Diagnostic Dilemma for Low Viremia with Significant Fibrosis; is Hepatitis B Virus DNA Threshold Level a Good Indicator for Predicting Liver Damage?

Abstract

Background:The most important difficulties about management of hepatitis B are still determining the liver damage and the right time to start antiviral therapy.Aims:To reveal the role of hepatitis B virus DNA threshold level for prediction of liver fibrosis and inflammation in young-aged hepatitis B e-antigen negative chronic hepatitis B patients.Study Design:Diagnostic accuracy study.Methods:A total of 273 hepatitis B e-antigen negative young chronic hepatitis B patients with any hepatitis B virus DNA levels between 2008 and 2016, who had liver biopsy after at least 6 months follow up period, enrolled in this retrospective study. We created two groups as case and control, cases with hepatitis B virus DNA levels below 2000 IU/mL and controls with hepatitis B virus DNA levels over 2000 IU/mL. Having histological activity index ≥4 or/and fibrosis scores ≥2 were defined as significant histological abnormality. Then, we analyzed the relationship between these groups.Results:We showed that significant fibrosis may occur in one third of young chronic hepatitis B patients with low viremia (30.2%, n=42/139 in cases, 55.2%, n=74/134 in controls). Among the 42 cases with low viremia and significant fibrosis, 21.4% had alanine aminotransferase level between 40-59 U/L, 42.8% had alanine aminotransferase level between 60-79 U/L, and 35.7% had alanine aminotransferase level over 80 U/L. There was weak correlation between hepatitis B virus DNA threshold level and fibrosis score (p<0.001, rho=0.253). The optimum serum hepatitis B virus DNA threshold level in our study for predicting significant fibrosis was 1293 IU/mL (p<0.001, AUC: 0.657±0.034). The optimum alanine aminotransferase threshold level for predicting significant histological activity index and fibrosis was 64.5 and 59.5 U/L, respectively. The sensitivity and the specificity of 1293 vs 2000 IU/mL hepatitis B virus DNA threshold with 60 U/L alanine aminotransferase threshold level for predicting F≥2 fibrosis score were similar (sensitivity: 0.43 and 0.38, specificity: 0.76 and 0.77, respectively).Conclusion:Significant fibrosis may occur even in young cases with low viremia. It is not possible to define a single threshold hepatitis B virus DNA level for differentiating inactive carriers from patients with hepatitis B e-antigen-negative chronic hepatitis. Diagnostic accuracy of hepatitis B virus DNA with alanine aminotransferase thresholds for the prediction of significant fibrosis is weak.

Are there optimal alanine aminotransferase and HBV DNA thresholds for discriminating HBeAg-positive chronic infection from chronic hepatitis?

“…It is argued to decrease the ALT threshold levels as 19-25 U/L for females and 30-33 U/L for males in the WHO and AASLD guidelines, and the latest AASLD guideline support the ALT threshold levels as 25 U/L for females and 35 U/L for males in the management procedure of chronic HBV. On the contrary, APASL and EASL accept that there are no available data to support the need for lowering the traditional thresholds for the ULN of ALT values 6. And also in literature, ALT levels between 25 and 40 U/L is considered as high normal, in which histopathological changes is more likely to occur 7…”

“…In literature, there are few studies in HBeAg-positive cases aiming on correlation or relationship between HBV-DNA and liver fibrosis and/or necroinflammation; studies are mostly in HBeAg-negative cases 6,16-19. Hepatitis B virus-DNA threshold level for the treatment indication of CHB due to the reimbursement arrangements of Turkey is 2,000 IU/mL; same level for both HBeAg-positive and negative CHB cases 13.…”

HBeAg-negative Patients with Chronic Hepatitis B Virus Infection and Normal Alanine Aminotransferase: Wait or Treat?

“…A previous study by Deng et al 14 reported disease progression in those with low HBV DNA loads. Yenilmez et al 19 also found that the risk of liver fibrosis cannot be ignored in CHB patients with low viral loads. In brief, the risk of disease progression exists as long as we can detect virus replication with an available assay, which is equivalent to an antiviral therapy indication.…”

Risk Factors and Prevention of Viral Hepatitis-Related Hepatocellular Carcinoma

“…For patients with liver cirrhosis, the risk of HBV DNA levels not reaching 2000 IU/mL is still very high ( 58 ). However, current studies indicate that low-level viremia can also cause HCC ( 59 ). Low-level viremia (LLV) is defined as a level of HBV DNA continuously or intermittently greater than the detection limit but less than 2000 IU/mL.…”