Liver Stiffness and Fibrosis Used as Early Diagnosis of Patients with Chronic Liver Disease in A Retrospective Cross-Sectional Study

Ahmed Saadi Mohammed ^1*, Hiwa Abubakr Hussein ², Saad Ahmed Ali Jadoo ³, Mohanned H. Alsalaumy ⁴, Laith Falah Hassan ⁵, Muhammad Rasul Hussein ⁶

Early diagnosis of chronic liver disease is vital for intervention. Transient elastography aids in predicting fibrosis, guiding treatment decisions effectively.

Abstract

Background: Chronic liver disease (CLD) is a significant health concern globally, often linked to lifestyle factors such as alcohol consumption and obesity. Early identification and intervention are crucial for preventing disease progression. Liver stiffness measurement (LSM) using transient elastography (FibroScan) is a non-invasive method for assessing liver fibrosis, but factors influencing its accuracy need further exploration. This study aims to investigate predictors of liver stiffness and fibrosis in patients with CLD. Methods: A retrospective cross-sectional study was conducted at the Kurdistan Center for Gastroenterology and Hepatology (KCGH) in Iraq from June to December 2019. Medical records of 609 CLD patients who underwent LSM by FibroScan were analyzed. Sociodemographic data, liver function tests, liver size, and fibrosis stage were collected. Multivariate linear regression analysis was performed to identify predictors of LSM. Results: Hepatitis B (47.3%) and non-alcoholic fatty liver disease (NAFLD) (17.9%) were prevalent diagnoses. Liver stiffness ranged from 2.7 to 71.6 kPa, with a mean of 8.8 kPa. Fibrosis staging revealed 38.3% at F0, 23.5% at F1, and 9.2% at F4. Significant associations were found between liver enzyme abnormality, liver size, controlled attenuation parameter (CAP), and fibrosis. Multivariate regression identified fibrosis grade (OR: 4.431), liver disease type (OR: 0.338), and liver size (OR: 3.025) as predictive of FibroScan liver stiffness values (p<0.001). Advanced fibrosis (F4) correlated with elevated alanine aminotransferase (ALT) levels and hepatomegaly. Conclusion: Liver stiffness, fibrosis stage, liver enzyme abnormalities, and liver size are important predictors of fibrosis in patients with CLD. Early detection and intervention are crucial in managing CLD patients, especially those with hepatitis B and NAFLD. Further research is needed to explore additional predictors and refine diagnostic algorithms for better risk stratification and treatment guidance in CLD.

Keywords: Chronic Liver Disease, FibroScan, Liver Stiffness Measurement, Predictors of Fibrosis, Non-Invasive Assessment

References

Abou Zaghla, H. M. A., El Sebai, A. A., Ahmed, O. A., Ahmed, A. F., & Saab, A. A. R. (2021). Growth differentiation factor 15: an emerging diagnostic biomarker of liver fibrosis in chronic hepatitis C patients. Egyptian Liver Journal, 11, 1-10.

Bondini, S., & Younossi, Z. M. (2006). Non-alcoholic fatty liver disease and hepatitis C infection. Minerva gastroenterologica e dietologica, 52(2), 135-143.

Burke, A., & Lucey, M. R. (2004). Non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and orthotopic liver transplantation. American Journal of Transplantation, 4(5), 686-693.

Elzawawy, M. S., Hassanein, S. A., & El Nomrosy, R. M. (2018). The role of fibroscan in assessment of liver cirrhosis in patients with chronic liver disease. Menoufia Medical Journal, 31(2), 520.

Fernandez, M., Trépo, E., Degré, D., Gustot, T., Verset, L., Demetter, P., ... & Moreno, C. (2015). Transient elastography using Fibroscan is the most reliable noninvasive method for the diagnosis of advanced fibrosis and cirrhosis in alcoholic liver disease. European Journal of Gastroenterology & Hepatology, 27(9), 1074-1079.

Ferraioli, G., Tinelli, C., Dal Bello, B., Zicchetti, M., Lissandrin, R., Filice, G., ... & Zaramella, M. (2013). Performance of liver stiffness measurements by transient elastography in chronic hepatitis. World journal of gastroenterology: WJG, 19(1), 49.

Geng, X. X., Huang, R. G., Lin, J. M., Jiang, N., & Yang, X. X. (2016). Transient elastography in clinical detection of liver cirrhosis: A systematic review and meta-analysis. Saudi Journal of Gastroenterology, 22(4), 294-303.

Graupera, I., & Lammert, F. (2018). Screening is caring: Community-based non-invasive diagnosis and treatment strategies for hepatitis C to reduce liver disease burden. Journal of Hepatology, 69(3), 562-563.

Harman, D. J., Ryder, S. D., James, M. W., Jelpke, M., Ottey, D. S., Wilkes, E. A., ... & Guha, I. N. (2015). Direct targeting of risk factors significantly increases the detection of liver cirrhosis in primary care: a cross-sectional diagnostic study utilising transient elastography. BMJ open, 5(4), e007516.

Hart, C. L., Morrison, D. S., Batty, G. D., Mitchell, R. J., & Smith, G. D. (2010). Effect of body mass index and alcohol consumption on liver disease: analysis of data from two prospective cohort studies. Bmj, 340.

Hashimoto, K., Murakami, T., Dono, K., Hori, M., Kim, T., Kudo, M., ... & Monden, M. (2006). Assessment of the severity of liver disease and fibrotic change: the usefulness of hepatic CT perfusion imaging. Oncology reports, 16(4), 677-683.

Jadoo, S. A. A., Alhusseiny, A. H., Yaseen, S. M., Al-Samarrai, M. A. M., & Mahmood, A. S. (2021). Evaluation of health system in Iraq from people's point of view: a comparative study of two different eras. Journal of Ideas in Health, 4(2), 380-388.

Jiang, B., Yuan, G., Wu, J., Wu, Q., Li, L., & Jiang, P. (2022). Prevotella copri ameliorates cholestasis and liver fibrosis in primary sclerosing cholangitis by enhancing the FXR signalling pathway. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1868(3), 166320.

Jung, K. S., Kim, S. U., Ahn, S. H., Park, Y. N., Kim, D. Y., Park, J. Y., ... & Han, K. H. (2011). Risk assessment of hepatitis B virus–related hepatocellular carcinoma development using liver stiffness measurement (FibroScan). Hepatology, 53(3), 885-894.

Kaplan, M. M. (2002). Alanine aminotransferase levels: what's normal?. Annals of internal medicine, 137(1), 49-51.

Kumar, R., Rastogi, A., Sharma, M. K., Bhatia, V., Tyagi, P., Sharma, P., ... & Sarin, S. K. (2013). Liver stiffness measurements in patients with different stages of nonalcoholic fatty liver disease: diagnostic performance and clinicopathological correlation. Digestive Diseases and Sciences, 58, 265-274.

Lai, M., & Afdhal, N. H. (2019). Liver fibrosis determination. Gastroenterology Clinics of North America, 48(2), 281-289.

Lai, M., Hyatt, B. J., Nasser, I., Curry, M., & Afdhal, N. H. (2007). The clinical significance of persistently normal ALT in chronic hepatitis B infection. Journal of hepatology, 47(6), 760-767.

Lallukka, S., Sädevirta, S., Kallio, M. T., Luukkonen, P. K., Zhou, Y., Hakkarainen, A., ... & Yki-Järvinen, H. (2017). Predictors of Liver Fat and Stiffness in Non-Alcoholic Fatty Liver Disease (NAFLD)–an 11-Year Prospective Study. Scientific reports, 7(1), 14561.
 

Lee, J. H., Lee, S. M., Yoon, J. H., Kim, M. J., Ha, H. I., Park, S. J., ... & Lee, J. M. (2021). Impact of respiratory motion on liver stiffness measurements according to different shear wave elastography techniques and region of interest methods: a phantom study. Ultrasonography, 40(1), 103.

Li, C., Li, R., & Zhang, W. (2018). Progress in non-invasive detection of liver fibrosis. Cancer biology & medicine, 15(2), 124.

Liaw, Y. F., & Chu, C. M. (2009). Hepatitis B virus infection. The lancet, 373(9663), 582-592.

Liu, Z., Que, S., Xu, J., & Peng, T. (2014). Alanine aminotransferase-old biomarker and new concept: a review. International journal of medical sciences, 11(9), 925.

Mokdad, A. A., Lopez, A. D., Shahraz, S., Lozano, R., Mokdad, A. H., Stanaway, J., ... & Naghavi, M. (2014). Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis. BMC medicine, 12, 1-24.

Pang, J. X., Zimmer, S., Niu, S., Crotty, P., Tracey, J., Pradhan, F., ... & Myers, R. P. (2014). Liver stiffness by transient elastography predicts liver-related complications and mortality in patients with chronic liver disease. PloS one, 9(4), e95776.

Raizner, A., Shillingford, N., Mitchell, P. D., Harney, S., Raza, R., Serino, J., ... & Lee, C. K. (2017). Hepatic inflammation may influence liver stiffness measurements by transient elastography in children and young adults. Journal of pediatric gastroenterology and nutrition, 64(4), 512-517.

Ramírez Mena, A., Ngom, N. F., Tine, J., Ndiaye, K., Fortes, L., Ndiaye, O., ... & Wandeler, G. (2022). Prevalence and Predictors of Liver Fibrosis in People Living with Hepatitis B in Senegal. Viruses, 14(8), 1614.

Ramírez-Vélez, R., García-Hermoso, A., Correa-Rodríguez, M., & Izquierdo, M. (2022). Defining values for controlled attenuation parameter and liver stiffness in youth without liver disease. Pediatric Research, 91(4), 912-920.

Salkic, N. N., Jovanovic, P., Hauser, G., & Brcic, M. (2014). FibroTest/Fibrosure for significant liver fibrosis and cirrhosis in chronic hepatitis B: a meta-analysis. Official journal of the American College of Gastroenterology| ACG, 109(6), 796-809.

Salman, A. D., Ali, I. A., & Hwaid, A. H. (2022). Prevalence of occult hepatitis B infection in Diyala province, Iraq. Journal of Ideas in Health, 5(2), 685-692.

Seppelt, D., Ittermann, T., Kromrey, M. L., Kolb, C., VWahsen, C., Heiss, P., ... & Kühn, J. P. (2022). Simple diameter measurement as predictor of liver volume and liver parenchymal disease. Scientific Reports, 12(1), 1257.

Setiawan, V. W., Stram, D. O., Porcel, J., Lu, S. C., Le Marchand, L., & Noureddin, M. (2016). Prevalence of chronic liver disease and cirrhosis by underlying cause in understudied ethnic groups: the multiethnic cohort. Hepatology, 64(6), 1969-1977.

Shi, K. Q., Fan, Y. C., Pan, Z. Z., Lin, X. F., Liu, W. Y., Chen, Y. P., & Zheng, M. H. (2013). Transient elastography: a meta-analysis of diagnostic accuracy in evaluation of portal hypertension in chronic liver disease. Liver International, 33(1), 62-71.

Sporea, I., Sirli, R., Deleanu, A., Tudora, A., Popescu, A., Curescu, M., & Bota, S. (2010). Liver stiffness measurements in patients with HBV vs HCV chronic hepatitis: a comparative study. World journal of gastroenterology: WJG, 16(38), 4832.

Tran, L. C., Ley, D., Bourdon, G., Coopman, S., Lerisson, H., Tillaux, C., ... & Aumar, M. (2022). Noninvasive pediatric liver fibrosis measurement: Two-dimensional shear wave elastography compared with transient elastography. Frontiers in Pediatrics, 10, 849815.

Vaz, J., Eriksson, B., Strömberg, U., Buchebner, D., & Midlöv, P. (2020). Incidence, aetiology and related comorbidities of cirrhosis: a Swedish population-based cohort study. BMC gastroenterology, 20, 1-8.

Vivarelli, M., Montalti, R., & Risaliti, A. (2013). Multimodal treatment of hepatocellular carcinoma on cirrhosis: an update. World journal of gastroenterology: WJG, 19(42), 7316.

Vivarelli, M., Montalti, R., & Risaliti, A. (2013). Multimodal treatment of hepatocellular carcinoma on cirrhosis: an update. World journal of gastroenterology: WJG, 19(42), 7316.

Wong, V. W. S., Wong, G. L. H., Woo, J., Abrigo, J. M., Chan, C. K. M., Shu, S. S. T., ... & Chu, W. C. W. (2021). Impact of the new definition of metabolic associated fatty liver disease on the epidemiology of the disease. Clinical Gastroenterology and Hepatology, 19(10), 2161-2171.

Xu, X., Zhu, H., Li, R., Lin, H., Grimm, R., Fu, C., & Yan, F. (2021). Whole-liver histogram and texture analysis on T1 maps improves the risk stratification of advanced fibrosis in NAFLD. European radiology, 31, 1748-1759.

Yan, J. Y., Li, Z. Q., Yu, Z. J., & Kan, Q. C. (2019). Management of individuals with chronic hepatitis B virus infection and persistent normal or mildly elevated aminotransferase levels. Journal of Cellular Biochemistry, 120(4), 6632-6641.

Yoneda, M., Mawatari, H., Fujita, K., Endo, H., Iida, H., Nozaki, Y., ... & Nakajima, A. (2008). Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD). Digestive and Liver Disease, 40(5), 371-378.

Zhang, G. L., Zhao, Q. Y., Lin, C. S., Hu, Z. X., Zhang, T., & Gao, Z. L. (2019). Transient elastography and ultrasonography: Optimal evaluation of liver fibrosis and cirrhosis in patients with chronic hepatitis B concurrent with nonalcoholic fatty liver disease. BioMed Research International, 2019.

Zhang, G. L., Zhao, Q. Y., Lin, C. S., Hu, Z. X., Zhang, T., & Gao, Z. L. (2019). Transient elastography and ultrasonography: Optimal evaluation of liver fibrosis and cirrhosis in patients with chronic hepatitis B concurrent with nonalcoholic fatty liver disease. BioMed Research International, 2019.

Zhang, W., Wang, L., Wang, L., Li, G., Huang, A., Yin, P., ... & Wang, L. (2015). Liver stiffness measurement, better than APRI, Fibroindex, Fib-4, and NBI gastroscopy, predicts portal hypertension in patients with cirrhosis. Cell biochemistry and biophysics, 71, 865-873.