Establishing Cut-Offs for Non-Invasive Liver Tests to Detect Cirrhosis at a High Sensitivity

Andrejs Ernests Zirnis 1 , Zane Straume 1 , 2 , Raisa Bērziņa 1 , Justīne Māliņa-Bambīte 1 , Aleksejs Derovs 1 , 2  and Inese Zeltiņa 1 , 2
  • 1 Rīga Stradiņš University, , 1007, Rīga, Latvia
  • 2 Rīga East Clinical University Hospital, , 1038, Rīga, Latvia


Liver cirrhosis is the end stage of chronic liver diseases. The current gold standard for diagnosing this condition, liver biopsy, has too many drawbacks, and research for better alternatives is ongoing. One major diagnostic arsenal includes various serological composition scores or so-called formulas. They are constantly being validated for development of new formulas. In our retrospective study of 215 patients case files who had confirmed cirrhosis of various etiologies, we examined the sensitivity and set new cut-offs for five of the most well-documented formulas. Data was obtained from the Rīga East University Hospital from 2012 to 2017 and analysed using SPSS V.22.00. In our study we found that FIB-4 at cut-off > 1.45 had over 95% sensitivity for excluding advanced fibrosis regardless of cirrhosis etiology. None of evaluated formulas had high sensitivity for detecting cirrhosis of alcohol etiology. For the viral hepatitis C genesis group, the best choice was deRitis index with almost 90% sensitivity. FIB-4 at cut-off > 2.75 was the best choice for the combined alcohol and viral hepatitis C group; BONACINI at score 8+ and FIB-4 at > 3.25 were the most sensitive in the main group containing all patients irrespective of cirrhosis etiology.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • Adams, L. A. (2015). Non invasive diagnosis of fibrosis in NAFLD, How reliable is it? In: The International Liver Congress. EASL Postgraduate Course: Metabolic Liver Disease, Vienna, 22-–23 April 2015. Vienna, pp. 24–25.

  • Anonymous (2014). Guidelines for the Screening, Care and Treatment of Persons with Hepatitis C Infection. World Health Organization, Geneva. 56 pp.

  • Hussain, A., Gul, M. A., Khalid, M. U. (2019). Validation of novel fibrosis index (NFI) for assessment of liver fibrosis: Comparison with transient elastography (FibroScan). Brit. Med. J. Open Gastroenterol., 6 (1), e000316.

  • Bedossa, P., Dargere, D., Paradis, V. (2003). Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology, 38, 1449–1457.

  • Bonacini, M., Hadi, G., Govindarajan, S., Lindsay, K. L. (1997). Utility of a discriminant score for diagnosing advanced fibrosis or cirrhosis in patients with chronic hepatitis C virus infection. Amer. J. Gastroenterol., 92 (8), 1302–1304.

  • Botros, M., Sikaris, K. A. (2013). The De Ritis ratio: The test of time. Clin. Biochem. Rev., 34 (3), 117–130.

  • Cholongitas, E., Senzolo, M., Standish, R., Marelli, L., Quaglia, A., Patch, D., Dhillon, A. P., Burroughs, A. K. (2006). A systematic review of the quality of liver biopsy specimens. Amer. J. Clin. Pathol., 125, 710–721.

  • Crawford, J. M. (2002). Liver cirrhosis. In: MacSween, R. N. M., Burt, A. D., Portmann, B. C. (eds.). Pathology of the Liver. 4th ed. Churchill Livingstone, London, pp. 575–619.

  • D’Amico, G., Garcia-Tsao, G., Pagliaro, L. (2006). Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies. J. Hepatol., 44, 217–231.

  • De Ritis, F., Coltorti, M., Giusti, G. (1957). An enzymic test for the diagnosis of viral hepatitis: The transaminase serum activities. Clin. Chim. Acta, 2 (1), 70–74.

  • Forns, X., Ampurdančs, S., Llovet, J. M., Aponte, J., Quintó, L., Martínez-Bauer, E., Bruguera, M., Sánchez-Tapias, J. M., Rodés, J. (2002). Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology, 36, 986–992.

  • Grünhage, F., Lammert, F. (2018). Chapter 19. Assesement of hepatic fibrosis and steatosis. In: Hepatology — a Clinical Textbook. 9th edn. Mauss, Berg, Rockstroh, Sarazzin, Wedemeyer.

  • Friedman, S. L. (2008). Hepatic stellate cells: Protean, multifunctional, and enigmatic cells of the liver. Physiol. Rev., 88, 125–172.

  • Garcia-Tsao, G., Friedman, S., Iredale, J., Pinzani, M. (2010). Now there are many (stages) where before there was one: In search of a patho-physiological classification of cirrhosis. Hepatology, 51 (4), 1445–1449.

  • Giannini, E., Botta, F., Fasoli, A., Ceppa, P., Risso, D., Lantieri, P. B., Celle, G., Testa, R. (1999). Progressive liver functional impairment is associated with an increase in AST/ALT ratio. Dig. Dis. Sci., 44, 1249–1253.

  • Gines, P., Quintero, E., Arroyo, V., Teres, J., Bruguera, M., Rimola, A., Caballeria, J., Rodes, J., Rozman, C. (1987). Compensated cirrhosis: Natural history and prognostic factors. Hepatology, 7, 122–128.

  • Huwart, L., Sempoux, C., Vicaut, E., Salameh, N., Annet, L., Danse, E., Peeters, F., Beek, L. C., Rahier, J., Sinkus, R., Horsmans, Y., van Beers, B. E. (2008). Magnetic resonance elastography for the noninvasive staging of liver fibrosis. Gastroenterology, 135, 32–40.

  • Kelly, M. L., Riordan, S. M., Bopage, R., Lloyd, A. R., Post, J. J. (2018). Capacity of non-invasive hepatic fibrosis algorithms to replace transient elastography to exclude cirrhosis in people with hepatitis C virus infection: A multi-centre observational study. PLOS ONE, 13 (2), e0192763.

  • Kose, S., Ersan, G., Tatar, B., Adar, P., Sengel, B. E. (2015). Evaluation of percutaneous liver biopsy complications in patients with chronic viral hepatitis. Eurasian J. Med., 47,161–164.

  • Lieber, C. S., Weiss, D. G., Morgan, T. R., Paronetto, F. (2006). Aspartate aminotransferase to platelet ratio index in patients with alcoholic liver fibrosis. Amer. J. Gastroenterol., 101, 1500–1508.

  • Lurie, Y., Webb, M., Cytter-Kuint, R., Shteingart, S., Lederkremer, G. Z. (2015). Non-invasive diagnosis of liver fibrosis and cirrhosis. World J. Gastroenterol., 21, 11567–11583.

  • Machado, N. N., Jackson, T., Ladhani, H. A., Marks, J. M. (2017). Managing complications in endoscopic procedures: Bleeding from a biopsy site. Minerva Chir., 72, 36–43.

  • Mak, K. M., Chen, L. L., Lee, T.-F. (2013). Codistribution of collagen type IV and laminin in liver fibrosis of elderly cadavers: Immunohistochemical marker of perisinusoidal basement membrane formation. Anat. Rec., 296, 953–964.

  • Minuk, G. Y. (2003). Hepatic regeneration: If it ain’t broke, don’t fix it. Can. J. Gastroenterol., 17 (7), 418–424.

  • Orasan, O. H., Ciulei, G., Cozma, A., Sava, M., Dumitrascu, D. L. (2016). Hyaluronic acid as a biomarker of fibrosis in chronic liver diseases of different etiologies. Clujul. Med., 89 (1), 24–31.

  • Park, G. J., Lin, B. P., Ngu, M. C., Jones, D. B., Katelaris, P. H. (2000). Aspartate aminotransferase. Alanine aminotransferase ratio in chronic hepatitis C infection: Is it a useful predictor of cirrhosis? J. Gastroenterol. Hepatol., 15 (4), 386–390.

  • Park, S. Y., Kang, K. H., Park, J. H., Lee, J. H., Cho, C. M., Tak, W. Y., Kweon, Y. O., Kim, S. K., Choi, Y. H. (2004). Clinical efficacy of AST/ALT ratio and platelet counts as predictors of degree of fibrosis in HBV infected patients without clinically evident liver cirrhosis. Korean J. Gastroenterol., 43, 246–251.

  • Pinzani, M., Rombouts, K., Colagrande, S. (2005). Fibrosis in chronic liver diseases: Diagnosis and management. J. Hepatol., 42 (Suppl. 1), S22–S36.

  • Poynard, T, Bedossa, P. (1996). An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology, 24, 289–293.

  • Pohl, A., Behling, C., Oliver, D., Kilani, M., Monson, P., Hassanein, T. (2001). Serum aminotransferase levels and platelet counts as predictors of degree of fibrosis in chronic hepatitis C virus infection. Amer. J. Gastroenterol., 96 (11), 3142–3146.

  • Regev, A., Berho, M., Jeffers, L. J., Milikowski, C., Molina, E. G., Pyrsopoulos, N. T., Feng, Z. Z., Reddy, K. R., Schiff, E. R. (2002). Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Amer. J. Gastroenterol., 97 (10), 2614–2618.

  • Sande, J. A., Verjee, S., Vinayak, S., Amersi, F., Ghesani, M. (2017). Ultra-sound shear wave elastography and liver fibrosis: A prospective multi-center study. World J. Hepatol., 9, 38–47.

  • Shaheen, A. A., Myers, R. P. (2007). Diagnostic accuracy of the aspartate aminotransferase-to-platelet ratio index for the prediction of hepatitis C-related fibrosis: A systematic review. Hepatology, 46, 912–921.

  • Sheth, S. G., Flamm, S. L., Gordon, F. D., Chopra, S. (1998). AST/ALT ratio predicts Cirrhosis in patients with chronic hepatitis C virus infection. Amer. J. Gastroenterol., 93, 44–48.

  • Soresi, M., Lydia, G., Cervello, M., Licata, A., Montalto, G. (2014). Noninvasive tools for the diagnosis of liver cirrhosis. World J. Gatroenterol., 20 (48), 18131–18150.

  • Sterling, R. K., Lissen, E., Clumeck, N., Sola, R., Correa, M. C., Montaner, J., Sulkowski, M. S., Torriani, F. J., Dieterich, D. T., Thoms, D. L., Messinger, D., Nelson, M., APRICOT Clinical Investigators (2006). Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology, 43, 1317–1325.

  • Tchatalbachev, V. V., Kirkpatrick, D. L., Duff, D. J., Travis, M. D. (2015). Seeding of the rectus sheath with hepatocellular carcinoma after image guided percutaneous liver biopsy using coaxial biopsy needle system. J. Radiol. Case Rep., 9, 18–25.

  • Ustündag, Y., Bilezikēi, B., Boyaciošlu, S., Kayataž, M., Odemir, N. (2000). The utility of AST/ALT ratio as a noninvasive demonstration of the degree of liver fibrosis in chronic HCV patients on long-term haemodialysis. Nephrol. Dial Transplant, 15, 1716–1717.

  • Vallet-Pichard, A., Mallet, V., Nalpas, B., Verkarre, V., Nalpas, A., Dhalluin-Venier, V., Fontaine, P., Pol, S. (2007). FIB-4: An inexpensive and accurate marker of fibrosis in HCV infection. Comparison with liver biopsy and fibrotest. Hepatology, 46, 32–36.

  • Wai, C. T., Greenson, J. K., Fontana, R. J., Kalbfleisch, J. D., Marrero, J. A., Conjeevaram, H. S., Lok, A. S. (2003). A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology, 38, 518–526.

  • Williams, A. L., Hoofnagle, J. H. (1998). Ratio of serum aspartate to alanine aminotransferase in chronic hepatitis. Relationship to cirrhosis. Gastroenterology, 95, 734–739.


Journal + Issues