Expanding antiviral therapy indications for HBeAg-negative chronic hepatitis B patients with normal ALT and positive HBV DNA

Abstract

With the improved efficacy and accessibility of antiviral agents as well as the concerns about disease progression, there is a hot discussion on whether HBeAg-negative chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and positive HBV DNA should be treated. According to the international guidelines on the stages of the natural history of HBV infection, HBeAg-negative CHB patients with normal ALT and positive HBV DNA can be divided into two groups: one is the well-known “inactive carrier phase”, which is defined as serum HBV DNA < 2000 IU/ml and no significant liver inflammation; and the other is the “indeterminate phase”, which is defined as serum HBV DNA ≥ 2000 IU/mL regardless of the pathological changes in liver tissue, or HBV DNA < 2000 IU/mL but accompanied by significant pathological changes in the liver. In this review, we will expound the disease characteristics, disease progression, and clinical management status of these two groups. Based on the analysis, we propose that HBeAg-negative patients with normal ALT but detectable serum HBV DNA should be treated, regardless of their age, family history of hepatocellular carcinoma (HCC) or the severity of liver necroinflammation. Expanding the indications of antiviral therapy will help improve the survival and quality of life of patients by preventing disease progression, and consequently reduce the risk of HCC development.

Antiviral Therapy Favors a Lower Risk of Liver Cirrhosis in HBeAg-negative Chronic Hepatitis B with Normal Alanine Transaminase and HBV DNA Positivity

“…We suggest increasing the weight of serum HBV DNA in antiviral treatment decisions rather than rigidly adhering to ALT level, age, or family history of cirrhosis/HCC, considering HBeAg-negative patients with high viral loads are common in clinical practice, and antiviral therapy decreases the long-term risk of adverse liver events. 5 , 29 , 30 Recent Chinese hepatitis B guidelines (version 2022) have lowered the ALT level for initiating treatment to 30 U/L for men and 19 U/L for women. 31 That will enable more patients to meet treatment standards but still fails to include some patients with a high risk of disease progression, such as those with ALT levels below the ULN but with high viral loads ≥2,000 IU/mL.…”

The urgency to expand the antiviral indications of general chronic hepatitis B patients

“…With the development of therapeutic drugs for CHB, the accumulation of antiviral experience of clinicians, and the improvement of patient awareness of the disease and treatment compliance, it is imperative to expand the indications for the antiviral treatment of chronic hepatitis B (53). What differs from the previous situation is that the price of antiviral drugs has dropped significantly, and the accessibility of antiviral treatment is no longer a problem.…”

Letter: Determining optimal ALT cut‐off values for predicting significant hepatic histological changes in chronic hepatitis B virus infection

“…Continuous nucleos(t)ide analogue treatment helps to lower the risk of cirrhosis in HBeAg-negative CHB patients with normal ALT, especially in those with HBV DNA ≥ 2000 IU/mL. 10 Among the patients included in Kang et al, 8 74.7% were with HBV DNA > 2 × 10 3 IU/mL. Antiviral therapy should be recommended for these patients regardless of ALT level.…”