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Rabindranath M, Zaya R, Prayitno K, Orchanian-Cheff A, Patel K, Jaeckel E, Bhat M. A Comprehensive Review of Liver Allograft Fibrosis and Steatosis: From Cause to Diagnosis. Transplant Direct 2023; 9:e1547. [PMID: 37854023 PMCID: PMC10581596 DOI: 10.1097/txd.0000000000001547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 09/11/2023] [Accepted: 09/14/2023] [Indexed: 10/20/2023] Open
Abstract
Despite advances in posttransplant care, long-term outcomes for liver transplant recipients remain unchanged. Approximately 25% of recipients will advance to graft cirrhosis and require retransplantation. Graft fibrosis progresses in the context of de novo or recurrent disease. Recurrent hepatitis C virus infection was previously the most important cause of graft failure but is now curable in the majority of patients. However, with an increasing prevalence of obesity and diabetes and nonalcoholic fatty liver disease as the most rapidly increasing indication for liver transplantation, metabolic dysfunction-associated liver injury is anticipated to become an important cause of graft fibrosis alongside alloimmune hepatitis and alcoholic liver disease. To better understand the landscape of the graft fibrosis literature, we summarize the associated epidemiology, cause, potential mechanisms, diagnosis, and complications. We additionally highlight the need for better noninvasive methods to ameliorate the management of graft fibrosis. Some examples include leveraging the microbiome, genetic, and machine learning methods to address these limitations. Overall, graft fibrosis is routinely seen by transplant clinicians, but it requires a better understanding of its underlying biology and contributors that can help inform diagnostic and therapeutic practices.
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Affiliation(s)
- Madhumitha Rabindranath
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Rita Zaya
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Khairunnadiya Prayitno
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Ani Orchanian-Cheff
- Library and Information Services, University Health Network, Toronto, ON, Canada
| | - Keyur Patel
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Elmar Jaeckel
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Mamatha Bhat
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
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Javed N, Ghazanfar H, Jyala A, Patel H. Associations of Real-Time Ultrasound and Strain and Shear Wave Elastography with Gastrointestinal Organs: A Systematic Review. Diagnostics (Basel) 2023; 13:3302. [PMID: 37958199 PMCID: PMC10649379 DOI: 10.3390/diagnostics13213302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 10/18/2023] [Accepted: 10/24/2023] [Indexed: 11/15/2023] Open
Abstract
Ultrasound elastography is gaining attention for its diagnostic potential across various medical fields, and its physical properties make it valuable in modern clinical medicine. However, its specific attributes, especially in the context of recent medical advancements, remain relatively unexplored. This study aimed to identify instrument-specific characteristics and applications of real-time ultrasound elastography, shear wave elastography, and strain elastography, particularly within gastroenterology. Following PRISMA guidelines, the study examined elastography articles on databases like PubMed, resulting in 78 included articles. Data on patient demographics, organ involvement, specificity, sensitivity, accuracy, positive predictive value, and negative predictive value were extracted. Statistical analysis involved SPSS version 21, with significance set at p < 0.05. The majority of patients were male (50.50%), with a mean age of 42.73 ± 4.41 years. Shear wave elastography was the most prevalent technique (48.7%), and liver investigations were predominant in gastroenterology (34.6%). Gastrointestinal applications showed higher sensitivity, positive predictive value, and negative predictive values (p < 0.05) but lower specificity (p < 0.05). Real-time ultrasound elastography exhibited increased specificity, accuracy, and predictive values (p < 0.05). Ultrasound elastography appears more accurate and effective in gastroenterological settings. Nonetheless, its performance depends on instrument-specific and operator-dependent factors. While promising, further studies are necessary to ascertain optimal utilization in both gastrointestinal and non-gastrointestinal conditions.
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Affiliation(s)
- Nismat Javed
- Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA;
| | - Haider Ghazanfar
- Department of Gastroenterology, BronxCare Health System, Bronx, NY 10457, USA; (H.G.); (A.J.)
| | - Abhilasha Jyala
- Department of Gastroenterology, BronxCare Health System, Bronx, NY 10457, USA; (H.G.); (A.J.)
| | - Harish Patel
- Department of Gastroenterology, BronxCare Health System, Bronx, NY 10457, USA; (H.G.); (A.J.)
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Rinaldi L, Giorgione C, Mormone A, Esposito F, Rinaldi M, Berretta M, Marfella R, Romano C. Non-Invasive Measurement of Hepatic Fibrosis by Transient Elastography: A Narrative Review. Viruses 2023; 15:1730. [PMID: 37632072 PMCID: PMC10459581 DOI: 10.3390/v15081730] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/04/2023] [Accepted: 08/11/2023] [Indexed: 08/27/2023] Open
Abstract
Transient elastography by FibroScan® (Echosens, Paris, France) is a non-invasive method that can provide a reliable measurement of liver fibrosis through the evaluation of liver stiffness. Despite its limitations and risks, liver biopsy has thus far been the only procedure able to provide data to quantify fibrosis. Scientific evidence and clinical practice have made it possible to use FibroScan® in the diagnostic work-up of several liver diseases to monitor patients' long-term treatment response and for complication prevention. For these reasons, this procedure is widely used in clinical practice and is still being investigated for further applications. The aim of this narrative review is to provide a comprehensive overview of the main applications of transient elastography in the current clinical practice.
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Affiliation(s)
- Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Chiara Giorgione
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Andrea Mormone
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Francesca Esposito
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Michele Rinaldi
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, “Federico II” University of Naples, 80131 Naples, Italy;
| | - Massimiliano Berretta
- Department of Clinical and Experimental Medicine, University of Messina, 98121 Messina, Italy;
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Ciro Romano
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
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Eshraghian A, Fattahi MR, Taghavi A, Shamsaeefar A, Mansoorian M, Kazemi K, Nikeghbalian S, Malek-Hosseini SA. Metabolic syndrome, hepatic fibrosis, and steatosis diagnosed by liver stiffness measurement and controlled attenuation parameter after liver transplantation: the impact on long-term survival. Expert Rev Gastroenterol Hepatol 2022; 16:1003-1009. [PMID: 36254767 DOI: 10.1080/17474124.2022.2137488] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) are used for diagnosis of liver fibrosis and steatosis. This study aimed to noninvasively evaluate hepatic steatosis and fibrosis in liver transplant recipients using CAP and LSM and the impact on survival of patients. METHODS In a prospective study, adult liver transplant recipients were included. CAP and LSM obtained during transient elastography (TE) were used for assessment of hepatic steatosis and fibrosis. Patients were followed during 4 years for mortality as the main outcome after liver transplantation. RESULTS From 296 patients, 24.7% and 25% of liver transplant recipients had liver steatosis and fibrosis in CAP and LSM, respectively. In multivariable Cox regression analysis, etiology of liver disease (NASH versus non-NASH) (HR: 3.125; 95% CI: 1.594-6.134; p = 0.001), and post-transplant diabetes mellitus (PTDM) (HR: 2.617; 95% CI: 1.396-4.926; p = 0.003) were associated with hepatic steatosis after liver transplantation. In multivariable Cox regression analysis, liver fibrosis was an independent predictor of mortality after liver transplantation (HR: 4.926; 95%CI: 1.779-13.513; p = 0.002). CONCLUSION CAP and LS measurement during TE are useful methods for diagnosis of hepatic steatosis and fibrosis in liver transplant recipients. LS measurement might predict long-term survival of patients.
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Affiliation(s)
- Ahad Eshraghian
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz, Iran
| | - Mohammad Reza Fattahi
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alireza Taghavi
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alireza Shamsaeefar
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohsenreza Mansoorian
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Kourosh Kazemi
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Saman Nikeghbalian
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Ali Malek-Hosseini
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
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Costantino A, Piagnani A, Nandi N, Sciola V, Maggioni M, Donato F, Vecchi M, Lampertico P, Casazza G, Fraquelli M. Reproducibility and diagnostic accuracy of pocket-sized ultrasound devices in ruling out compensated cirrhosis of mixed etiology. Eur Radiol 2022; 32:4609-4615. [PMID: 35238968 PMCID: PMC9213370 DOI: 10.1007/s00330-022-08572-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 12/27/2021] [Accepted: 01/07/2022] [Indexed: 11/10/2022]
Abstract
OBJECTIVE Fibrosis is the key prognostic factor in chronic liver disease patients. Liver surface nodularity (LSN) is the ultrasonographic sign with the highest accuracy to detect advanced liver fibrosis. The use of pocket-sized ultrasound devices (PUDs) has been assessed in several clinical settings but never as regards chronic liver disease (CLD) severity. Our study aimed at evaluating the feasibility, reproducibility, and diagnostic accuracy of PUD in LSN identification. METHODS We enrolled all the consecutive adults referred for percutaneous liver biopsy. Two independent operators evaluated LSN by PUD; one sonographer used standard ultrasound (US). Transient elastography (TE) and liver biopsy were performed on all the patients. PUD reproducibility was evaluated by Cohen's k statistic. PUD, standard US, and TE results were compared with histology staging. RESULTS A total of 104 consecutive patients (aged 54 ± 14 years) with mixed-etiology CLD were studied. Assessment by PUD was feasible in all the patients and showed very good inter-observer agreement with Cohen's k = 0.87 (95% CI 0.72-0.95). The diagnostic accuracy estimates for PUD in diagnosing compensated cirrhosis (F = 4) were 87.5% sensitivity, 76.8% specificity, positive likelihood ratio (LR) 3.78, and negative likelihood ratio (LR-) 0.16, while those for standard US and TE (> 12.5 kPa) were, respectively, 87.5% sensitivity, 72.6% specificity, LR+ 3.2, and LR- 0.17, and 87.5% sensitivity, 90.5% specificity, LR + 9.2, and LR- 0.13. CONCLUSIONS PUD reproducibility in assessing LSN was excellent even with operators of different experience. PUD performed very well in excluding advanced CLD. PUD can be used as a first-line tool for screening patients to undergo more invasive techniques, thus shortening the time for clinical decision-making. KEY POINTS • PUD is highly reproducible in assessing the sign of liver surface nodularity. • PUD showed high diagnostic accuracy in excluding the presence of advanced chronic liver disease. • PUD can be used as a first-line tool for screening patients with CLD who should undergo more invasive techniques.
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Affiliation(s)
- Andrea Costantino
- Gastroenterology and Endoscopy Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | | | | | - Valentina Sciola
- Gastroenterology and Endoscopy Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Marco Maggioni
- Pathology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Francesca Donato
- Gastroenterology and Hepatology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Maurizio Vecchi
- Gastroenterology and Endoscopy Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Pietro Lampertico
- Gastroenterology and Hepatology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Giovanni Casazza
- CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
- Department of Biomedical and Clinical Sciences, "L. Sacco" Hospital, University of Milan, Milan, Italy
| | - Mirella Fraquelli
- Gastroenterology and Endoscopy Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
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Caviglia GP, Troshina G, Santaniello U, Rosati G, Bombaci F, Birolo G, Nicolosi A, Saracco GM, Ciancio A. Long-Term Hepatocellular Carcinoma Development and Predictive Ability of Non-Invasive Scoring Systems in Patients with HCV-Related Cirrhosis Treated with Direct-Acting Antivirals. Cancers (Basel) 2022; 14:828. [PMID: 35159094 PMCID: PMC8834182 DOI: 10.3390/cancers14030828] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 01/31/2022] [Accepted: 02/04/2022] [Indexed: 02/07/2023] Open
Abstract
Patients with hepatitis C virus (HCV)-related cirrhosis treated with direct-acting antivirals (DAA) are still at risk of developing hepatocellular carcinoma (HCC). We investigated the accuracy of non-invasive scoring systems (NSS) for the prediction of de novo HCC development in patients treated with DAA on long-term follow-up (FU). We analyzed data from 575 consecutive patients with cirrhosis and no history of HCC who achieved a sustained virologic response (SVR) to DAA therapy. NSS (i.e., Forns index, APRI, FIB-4, ALBI, and aMAP) were calculated at 3 months after the end of therapy. Performance for de novo HCC prediction was evaluated in terms of area under the curve (AUC) and Harrell's C-index. During a median FU of 44.9 (27.8-58.6) months, 57 (9.9%) patients developed de novo HCC. All five NSS were associated with the risk of de novo HCC. At multivariate analysis, only the ALBI score resulted in being significantly and independently associated with de novo HCC development (adjusted hazard ratio = 4.91, 95% CI 2.91-8.28, p < 0.001). ALBI showed the highest diagnostic accuracy for the detection of de novo HCC at 1-, 3-, and 5-years of FU, with AUC values of 0.81 (95% CI 0.78-0.85), 0.71 (95% CI 0.66-0.75), and 0.68 (95% CI 0.59-0.76), respectively. Consistently, the best predictive performance assessed by Harrell's C-statistic was observed for ALBI (C-index = 0.70, 95% CI 0.62-0.77). ALBI score may represent a valuable and inexpensive tool for risk stratification and the personalization of an HCC surveillance strategy for patients with cirrhosis and previous history of HCV infection treated with DAA.
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Affiliation(s)
- Gian Paolo Caviglia
- Liver Unit, Department of Medical Sciences, University of Torino, 10126 Turin, Italy; (G.T.); (U.S.); (G.R.); (F.B.); (G.B.); (A.N.); (G.M.S.)
| | - Giulia Troshina
- Liver Unit, Department of Medical Sciences, University of Torino, 10126 Turin, Italy; (G.T.); (U.S.); (G.R.); (F.B.); (G.B.); (A.N.); (G.M.S.)
| | - Umberto Santaniello
- Liver Unit, Department of Medical Sciences, University of Torino, 10126 Turin, Italy; (G.T.); (U.S.); (G.R.); (F.B.); (G.B.); (A.N.); (G.M.S.)
| | - Giulia Rosati
- Liver Unit, Department of Medical Sciences, University of Torino, 10126 Turin, Italy; (G.T.); (U.S.); (G.R.); (F.B.); (G.B.); (A.N.); (G.M.S.)
| | - Francesco Bombaci
- Liver Unit, Department of Medical Sciences, University of Torino, 10126 Turin, Italy; (G.T.); (U.S.); (G.R.); (F.B.); (G.B.); (A.N.); (G.M.S.)
| | - Giovanni Birolo
- Liver Unit, Department of Medical Sciences, University of Torino, 10126 Turin, Italy; (G.T.); (U.S.); (G.R.); (F.B.); (G.B.); (A.N.); (G.M.S.)
| | - Aurora Nicolosi
- Liver Unit, Department of Medical Sciences, University of Torino, 10126 Turin, Italy; (G.T.); (U.S.); (G.R.); (F.B.); (G.B.); (A.N.); (G.M.S.)
| | - Giorgio Maria Saracco
- Liver Unit, Department of Medical Sciences, University of Torino, 10126 Turin, Italy; (G.T.); (U.S.); (G.R.); (F.B.); (G.B.); (A.N.); (G.M.S.)
- Gastroenterology Unit, Department of General and Specialistic Medicine, A.O.U. Città della Salute e della Scienza—Molinette Hospital, 10126 Turin, Italy
| | - Alessia Ciancio
- Liver Unit, Department of Medical Sciences, University of Torino, 10126 Turin, Italy; (G.T.); (U.S.); (G.R.); (F.B.); (G.B.); (A.N.); (G.M.S.)
- Gastroenterology Unit, Department of General and Specialistic Medicine, A.O.U. Città della Salute e della Scienza—Molinette Hospital, 10126 Turin, Italy
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Boeken T, Lucidarme O, Mbarki E, Scatton O, Savier E, Wagner M. Association of shear-wave elastography with clinical outcomes post-liver transplantation. Clin Res Hepatol Gastroenterol 2021; 45:101554. [PMID: 33172788 DOI: 10.1016/j.clinre.2020.09.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 09/26/2020] [Accepted: 09/28/2020] [Indexed: 02/08/2023]
Abstract
PURPOSE Two-dimensional shear-wave elastography (2D-SWE) assessment of liver stiffness has the advantage of being obtained during conventional ultrasound. Liver-stiffness values on 2D-SWE for grafted livers are unknown, as are their potential link to post-transplantation morbidity. This study was undertaken to determine liver-stiffness values on 2D-SWE for grafted livers without complications, and examine relationships between liver-stiffness values on 2D-SWE and early post-operative arterial or biliary complications. METHODS In our facility, all liver-transplant recipients are entered in a comprehensive surgical database, where donor, procedure and recipient characteristics are described. All patients underwent systematic 2D-SWE assessment. Potential relationships were analyzed between liver-stiffness findings and donor, procedure and recipient characteristics, and follow-up events, including death, arterial or biliary complications, graft removal and allograft-dysfunction scores. RESULTS Liver-stiffness values on 2D-SWE of 337 ultrasound examinations from 165 liver-transplant recipients were collected retrospectively. Median time from transplantation to 2D-SWE examination was 149 days, with median follow-up at 36 months. The mean±SD stiffness value for grafts without complications was 7.3±2.3kPa; it was significantly higher during the first 90 days (8.2±2.5kPa) post-transplant than after 1year (7.0±2.4kPa) (P=0.01). Patients with biliary complications during the first-year post-transplantation had significantly higher mean liver-stiffness values on 2D-SWE than those without, respectively: 9.8±7.0 vs 7.5±1.8kPa (P=0.01). CONCLUSIONS Post-transplantation patients without complications had stiffer livers than the general population, with higher values during the first 90 days after surgery. Liver-stiffness values on 2D-SWE were significantly higher for patients with biliary, but not arterial, complications.
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Affiliation(s)
- Tom Boeken
- Université Paris Descartes - Sorbonne - Paris Cité, France; Radiologie Polyvalente et Oncologique, Hôpital Pitié-Salpêtrière, 47, bd de l'Hôpital, 75651 Paris Cedex 13, France.
| | - Olivier Lucidarme
- Radiologie Polyvalente et Oncologique, Hôpital Pitié-Salpêtrière, 47, bd de l'Hôpital, 75651 Paris Cedex 13, France; Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale (LIB), Service de Radiologie, APHP, Hôpital Pitié-Salpêtrière, Paris, France
| | - Elsa Mbarki
- Université Paris Descartes - Sorbonne - Paris Cité, France; Radiologie Polyvalente et Oncologique, Hôpital Pitié-Salpêtrière, 47, bd de l'Hôpital, 75651 Paris Cedex 13, France
| | - Olivier Scatton
- Chirurgie Digestive et Hépato-BIlio-Pancréatique, Hôpital Pitié-Salpêtrière, 47 blvd de l'Hôpital, 75013, Paris, France; Service de chirurgie digestive hépato-bilio-pancréatique transplantation hépatique, Sorbonne Université, Inserm, Institute of Cardiometabolism and Nutrition, ICAN, Centre de Recherche Saint-Antoine, CRSA, AP-HP, CHU Pitie-Salpetriere, Paris, France
| | - Eric Savier
- Chirurgie Digestive et Hépato-BIlio-Pancréatique, Hôpital Pitié-Salpêtrière, 47 blvd de l'Hôpital, 75013, Paris, France; Service de chirurgie digestive hépato-bilio-pancréatique transplantation hépatique, Sorbonne Université, Inserm, Institute of Cardiometabolism and Nutrition, ICAN, Centre de Recherche Saint-Antoine, CRSA, AP-HP, CHU Pitie-Salpetriere, Paris, France
| | - Mathilde Wagner
- Radiologie Polyvalente et Oncologique, Hôpital Pitié-Salpêtrière, 47, bd de l'Hôpital, 75651 Paris Cedex 13, France; Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale (LIB), Service de Radiologie, APHP, Hôpital Pitié-Salpêtrière, Paris, France
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8
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Navin PJ, Olson MC, Knudsen JM, Venkatesh SK. Elastography in the evaluation of liver allograft. Abdom Radiol (NY) 2021; 46:96-110. [PMID: 31950204 DOI: 10.1007/s00261-019-02400-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Elastography is an established technique in the evaluation of chronic liver diseases. While there is a large clinical experience and data available regarding the performance of elastography in native liver, elastography experience with liver grafts is limited and still growing. Both ultrasound-based elastography techniques and MR Elastography (MRE) are useful in the assessment of liver fibrosis in liver transplants. Technical modifications for performing elastography will be required for optimum evaluation of the graft. In general, caution needs to be exercised regarding the use of elastography immediately following transplantation as post-operative changes, perioperative conditions/complications, inflammation, and rejection can cause increased stiffness in the graft. In the follow-up, detection of increased stiffness with elastography is useful for predicting development of fibrosis in the graft. Adjunctive MRI or ultrasound with Doppler also provides comprehensive evaluation of anatomy, vascular anastomosis and patency, biliary tree, and stiffness for fibrosis. In this review, we provide a brief overview of elastography techniques available followed by the literature review of elastography in the evaluation of grafts and illustration with clinical examples.
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Mangia A, Bellini D, Cillo U, Laghi A, Pelle G, Valori VM, Caturelli E. Hepatocellular carcinoma in adult thalassemia patients: an expert opinion based on current evidence. BMC Gastroenterol 2020; 20:251. [PMID: 32746786 PMCID: PMC7398335 DOI: 10.1186/s12876-020-01391-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 07/21/2020] [Indexed: 02/07/2023] Open
Abstract
Beta-thalassemia represents a heterogeneous group of haemoglobin inherited disorders, among the most common genetic diseases in the world, frequent in the Mediterranean basin. As beta-thalassemia patients' survival has increased over time, previously unknown complications are observed with increasing frequency. Among them, an increased risk of hepatocellular carcinoma (HCC) has been registered. Our aim is to reduce inequalities in diagnosis and treatment and to offer patients univocal recommendations in any institution.The members of the panel - gastroenterologists, radiologists, surgeons and oncologists -were selected on the basis of their publication records and expertise. Thirteen clinical questions, derived from clinical needs, and an integration of all the committee members' suggestions, were formulated. Modified Delphi approach involving a detailed literature review and the collective judgement of experts, was applied to this work.Thirteen statements were derived from expert opinions' based on the current literature, on recently developed reviews and on technological advancements. Each statement is discussed in a short paragraph reporting the current key evidence. As this is an emerging issue, the number of papers on HCC in beta-thalassemia patients is limited and based on anecdotal cases rather than on randomized controlled studies. Therefore, the panel has discussed, step by step, the possible differences between beta-thalassemia and non beta-thalassemia patients. Despite the paucity of the literature, practical and concise statements were generated.This paper offers a practical guide organized by statements describing how to manage HCC in patients with beta-thalassemia.
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Affiliation(s)
- Alessandra Mangia
- Liver Unit, Department of Medical Sciences, Fondazione IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy
| | - Davide Bellini
- Department of Radiological Sciences, Oncology and Pathology, “SAPIENZA” University of Rome; I.C.O.T. Hospital, Latina, Italy
| | - Umberto Cillo
- Hepatobiliary surgery and Liver Transplant Unit, University of Padua, Padova, Italy
| | - Andrea Laghi
- Department of Surgical Medical Sciences and Translational Medicine, “SAPIENZA” University of Rome; Sant’Andrea University Hospital, Rome, Italy
| | - Giuseppe Pelle
- Oncology Unit, Oncohematology Department IRCCS, “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy
| | - Vanna Maria Valori
- Diagnostic And Interventional Radiology Department, SM Goretti Hospital, Latina, Italy
| | - Eugenio Caturelli
- Diagnostic and interventional ultrasound unit, Medical Sciences Department, “Belcolle Hospital”, Viterbo, Italy
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10
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Winters AC, Mittal R, Schiano TD. A review of the use of transient elastography in the assessment of fibrosis and steatosis in the post-liver transplant patient. Clin Transplant 2019; 33:e13700. [PMID: 31441967 DOI: 10.1111/ctr.13700] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2019] [Revised: 07/21/2019] [Accepted: 08/18/2019] [Indexed: 12/13/2022]
Abstract
Liver biopsy is considered the gold standard method for diagnosing and staging liver disease, particularly in the post-liver transplant setting. Given the invasive nature of biopsy, alternate means for accurately assessing liver fibrosis and steatosis are preferred especially as the number of patients with fatty liver disease is increasing. Transient elastography has been validated as a useful tool for evaluation of liver fibrosis, as has controlled attenuation parameter index as a tool for assessing steatosis. It is a non-invasive, rapid, and highly reproducible approach to demonstrate the presence of fibrosis among non-transplant patients with chronic liver disease of various etiologies. However, it has not yet found wide acceptance in liver transplant recipients. There are few published studies evaluating the merits and applicability of transient elastography to assess allografts after liver transplantation. We review the published data on the use of transient elastography with concurrent controlled attenuation parameter in liver transplant recipients and recommend its greater use to follow allograft function over time.
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Affiliation(s)
- Adam C Winters
- Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, CA, USA
| | - Rasham Mittal
- Transplant Hepatology, Southern California Permanente Medical Group, Kaiser Permanente, Los Angeles, CA, USA
| | - Thomas D Schiano
- Department of Medicine, Division of Liver Diseases, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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11
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Ji SS, Jiang HD, Jiang JC, Li J, Lin ST, Chen B, Xu SH. Applicability of liver stiffness measurement based nomograms to the assessments of hepatitis B related significant fibrosis and cirrhosis. Clin Chim Acta 2018; 489:75-82. [PMID: 30471249 DOI: 10.1016/j.cca.2018.11.029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 11/07/2018] [Accepted: 11/20/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND We evaluated liver fibrosis in patients with chronic hepatitis B (CHB) and mildly raised alanine transaminase (ALT) activities between 1-2 times the upper limit of normal (ULN) which was near the threshold for initiating treatment. METHODS Nomogram-Fibrosis and Nomogram-Cirrhosis were elaborated with variables independently associated with significant fibrosis and cirrhosis determined by multivariate logistic regression. Calibration, receiver operator characteristic (ROC) and decision curves were applied to comparing nomograms with aspartate aminotransferase (AST) to platelet count (PLT) ratio index (APRI), age-AST-PLT-ALT index (FIB-4) and liver stiffness measurement (LSM). RESULTS The Nomogram-Fibrosis was constructed with LSM, PLT, and gamma-glutamyl transpeptidase (GGT). Nomogram-Cirrhosis contained one more variable of age other than Nomogram-Fibrosis. The calibration demonstrated that the assessments of significant fibrosis or cirrhosis by nomograms were in line with liver biopsy. The AUROC of Nomogram-Fibrosis was 0.788, lager than APRI (0.586), FIB-4 (0.656) and LSM (0.735). The AUROC of Nomogram-Cirrhosis was 0.889, larger than APRI (0.642), FIB-4 (0.725) and LSM (0.837). Furthermore, the decision curve analysis suggested the most net benefits were provided by the nomograms. CONCLUSIONS Nomogram-Fibrosis and Nomogram-Cirrhosis could be promising tools for recognizing significant fibrosis and cirrhosis for CHB patients with mild raised ALT activities.
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Affiliation(s)
- Si-Si Ji
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Hai-Dan Jiang
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Jia-Chun Jiang
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Jia Li
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Shu-Ting Lin
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Bin Chen
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China.
| | - Shi-Hao Xu
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China.
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12
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Vinciguerra T, Brunati A, David E, Longo F, Pinon M, Ricceri F, Castellino L, Piga A, Giraudo MT, Tandoi F, Cisarò F, Dell Olio D, Isolato G, Romagnoli R, Salizzoni M, Calvo PL. Transient elastography for non-invasive evaluation of post-transplant liver graft fibrosis in children. Pediatr Transplant 2018; 22. [PMID: 29369488 DOI: 10.1111/petr.13125] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/15/2017] [Indexed: 12/15/2022]
Abstract
As graft survival in pediatric LT is often affected by progressive fibrosis, numerous centers carry out protocol liver biopsies. Follow-up biopsy protocols differ from center to center, but all biopsies are progressively spaced out, as time from transplant increases. Therefore, there is a need for non-invasive techniques to evaluate graft fibrosis progression in those children who have no clinical or serological signs of liver damage. Indirect markers, such as the APRI, should be relied on with caution because their sensitivity in predicting fibrosis can be strongly influenced by the etiology of liver disease, severity of fibrosis, and patient age. A valid alternative could be TE, a non-invasive technique already validated in adults, which estimates the stiffness of the cylindrical volume of liver tissue, 100-fold the size of a standard needle biopsy sample. The aims of this study were to evaluate the reliability of TE in children after LT and to compare both the TE and the APRI index results with the histological scores of fibrosis on liver biopsies. A total of 36 pediatric LT recipients were studied. All patients underwent both TE and biopsy within a year (median interval -0.012 months) at an interval from LT of 0.36 to 19.47 years (median 3.02 years). Fibrosis was assessed on the biopsy specimens at histology and staged according to METAVIR. There was a statistically significant correlation between TE stiffness values and METAVIR scores (P = .005). The diagnostic accuracy of TE for the diagnosis of significant fibrosis (F ≥ 2) was measured as the area under the curve (AUROC = 0.865), and it demonstrated that the method had a good diagnostic performance. APRI was not so accurate in assessing graft fibrosis when compared to METAVIR (AUROC = 0.592). A liver stiffness cutoff value of 5.6 kPa at TE was identified as the best predictor for a significant graft fibrosis (METAVIR F ≥ 2) on liver biopsy, with a 75% sensitivity, a 95.8% specificity, a 90% positive predictive value, and an 88.5% negative predictive value. These data suggest that TE may represent a non-invasive, reliable tool for the assessment of graft fibrosis in the follow-up of LT children, alerting the clinicians to the indication for a liver biopsy, with the aim of reducing the number of protocol liver biopsies.
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Affiliation(s)
- Tiziana Vinciguerra
- Gastroenterologia e Epatologia Pediatrica, Department of Pediatrics, Azienda Ospedaliera-Universitaria Citta`della Salute e della Scienza, Turin, Italy
| | - Andrea Brunati
- Liver Transplantation Center, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Ezio David
- Department of Pathology, Azienda Ospedaliera-Universitaria Citta`della Salute e della Scienza, Turin, Italy
| | - Filomena Longo
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Michele Pinon
- Gastroenterologia e Epatologia Pediatrica, Department of Pediatrics, Azienda Ospedaliera-Universitaria Citta`della Salute e della Scienza, Turin, Italy
| | - Fulvio Ricceri
- Epidemiology Unit, Regional Health Services ASL TO3, Grugliasco, Italy.,Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Luisa Castellino
- Department of Mathematics "G. Peano", University of Turin, Turin, Italy
| | - Antonio Piga
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | | | - Francesco Tandoi
- Liver Transplantation Center, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Fabio Cisarò
- Gastroenterologia e Epatologia Pediatrica, Department of Pediatrics, Azienda Ospedaliera-Universitaria Citta`della Salute e della Scienza, Turin, Italy
| | - Dominic Dell Olio
- Regional Transplant Center, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, Turin, Italy
| | - Giuseppe Isolato
- Institute of Diagnostic and Interventional Radiology, Azienda Ospedaliera-Universitaria Citta`della Salute e della Scienza, Turin, Italy
| | - Renato Romagnoli
- Liver Transplantation Center, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Mauro Salizzoni
- Liver Transplantation Center, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Pier Luigi Calvo
- Gastroenterologia e Epatologia Pediatrica, Department of Pediatrics, Azienda Ospedaliera-Universitaria Citta`della Salute e della Scienza, Turin, Italy
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13
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Saxena V, Terrault NA. Recurrent Primary Disease After Liver Transplantation. ZAKIM AND BOYER'S HEPATOLOGY 2018:784-815.e14. [DOI: 10.1016/b978-0-323-37591-7.00053-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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14
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Performance of transient elastography and serum fibrosis biomarkers for non-invasive evaluation of recurrent fibrosis after liver transplantation: A meta-analysis. PLoS One 2017; 12:e0185192. [PMID: 28953939 PMCID: PMC5617176 DOI: 10.1371/journal.pone.0185192] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Accepted: 09/07/2017] [Indexed: 02/06/2023] Open
Abstract
Recurrent fibrosis after liver transplantation (LT) impacts on long-term graft and patient survival. We performed a meta-analysis to compare the accuracy of non-invasive methods to diagnose significant recurrent fibrosis (stage F2-F4) following LT. Studies comparing serum fibrosis biomarkers, namely AST-to-platelet ratio index (APRI), fibrosis score 4 (FIB-4), or transient elastography (TE) with liver biopsy in LT recipients were systematically identified through electronic databases. In the meta-analysis, we calculated the weighted pooled odds ratio and used a fixed effect model, as there was no significant heterogeneity between studies. Eight studies were included for APRI, four for FIB-4, and twelve for TE. The mean prevalence of significant liver fibrosis was 37.4%. The summary odds ratio was significantly higher for TE (21.17, 95% CI confidence interval 14.10–31.77, p = 1X10-30) as compared to APRI (9.02, 95% CI 5.79–14.07; p = 1X10-30) and FIB-4 (7.08, 95% CI 4.00–12.55; p = 1.93X10-11). In conclusion, TE performs best to diagnose recurrent fibrosis in LT recipients. APRI and FIB-4 can be used as an estimate of significant fibrosis at centres where TE is not available. Longitudinal assessment of fibrosis by means of these non-invasive tests may reduce the need for liver biopsy.
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15
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Gambato M, Crespo G, Torres F, LLovet L, Carrión J, Londoño M, Lens S, Mariño Z, Bartres C, Miquel R, Navasa M, Forns X. Simple prediction of long-term clinical outcomes in patients with mild hepatitis C recurrence after liver transplantation. Transpl Int 2017; 29:698-706. [PMID: 26661662 DOI: 10.1111/tri.12730] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 08/20/2015] [Accepted: 12/01/2015] [Indexed: 01/11/2023]
Abstract
Little is known about the long-term outcomes of mild hepatitis C recurrence after liver transplantation (LT). In an era where most patients request treatment with direct acting antivirals (DAAs), data on the natural history in these patients are relevant. We have prospectively assessed the clinical outcomes of 173 patients with mild hepatitis C recurrence 1 year after LT. The endpoints were cirrhosis development (F = 4, HVPG ≥10 mmHg, liver stiffness measurement ≥14 kPa) and HCV-related graft loss. After a median follow-up of 80 months, the cumulative probability (CP) of HCV-related graft loss 5 and 10 years after LT were only 3% and 10%, respectively. Graft cirrhosis developed in 26 (15%) patients over time, with a CP of 13% and 30% at 5 and 10 years after LT, respectively. The CP of cirrhosis 5 years after LT was only 8% in patients with a donor <50 years and AST <60 IU/l 1 year after LT (n = 67), compared with 46% in those 24 individuals with both risk factors. Our data support an excellent long-term outcome of patients with mild hepatitis C recurrence 1 year after LT. There are, however, some patients progressing to cirrhosis who can be easily identified and who should receive prompt antiviral therapy.
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Affiliation(s)
- Martina Gambato
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Gonzalo Crespo
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Ferran Torres
- Medical Statistics Core Facility, Hospital Clinic, IDIBAPS, Barcelona, Spain.,Biostatistics Unit, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Laura LLovet
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - José Carrión
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - María Londoño
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Sabela Lens
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Zoe Mariño
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Concepció Bartres
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Rosa Miquel
- Pathology Department, Hospital Clínic, Barcelona, Spain
| | - Miquel Navasa
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
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16
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Joo I, Lee JY, Lee DH, Jeon JH, Kim H, Yi NJ, Lee KW, Suh KS. Contrast-Enhanced Ultrasound Using Perfluorobutane-Containing Microbubbles in the Assessment of Liver Allograft Damage: An Exploratory Prospective Study. ULTRASOUND IN MEDICINE & BIOLOGY 2017; 43:621-628. [PMID: 28041745 DOI: 10.1016/j.ultrasmedbio.2016.11.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Revised: 11/15/2016] [Accepted: 11/21/2016] [Indexed: 06/06/2023]
Abstract
This prospective study investigated the usefulness of contrast (perfluorobutane-containing microbubbles)-enhanced ultrasound in the non-invasive assessment of liver allograft damage. Forty-one liver recipients underwent contrast-enhanced ultrasound followed by a liver biopsy. The hepatic filling rate (time between the arrival of contrast agent in the right hepatic artery and the maximum intensity of hepatic parenchyma) and parenchymal intensity difference before and after instantaneous high-power emission in the Kupffer phase were measured. Patients with allograft damage had higher hepatic filling rates and lower parenchymal intensity differences than those without damage (42.0 ± 16.9 vs. 30.5 ± 7.7 s, p = 0.005; 6.1 ± 7.4 vs. 16.6 ± 16.1 dB, p = 0.047, respectively). In the diagnosis of liver allograft damage, hepatic filling rate and parenchymal intensity difference had sensitivities of 61.5% and 90.9% and specificities of 92.6% and 63.6% using cutoffs of >38.5 s and ≤10.3 dB, respectively. In conclusion, contrast-enhanced ultrasound may be a promising tool in the detection of liver allograft damage.
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Affiliation(s)
- Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea; Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Young Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea; Department of Radiology, Seoul National University College of Medicine, Seoul, Korea; Institute of Radiation Medicine, Seoul National University Hospital, Seoul, Korea.
| | - Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea; Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Ju Hyeon Jeon
- Department of Radiology, Sejong General Hospital, Gyeonggi-do, Korea
| | - Hyeyoung Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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17
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Affiliation(s)
- Manjiri Dighe
- Department of Radiology, University of Washington, Seattle, WA.
| | - Matthew Bruce
- Applied Physics Laboratory, University of Washington Seattle, WA
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18
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Van Biervliet S, Verdievel H, Vande Velde S, De Bruyne R, De Looze D, Verhelst X, Geerts A, Robberecht E, Van Vlierberghe H. Longitudinal Transient Elastography Measurements Used in Follow-up for Patients with Cystic Fibrosis. ULTRASOUND IN MEDICINE & BIOLOGY 2016; 42:848-854. [PMID: 26806442 DOI: 10.1016/j.ultrasmedbio.2015.11.011] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Revised: 11/07/2015] [Accepted: 11/12/2015] [Indexed: 06/05/2023]
Abstract
Cystic fibrosis-related liver disease (CFLD) is diagnosed using a combination of criteria. Transient elastography (TE), an ultrasonographic method to evaluate liver stiffness, can differentiate patients with and without liver disease. This retrospective study (2007-2013) aimed to detect developing CFLD using consequent TE measurements. All cystic fibrosis patients with TE measurements between 2007 and 2013 (n = 150, median age 17 (9-24) y) were included, of which 118 had a median of three (range, 2-4) measurements with an interval of 1 (1-2) y. Twenty (14%) had CFLD at the first TE measurement; five (3%) developed CFLD during follow-up. The median TE value in CFLD was 14 kPa (8.7-32.2) compared with 5.3 (4.9-5.7) in cystic fibrosis patients without liver disease (CFnoLD; p = 0.0001). In CFnoLD, TE was correlated with age (p = 0.031). A TE result >6.8 kPa had a sensitivity of 91.5% and a specificity of 91.7% in predicting CFLD, according to the receiver operating characteristics analysis. It also has a positive predictive value of 88.6% and a negative predictive value of 86.9%, increasing to 91.7% and 98%, respectively, in patients at risk (<14 y) for developing CFLD. Patients with developing CFLD had progressively increasing consecutive TE measurements.
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Affiliation(s)
- Stephanie Van Biervliet
- Cystic fibrosis Centre Ghent, Ghent University Hospital, Ghent, Belgium; Department of Pediatric Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.
| | - Hugo Verdievel
- Department of Adult Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Saskia Vande Velde
- Department of Pediatric Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Ruth De Bruyne
- Department of Pediatric Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Danny De Looze
- Cystic fibrosis Centre Ghent, Ghent University Hospital, Ghent, Belgium
| | - Xavier Verhelst
- Department of Adult Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Anja Geerts
- Department of Adult Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Eddy Robberecht
- Cystic fibrosis Centre Ghent, Ghent University Hospital, Ghent, Belgium
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19
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Crespo G, Castro-Narro G, García-Juárez I, Benítez C, Ruiz P, Sastre L, Colmenero J, Miquel R, Sánchez-Fueyo A, Forns X, Navasa M. Usefulness of liver stiffness measurement during acute cellular rejection in liver transplantation. Liver Transpl 2016; 22:298-304. [PMID: 26609794 DOI: 10.1002/lt.24376] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 10/19/2015] [Accepted: 10/22/2015] [Indexed: 12/11/2022]
Abstract
Liver stiffness measurement (LSM) is a useful method to estimate liver fibrosis and portal hypertension. The inflammatory process that takes place in post-liver transplant acute cellular rejection (ACR) may also increase liver stiffness. We aimed to explore the association between liver stiffness and the severity of ACR, as well as to assess the relationship between liver stiffness and response to rejection treatment in a prospective study that included 27 liver recipients with biopsy-proven ACR, 30 stable recipients with normal liver tests, and 30 hepatitis C virus (HCV)-infected LT recipients with histologically diagnosed HCV recurrence. Patients with rejection were stratified into 2 groups (mild and moderate/severe) according to the severity of rejection evaluated with the Banff score. Routine biomarkers and LSM with FibroScan were performed at the time of liver biopsy (baseline) and at 7, 30, and 90 days in patients with rejection and at baseline in control patients. Median baseline liver stiffness was 5.9 kPa in the mild rejection group, 11 kPa in the moderate/severe group (P = 0.001), 4.2 kPa in stable recipients (P = 0.02 versus mild rejection), and 13.6 kPa in patients with recurrent HCV (P = 0.17 versus moderate/severe rejection). The area under the receiver operator characteristic curve of LSM to discriminate mild versus moderate/severe ACR was 0.924, and a LSM value of 8.5 kPa yielded a positive predictive value of 100% to diagnose moderate/severe rejection. Liver stiffness improved in 7%, 21%, and 64% of patients with moderate/severe rejection at 7, 30, and 90 days. In conclusion, according to the results of this exploratory study, LSM is associated with the severity of ACR in liver transplantation and thus may be of help in its assessment.
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Affiliation(s)
| | - Graciela Castro-Narro
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico DF, Mexico
| | - Ignacio García-Juárez
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico DF, Mexico
| | - Carlos Benítez
- Liver Transplant Unit, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile
| | - Pablo Ruiz
- Liver Unit, University of Barcelona, Barcelona, Spain
| | - Lydia Sastre
- Liver Unit, University of Barcelona, Barcelona, Spain
| | | | - Rosa Miquel
- Pathology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Spain
| | | | - Xavier Forns
- Liver Unit, University of Barcelona, Barcelona, Spain
| | - Miquel Navasa
- Liver Unit, University of Barcelona, Barcelona, Spain
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20
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Chang PE, Goh GBB, Ngu JH, Tan HK, Tan CK. Clinical applications, limitations and future role of transient elastography in the management of liver disease. World J Gastrointest Pharmacol Ther 2016; 7:91-106. [PMID: 26855815 PMCID: PMC4734958 DOI: 10.4292/wjgpt.v7.i1.91] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 09/05/2015] [Accepted: 10/27/2015] [Indexed: 02/06/2023] Open
Abstract
Transient elastography (TE) is a reliable tool for the non-invasive assessment of liver fibrosis in routine clinical practice. TE is currently approved for use in Europe, Asia and the United States. The widespread adoption of this technology is certain to increase the use of TE worldwide. Although TE has been well validated in chronic viral hepatitis, its clinical role in other liver diseases remains less clear. The advent of new treatment for chronic hepatitis C and emerging prevalence of non-alcoholic steatohepatitis raises new questions on the role of TE in current clinical practice. This review aims to examine the clinical applications, limitations and future role of TE in current clinical practice in light of the changing epidemiology of liver diseases and new clinical management paradigms. In current clinical practice, TE is the most accurate non-invasive method for diagnosis of liver cirrhosis. TE is useful to rule out fibrosis and cirrhosis but does not have sufficient accuracy to discern between various stages of fibrosis. The clinical role of TE has evolved from cross-sectional point-in-time assessment of fibrosis and cirrhosis to the more relevant role of prediction of vital clinical end-points. This provides clinicians with the ability to modify treatment strategies based on the information provided by TE. TE has evolved over the past decade to become an essential tool to assist the clinician in the management of chronic liver disease.
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21
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Ultrasound Elastography and MR Elastography for Assessing Liver Fibrosis: Part 2, Diagnostic Performance, Confounders, and Future Directions. AJR Am J Roentgenol 2015; 205:33-40. [PMID: 25905762 DOI: 10.2214/ajr.15.14553] [Citation(s) in RCA: 147] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE The purpose of the article is to review the diagnostic performance of ultra-sound and MR elastography techniques for detection and staging of liver fibrosis, the main current clinical applications of elastography in the abdomen. CONCLUSION Technical and instrument-related factors and biologic and patient-related factors may constitute potential confounders of stiffness measurements for assessment of liver fibrosis. Future developments may expand the scope of elastography for monitoring liver fibrosis and predict complications of chronic liver disease.
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Abstract
Chronic HCV infection is the leading indication for liver transplantation. However, as a result of HCV recurrence, patient and graft survival after liver transplantation are inferior compared with other indications for transplantation. HCV recurrence after liver transplantation is associated with considerable mortality and morbidity. The development of HCV-related fibrosis is accelerated after liver transplantation, which is influenced by a combination of factors related to the virus, donor, recipient, surgery and immunosuppression. Successful antiviral therapy is the only treatment that can attenuate fibrosis. The advent of direct-acting antiviral agents (DAAs) has changed the therapeutic landscape for the treatment of patients with HCV. DAAs have improved tolerability, and can potentially be used without PEG-IFN for a shorter time than previous therapies, which should result in better outcomes. In this Review, we describe the important risk factors that influence HCV recurrence after liver transplantation, highlighting the mechanisms of fibrosis and the integral role of hepatic stellate cells. Indirect and direct assessment of fibrosis, in addition to new antiviral therapies, are also discussed.
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23
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Wildner D, Strobel D, Konturek PC, Görtz RS, Croner RS, Neurath MF, Zopf S. Impact of acoustic radiation force impulse imaging in clinical practice of patients after orthotopic liver transplantation. Med Sci Monit 2014; 20:2027-35. [PMID: 25342166 PMCID: PMC4218901 DOI: 10.12659/msm.891126] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background Acoustic radiation force impulse (ARFI) elastography is a reliable diagnostic device for quantitative non-invasive assessment of liver fibrosis in patients with chronic liver disease. The aim of our prospective study was to evaluate the impact of ARFI in patients after orthotopic liver transplantation (OLT). Therefore, we compared ARFI shear wave velocities with clinical features, non-invasive markers, and the histology of patients following OLT. Material/Methods Post-transplant patients underwent a clinical examination and blood samples were taken. B-mode and Doppler ultrasound (US) of the portal vein and the hepatic artery were performed. Subsequently, a minimum of 10 valid ARFI values were measured in the left and right liver lobe. Liver biopsy was performed if indicated. Results Between May 2012 and May 2014, 58 Patients after OLT were included in the prospective study. Laboratory markers and aspartate aminotransferase-to-platelet ratio index (APRI) correlated with ARFI values (r=0.44, p<0.001). The histological (n=22) fibrosis score (Ludwig) was significantly correlated with the ARFI of the biopsy site (r=0.55, p=0.008). The mean shear-wave velocities were significantly increased in advanced fibrosis (F≤2 1.57±0.57 m/s; F≥3 2.85±0.66 m/s; p<0.001), obstructive cholestasis and active viral hepatitis. The area under the receiver operating characteristic (AUROC) curves for the accuracy of ARFI were 74% (F≥1), 73% (F≥2), 93% (F≥3), and 80% (=F4). Conclusions ARFI elastography correlates well with laboratory values and with noninvasive and invasive markers of fibrosis in patients after OLT. In this regard, elevated ARFI-velocities should be interpreted with caution in the context of obstructive cholestasis and active viral disease.
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Affiliation(s)
- Dane Wildner
- Department of Internal Medicine 1, University Hospital Erlangen, Erlangen, Germany
| | - Deike Strobel
- Department of Internal Medicine 1, University Hospital Erlangen, Erlangen, Germany
| | - Peter C Konturek
- Department of Internal Medicine II, Thüringen-Klinik, Saalfeld, Germany
| | - Rüdiger S Görtz
- Department of Internal Medicine 1, University Hospital Erlangen, Erlangen, Germany
| | - Roland S Croner
- Department of Surgery, University Hospital Erlangen, Erlangen, Germany
| | - Markus F Neurath
- Department of Internal Medicine 1, University Hospital Erlangen, Erlangen, Germany
| | - Steffen Zopf
- Department of Internal Medicine 1, University Hospital Erlangen, Erlangen, Germany
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24
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Wong GLH. Prediction of fibrosis progression in chronic viral hepatitis. Clin Mol Hepatol 2014; 20:228-36. [PMID: 25320725 PMCID: PMC4197170 DOI: 10.3350/cmh.2014.20.3.228] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Accepted: 07/07/2014] [Indexed: 02/06/2023] Open
Abstract
Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools.
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Affiliation(s)
- Grace Lai-Hung Wong
- Institute of Digestive Disease, Department of Medicine and Therapeutics, and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
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25
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Zaiton F, Dawoud H, El Fiki IM, Hadhoud KM. Diffusion weighted MRI and transient elastography assessment of liver fibrosis in hepatitis C patients: Validity of non invasive imaging techniques. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2014. [DOI: 10.1016/j.ejrnm.2014.02.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
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26
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Trembling PM, Lampertico P, Parkes J, Tanwar S, Viganò M, Facchetti F, Colombo M, Rosenberg WM. Performance of Enhanced Liver Fibrosis test and comparison with transient elastography in the identification of liver fibrosis in patients with chronic hepatitis B infection. J Viral Hepat 2014; 21:430-8. [PMID: 24750297 PMCID: PMC4298014 DOI: 10.1111/jvh.12161] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Assessment of liver fibrosis is important in determining prognosis, disease progression and need for treatment in patients with chronic hepatitis B (CHB). Limitations to the use of liver biopsy in assessing fibrosis are well recognized, and noninvasive tests are being increasingly evaluated including transient elastography (TE) and serum markers such as the Enhanced Liver Fibrosis (ELF) test. We assessed performance of ELF and TE in detecting liver fibrosis with reference to liver histology in a cohort of patients with CHB (n = 182), and compared the performance of these modalities. Median age was 46 and mean AST 70 IU/L. Cirrhosis was reported in 20% of liver biopsies. Both modalities performed well in assessing fibrosis at all stages. Area under receiver operator characteristic (AUROC) curves for detecting METAVIR fibrosis stages F ≥ 1, F ≥ 2, F ≥ 3 and F4 were 0.77, 0.82, 0.80 and 0.83 for ELF and 0.86, 0.86, 0.90 and 0.95 for TE. TE performed significantly better in the assessment of severe fibrosis (AUROC 0.80 for ELF and 0.90 for TE, P < 0.01) and cirrhosis (0.83 for ELF and 0.95 for TE, P < 0.01). This study demonstrates that ELF has good performance in detection of liver fibrosis in patients with CHB, and when compared, TE performs better in detection of severe fibrosis/cirrhosis.
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Affiliation(s)
- P M Trembling
- Institute for Liver and Digestive Health, Division of Medicine, University College LondonLondon, UK
| | - P Lampertico
- AM and A Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Department of Medicine, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di MilanoMilan, Italy
| | - J Parkes
- Public Health Sciences and Medical Statistics, Faculty of Medicine, University of SouthamptonSouthampton, UK
| | - S Tanwar
- Institute for Liver and Digestive Health, Division of Medicine, University College LondonLondon, UK
| | - M Viganò
- AM and A Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Department of Medicine, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di MilanoMilan, Italy,UO Epatologia, Ospedale San Giuseppe, Università degli Studi di MilanoMilan, Italy
| | - F Facchetti
- AM and A Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Department of Medicine, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di MilanoMilan, Italy
| | - M Colombo
- AM and A Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Department of Medicine, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di MilanoMilan, Italy
| | - W M Rosenberg
- Institute for Liver and Digestive Health, Division of Medicine, University College LondonLondon, UK
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27
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Alten TA, Negm AA, Voigtländer T, Jaeckel E, Lehner F, Brauner C, Wedemeyer H, Manns MP, Lankisch TO. Safety and performance of liver biopsies in liver transplant recipients. Clin Transplant 2014; 28:585-9. [DOI: 10.1111/ctr.12352] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/05/2014] [Indexed: 12/18/2022]
Affiliation(s)
- Tim A. Alten
- Department of Radiology; Hannover Medical School; Hannover Germany
| | - Ahmed A. Negm
- Department of Gastroenterology, Hepatology and Endocrinology; Hannover Medical School; Hannover Germany
- Integrated Research and Treatment Center - Transplantation (IFB-Tx); Hannover Medical School; Hannover Germany
| | - Torsten Voigtländer
- Department of Gastroenterology, Hepatology and Endocrinology; Hannover Medical School; Hannover Germany
- Integrated Research and Treatment Center - Transplantation (IFB-Tx); Hannover Medical School; Hannover Germany
| | - Elmar Jaeckel
- Department of Gastroenterology, Hepatology and Endocrinology; Hannover Medical School; Hannover Germany
- Integrated Research and Treatment Center - Transplantation (IFB-Tx); Hannover Medical School; Hannover Germany
| | - Frank Lehner
- Department of Visceral Surgery; Hannover Medical School; Hannover Germany
| | - Christin Brauner
- Integrated Research and Treatment Center - Transplantation (IFB-Tx); Hannover Medical School; Hannover Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology; Hannover Medical School; Hannover Germany
- Integrated Research and Treatment Center - Transplantation (IFB-Tx); Hannover Medical School; Hannover Germany
| | - Michael P. Manns
- Department of Gastroenterology, Hepatology and Endocrinology; Hannover Medical School; Hannover Germany
- Integrated Research and Treatment Center - Transplantation (IFB-Tx); Hannover Medical School; Hannover Germany
| | - Tim O. Lankisch
- Department of Gastroenterology, Hepatology and Endocrinology; Hannover Medical School; Hannover Germany
- Integrated Research and Treatment Center - Transplantation (IFB-Tx); Hannover Medical School; Hannover Germany
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28
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Schiavon LDL, Narciso-Schiavon JL, Carvalho-Filho RJD. Non-invasive diagnosis of liver fibrosis in chronic hepatitis C. World J Gastroenterol 2014; 20:2854-2866. [PMID: 24659877 PMCID: PMC3961992 DOI: 10.3748/wjg.v20.i11.2854] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 12/10/2013] [Accepted: 01/14/2014] [Indexed: 02/06/2023] Open
Abstract
Assessment of liver fibrosis in chronic hepatitis C virus (HCV) infection is considered a relevant part of patient care and key for decision making. Although liver biopsy has been considered the gold standard for staging liver fibrosis, it is an invasive technique and subject to sampling errors and significant intra- and inter-observer variability. Over the last decade, several noninvasive markers were proposed for liver fibrosis diagnosis in chronic HCV infection, with variable performance. Besides the clear advantage of being noninvasive, a more objective interpretation of test results may overcome the mentioned intra- and inter-observer variability of liver biopsy. In addition, these tests can theoretically offer a more accurate view of fibrogenic events occurring in the entire liver with the advantage of providing frequent fibrosis evaluation without additional risk. However, in general, these tests show low accuracy in discriminating between intermediate stages of fibrosis and may be influenced by several hepatic and extra-hepatic conditions. These methods are either serum markers (usually combined in a mathematical model) or imaging modalities that can be used separately or combined in algorithms to improve accuracy. In this review we will discuss the different noninvasive methods that are currently available for the evaluation of liver fibrosis in chronic hepatitis C, their advantages, limitations and application in clinical practice.
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29
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Crespo G, Lens S, Gambato M, Carrión JA, Mariño Z, Londoño MC, Miquel R, Bosch J, Navasa M, Forns X. Liver stiffness 1 year after transplantation predicts clinical outcomes in patients with recurrent hepatitis C. Am J Transplant 2014; 14:375-83. [PMID: 24410892 DOI: 10.1111/ajt.12594] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2013] [Revised: 10/21/2013] [Accepted: 11/14/2013] [Indexed: 01/25/2023]
Abstract
The value of transient elastography (TE) to assess clinical outcomes in hepatitis C recurrence after liver transplantation (LT) has not been explored so far. We studied 144 hepatitis C-infected and 48 non-hepatitis C virus (HCV)-infected LT recipients and evaluated the prognostic value of TE 1 year after transplantation to predict clinical decompensations and graft and patient survival. In HCV patients, cumulative probabilities of liver decompensation 5 years after LT were 8% for patients with liver stiffness measurement (LSM) <8.7 kilopascals (kPa) versus 47% for patients with LSM ≥ 8.7 kPa (p<0.001). Five-year graft and patient cumulative survival were 90% and 92% in patients with LSM<8.7 kPa (p<0.001) and 63% and 64% in patients with LSM ≥ 8.7 kPa, respectively (p<0.001). Patients with low LSM 1 year after LT had excellent outcomes independently from receiving antiviral treatment or achieving sustained virological response (SVR). In contrast, graft survival significantly improved in patients with LSM ≥ 8.7 kPa who achieved SVR. No association between outcomes and LSM at 12 months was observed in non-HCV patients. In conclusion, LSM 1 year after LT is a valuable tool to predict hepatitis C-related outcomes in recurrent hepatitis C and can be used in clinical practice to identify the best candidates for antiviral therapy.
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Affiliation(s)
- G Crespo
- Liver Unit, Hospital Clinic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain
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30
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Shetty S, Adams DH, Hubscher SG. Post-transplant liver biopsy and the immune response: lessons for the clinician. Expert Rev Clin Immunol 2014; 8:645-61. [DOI: 10.1586/eci.12.65] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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31
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Howell J, Angus P, Gow P. Hepatitis C recurrence: the Achilles heel of liver transplantation. Transpl Infect Dis 2013; 16:1-16. [PMID: 24372756 DOI: 10.1111/tid.12173] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Revised: 06/12/2013] [Accepted: 08/03/2013] [Indexed: 12/18/2022]
Abstract
Hepatitis C virus (HCV) infection is the most common indication for liver transplantation worldwide; however, recurrence post transplant is almost universal and follows an accelerated course. Around 30% of patients develop aggressive HCV recurrence, leading to rapid fibrosis progression (RFP) and culminating in liver failure and either death or retransplantation. Despite many advances in our knowledge of clinical risks for HCV RFP, we are still unable to accurately predict those most at risk of adverse outcomes, and no clear consensus exists on the best approach to management. This review presents a critical overview of clinical factors shown to influence the course of HCV recurrence post transplant, with particular focus on recent data identifying the important role of metabolic factors, such as insulin resistance, in HCV recurrence. Emerging data for genetic markers of HCV recurrence and their usefulness for predicting adverse outcomes will also be explored.
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Affiliation(s)
- J Howell
- Liver Transplant Unit, Austin Hospital, Melbourne, Australia; Department of Medicine, University of Melbourne, Melbourne, Australia
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32
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Crespo G, Forns X, Navasa M. [Serum markers of liver fibrosis in patients with chronic hepatitis C infection. Prognostic value of noninvasive markers of fibrosis in liver transplantation]. GASTROENTEROLOGIA Y HEPATOLOGIA 2013; 35 Suppl 2:17-22. [PMID: 23298655 DOI: 10.1016/s0210-5705(12)70045-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Liver fibrosis must be evaluated in patients with chronic hepatitis C, since its severity will affect prognosis and the indication of antiviral therapy. Combining serological markers of fibrosis in algorithms or scores can identify a substantial number of patients with significant fibrosis and most patients with liver cirrhosis, thus potentially avoiding a large number of biopsies. Although these algorithms should be interpreted with caution, due to their possible limitations, their high reproducibility, applicability and availability make them an essential tool in the current evaluation of patients with chronic hepatitis C infection. In contrast, serological markers have been found to be less effective in the diagnosis of fibrosis in the context of recurrent hepatitis C infection after liver transplantation. However, an algorithm for direct markers has shown excellent predictive ability in liver transplant recipients with hepatitis C. Consequently, this algorithm seems to be an excellent tool to establish prognosis and indicate antiviral therapy.
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Affiliation(s)
- Gonzalo Crespo
- Servicio de Hepatología, Institut de Malalties Digestives, IDIBAPS, CIBERehd Hospital Clínic, Barcelona, España
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33
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Poustchi H, Eslami M, Ostovaneh MR, Modabbernia A, Saeedian FS, Taslimi S, George J, Malekzadeh R, Zamani F. Transient elastography in hepatitis C virus-infected patients with beta-thalassemia for assessment of fibrosis. Hepatol Res 2013; 43:1276-83. [PMID: 23489382 DOI: 10.1111/hepr.12088] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2012] [Revised: 01/31/2013] [Accepted: 02/04/2013] [Indexed: 02/08/2023]
Abstract
AIM We sought to evaluate the performance of transient elastography (TE) for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients with beta-thalassemia. METHODS Seventy-six CHC patients with beta-thalassemia underwent TE, liver biopsy, T2 -weighted magnetic resonance imaging (MRI) for the assessment of liver iron content (LIC) and laboratory evaluation. The accuracy of TE and its correlation with the other variables was assessed. RESULTS TE values increased proportional to fibrosis stage (r = 0.404, P < 0.001), but was independent of T2 -weighted MRI-LIC (r = 0.064, P = 0.581). In multivariate analysis, fibrosis stage was still associated with the log-transformed TE score(standardized β = 0.42 for F4 stage of METAVIR, P = 0.001). No correlation was noted between LIC and TE score (standardized β = 0.064, P = 0.512). The area under the receiver operating characteristic curve for prediction of cirrhosis was 80% (95% confidence interval, 59-100%). A cut-off TE score of 11 had a sensitivity of 78% and specificity of 88.1% for diagnosing cirrhosis. The best cut-off values for "TE-FIB-4 cirrhosis score" comprising TE and FIB-4 and "TE-APRI cirrhosis score" combining TE with aspartate aminotransferase-to-platelet ratio index (APRI) both had 87.5% sensitivity and 91.04% specificity for the diagnosis of cirrhosis. CONCLUSION Regardless of LIC, TE alone or when combined with FIB-4 or APRI, is a diagnostic tool with moderate to high accuracy to evaluate liver fibrosis in CHC patients with beta-thalassemia. However, because splenectomy in a proportion of our subjects might have affected the platelet count, the scores utilizing APRI and FIB-4 should be interpreted cautiously.
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Affiliation(s)
- Hossein Poustchi
- Digestive Diseases Research Institute, Shariati Hospital, Tehran, Iran
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34
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Inoue Y, Kokudo N. Elastography for hepato-biliary-pancreatic surgery. Surg Today 2013; 44:1793-800. [PMID: 24292652 PMCID: PMC4162976 DOI: 10.1007/s00595-013-0799-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2013] [Accepted: 09/03/2013] [Indexed: 12/11/2022]
Abstract
Palpation is a subjective and non-sharable diagnostic method. Recently, palpation has been supported and replaced by elastography, which provides a novel parameter of “stiffness” as a visual representation or quantified value. Today, elastography is performed using two major modalities: strain elastography and shear wave elastography. Strain elastography converts the extent of deformation during external compression into colors, displaying these colors as a strain map in a motion picture representing the relative elasticity inside the region of interest. Shear wave elastography can quantify the elasticity of a target by calculating the velocity of shear waves generated by a probe. In addition to superficial organs, elastography has also been applied to upper abdominal organs, including the liver, pancreas and spleen. The visualization of the stiffness of focal lesions in the liver or the pancreas has enabled a more sensitive and specific depiction of small, non-palpable nodules, which are difficult to depict using B-mode ultrasonography. The quantification of stiffness also enables non-invasive estimates of liver fibrosis, the risk of postoperative liver insufficiency and the risk of recurrence of viral hepatitis after transplantation. In this article, we review the major reports that have recently been published describing the effective application of elastography to solid upper abdominal organs in a clinical setting.
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Affiliation(s)
- Yosuke Inoue
- Department of Gastrointestinal Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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35
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Bota S, Herkner H, Sporea I, Salzl P, Sirli R, Neghina AM, Peck-Radosavljevic M. Meta-analysis: ARFI elastography versus transient elastography for the evaluation of liver fibrosis. Liver Int 2013; 33:1138-1147. [PMID: 23859217 DOI: 10.1111/liv.12240] [Citation(s) in RCA: 327] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2012] [Accepted: 05/27/2013] [Indexed: 12/11/2022]
Abstract
AIMS This meta-analysis aims to compare the diagnostic performance of acoustic radiation force impulse (ARFI) elastography and transient elastography (TE) in the assessment of liver fibrosis using liver biopsy (LB) as 'gold-standard'. METHODS PubMed, Medline, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases were searched for all studies published until 31 May 2012 that evaluated the liver stiffness by means of ARFI, TE and LB. Information abstracted from each study according to a fixed protocol included study design and methodological characteristics, patient characteristics, interventions, outcomes and missing outcome data. RESULTS Thirteen studies (11 full-length articles and 2 abstracts) including 1163 patients with chronic hepatopathies were included in the analysis. Inability to obtain reliable measurements was more than thrice as high for TE as that of ARFI (6.6% vs. 2.1%, P < 0.001). For detection of significant fibrosis, (F ≥ 2) the summary sensitivity (Se) was 0.74 (95% CI: 0.66-0.80) and specificity (Sp) was 0.83 (95% CI: 0.75-0.89) for ARFI, while for TE the Se was 0.78 (95% CI: 0.72-0.83) and Sp was 0.84 (95% CI: 0.75-0.90). For the diagnosis of cirrhosis, the summary Se was 0.87 (95% CI: 0.79-0.92) and Sp was 0.87 (95% CI: 0.81-0.91) for ARFI elastography, and, respectively, 0.89 (95% CI: 0.80-0.94) and 0.87 (95% CI: 0.82-0.91) for TE. The diagnostic odds ratio of ARFI and TE did not differ significantly in the detection of significant fibrosis [mean difference in rDOR = 0.27 (95% CI: 0.69-0.14)] and cirrhosis [mean difference in rDOR = 0.12 (95% CI: 0.29-0.52)]. CONCLUSION Acoustic radiation force impulse elastography seems to be a good method for assessing liver fibrosis, and shows higher rate of reliable measurements and similar predictive value to TE for significant fibrosis and cirrhosis.
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Affiliation(s)
- Simona Bota
- Department of Gastroenterology and Hepatology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
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36
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Barrault C, Roudot-Thoraval F, Tran Van Nhieu J, Atanasiu C, Kluger MD, Medkour F, Douvin C, Mallat A, Zafrani ES, Cherqui D, Duvoux C. Non-invasive assessment of liver graft fibrosis by transient elastography after liver transplantation. Clin Res Hepatol Gastroenterol 2013; 37:347-52. [PMID: 23318116 DOI: 10.1016/j.clinre.2012.11.003] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2011] [Revised: 11/13/2012] [Accepted: 11/20/2012] [Indexed: 02/09/2023]
Abstract
BACKGROUND Liver stiffness measurement (LSM) by transient elastography (TE) (FibroScan) is a validated method of quantifying liver fibrosis in non-transplanted patients with hepatitis C virus (HCV). It could be useful in follow-up after liver transplantation (LT). The aim of this study was to assess the diagnostic accuracy of LSM in evaluating liver fibrosis after LT in patients with and without recurrent HCV. PATIENTS AND METHODS Forty-three patients (mean age 57.6 ± 9.9 years), 28 (65.1%) HCV-positive patients and 15 (34.9%) HCV-negative patients underwent gold standard liver biopsy and TE 55.8 ± 4.9 months after transplantation. Liver fibrosis was scored on biopsy specimens according to METAVIR (F0-F4). Accuracy of TE and optimal stiffness cut-off values for fibrosis staging were determined by a receiver-operating characteristics (ROC) curve analysis. RESULTS Median stiffness values were significantly different for METAVIR score less than 2 (5.8 kPa) vs. METAVIR score greater to equal to 2 (9.6 kPa) (P<0.001). The area under the ROC curve was 0.83 for METAVIR score greater to equal to 2 (95%CI: 0.71-0.95). The optimal stiffness cut-off value was 7 kPa for METAVIR scores greater to equal to 2. The results were similar whether the patients had recurrent HCV infection or not. CONCLUSIONS These results indicate that transient elastography accurately identifies LT recipients with significant fibrosis, irrespective of HCV status. It is a promising non-invasive tool to assess graft fibrosis progression after LT in patients with HCV recurrence, as well as for screening of late graft fibrosis of other etiologies. Transient elastography could reduce the use of invasive protocol biopsies.
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Affiliation(s)
- Camille Barrault
- Liver Transplantation Unit, hôpital Henri-Mondor, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94000 Créteil, France.
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Isgro G, Calvaruso V, Andreana L, Luong TV, Garcovich M, Manousou P, Alibrandi A, Maimone S, Marelli L, Davies N, Patch D, Dhillon AP, Burroughs AK. The relationship between transient elastography and histological collagen proportionate area for assessing fibrosis in chronic viral hepatitis. J Gastroenterol 2013; 48:921-929. [PMID: 23124603 DOI: 10.1007/s00535-012-0694-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2012] [Accepted: 09/11/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND Collagen proportionate area (CPA) has a better correlation with hepatic venous pressure gradient (HVPG) than with Ishak stage. Liver stiffness measurement (LSM) is proposed as non invasive marker of portal hypertension/disease progression. Our aim was to compare LSM and CPA with Ishak staging in chronic viral hepatitis, and HVPG in HCV hepatitis after transplantation. METHODS One hundred and sixty-nine consecutive patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections pre/post liver transplantation (LT), had a liver biopsy combined with LSM (transient elastography), CPA (biopsies stained with Sirius Red and evaluated by digital image analysis and expressed as CPA) and HVPG (measured contemporaneously with transjugular biopsies in LT HCV patients). RESULTS LSM was dependent on CPA in HBV (r (2) = 0.61, p < 0.0001), HCV (r (2) = 0.59, p < 0.0001) and LT groups (r (2) = 0.64, p < 0.0001). In all three groups, CPA and Ishak were predictors of LSM, but multivariately CPA was better related to LSM (HBV: r (2) = 0.61, p < 0.0001; HCV: r (2) = 0.59, p < 0.0001; post-LT: r (2) = 0.68, p < 0.0001) than Ishak stage. In the LT group, multiple regression analysis including HVPG, LSM, aspartate aminotransferase to platelet ratio index (APRI) and Ishak stage/grade, showed that only CPA was related to HVPG (r (2) = 0.41, p = 0.01), both for HVPG ≥6 mmHg (OR 1.34, 95 % CI 1.14-1.58; p < 0.0001) or ≥10 mmHg (OR 1.25, 95 % CI 1.06-1.47; p = 0.007). CONCLUSION CPA was related to LSM in HBV or HCV hepatitis pre/post-LT. CPA was better related to LSM than Ishak stage. In the LT HCV group, CPA was better related to HVPG than Ishak stage/grade, LSM or APRI. CPA may represent a better comparative histological index for LSM, rather than histological stages.
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Affiliation(s)
- Graziella Isgro
- The Royal Free Sheila Sherlock Liver Centre and University Department of Surgery UCL, Royal Free Hospital, Pond Street, Hampstead, London, NW3 2QG, UK
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Crespo S, Bridges M, Nakhleh R, McPhail A, Pungpapong S, Keaveny AP. Non-invasive assessment of liver fibrosis using magnetic resonance elastography in liver transplant recipients with hepatitis C. Clin Transplant 2013; 27:652-8. [PMID: 23837611 DOI: 10.1111/ctr.12180] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/04/2013] [Indexed: 12/24/2022]
Abstract
BACKGROUND Liver biopsy has been the reference standard when evaluating fibrosis due to recurrent hepatitis after liver transplantation. Magnetic resonance elastography estimates liver stiffness, correlating to fibrosis. AIM To investigate the utility of elastography in staging liver fibrosis in transplant recipients with hepatitis C. METHODS Fifty-four patients, ≥12 months post-transplant, underwent elastography within three months of biopsy. Discriminatory capability for METAVIR fibrosis stages F0-2 vs. F3-4 and receiver operating characteristic curve (ROC) analysis were determined. RESULTS On biopsy, 27 patients had METAVIR fibrosis score 0-1; 12 had a 3 or 4. There was significant correlation between histologic fibrosis and shear stiffness (R² = 0.588, p < 0.0001). Using a cutoff value of 3.5 kPa, elastography was 91% sensitive and 72% specific in differentiating fibrosis scores of ≥3 from 0 to 1. The AUC of elastography in predicting a fibrosis score of ≥3 was 0.92. Multivariate analysis revealed no correlation between the grade of histologic inflammation and liver stiffness measured by magnetic resonance elastography (R² = 0.265, p = 0.47). CONCLUSION Magnetic resonance elastography is an accurate non-invasive technique for excluding stage ≥3 graft in recipients with hepatitis C.
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Affiliation(s)
- Sergio Crespo
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Jacksonville, FL, USA
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Abd El Rihim AY, Omar RF, Fathalah W, El Attar I, Hafez HA, Ibrahim W. Role of fibroscan and APRI in detection of liver fibrosis: a systematic review and meta-analysis. Arab J Gastroenterol 2013; 14:44-50. [PMID: 23820499 DOI: 10.1016/j.ajg.2013.05.002] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Revised: 03/23/2013] [Accepted: 05/09/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND STUDY AIMS Fibroscan and APRI are promising noninvasive alternatives to liver biopsy for detecting hepatic fibrosis. However, their overall test performance in various settings remains questionable. The aim of our study was to perform a systematic review and meta-analysis of diagnostic accuracy studies comparing fibroscan and APRI with liver biopsy for hepatic fibrosis. PATIENTS AND METHODS Electronic and manual bibliographic searches to identify potential studies were performed. Selection of studies was based on reported accuracy of fibroscan and APRI compared with liver biopsy. Data extraction was performed independently by two reviewers. Meta-analysis combined the sensitivities, specificities, and likelihood ratios of individual studies. Extent and reasons for heterogeneity were assessed. RESULTS 23 studies for fibroscan and 20 studies for APRI in full publication were identified. For patients with stage IV fibrosis (cirrhosis), the pooled estimates for sensitivity of fibroscan were 83.4% (95% confidence interval [CI], 71.7-95.0%) and specificity 92.4% (95% CI, 85.6-99.2%). For patients with stage IV fibrosis (cirrhosis), the pooled estimates for sensitivity of APRI at cutoff point of 1.5 were 66.5% (95% CI, 25.0-100%) and specificity 71.7% (95% CI, 35.0-100%). Diagnostic threshold bias was identified as an important cause of heterogeneity for pooled results in both patient groups. CONCLUSIONS Fibroscan and APRI appear to be clinically useful tests for detecting cirrhosis however not useful tools in early stages of fibrosis.
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Wong GLH. Transient elastography: Kill two birds with one stone? World J Hepatol 2013; 5:264-274. [PMID: 23717737 PMCID: PMC3664284 DOI: 10.4254/wjh.v5.i5.264] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2013] [Revised: 03/01/2013] [Accepted: 03/07/2013] [Indexed: 02/06/2023] Open
Abstract
Assessment of liver fibrosis and steatosis is crucial in chronic liver diseases in order to determine the prognosis, the need of treatment, as well as monitor disease progression and response to treatment. Liver biopsy is limited by its invasiveness and patient acceptability. Transient elastography (TE, Fibroscan®) is a non-invasive tool with satisfactory accuracy and reproducibility to estimate liver fibrosis and steatosis. TE has been well validated in major liver diseases including chronic hepatitis B and C, non-alcoholic fatty liver disease, alcoholic liver disease, primary biliary cirrhosis, and primary sclerosing cholangitis. As alanine aminotransferase (ALT) is one of the major confounding factors of liver stiffness in chronic hepatitis B, an ALT-based algorithm has been developed and higher liver stiffness measurements (LSM) cutoff values for different stages of liver fibrosis should be used in patients with elevated ALT levels up to 5 times of the upper limit of normal. Otherwise falsely-high LSM results up to cirrhotic range may occur during ALT flare. TE is also useful in predicting patient prognosis such as development of hepatocellular carcinoma (HCC), portal hypertension, post-operative complications in HCC patients, and also survival. Unfortunately, failed acquisition of TE is common in obese patients. Furthermore, obese patients may have higher LSM results even in the same stage of liver fibrosis. The new XL probe, a larger probe with lower ultrasound frequency and deeper penetration, increases the success rate of TE in obese patients. The median LSM value with XL probe was found to be lower than that by the conventional M probe, hence cutoff values approximately 1.2 to 1.3 kPa lower than those of M probe should be adopted. Recent studies revealed a novel ultrasonic controlled attenuation parameter (CAP) of the machine is a useful parameter to detect even low-grade steatosis noninvasively. CAP may also be used to quantify liver steatosis by applying different cutoff values. As both LSM and CAP results are instantly available at same measurement, this makes TE a very convenient tool to assess any patients who are suspected or confirmed to suffer from chronic liver diseases.
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Berenguer M, Schuppan D. Progression of liver fibrosis in post-transplant hepatitis C: mechanisms, assessment and treatment. J Hepatol 2013; 58:1028-41. [PMID: 23262248 DOI: 10.1016/j.jhep.2012.12.014] [Citation(s) in RCA: 118] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2012] [Revised: 12/10/2012] [Accepted: 12/10/2012] [Indexed: 12/12/2022]
Abstract
Liver fibrosis results from an excessive wound healing response in most chronic liver diseases, such as hepatitis C. Despite great advances in antiviral therapy in recent years, progressive liver fibrosis remains a major problem for patients with recurrent hepatitis C after liver transplantation. Liver biopsy remains a central tool in the management of HCV-positive liver transplant recipients, but reliable non-invasive methods for the assessment of liver fibrosis, such as ultrasound elastography, are increasingly being incorporated in the management of post-transplant patients, helping predict prognosis, guide treatment decisions, and stratify patients for emerging antifibrotic therapies. In this manuscript, we will review the natural history as well as tools to monitor fibrosis progression in the HCV-positive liver transplant recipient, the mechanisms underlying rapid fibrosis progression in up to 30% of these patients, the effect of antiviral therapies and highlight promising antifibrotic approaches.
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Affiliation(s)
- Marina Berenguer
- University Valencia, Dept. of Medicine, Hepatology & Liver Transplantation Unit, La Fe Hospital and CIBEREHD, National Network Center for Hepatology and Gastroenterology Research, Instituto de Salud Carlos III, Spain.
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Abstract
Conventional imaging techniques cannot provide information about tissue mechanical properties. Many injuries can cause changes in tissue stiffness, especially tumors and fibrosis. In recent years, various non-invasive ultrasound methods have been developed to study tissue elasticity for a large number of applications (breast, thyroid, prostate, kidneys, blood vessels, liver…). For non-invasive assessment of liver diseases, several ultrasound elastography techniques have been investigated: Transient elastography (the most extensively used), Real Time Elastography (RTE), Acoustic Radiation Force Impulse Imaging (ARFI) and more recently Shear Wave Elastography (SWE). Even if evaluation of liver fibrosis in chronic liver disease remains the principal application, there are many others applications for liver: predicting cirrhosis-related complications; monitoring antiviral treatments in chronic viral liver disease; characterizing liver tumors; monitoring local treatments, etc. The aim of this article is to report on the different hepatic ultrasound elastography techniques, their advantages and disadvantages, their diagnostic accuracy, their applications in clinical practice.
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Karnik GS, Shetty K. Management of recurrent hepatitis C in orthotopic liver transplant recipients. Infect Dis Clin North Am 2013; 27:285-304. [PMID: 23714341 DOI: 10.1016/j.idc.2013.02.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
End-stage liver disease and hepatocellular carcinoma from chronic hepatitis C are the most common indications for orthotopic liver transplantation and the incidence of both are projected to increase over the next decade. Recurrent hepatitis C virus infection of the allograft is associated with an accelerated progression to cirrhosis, graft loss, and death. This article presents an overview of the natural history of hepatitis C virus recurrence in liver transplant recipients and guidance on optimal management strategies.
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Affiliation(s)
- Geeta S Karnik
- Department of Infectious Diseases, Georgetown University Hospital, Washington, DC 20007, USA.
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Abstract
Background: Assessment of liver fibrosis and steatosis is now almost indispensable in most of the chronic liver diseases in order to determine prognosis and need for treatment, and to monitor disease progression and response to treatment. Liver biopsy is limited by its invasiveness and patient acceptability. Transient elastography (TE; Fibroscan) is a non-invasive tool with satisfactory accuracy and reproducibility to estimate liver fibrosis. Aims & Methods: To review the existing evidence concerning the clinical applications of TE in major liver diseases, including chronic hepatitis B and -C, non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, primary biliary cirrhosis and primary sclerosing cholangitis. Results: As alanine aminotransferase (ALT) is one of the major confounding factors of liver stiffness in chronic hepatitis B, an ALT-based algorithm has been developed and higher liver stiffness measurements (LSM) cut-off values for different stages of liver fibrosis should be used in patients with elevated ALT levels up to five times the upper limit of normal. Furthermore, falsely-high LSM results up to the cirrhotic range may occur during ALT flare. TE is also useful predicting patient prognosis in the development of hepatocellular carcinoma (HCC), portal hypertension, postoperative complications in HCC patients and survival. Unfortunately, failed acquisition of TE is common in obese patients. Furthermore, obese patients may have higher LSM results, even in the same stage of liver fibrosis. To better evaluate NAFLD a new XL probe, with a larger probe with lower ultrasound frequency and deeper penetration, increases the success rate of TE in obese patients. The median LSM value with the XL probe was found to be lower than that by the conventional M probe, hence cut-off values were approximately 1.2 to 1.3 kilopascals lower than those of the M probe, suggesting its adoption. Studies reveal that a novel ultrasonic controlled attenuation parameter is potentially useful to detect and quantify hepatic steatosis non-invasively. Conclusion: TE is a non-invasive, accurate and reproducible test of liver fibrosis and possibly hepatic steatosis and has been validated in a wide spectrum of liver diseases. TE is also useful to predict patient outcomes.
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Affiliation(s)
- Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
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Ferraioli G, Tinelli C, Dal Bello B, Zicchetti M, Lissandrin R, Filice G, Filice C, Above E, Barbarini G, Brunetti E, Calderon W, Di Gregorio M, Gulminetti R, Lanzarini P, Ludovisi S, Maiocchi L, Malfitano A, Michelone G, Minoli L, Mondelli M, Novati S, Patruno SFA, Perretti A, Poma G, Sacchi P, Zanaboni D, Zaramella M. Performance of liver stiffness measurements by transient elastography in chronic hepatitis. World J Gastroenterol 2013; 19:49-56. [PMID: 23326162 PMCID: PMC3542745 DOI: 10.3748/wjg.v19.i1.49] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2012] [Revised: 10/24/2012] [Accepted: 10/30/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To compare results of liver stiffness measurements by transient elastography (TE) obtained in our patients population with that used in a recently published meta-analysis. METHODS This was a single center cross-sectional study. Consecutive patients with chronic viral hepatitis scheduled for liver biopsy at the outpatient ward of our Infectious Diseases Department were enrolled. TE was carried out by using FibroScan™ (Echosens, Paris, France). Liver biopsy was performed on the same day as TE, as day case procedure. Fibrosis was staged according to the Metavir scoring system. The diagnostic performance of TE was assessed by using receiver operating characteristic (ROC) curves and the area under the ROC curve analysis. RESULTS Two hundred and fifty-two patients met the inclusion criteria. Six (2%) patients were excluded due to unreliable TE measurements. Thus, 246 (171 men and 75 women) patients were analyzed. One hundred and ninety-five (79.3%) patients had chronic hepatitis C, 41 (16.7%) had chronic hepatitis B, and 10 (4.0%) were coinfected with human immunodeficiency virus. ROC curve analysis identified optimal cut-off value of TE as high as 6.9 kPa for F ≥ 2; 7.9 kPa for F ≥ 3; 9.6 kPa for F = 4 in all patients (n = 246), and as high as 6.9 kPa for F ≥ 2; 7.3 kPa for F ≥ 3; 9.3 kPa for F = 4 in patients with hepatitis C (n = 195). Cut-off values of TE obtained by maximizing only the specificity were as high as 6.9 kPa for F ≥ 2; 9.6 kPa for F ≥ 3; 12.2 kPa for F = 4 in all patients (n = 246), and as high as 7.0 kPa for F ≥ 2; 9.3 kPa for F ≥ 3; 12.3 kPa for F = 4 in patients with hepatitis C (n = 195). CONCLUSION The cut-off values of TE obtained in this single center study are comparable to that obtained in a recently published meta-analysis that included up to 40 studies.
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Perumpail RB, Levitsky J, Wang Y, Lee VS, Karp J, Jin N, Yang GY, Bolster BD, Shah S, Zuehlsdorff S, Nemcek AA, Larson AC, Miller FH, Omary RA. MRI-guided biopsy to correlate tissue specimens with MR elastography stiffness readings in liver transplants. Acad Radiol 2012; 19:1121-6. [PMID: 22877987 DOI: 10.1016/j.acra.2012.05.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2011] [Revised: 03/23/2012] [Accepted: 05/16/2012] [Indexed: 12/11/2022]
Abstract
RATIONALE AND OBJECTIVES Magnetic resonance elastography (MRE) can noninvasively measure the stiffness of liver tissue and display this information in anatomic maps. Magnetic resonance imaging (MRI) guidance has not previously been used to biopsy segments of heterogeneous stiffness identified on MRE. Dedicated study of MRE in post-liver transplant patients is also limited. In this study, the ability of real-time MRI to guide biopsies of segments of the liver with different MRE stiffness values in the same post-transplant patient was assessed. MATERIALS AND METHODS MRE was performed in 9 consecutive posttransplant patients with history of hepatitis C. Segments of highest and lower stiffness on MRE served as targets for subsequent real-time MRI-guided biopsy using T2-weighted imaging. The ability of MRI-guided biopsy to successfully obtain tissue specimens was assessed. The Wilcoxon signed-rank test was used to compare mean stiffness differences for highest and lower MRE stiffness segments, with α = 0.05. RESULTS MRI guidance allowed successful sampling of liver tissue for all (18/18) biopsies. There was a statistically significant difference in mean MRE stiffness values between highest (4.61 ± 1.99 kPa) and lower stiffness (3.03 ± 1.75 kPa) (P = .0039) segments biopsied in the 9 posttransplant patients. CONCLUSION Real-time MRI can guide biopsy in patients after liver transplantation based on MRE stiffness values. This study supports the use of MRI guidance to sample tissue based on functional information.
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Affiliation(s)
- Ryan B Perumpail
- Department of Radiology, Northwestern University, Chicago, IL 60611, USA
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Akamatsu N, Sugawara Y. Liver transplantation and hepatitis C. Int J Hepatol 2012; 2012:686135. [PMID: 22900194 PMCID: PMC3412106 DOI: 10.1155/2012/686135] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2012] [Accepted: 05/21/2012] [Indexed: 02/07/2023] Open
Abstract
Hepatitis-C-virus- (HCV-) related end-stage cirrhosis is the primary indication for liver transplantation in many countries. Unfortunately, however, HCV is not eliminated by transplantation and graft reinfection is universal, resulting in fibrosis, cirrhosis, and finally graft decompensation. The use of poor quality organs, particularly from older donors, has a highly negative impact on the severity of recurrence and patient/graft survival. Although immunosuppressive regimens have a considerable impact on the outcome, the optimal regimen after liver transplantation for HCV-infected patients remains unclear. Disease progression monitoring with protocol biopsy and new noninvasive methods is essential for predicting patient/graft outcome and starting antiviral treatment with the appropriate timing. Antiviral treatment with pegylated interferon and ribavirin is currently considered the most promising regimen with a sustained viral response rate of around 30% to 35%, although the survival benefit of this regimen remains to be investigated. Living-donor liver transplantation is now widely accepted as an established treatment for HCV cirrhosis and the results are equivalent to those of deceased donor liver transplantation.
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Affiliation(s)
- Nobuhisa Akamatsu
- Department of Hepato-Biliary-Pancreatic Surgery, Saitama Medical Center, Saitama Medical University, 1981 Tsujido-cho, Kamoda, Kawagoe, Saitama 350-8550, Japan
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Yasuhiko Sugawara
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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Bota S, Sporea I, Sirli R, Popescu A, Danila M, Costachescu D. Intra- and interoperator reproducibility of acoustic radiation force impulse (ARFI) elastography--preliminary results. ULTRASOUND IN MEDICINE & BIOLOGY 2012; 38:1103-1108. [PMID: 22579536 DOI: 10.1016/j.ultrasmedbio.2012.02.032] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2012] [Revised: 02/20/2012] [Accepted: 02/26/2012] [Indexed: 05/31/2023]
Abstract
Our study assessed acoustic radiation force impulse (ARFI) reproducibility and the factors influencing it. The intra- and interoperator reproducibility were studied in 33 and 58 patients, respectively. Intraclass correlation coefficient (ICC) was used to assess ARFI reproducibility. The overall intraoperator agreement was better than the interoperator one: ICC 0.90 vs. ICC 0.81. The correlation of repeated ARFI measurements was higher, but not significantly so, in cases in which intraoperator reproducibility was assessed compared with the ones in which interoperator reproducibility was studied: r = 0.848 vs. r = 0.694 (p = 0.08). For both intra- and interoperator reproducibility, the ICCs were smaller in women vs. men (0.88 vs. 0.91 and 0.67 vs. 0.86, respectively), in patients with high body mass index (BMI) ≥25 kg/m² vs. <25 kg/m² (0.88 vs. 0.91 and 0.79 vs. 0.82, respectively), in patients with ascites vs. no ascites (0.80 vs. 0.93 and 0.78 vs. 0.84, respectively) and in noncirrhotic vs. cirrhotic patients (0.77 vs. 0.82 and 0.70 vs. 0.83, respectively).
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Affiliation(s)
- Simona Bota
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy, Timisoara, Romania.
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Abstract
Chronic liver disease represents a major public health problem, accounting for significant morbidity and mortality worldwide. As prognosis and management depend mainly on the amount and progression of liver fibrosis, accurate quantification of liver fibrosis is essential for therapeutic decision-making and follow-up of chronic liver diseases. Even though liver biopsy is the gold standard for evaluation of liver fibrosis, non-invasive methods that could substitute for invasive procedures have been investigated during past decades. Transient elastography (TE, FibroScan®) is a novel non-invasive method for assessment of liver fibrosis with chronic liver disease. TE can be performed in the outpatient clinic with immediate results and excellent reproducibility. Its diagnostic accuracy for assessment of liver fibrosis has been demonstrated in patients with chronic viral hepatitis; as a result, unnecessary liver biopsy could be avoided in some patients. Moreover, due to its excellent patient acceptance, TE could be used for monitoring disease progression or predicting development of liver-related complications. This review aims at discussing the usefulness of TE in clinical practice.
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Affiliation(s)
- Kyu Sik Jung
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Korea
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Berenguer M, Charco R, Manuel Pascasio J, Ignacio Herrero J. Spanish society of liver transplantation (SETH) consensus recommendations on hepatitis C virus and liver transplantation. Liver Int 2012; 32:712-31. [PMID: 22221843 DOI: 10.1111/j.1478-3231.2011.02731.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2011] [Accepted: 11/23/2011] [Indexed: 02/06/2023]
Abstract
In November 2010, the Spanish Society of Liver Transplantation (Sociedad Española de Trasplante Hepático, SETH) held a consensus conference. One of the topics of debate was liver transplantation in patients with hepatitis C. This document reviews (i) the natural history of post-transplant hepatitis C, (ii) factors associated with post-transplant prognosis in patients with hepatitis C, (iii) the role of immunosuppression in the evolution of recurrent hepatitis C and response to antiviral therapy, (iv) antiviral therapy, both before and after transplantation, (v) follow-up of patients with recurrent hepatitis C and (vi) the role of retransplantation.
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Affiliation(s)
- Marina Berenguer
- Spanish Society of Liver Transplantation (Sociedad Española de Trasplante Hepático, SETH)
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