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Pathology and Immunopathology of Acute and Chronic Hepatitis B
| Content Provider | Semantic Scholar |
|---|---|
| Copyright Year | 2010 |
| Abstract | In this paper, I wilI deseribe the pathologic characteristics of acute and chronic hepatitis B, as derived from our current konwledge of the biology of hepatitis B virus (HBV) (1) and of the immunopathology of the disease (2). Since the exact mechanism of hepatocyte necrosis by HBV is still unknown, some of the information presented here is speculative. Severallines of evidence indicate that HBV is not directly cytopathic for hepatocytes. First, there is no correlation between the amount of HBV antigens in the serum or liver of patients with hepatitis B and the severity of liver damage(36). In fact, the relationship is of ten inverse (7-10). Second, infected hepatocytes containing HBV or its antigens show only minor, if any degenerative changes at light and eleeton rnic-roskopic levels (11).Many HBV carriers have normalliver morphology and function, although their hepatocytes frequently express abundant amounts of HBV or its antigens (12-14). Third, there is no cytopathic effect in cultured human hepatoma cells which actively repIicate HBV and produce mature infectious Dane particles, as recently reported by several groups of investigators (l5-~7). In the absence of a direct viropathic effect, it is likely that the immune response of the patient mediates hepatocyte injury in acute and chronic HBV infection. This is supported by the predominance of lymphocytes and macrophages rather than polymorphonuclear leukocytes in the infected liver. In acute hepatitis B, conspicuous numbers of Iymphocytes and other mononuclear cells infiltrate porta! tracts and sinusoids throughout the hepatic 10bules and are of ten in apposition to hepatocytes. The latter show evidence of cell injury which may present in 2 form s, i.e. ballooning degeneration and cytolysis or coagulative necrosis and formation of acidophilic or apoptotic bodies. Sometimes, Iympocytes are seen within the cytoplasm of hepatocytes (emperipolesis) (l8). Close contact between lymphocytes and damaged hepatocytes (peripolesis) or acidophilic bodies has been deseribed as a characteristic finding in hepatitis B in contrast to one form of non-A, non-B hepatitis which may be mediated by a direct viropathic mechanism. Regeneration in acute viral hepatitis is reflected in mitoses and bi-or multinuCıeation of hepatocytes. The combination of these features,i.e. hepatocyte degeneration and regenaration, sinusoidal cell acıivation, and diffuse inflammation result in the characteristic overall picture of lobular disarray, hepatoeyte plemorphism and hypercellularity (19-28). What is the phenotype, target and effect of the lymphocytes in the liver of patients with hepatitis B ? The life cycle of HBV may shed some light on these questions. Studies of the natural history of hepatitis B suggest that HBV infection proceeds through two stages, an early replicative (permissive) stage and alater non-replicative (rıon-permissive) stage (2931). During acute infection and the initial period of chronic infection, the viral DNA is present in episomal (free or extrachromos~ma1) form and the virus replicates in the hep atocyte with complete transeription of the genome resulting in production of mature infectious virions, HBV, DNA, DNA polymerase, HBsAg, HBcAg and HBeAg. HBV replication appears to occur primariIy in the cytoplasm (32) with concamitant expresion of HBcAg or HBeAg on the cell surface (33). This replicative phase of HBV infection is associated with progressive liver disaese (34-37). Immunohistochemical studies of Iymhocyte subsets in liver sections revealed that CD8 positive lymhocytes accumulated in areas of focal necrosis in acute hepatiıis B and of piecemeal necrosis in chronic active hepatitis B (38-46). These cells probably represent cytotoxic T lymphocytes which recognize HBcAg or HBeAg on the surface of infected cells in the context of class I HLA antigens (2) A series of cytotoxicity studies of peripheral blood lyrnphocytes against autologous hepatocytes in patients with chronic HBV infection suggested that T Iymphocytes were cytotoxic for hepatocytes with HBcAg or HBeAg, but not for hepatocytes with HBsAg, on the cell surface (47-52). if confırmed, it follows that hepatocytes with active HBV replication and expression of nucleocapsid antigens on the cell surface may be attacked by cytotoxic T Iymhocytes. This mechanism may result in the elimination of the virus and termination of the infection. The necrotic debris is phagocytosed by macrophages or Kupffer cells. These phagocytes are recognized by their PAS potive diastase resistant cytoplasm and are seen in the hepatic lobules,often in clusters, and in the portal tracts during the Iate or residual stage of acute hepatitis B. It is not known why a smaIl percentage (less than 5 %) ofpatients with acute hepatitis B does not eliminate the virus and develops chronic hepatitis B. It is very difficult for the Pathologist to recognize transition to chronicity in the liver biopsy specimen of a patient with prolonged viral hepatitis B (Table 28) (53-56). The presence of HBsAg containing groundglass hepatocytes appears to be the only reliable criterion indicating the development of chronicity (53) with the possible exception of piecemeal necrosis in the absence of hepatitis A (55). The extraordinary variations in the course and outcome of chronic hepatitis B may be related to the genetic background of the iııdividual (57-59), modulatory factors such as antibodies to viral antigens or to idiotypes (60-61), serum-, cell-, or liverderived immunoregulatory molecules (62) or immunoregulatory cells (63).Environmenta! factors such as super or coinfection by other viruses may also play a role (see beIowj.For instance, antiviral antibodies such as anti-HBc, can bind to the cell surface and mask HBcAg expression on infected hepatocytes (33) which then may escape immune clearance and support persistence of HBV.Continued active viral replication will result in the development of chronic active |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.klimikdergisi.org/sayilar/72/buyuk/52-57.pdf |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Abnormal degeneration Acute hepatitis Amylases Antigens, Viral Antiviral Agents Balloon Dilatation Biological specimen Biopsy Specimen Biopsy of liver (procedure) CDISC SEND Chronicity Terminology Cell surface Chemical and Drug Induced Liver Injury Coinfection DNS-based Authentication of Named Entities FOCAL (programming language) Fifty Nine Hematological Disease Hepatitis B Core Antigen Hepatitis B Surface Antigens Hepatitis B Virus Hepatitis B e Antigens Hepatitis B, Chronic Hepatitis, Chronic Hepatocyte Hepatolenticular Degeneration Herpesvirus 1, Cercopithecine Hyperplasia Immunoglobulin Idiotypes Leukemia, Myelocytic, Acute Liver diseases Lobule Mathematical morphology Mitosis Murine sarcoma viruses Natural History Necrosis Object lifetime Patients Peripheral Neuropathy Persistence (computer science) Phagocytes Portal System PuTTY Speculative execution Viral hepatitis Virion Virus Replication immunopathology specialty neutrophil non-T, non-B childhood acute lymphoblastic leukemia pathologic cytolysis viral nucleocapsid location |
| Content Type | Text |
| Resource Type | Article |
