Fibrofast and Fibrosis-4 versus Fibroscan as Indicators of Hepatic Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Cross-Sectional Study

Badawi, Rehab; Hussein, Boshra El-sayed; Watany, Mona Mohamed; Elsabagh, Hala Moustafa; Elkhalawany, Walaa

doi:10.21608/ajgh.2022.153872.1010

	Fibrofast and Fibrosis-4 versus Fibroscan as Indicators of Hepatic Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Cross-Sectional Study
African Journal of Gastroenterology and Hepatology
Volume 5, Issue 1, January 2022, Page 58-75 PDF (632.82 K)
Document Type: Original Clinical
DOI: 10.21608/ajgh.2022.153872.1010
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Authors
Rehab Badawi ¹; Boshra El-sayed Hussein¹; Mona Mohamed Watany²; Hala Moustafa Elsabagh³; Walaa Elkhalawany¹
¹Tropical Medicine and Infectious Diseases Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
²Clinical Pathology Department, Faculty of Medicine, Tanta University Hospital, El-Geesh St., Tanta, Egypt
³Basic Medical Science Department, Faculty of Dentistry, Majmaah University, Majmaah, 11952, Saudi Arabia. Public Health and Community Department, Faculty of Medicine, Tanta University, El-Geesh St., Tanta, Egypt
Abstract
Aims: Non-alcoholic fatty liver disease (NAFLD) is a broad category for a disease spectrum that includes simple steatosis, which can proceed to non-alcoholic steatohepatitis, cirrhosis, and, finally, hepatocellular carcinoma. Due to the invasive nature of liver biopsy, non-invasive diagnostic tools were required. Objective: To compare the performance of simple biochemical scores (fibroblast) FIB-5 and (fibrosis-4) FIB-4 with fibroscan to differentiate mild to moderate fibrosis (MF; F0 to F2) from advanced fibrosis (AF; F3 to F4) in patients with NAFLD. Patients and methods: This cross-sectional study was done on 116 NAFLD patients. All patients were scanned with the FibroScan examination. FIB-5 and FIB-4 were calculated for all patients. Results: The mean kPa score (liver stiffness measurement score) of the patients belonging to advanced fibrosis [9.53 ± 1.05]. The FIB-4 score was significantly higher in patients with advanced fibrosis (1.54 ± 0.38) compared with patients with mild to moderate fibrosis (1.18 ± 0.44), p-value = 0.001, whereas the FIB-5 score was insignificant between patients. Conclusion: FIB-4 is superior to FIB-5 as a simple, non-invasive marker for diagnosing advanced fibrosis in NAFLD patients.
Keywords
fibroscan; liver biopsy; non-invasive markers; FIB-5; FIB-4; non-alcoholic fatty liver disease; CAP; liver fibrosis; LSM; fatty liver
Supplementary Files Fibrofast and Fibrosis-4 versus Fibroscan as Indicators of Hepatic Fibrosis in Non-Alcoholic Fatty Liver Disease Patients.docx the relatioship between hepatitis c related hepatocellular carcinoma.jpeg

Full Text
01-September-2022 Dear Prof Dr. Rehab Badawi, Manuscript ID AJGH-2208-1010 entitled "Fibrofast and Fibrosis-4 versus Fibroscan as Indicators of Hepatic Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Cross-Sectional Study," which you submitted to the African Journal of gastroenterology and hepatology, has been reviewed. The reviewer's comments (s) are included at the end of this email. The reviewers have requested revisions to your manuscript. Therefore, I invite you to respond to the reviewers' comments and revise your manuscript. Instructions on how to do this can be found at the bottom of this email. Because we are trying to facilitate the timely publication of manuscripts submitted to the African journal of gastroenterology and hepatology, your revised manuscript should be submitted as soon as possible. Once again, thank you for submitting your manuscript to the African Journal of gastroenterology and hepatology, and I look forward to receiving your revision. Sincerely, Salem Y Mohamed Chief Editor, African Journal of gastroenterology and hepatology Please, revise your manuscript using a word processing program and save it on your computer. Please also highlight the changes to your manuscript within the document using the track changes mode in MS Word or using bold or colored text. Once the revised manuscript is prepared, you can send it to me via email. Please provide your responses and details of changes made to each comment in an Author Response Letter when submitting your revised manuscript. To expedite the processing of the revised manuscript, please be as specific as possible in your response to the reviewers. Reviewer Comments to Author: Reviewer1: Write full term before abbreviation for the first time (AF in the abstract, SD in methods, for example) - The writing font is not uniform all over the paper. _ The title is a comparison between Scores and fibroscan; however, the conclusion are that FIB4 is superior to FIB5. - Methodology: no details upon biochemical measurements (kits, instruments, place) To evaluate their results. - poor English editing with too many mistakes (especially in statistical analysis, results, and discussion) - Transfer the sentence that all authors agreed on from methods to the end of the paper under the title Authors contributions. - Remove unnecessary subtitles (inclusion criteria, Exclusion criteria, Calculation, and Definition). Instead, add these subtitles to the text as complete sentences. Inclusion criteria were. The score was calculated… - Put table mention in the text between brackets (Table ...) and put p values. - Rewrite the sections (statistical analysis, results, and discussion) because editing errors made them not clear. - The paragraph including ROC curve data of previous papers needs rewriting or be represented in a table for better comparison and understanding. - The titles of tables need grammatical and editing revision. - The values of validity should be represented as % - The authors in the discussion mentioned, " So in our study, we saw diagnostic......" I found it extra ambiguous and not in its correct place. - Table 5: Transfer AUROC under the table as a footnote. -Table 3: mention the units for platelet count(×10³) and BMI (kg/ m²), waist instead of west -Tables 2, 3, and 4 write the number of groups in column headings (n=) Reviewer 2: some words are marked in red to be corrected by explanation or give the full name. Some words marked in blue color have been corrected already. Reviewer 3: The idea of this research is valuable. To help this manuscript to be accepted for publication, some minor corrections are to be made. 1 - The manuscript needs English editing 2- The authors' title does not agree with the data they provided in their study, "Fibrofast and Fibrosis-4 versus Fibroscan as Indicators of Hepatic Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Cross-Sectional Study." • as they already design their study groups depending on ultrasonography • they did not evaluate the US. They only evaluated fibroscan 3- The aim is not precise. The authors reported, "To compare the performance of simple biochemical scores (fibroblast ) FIB-5, and FIB-4 (fibrosis-4) with fibroscan to differentiate non-significant fibrosis ( NSF; F0 to F1) and significant fibrosis (SF; F2 to F4) in patients with NAFLD." in the manuscript there is no data differentiate between early and late diagnosis of NAFLD and no data about the classification of NAFLD cases into mild or severe 4 - Inpatient and methods a- The type of study should be written b- The inclusion criteria are not clear c- The clinical evaluation of patients was not provided "only waist circumference." d- The authors should provide detailed data about how did they assess the NAFLD and provide a reference 5- Regarding the results, a- All abbreviations should be written below the tables b- There are no comments on the results shortage. They should be more apparent. c- Where the ROC curve should contain a line for combination, and the AUC should be provided. 6 - Discussion better contain more explanations for the obtained results. 7- the conclusion should be reformulated. Reviewer 4: It is an exciting study discussing non-invasive methods to detect fibrosis in NAFLD patients, which is a health problem worldwide 1- The authors mentioned the Objective in the abstract section To compare the performance of simple biochemical scores (fibroblast ) FIB-5 and FIB-4 (fibrosis-4) with fibroscan to differentiate non-significant fibrosis ( NSF; F0 to F1) and significant fibrosis (SF; F2 to F4) in patients with NAFLD. Moreover, in the introduction section, the Objective of this study was to compare the performance of simple biochemical scores FIB-5 and FIB-4 with fibroscan to differentiate early fibrosis (F0 to F1) and advanced fibrosis (SF; F2 to F4) in patients with NAFLD. And in the results section, significant fibrosis F3, F4 Please unify the staging of fibrosis 2- Methodology - What is the point of view that the operator was blinded to the patient's diagnosis? I think if the operator knew the diagnosis, the interpretation of the data would be more accurate. - Correct dBm1 to dB/ m 3- According to the results: - Correct p value 0.000 - Add % to sensitivity 42.9, specificity 77.3. also, in discussion 4- References: - Correct ref 6 - Remove highlights. Editor Comments to Author: 1. Please check the author names and affiliations included on your Title Page, mainly that the spelling of all authors' names is correct. They are cited in the order you wish them to appear in the final article. Each author's affiliation details are correct. 2. Please include a 'Structured Abstract': not more than 250 words, broken down into, i.e., Aims, Patients & Methods/Materials & Methods, Results, and Conclusions. For authors presenting the results of clinical trials, the guidelines recommended by CONSORT should be followed when writing the abstract (http://www.consort-statement.org/), and the clinical trial registration number should be included at the end of the abstract, where available. 3. Please include up to 10 keywords in your revised manuscript (including the four keywords you selected as part of the submission process). 4. Please amend the references as per the author guidelines: a. References should be numerically listed in the reference section in the order in which they occur in the text. b. References should appear as a number, i.e., [1, 2] in the text. c. References should cite three authors et al.: it is our house style to list a maximum of six authors, and if there is more than this, three authors et al. 5. Please ensure that all tables and boxes are titled and cited in the text. Please find a link to the African Journal of gastroenterology and hepatology Author Guidelines which explains these sections in more detail: https://ajgh.journals.ekb.eg/journal/authors.note. 6. please check the PDF file of your manuscript regarding plagiarism checking. 7. Please add the scale bar, annotations, magnifications, and program that generated these figures. Also, it is better to submit figures with high resolution and brightness.
References
1- Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980;55(7):434-438. 2 - Zelber-Sagi S, Shoham D, Zvibel I, Abu-Abeid S, Shibolet O, Fishman S. Predictors for advanced fibrosis in morbidly obese non-alcoholic fatty liver patients. World Journal of Hepatol. 2017;9(2):91. 3- Loria P, Lonardo A, Carulli N. Should nonalcoholic fatty liver disease be renamed? Dig Dis. 2005;23(1):72-82. doi: 10.1159/000084728. PMID: 15920328. 4- Dufour JF. Time to Abandon NASH? Hepatol 2016;63(1):9-10.5. 5- Bellentani S and Tiribelli C. Is it time to change NAFLD and NASH nomenclature? Lancet Gastroenterol Hepatol 2017;2(8):547-548. 6- Eslam M, Sanyal AJ, George J. Toward. More Accurate Nomenclature for Fatty Liver Diseases. Gastroenterology 2019;157(3):590-593. 7- Sivell C. Nonalcoholic Fatty Liver Disease: A Silent Epidemic. Gastroenterol Nurs. 2019 Sep/Oct;42(5):428-434. doi: 10.1097/SGA.0000000000000443. PMID: 31574071. 8- Huang DQ, El-Serag HB and Loomba R: Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2021, 18:223-238. 9- Park CC, Nguyen P, Hernandez C, Bettencourt R, Ramirez K, Fortney L, et al. Magnetic Resonance Elastography vs. Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease. Gastroenterol. 2017;152(5): S70. 10 - Boursier J, Vergniol J, Guillet A, Hiriart J-B, Lannes A, Le Bail B, et al. Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease. J Hepatol 2016; 65: 570–578. 11- Attallah AM, Shiha GE and Omran MM. A discriminant score based on four routine laboratory blood tests for accurate diagnosis of severe fibrosis and/or liver cirrhosis in Egyptian patients with chronic hepatitis C. Hepatol Res 2006; 34:163–169. 12- Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, S Sulkowski M, Torriani FJ, Dieterich DT, Thomas DL, Messinger D, Nelson M; APRICOT Clinical Investigators. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006 Jun;43(6):1317-25. doi: 10.1002/hep.21178. PMID: 16729309. 13- Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. Comparison with liver biopsy and fibrotest. Hepatol 2007; 46:32–6. 14- Sandrin L, Tanter M, Gennisson JL, Catheline S, Fink M. Shear elasticity probe for soft tissues with 1-D transient elastography. IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control. 2002;49(4):436–446. 15- Castéra L, Bail BL, Roudot-Thoraval F, Bernard P-H, Foucher J, Merrouche W, et al. Early detection in routine clinical practice of cirrhosis and oesophageal varices in chronic hepatitis C: Comparison of transient elastography (FibroScan) with standard laboratory tests and non-invasive scores. J Hepatol. 2009;50(1):59–68. 16- Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HLY, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2015, 13;10(1):1–98. 17- EASL Clinical Practice Guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012 57(1):167–85. 18- Frith J, Day CP, Henderson E, Burt AD, Newton JL. Non- Alcoholic Fatty Liver Disease in Older People. Gerontol. 2009;55(6):607–13. 19- Moran-Lev H, Cohen S, Webb M, Yerushalmy-Feler A, Amir A, Gal DL, et al. Higher BMI predicts liver fibrosis among obese children and adolescents with NAFLD - an interventional pilot study. BMC Pediatrics. 2021 3;21(1). 20-Ratziu V, Giral P, Charlotte F, Bruckert E, Thibault V, Theodorou I, et al. Liver fibrosis in overweight patients. Gastroenterol. 2000; 118(6):1117–1123. 21-Shimada M. Nonalcoholic steatohepatitis: risk factors for liver fibrosis. Hepatol Research. 2002 Dec;24(4):429–38. 22- Ballestri S, Mantovani A, Baldelli E, Lugari S, Maurantonio M, Nascimbeni F, Marrazzo A, Romagnoli D, Targher G, Lonardo A. Liver Fibrosis Biomarkers Accurately Exclude Advanced Fibrosis and Are Associated with Higher Cardiovascular Risk Scores in Patients with NAFLD or Viral Chronic Liver Disease. Diagnostics (Basel). 2021 Jan 9;11(1):98. doi: 10.3390/diagnostics11010098. PMID: 33435415; PMCID: PMC7827076. 23- Kumari B, Kumar R, Sharma S, Banerjee A, Kumar V, Kumar P, et al. Diagnostic Accuracy of FIB-4 and FIB-5 Scores as Compared to Fibroscan for Assessment of Liver Fibrosis in Patients With Non-Alcoholic Fatty Liver Disease. Cureus. 2021 31; e17622. 24- Amernia B, Moosavy SH, Banookh F, Zoghi G. FIB-4, APRI, and AST/ALT ratio compared to FibroScan for the assessment of hepatic fibrosis in patients with non-alcoholic fatty liver disease in Bandar Abbas, Iran. BMC Gastroenterol. 2021 Dec [cited 2022 May 4];21(1). Available from: https://dx.doi.org/10.1186%2Fs12876-021-02038. 25- Sumida Y, Yoneda M, Tokushige K, Kawanaka M, Fujii H, Yoneda M, Imajo K, Takahashi H, Eguchi Y, Ono M, Nozaki Y, Hyogo H, Koseki M, Yoshida Y, Kawaguchi T, Kamada Y, Okanoue T, Nakajima A, Japan Study Group Of Nafld Jsg-Nafld. FIB-4 First in the Diagnostic Algorithm of Metabolic-Dysfunction-Associated Fatty Liver Disease in the Era of the Global Metabodemic. Life (Basel). 2021 Feb 14;11(2):143. doi: 10.3390/life11020143. PMID: 33672864; PMCID: PMC7917687. 26- Metwally K, Elsabaawy M, Abdel-Samiee M, Morad W, Ehsan N, Abdelsameea E. FIB-5 versus FIB-4 index for assessment of hepatic fibrosis in chronic hepatitis B affected patients. Clinical and Experimental Hepatol. 2020; 6(4):335–338. 27-Shiha G, Seif S, Eldesoky A, Elbasiony M, Soliman R, Metwally A, et al. A simple bedside blood test (Fibrofast; FIB-5) is superior to FIB-4 index for the differentiation between non-significant and significant fibrosis in patients with chronic hepatitis C. Hepatol Int. 2017 19;11(3):286–291. 28- Kolhe KM, Amarapurkar A, Parikh P, Chaubal A, Chauhan S, Khairnar H, et al. Aspartate transaminase to platelet ratio index (APRI) but not FIB-5 or FIB-4 is accurate in ruling out significant fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) in an urban slum-dwelling population. BMJ Open Gastroenterol. 2019;6(1): e000288. 29- Singh D, Das CJ, Baruah MP. Imaging of non-alcoholic fatty liver disease: A road less travelled. Indian J Endocrinol Metab. 2013 Nov;17(6):990-5. doi: 10.4103/2230-8210.122606. PMID: 24381873; PMCID: PMC3872717. 30- Kamali L, Adibi A, Ebrahimian S, Jafari F, Sharifi M. Diagnostic Performance of Ultrasonography in Detecting Fatty Liver Disease in Comparison with Fibroscan in People Suspected of Fatty Liver. Adv Biomed Res. 2019 Nov 27;8:69. doi: 10.4103/abr.abr_114_19. PMID: 31897407; PMCID: PMC6909544.
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