Chronic Viral Hepatitis: Diagnosis and Therapeutics (Clinical Gastroenterology)

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From the New England Journal of Medicine, April 18, 2002
More than 2 billion people worldwide are infected with either hepatitis B virus (HBV) or hepatitis C virus (HCV) or both, and an estimated 500 million (about 3 million in the United States alone) have chronic infection with these viruses. The principal long-term sequelae of chronic HBV and HCV infection are cirrhosis and primary liver cancer. These diseases are prominent in countries where HBV infection is highly endemic and usually acquired in childhood, allowing their development in young adults. In the United States, where both HBV and HCV infection are generally acquired later in life and where the two infections have different rates of chronicity, chronic HCV infection has a far greater clinical impact than HBV infection. Both infections decrease patients' quality of life even in the precirrhotic stage, often because of extrahepatic complications.

The availability of a safe and effective vaccine and the absence of an animal reservoir will make the prospects of eradication of HBV a reality within the next few decades. In contrast, the development of a vaccine against HCV has proved difficult, and because of heterogeneity of the virus there is currently little hope of inducing immunity. Moreover, because of a wave of new infections, the clinical (and economic) impact of chronic hepatitis C will probably increase in the next 20 years, and the mortality rate should double or triple by the year 2015. End-stage liver disease due to HCV infection is currently the single most important indication for liver transplantation, and the future demand for liver grafts is bound to increase accordingly.

Within this context, we have all greeted the advent of new, effective therapeutic agents. Today we have a panoply of antiviral agents against HBV, many of them borrowed from our colleagues in retrovirology (HBV replicates by way of a step involving reverse transcriptase). As for HCV, ribavirin and pegylated interferons can cure 50 percent of patients. The opposite side of the coin is that some of these drugs have several side effects and contraindications, may be toxic, and are expensive. As a result, as many as 20 percent of patients who are otherwise eligible for treatment choose not to be treated because of their fear of side effects or prefer to postpone therapy and wait for more tolerable regimens.

Chronic Viral Hepatitis is another valuable guide to the proper care of patients with chronic viral hepatitis. One may wonder whether this new book simply adds to the plethora of books on chronic viral hepatitis and may wonder what its shelf life will be in an era of electronic information. But this comprehensive overview has a very practical and down-to-earth perspective that should appeal to a wide audience. The book starts with a concise, clinically oriented introduction on the molecular virology of both viruses, followed by a brief but complete discussion of their epidemiology and natural history. The real strength of the book is a number of chapters devoted to practical aspects of the management of chronic viral hepatitis. These chapters cover not only general, up-to-date guidelines for therapy, but also the development of individualized therapeutic plans, the medical support of patients during treatment, and the care of patients who have coexisting extrahepatic illnesses or who are pregnant.

An interesting survey of the most common complementary and alternative treatments for liver disease is also presented. This chapter contains timely information, if we consider that 42 percent of Americans report the use of alternative or complementary medicine, at an annual cost (in 1997) of $21.2 billion, most of it out of pocket. The authors conclude with a candid and balanced assessment of the current situation with respect to these remedies in the United States: because of the lack of regulation of their sale and manufacture, special care must be taken to avoid unforeseen effects or interactions between alternative treatments and established antiviral agents. This task is not easy, given that so many patients are hesitant to discuss the use of alternative regimens with their primary physicians. Whether we like it or not, we must concede that complementary approaches do play a part in medical practice and that some of these techniques and drugs may benefit some patients. A crucial step, as rightly emphasized in the book, is to increase our awareness of the motivations behind our patients' choices.

The book ends with a chapter on prophylaxis against viral hepatitis, written by R.S. Koff, a long-standing champion of vaccination campaigns. The chapter starts with a thorough discussion of the measures aimed at decreasing exposure to these blood-borne agents. It then deals with different strategies for passive and active immunoprophylaxis, underlining how one decade of mass vaccination against HBV in Taiwan was sufficient to decrease the incidence of primary liver cancer, making this vaccine the first one to be effective in preventing a human tumor. This optimism, however, is dimmed by the persistent difficulties involved in developing an effective vaccine against HCV. Alternative approaches are under consideration, but it will be some time before we can claim victory.

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