High risk of clinical events in untreated HBeAg‐negative chronic hepatitis B patients with high viral load and no significant ALT elevation

Abstract

Background: It remains unknown whether antiviral treatment for HBeAg-negative chronic hepatitis B (CHB) patients having high viral loads without significant elevation of alanine aminotransferase (ALT) levels would reduce the risks of clinical events. Aim: To compare clinical outcomes of high viral load CHB patients untreated for normal or mildly elevated ALT vs those treated for ALT ≥ 2 upper limit of normal (ULN). Methods: This historical cohort study included 5414 HBeAg-negative CHB patients without cirrhosis at a tertiary hospital in Korea from 2000 to 2013. Inactive phase was defined as serum hepatitis B virus [HBV] DNA < 2000 IU/mL and persistently normal ALT (n = 3572). High viral load (HBV DNA ≥ 2000 IU/mL) patients were classified into three phases by ALT levels: Replicative (persistently normal ALT, n = 900);Mildly active (ALT 1-2ULN, n = 396); and Active (ALT ≥ 2ULN, n = 546) phases. All Active phase patients were treated with nucleos(t)ide analogues. Results:The mean age of the patients was 47 years without a significant difference among the groups. Compared with the treated Active phase group, the untreated Replicative phase group showed a significantly higher risk of hepatocellular carcinoma (HCC; HR 1.76; 95% CI 1.00 -3.10, P = 0.05) and death/transplantation (HR 2.14; 5% CI 1.09 -4.21, P = 0.03) by propensity score-matched analysis. The untreated mildly active phase patients had further increase in risk of HCC and death/ transplantation compared with the treated Active phase group by unadjusted, PSmatched, competing risks, and multivariable-adjusted analyses. Conclusions: Untreated high viral load HBeAg-negative CHB patients without significant ALT elevation had higher risks of clinical events than treated Active phase patients with elevated ALT. S U PP O RTI N G I N FO R M ATI O N Additional supporting information will be found online in the Supporting Information section at the end of the article. How to cite this article: Choi GH, Kim G-A, Choi J, Han S, Lim Y-S. High risk of clinical events in untreated HBeAg-negative chronic hepatitis B patients with high viral load and no significant ALT elevation. Aliment Pharmacol Ther. 2019;50: 215-226. https ://doi.

Letter: risk of developing hepatocellular carcinoma in untreated HBeAg‐negative chronic hepatitis B patients with high viral load and no significant ALT elevation

“…We read with interest the article by Choi et al who compared the long-term clinical outcomes of HBeAg-negative chronic hepatitis B (CHB) patients with high viral loads and normal or mildly elevated alanine aminotransferase (ALT) levels with those treated with elevated ALT levels in a large cohort. 1 They concluded that untreated high viral load HBeAg-negative CHB patients without significant ALT elevation had significantly higher risks of hepatocellular carcinoma (HCC) and death/transplantation compared with treated active phase patients with elevated ALT levels. 1 Although these data could provide more evidence about the long-term risks of HCC and death/transplantation in replicative and mildly active phase patients, several issues are worthy of discussion.…”

“…1 They concluded that untreated high viral load HBeAg-negative CHB patients without significant ALT elevation had significantly higher risks of hepatocellular carcinoma (HCC) and death/transplantation compared with treated active phase patients with elevated ALT levels. 1 Although these data could provide more evidence about the long-term risks of HCC and death/transplantation in replicative and mildly active phase patients, several issues are worthy of discussion.…”

“…2 However, using only clinical and radiological criteria for diagnosing cirrhosis, the authors might not have been able to correctly identify cirrhotic patients. 1…”

“…We thank Huang et al for their letter regarding our recent article. 1,2 They have highlighted the importance of family history in the assessment of hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. However, a family history of a cancer by self-reported data may be prone to recall bias, and its completeness and accuracy are greatly influenced by age at interview and patients' educational level.…”

Letter: risk of developing hepatocellular carcinoma in untreated HBeAg‐negative chronic hepatitis B patients with high viral load and no significant ALT elevation. Authors' reply

“…We were pleased that an updated meta-analysis 1 Furthermore, the publication includes erroneous data.…”