1 Viral markers
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5 HAV Antigens and Host Antibody Responses
6 Because serologic testing for hepatitis A antibody is likely to be negative this early in the illness, a stool or serum PCR test for HAV would best confirm a diagnosis of acute HAV infection. Anti-hepatitis A IgM is almost always detectable at the onset of symptoms. In the rare case in which the initial test is negative but a strong clinical suspicion for hepatitis A remains, a repeat test is recommended in 1 to 2 weeks. Testing of stool or serum for HAV using PCR-based techniques is not routinely performed for diagnostic purposes.
7 IgM anti-HAV antibodies indicate a recent infection with hepatitis A virus. IgM anti-HAV antibodies generally can be detected in the blood as early as 2 weeks after the initial HAV infection. These antibodies disappear from the blood 3 to 12 months after the infection. IgG anti-HAV antibodies mean that you have had a hepatitis A viral infection. About 8 to 12 weeks after the initial infection with hepatitis A virus, IgG anti-HAV antibodies appear and remain in the blood for lifelong protection (immunity) against HAV.
8 Hepatitis A is an acute illness without a carrier state or chronic phase. Peak AST and ALT levels are commonly greater than 500 units/L. The mean duration of time from HAV exposure to symptom onset is approximately 30 days, and jaundice typically occurs within a week of the onset of prodromal symptoms.
9 HBV Antigens and Host Antibody Responses
10 Serologic testing for the diagnosis of hepatitis B virus (HBV) infection involves measurement of a panel of distinct HBV-specific antigens and host antibodies that react to these antigens
11 The interpretation of these tests can be complicated, and multiple possibilities exist based on the overall panel of response
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42 Following acute HBV infection, the evolution of the pattern of serologic markers depends on the outcome of the host immune response[5]. The likelihood of the patient resolving HBV infection correlates with their age and the strength of the initial immune response to HBV[2,3]. Following acute HBV infection, approximately 90% of adults will resolve the HBV infection, whereas 30 to 90% of young children will fail to resolve the infection and thus develop chronic HBV infection. The weak immune response generated by young children acutely infected with HBV generally corresponds with minimal killing of HBV-infected hepatocytes; for this reason, clinical symptoms suggestive of acute HBV infection are frequently absent in this patient population[8]. For those patients who resolve their infection, HBsAg disappears at about 3 to 6 months, often just prior to the detection of antibodies to hepatitis B surface antigen (anti-HBs). The presence of anti-HBs following acute infection generally indicates recovery and protective immunity against re-infection. In addition, patients with resolution of infection have disappearance of HBeAg and development of antibodies to hepatitis B e antigen (anti-HBe). Patients with resolved infection have persistence of anti-HBc for life, but about 4 to 6 months after the appearance of anti-HBc, the total anti-HBc predominantly consists of IgG. Some patients with self-limited infection, however, may still have low levels of HBV DNA in blood; whether the HBV DNA is part of intact virions remains unknown[8,9].
43 Patients who develop chronic (persistent) HBV infection have a serologic response in the acute phase of HBV infection that is similar to patients who subsequently resolve the HBV infection. With chronic (persistent) HBV infection, HBsAg and anti-HBc (IgG antibodies) generally persist for life and HBV DNA can usually be detected by nucleic acid amplification methods (Figure 4)[5]. The presence of HBsAg for longer than 6 months after acute infection indicates chronic infection. The detection of HBsAg and absence of IgM anti-HBc in a single serum specimen also generally indicates chronic HBV infection. Although most persons with chronic HBV infection are without symptoms, they are at risk for subsequently developing chronic hepatitis, cirrhosis, and livercancer[2]. The continued presence of HBeAg generally reflects higher HBV DNA levels and greater infectiousness. Some patients with chronic HBV infection may have resolution of their HBeAg along with appearance of anti-HBe, and this usually correlates with low (or absent) HBV levels and relatively normal levels of hepatic aminotransferase levels (Figure 5)[5]. Previously, investigators believed that HBV DNA disappeared in all patients with the onset of anti-HBe, but older studies had used the less sensitive HBV DNA hybridization assays[8,10]. Newer, more sensitive PCR assays have shown that greater than 70% of persons who develop anti-HBe have persistent HBV DNA, typically in the range of 200 to 2,000 IU/ml [8,11]. In addition, some patients with chronic HBV infection have absent HBeAg, increased aminotransferase levels, and relatively high HBV DNA levels; these findings generally occur in association with precore or core promoter mutations. These mutations prevent (or diminish) HBeAg formation by an otherwise normally replicating HBV[8,12].
44 HCV Antigens and Host Antibody Responses
45 Do not rely on transaminasesDo not rely on transaminases! There is no correlation between transaminase levels and disease severity. HCV ELISA antibody screening + Antibody means “infected at some point”, need to determine if active or chronic infection HCV RNA PCR confirms or excludes active disease + Viral load means “active hepatitis”
46 Tests for the hepatitis C virusIf your doctor thinks that you may have hepatitis C, he or she may order: A hepatitis C virus test. This is a blood test that looks for antibodies (HCV IgM) against the hepatitis C virus. It shows whether you have been exposed to the virus. A blood test that looks for the genetic material (RNA) of the hepatitis C virus. This test shows whether you are infected with the virus now. A blood test to find out the kind of hepatitis C virus (genotype) you have. Knowing your genotype will help you and your doctor decide if and how you should be treated.
47 Alpha fetoprotein levels are used to screen for hepatocellular carcinoma. This test is not used to determine whether a patient has active hepatitis C virus infection. A positive HCV RNA test result (preferably performed as a quantitative assay) confirms that the patient has chronic HCV infection, and provides the basis for prompt initiation of counseling and pre-treatment evaluation.
48 Alpha-2-macroglobulin Haptoglobin Apolipoprotein A1 GGT Fibro Test and Acti Test are non-invasive diagnostic tools for hepatitis C. Alpha-2-macroglobulin Haptoglobin Apolipoprotein A1 GGT Total bilirubin ALT Fibro Test Acti Test
49 Fibro Test Score Regression Coefficient = 4.467 x log10 (α2macroglobulin “g/L”)- 1.357 x log10 (haptoglobin “g/L”) + 1.017 x log10 (GGT “IU/L”) + x (age “years”) + 1.737 x log10 (bilirubin “μmol/L”) – 1.184 x (apoA1 “g/L”) + 0.301 x Sex (female = 0, male = 1) – 5.54
50 Fibro Test measures the hepatic fibrosis stage with a blood test.Minimal Moderate Severe
51 Acti Test measures the degree of necroinflammatory activity of viral origin (HBV and HCV).Minimal Moderate Severe
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