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Figure 15 3 shows the typical course of HCV infection HCV is a single-stranded RNA virus (hepacivirus) with properties similar to those of flavivirus At least six major genotypes of HCV have been identified In the past, HCV was responsible for over 90% of cases of posttransfusion hepatitis, yet only 4% of cases of hepatitis C were attributable to blood transfusions Over 50% of cases are transmit-
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HDV is a defective RNA virus that causes hepatitis only in association with hepatitis B infection and specifically only in the presence of HBsAg; it is cleared when the latter is cleared HDV may coinfect with HBV or may superinfect a person with chronic hepatitis B, usually by percutaneous exposure When acute hepatitis D is coincident with acute HBV infection, the infection is generally similar in severity to acute hepatitis B alone In chronic hepatitis B, superinfection by HDV appears to carry a worse short-term prognosis, often resulting in fulminant hepatitis or severe chronic hepatitis that progresses rapidly to cirrhosis In the 1970s and early 1980s, HDV was endemic in some areas, such as the Mediterranean countries, where up to 80% of HBV carriers were superinfected with it In the United States, HDV occurred primarily among injection
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Figure 15 3 The typical course of acute and chronic hepatitis C (ALT, alanine aminotransferase; Anti-HCV, antibody to hepatitis C virus by enzyme immunoassay; HCV RNA [PCR], hepatitis C viral RNA by polymerase chain reaction)
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reduce the risk of transfusion-associated hepatitis C from 10% in 1990 to about 1 case per 2 million units today
ted by injection drug use Intranasal cocaine use, body piercing, tattoos, and hemodialysis may be risk factors The risk of sexual and maternal neonatal transmission is low and may be greatest in a subset of patients with high circulating levels of HCV RNA Having multiple sexual partners may increase the risk of HCV infection Transmission via breast-feeding has not been documented An outbreak of hepatitis C in patients with immune deficiencies occurred in some recipients of intravenous immune globulin, and nosocomial transmission has occurred via multidose vials of saline used to flush Portacaths, through reuse of disposable syringes and contamination of shared saline bags and radiopharmaceutical and sclerosant vials, and between hospitalized patients on a liver unit Covert transmission during bloody fisticuffs has even been reported In many patients, the source of infection is unknown Coinfection with HCV is found in at least 30% of persons infected with HIV; HIV infection leads to an increased risk of acute hepatic failure and more rapid progression of chronic hepatitis C to cirrhosis; in addition, HCV increases the hepatotoxicity of highly active antiretroviral therapy There are more than 27 million HCV carriers in the United States and another 13 million previously exposed persons who have cleared the virus The incubation period averages 6 7 weeks, and clinical illness is often mild, usually asymptomatic, and characterized by waxing and waning aminotransferase elevations and a high rate (> 80%) of chronic hepatitis In pregnant patients, serum aminotransferase levels frequently normalize despite persistence of viremia, only to increase again after delivery HCV is a pathogenetic factor in mixed cryoglobulinemia and membranoproliferative glomerulonephritis and may be related to lichen planus, autoimmune thyroiditis, lymphocytic sialadenitis, idiopathic pulmonary fibrosis, sporadic porphyria cutanea tarda, monoclonal gammopathies, and lymphoma Hepatitis C may induce insulin resistance (which in turn increases the risk of hepatic fibrosis), and the risk of type 2 diabetes mellitus is increased in persons with chronic hepatitis C Hepatic steatosis is a particular feature of infection with HCV genotype 3 and may also occur in patients with risk factors for fatty liver (see below) Diagnosis of hepatitis C is based on an enzyme immunoassay that detects antibodies to HCV Anti-HCV is not protective, and in patients with acute or chronic hepatitis its presence in serum generally signifies that HCV is the cause Limitations of the enzyme immunoassay include moderate sensitivity (false-negatives) for the diagnosis of acute hepatitis C early in the course and in healthy blood donors and low specificity (false-positives) in some persons with elevated -globulin levels In these situations, a diagnosis of hepatitis C may be confirmed by using an assay for HCV RNA and, in some cases, a supplemental recombinant immunoblot assay (RIBA) for anti-HCV Most RIBA-positive persons are potentially infectious, as confirmed by use of polymerase chain reaction-based tests to detect HCV RNA Occasional persons are found to have anti-HCV in serum, confirmed by RIBA, without HCV RNA in serum, suggesting recovery from HCV infection in the past Testing donated blood for HCV has helped
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