The acute increase of ALT during interferon treatment is related to the decrease of HBsAg!

Introduction Since current treatment methods still cannot cure hepatitis B virus (HBV) infection, the best treatment endpoint for chronic hepatitis B (CHB) is to achieve a functional cure
.

Pegylated interferon alpha (PEG IFNα) has been increasingly used in combination with new drugs to treat CHB
.

Recently, Choi et al.
published a study to evaluate the relationship between acute elevation of alanine aminotransferase (ALT) and serum hepatitis B surface antigen (HBsAg) and HBV RNA dynamics in CHB patients receiving PEG IFNα therapy.
Relationship between
.

The results showed that the acute increase in ALT during PEG IFNα treatment was related to the subsequent decrease in HBsAg and HBV RNA
.

Research methods: Four international randomized trials were analyzed after the fact
.

Include 269 patients receiving PEG IFNα monotherapy, 130 patients receiving initial combination therapy of PEG IFNα and nucleoside (acid) analog (NA), 124 patients receiving NA plus PEG IFNα treatment and 128 patients receiving NA monotherapy
.

To assess the correlation between acute elevation of ALT and changes in HBsAg and HBV RNA
.

Acute elevation of ALT is defined as ALT elevation ≥ 5 × upper limit of normal (ULN)
.

Research results 1.
Features of acute ALT elevation A total of 83/651 patients (13%) had acute elevation of ALT during treatment
.

Compared with patients without acute elevation of ALT, patients with acute elevation of ALT are more often white people with genotype A/D, and have higher baseline ALT, HBV DNA, HBV RNA, and HBsAg levels
.

Compared with NA plus PEG IFNα therapy (2%) or NA monotherapy (1%), PEG IFNα monotherapy (18%) and initial combination therapy of PEG IFNα and NA (24%) showed acute elevation of ALT There were more patients (P<0.
001) (Figure 1)
.

Figure 1 The incidence of acute elevation of ALT during treatment in each group of patients 2.
Acute elevation of ALT during PEG IFNα treatment is related to the decline of HBsAg and HBV RNA.
In the entire cohort, 89 patients (14%) reached HBsAg at the final follow-up Response (decrease ≥1 log10)
.

Multivariate analysis adjusted for various factors and found that acute elevation of ALT during treatment was the most important independent predictor of HBsAg response (adjusted OR 4.
8; 95% CI 2.
6-8.
6; P<0.
001)
.

In the cohort of 543 patients with the highest ALT levels observed during treatment, 231 (43%) achieved an HBV RNA response (drop ≥1 log10) at the final follow-up
.

After adjusting for factors such as age, the acute increase in ALT during treatment was also significantly correlated with HBV RNA response (adjusted OR 1.
9; 95% CI 1.
1-3.
3; P=0.
016)
.

At the final follow-up, a total of 22 patients achieved HBsAg disappearance, of which 16 patients (73%) had acute elevation of ALT during treatment
.

The study concluded that the acute increase of ALT level in CHB patients during treatment is closely related to the subsequent decrease of serum viral markers
.

Among patients who achieved functional cure (ie disappearance of serum HBsAg), 73% had acute elevation of ALT during treatment
.

Almost all acute elevations of ALT occurred during PEG IFN immunomodulatory treatment
.

Patients receiving NA treatment rarely experience acute elevation of ALT
.

In conclusion, the acute increase in ALT during PEG IFNα treatment is associated with the subsequent decline in HBsAg and HBV RNA, and can predict the subsequent disappearance of HBsAg
.

The results of this study support the combined use of PEG IFN (possibly short-term) in a new treatment plan to achieve functional cure
.

References: Choi HSJ, Sonneveld MJ, Farag MS, et al.
Effects of on-treatment ALT flares on serum HBsAg and HBV RNA in patients with chronic HBV infection[J].
J Viral Hepat.
2021 Sep 12.
doi: 10.
1111/ jvh.
13613.
Contribution email: tougao@medlive.
cn