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

Yıl 2018, Cilt: 35 Sayı: 4, 326 - 332, 01.07.2018

Ercan Yenilmez Rıza Aytaç Çetinkaya Ersin Tural

Öz

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.

Anahtar Kelimeler

Chronic hepatitis B, fibrosis, HBV DNA, prediction, viremia

Kaynakça

• 1. Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016;10:1-98.
• 2. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology 2016;63:261- 83.
• 3. European Association for the Study of the Liver. Electronic address: easloffice@ easloffice.eu; European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67:370-98.
• 4. Guidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection. Geneva: World Health Organization; 2015 Mar. WHO Guidelines Approved by the Guidelines Review Committee 2015.
• 5. Eren M, Reyhanioglu S, Ciftci E, Dundar E, Us T, Dinleyici CE, et al. Correlation of Liver Enzymes and Liver Histology in Chronic Hepatitis B Virus Infection. J Clin Anal Med 2016;7:639-42.
• 6. Shafaei S, Soleimani Amiri S, Hajiahmadi M, Sadeghi-Haddad-Zavareh M, Bayani M. Histological grading and staging of liver and its relation to viral loads in chronic anti-HBe positive hepatitis. Caspian J Intern Med 2013;4:681-5.
• 7. Kumar M, Sarin SK, Hissar S, Pande C, Sakhuja P, Sharma BC, et al. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT. Gastroenterology 2008;134:1376-84.
• 8. Bruden DJT, McMahon BJ, Townshend-Bulson L, Gounder P, Gove J, Plotnik J, et al. Risk of end-stage liver disease, hepatocellular carcinoma, and liver-related death by fibrosis stage in the hepatitis C Alaska Cohort. Hepatology 2017;66:37-45.
• 9. Can A, Dogan E, Bayoglu IV, Tatli AM, Besiroglu M, Kocer M, et al. Multicenter epidemiologic study on hepatocellular carcinoma in Turkey. Asian Pac J Cancer Prev 2014;15:2923-7.
• 10. Kao JH. Risk stratification of HBV infection in Asia-Pacific region. Clin Mol Hepatol 2014;20:223-7.
• 11. Charatcharoenwitthaya P, Phisalprapa P, Pausawasdi N, Rungkaew P, Kajornvuthidej S, Bandidniyamanon W, et al. Alanine aminotransferase course, serum hepatitis B virus DNA, and liver stiffness measurement for therapeutic decisions in hepatitis B e antigen-negative chronic hepatitis B. Hepatol Res 2016;46:1347-57.
• 12. Papatheodoridis GV, Manolakopoulos S, Liaw YF, Lok A. Follow-up and indications for liver biopsy in HBeAg-negative chronic hepatitis B virus infection with persistently normal ALT: a systematic review. J Hepatol 2012;57:196-202.
• 13. Seto WK, Lai CL, Ip PP, Fung J, Wong DK, Yuen JC, et al. A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B. PLoS One 2012;7:e32622.
• 14. Nguyen LH, Chao D, Lim JK, Ayoub W, Nguyen MH. Histologic changes in liver tissue from patients with chronic hepatitis B and minimal increases in levels of alanine aminotransferase: a meta-analysis and systematic review. Clin Gastroenterol Hepatol 2014;12:1262-6.
• 15. Barut S, Gemici Ü, Güneş F, Demir O, Duygu F. Predictors of histological indication for treatment in HBeAg negative chronic HBV infection. J Med Virol 2017;89:1952-7.
• 16. Sanai FM, Babatin MA, Bzeizi KI, Alsohaibani F, Al-Hamoudi W, Alsaad KO, et al. Accuracy of international guidelines for identifying significant fibrosis in hepatitis B e antigen--negative patients with chronic hepatitis. Clin Gastroenterol Hepatol 2013;11:1493-9.