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, in which the activity of inflammation subsides occurs the phase of remission of the disease (inactive phase). The marker of the replication phase is HBeAg.

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

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

It should also be allocated a mutant HBeAg-negative variant of chronic hepatitis with persistent replicative activity.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]

Stages of HBV infection

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

Children and young people have a stage of immune clearance. The content of serum HBV-DNA falls, but HBeAg remains positive. Mononuclear cells in zone 3 are mainly OCT3 (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 there is a rapid progression of the inflammation of the liver.

Phases of HBV infection

	The replication phase	Integration phase
Contagiousness	High	Low
Serum counts
HBeAg	+	-
Anti-HBe	-	+
HBV-DNA	+	-
Hepatocytes
Viral DNA	Non-integrated	Integrated
Histology	Active HAG, CP	Inactive HCP, CP, HCC
Portal area
Amount:
Suppressors	Increased	Normal
Inducers	Decreased	Decreased
Treatment	Antiviral (?)	?

XAG - chronic active hepatitis; CP - cirrhosis of the liver; ChPG - chronic persistent hepatitis; Fcc hepatocellular carcinoma.

Stages of HBV infection

Age of patients Stage The content of HBV-DNA ASAT activity Biopsy Newborns Immune Tolerance +++ Normal HG (light) 10-20 years old Immune clearance ++ +++ HG (Heavy) Older than 35 years Latent Low Normal Cirrhosis, HCC

HG - chronic hepatitis; HCC - hepatocellular carcinoma.

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

The activity of serum transaminases is normal or moderately elevated, and liver biopsy reveals a picture of inactive chronic hepatitis, liver cirrhosis or HCC. In some young patients, viral replication, however, continues steadily, and HBV-DNA can be detected in the nucleus of hepatocytes in an integrated form. Inflammatory infiltrate resembles that of autoimmune chronic hepatitis with a large number of T-lymphocytes-helpers and B-lymphocytes.

There are significant mismatches in time between these different phases, both in children and in adults. The geographical features of the region also influence the course of the infection. Residents of Asia are particularly characterized by a prolonged phase of viremia with immune tolerance.

Markers of hepatitis B 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 can be diffuse in asymptomatic carriers, patients with inactive disease and immunodeficiency and focal in patients with a marked inflammatory process in the liver or late stage of the disease.

X-protein HBV can be detected in a liver biopsy and correlated by viral replication.

HBV-DNA can be detected in fixed formalin, encapsulated in paraffin of the hepatic tissue by polymerase chain reaction (PCR).

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