disease. 2 Many of these studies identified pretreatment pa-Alpha interferon is the only drug that has been shown to tient characteristics that are associated with a greater or lesser be effective in the treatment of chronic hepatitis C, but only likelihood of response to interferon (Table 1). The most clinihalf of patients respond, either transiently or permanently.
cally important of these factors were the level of serum HCV Pretreatment features that are associated with a greater likeli-RNA, viral genotype, and the histology of the pretreatment hood of response to short courses of interferon include low liver biopsy specimen. [3][4][5] Indeed, each of these factors has hepatitis C virus (HCV) RNA levels, viral genotypes 2 or 3, been shown by multivariate analysis to be independently and the absence of fibrosis or cirrhosis on liver biopsy. Each associated with response by the end of the course of interof these features is more predictive of sustained response feron treatment, known as end-of-treatment response (ETR; (SR) than the end-of-treatment response (ETR). However, the previously termed complete response), and sustained reaccuracy of these features in predicting response in individual sponse (SR; response persisting for at least 6 months after patients is poor. Furthermore, there are several limitations to the discontinuation of treatment). The clinical application of using these factors in the clinical management of patients.
these predictive factors has taken several forms. First, and Most importantly, they were identified in 6-month treatment most importantly, it has allowed clinical investigators to detrials. Longer treatment or combination of interferon with sign better studies by stratifying for these factors that influribavirin reduces relapses and will therefore lessen the associence response. It has also allowed investigators to understand ation of these factors with long-term response. In addition, differences in response rates in studies conducted in different changes in the definition of treatment end points and the populations. However, it has also led to changes in treatment technology used to measure HCV RNA might change the assopatterns. In an attempt to improve response rates and reduce ciation between these predictive factors and response. The the cost of interferon treatment, some have suggested exclubest predictor of a treatment response is the early normalizasion of patients from treatment if they have one or more of tion of the serum alanine aminotransferase (ALT) level during the pretreatment markers that have been associated with a interferon treatment. HCV RNA loss during treatment may reduced likelihood of response. Some physicians routinely also be helpful in predicting response, but it is probably no exclude patients with cirrhosis from treatment and some clinbetter than serum ALT levels and is expensive. In summary, ical trials have excluded them to increase response rates. 6 several clinical and virological features are associated with Furthermore, commercial advertisements in medical journals higher response rates to interferon treatment. Although prehave recently begun to encourage physicians to test viral treatment factors do not accurately predict treatment outcome genotypes and serum HCV RNA levels to select patients for in individuals, they may be helpful in counseling patients and treatment. The validity of using such patient selection stratemaking treatment decisions. (HEPATOLOGY 1997;26(Suppl gies has not been critically examined.
1):122S-127S.)
The purpose of this review is to examine how accurately clinical and virological features predict a response to inter-Alpha interferon was the first agent shown to have activity feron treatment in patients with chronic hepatitis C. Furtheragainst the hepatitis C virus (HCV), and it remains the only more, the implications of patient selection strategies based drug that is effective in the treatment of chronic hepatitis on pretreatment characteristics are evaluated. Finally, the C. 1 At least 88 trials of interferon treatment, 37 of which practical use and limitations of these predictive factors as were controlled, have been performed in patients with this they apply to patients and clinicians are discussed.
PUBLISHED REPORTS OF PREDICTIVE FACTORS
To examine the practical implications of selecting patients Abbreviations: HCV, hepatitis C virus; ETR, end-of-treatment response; SR, susby pretreatment criteria, studies were selected in which treattained response; ALT, alanine amino transferase; ISDR, interferon sensitivity determining region.