular Cancer Sigal Tal-Kremer, Christopher P. Day and Helen L. Reeves
273-308
Introduction 273 Mechanisms of gene deregulation in HCC 274 Genetic instability in hepatocellular cancer 278 Cell cycle regulation and its disruption in HCC 281 Inactivation of p53 286 Wnt/p-catenin pathway 289 Apoptosis 291 Roles of various aetiologies of chronic liver disease in initiation and progression of HCC 295 Future directions 301
17. Haemochromatosis: Recent Advances AJM Davis and WM Rosenberg
309-330
Introduction 309 Iron biology 309 Genetics of HH-HFE 311 HFE epidemiology 311 HFE molecule 311 Effect of HFE mutations 313 Other genetic causes of iron overload 313 Rare HFE mutations 315 Other genes causing HH 315 Prevalence of HH 316 Role of HFE in other liver disorders 320 Role of HFE in extrahepatic disorders 320 Advances in diagnosis 322 Management of HFE 322 Screening for HH 324 Concluding remarks 324
18. Pathophysiology of Cirrhotic Ascites: Recent Advances George Therapondos and Florence Wong
331-350
Introduction 331 Historical perspective 331 Currently accepted hypothesis: peripheral arterial vasodilatation 332 Evolving concepts 332 Pathogenesis of sodium retention at various stages of cirrhosis 343
19. Cryptogenic Hepatitis Isabelle Chemin
351-366
Introduction 351 Diagnostic settings 352 External agents 352 Common aetiologies to eliminate 352 Other forms of cryptogenic hepatitis 354 Identification of new hepatitis viruses 357 'Candidates' viruses in the field of cryptogenic hepatitis 357 Conclusion 361
20. HIV1 and the Liver Sandro Vento, M . D. and Francesca Cainelli, M. D.
