Therapeutic approach to acute hepatitis C

Abstract

It is estimated that 150 to 200 million individuals arecurrently infected with the hepatitis C virus (HCV) [1-3], andthat, annually, there are 3 to 4 million new cases of infectionworldwide [4]. In view of the impossibility ofimmunoprevention [5] - either through vaccines or the use ofpost-exposure immunoglobulin - and the risk of chronicity inindividuals exposed to the disease, which is estimated to bebetween 50% and 85% [2,4,6-9,33], the definition of strategiesaimed at early detection and treatment of infected individuals,preferably during the acute phase of the infection [2,4], hasbeen widely discussed in recent years.In individuals presenting symptoms consistent with acutehepatitis C (AHC), it is known that the possibility ofspontaneous viral clearance, among various factors, dependsespecially on a potent initial cellular immune response mediatedby cytotoxic T lymphocytes - initially by HCV-specific CD8+T lymphocytes and, subsequently, CD4+ T lymphocytes [10-12]. Other factors associated with a higher rate of sustainedvirological response (SVR) are the specific characteristics ofthe patients. Individuals who are Asian or Caucasian, female,young, and HIV-negative, as well as presenting a rapid dropin HCV RNA levels and presenting specific human leukocyteantigen class II alleles, together with the previously mentionedT cytotoxic response, also respond better to treatment[16,17,33]. Better responses are also found in cases ofinfections with shorter incubation period produced by smallerinoculates. In addition, in a prospective study conducted bySantantoni et al., a higher rate of spontaneous viral clearancewas observed in patients infected with genotype 3 [7].A diagnosis of acute infection with HCV remains a rareevent in clinical practice. In 70%-80% of infected patients,AHC is asymptomatic, and 75% are anicteric [4,8,13-15,33].Individuals with AHC present elevated serum levels of alanineaminotransferase (ALT) and aspartate aminotransferase(AST), with or without a clinical profile of acute hepatitis,detection of (previously undetectable) HCV RNA andseroconversion for anti-HCV antibodies. It is estimated thatinfection with HCV accounts for only 20% of all diagnosedcases of acute hepatitis [13]. In the United States, there are40,000 cases of AHC annually [12], and only a small percentageof those are clinically diagnosed in this phase.Considering the high risk of developing chronic hepatitisC and the favorable evidence, in terms of therapeutic response,it is fundamental to improve our capacity to properly detectand treat cases of acute infection with HCV [12].