Is there a meaningful serum hepatitis B virus DNA cutoff level for therapeutic decisions in hepatitis B e antigen-negative chronic hepatitis B virus infection?

Abstract

The diagnosis of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B indicating therapeutic intervention currently requires serum hepatitis B virus (HBV) DNA >2,000 IU/mL. We evaluated the severity of liver histology and the presence of histological indication for treatment in patients with HBeAg-negative chronic HBV infection focusing on those with low viremia and/or normal alanine aminotransferase (ALT). In total, 399 patients with increased ALT and detectable serum HBV DNA (chronic hepatitis B patients) and 35 cases with persistently normal ALT and HBV DNA >2,000 IU/mL (inactive carriers) were included. Histological indication for treatment (grading score >7 and/or stage >2 in Ishak's classification) was found in 91% (185/203), 82% (75/91), 75% (47/63), and 62% (26/42) of chronic hepatitis B patients with HBV DNA >200,000, 20,000-199,999, 2,000-19,999, and <2,000 IU/mL, respectively (P < 0.001). Histological indication for treatment was more frequent in chronic hepatitis B patients with persistently elevated ALT (86% or 275/321), but it was also found in 74% (58/78) of those with transiently normal ALT (P ‫؍‬ 0.025). All inactive carriers had HBV DNA <20,000 IU/mL. Histological indication for treatment was present in 17% (6/35) of inactive carriers always due to moderate (stage 2) fibrosis without active necroinflammation. Conclusion: HBeAg-negative chronic HBV patients with persistently or transiently increased ALT and HBV DNA >20,000 IU/mL almost always require therapeutic intervention, but histological indications for treatment are also present in the majority of such cases with HBV DNA <20,000 and even <2,000 IU/mL. In contrast, minimal histological lesions are observed in the majority of HBeAg-negative patients with persistently normal ALT and HBV DNA >2,000 IU/mL, who may not require immediate liver biopsy and treatment but only close follow-up.

Early termination of immune tolerance state of hepatitis B virus infection explains liver damage

“…Kumar et al [19] from India showed that more than 50% of their 1387 incidentallydetected chronic HBV carriers had evidence of progressive liver diseases for which treatment was indicated. A similar outcome has also been reported from Pakistan, Egypt and other countries [20][21][22][23][24][25] . There are studies from Bangladesh, India, South Korea and Turkey suggesting that HBeAg negative CHB patients as a whole tend to develop more significant liver fibrosis than those who are HBeAg positive [26][27][28][29][30] .…”

Core Antigen Expression Is Associated with Hepatic Necroinflammation in e Antigen-Negative Chronic Hepatitis B Patients with Low DNA Loads

“…It is well accepted that high HBV DNA levels play an adverse role in liver histological grading. For HBeAg-negative CHB, an HBV DNA load higher than 20,000 IU/ml or 1 ϫ 10 5 cp/ml is a common criterion for safety diagnosis; however, the finding of low HBV DNA load could not exclude the possibility of active hepatic necroinflammation (28). A previous study could not explain why significant necroinflammation existed in HBeAg-negative CHB patients with low HBV viral loads.…”

“…Measurement of HBV DNA levels is now a useful test for evaluating HBV replication and is considered a marker to determine not only the start and the endpoint of antiviral treatment but also the risk of HCC development (23,28). The clinical significance of reappearance of intrahepatic HBcAg in the reactivation phase of CHB based on HBV viral loads had not been well evaluated.…”

Systematic review with meta‐analysis: the proportion of chronic hepatitis B patients with normal alanine transaminase ≤40 IU/L and significant hepatic fibrosis

“…[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Another eight studies did not report detailed histological findings of study patients and were also excluded, [27][28][29][30][31][32][33][34] and another three studies were eliminated due to small study sizes (N < 30 patients). [35][36][37] One other study was excluded because it also included patients infected with hepatitis C virus, 38 and another study was excluded as it involved patients with significant alcohol use.…”