Are non-invasive fibrosis markers for chronic hepatitis B reliable in sub-Saharan Africa?

Hailemichael Desalegn, Hanna Aberra, Nega Berhe, Svein G Gundersen, Asgeir Johannessen, Hailemichael Desalegn, Hanna Aberra, Nega Berhe, Svein G Gundersen, Asgeir Johannessen

Abstract

Background: In the absence of liver biopsy, the World Health Organization recommends non-invasive tests, such as aspartate aminotransferase to platelet ratio index and FIB-4, to assess liver fibrosis in patients with chronic hepatitis B. However, these tests are not well validated in sub-Saharan Africa. Recently, a new marker, gamma-glutamyl transpeptidase to platelet ratio, was found to be more accurate in an African setting, but this needs confirmation in other cohorts.

Methods: A treatment program for chronic hepatitis B was initiated in Addis Ababa, Ethiopia, in 2015. Non-invasive tests were compared with transient elastography (Fibroscan 402, Echosense, France) using the following thresholds: no fibrosis (≤7.9 kPa), significant fibrosis (>7.9 kPa) and cirrhosis (>11.7 kPa). The diagnostic accuracy was estimated by calculating the area under the receiver operating characteristics curve.

Results: Of 582 treatment-naïve patients, 141 (24.2%) had significant fibrosis and 90 (15.5%) had cirrhosis. The area under the receiver operating characteristics curve of aspartate aminotransferase to platelet ratio index, FIB-4 and gamma-glutamyl transpeptidase to platelet ratio was high both to diagnose significant fibrosis (0.79 [95% CI 0.75-0.84], 0.79 [95% CI 0.75-0.84], 0.80 [95% CI 0.75-0.85]) and cirrhosis (0.86 [95% CI 0.81-0.91], 0.86 [95% CI 0.81-0.91], 0.87 [95% CI 0.82-0.91]). The specificity was high for all tests (94%-100%); however, the sensitivity was poor both to detect fibrosis (10%-45%) and cirrhosis (10%-36%).

Conclusions: Aspartate aminotransferase to platelet ratio index, FIB-4 and gamma-glutamyl transpeptidase to platelet ratio had good diagnostic properties to detect liver fibrosis and cirrhosis in patients with chronic hepatitis B in East Africa. However, the sensitivity was low, and only 10% of patients with cirrhosis were detected using aspartate aminotransferase to platelet ratio index at the World Health Organization recommended threshold.

Trial registration: ClinicalTrials.gov NCT02344498.

Keywords: hepatitis B virus; liver fibrosis; non-invasive tests; sub-Saharan Africa.

© 2017 The Authors. Liver International Published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Box plots of (A) GPR, (B) APRI, and (C) FIB‐4 compared to the degree of fibrosis in a cohort of patients with chronic hepatitis B in Ethiopia. Fibroscan categories were: normal (≤7.9 kPa), fibrosis (8.0‐11.7 kPa), cirrhosis (>11.7 kPa)
Figure 2
Figure 2
Receiver operating curves for APRI, FIB‐4 and GPR to detect (A) significant fibrosis (Fibroscan >7.9 kPa) and (B) cirrhosis (Fibroscan >11.7 kPa) in patients with chronic hepatitis B in Ethiopia

References

    1. Te HS, Jensen DM. Epidemiology of hepatitis B and C viruses: a global overview. Clin Liver Dis. 2010;14:1‐21. vii.
    1. Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006;45:529‐538.
    1. WHO . Hepatitis B Fact Sheet. 2016. . Accessed December 30, 2016.
    1. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661‐662.
    1. EASL clinical practice guidelines . Management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167‐185.
    1. Liaw YF, Leung N, Kao JH, et al. Asian‐Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hep Intl. 2008;2:263‐283.
    1. Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65‐73.
    1. Iloeje UH, Yang HI, Su J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130:678‐686.
    1. Niederau C, Lange S, Heintges T, et al. Prognosis of chronic hepatitis C: results of a large, prospective cohort study. Hepatology. 1998;28:1687‐1695.
    1. Hallager S, Brehm Christensen P, Ladelund S, et al. Mortality in patients with Chronic Hepatitis C and cirrhosis compared to the general population ‐ a Danish cohort study. J Infect Dis 2017;215:192‐201.
    1. van der Meer AJ, Feld JJ, Hofer H, et al. Risk of cirrhosis‐related complications in patients with advanced fibrosis following hepatitis C virus eradication. J Hepatol 2017;66:485‐493.
    1. Piccinino F, Sagnelli E, Pasquale G, Giusti G. Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies. J Hepatol. 1986;2:165‐173.
    1. Marcellin P, Ziol M, Bedossa P, et al. Non‐invasive assessment of liver fibrosis by stiffness measurement in patients with chronic hepatitis B. Liver Int. 2009;29:242‐247.
    1. Ziol M, Handra‐Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005;41:48‐54.
    1. Zarski JP, Sturm N, Guechot J, et al. Comparison of nine blood tests and transient elastography for liver fibrosis in chronic hepatitis C: the ANRS HCEP‐23 study. J Hepatol. 2012;56:55‐62.
    1. Degos F, Perez P, Roche B, et al. Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: a multicenter prospective study (the FIBROSTIC study). J Hepatol. 2010;53:1013‐1021.
    1. Afdhal NH, Bacon BR, Patel K, et al. Accuracy of fibroscan, compared with histology, in analysis of liver fibrosis in patients with hepatitis B or C: a United States multicenter study. Clin Gastroenterol Hepatol. 2015;13:772‐779. e771‐773.
    1. Zhu X, Wang LC, Chen EQ, et al. Prospective evaluation of FibroScan for the diagnosis of hepatic fibrosis compared with liver biopsy/AST platelet ratio index and FIB‐4 in patients with chronic HBV infection. Dig Dis Sci. 2011;56:2742‐2749.
    1. Nguyen‐Khac E, Chatelain D, Tramier B, et al. Assessment of asymptomatic liver fibrosis in alcoholic patients using fibroscan: prospective comparison with seven non‐invasive laboratory tests. Aliment Pharmacol Ther. 2008;28:1188‐1198.
    1. Chon YE, Choi EH, Song KJ, et al. Performance of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B: a meta‐analysis. PLoS ONE 2012;7:e44930.
    1. Singh S, Fujii LL, Murad MH, et al. Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: a systematic review and meta‐analysis. Clin Gastroenterol Hepatol 2013;11:1573‐1584. e1571‐1572; quiz e1588‐1579.
    1. WHO . Guidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection. Geneva: World Health Organization; 2015.
    1. Bates I, Olayemi E. Chapter 67: Blood disorders In: Mabey D, Gill G, Parry D, Mabey E, Weber MW, Whitty CJM, eds., Principles of medicine in Africa. Fourth Edition. New York, NY; Cambridge University Press; 2013:640‐655.
    1. Lemoine M, Shimakawa Y, Nayagam S, et al. The gamma‐glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa. Gut. 2016;65:1369‐1376.
    1. Bonnard P, Sombie R, Lescure FX, et al. Comparison of elastography, serum marker scores, and histology for the assessment of liver fibrosis in hepatitis B virus (HBV)‐infected patients in Burkina Faso. Am J Trop Med Hyg. 2010;82:454‐458.
    1. Mbaye PS, Sarr A, Sire JM, et al. Liver stiffness measurement and biochemical markers in Senegalese chronic hepatitis B patients with normal ALT and high viral load. PLoS ONE. 2011;6:e22291.
    1. Abebe A, Nokes DJ, Dejene A, Enquselassie F, Messele T, Cutts FT. Seroepidemiology of hepatitis B virus in Addis Ababa, Ethiopia: transmission patterns and vaccine control. Epidemiol Infect. 2003;131:757‐770.
    1. Tsega E, Nordenfelt E, Hansson BG. Hepatitis C virus infection and chronic liver disease in Ethiopia where hepatitis B infection is hyperendemic. Trans R Soc Trop Med Hyg. 1995;89:171‐174.
    1. Kefene H, Rapicetta M, Rossi GB, et al. Ethiopian National Hepatitis B Study. J Med Virol. 1988;24:75‐84.
    1. Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518‐526.
    1. Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317‐1325.
    1. DeLong ER, DeLong DM, Clarke‐Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837‐845.
    1. Bossuyt PM, Reitsma JB, Bruns DE, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: The STARD Initiative. Ann Intern Med. 2003;138:40‐44.
    1. Xiao G, Yang J, Yan L. Comparison of diagnostic accuracy of aspartate aminotransferase to platelet ratio index and fibrosis‐4 index for detecting liver fibrosis in adult patients with chronic hepatitis B virus infection: a systemic review and meta‐analysis. Hepatology. 2015;61:292‐302.
    1. Li Q, Song J, Huang Y, et al. The Gamma‐Glutamyl‐Transpeptidase to Platelet Ratio Does not Show Advantages than APRI and Fib‐4 in Diagnosing Significant Fibrosis and Cirrhosis in Patients With Chronic Hepatitis B: A Retrospective Cohort Study in China. Medicine. 2016;95:e3372.
    1. Schiavon LL, Narciso‐Schiavon JL, Ferraz ML, Silva AE, Carvalho‐Filho RJ. The gamma‐glutamyl transpeptidase to platelet ratio (GPR) in HBV patients: just adding up? Gut 2017;66:1169‐1170.
    1. MoH . National guideline for prevention and control of viral hepatitis in Ethiopia. Addis Ababa: Ethiopian Ministry of Health; 2016.
    1. Chen CF, Lee WC, Yang HI, et al. Changes in serum levels of HBV DNA and alanine aminotransferase determine risk for hepatocellular carcinoma. Gastroenterology 2011;141:1240‐1248. 1248 e1241‐1242.
    1. Merican I, Guan R, Amarapuka D, et al. Chronic hepatitis B virus infection in Asian countries. J Gastroenterol Hepatol. 2000;15:1356‐1361.
    1. Siddique I, El‐Naga HA, Madda JP, Memon A, Hasan F. Sampling variability on percutaneous liver biopsy in patients with chronic hepatitis C virus infection. Scand J Gastroenterol. 2003;38:427‐432.
    1. Robert M, Sofair AN, Thomas A, et al. A comparison of hepatopathologists’ and community pathologists’ review of liver biopsy specimens from patients with hepatitis C. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association. 2009;7:335‐338.
    1. Lemoine M, Shimakawa Y, Njie R, et al. Food intake increases liver stiffness measurements and hampers reliable values in patients with chronic hepatitis B and healthy controls: the PROLIFICA experience in The Gambia. Aliment Pharmacol Ther. 2014;39:188‐196.
    1. Fung J, Lai CL, But D, et al. Reduction of liver stiffness following resolution of acute flares of chronic hepatitis B. Hep Intl. 2010;4:716‐722.

Source: PubMed

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