Hepatitis B virus pre-S/S variants in liver diseases

Area of Science:

• Hepatology
• Virology
• Molecular Biology

Background:

• Chronic hepatitis B is a significant global health issue with severe clinical outcomes.
• Hepatitis B virus (HBV) genome evolution, driven by reverse transcriptase errors and host immunity, can lead to pre-S/S variants.
• These variants are increasingly associated with chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

Purpose of the Study:

• To review the function of the pre-S/S region in HBV.
• To summarize recent findings on the role of pre-S/S variants in liver disease.
• To discuss the association of pre-S/S variants with HBV genotypes and their pathogenesis.

Main Methods:

• Literature review of studies on pre-S/S variants in chronic hepatitis B.
• Analysis of identified pre-S/S variant types: pre-S deletion, point mutation, splice variant, and nonsense mutation.
• Discussion of proposed pathogenic mechanisms, including intracellular protein retention and endoplasmic reticulum stress.

Main Results:

• Five types of pre-S/S variants have been identified.
• Pre-S/S variants are frequently found in patients with chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma.
• Mechanisms often involve intracellular retention of HBV envelope proteins and endoplasmic reticulum stress, leading to liver damage.

Conclusions:

• Pre-S/S variants may contribute to liver disease progression and hepatocarcinogenesis in chronic hepatitis B.
• Routine determination of pre-S/S variants in HBV carriers can aid in identifying individuals at high risk for adverse outcomes.
• Further research is needed to elucidate the precise molecular mechanisms underlying the pathogenesis of each pre-S/S variant stage.