Студопедия
Случайная страница | ТОМ-1 | ТОМ-2 | ТОМ-3
АвтомобилиАстрономияБиологияГеографияДом и садДругие языкиДругоеИнформатика
ИсторияКультураЛитератураЛогикаМатематикаМедицинаМеталлургияМеханика
ОбразованиеОхрана трудаПедагогикаПолитикаПравоПсихологияРелигияРиторика
СоциологияСпортСтроительствоТехнологияТуризмФизикаФилософияФинансы
ХимияЧерчениеЭкологияЭкономикаЭлектроника

Hepatitis B

Читайте также:
  1. Hepatitis A
  2. Hepatitis C
  3. Hepatitis D
  4. Hepatitis E
  5. Hepatitis viruses
  6. Persistence of the virus. Hepatitis D

Background: In 1965, Blumberg et al reported the discovery of the hepatitis B surface antigen (HBsAg), also known as Australia antigen, and its antibody, hepatitis B surface antibody (HBsAb). A few years later, in 1970, Dane visualized the hepatitis B virus (HBV) virion. Since then, considerable progress has been made regarding the epidemiology, virology, natural history, and treatment of this hepatotropic virus.

Hepatitis B is a worldwide health care problem, especially in developing areas. An estimated one third of the global population has been infected with this virus. Approximately 350 million people are lifelong carriers, and only 2% spontaneously seroconvert annually. Ongoing vaccination programs appear to be promising in the attempt to decrease the prevalence of this disease.

HBV is transmitted hematogenously and sexually. The outcome of this infection is a complicated viral-host interaction resulting in either an acute symptomatic disease or an asymptomatic disease. Patients may become immune to HBV or may develop a chronic carrier state. Later consequences are cirrhosis and the development of hepatocellular carcinoma (HCC). Antiviral treatment may be effective in approximately one third of the patients who receive it, and for selected candidates, liver transplantation currently seems to be the only viable treatment for the latest stages of this disease.

Pathophysiology: HBV is a Hepadna virus. It is an extremely resistant strain capable of withstanding extreme temperatures and humidity. It can survive when stored for 15 years at -20°C, for 24 months at -80°C, for 6 months at room temperatures, and for 7 days at 44°C. The viral genome consists of a partially double-stranded circular DNA of 3.2 kilobase pairs that encodes 4 overlapping open reading frames, as follows:

An upstream region for the S and C genes has been found, named pre-S and pre-C, respectively. The structure of this virion is a 42-nm spherical double-shelled particle consisting of small spheres and rods, with an average width of 22 nm.

The S gene encodes the viral envelope. There are 5 mainly antigenic determinants: a, common to all HBsAg, and d, y, w, and r, which are epidemiologically important. The core antigen, HBcAg, is the protein that encloses the viral DNA. It also can be expressed on the surface of the hepatocytes, initiating a cellular immune response. The e antigen, HBeAg, comes from the core gene and is a marker of active viral replication. Usually, HBeAg can be detected in patients with circulating serum HBV DNA.

The best indication of active viral replication is the presence of HBV DNA in the serum. Hybridization or more sensitive polymerase chain reaction (PCR) techniques are used to detect the viral genome in the serum.

The role of the X gene is to encode proteins that act as transcriptional transactivators aiding viral replication. Evidence strongly suggests that these transactivators may be involved in carcinogenesis.

The production of antibodies against HBsAg confers protective immunity and can be detected in patients who have recovered from HBV infection or in those who have been vaccinated. Antibody to HBcAg is detected in almost every patient with previous exposure to HBV. The immunoglobulin, immunoglobulin M (IgM) subtype, is indicative of acute infection or reactivation, while the immunoglobulin G (IgG) subtype is indicative of chronic infection. With this marker alone, one cannot understand the activity of the disease. Antibody to HBeAg is suggestive of a nonreplicative state, and the antigen has been cleared.

With the newest PCR techniques, scientists are able to identify variations in the HBV genome (variant strains). A mutation at the 1896 nucleotide (precore/core region) processing the production of the HBeAg was identified first. The prevalence of this mutant virus varies among different areas. Estimates indicate that 50-60% of the patients from southern Europe, the Middle East, Asia, and Africa and 10-30% of patients in the United States and Europe who have chronic HBV infection have been infected by this strain.

The pathogenesis and clinical manifestations are due to the interaction of the virus and the host immune system. The latter attacks the HBV and causes liver injury. Activated CD4+ and CD8+ lymphocytes recognize various HBV-derived peptides located on the surface of the hepatocytes, and an immunologic reaction occurs. Impaired immune reactions (eg, cytokine release, antibody production) or relatively tolerant immune status results in chronic hepatitis. In particular, a restricted T cell–mediated lymphocytic response occurs against the HBV-infected hepatocytes.

The final state of the disease is cirrhosis. Patients with cirrhosis and HBV infection are likely to develop HCC. In the United States, the most common presentation is that of patients of Asian origin who acquired the disease as newborns (vertical transmission). Four different stages have been identified in the viral life cycle.

The first stage is immune tolerance. The duration of this stage for healthy adults is approximately 2-4 weeks and represents the incubation period. For newborns, the duration of this period often is decades. Active viral replication is known to continue despite little or no elevation in the aminotransferase levels and no symptoms of illness.

In the second stage, an inflammatory reaction with a cytopathic effect occurs. HBeAg can be identified in the sera, and a decline of the levels of HBV DNA is seen. The duration of this stage for patients with acute infection is approximately 3-4 weeks (symptomatic period). For patients with chronic infection, 10 years or more may elapse before cirrhosis develops.

In the third stage, the host can target the infected hepatocytes and the HBV. Viral replication no longer occurs, and HBeAb can be detected. The HBV DNA levels are lower or undetectable, and aminotransferase levels are within the reference range. In this stage, an integration of the viral genome into the host's hepatocyte genome takes place. HBsAg still is present.

In the fourth stage, the virus cannot be detected and antibodies to various viral antigens have been produced. Different factors have been postulated to influence the evolution of these stages, including age, sex, immunosuppression, and co-infection with other viruses.

Eight different genotypes A through H representing a divergence of the viral DNA at around 8% have been identified. The prevalence of the genotypes varies in different countries. The progression of the disease seems to be more accelerated, and the response to treatment with antivirals is less favorable for patients infected by genotype C compared with those infected by genotype B

History: The spectrum of the symptomatology varies from subclinical hepatitis to icteric hepatitis to hyperacute, acute, and subacute hepatitis during the acute phase and from an asymptomatic carrier state to chronic hepatitis, cirrhosis, and HCC during the chronic phase.

Physical: The physical examination findings vary from minimal to impressive (patients with hepatic decompensation) according to the stage of disease.

Lab Studies:

Imaging Studies:

Procedures:

Histologic Findings: Although liver biopsy is not indicated for patients with acute hepatitis B, the findings are predominantly lobular, with degenerative and regenerative hepatocellular changes and accompanying inflammation. Necrosis may be predominantly centrilobular.

Ground-glass cells are seen in approximately 50-75% of livers affected by chronic HBV infection, and they stain positive for HBsAg (see Image 1). Immunohistochemical staining of the specimen can help identify the presence of HBsAg or HBcAg (ie, chronic infection).

Staging:

Medical Care: Therapy is currently recommended for patients with evidence of chronic active disease (ie, high aminotransferase levels, positive HBV DNA findings, HBeAg). See the Medication section. Currently, interferon alfa (IFN-a), lamivudine, adefovir dipivoxil, and entecavir are the main drugs approved globally, although ongoing trials are investigating new types of medications, such as tenofovir disoproxil in combination with emtricitabine, BL-thymidine (L-dT), DAPD, clevudine (l-FMAU), thymosin, and therapeutic vaccines. No clear-cut guidelines are available as to which medication should be chosen.

Patients who have lost HBeAg and in whom HBV DNA is undetectable have an improved clinical outcome (ie, slower rate of progression, prolonged survival without complications, reduced rate of HCC, and clinical and biochemical improvement after decompensation).

Special attention must be given to patients on transplantation lists. Initiation of treatment with adefovir or entecavir or in combination with lamivudine is of cardinal importance before and after liver transplantation to achieve viral suppression and to prevent recurrence of the disease after the procedure.

Surgical Care: Orthotopic liver transplantation (OLT) is the treatment of choice for patients with fulminant hepatic failure who do not recover and for patients with end-stage liver disease. The implementation of hepatitis B immunoglobulin (HBIG) during and post-OLT period, and of lamivudine or adefovir in the pre-OLT period and post-OLT period, dramatically improves the recurrence rate of HBV infection.

Diet:


Drug Category: Antivirals -- Interfere with replication; weaken or abolish viral activity ….Interferon alfa-2b (Intron A) or alfa-2a (Roferon-A) -- Protein product manufactured by recombinant DNA technology. Mechanism of antiviral activity is not clearly understood. However, modulation of host immune responses enhances cytolytic T-cell activity; stimulates natural killer cell activity and amplifies HLA class I protein on infected cells. Direct antiviral activity activates viral ribonucleases, inhibits viral entry to cells, and inhibits viral replication. Direct antifibrotic effect has been postulated. Prior to initiation of therapy, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cells, and bone marrow hairy cells; monitor periodically (eg, monthly) during treatment to determine response to treatment; if patient does not respond within 4 mo, discontinue treatment. If a response occurs, continue treatment until no further improvement is observed. Whether continued treatment is beneficial after that time remains unknown….

Entecavir (Baraclude) -- Guanosine nucleoside analogue with activity against HBV polymerase. Competes with natural substrate deoxyguanosine triphosphate to inhibit HBV polymerase activity (ie, reverse transcriptase). Less effective for lamivudine-refractory HBV infection. Indicated for treatment of chronic HBV infection. Available as tab and as oral solution (0.05 mg/mL; 0.5 mg = 10 mL).

 

Telbivudine (Tyzeka) -- Nucleoside analogue approved by FDA for chronic hepatitis B treatment. Inhibits hepatitis B viral DNA polymerase. Indicated for patients with evidence of ongoing hepatitis B viral replication and either persistent elevated aminotransferase activity or histologic evidence of active liver disease. Consider for patients who did not or are unlikely to respond to interferon or for patients who cannot tolerate interferon. Emergence of resistance is major drawback of nucleoside analogue monotherapy..

 

 


Дата добавления: 2015-10-29; просмотров: 144 | Нарушение авторских прав


Читайте в этой же книге: Ray Bradbury. Henry the Ninth | Hepatitis D | Hepatitis E | Hepatitis viruses |
<== предыдущая страница | следующая страница ==>
Hepatitis A| Hepatitis C

mybiblioteka.su - 2015-2024 год. (0.01 сек.)