HBV DNA level could predict significant liver fibrosis in HBeAg negative chronic hepatitis B patients with biopsy indication

BMC Gastroenterology

Teerha Piratvisuth¹  Roongrueng Jarumanokul²  Samornmas Kanngurn⁴  Pimsiri Sripongpun³  Naichaya Chamroonkul³  Surat Praneenararat³ 

[1] NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla, Thailand;Division of Immunology, Prince of Songkla University, Songkhla, Thailand;Division of Gastroenterology, Department of Medicine, Prince of Songkla University, Songkhla, Thailand;Division of Pathology, Department of Pathology, Prince of Songkla University, Songkhla, Thailand

关键词: Liver fibrosis;    HBV DNA;    HBeAg negative;    Chronic hepatits B;    Predictor;   

Others  :  1121728
DOI  :  10.1186/s12876-014-0218-6

 received in 2014-08-31, accepted in 2014-12-11,  发布年份 2014

【 摘 要 】

Background

Non-invasive models and methods to substitute liver biopsy in chronic hepatitis B (CHB) patients were investigated but their roles as predictors of significant liver histology for diagnosis of HBeAg-negative CHB patients who had indication for liver biopsy according to The American Association for the Study of Liver Diseases (AASLD) and The Asian Pacific Association for the Study of the Liver (APASL) guidelines are still unknown. This study was designed to identify predictors of significant liver necroinflammation as defined by a Histology Activity Index of necroinflammatory score ≥ 4 or Metavir necroinflammatory activity score ≥ 2 and significant liver fibrosis as defined by a Metavir fibrosis score ≥ 2 in HBeAg-negative CHB patients that had a hepatitis B virus (HBV) DNA level ≥ 2,000 IU/ml and age ≥ 40 years or elevated alanine aminotransferase level between 1–2 times the upper limit of normal.

Methods

Twenty-two patients were prospectively included and performed liver biopsies. Clinical and laboratory parameters including age, gender, underlying disease, family history of cirrhosis or hepatocellular carcinoma, body mass index (BMI), HBV DNA level, HBsAg level, liver function test, complete blood count, aspartate aminotransferase-to-platelet ratio index and transient elastography were collected and analyzed with liver histology profiles.

Results

Five patients (23%) had significant liver inflammation and 7 patients (32%) had significant liver fibrosis. Factors associated with significant liver inflammation were a lower BMI and higher alkaline phosphatase level while a factor associated with significant liver fibrosis was lower age. On multivariate analysis, only HBV DNA level > 5.5 log IU/ml could predict significant liver fibrosis (odds ratio 28.012, 95% CI, 1.631-481.240, p = 0.022) and its sensitivity, specificity, positive predictive value and negative predictive value were 71.4%, 93.3%, 83.3% and 87.5% respectively.

Conclusions

An HBV DNA level of > 5.5 log IU/ml was able to predict significant liver fibrosis for treatment of HBeAg-negative CHB patients that had indication for liver biopsy as recommended by AASLD and APASL guidelines.

【 授权许可】

   
2014 Praneenararat et al.; licensee BioMed Central.

【 参考文献 】

• [1]Lok AS, McMahon BJ: Chronic hepatitis B: update 2009. Hepatology 2009, 50(3):661-662.
• [2]European Association For The Study Of The Liver: EASL clinical practice guidelines: management of chronic hepatitis B virus infection J Hepatol 2012, 57:167-185.
• [3]Liaw YF, Kao JH, Piratvisuth T, Chan HL, Chien RN, Liu CJ, Gane E, Locarnini S, Lim SG, Han KH, Amarapurkar D, Cooksley G, Jafri W, Mohamed R, Hou JL, Chuang WL, Lesmana LA, Sollano JD, Suh DJ, Omata M: Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int 2012, 6:531-561.
• [4]Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD: American association for the study of liver diseases: liver biopsy. Hepatology 2009, 49(3):1017-1044.
• [5]Castera L: Hepatitis B: are non-invasive markers of liver fibrosis reliable? Liver Int 2014, 34((Suppl 1)):91-96.
• [6]Thai Association for the Study of the Liver: Thailand Practice Guideline for Management of Chronic Hepatitis B. 2012. http://www.thasl.org/files/24.HBV_and_HCV_Guideline_2012(update).pdf.
• [7]Su TH, Hsu CS, Chen CL, Liu CH, Huang YW, Tseng TC, Liu CJ, Chen PJ, Lai MY, Chen DS, Kao JH: Serum hepatitis B surface antigen concentration correlates with HBV DNA level in patients with chronic hepatitis B. Antivir Ther 2010, 15:1133-1139.
• [8]Tseng TC, Liu CJ, Su TH, Wang CC, Chen CL, Chen PJ, Chen DS, Kao JH: Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters. Gastroenterology 2011, 141:517-525. 525.e1-2
• [9]Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F, Christidis C, Ziol M, Poulet B, Kazemi F, Beaugrand M, Palau R: Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol 2003, 29:1705-1713.
• [10]Guido M, Rugge M: Liver biopsy sampling in chronic viral hepatitis. Semin Liver Dis 2004, 24(1):89-97.
• [11]Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, Kiernan TW, Wollman J: Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981, 1(5):431-435.
• [12]Bedossa P, Poynard T: An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 1996, 24:289-293.
• [13]Croagh CM, Bell SJ, Slavin J, Kong YX, Chen RY, Locarnini S, Desmond PV: Increasing hepatitis B viral load is associated with risk of significant liver fibrosis in HBeAg-negative but not HBeAg-positive chronic hepatitis B. Liver Int 2010, 30(8):1115-1122.
• [14]Mohamadnejad M, Montazeri G, Fazlollahi A, Zamani F, Nasiri J, Nobakht H, Forouzanfar MH, Abedian S, Tavangar SM, Mohamadkhani A, Ghoujeghi F, Estakhri A, Nouri N, Farzadi Z, Najjari A, Malekzadeh R: Noninvasive markers of liver fibrosis and inflammation in chronic hepatitis B-virus related liver disease. Am J Gastroenterol 2006, 101(11):2537-2545.
• [15]Xiao L, Xian J, Li Y, Geng A, Yang X, Han L, Xu H: Parameters Associated with Significant Liver Histological Changes in Patients with Chronic Hepatitis B.ISRN Gastroenterol 2014, 2014:913890.
• [16]Seto WK, Wnog DKH, Fung J, Ip PP, Yuen JC, Hung IF, Lai CL, Yuen MF: High hepatitis B surface b antigen levels predict insignificant fibrosis in hepatitis B e antigen positive chronic hepatitis B. PLoS One 2012, 7(8):e43087.
• [17]Friedrich-Rust M, Ong MF, Martens S, Sarrazin C, Bojunga J, Zeuzem S, Herrmann E: Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology 2008, 134(4):960-974.
• [18]Tsochatzis EA, Gurusamy KS, Ntaoula S, Cholongitas E, Davidson BR, Burroughs AK: Elastography for the diagnosis of severity of fibrosis in chronic liver disease: a meta-analysis of diagnostic accuracy. J Hepatol 2011, 54(4):650-659.
• [19]Chon YE, Choi EH, Song KJ, Park JY, Kim Do Y, Han KH, Chon CY, Ahn SH, Kim SU: Performance of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B: a meta-analysis. PLoS One 2012, 7(9):e44930.
• [20]Degos F, Perez P, Roche B, Mahmoudi A, Asselineau J, Voitot H, Bedossa P: Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: a multicenter prospective study (the FIBROSTIC study). J Hepatol 2010, 53(6):1013-1021.
• [21]Arena U, Vizzutti F, Corti G, Ambu S, Stasi C, Bresci S, Moscarella S, Boddi V, Petrarca A, Laffi G, Marra F, Pinzani M: Acute viral hepatitis increases liver stiffness values measured by transient elastography. Hepatology 2008, 47(2):380-384.
• [22]Sagir A, Erhardt A, Schmitt M, Häussinger D: Transient elastography is unreliable for detection of cirrhosis in patients with acute liver damage. Hepatology 2008, 47(2):592-595.
• [23]Brunetto MR, Oliveri F, Colombatto P, Moriconi F, Ciccorossi P, Coco B, Romagnoli V, Cherubini B, Moscato G, Maina AM, Cavallone D, Bonino F: Hepatitis B surface antigen serum levels help to distinguish active from inactive hepatitis B virus genotype D carriers. Gastroenterology 2010, 139(2):483-490.
• [24]Tseng TC, Liv CJ, Yang HC, Su TH, Wang CC, Chen CL, Kuo SF, Liu CH, Chen PJ, Chen DS, Kao JH: High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load. Gastroenterology 2012, 142(5):1140-1149.
• [25]Tseng TC, Liu CJ, Yang HC, Su TH, Wang CC, Chen CL, Kuo SF, Liu CH, Chen PJ, Chen DS, Kao JH: Determinants of spontaneous surface antigen loss in hepatitis B e antigen-negative patients with a low viral load. Hepatology 2012, 55(1):68-76.
• [26]Guner R, Karahocagil M, Buyukberber M, Kandemir O, Ural O, Usluer G, Inan D, Koksal I, Baykam N, Hizel K, Yamazhan T, Esen S, Tasyaran MA: Correlation between intrahepatic hepatitis B virus cccDNA levels and other activity markers in patients with HBeAg-negative chronic hepatitis B infection. Eur J Gastroenterol Hepatol 2011, 23(12):1185-1191.
• [27]Martinot-Peignoux M, Carvalho RJ, Cardoso AC, Lapalus M, Lada O, Asselah T, Krause F, Marcellin P: Significant genotype-specific association of hepatitis B surface antigen level and severity of liver disease in patients with chronic hepatitis B. Hepatology 2011, 54(Suppl):1078A.