Pathogenesis of hepatitis b virus ppt

It is located under the right diaphragm and is divided into right and left lobes. The liver weighs approximately 1. The liver is a highly vascular organ. For example, the liver converts glucose during fasting and stores glycogen as muscle fuel. It produces plasma proteins and filters and detoxifies the blood by removing and harmful or toxins from the body. In addition, the liver removes ammonia from the body and converts it to urea that excreted by the urine Berkowitz, Unfortunately, when there is liver failure or damage to the liver cells; many areas in the body are affected.

The body will have an increased risk of bleeding due to decreased in protein production. Fasting hypoglycemia may occur due to decrease in gluconeogenesis. A decrease. Lastly, jaundice may occur because of the failure of the liver to secrete conjugated bilirubin Berkowitz, Viral hepatitis is a disease which initially affects the liver. Hepatitis has several different routes of transmission and comes in several different forms such as Hepatitis A, B, C, D and E. Below are more details on the pathophysiology of disease.

Viruses enter the blood stream and spread to the liver. They infect the hepatocytes and multiply. They change the antigen structure on the virus site. The body begins to use self-mediated immune response attempting to damage the hepatocytes. In Hep B and C, they can continue this process over and over for years. There are three stage of symptoms: prodromal, icteric and convalescent. Thus, if integration of the HBV genome contributes to hepatocarcinogenesis, it is likely to be secondary to procarcinogenic events that trigger hepatocyte turnover e.

For example, the HBV X HBx gene product has been shown to transactivate cellular genes associated with cellular growth control [ 78 — 80 ]. Furthermore, HBx sequences with C-terminal deletions and point mutations have been detected in chronic hepatitis and HCC [ 82 , 83 ], and since these mutations seem to arise before the development of HCC [ 84 ], these results suggest that deregulated X gene expression from integrated fragments of subviral DNA could play a role in hepatocarcinogenesis [ 67 , 85 ].

Almost all cases of HCC take place after many years of chronic immune-mediated hepatitis [ 6 ] characterized by continuous cycles of low-level liver cell destruction and regeneration that over long periods of time lead to fibrosis, cirrhosis, steatosis, and probably HCC.

Indeed, transgenic mice that produce hepatotoxic quantities of L-HBs [ 91 — 94 ] display hepatocellular injury, regenerative hyperplasia, chronic inflammation, Kupffer cell hyperplasia, oxygen radical production, glutathione depletion, oxidative DNA damage, transcriptional deregulation and aneuploidy that inexorably progresses to HCC. Importantly, the appearance of HCC in these settings occurs despite the absence of cofactors such as viral integration and X gene expression that have been discussed above.

Since the immunological, virological and histological features of this chronic immune-mediated HCC model closely resemble the features of human chronic hepatitis, the results suggest that an ineffective immune response is a critical oncogenic factor during chronic HBV infection in man.

The pathogenetic importance of immune-mediated hepatocellular injury in hepatocarcinogenesis in HBV is strengthened by the fact that hepatocellular carcinoma occurs in the context of necrosis, inflammation and regeneration cirrhosis in several human liver diseases other than hepatitis B, including chronic hepatitis C [ ], alcoholism, [ ] hemochromatosis, [ ] glycogen storage disease, [ ] aantitrypsin deficiency, [ , ] and primary biliary cirrhosis.

If these processes are sustained for a sufficiently long period of time, they would be expected to cause the multiple genetic and chromosomal changes necessary to trigger the development of hepatocellular carcinoma Figure 5. In summary, HBV acts like a stealth virus early in infection, remaining undetected and spreading until the onset of the adaptive immune response several weeks later.

The relative invisibility of HBV to the innate sensing machinery of the cells probably reflects its replication strategy with the replicating viral genome being sheltered within viral capsid particles in the cytoplasm. The inefficient immune response to HBV during chronic HBV infection results in low-level liver cell destruction and regeneration over long periods of time that lead to fibrosis, cirrhosis, steatosis, and eventually HCC.

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Francis V. Chisari , Masanori Isogawa , and Stefan F. Author information Copyright and License information Disclaimer. Corresponding Author: Francis V. Chisari, M. Copyright notice. The publisher's final edited version of this article is available at Pathol Biol Paris. See other articles in PMC that cite the published article.

Abstract The adaptive immune response is thought to be responsible for viral clearance and disease pathogenesis during hepatitis B virus infection. Keywords: cytotoxic T cells, liver cirrhosis, hepatocellular carcinoma, innate immune response, adaptive immune response, chronic infection.

Introduction Viral hepatitis is a necroinflammatory liver disease of variable severity. Open in a separate window. Figure 1. The CD4 T Cell Response The peripheral blood CD4 T cell response to HBV is vigorous, and multispecific in patients with acute hepatitis who ultimately clear the virus, while it is relatively weak in persistently infected patients with chronic hepatitis [ 32 ].

Figure 2. Figure 3. Figure 4. Figure 5. Role of viral proteins In addition to integration, it is possible that certain HBV proteins may directly participate in HCC development. Immune mediated liver injury Almost all cases of HCC take place after many years of chronic immune-mediated hepatitis [ 6 ] characterized by continuous cycles of low-level liver cell destruction and regeneration that over long periods of time lead to fibrosis, cirrhosis, steatosis, and probably HCC.

Summary and Conclusions In summary, HBV acts like a stealth virus early in infection, remaining undetected and spreading until the onset of the adaptive immune response several weeks later. Footnotes Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. References [1] Chisari FV. Rous-Whipple Award Lecture.

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