Acute Infection

 In an HBsAg-positive individual, the differential diagnosis should include acute hepatitis B, reactivation of chronic HBV infection, HBeAg seroconversion to anti-HBe flare, superinfection by other hepatitis viruses, and liver injury resulting from other causes (e.g., drug-induced, alcoholic, or ischemic hepatitis). Accurate diagnosis requires testing for serologic markers and sequential studies.

The first antibody to appear during an acute HBV infection is antibody to hepatitis B core antigen (anti-HBc). Anti-HBc becomes measurable shortly after HBsAg is detected and reaches peak levels within several weeks of onset of infection. It persists long after the disappearance of HBsAg. Initially, the predominant immunoglobulin class of anti-HBc is IgM. Early after the development of serologic tests for HBV markers, when tests for anti-HBs were less sensitive than current assays, a window period between the loss of HBsAg and the appearance of anti-HBs was recognized. During this infrequently encountered window, or when levels of HBsAg do not reach detection thresholds, the detection of IgM anti-HBc is the sole marker of acute HBV infection. Over several weeks to months, the titer of IgM anti-HBc falls, tending to become undetectable after 6 months. Total anti-HBc reactivity declines at a considerably slower rate; the predominant immunoglobulin form of anti HBc during the late recovery phase is IgG. This IgG anti-HBc persists in slowly declining titers for many years to decades after acute infection.

Within a few days to 1 or 2 weeks of the appearance of HBsAg, hepatitis Be antigen (HBeAg) also becomes detect able in the circulation of acutely infected individuals. HBeAg, a nonstructural nucleocapsid protein, is a marker of HBV replication; its presence is correlated with the presence of complete HBV particles and HBV DNA in the circulation. In acute HBV infection, patients are most infectious during the period in which HBeAg can be detected. In self-limited HBV infection, HBeAg disappears before HBsAg disappears. With the disappearance of HBeAg, its corresponding antibody, anti-HBe, becomes detectable and persists for a prolonged period.

HBV DNA, and possibly HBV virions, may persist in circulating immune complexes. The viral genome can remain in an active form in peripheral blood mononuclear cells for more than 5 years after complete clinical and serologic recovery from acute viral hepatitis B.

Chronic Infection

 Recent statistics have indicated that 800,000 to 1.4 million persons are living with chronic hepatitis B infection; 3000 patients die annually as the result of chronic liver disease associated with hepatitis B.

Progression from acute to chronic HBV is influenced by a patient’s age at acquisition of the virus. Clinical expression of HBV infection is high in Asian but low in Western countries. In the Far East, where HBV infection is acquired perinatally, the immune system does not recognize the difference between the virus and the host. Consequently, a high level of immunologic tolerance emerges. The cellular immune responses to hepatocyte membrane HBV protein associated with acute hepatitis do not occur and chronic, usually lifelong, infection is established in more than 90% of infected patients. In Western countries, most acute HBV infections occur during adolescence and early adulthood. These segments of immunocompetent, HBV-infected patients produce a strong cellular immune response to foreign HBV proteins expressed by hepatocytes, with resulting, clinically apparent acute hepatitis. All but about 1% of infected patients clear the HBV infection.

Hepatitis B virus can lead to chronic infection and HBV patients have been shown to have the viral DNA actually incorporated into the DNA of their liver cells. This integration may be an important factor in the eventual development of liver cell cancer, hepatocellular carcinoma, a well-known long term outcome of chronic HBV infection.

The hepatitis B virus is not directly cytopathic and the hepatocellular necrosis results from the host’s immune response to the viral antigens of the replicating virus present in infected hepatocytes. Cytotoxic T cells recognize histocompatibility and HBcAg receptors on the liver cell membrane surface. Attachment of T cells to the receptors, together with natural killer (NK) cells, results in hepatocellular necrosis; in the setting of an effective immune response, HBV replication ceases.

Studies of peripheral blood mononuclear cells have revealed that patients with acute HBV produce vigorous T cell responses against multiple HBV antigenic determinants located on the viral core, envelope, and polymerase proteins, whereas patients with chronic infection have a very weak or undetectable cellular immune response. These findings suggest that a prompt, vigorous, and broad-based cellular immune response results in clearance of the virus from the liver, whereas a qualitatively or quantitatively less efficient or restricted immune response may permit the persistence of virus and the development of ongoing, immunologically mediated liver cell injury. In addition to a patient’s immune response, viral factors (HBV genome) may also be important in determining the course of HBV infection.

Chronic HBV occurs in two phases, a more infectious replicative phase (high levels of circulating virions, HBV DNA, HBeAg) and a minimally infectious nonreplicative phase (few virions, circulating spherical and tubular forms of HBsAg, undetectable HBV DNA and HBeAg, but circulating anti HBe and integrated HBV DNA in hepatocytes). In patients with chronic HBV infection, HBsAg remains detectable for more than 6 months and, in rare cases, HBsAg persists for decades. Spontaneous HBsAg clearance in chronic infection is unusual. Clearance of the virus results in complete clinical and histologic recovery, ultimately leaving the patient with a serologic pattern characterized by hepatitis B core antibody (IgG anti-HBc) and anti-HBs, with the latter conferring immunity.

Asymptomatic individuals in whom test results for HBsAg remain positive are labeled HBsAg carriers. Other chronically infected HBsAg-positive individuals may have clinical or laboratory evidence of chronic liver disease. Anti-HBc is present in all chronic HBV infections. In most chronically infected patients, IgM anti-HBc is a minor fraction of total anti-HBc reactivity. In all patients with HBV infection, HBeAg can be detected during the early phase of infection, but in contrast to the situation with acute self-limited HBV infection, HBeAg may remain detectable in chronically infected individuals for many months to years. In these patients, HBV DNA is also readily detected in the circulation. The presence of circulating HBV DNA is highly correlated with the presence of whole virus replication, and thus with the potential infectivity of the patient. HBV DNA is also detectable in the hepatocytes of individuals with chronic HBV infection. For a variable but generally prolonged period, this hepatic HBV DNA is present in a free, episomal replicating form. In some patients, HBV DNA becomes integrated into the genome of the host hepatocyte. Viral replication may diminish spontaneously over time or after treatment, signaled by the decline or disappearance of serum HBV DNA, loss of HBeAg, and appearance of anti-HBe in the circulation, as detected by commercial assays. Research has suggested that both anti-HBe and anti-HBs may be present early in chronic hepatitis B complexed to HBeAg and HBsAg.

In 10% to 40% of patients with chronic HBV infection, anti-HBs is detected concurrently with HBsAg. The presence of anti-HBs does not signal reduced infectivity or imminent clearance of HBsAg.

Carrier State

There are an estimated 400 to 500 million HBV carriers worldwide. In the United States, 50,000 to 100,000 people acquire HBV infection each year, even though a highly effective vac cine is available. Immunocompromised patients, including those with human immunodeficiency virus (HIV) infection, are at increased risk for chronic HBV infection. Age at the time of acquisition of HBV infection is a major determinant of chronicity, as reflected by the development of the HBsAg carrier state. As many as 90% of infected neonates become carriers. The rate falls progressively with increasing age at the time of infection, so that only 1% to 10% of newly infected adults fail to clear HBsAg. Another important risk factor for chronicity is the presence of intrinsic or iatrogenic immunosuppression. Immunosuppressed individuals are at increased risk of becoming carriers after HBV infection. Gender is a determinant of chronicity. Women are more likely than men to clear HBsAg; therefore, men predominate in all populations of HBsAg carriers.

The worldwide prevalence of the HBsAg carrier state varies widely. In the United States, as in many Western nations, carriers account for approximately 0.2% of the general population. However, among certain groups (e.g., homosexual men, intra venous drug abusers) in the general population, carrier rates 4 to 10 times greater have been identified. Carrier rates as high as 25% have been recognized among Alaskan natives in some Alaskan villages.

Perinatal transmission continues to occur. This rate should be reduced significantly by the implementation of routine screening of all pregnant women for HBsAg, followed by vaccination of their newborns. Hepatitis B vaccination is gradually being incorporated into routine infant immunization programs. A newer multivalent, triple-antigen HBV vaccine should have wide practical application.

Carriers can be divided into two categories based on differing infectivity, depending on the presence in their serum of another antigen, HBeAg, or its antibody (anti-HBe). The types of carrier states include the following:

 • The more frequently identified carriers have anti-HBe in their serum and are at a later stage of infection.

• Anti-HBe carriers are less infectious but may transmit infection through blood transfusion.

• HBsAg-positive carriers will become anti-HBe–positive carriers at a rate of about 5% to 10%/year.

• All HBsAg-positive individuals must be excluded from giving blood for transfusion.

 • About one in four carriers has HBeAg in their serum. It is likely that these individuals have recently become carriers and that their blood is highly infectious.

 • Patients with HBeAg-negative chronic HBV infection, in which precore or core promoter gene mutations preclude or reduce the synthesis of HBeAg, accounts for an increasing proportion of cases. These patients tend to have progressive liver injury, fluctuating liver enzyme activity, and lower levels of HBV DNA than patients with HBeAg-reactive HBV infection.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم شؤون المعارف ينظم دورة متقدمة في تحقيق المخطوطات لملاكاته

قسم الشؤون الفكرية يصدر العدد العشرين من مجلة دراسات إفريقية

المجمَع العلمي يكرم الأساتذة المشاركين في مشروع الدورات القرآنية الصيفية في كربلاء

العتبة العباسية المقدسة تختتم فعاليات البرنامج المركزي الأسبوعي لمنتسبيها

المزيد

الآخبار الصحية

تحذير من "عدوى بكتيرية" تسبب نوبات قلبية

ماذا يحصل لجسمك عند التوقف عن استخدام الزيت في الطهي؟

الأمل في كبسولة.. "فيتامين شهير" يبطئ التقدم في العمر

اشتهاء أطعمة بشكل مفاجئ.. ناقوس خطر للسرطان ؟!

المزيد

الآخبار التكنلوجية

زلزال أفغانستان يحصد أكثر من ألف قتيل.. ويدمر آلاف المنازل !

ناجٍٍ وحيد من انزلاق أرضي.. دمّر قرية سودانية بأكملها !

نهر الفرات.. مورد مائي بين الندرة والتقاسم

ما السر وراء مشية إيلون ماسك الغريبة والسريعة ؟

المزيد

مواضيع ذات صلة

Pathogenesis and clinical significance of HIV

Transmission of HIV

HIV replication

Hepatitis D

Prevention and Treatment of hepatitis B

Flaviviridae

Togaviridae

Caliciviridae

Picornaviridae

Laboratory Assays of Hepatitis B

Epidemiology of Hepatitis B

Hepatitis A