June 27, 2022

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Treatment for Patients with chronic HBV infection and immune tolerance stage

Patients with chronic HBV infection and immune tolerance stage should be treated with precision antiviral therapy

 

Treatment for Patients with chronic HBV infection and immune tolerance stage.  Whether patients with chronic HBV infection and immune tolerance stage should be treated with antiviral therapy has always been controversial.

At present, the definition of immune tolerance period and treatment opinions on hepatitis B guidelines in various countries are not completely consistent, which is mainly reflected in the definition of different levels of HBV DNA, and most of the guidelines do not clearly define the titer of HBsAg, which leads to immune tolerance. The definition of maturity is not clear.

At present, researches believe that patients with chronic HBV infection in the immune tolerance stage have no inflammation in their liver and their ALT is normal, so they do not need treatment, and the possibility of liver cancer is relatively small. However, studies have also shown that in chronic hepatitis B (CHB) patients with high viral load and normal transaminase, approximately 20% of CHB patients with persistently normal ALT levels have potential liver inflammation.


Although patients in the immune tolerance stage can rule out potential liver inflammation or fibrosis through histological evidence of liver biopsy. However, it is impractical to determine whether a patient has liver inflammation through regular liver biopsy.

Relevant immunological studies have shown that patients in the immune tolerance stage may not have the immune characteristics of T lymphocyte tolerance. Kennedy et al. found that there is no significant difference in T lymphocyte factor profiles between patients in the immune tolerance phase and those in the immune active phase.

These studies indicate that although the transaminase is normal in patients with immune tolerance, it does not mean that there is no inflammation and fibrosis in the liver. The integration rate of HBV DNA is an important risk factor for predicting the onset of liver cancer.

Evidence has shown that patients with chronic HBV infection in the immune tolerance stage have significant liver pathological changes and are at high risk of liver cancer or death. This part of the population can also obtain a higher immune response rate if antiviral therapy is taken early.

 

Kim et al. established a Markov model and found that starting antiviral therapy in patients with CHB in the immune tolerance stage can reduce the risk of liver cirrhosis and liver cancer compared with postponing treatment to the active hepatitis stage.

Regardless of whether patients in the immune tolerance stage are supported to receive antiviral therapy at this stage, researchers have emphasized the importance of antiviral therapy in the management of CHB, and agreed that antiviral therapy for CHB patients can delay disease progression and improve survival time and life. quality.

 


How to formulate precise treatment strategies for patients with chronic HBV infection in the immune tolerance phase, determine a more appropriate treatment plan, and accurately define the immune tolerance phase of CHB patients is the key.

 

To clarify the immune tolerance period, the following predictive factors need to be considered:

(1) For CHB patients in the immune tolerance phase, if ALT is elevated, the influence of fatty liver should be considered (the incidence of fatty liver in Asia is about 29.6%). Patients in the immune clearance phase may have normal ALT during a certain period of time. Therefore, it cannot be defined only by ALT level;


(2) HBeAg-positive CHB patients with normal ALT, and when HBV DNA is less than 107 IU/ml, it is necessary to determine whether they are really in the immune tolerance phase and whether it is possible to enter the immune clearance phase;

(3) HBsAg can be used to define the immune tolerance period, and the specific value needs to be further clarified;

(4) Non-invasive examinations such as liver biopsy and liver elasticity examination are helpful to judge patients in the immune tolerance stage. Sonneveld et al. believe that if a non-invasive method can be used to rule out liver fibrosis, liver biopsy is not encouraged for the sole purpose of assessing inflammatory activity;

(5) Serum HBV RNA can be considered as a clinical marker for patients with immune tolerance;

(6) Use new methods such as metabolomics to predict the period of immune tolerance.

(7) Active antiviral therapy is also needed for patients with immune tolerance stage with family history of liver cirrhosis and liver cancer.

 


Schoeman et al. found that there was a decrease in glycerophospholipid and an increase in plasma proteinogens in patients with immune tolerance. It is speculated that HBV may affect the glycerol-3-phosphate-NADH shuttle system, causing a continuous decrease in choline glycerophospholipid, which can be used as a predictor Metabolism markers in the immune tolerance phase.

A large-scale longitudinal multi-omics spectrum integrated analysis recently published by Nature Communications found that everyone has a unique and stable molecular spectrum, laying the foundation for precision medicine based on longitudinal monitoring in the future. Based on this, a multi-omics atlas can be established to predict patients in the immune tolerance stage in the future.

 

In the future, the clinical stage characteristics of chronic HBV infections can be modeled. The characteristic parameters in the model should not only include the patient’s HBV DNA, HBV DNA genotype/subgenotype, HBV RNA, ALT, HBeAg serum level and other clinical data, but also Including metabonomic parameters such as choline glycerophospholipid, and further applying artificial intelligence and systems biology technology to integrate and analyze the clinical data, image data and multi-omics data of CHB patients to achieve precise treatment of CHB patients.

 

In short, patients in the immune tolerance stage should consider receiving antiviral therapy to increase the overall treatment rate of CHB and reduce the risk of liver cirrhosis and liver cancer.

 

 

(source:internet, reference only)


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