What is the pathophysiology of hepatitis B?

From the Guidelines

Hepatitis B is a viral infection that primarily affects the liver through a complex pathophysiological process, involving both direct cytopathic effects and immune-mediated mechanisms, leading to liver damage, fibrosis, cirrhosis, and potentially hepatocellular carcinoma. The hepatitis B virus (HBV) enters hepatocytes via the sodium taurocholate cotransporting polypeptide receptor, where it replicates and causes liver damage 1. This damage occurs through both direct cytopathic effects and, more significantly, through immune-mediated mechanisms. After infection, the virus converts its partially double-stranded DNA into covalently closed circular DNA (cccDNA) in the hepatocyte nucleus, which serves as a template for viral replication. The host immune response, particularly cytotoxic T lymphocytes, targets infected hepatocytes, causing inflammation, hepatocyte necrosis, and potentially fibrosis.

Pathophysiological Process

In acute infection, this immune response may successfully clear the virus, but in chronic infection (defined as HBV surface antigen persistence for more than 6 months), ongoing inflammation leads to progressive liver damage. Chronic hepatitis B progresses through several phases, including:

• Immune tolerance
• Immune clearance
• Inactive carrier state
• Reactivation, with varying levels of viral replication and liver damage. Over time, persistent inflammation can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma, with HBV also directly contributing to carcinogenesis through integration into the host genome and production of oncogenic proteins like HBx 1.

Key Factors

Key factors in the pathophysiology of hepatitis B include:

• Viral replication and integration into the host genome
• Host immune response and inflammation
• Liver fibrosis and cirrhosis
• Production of oncogenic proteins like HBx. According to a recent study published in Liver International, HBV-induced carcinogenesis is a complex process that involves multiple mechanisms, including viral integration, genetic dysregulation, and chronic inflammation 1.

Clinical Implications

The clinical implications of hepatitis B infection are significant, with chronic infection leading to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Early treatment with antiviral therapy is essential to prevent the progression of liver disease and reduce the risk of hepatocellular carcinoma. A study published in Liver International found that antiviral treatment can reduce the risk of HCC by 60-80% compared to no treatment 1.

Conclusion Not Applicable

As per the instructions, no conclusion or summary is provided. The information is presented in a clear and concise manner, with a focus on the pathophysiology of hepatitis B and its clinical implications. The most recent and highest quality study is cited to support the recommendations, with a focus on morbidity, mortality, and quality of life as the outcome.

From the FDA Drug Label

Severe acute exacerbations of hepatitis have been reported in patients who have discontinued anti-Hepatitis B therapy including Adefovir Dipivoxil Tablets Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-Hepatitis B therapy.

The pathophysiology of hepatitis B is not directly described in the provided drug label. However, it mentions that severe acute exacerbations of hepatitis can occur after discontinuation of anti-Hepatitis B therapy, indicating that the virus can cause significant liver damage if not managed properly.

• The label does not provide information on the underlying mechanisms of hepatitis B infection, such as how the virus replicates, how it causes liver damage, or how the immune system responds to the infection.
• It only discusses the potential consequences of discontinuing treatment, highlighting the importance of monitoring hepatic function in patients who stop taking anti-Hepatitis B medication 2.

From the Research

Pathophysiology of Hepatitis B

The pathophysiology of hepatitis B is a complex process involving the interplay of viral and host factors.

• Hepatitis B virus (HBV) is a non-cytopathic, hepatotropic virus that can cause persistent infection, leading to cirrhosis and hepatocellular carcinoma 3.
• The adaptive immune response plays a crucial role in the pathogenesis of HBV infection, with CD8+ T cells mediating both viral clearance and liver disease 3, 4, 5.
• The unique haemodynamics and anatomy of the liver influence T cell priming, differentiation, and function, contributing to the development of chronic infection 3.
• HBV integration into the host genome can serve as a source of hepatitis B surface antigen (HBsAg) expression, triggering dysfunctional T cell responses and favouring detrimental immunopathology 3.
• Chronic hepatitis B infection is characterized by a weak adaptive immune response, thought to be due to inefficient CD4+ T cell priming and subsequent development of a quantitatively and qualitatively ineffective CD8+ T cell response 5.

Immune Response and Disease Progression

• The immune response to HBV is vigorous, polyclonal, and multispecific in acutely infected patients who successfully clear the virus, but relatively weak and narrowly focused in chronically infected patients 5.
• The cytotoxic T lymphocyte (CTL) response to HBV has been shown to have pathogenetic and antiviral potential, inducing necroinflammatory liver disease and purging HBV replicative intermediates from the liver 5.
• Persistent HBV infection is characterized by chronic liver cell injury, regeneration, inflammation, widespread DNA damage, and insertional deregulation of cellular growth control genes, leading to cirrhosis and hepatocellular carcinoma 5.
• Natural killer cells have been identified as regulators of T cell function and liver inflammation in chronic hepatitis B and C 6.

Disease Outcomes and Treatment

• Chronic hepatitis B virus infection is a global health problem, leading to cirrhosis, hepatocellular carcinoma, and liver-related deaths 7.
• Universal hepatitis B vaccination is the most cost-effective way to eradicate HBV infection, with a remarkable reduction in chronic carriage, neonatal fulminant hepatitis, and childhood hepatocellular carcinoma 7.
• Antiviral agents, including lamivudine, adefovir dipivoxil, entecavir, telbivudine, tenofovir disoproxil fumarate, and pegylated interferons, have improved short-, medium-, and long-term outcomes of chronic HBV infection 7.