Chronic hepatitis B: stages of HBV infection

In the life of the hepatitis B virus, two periods are distinguished - the period of virus replication, accompanied by the activity of the inflammatory process in the liver, and the period of virus integration, during which the activity of inflammation subsides and the remission phase of the disease begins (inactive phase). The marker of the replication phase is HBeAg.

In this regard, in the classification of chronic viral hepatitis B it is advisable to distinguish:

• phase associated with viral replication (i.e. active period of varying severity, HBeAg-positive);
• phase associated with integration of the virus (i.e., a virtually inactive period or period of minimal activity, HBeAg-negative).

It is also necessary to distinguish a mutant HBeAg-negative variant of chronic hepatitis with persistent replicative activity.

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Stages of HBV infection

Newborns are in a state of immune tolerance. A significant amount of HBV DNA circulates in the blood and HBeAg is detected, but transaminase activity is normal, and liver biopsy reveals a picture of mild chronic hepatitis.

In children and young adults, the immune clearance stage is observed. The serum HBV DNA content falls, but HBeAg remains positive. Mononuclear cells in zone 3 are mainly OKT3 (all T cells) and T-8 lymphocytes (cytotoxic suppressors).

HBeAg and possibly other viral antigens appear on the hepatocyte membrane. During this period, the patient is highly contagious and liver inflammation progresses rapidly.

Phases of HBV infection

	Replication phase	Integration phase
Contagiousness	Tall	Low
Serum indices
HBeAg	+	-
Anti-NVE	-	+
HBV DNA	+	-
Hepatocytes
Viral DNA	Non-integrated	Integrated
Histology	Active HAG, CPU	Inactive HPG, CP, HCC
Portal Zone
Quantity:
Suppressors	Enlarged	Normal
Inductors	Reduced	Reduced
Treatment	Antiviral (?)	?

CAH - chronic active hepatitis; LC - liver cirrhosis; CPH - chronic persistent hepatitis; HCC - hepatocellular carcinoma.

Stages of HBV infection

Age of patients Stage HBV DNA content AST activity Biopsy Newborns Immune tolerance +++ Normal HCG (light) 10-20 years Immune clearance ++ +++ HCG (heavy) Over 35 years old Latent Low Normal Cirrhosis, HCC

CH - chronic hepatitis; HCC - hepatocellular carcinoma.

Ultimately, in elderly patients the disease becomes moot, the circulating HBV DNA content is low, the serum HBeAg test is negative, and the anti-HBe test is positive. Hepatocytes secrete HBsAg, but core markers are not produced.

Serum transaminase activity is normal or moderately elevated, and liver biopsy reveals a picture of inactive chronic hepatitis, cirrhosis, or HCC. In some young patients, however, viral replication continues relentlessly, and HBV DNA can be detected in the nuclei of hepatocytes in integrated form. The inflammatory infiltrate resembles that of autoimmune chronic hepatitis with a large number of T-helper lymphocytes and B-lymphocytes.

There is considerable time discrepancy between these different phases in both children and adults. The course of infection is also influenced by the geographical features of the region. Residents of Asia are particularly prone to a prolonged phase of viremia with immune tolerance.

Hepatitis B markers in the liver

HBsAg, usually in high titers, is found in healthy carriers. In the replicative phase, HBeAg is undoubtedly located in the liver. Its distribution may be diffuse in asymptomatic carriers, patients with inactive disease and immunodeficiency, and focal in patients with severe liver inflammation or late-stage disease.

HBV X-protein can be detected in liver biopsy and correlates with viral replication.

HBV DNA can be detected in formalin-fixed, paraffin-embedded liver tissue using polymerase chain reaction (PCR).

HBeAg can be detected by immunoelectron microscopy in the endoplasmic reticulum and cytosol.