Drug-Induced Liver Disease PDF

Preface to the Second Edition

The high productivity of the pharmaceutical industry has provided exciting, efficacious new drugs. However, with efficacy always comes the potential for toxicity, and the growth in new pharmaceuticals has been accompanied by several new drugs linked to liver toxicity. At the same time, epidemiological studies have found that drugs are now the most common causes of liver failure. This has led to a resurgence of interest in drug-induced liver disease in general and has spurred an influx of clinical researchers into this area. Basic research in this area has also thrived over the last decade, due to innovations in biomedical research that have given us tools that have provided new insights into the mechanisms of drug toxicity. The time was therefore ripe to compile a volume with contributions from scientists around the world with expertise in pathogenesis and clinical presentation, as well as authorities on the various categories of drugs and toxins of importance to this field.

We have been gratified by the outstanding reviews of the first edition. However, we believe that in this fast-moving field, a book would only remain of value if it can be revised in a timely enough fashion to keep abreast of recent developments. In the second edition, 16 out of the 36 chapters have new authors or cover new topics. New topics include pharmacogenomics and toxicogenomics, causality assessment, risk factors for drug-induced liver disease, management of drug-induced liver disease, and mushroom poisoning. Pharmacogenomics and toxicogenomics are new fields that provide the hope for rational strategies for the pharmaceutical industry in weeding out toxic drugs earlier in development, but may also devise novel approaches to prevent drug toxicity in the susceptible few without exclusion of new drugs efficacious for the many. The new chapters "Causality Assessment" and "Risk Factors for Drug-Induced Liver Disease" expand the Diagnosis and Management section and provide more background on the fundamentals of the field. We have also added a chapter on management to address issues as such liver transplantation and the use of steroids and ursodeoxycholic acid, and we have addressed therapy in individual chapters as well.

The second edition is divided into four sections. Section I focuses on mechanisms of hepatotoxicity, often illustrated by examples of specific drugs. The newly expanded Section II reviews general principles of clinical presentation, histopathology, predisposition to toxicity, diagnosis, and management. Each chapter in Section III examines a class of drugs, toxins, or drugs used within a clinical specialty. This section provides a systematic review of the major xenobiotics associated with drug-induced liver disease and also serves as a reference for clinicians dealing with a possible case of drug-induced liver disease. Section IV contains a completely rewritten chapter on drug toxicity from a regulatory perspective.

We are pleased with the second edition, which has allowed us to improve and expand coverage of the field and to update the rapidly advancing knowledge of pathogenesis. We believe this volume will be a great value to hepatologists, physicians in all fields of medicine, toxicologists and pharmacologists, and scientists working in preclinical and clinical drug development in both academia and industry.