Hepatitis B-Relevance of Serological markers

hep.bDr.G.Siva Prasad

ABSTRACT: The purpose of this article is to provide the information regarding markers of Hepatitis B virus infection and their importance in Diagnosis, Treatment and assessment of Prognosis in Hepatitis B cases.

INTRODUCTION:  There are many parameters like HBsAg, Anti HBs, HBeAg, Anti HBe, Anti-HBc and HBV DNA are present in relation with Hepatitis B infection, which creates confusion in patients as well as physicians. And have many doubts like, ‘is HBsAg positive became HBsAg negative?. This article gives proper information regarding the importance of serological markers in Hepatitis B cases and clears these confusions. The WHO has estimated that over 350 million people worldwide are chronically infected with HBV, high prevalence regions include most of Asia.

Hepatitis B is an infection of the liver caused by the hepatitis B virus (HBV), a double stranded DNA virus which replicates by reverse transcription(Hepadnaviridae family).

HBV MARKERS: The parameters used to define and characterise HBV infection include:   1.Serological markers – HBV Antigens and host antibodies.

  1. Virological markers – HBV DNA and genotype.
  2. Biochemical markers – Aminotransferases.
  3. Histological markers – Liver biopsy.

Hepatitis B is a complex disease, which can be defined using above parameters and Management decisions are based on an interpretation of these parameters.

SEROLIGICAL MARKERS:
1.HBsAg: Hepatitis B surface antigen (HBsAg. Australian antigen) is an antigen on the three proteins that make up the envelope of the HBV virion. In acute infection, HBsAg characteristically appears during the incubation period, usually 1 to 6 weeks before clinical or biochemical illness develops, and disappears during convalescence, when the corresponding antibody (Anti HBs) appears (so in acute HBV infection cases HBsAg positive may become HBsAg negative). This anti HBs usually persists for life; its detection therefore implies hepatitis B infection in the past and relative protection against future infection.

In up to 10 % of cases HBsAg persists following acute infection and anti-HBs does not develop. These patients can develop chronic hepatitis or become asymptomatic carriers of the virus. So chronic HBV infection is defined by the persistence of HBsAg for more than six months.

2.Anti-HBs (Antibody to surface antigen): This is the protective antibody that develops with the resolution of acute infection or following the successful vaccination against HBV.

3.Antibody to Core antigen (anti-HBc):  The HBV core antigen is not found as a discrete protein in the serum. It is produced in the hepatocyte cytosol during HBV replication, surrounding the viral genome and the associated polymerse. It is then packaged within an envelope before secretion from the hepatocyte. The antibody to HBV core (anti-HBc) is an antibody to a peptide of this core protein, which has been processed with in an antigen presenting cell. In acute infection, anti-HBc IgM is found in high concentrations which gradually decline, complementing the corresponding increase in anti-HBc IgG over a three to six month period. Elevation of anti-HBc IgM usually signifies acute infection, but low elevations may also occur during the reactivation of chronic HBV. Anti-HBc IgG remains positive for life following exposure to HBV, however, unlike anti-HBs, anti-HBc is not a protective antibody.

4.HBeAg: It is an accessory protein from the precore region of the HBV genome. It is produced during active viral replication and may act as an immunogen or a tolerogen leading to persistent infection.

5.Antibody to e antigen (Anti-HBeAg):  while anti-HBe is not a protective antibody, its appearance usually coincides with a significant immune change associated with lower HBV DNA replication. The loss of HBeAg and the development anti-HBe is termed HBeAg seroconversion, and has been used as an end point for treatment in HBeAg positive people, as it has been shown that seroconversion is associated with a lower risk of disease progression.

KEY POINTS –SEROLOGICAL MARKERS:

  • HBsAg is the only serological marker detected during the first 3-5 weeks after being infected.
  • The persistence of HBsAg for >6 months defines carrier status or chronic hepatitis. This follows 5-10% of infections:
    • Among those who are HBsAg-positive, those in whom HBeAg is also detected in the serum, are the most infectious.
    • Those who are HBsAg-positive and HBeAg-negative (usually anti-HBe-positive) are infectious but generally of lower infectivity.
  • The presence of HBeAg implies high infectivity. HBeAg is usually present for 1½-3 months after the acute illness.
  • Antibodies to hepatitis B core antigen (HBcAg) –  anti-HBc – imply past infection.
  • Antibodies to HBsAg –  anti-HBs – alone imply vaccination
  • Patients with acute infection have raised levels of IgM to HBcAg (anti-HBc) 

VIROLOGICAL MARKERS:
1.HBV DNA: PCR based assays involve a process of lysing the virion and purifying the DNA, which is then amplified and quantified. Initially the unit of measurement was copies/ml, now changed to IU/ml (1IU/ml=5-6 genome copies/ml). The level of 20000 IU/ml (around 105 copies/ml) has been arbitrarily selected as the level below which there is a relatively low likelihood of hepatic damage.  The level of circulating HBV has recently been shown to be the strongest predictor of the development of cirrhosis and hepatocellular carcinoma if more than 20000IU/ml.

HBV DNA testing is now a vital part of the pre treatment evaluation and easement if the efficacy of treatment. HBV DNA testing recommending one pre treatment assay for monitoring of patients not on treatment and up to four assays over 12 months for those on treatment.

2.HBV GENOTYPING: Genotyping is determined by sequencing the HBV genome. There are eight currently recognised genotypes (A-H), which vary geographically with the four most common genotypes being A-D. The most prominent genotypes in the Asia region are B and C. Genotype may have a important influence on disease progression and treatment response. Genotype B has increased rates of HBeAg seroconversion, less aggressive liver diasease and lower rates of HCC. Further more it has been observed that genotypes A and B have better response rates to interferon when compared to genotypes C and D.

BIOCHEMICAL MARKERS-ALANINE AMONOTRANSFERASE(ALT):
Striking transaminase elevations are the hallmark of this disease. High values appear early in the prodromal phase, peak before jaundice is maximal, and slowly fall during the recovery phase. The main biochemical marker used in viral hepatitis is the serum ALT level, used as a surrogate marker for necroinflammation in the liver.

HISTOLOGICAL MARKERES:

LIVER BIOPSY:  the two histological features on liver biopsy used in the assessment of HBV are fibrosis and necroinflammation. Liver fibrosis is usually graded from 0-4 (1-limited portal fibrosis; 2-perportal fibrosis; 3-septal fibrosis linking portal tracts or central vein; 4-cirrhosis with development of nodules and thick fibrous septa). Liver biopsy is the gold-standard investigation for determining the stage of HBV.

    SEROLOGICAL,VIROLOGICAL,BIOCHEMICAL PROFILES OF HBV

  HBsAg Anti-HBs Anti-Hbc total Anti-Hbc IgM HBeAG Anti-HBe HBV DNA ALT
Acute HBV + + + + +/- High
Natural HBV immunity- resolved infection + + +/- Absent N
Vaccination + Absent N
Chronic HBeAg Positive
Immune tolerance phase + + + >20000

IU/ml

N
Immune clearance phase + + + +/- >20000

IU/ml

Chronic HBeAg negative
Immune control phase + + + <2000

IU/ml

N
Immune clearance phase + + + >2000

IU/ml

Reactivation of HBV + + +/- + +/- >20000

IU/ml

+=positive. -=negative. ↑=elevated. N=normal.

SUMMARY: While hepatitis B is a complex disease, an understanding of the parameters used to define HBV infection is crucial for the assessment and management. Whatever the mode of treatment either Homoeopathy or Allopathy, the prognostic criteria like HBeAg seroconversion, HBV DNA quantitative analysis are play a key role in the planning of treatment.

BIBILIOGRAPHY:

  1. Harrison’s Principles of Internal Medicine – 17ed.
  2. Davidson’s Principles and practice of Medicine-20 ed.
  3. wikipedia.org 

DR.G.SIVA PRASAD, MD (H)
GUDIVADA.
EMAIL: drsivahomoeo@gmail.com
CELL:9550368653

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