Nutritional Status and Non-Invasive Biomarkers in the Assessment of Liver Fibrosis among Patients with Chronic HBV Infection
Main Article Content
Abstract
Introduction: Liver fibrosis is the principal determinant of long-term outcomes in chronic hepatitis B virus (HBV) infection, predicting progression to cirrhosis, hepatocellular carcinoma (HCC), and mortality. Liver biopsy remains the histological reference standard but is invasive, costly, and prone to sampling error; non-invasive serum biomarkers and transient elastography have therefore emerged as central tools for fibrosis staging. In parallel, nutritional status — encompassing malnutrition, sarcopenia, and micronutrient deficiencies — is increasingly recognized as an independent prognostic factor in chronic HBV. Objective: To synthesize current evidence on nutritional status and non-invasive biomarkers in the assessment of liver fibrosis among adults with chronic HBV infection, and to propose an integrated, nutrology-informed framework for clinical use. Methods: A structured narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library for studies published between January 2000 and December 2025. Search terms combined "hepatitis B," "liver fibrosis," "non-invasive biomarker," "FIB-4," "APRI," "transient elastography," "FibroScan," "malnutrition," "sarcopenia," and "nutritional assessment." Original research, systematic reviews, and clinical guidelines published in English were eligible. Results: FIB-4 and the AST-to-platelet ratio index (APRI) are the most extensively validated serum-based scores in chronic HBV, with strong diagnostic performance for advanced fibrosis and cirrhosis and inclusion in WHO and EASL guidelines. The gamma-glutamyl transpeptidase-to-platelet ratio (GPR), albumin–bilirubin (ALBI), and AST-to-ALT ratio (AAR) provide complementary information. Transient elastography (FibroScan) consistently outperforms simple serum scores and predicts liver-related events, mortality, and fibrosis regression on antiviral therapy. Malnutrition and sarcopenia are highly prevalent in advanced HBV-related liver disease and independently predict decompensation, HCC, and survival. Vitamin D deficiency, hypoalbuminemia, and low handgrip strength carry independent prognostic value beyond conventional scoring systems. Conclusion: Integrating nutritional assessment with validated non-invasive biomarkers provides a clinically meaningful, biopsy-sparing approach to fibrosis staging and prognostication in chronic HBV. Standardized algorithms combining FIB-4, APRI, transient elastography, and structured nutritional screening should be incorporated into routine hepatology and nutrology practice.
Article Details
Section
How to Cite
References
1. World Health Organization. Global Hepatitis Report 2024: action for access in low- and middle-income countries. Geneva: World Health Organization; 2024.
2. World Health Organization. Hepatitis B fact sheet. Geneva: World Health Organization; 2024.
3. Yuen MF, Chen DS, Dusheiko GM, Janssen HLA, Lau DTY, Locarnini SA, et al. Hepatitis B virus infection. Nat Rev Dis Primers. 2018;4:18035.
4. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24(2):289-93.
5. 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(2):370-98.
6. 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):1-98.
7. Bedossa P, Dargère D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology. 2003;38(6):1449-57.
8. Regev A, Berho M, Jeffers LJ, Milikowski C, Molina EG, Pyrsopoulos NT, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol. 2002;97(10):2614-8.
9. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update. J Hepatol. 2021;75(3):659-89.
10. World Health Organization. Guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection. Geneva: World Health Organization; 2024.
11. 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(1):292-302.
12. Goyal R, Mallick SR, Mahanta M, Kedia S, Shalimar, Dhingra R, et al. Fibroscan can avoid liver biopsy in Indian patients with chronic hepatitis B. J Gastroenterol Hepatol. 2013;28(11):1738-45.
13. Aida S, Wei Y, Zhang Q, Wu J, Lin Y, Yang Y, et al. The non-invasive serum biomarkers contribute to indicate liver fibrosis staging and evaluate the progress of chronic hepatitis B. BMC Infect Dis. 2024;24(1):634.
14. Tomeva E, Karadzov-Nikolic A, Genadieva-Dimitrova M, Pivkova-Veljanovska A, Stojanovski A, Spasovski G, et al. Noninvasive biomarkers in assessment of liver fibrosis in patients with HBeAg negative chronic hepatitis B. Open Access Maced J Med Sci. 2018;6(5):811-7.
15. Castera L, Friedrich-Rust M, Loomba R. Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease. Gastroenterology. 2019;156(5):1264-81.e4.
16. Chan HL, Wong GL, Choi PC, Chan AW, Chim AM, Yiu KK, et al. Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B. J Viral Hepat. 2009;16(1):36-44.
17. Kim BK, Fung J, Yuen MF, Kim SU. Clinical application of liver stiffness measurement using transient elastography in chronic liver disease from longitudinal perspectives. World J Gastroenterol. 2013;19(12):1890-900.
18. Kim SU, Han KH, Park JY, Ahn SH, Chung HJ, Chon CY, et al. Prediction of liver-related events using FibroScan in chronic hepatitis B patients showing advanced liver fibrosis. PLoS One. 2012;7(5):e36676.
19. Wu D, Wang Z, Li J, Lv L, Wang J, Xu L, et al. Longitudinal monitoring of liver fibrosis status by transient elastography in chronic hepatitis B patients during long-term entecavir treatment. Clin Exp Med. 2018;18(3):433-43.
20. Tandon P, Raman M, Mourtzakis M, Merli M. A practical approach to nutritional screening and assessment in cirrhosis. Hepatology. 2017;65(3):1044-57.
21. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on nutrition in chronic liver disease. J Hepatol. 2019;70(1):172-93.
22. Tantai X, Liu Y, Yeo YH, Praktiknjo M, Mauro E, Hamaguchi Y, et al. Effect of sarcopenia on survival in patients with cirrhosis: a meta-analysis. J Hepatol. 2022;76(3):588-99.
23. Traub J, Reiss L, Aliwa B, Stadlbauer V. Malnutrition in patients with liver cirrhosis. Nutrients. 2021;13(2):540.
24. Ebadi M, Bhanji RA, Mazurak VC, Montano-Loza AJ. Sarcopenia in cirrhosis: from pathogenesis to interventions. J Gastroenterol. 2019;54(10):845-59.
25. Topan MM, Sporea I, Dănilă M, Popescu A, Ghiuchici AM, Lupuşoru R, et al. Comparison of different nutritional assessment tools in detecting malnutrition and sarcopenia among cirrhotic patients. Diagnostics (Basel). 2022;12(4):893.
26. Chen LW, Chien CW, Yang KL, Kuo SF, Chen CH, Chien RN. Prognostic significance of sarcopenia and severe vitamin D deficiency in patients with cirrhosis. JGH Open. 2023;7(5):350-7.
27. Hoan NX, Khuyen N, Binh MT, Giang DP, Van Tong H, Hoan PQ, et al. Association of vitamin D deficiency with hepatitis B virus-related liver diseases. BMC Infect Dis. 2016;16(1):507.
28. Baethge C, Goldbeck-Wood S, Mertens S. SANRA — a scale for the quality assessment of narrative review articles. Res Integr Peer Rev. 2019;4:5.
29. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
30. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.
31. Lemoine M, Shimakawa Y, Nayagam S, Khalil M, Suso P, Lloyd J, 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(8):1369-76.
32. Affoue Kouakou Y, Doffou SA, Diakité M, Bangoura AD, Mahassadi AK, Attia KA. Interest of non-invasive markers (APRI, FIB-4) for assessing hepatic fibrosis in patients with chronic viral hepatitis B without cytolysis and with low viral replication. Open J Gastroenterol. 2024;14:209-22.
33. Shaheen AA, Myers RP. Diagnostic accuracy of the aspartate aminotransferase-to-platelet ratio index for the prediction of hepatitis C-related fibrosis: a systematic review. Hepatology. 2007;46(3):912-21.
34. Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38(2):518-26.
35. Johnson PJ, Berhane S, Kagebayashi C, Satomura S, Teng M, Reeves HL, et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach—the ALBI grade. J Clin Oncol. 2015;33(6):550-8.
36. Parkes J, Roderick P, Harris S, Day C, Mutimer D, Collier J, et al. Enhanced liver fibrosis test can predict clinical outcomes in patients with chronic liver disease. Gut. 2010;59(9):1245-51.
37. Cardoso AC, Carvalho-Filho RJ, Stern C, Dipumpo A, Giuily N, Ripault MP, et al. Direct comparison of diagnostic performance of transient elastography in patients with chronic hepatitis B and chronic hepatitis C. Liver Int. 2012;32(4):612-21.
38. Wong GL, Wong VW, Choi PC, Chan AW, Chum RH, Chan HK, et al. Assessment of fibrosis by transient elastography compared with liver biopsy and morphometry in chronic liver diseases. Clin Gastroenterol Hepatol. 2008;6(9):1027-35.
39. Singh S, Venkatesh SK, Wang Z, Miller FH, Motosugi U, Low RN, et al. Diagnostic performance of magnetic resonance elastography in staging liver fibrosis: a systematic review and meta-analysis of individual participant data. Clin Gastroenterol Hepatol. 2015;13(3):440-51.
40. Dasarathy S, Merli M. Sarcopenia from mechanism to diagnosis and treatment in liver disease. J Hepatol. 2016;65(6):1232-44.
41. Lai JC, Tandon P, Bernal W, Tapper EB, Ekong U, Dasarathy S, et al. Malnutrition, frailty, and sarcopenia in patients with cirrhosis: 2021 practice guidance by the AASLD. Hepatology. 2021;74(3):1611-44.
42. Iruzubieta P, Terán Á, Crespo J, Fábrega E. Vitamin D deficiency in chronic liver disease. World J Hepatol. 2014;6(12):901-15.
43. Weng X, Zhao Y, Shi J, Chen Z, Zhuang H. Narrative review of nutritional characteristics and supportive treatment of hepatitis B virus-related liver diseases. Dig Med Res. 2020;3:73.
44. Liaw YF, Kao JH, Piratvisuth T, Chan HL, Chien RN, Liu CJ, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012;6(3):531-61.
45. Stickel F, Hellerbrand C. Non-alcoholic fatty liver disease as a risk factor for hepatocellular carcinoma: mechanisms and implications. Gut. 2010;59(10):1303-7.
46. Yang W, Sui J, Ma Y, Simon TG, Petrick JL, Lai M, et al. Dietary patterns and hepatocellular carcinoma risk among US adults. Nutrients. 2021;13(6):2080.
47. Barbería-Latasa M, Martínez-Urbistondo D, Martínez-González MA. The role of the Mediterranean diet and alcohol consumption in chronic liver disease prevention: a narrative review. Medicina (Kaunas). 2025;61(10):1777.