Hepatitis C Virus: From Laboratory to Clinic (Repost)

Hepatitis C virus (HCV) has received a lot of media attention and has been called a "silent epidemic." This virus infects more than 170 million people worldwide and at least 1.8 million in the United States alone. Although the number of new cases of HCV infection appears to be declining, many people with chronic infection were infected between 1970 and 1990 and thus have had the disease for decades. Since the onset of clinically apparent liver disease typically occurs between 10 and 20 years after HCV infection, we are now seeing the effects of long-standing infection -- namely, end-stage liver disease, cirrhosis, liver cancer, and death. Recent publications in the Journal and elsewhere have described the increasing burden of liver disease caused by HCV. The rate of hepatocellular carcinoma, which in this country is most often due to HCV-induced cirrhosis, has tripled over the past decade, and the costs associated with the care of persons with chronic HCV infection are expected to continue to increase. HCV was identified in 1989 with the use of a unique molecular technique, and since that time there has been an explosion of knowledge regarding the virus. The virus is difficult to study because there is no robust tissue-culture system and no small-animal model of infection. Thus, much of the literature on the biology of HCV has revolved around novel molecular tools, and clinicians wishing to understand the basic-science literature need an approachable summary. The liver disease caused by this virus is also difficult to study because of its highly variable clinical manifestations, ranging from asymptomatic viremia to cirrhosis, and because of the prolonged period of time needed to meet the definition of "cure" in clinical trials. Research scientists who want to become familiar with the current understanding of clinical issues also need an approachable summary. This book has five sections, which cover basic principles (including replication, natural history, and pathogenesis), recent advances, experimental approaches, protocols and techniques, and emerging areas of research. By aiming his book at both clinicians and research scientists, Feitelson has assumed a difficult task, especially as a single author. Each chapter may have advantages and disadvantages for the two target audiences. Given that a research scientist wrote it, the book tends to fall short in covering the clinical features of HCV infection. For example, the discussion of the natural history of the infection does not do justice to the wide variations reported in the rates of development of cirrhosis and of death from liver disease, which range from 2 percent to 30 percent, depending on the cohort of patients. Feitelson does, however, discuss some of the clinical features associated with the higher rates, such as concomitant use of alcohol, male sex, and age at the time of infection. Similarly, the chapter on treatment does not provide a comprehensive explanation of the presumed mechanisms of action of pegylated interferon and ribavirin, which are the currently approved therapies. Furthermore, the discussion of the use and benefits of pegylated interferon, which is the current therapy of choice, appears in a chapter about new systems for understanding the biology of HCV. A discussion of the use of early viral kinetics to guide future therapeutic trials might have been helpful for researchers interested in drug development. There is no discussion of HCV in immunocompromised patients, who represent an important subgroup of patients infected with HCV. The book is more successful in reviewing the basic-science literature for the clinician. The section on basic science will be especially useful to the clinician who is participating in clinical trials and wishes to have a better dialogue with scientists who are doing ancillary studies. The chapter on pathogenesis is particularly informative. There is a balanced discussion of the role of the virus and the host immune response in liver injury, accompanied by a table that lists the pros and cons of the evidence that HCV infection is cytopathic, and of the role that immune responses have in liver injury. Similar tables appear throughout the book. References usually are not provided in the tables, but the work is well referenced in general, and the primary sources of information can be located without difficulty. The excellent discussion of the pathogenesis of HCV infection is a very good review of the current literature on this important topic. The section on protocols and techniques is the most problematic one in the book. The methods used in HCV research are described in the briefest of detail. This level of coverage might be sufficient for a clinician interested in an overview of the assays, but it is not adequate for someone unfamiliar with the techniques. Some important areas are not discussed in sufficient detail. For example, in the absence of a robust tissue-culture system, many in the field believe that the replicon system is a key advance. When I tried to determine whether this book would be useful to a clinician interested in replicon systems, I found that the index cites only a single page, in the chapter titled "New Systems to Understand Hepatitis C Biology." In fact, there is a more complete, though still inadequate, discussion of replicons in another chapter, one about cell types that support viral replication. Which audience will best be served by this book? Research scientists might not gain a sufficient understanding of some of the complexities of the clinical issues and might be better served by review articles or chapters in standard textbooks of clinical medicine. On the other hand, clinicians wishing for a brief but comprehensive summary of the current state of the art in laboratory-based investigation of HCV and HCV infection will find this book an excellent place to start.