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. 2020 Oct;52(8):1399-1406.
doi: 10.1111/apt.16067. Epub 2020 Sep 4.

Very low probability of significant liver inflammation in chronic hepatitis B patients with low ALT levels in the absence of liver fibrosis

Milan J Sonneveld  1 , Willem P Brouwer  1 , Bettina E Hansen  2 , Henry L-Y Chan  3 , Teerha Piratvisuth  4 , Ji-Dong Jia  5 , Stefan Zeuzem  6 , Rong-Nan Chien  7 , Hannah Choi  2 , Robert J de Knegt  1 , Cynthia Wat  8 , Vedran Pavlovic  8 , Anuj Gaggar  9 , Qing Xie  10 , Maria Buti  11 , Robert A de Man  1 , Harry L A Janssen  1   2 ; SONIC-B Study Group
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Very low probability of significant liver inflammation in chronic hepatitis B patients with low ALT levels in the absence of liver fibrosis

Milan J Sonneveld et al. Aliment Pharmacol Ther. 2020 Oct.

Abstract

Background: Guidelines recommend liver biopsy to rule out significant inflammatory activity in chronic hepatitis B (CHB) patients with elevated hepatitis B virus (HBV) DNA but without other indications for treatment.

Aim: To study rates and determinants of clinically significant liver inflammation.

Methods: We selected patients with HBV DNA > 2000 IU/mL from the SONIC-B database. The presence of significant inflammation (METAVIR ≥ A2 or HAI ≥ 9) was assessed by liver biopsy and correlated with alanine aminotransferase (ALT) levels (according to AASLD upper limits of normal [ULN]) and stratified by the presence of significant liver fibrosis (Ishak ≥ 3 or METAVIR ≥ F2).

Results: The cohort included 2991 patients; 1672 were HBeAg-positive. ALT was < ULN in 270 (9%), 1-2 times ULN in 852 (29%) and > 2 times ULN in 1869 (63%). Significant fibrosis was found in 1419 (47%) and significant inflammatory activity in 630 (21%). Significant inflammatory activity was found in 34% of patients with liver fibrosis, compared to 9.5% of those without (P < 0.001). Among patients without fibrosis, significant inflammatory activity was detected in 3.6% of those with normal ALT, 5.0% of those with ALT 1-2 times ULN and in 13% of those with ALT > 2 times ULN (P < 0.001). ALT < 2 times ULN had a negative predictive value of 95% for ruling out significant inflammatory activity among patients without liver fibrosis.

Conclusions: Among patients without significant fibrosis, an ALT level < 2 times ULN is associated with < 5% probability of significant inflammatory activity. If fibrosis can be ruled out using non-invasive methods, liver biopsy solely to assess inflammatory activity should be discouraged.

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Figures

Figure 1
Figure 1
Patient disposition
Figure 2
Figure 2
Relationship between ALT levels and inflammatory activity across fibrosis strata. Liver fibrosis was defined as no significant fibrosis (Ishak 0‐2/METAVIR F0‐F1), significant fibrosis (Ishak 3‐4/METAVIR F2‐F3) or cirrhosis (Ishak 5‐6/METAVIR F4). Liver inflammation was defined as no inflammation (METAVIR A0/HAI 0‐3), mild inflammation (METAVIR A1/ HAI 4‐8), moderate inflammation (METAVIR A2/HAI 9‐12) or severe inflammation (METAVIR A3/HAI 13‐18). HAI: histologic activity index
Figure 3
Figure 3
Recommendations on performing liver biopsy to assess liver inflammatory activity based on the findings from the current study. ULN, upper limit of normal. Significant fibrosis: Ishak ≥ 3 or METAVIR ≥ F2
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