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Published in: European Radiology 2/2024

Open Access 15-08-2023 | Primary Biliary Cholangitis | Hepatobiliary-Pancreas

Noninvasive prediction of insufficient biochemical response after ursodeoxycholic acid treatment in patients with primary biliary cholangitis based on pretreatment nonenhanced MRI

Authors: Yun Zhang, Xiaoli Fan, Bin Song, Yifeng Liu, Yidi Chen, Tianying Zheng, Yuxin Guo, Ting Duan, Zixing Huang, Li Yang

Published in: European Radiology | Issue 2/2024

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Abstract

Objectives

To explore the feasibility of pretreatment nonenhanced magnetic resonance imaging (MRI) in predicting insufficient biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC).

Methods

From January 2009 to April 2022, consecutive PBC patients who were treated with UDCA and underwent nonenhanced MRI within 30 days before treatment were retrospectively enrolled. All MR images were independently evaluated by two blinded radiologists. Uni- and multivariable logistic regression analyses were performed to develop a predictive model for 12-month insufficient biochemical response. Model performances were evaluated by computing the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.

Results

A total of 74 patients (50.6 ± 11.9 years; 62 females) were included. Three pretreatment MRI features, including hepatomegaly (odds ratio [OR]: 4.580; p = 0.011), periportal hyperintensity on T2-weighted imaging (T2WI) (OR: 4.795, p = 0.008), and narrowing of the bile ducts (OR: 3.491; p = 0.027) were associated with 12-month insufficient biochemical response in the multivariable analysis. A predictive model based on the above indicators had an AUC of 0.781, sensitivity of 85.4%, and specificity of 61.5% for predicting insufficient biochemical response.

Conclusions

A noninvasive model based on three pretreatment MRI features could accurately predict 12-month insufficient biochemical response to UDCA in patients with PBC. Early identification of PBC patients at increased risk for insufficient response can facilitate the timely initiation of additional treatment.

Clinical relevance statement

A noninvasive predictive model constructed by incorporating three pretreatment MRI features may help identify patients with primary biliary cholangitis at high risk of insufficient biochemical response to ursodeoxycholic acid and facilitate the timely initiation of additional treatment.

Key Points

• Noninvasive imaging features based on nonenhanced pretreatment MRI may predict an insufficient biochemical response to UDCA in PBC patients.
• A combined model based on three MRI features (hepatomegaly, periportal hyperintensity on T2-weighted imaging, and narrowing of the bile ducts) further improved the predictive efficacy for an insufficient biochemical response to UDCA in PBC patients, with high sensitivity and specificity.
• The nomogram of the combined model showed good calibration and predictive efficacy for an insufficient biochemical response to UDCA in PBC patients. In particular, the calibration curve visualised the clinical applicability of the prediction model.
Appendix
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Literature
1.
go back to reference Gulamhusein AF, Hirschfield GM (2020) Primary biliary cholangitis: pathogenesis and therapeutic opportunities. Nat Rev Gastroenterol Hepatol 17:93–110PubMed Gulamhusein AF, Hirschfield GM (2020) Primary biliary cholangitis: pathogenesis and therapeutic opportunities. Nat Rev Gastroenterol Hepatol 17:93–110PubMed
2.
go back to reference You H, Ma X, Efe C et al (2022) APASL clinical practice guidance: the diagnosis and management of patients with primary biliary cholangitis. Hepatol Int 16:1–23PubMed You H, Ma X, Efe C et al (2022) APASL clinical practice guidance: the diagnosis and management of patients with primary biliary cholangitis. Hepatol Int 16:1–23PubMed
3.
go back to reference Lv T, Chen S, Li M, Zhang D, Kong Y, Jia J (2021) Regional variation and temporal trend of primary biliary cholangitis epidemiology: a systematic review and meta-analysis. J Gastroenterol Hepatol 36:1423–1434PubMed Lv T, Chen S, Li M, Zhang D, Kong Y, Jia J (2021) Regional variation and temporal trend of primary biliary cholangitis epidemiology: a systematic review and meta-analysis. J Gastroenterol Hepatol 36:1423–1434PubMed
4.
go back to reference Kim KA, Ki M, Choi HY, Kim BH, Jang ES, Jeong SH (2016) Population-based epidemiology of primary biliary cirrhosis in South Korea. Aliment Pharmacol Ther 43:154–162PubMed Kim KA, Ki M, Choi HY, Kim BH, Jang ES, Jeong SH (2016) Population-based epidemiology of primary biliary cirrhosis in South Korea. Aliment Pharmacol Ther 43:154–162PubMed
5.
go back to reference Tanaka A, Mori M, Matsumoto K, Ohira H, Tazuma S, Takikawa H (2019) Increase trend in the prevalence and male-to-female ratio of primary biliary cholangitis, autoimmune hepatitis, and primary sclerosing cholangitis in Japan. Hepatol Res 49:881–889PubMed Tanaka A, Mori M, Matsumoto K, Ohira H, Tazuma S, Takikawa H (2019) Increase trend in the prevalence and male-to-female ratio of primary biliary cholangitis, autoimmune hepatitis, and primary sclerosing cholangitis in Japan. Hepatol Res 49:881–889PubMed
6.
go back to reference Cheung KS, Seto WK, Fung J, Lai CL, Yuen MF (2017) Epidemiology and natural history of primary biliary cholangitis in the Chinese: a territory-based study in Hong Kong between 2000 and 2015. Clin Transl Gastroenterol 8:e116PubMedPubMedCentral Cheung KS, Seto WK, Fung J, Lai CL, Yuen MF (2017) Epidemiology and natural history of primary biliary cholangitis in the Chinese: a territory-based study in Hong Kong between 2000 and 2015. Clin Transl Gastroenterol 8:e116PubMedPubMedCentral
7.
go back to reference Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M (2019) Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology 69:394–419 Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M (2019) Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology 69:394–419
8.
go back to reference European Association for the Study of the Liver (2017) EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol 67:145–172 European Association for the Study of the Liver (2017) EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol 67:145–172
9.
go back to reference Chinese Society of Hepatology, Chinese Medical Association, Chinese Society of Gastroenterology, Chinese Medical Association, Chinese Society of Infectious Diseases, Chinese Medical Association (2016) Consensus on the diagnosis and management of primary biliary cirrhosis (cholangitis). Zhonghua Gan Zang Bing Za Zhi 24:5–13 Chinese Society of Hepatology, Chinese Medical Association, Chinese Society of Gastroenterology, Chinese Medical Association, Chinese Society of Infectious Diseases, Chinese Medical Association (2016) Consensus on the diagnosis and management of primary biliary cirrhosis (cholangitis). Zhonghua Gan Zang Bing Za Zhi 24:5–13
10.
go back to reference Lammers WJ, van Buuren HR, Hirschfield GM et al (2014) Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study. Gastroenterol 147:1338–1349.e1335 quiz e1315 Lammers WJ, van Buuren HR, Hirschfield GM et al (2014) Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study. Gastroenterol 147:1338–1349.e1335 quiz e1315
11.
go back to reference Corpechot C, Abenavoli L, Rabahi N et al (2008) Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology 48:871–877 Corpechot C, Abenavoli L, Rabahi N et al (2008) Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology 48:871–877
12.
go back to reference Harms MH, Lammers WJ, Thorburn D et al (2018) Major hepatic complications in ursodeoxycholic acid-treated patients with primary biliary cholangitis: risk factors and time trends in incidence and outcome. Am J Gastroenterol 113:254–264PubMed Harms MH, Lammers WJ, Thorburn D et al (2018) Major hepatic complications in ursodeoxycholic acid-treated patients with primary biliary cholangitis: risk factors and time trends in incidence and outcome. Am J Gastroenterol 113:254–264PubMed
13.
go back to reference Nevens F, Andreone P, Mazzella G et al (2016) A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med 375:631–643PubMed Nevens F, Andreone P, Mazzella G et al (2016) A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med 375:631–643PubMed
14.
go back to reference Parés A, Caballería L, Rodés J (2006) Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic acid. Gastroenterol 130:715–720 Parés A, Caballería L, Rodés J (2006) Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic acid. Gastroenterol 130:715–720
15.
go back to reference Kumagi T, Guindi M, Fischer SE et al (2010) Baseline ductopenia and treatment response predict long-term histological progression in primary biliary cirrhosis. Am J Gastroenterol 105:2186–2194PubMed Kumagi T, Guindi M, Fischer SE et al (2010) Baseline ductopenia and treatment response predict long-term histological progression in primary biliary cirrhosis. Am J Gastroenterol 105:2186–2194PubMed
16.
go back to reference Cebada Chaparro E, Lloret Del Hoyo J, Méndez Fernández R (2020) Chronic cholangitides: differential diagnosis and role of MRI. Radiologia (Engl Ed) 62:452–463PubMed Cebada Chaparro E, Lloret Del Hoyo J, Méndez Fernández R (2020) Chronic cholangitides: differential diagnosis and role of MRI. Radiologia (Engl Ed) 62:452–463PubMed
17.
go back to reference Sohns JM, Staab W, Dabir D et al (2014) Current role and future potential of magnetic resonance cholangiopancreatography with an emphasis on incidental findings. Clin Imaging 38:35–41PubMed Sohns JM, Staab W, Dabir D et al (2014) Current role and future potential of magnetic resonance cholangiopancreatography with an emphasis on incidental findings. Clin Imaging 38:35–41PubMed
18.
go back to reference Idilman IS, Venkatesh SH, Eaton JE et al (2020) Magnetic resonance imaging features in 283 patients with primary biliary cholangitis. Eur Radiol 30:5139–5148PubMed Idilman IS, Venkatesh SH, Eaton JE et al (2020) Magnetic resonance imaging features in 283 patients with primary biliary cholangitis. Eur Radiol 30:5139–5148PubMed
19.
go back to reference Kovač JD, Ješić R, Stanisavljević D et al (2012) Integrative role of MRI in the evaluation of primary biliary cirrhosis. Eur Radiol 22:688–694PubMed Kovač JD, Ješić R, Stanisavljević D et al (2012) Integrative role of MRI in the evaluation of primary biliary cirrhosis. Eur Radiol 22:688–694PubMed
20.
go back to reference Haliloglu N, Erden A, Erden I (2009) Primary biliary cirrhosis: evaluation with T2-weighted MR imaging and MR cholangiopancreatography. Eur J Radiol 69:523–527PubMed Haliloglu N, Erden A, Erden I (2009) Primary biliary cirrhosis: evaluation with T2-weighted MR imaging and MR cholangiopancreatography. Eur J Radiol 69:523–527PubMed
21.
go back to reference Nilsson H, Blomqvist L, Douglas L, Nordell A, Jonas E (2010) Assessment of liver function in primary biliary cirrhosis using Gd-EOB-DTPA-enhanced liver MRI. HPB (Oxford) 12:567–576 Nilsson H, Blomqvist L, Douglas L, Nordell A, Jonas E (2010) Assessment of liver function in primary biliary cirrhosis using Gd-EOB-DTPA-enhanced liver MRI. HPB (Oxford) 12:567–576
22.
go back to reference Han D, Liu J, Jin E, He W (2019) Liver assessment using Gd-EOB-DTPA-enhanced magnetic resonance imaging in primary biliary cholangitis patients. Jpn J Radiol 37:412–419PubMed Han D, Liu J, Jin E, He W (2019) Liver assessment using Gd-EOB-DTPA-enhanced magnetic resonance imaging in primary biliary cholangitis patients. Jpn J Radiol 37:412–419PubMed
23.
go back to reference Morgan MA, Sundaram KM (2023) Primary biliary cholangitis: review for radiologists. Abdom Radiol (NY) 48:127–135 Morgan MA, Sundaram KM (2023) Primary biliary cholangitis: review for radiologists. Abdom Radiol (NY) 48:127–135
24.
go back to reference Kuiper EM, Zondervan PE, van Buuren HR (2010) Paris criteria are effective in diagnosis of primary biliary cirrhosis and autoimmune hepatitis overlap syndrome. Clin Gastroenterol Hepatol 8:530–534 Kuiper EM, Zondervan PE, van Buuren HR (2010) Paris criteria are effective in diagnosis of primary biliary cirrhosis and autoimmune hepatitis overlap syndrome. Clin Gastroenterol Hepatol 8:530–534
25.
go back to reference Wenzel JS, Donohoe A, Ford KL 3rd, Glastad K, Watkins D, Molmenti E (2001) Primary biliary cirrhosis: MR imaging findings and description of MR imaging periportal halo sign. AJR Am J Roentgenol 176:885–889PubMed Wenzel JS, Donohoe A, Ford KL 3rd, Glastad K, Watkins D, Molmenti E (2001) Primary biliary cirrhosis: MR imaging findings and description of MR imaging periportal halo sign. AJR Am J Roentgenol 176:885–889PubMed
26.
go back to reference Khoshpouri P, Habibabadi RR, Hazhirkarzar B, Ameli S, Ghadimi M, Ghasabeh MA (2019) Imaging features of primary sclerosing cholangitis: from diagnosis to liver transplant follow-up. Radiographics 39:1938–1964PubMed Khoshpouri P, Habibabadi RR, Hazhirkarzar B, Ameli S, Ghadimi M, Ghasabeh MA (2019) Imaging features of primary sclerosing cholangitis: from diagnosis to liver transplant follow-up. Radiographics 39:1938–1964PubMed
27.
go back to reference Blachar A, Federle MP, Brancatelli G (2001) Primary biliary cirrhosis: clinical, pathologic, and helical CT findings in 53 patients. Radiology 220:329–336PubMed Blachar A, Federle MP, Brancatelli G (2001) Primary biliary cirrhosis: clinical, pathologic, and helical CT findings in 53 patients. Radiology 220:329–336PubMed
28.
go back to reference Cannella R, Dasyam N, Seo SH, Furlan A, Borhani AA (2021) Performance of morphologic criteria for the diagnosis of cirrhosis in patients with non-alcoholic steatohepatitis compared to other etiologies of chronic liver disease: effect of level of training and experience. Abdom Radiol (NY) 46:960–968 Cannella R, Dasyam N, Seo SH, Furlan A, Borhani AA (2021) Performance of morphologic criteria for the diagnosis of cirrhosis in patients with non-alcoholic steatohepatitis compared to other etiologies of chronic liver disease: effect of level of training and experience. Abdom Radiol (NY) 46:960–968
29.
go back to reference Ludwig DR, Fraum TJ, Ballard DH, Narra VR, Shetty AS (2021) Imaging biomarkers of hepatic fibrosis: reliability and accuracy of hepatic periportal space widening and other morphologic features on MRI. AJR Am J Roentgenol 216:1229–1239PubMedPubMedCentral Ludwig DR, Fraum TJ, Ballard DH, Narra VR, Shetty AS (2021) Imaging biomarkers of hepatic fibrosis: reliability and accuracy of hepatic periportal space widening and other morphologic features on MRI. AJR Am J Roentgenol 216:1229–1239PubMedPubMedCentral
30.
go back to reference Venkatesh SK, Yin M, Takahashi N, Glockner JF, Talwalkar JA, Ehman RL (2015) Non-invasive detection of liver fibrosis: MR imaging features vs. MR Elastography. Abdom Imaging 40:766–775 Venkatesh SK, Yin M, Takahashi N, Glockner JF, Talwalkar JA, Ehman RL (2015) Non-invasive detection of liver fibrosis: MR imaging features vs. MR Elastography. Abdom Imaging 40:766–775
31.
go back to reference Zhang Y, Zhang XM, Prowda JC et al (2009) Changes in hepatic venous morphology with cirrhosis on MRI. J Magn Reson Imaging 29:1085–1092PubMed Zhang Y, Zhang XM, Prowda JC et al (2009) Changes in hepatic venous morphology with cirrhosis on MRI. J Magn Reson Imaging 29:1085–1092PubMed
32.
go back to reference Sarcognato S, Sacchi D, Grillo F et al (2021) Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis. Pathologica 113:170–184PubMedPubMedCentral Sarcognato S, Sacchi D, Grillo F et al (2021) Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis. Pathologica 113:170–184PubMedPubMedCentral
33.
go back to reference Ludwig J, Dickson ER, McDonald GS (1978) Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis). Virchows Archiv A Pathol Anat Histol 379:103–112 Ludwig J, Dickson ER, McDonald GS (1978) Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis). Virchows Archiv A Pathol Anat Histol 379:103–112
34.
go back to reference Perez AA, Noe-Kim V, Lubner MG et al (2022) Deep learning CT-based quantitative visualisation tool for liver volume estimation: defining normal and hepatomegaly. Radiology 302:336–342PubMed Perez AA, Noe-Kim V, Lubner MG et al (2022) Deep learning CT-based quantitative visualisation tool for liver volume estimation: defining normal and hepatomegaly. Radiology 302:336–342PubMed
35.
go back to reference Henderson JM, Heymsfield SB, Horowitz J, Kutner MH (1981) Measurement of liver and spleen volume by computed tomography. Assessment of reproducibility and changes found following a selective distal splenorenal shunt. Radiology 141:525–527PubMed Henderson JM, Heymsfield SB, Horowitz J, Kutner MH (1981) Measurement of liver and spleen volume by computed tomography. Assessment of reproducibility and changes found following a selective distal splenorenal shunt. Radiology 141:525–527PubMed
36.
go back to reference Akai H, Kiryu S, Ohta Y et al (2017) The natural history of streptozotocin-stimulated non-alcoholic steatohepatitis mice followed by Gd-EOB-DTPA-enhanced MRI: comparison with simple steatosis mice. Magn Reson Imaging 38:123–128PubMed Akai H, Kiryu S, Ohta Y et al (2017) The natural history of streptozotocin-stimulated non-alcoholic steatohepatitis mice followed by Gd-EOB-DTPA-enhanced MRI: comparison with simple steatosis mice. Magn Reson Imaging 38:123–128PubMed
37.
go back to reference Muggli D, Müller MA, Karlo C, Fornaro J, Marincek B, Frauenfelder T (2009) A simple method to approximate liver size on cross-sectional images using living liver models. Clin Radiol 64:682–689PubMed Muggli D, Müller MA, Karlo C, Fornaro J, Marincek B, Frauenfelder T (2009) A simple method to approximate liver size on cross-sectional images using living liver models. Clin Radiol 64:682–689PubMed
38.
go back to reference Dodd GD 3rd, Baron RL, Oliver JH 3rd, Federle MP (1999) Spectrum of imaging findings of the liver in end-stage cirrhosis: part I, gross morphology and diffuse abnormalities. AJR Am J Roentgenol 173:1031–1036PubMed Dodd GD 3rd, Baron RL, Oliver JH 3rd, Federle MP (1999) Spectrum of imaging findings of the liver in end-stage cirrhosis: part I, gross morphology and diffuse abnormalities. AJR Am J Roentgenol 173:1031–1036PubMed
39.
go back to reference Dodd GD 3rd, Baron RL, Oliver JH 3rd, Federle MP (1999) Spectrum of imaging findings of the liver in end-stage cirrhosis: part II, focal abnormalities. AJR Am J Roentgenol 173:1185–1192PubMed Dodd GD 3rd, Baron RL, Oliver JH 3rd, Federle MP (1999) Spectrum of imaging findings of the liver in end-stage cirrhosis: part II, focal abnormalities. AJR Am J Roentgenol 173:1185–1192PubMed
40.
go back to reference Bergasa NV, Jones EA (2017) Assessment of the visual analogue score in the evaluation of the pruritus of cholestasis. J Clin Translat Hepatol 5:203–207 Bergasa NV, Jones EA (2017) Assessment of the visual analogue score in the evaluation of the pruritus of cholestasis. J Clin Translat Hepatol 5:203–207
41.
go back to reference Tian S, Liu Y, Sun K et al (2020) A nomogram based on pretreatment clinical parameters for the prediction of inadequate biochemical response in primary biliary cholangitis. J Clin Lab Anal 34:e23501PubMedPubMedCentral Tian S, Liu Y, Sun K et al (2020) A nomogram based on pretreatment clinical parameters for the prediction of inadequate biochemical response in primary biliary cholangitis. J Clin Lab Anal 34:e23501PubMedPubMedCentral
42.
go back to reference Corpechot C, Chazouillères O, Poupon R (2011) Early primary biliary cirrhosis: biochemical response to treatment and prediction of long-term outcome. J Hepatol 55:1361–1367PubMed Corpechot C, Chazouillères O, Poupon R (2011) Early primary biliary cirrhosis: biochemical response to treatment and prediction of long-term outcome. J Hepatol 55:1361–1367PubMed
Metadata
Title
Noninvasive prediction of insufficient biochemical response after ursodeoxycholic acid treatment in patients with primary biliary cholangitis based on pretreatment nonenhanced MRI
Authors
Yun Zhang
Xiaoli Fan
Bin Song
Yifeng Liu
Yidi Chen
Tianying Zheng
Yuxin Guo
Ting Duan
Zixing Huang
Li Yang
Publication date
15-08-2023
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 2/2024
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-023-10080-w

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