Noninvasive Assessment of Liver Fibrosis in Patients with Chronic Hepatitis C (and Congenital Bleeding Disorders): Where Do We Stand?

 

 Buy Article Permissions and Reprints

Abstract

The assessment and monitoring of liver fibrosis (LF) is a key issue in the management and definition of prognosis of patients with chronic hepatitis C (CHC). In this respect, despite recognized limitations (invasive nature, sampling errors, interobserver variability, nondynamic evaluation of LF), liver biopsy is traditionally considered the reference standard. These limitations stimulated the search for noninvasive approaches for the assessment of LF, particularly attractive in patients with hemophilia and other congenital bleeding disorders (CBD). In patients with congenital bleeding disorders (CBD), who often suffer from CHC because of the past use of nonvirally inactivated plasma-derived products, the risk of bleeding hamper to routinely obtain histological data for LF staging. A variety of methods have been proposed and, in some cases, validated in patients with CHC and other liver diseases, including biomarkers directly or indirectly associated with LF, often combined in scores or algorithms, and the more recently developed physical approaches, evaluating the properties of the liver parenchyma with instrumental techniques studying the propagation of specific signals, that is, transient elastography (TE), acoustic radiation force impulse imaging elastography, and magnetic resonance elastography. This review will describe the available strategies for noninvasive assessment of LF, with more details on the latter promising instrumental approaches. Moreover, although lacking of validation against liver biopsy, recent studies extending the use of noninvasive methods (particularly TE) in the setting of patients with CBD will be discussed.

• References

• 1 Kernoff PBA, Lee CA, Karayiannis P, Thomas HC. High risk of non-A non-B hepatitis after a first exposure to volunteer or commercial clotting factor concentrates: effects of prophylactic immune serum globulin. Br J Haematol 1985; 60 (3) 469-479
  CrossrefPubMedGoogle Scholar
• 2 Rumi MG, Colombo M, Gringeri A, Mannucci PM. High prevalence of antibody to hepatitis C virus in multitransfused hemophiliacs with normal transaminase levels. Ann Intern Med 1990; 112 (5) 379-380
  CrossrefPubMedGoogle Scholar
• 3 Mauser-Bunschoten EP, Bresters D, van Drimmelen AAJ , et al. Hepatitis C infection and viremia in Dutch hemophilia patients. J Med Virol 1995; 45 (3) 241-246
  CrossrefPubMedGoogle Scholar
• 4 Franchini M, Rossetti G, Tagliaferri A , et al. The natural history of chronic hepatitis C in a cohort of HIV-negative Italian patients with hereditary bleeding disorders. Blood 2001; 98 (6) 1836-1841
  CrossrefPubMedGoogle Scholar
• 5 Eyster ME, Sanders J, Goedert JJ. Viral clearance occurs very early during the natural resolution of hepatitis C virus infection in persons with haemophilia. Haemophilia 2004; 10 (1) 75-80
  CrossrefPubMedGoogle Scholar
• 6 Yee TT, Griffioen A, Sabin CA, Dusheiko G, Lee CA. The natural history of HCV in a cohort of haemophilic patients infected between 1961 and 1985. Gut 2000; 47 (6) 845-851
  CrossrefPubMedGoogle Scholar
• 7 Rumi MG, De Filippi F, Santagostino E, Colombo M. Hepatitis C in haemophilia: lights and shadows. Haemophilia 2004; 10 (Suppl. 04) 211-215
  CrossrefPubMedGoogle Scholar
• 8 Alter MJ, Margolis HS, Krawczynski K , et al. The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team. N Engl J Med 1992; 327 (27) 1899-1905
  CrossrefPubMedGoogle Scholar
• 9 Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997; 349 (9055) 825-832
  CrossrefPubMedGoogle Scholar
• 10 Seeff LB, Miller RN, Rabkin CS , et al. 45-year follow-up of hepatitis C virus infection in healthy young adults. Ann Intern Med 2000; 132 (2) 105-111
  PubMedGoogle Scholar
• 11 Telfer P, Sabin C, Devereux H, Scott F, Dusheiko G, Lee C. The progression of HCV-associated liver disease in a cohort of haemophilic patients. Br J Haematol 1994; 87 (3) 555-561
  CrossrefPubMedGoogle Scholar
• 12 Darby SC, Ewart DW, Giangrande PL , et al. Mortality from liver cancer and liver disease in haemophilic men and boys in UK given blood products contaminated with hepatitis C. UK Haemophilia Centre Directors' Organisation. Lancet 1997; 350 (9089) 1425-1431
  CrossrefPubMedGoogle Scholar
• 13 Abergel A, Darcha C, Chevallier M , et al; French Multicentre Study Group. Histological response in patients treated by interferon plus ribavirin for hepatitis C virus-related severe fibrosis. Eur J Gastroenterol Hepatol 2004; 16 (11) 1219-1227
  CrossrefPubMedGoogle Scholar
• 14 Cadranel JF, Rufat P, Degos F ; For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF). Practices of liver biopsy in France: results of a prospective nationwide survey. Hepatology 2000; 32 (3) 477-481
  CrossrefPubMedGoogle Scholar
• 15 Ghany MG, Strader DB, Thomas DL, Seeff LB ; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49 (4) 1335-1374
  CrossrefPubMedGoogle Scholar
• 16 Yano M, Kumada H, Kage M , et al. The long-term pathological evolution of chronic hepatitis C. Hepatology 1996; 23 (6) 1334-1340
  CrossrefPubMedGoogle Scholar
• 17 Stieltjes N, Ounnoughene N, Sava E , et al. Interest of transjugular liver biopsy in adult patients with haemophilia or other congenital bleeding disorders infected with hepatitis C virus. Br J Haematol 2004; 125 (6) 769-776
  CrossrefPubMedGoogle Scholar
• 18 Saab S, Cho D, Quon DVK , et al. Same day outpatient transjugular liver biopsies in haemophilia. Haemophilia 2004; 10 (6) 727-731
  CrossrefPubMedGoogle Scholar
• 19 Castera L. Noninvasive methods to assess liver disease in patients with hepatitis B or C. Gastroenterology 2012; 142 (6) 1293-1302 , e4
  CrossrefPubMedGoogle Scholar
• 20 Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T ; MULTIVIRC Group. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet 2001; 357 (9262) 1069-1075
  CrossrefPubMedGoogle Scholar
• 21 Bourliere M, Penaranda G, Renou C , et al. Validation and comparison of indexes for fibrosis and cirrhosis prediction in chronic hepatitis C patients: proposal for a pragmatic approach classification without liver biopsies. J Viral Hepat 2006; 13 (10) 659-670
  CrossrefPubMedGoogle Scholar
• 22 Sebastiani G, Vario A, Guido M , et al. Stepwise combination algorithms of non-invasive markers to diagnose significant fibrosis in chronic hepatitis C. J Hepatol 2006; 44 (4) 686-693
  CrossrefPubMedGoogle Scholar
• 23 Halfon P, Bacq Y, De Muret A , et al. Comparison of test performance profile for blood tests of liver fibrosis in chronic hepatitis C. J Hepatol 2007; 46 (3) 395-402
  CrossrefPubMedGoogle Scholar
• 24 Poynard T, Munteanu M, Imbert-Bismut F , et al. Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C. Clin Chem 2004; 50 (8) 1344-1355
  CrossrefPubMedGoogle Scholar
• 25 Leroy V, Hilleret MN, Sturm N , et al. Prospective comparison of six non-invasive scores for the diagnosis of liver fibrosis in chronic hepatitis C. J Hepatol 2007; 46 (5) 775-782
  CrossrefPubMedGoogle Scholar
• 26 Sebastiani G, Halfon P, Castera L , et al. SAFE biopsy: a validated method for large-scale staging of liver fibrosis in chronic hepatitis C. Hepatology 2009; 49 (6) 1821-1827
  CrossrefPubMedGoogle Scholar
• 27 Sebastiani G, Halfon P, Castera L , et al. Comparison of three algorithms of non-invasive markers of fibrosis in chronic hepatitis C. Aliment Pharmacol Ther 2012; 35 (1) 92-104
  CrossrefPubMedGoogle Scholar
• 28 Boursier J, de Ledinghen V, Zarski JP , et al; multicentric groups from SNIFF 32, VINDIAG 7, and ANRS/HC/EP23 FIBROSTAR studies. Comparison of eight diagnostic algorithms for liver fibrosis in hepatitis C: new algorithms are more precise and entirely noninvasive. Hepatology 2012; 55 (1) 58-67
  CrossrefPubMedGoogle Scholar
• 29 Nahon P, Thabut G, Ziol M , et al. Liver stiffness measurement versus clinicians' prediction or both for the assessment of liver fibrosis in patients with chronic hepatitis C. Am J Gastroenterol 2006; 101 (12) 2744-2751
  CrossrefPubMedGoogle Scholar
• 30 Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem 2000; 275 (4) 2247-2250
  CrossrefPubMedGoogle Scholar
• 31 Knittel T, Janneck T, Müller L, Fellmer P, Ramadori G. Transforming growth factor beta 1-regulated gene expression of Ito cells. Hepatology 1996; 24 (2) 352-360
  CrossrefPubMedGoogle Scholar
• 32 Bachem MG, Meyer D, Melchior R, Sell KM, Gressner AM. Activation of rat liver perisinusoidal lipocytes by transforming growth factors derived from myofibroblastlike cells. A potential mechanism of self perpetuation in liver fibrogenesis. J Clin Invest 1992; 89 (1) 19-27
  CrossrefPubMedGoogle Scholar
• 33 Sanderson N, Factor V, Nagy P , et al. Hepatic expression of mature transforming growth factor β 1 in transgenic mice results in multiple tissue lesions. Proc Natl Acad Sci U S A 1995; 92 (7) 2572-2576
  CrossrefPubMedGoogle Scholar
• 34 Clouthier DE, Comerford SA, Hammer RE. Hepatic fibrosis, glomerulosclerosis, and a lipodystrophy-like syndrome in PEPCK-TGF-beta1 transgenic mice. J Clin Invest 1997; 100 (11) 2697-2713
  CrossrefPubMedGoogle Scholar
• 35 Castilla A, Prieto J, Fausto N. Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy. N Engl J Med 1991; 324 (14) 933-940
  CrossrefPubMedGoogle Scholar
• 36 Nelson DR, Gonzalez-Peralta RP, Qian K , et al. Transforming growth factor-beta 1 in chronic hepatitis C. J Viral Hepat 1997; 4 (1) 29-35
  CrossrefPubMedGoogle Scholar
• 37 Kanzler S, Baumann M, Schirmacher P , et al. Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue levels of transforming growth factor-β. J Viral Hepat 2001; 8 (6) 430-437
  CrossrefPubMedGoogle Scholar
• 38 Kondou H, Mushiake S, Etani Y, Miyoshi Y, Michigami T, Ozono K. A blocking peptide for transforming growth factor-beta1 activation prevents hepatic fibrosis in vivo. J Hepatol 2003; 39 (5) 742-748
  CrossrefPubMedGoogle Scholar
• 39 Inagaki Y, Nemoto T, Kushida M , et al. Interferon alfa down-regulates collagen gene transcription and suppresses experimental hepatic fibrosis in mice. Hepatology 2003; 38 (4) 890-899
  CrossrefPubMedGoogle Scholar
• 40 Tarantino G, Coppola A, Conca P, Cimino E, Di Minno G. Can serum TGF-beta 1 be used to evaluate the response to antiviral therapy of haemophilic patients with HCV-related chronic hepatitis?. Int J Immunopathol Pharmacol 2008; 21 (4) 1007-1012
  PubMedGoogle Scholar
• 41 Sandrin L, Fourquet B, Hasquenoph JM , et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol 2003; 29 (12) 1705-1713
  CrossrefPubMedGoogle Scholar
• 42 Castéra L, Vergniol J, Foucher J , et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 2005; 128 (2) 343-350
  CrossrefPubMedGoogle Scholar
• 43 Foucher J, Chanteloup E, Vergniol J , et al. Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut 2006; 55 (3) 403-408
  CrossrefPubMedGoogle Scholar
• 44 Shaheen AA, Wan AF, Myers RP. FibroTest and FibroScan for the prediction of hepatitis C-related fibrosis: a systematic review of diagnostic test accuracy. Am J Gastroenterol 2007; 102 (11) 2589-2600
  CrossrefPubMedGoogle Scholar
• 45 Kettaneh A, Marcellin P, Douvin C , et al. Features associated with success rate and performance of FibroScan measurements for the diagnosis of cirrhosis in HCV patients: a prospective study of 935 patients. J Hepatol 2007; 46 (4) 628-634
  CrossrefPubMedGoogle Scholar
• 46 Castera L. Transient elastography and other noninvasive tests to assess hepatic fibrosis in patients with viral hepatitis. J Viral Hepat 2009; 16 (5) 300-314
  CrossrefPubMedGoogle Scholar
• 47 Friedrich-Rust M, Ong MF, Martens S , et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology 2008; 134 (4) 960-974
  CrossrefPubMedGoogle Scholar
• 48 Nightingale KR, Palmeri ML, Nightingale RW, Trahey GE. On the feasibility of remote palpation using acoustic radiation force. J Acoust Soc Am 2001; 110 (1) 625-634
  CrossrefPubMedGoogle Scholar
• 49 Palmeri ML, Frinkley KD, Zhai L , et al. Acoustic radiation force impulse (ARFI) imaging of the gastrointestinal tract. Ultrason Imaging 2005; 27 (2) 75-88
  CrossrefPubMedGoogle Scholar
• 50 Dahl JJ, Pinton GF, Palmeri ML, Agrawal V, Nightingale KR, Trahey GE. A parallel tracking method for acoustic radiation force impulse imaging. IEEE Trans Ultrason Ferroelectr Freq Control 2007; 54 (2) 301-312
  CrossrefPubMedGoogle Scholar
• 51 Popescu A, Sporea I, Sirli R , et al. The mean values of liver stiffness assessed by Acoustic Radiation Force Impulse elastography in normal subjects. Med Ultrasound 2011; 13 (1) 33-37
  PubMedGoogle Scholar
• 52 Boursier J, Isselin G, Fouchard-Hubert I , et al. Acoustic radiation force impulse: a new ultrasonographic technology for the widespread noninvasive diagnosis of liver fibrosis. Eur J Gastroenterol Hepatol 2010; 22 (9) 1074-1084
  CrossrefPubMedGoogle Scholar
• 53 Friedrich-Rust M, Wunder K, Kriener S , et al. Liver fibrosis in viral hepatitis: noninvasive assessment with acoustic radiation force impulse imaging versus transient elastography. Radiology 2009; 252 (2) 595-604
  CrossrefPubMedGoogle Scholar
• 54 Rifai K, Cornberg J, Mederacke I , et al. Clinical feasibility of liver elastography by acoustic radiation force impulse imaging (ARFI). Dig Liver Dis 2011; 43 (6) 491-497
  CrossrefPubMedGoogle Scholar
• 55 Yoneda M, Suzuki K, Kato S , et al. Nonalcoholic fatty liver disease: US-based acoustic radiation force impulse elastography. Radiology 2010; 256 (2) 640-647
  CrossrefPubMedGoogle Scholar
• 56 Palmeri ML, Wang MH, Rouze NC , et al. Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with nonalcoholic fatty liver disease. J Hepatol 2011; 55 (3) 666-672
  CrossrefPubMedGoogle Scholar
• 57 Takahashi H, Ono N, Eguchi Y , et al. Evaluation of acoustic radiation force impulse elastography for fibrosis staging of chronic liver disease: a pilot study. Liver Int 2010; 30 (4) 538-545
  CrossrefPubMedGoogle Scholar
• 58 Sporea I, Sirli R, Popescu A, Danilă M. Acoustic Radiation Force Impulse (ARFI)—a new modality for the evaluation of liver fibrosis. Med Ultrasound 2010; 12 (1) 26-31
  PubMedGoogle Scholar
• 59 Talwalkar JA, Yin M, Fidler JL, Sanderson SO, Kamath PS, Ehman RL. Magnetic resonance imaging of hepatic fibrosis: emerging clinical applications. Hepatology 2008; 47 (1) 332-342
  CrossrefPubMedGoogle Scholar
• 60 Huwart L, Sempoux C, Vicaut E , et al. Magnetic resonance elastography for the noninvasive staging of liver fibrosis. Gastroenterology 2008; 135 (1) 32-40
  CrossrefPubMedGoogle Scholar
• 61 Sebastiani G, Alberti A. How far is noninvasive assessment of liver fibrosis from replacing liver biopsy in hepatitis C?. J Viral Hepat 2012; 19 (Suppl. 01) 18-32
  CrossrefPubMedGoogle Scholar
• 62 Robic MA, Procopet B, Métivier S , et al. Liver stiffness accurately predicts portal hypertension related complications in patients with chronic liver disease: a prospective study. J Hepatol 2011; 55 (5) 1017-1024
  CrossrefPubMedGoogle Scholar
• 63 Kim BK, Kim Y, Han KH , et al. Risk assessment of esophageal variceal bleeding in B-viral liver cirrhosis by a liver stiffness measurement-based model. Am J Gastroenterol 2011; 106 (9) 1654-1662 , 1730
  CrossrefPubMedGoogle Scholar
• 64 Masuzaki R, Tateishi R, Yoshida H , et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology 2009; 49 (6) 1954-1961
  CrossrefPubMedGoogle Scholar
• 65 National Institutes of Health. National Institutes of Health Consensus Development Conference Statement: Management of hepatitis C: 2002—June 10-12, 2002. Hepatology 2002; 36 (5) (Suppl. 01) S3-S20
  PubMedGoogle Scholar
• 66 European Association for the Study of the Liver clinical practice guidelines: management of hepatitis C virus infection. J Hepatol 2011; 55 (2) 245-264
  CrossrefPubMedGoogle Scholar
• 67 Hézode C, Forestier N, Dusheiko G , et al; PROVE2 Study Team. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med 2009; 360 (18) 1839-1850
  CrossrefPubMedGoogle Scholar
• 68 Kwo PY, Lawitz EJ, McCone J , et al; SPRINT-1 investigators. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. Lancet 2010; 376 (9742) 705-716
  CrossrefPubMedGoogle Scholar
• 69 Gane EJ, Roberts SK, Stedman CA , et al. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet 2010; 376 (9751) 1467-1475
  CrossrefPubMedGoogle Scholar
• 70 Lok AS, Gardiner DF, Lawitz E , et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med 2012; 366 (3) 216-224
  CrossrefPubMedGoogle Scholar
• 71 Ragni MV, Moore CG, Soadwa K , et al; HHH Study Group. Impact of HIV on liver fibrosis in men with hepatitis C infection and haemophilia. Haemophilia 2011; 17 (1) 103-111
  CrossrefPubMedGoogle Scholar
• 72 Maor Y, Bashari D, Kenet G , et al. Non-invasive biomarkers of liver fibrosis in haemophilia patients with hepatitis C: can you avoid liver biopsy?. Haemophilia 2006; 12 (4) 372-379
  CrossrefPubMedGoogle Scholar
• 73 Posthouwer D, Mauser-Bunschoten EP, Fischer K, VAN Erpecum KJ, DE Knegt RJ. Significant liver damage in patients with bleeding disorders and chronic hepatitis C: non-invasive assessment of liver fibrosis using transient elastography. J Thromb Haemost 2007; 5 (1) 25-30
  CrossrefPubMedGoogle Scholar
• 74 Kitson M, Roberts S, Kemp W , et al. The prevalence of significant liver fibrosis and cirrhosis in haemophilia patients infected with hepatitis C using FibroScan. Haemophilia 2011; 17 (2) 316-317
  CrossrefPubMedGoogle Scholar
• 75 Fransen van de Putte DE, Fischer K, de Knegt RJ , et al. Beneficial effect of successful HCV treatment in patients with inherited bleeding disorders, assessed by liver stiffness measurements. Haemophilia 2012; 18 (3) e266-e272
  CrossrefPubMedGoogle Scholar
• 76 Fransen van de Putte DE, Fischer K, de Knegt RJ, Posthouwer D, van Erpecum KJ, Mauser-Bunschoten EP. Liver stiffness measurements to assess progression of fibrosis in HCV-infected patients with inherited bleeding disorders. Haemophilia 2011; 17 (5) e975-e980
  PubMedGoogle Scholar
• 77 Maor Y, Halfon P, Bashari D , et al. Fibrotest or Fibroscan for evaluation of liver fibrosis in haemophilia patients infected with hepatitis C. Haemophilia 2010; 16 (1) 148-154
  CrossrefPubMedGoogle Scholar
• 78 Lucidarme D, Foucher J, Le Bail B , et al. Factors of accuracy of transient elastography (fibroscan) for the diagnosis of liver fibrosis in chronic hepatitis C. Hepatology 2009; 49 (4) 1083-1089
  CrossrefPubMedGoogle Scholar
• 79 Vidovic N, Lochowsky RS, Goldmann G , et al. Correlation of transient elastography with APRI and FIB-4 in a cohort of patients with congenital bleeding disorders and HCV or HIV/HCV coinfection. Haemophilia 2010; 16 (5) 778-785
  CrossrefPubMedGoogle Scholar
• 80 Plug I, Van Der Bom JG, Peters M , et al. Mortality and causes of death in patients with hemophilia, 1992-2001: a prospective cohort study. J Thromb Haemost 2006; 4 (3) 510-516
  CrossrefPubMedGoogle Scholar
• 81 Tagliaferri A, Rivolta GF, Iorio A , et al; Italian Association of Hemophilia Centers. Mortality and causes of death in Italian persons with haemophilia, 1990-2007. Haemophilia 2010; 16 (3) 437-446
  PubMedGoogle Scholar
• 82 Coppola A, Santoro C, Franchini M , et al. Emerging issues on comprehensive hemophilia care: preventing, identifying and monitoring age-related comorbidities. Semin Thromb Hemost 2013; 39 (7) 794-802
  Article in Thieme ConnectPubMedGoogle Scholar
• 83 Santagostino E, Colombo M, Rivi M , et al; Study Group of the Association of Italian Hemophilia Centers. A 6-month versus a 12-month surveillance for hepatocellular carcinoma in 559 hemophiliacs infected with the hepatitis C virus. Blood 2003; 102 (1) 78-82
  CrossrefPubMedGoogle Scholar
• 84 Bavu E, Gennisson JL, Couade M , et al. Noninvasive in vivo liver fibrosis evaluation using supersonic shear imaging: a clinical study on 113 hepatitis C virus patients. Ultrasound Med Biol 2011; 37 (9) 1361-1373
  CrossrefPubMedGoogle Scholar
• 85 Nedredal GI, Yin M, McKenzie T , et al. Portal hypertension correlates with splenic stiffness as measured with MR elastography. J Magn Reson Imaging 2011; 34 (1) 79-87
  CrossrefPubMedGoogle Scholar