Journal List > Korean J Gastroenterol > v.58(1) > 1006873

Jeon, Jang, Jeong, Park, Lee, Kim, Cheon, Kim, Cho, Moon, Kim, Lee, and Kim: HBV DNA Loss within 24 Weeks Predicts Late Viral Breakthrough in Chronic Hepatitis B

Abstract

Background/Aims

Sustained HBV DNA reduction is necessary for biochemical remission, histological improvement, and prevention of complications. We analyzed the time taken from HBV DNA loss to viral breakthrough after antiviral treatment in patients with chronic hepatitis B (CHB). The early fall of the HBV DNA level to undetectable levels assessed really whether it is related to late breakthrough.

Methods

A total of 91 patients whose HBV DNA levels dropped below undetectable levels were chosen from lamivudine-treated 306 patients and were analyzed retrospectively. The patients were divided into 4 groups (A≤12, 12< B≤24, 24< C≤48, D>48 wk) according to the time taken for the HBV DNA to decrease below undetectable levels. HBV DNA level was determined every 3 months.

Results

The mean time taken for loss of HBV DNA was 34±28 wk. The baseline ALT differed significantly among groups (A: 382±274, B: 340±30, C: 166±92, D: 54±100 IU/L) (p=0.007). Fifty nine of the 91 patients (64.8%) experienced viral breakthrough. The mean interval between HBV DNA loss and viral breakthrough was 65±40 wk and differed significantly between group A, B (82±43 wk) and group C, D (56±28 wk) (p=0.015). In multivariate analysis, only HBV DNA loss within 24 wk, was found to be independently associated with late viral breakthrough (p=0.035). Undetectable HBV DNA after 24 wk was associated with high odd ratio of 3.24 (95% CI, 1.09-9.67).

Conclusions

HBV DNA loss within 24 wk after antiviral treatment could predict the late breakthrough.

References

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Fig. 1.
Schematic representation of the long term follow-up of the chronic hepatitis B.
kjg-58-25f1.tif
Fig. 2.
Initial lamivudine treatment or change in regimen compared with time to undetectable HBV DNA. Twenty one of the 21 patients (100%), 23 of the 23 patients, (100%), 25 of the 26 patients (96%),13 of the 21 patients (62%) had undetectable viral loads without change of initial antiviral agent and there was a significant difference between groups A, B, C and group D (p=0.013).
a Percentage of patients without change of initial lamivudine regimen.
b Groups according to the time to undetectable HBV DNA.
kjg-58-25f2.tif
Fig. 3.
Comparison of baseline AST/ALT levels among 4 groups. Baseline AST/ALT levels showed 232±195/382±274 IU/L in group A, 197±121/340±306 IU/L in group B, 156±144/166±92 IU/L in group C and 119±89/154±100 IU/L in group D and showed a significant difference between each group (p=0.006/p=0.007).
a Groups according to the time to undetectable HBV DNA
kjg-58-25f3.tif
Fig. 4.
The time taken until viral breakthrough according to pretreatment HBeAg status. In HBeAg positive, the mean time period between HBV DNA loss and viral breakthrough was 77±44 wk in groups A and B and 49±19 wk in groups C and D (p=0.025). In HBeAg negative, the mean time period between HBV DNA loss and viral breakthrough was 89±43 wk in groups A and B and 59±22 wk in groups C and D (p=0.05).
a Groups according to the time to undetectable HBV DNA.
kjg-58-25f4.tif
Table 1.
Characteristics of the Patients with Undetectable HBV DNA
Characteristics (n=91)  
Undetectable HBV DNA (wk) 34±28
Follow up duration (wk) 152±82
Duration of therapy (wk) 129±83
Age (yr) Mean±SD 44±12
Male sex, n (%) 28 (69.2%)
AST (IU/L) Mean±SD 170±141
ALT (IU/L) Mean±SD 243±220
Total bilirubin (mg/dL) Mean±SD 1.1±0.6
Albumin (g/dL) Mean±SD Platelet (×103/m3) Mean±SD 3.9±0.5 169±67
Prothrombin time (INR) Mean±SD 1.1±0.23
HBeAg, n (%) 36 (39.5%)
Anti-HBc IgM, n (%) 20 (22%)
HBV DNA (log10 copies/mL) Mean±SD 6.18±1.11
Cirrhosis, n (%) 5 (5.5%)
Table 2.
Baseline Characteristics between 4 Groups (A≤12, 12<B ≤24, 24<C≤48, and D>48 wk)
Characteristics Group A (n=21) Group B (n=23) Group C (n=26) Group D (n=21) p-value
Age (yr) 41±11 42±12 46±13 45±12 0.689
Male sex, n (%) 17 (81%) 14 (60.8%) 16 (61.5%) 16 (76%) 0.845
AST (IU/L) 232±195 197±121 156±144 119±89 0.006
ALT (IU/L) 382±274 340±306 166±92 154±100 0.007
Total bilirubin (mg/dL) 1.1±0.5 1.2±1.0 1.0±0.5 1.1±0.4 0.345
Albumin (g/dL) 4.0±0.4 4.0±0.4 3.9±0.5 3.8±0.6 0.647
Platelet (×103/m3) 174±86 180±67 164±67 156±57 0.787
Prothrombin time (INR) 1.14±0.21 1.11±0.17 1.11±0.1 1.02±0.46 0.512
HBeAg, n (%) 11 (52.3%) 9 (39%) 11 (42%) 5 (24%) 0.46
Anti-HBc IgM, n (%) 7 (33.3%) 7 (30.4%) 3 (11.5%) 3 (14.2%) 0.67
HBV DNA (log10 copies/mL) 5.76±1.09 5.94±1.18 6.37±1.15 6.47±0.96 0.076
Cirrhosis, n (%) 2 (9.5%) 1 (4.3%) 1 (3.8%) 1 (4.8%) 0.834

p-values were calculated by Kruskal-Wallis test.

Table 3.
Multivariate Analysis of Factors Associated with Late Viral Breakthrough
Factors p-value OR (95% CI)
The time to undetectable HBV DNA (wk) 0.035 3.24 (1.09-9.67)
AST (IU/L) 0.291  
ALT (IU/L) 0.645  
HBeAg status 0.062  
HBV DNA (log copies/ml) 0.661  

p-values were calculated by logistic regression anlasis.

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ORCID iDs

Seong Ran Jeon
https://orcid.org/http://orcid.org/0000-0001-6970-9737

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