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| Clinical Background: |
Acute infection with HCV is frequently asymptomatic. The majority of patients (70-80%) develop chronic infection (positive anti-HCV and elevated serum aminotransferases for > 6 months) Most of these patients will have a mild, protracted course; only 15-20% will progress to cirrhosis and end-stage liver disease. The biologic basis for the development of chronic infection is not well understood. Preliminary studies suggest that the cellular immune response to HCV is relatively weak in patients with chronic infection compared to patients who clear HCV. Furthermore, it has been proposed that the ineffective cellular inflammatory response in chronic infection contributes to hepatocyte injury; this in turn may lead to fibrosis and cirrhosis. Although somewhat controversial, there appears to be little difference in disease severity or outcome based on the viral genotype.
The clinical signs and symptoms of chronic HCV infection can be nonexistent, mild and nonspecific, or in the case of a patient who has progressed to cirrhosis, quite prominent. Mild symptoms include fatigue, poor appetite, mild RUQ discomfort, nausea and muscle and joint pain. Cirrhotic patients may have, in addition to the symptoms above, dark urine, fluid retention and abdominal swelling. The physical examination may show hepatomegaly, splenomegaly, jaundice, muscle wasting, excoriations, ascites and peripheral edema. Approximately 1-2% of HCV patients have extrahepatic manifestations, most commonly, cryoglobulinemia.
Patients between the ages of 18 and 60 who have detectable HCV RNA, chronically elevated serum alanine aminotransferase levels, and liver biopsies with fibrosis or moderate inflammation should be treated for hepatitis C (3). Therapeutic options were initially limited to interferon alpha??however a number of studies have recently demonstrated that improved sustained response rates can be achieved with regimens that combine ribavirin and interferon alpha. A "sustained" response to therapy is defined as an undetectable level of HCV RNA six months after discontinuation of therapy. Interferon treatment alone results in an initial therapeutic response in 30-35% of patients, however almost half of these patients relapse when therapy is discontinued, resulting in a 15-20% sustained response rate. Combination therapy results in an initial loss of detectable HCV RNA in 50-55% of patients, and a sustained response in 35-45%. Patients infected with HCV genotypes 2 and 3 have better sustained response rates to interferon alpha and combined therapy than patients infected with genotype 1 (4, 7). |
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