Q&A: Pathophysiology of Hepatitis B Viral Infection

Hepatitis B virus (HBV) infection is a global public health problem. The spectrum of clinical manifestations of HBV infection varies in both acute and chronic disease. During the acute phase, manifestations range from subclinical hepatitis to anicteric hepatitis, icteric hepatitis, and fulminant hepatitis; during the chronic phase, manifestations range from an asymptomatic carrier state to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The clinical outcome of HBV infection depends upon the age at infection, the level of HBV replication, and the immune status of the host.

This article is for Medical Students & Professionals

This is a Question & Answer revision article designed for medical students and professionals preparing for the PLAB, MRCP or USMLE examinations. They are based on actual questions from these examinations. You may find the Hepatitis B article more useful, or one of our many articles on Diseases & Conditions, Medical Syndromes, Health & Wellness or Home Remedies.

In this article:
Viral characteristics and diagnosis
MCQ exam: clinical scenario
MCQ exam: answer
MCQ exam: explanation

Viral characteristics and diagnosis

Hepatitis B virus (HBV) belongs to the family of hepadnaviruses. The replication cycle of HBV begins with attachment of the virion to the hepatocyte membrane. The receptor for HBV (and hepatitis D virus) has been identified as a bile salt transporter, sodium taurocholate cotransporting polypeptide (NTCP), which binds to the pre-S1 region of the HBV envelope. The virion is uncoated in the hepatocyte cytoplasm and the viral genome enters the hepatocyte nucleus.

Inside the hepatocyte nucleus, synthesis of the plus strand HBV DNA is completed and the viral genome is converted into a covalently closed circular DNA (ccc DNA). The HBV genome replicates by reverse transcription via an RNA intermediate, the pregenomic RNA.

The diagnosis of acute HBV infection is based upon the detection of hepatitis B surface antigen (HBsAg) and IgM antibody to hepatitis B core antigen (anti-HBc). Treatment of acute HBV depends upon the clinical setting. However, appropriate measures should be taken to prevent infection in all exposed contacts, and hepatitis B immune globulin and hepatitis B vaccine should be administered to all household and sexual contacts who are not known to be immune.

The diagnosis of chronic HBV infection is based upon the persistence of hepatitis B surface antigen (HBsAg) for greater than six months. A number of risk factors for HBV infection have been identified, providing a rationale for screening.

MCQ exam: clinical scenario

A young man with anorexia, nausea, and brown urine is thought to have acute viral hepatitis following hepatitis B infection. Screening serologic studies show that IgM anti-HBV core AB is positive.

Which of the following mechanisms is likely to explain the hepatic injury in this patient?

a) Direct injury by viral surface antigen
b) Hepatocyte lysis by IgM antibody to viral core antigen
c) Obstruction of the microcirculation of the liver by B lymphocytes
d) Disruption of the hepatocyte membrane by the hepatitis B virus
e) T lymphocyte-mediated lysis of infected hepatic cells

MCQ exam: answer

The correct answer is E.

MCQ exam: explanation

The symptoms (anorexia, nausea, and brown urine) are typical of hepatitis. The body fights viral infections by CD8+ T cell-mediated lysis of infected cells that present viral antigens on their surface. The viral surface antigen does not directly injure hepatocyte membranes . The role of the host immune response in determining clinical outcome following hepatitis B virus (HBV) infection is well recognized.

In patients infected with hepatitis B, therapies, diseases, or conditions that impair specific lymphocyte responses lead to a high rate of chronic infection; in addition, the vigor of the host T-cell response to HBV-encoded antigenic peptides appears to correlate directly with the degree of acute hepatocellular injury and inversely with levels of HBV viremia. IgM directed against core antigen does not cause the hepatocytes to lyse.

Reference(s)
1). UpToDate: Characteristics of the hepatitis B virus and pathogenesis of infection. Available online: https://www.uptodate.com/contents/characteristics-of-the-hepatitis-b-virus-and-pathogenesis-of-infection
2). UpToDate: Hepatitis B virus: Overview of management. Available online: https://www.uptodate.com/contents/hepatitis-b-virus-overview-of-management