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Zhang Y, Huang C, Meng F, Hu X, Huang X, Chang J, Han X, Zhang T, Han J, Ge H. Non-invasive assessment of esophageal and fundic varices in patients with primary biliary cholangitis. Eur Radiol 2025; 35:2330-2338. [PMID: 39261335 PMCID: PMC11914228 DOI: 10.1007/s00330-024-11049-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Revised: 06/18/2024] [Accepted: 08/15/2024] [Indexed: 09/13/2024]
Abstract
OBJECTIVES The Baveno VII consensus recommends endoscopic screening for varicose veins in cases of liver stiffness measurement (LSM) ≥ 20 kPa or platelet count ≤ 150 × 109/L. Whether this approach was appropriate for patients with primary biliary cholangitis (PBC) remains uncertain. This study expanded the observed risk factors by adding analysis of ultrasound images as a non-invasive tool to predict the risk of esophageal or fundic varices. METHODS We enrolled 111 patients with PBC whose complete ultrasound images, measurement data, and LSM data were available. The value of the periportal hypoechoic band (PHB), splenic area, and LSM in determining the risk of varicose veins and variceal rupture was analyzed. A prospective cohort of 67 patients provided external validation. RESULTS The area under the receiver operating characteristic curve (AUC) for predicting varicose veins using LSM > 12.1 kPa or splenic areas > 41.2 cm2 was 0.806 (95% confidence interval (CI): 0.720-0.875) and 0.852 (95% CI: 0.772-0.912), respectively. This finding could assist in avoiding endoscopic screening by 76.6% and 83.8%, respectively, with diagnostic accuracy surpassing that suggested by Baveno VII guidelines. The AUCs for predicting variceal rupture using splenic areas > 56.8 cm2 was 0.717 (95% CI: 0.623-0.798). The diagnostic accuracy of PHB for variceal rupture was higher than LSM and splenic areas (75.7% vs. 50.5% vs. 68.5%). CONCLUSION We recommend LSM > 12.1 kPa as a cutoff value to predict the risk of varicosity presence in patients with PBC. Additionally, the splenic area demonstrated high accuracy and relevance for predicting varicose veins and variceal rupture, respectively. The method is simple and reproducible, allowing endoscopy to be safely avoided. CLINICAL RELEVANCE STATEMENT The measurement of the splenic area and identification of the periportal hypoechoic band (PHB) on ultrasound demonstrated high accuracy and relevance for predicting the risk of esophageal or fundic varices presence and variceal rupture, respectively. KEY POINTS Predicting varices in patients with primary biliary cholangitis (PBC) can reduce the morbidity and mortality of gastrointestinal hemorrhage. Transient elastography (TE) and ultrasound play an important role in predicting patients with PBC with varices. TE and ultrasound can predict varicose veins and variceal rupture. Liver stiffness measurement and splenic area measurements can allow endoscopy to be safely avoided.
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Affiliation(s)
- Yuan Zhang
- Beijing Youan Hospital, Capital Medical University, No. 8, Xitoutiao, Youanmenwai, Fengtai District, 100069, Beijing, China
| | - Chunyang Huang
- Beijing Youan Hospital, Capital Medical University, No. 8, Xitoutiao, Youanmenwai, Fengtai District, 100069, Beijing, China
| | - Fankun Meng
- Beijing Youan Hospital, Capital Medical University, No. 8, Xitoutiao, Youanmenwai, Fengtai District, 100069, Beijing, China
| | - Xing Hu
- Beijing Youan Hospital, Capital Medical University, No. 8, Xitoutiao, Youanmenwai, Fengtai District, 100069, Beijing, China
| | - Xiaojie Huang
- Beijing Youan Hospital, Capital Medical University, No. 8, Xitoutiao, Youanmenwai, Fengtai District, 100069, Beijing, China
| | - Jing Chang
- Beijing Youan Hospital, Capital Medical University, No. 8, Xitoutiao, Youanmenwai, Fengtai District, 100069, Beijing, China
| | - Xue Han
- Beijing Youan Hospital, Capital Medical University, No. 8, Xitoutiao, Youanmenwai, Fengtai District, 100069, Beijing, China
| | - Tieying Zhang
- Beijing Youan Hospital, Capital Medical University, No. 8, Xitoutiao, Youanmenwai, Fengtai District, 100069, Beijing, China
| | - Jing Han
- Beijing Youan Hospital, Capital Medical University, No. 8, Xitoutiao, Youanmenwai, Fengtai District, 100069, Beijing, China
| | - Huiyu Ge
- Beijing Chaoyang Hospital, Beijing, China.
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2
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Jain AK, Bundiwal AK, Jain S, Agrawal P, Jain D, Sircar S. Evaluation of liver and splenic stiffness by acoustic radiation force impulse for assessment of esophageal varices. Indian J Gastroenterol 2025; 44:163-170. [PMID: 37930496 DOI: 10.1007/s12664-023-01456-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 09/02/2023] [Indexed: 11/07/2023]
Abstract
BACKGROUND In routine clinical practice, assessment of portal hypertension (PHT) among patients with liver cirrhosis is done by a upper gastrointestinal endoscopy (UGIE); however, its invasive nature limits its use. Recent advances in ultrasound imaging make it possible to evaluate the tissue stiffness of the liver and spleen reflecting the severity of underlying fibrosis. Liver stiffness and spleen stiffness can be used to predict the presence of esophageal varices/PHT among cirrhotic patients. AIM To predict the presence or absence of esophageal varices by measuring the stiffness of the liver and spleen by ultrasonography (USG)-based acoustic radiation force impulse (ARFI). METHODS This cross-sectional study included 90 subjects with liver cirrhosis. Liver and splenic stiffness were measured along with the USG abdomen, UGIE and aspartate aminotransferase to platelet ratio index (APRI). RESULTS Liver and spleen stiffness were significantly higher in cirrhotic patients compared to chronic hepatitis B. The best cut-off value of liver stiffness (LS) obtained by the receiver operating characteristic (ROC) curve was 2.16 m/s for predicting esophageal varices (AUROC 0.78, p 0.0002). The best cut-off value of splenic stiffness (SS) obtained by the ROC curve was 3.04 m/s for predicting esophageal varices (AUROC 0.698, p 0.0274). When both LS and SS were taken together, the accuracy in predicting esophageal varices increased to 92.22%. An equation to predict "esophageal varices = (0.225 LS + 0.377SS) - 0.555" was derived. CONCLUSION LS and SS values of ≥ 2.16 m/s and 3.04 m/s, respectively, predict esophageal varices independently; however, combined assessment is better with 92% accuracy.
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Affiliation(s)
- Ajay K Jain
- Department of Gastroenterology, Choithram Hospital and Research Centre, Indore, 452 014, India.
| | - Amit K Bundiwal
- Department of Gastroenterology, Choithram Hospital and Research Centre, Indore, 452 014, India
| | - Suchita Jain
- Department of Radiodiagnosis and Imaging, Choithram Hospital and Research Centre, Indore, 452 014, India
| | - Praveen Agrawal
- Department of Radiodiagnosis and Imaging, Choithram Hospital and Research Centre, Indore, 452 014, India
| | - Deepika Jain
- Department of Biostatistics, Choithram Hospital and Research Centre, Indore, 452 014, India
| | - Shohini Sircar
- Department of Gastroenterology, Choithram Hospital and Research Centre, Indore, 452 014, India
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3
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Song WP, Zhang S, Li J, Shao YY, Xu JC, Yang CQ. Comparison of the diagnostic efficacy between virtual portal pressure gradient and hepatic venous pressure gradient in patients with cirrhotic portal hypertension. J Dig Dis 2024; 25:603-614. [PMID: 39726251 DOI: 10.1111/1751-2980.13319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 10/12/2024] [Accepted: 11/07/2024] [Indexed: 12/28/2024]
Abstract
OBJECTIVES This study aimed to evaluate the performance of virtual portal pressure gradient (vPPG) and its associated hemodynamic parameters of 3-dimensional (3D) model in patients with cirrhosis. METHODS Seventy cirrhotic patients who underwent both hepatic venous pressure gradient (HVPG) measurement and vPPG calculation were prospectively collected. The ideal-state model (ISM; n = 44) was defined by sinusoidal PH without hepatic vein shunt or portal vein thrombosis, whereas those not conforming to the criteria were classified as non-ISM (n = 26). Correlation analyses were conducted to determine the relationship between vPPG or its associated 3D hemodynamic parameters and HVPG. The diagnostic and predictive performance of vPPG and HVPG for cirrhotic-related complications was evaluated using the receiver operating characteristic (ROC) curve and Kaplan-Meier analysis. RESULTS In the ISM group, vPPG-associated hemodynamic parameters including total branch cross-sectional area (S2), average branch cross-sectional area (S), and average portal vein model length (h) were correlated with HVPG (r = 0.592, 0.536, -0.497; all p < 0.001), whereas vPPG was strongly correlated with HVPG (r = 0.832, p < 0.001). In the non-ISM group, vPPG, S2, S, and h were not related to HVPG (all p > 0.05). In the ISM group, both vPPG and HVPG showed significant diagnostic and predictive capabilities for cirrhosis-related complications. While in the non-ISM group, the diagnostic accuracy and predictive efficacy of vPPG surpassed those of HVPG. CONCLUSION HVPG exhibited superior diagnostic and predictive efficacy for cirrhotic PH in the ISM, whereas vPPG showed enhanced performance in non-ISM.
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Affiliation(s)
- Wei Ping Song
- Department of Gastroenterology and Hepatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Shuo Zhang
- Department of Gastroenterology and Hepatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jing Li
- Department of Gastroenterology and Hepatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yu Yang Shao
- School of Medicine, Tongji University, Shanghai, China
| | - Ji Chong Xu
- Department of Interventional Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Chang Qing Yang
- Department of Gastroenterology and Hepatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
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Forna L, Bozomitu L, Lupu VV, Lupu A, Trandafir LM, Adam Raileanu A, Cojocariu C, Anton C, Girleanu I, Muzica CM. Pediatric Perspectives on Liver Cirrhosis: Unravelling Clinical Patterns and Therapeutic Challenges. J Clin Med 2024; 13:4275. [PMID: 39064318 PMCID: PMC11278264 DOI: 10.3390/jcm13144275] [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: 04/28/2024] [Revised: 07/01/2024] [Accepted: 07/19/2024] [Indexed: 07/28/2024] Open
Abstract
Background: Liver cirrhosis presents significant challenges in the pediatric population due to a complex interplay of etiological factors, clinical manifestations, and limited therapeutic options. The leading contributors to cirrhosis among pediatric patients are chronic cholestasis, metabolic disorders present from birth, and long-term hepatitis. Materials and method: Our narrative review aimed to synthesize literature data on the etiology, clinical picture, diagnostic techniques, optimal management of complications, and timely transplantation. Results: The epidemiology of liver cirrhosis in pediatric patients is evolving. The introduction of a universal vaccination and effective long-term viral suppression in viral hepatitis have significantly decreased complications rates. Liver transplantation programs worldwide have also improved the management of cirrhosis complications. Conclusions: Early diagnosis, comprehensive management strategies, and advancements in treatment modalities are critical for improving outcomes. Understanding these differences is crucial in providing age-appropriate care and support for those affected by cirrhosis.
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Affiliation(s)
- Lorenza Forna
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, 700309 Iași, Romania; (L.F.); (V.V.L.); (A.L.); (L.M.T.); (A.A.R.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
| | - Laura Bozomitu
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, 700309 Iași, Romania; (L.F.); (V.V.L.); (A.L.); (L.M.T.); (A.A.R.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
| | - Vasile Valeriu Lupu
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, 700309 Iași, Romania; (L.F.); (V.V.L.); (A.L.); (L.M.T.); (A.A.R.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
| | - Ancuta Lupu
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, 700309 Iași, Romania; (L.F.); (V.V.L.); (A.L.); (L.M.T.); (A.A.R.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
| | - Laura Mihaela Trandafir
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, 700309 Iași, Romania; (L.F.); (V.V.L.); (A.L.); (L.M.T.); (A.A.R.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
| | - Anca Adam Raileanu
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, 700309 Iași, Romania; (L.F.); (V.V.L.); (A.L.); (L.M.T.); (A.A.R.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
| | - Camelia Cojocariu
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
- Department of Clinical Gastroenterology, “Sf. Spiridon” Clinical Emergency Hospital, 700111 Iași, Romania
| | - Carmen Anton
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
- Department of Clinical Gastroenterology, “Sf. Spiridon” Clinical Emergency Hospital, 700111 Iași, Romania
| | - Irina Girleanu
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
- Department of Clinical Gastroenterology, “Sf. Spiridon” Clinical Emergency Hospital, 700111 Iași, Romania
| | - Cristina Maria Muzica
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
- Department of Clinical Gastroenterology, “Sf. Spiridon” Clinical Emergency Hospital, 700111 Iași, Romania
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Romano A, Brocca A, Mariño Z, Pérez-del-Pulgar S, Lens S, Boix L, Reig M, Bruix J, Ceolotto G, Calvino V, Zilio G, Romero PP, Vukotic R, Guarneri V, Andreone P, Parisi SG, Russo FP, Piano S, Cillo U, Angeli P. miRNA Expression and HCC Occurrence in HCV Cirrhotic Patients Treated with Direct Acting Antivirals. LIVERS 2024; 4:275-286. [DOI: 10.3390/livers4020020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2025] Open
Abstract
Background: The risk of hepatocarcinoma in HCV cirrhotic patient responders after treatment with DAAs decrease, but HCC still occurs. A correlation between specific miRNAs and the development of hepatocarcinoma have been highlighted. Aim: To investigate miRNA expression in HCV-infected cirrhotic patients treated with DAAs, regarding whether or not they developed HCC at follow-up. Methods: A total of 73 outpatients with HCV-related cirrhosis treated with DAAs were enrolled, 28 of which had HCC. Samples were collected at the start and at the end of treatment. In the screening phase, 172 miRNAs were analyzed at baseline. Differentially expressed miRNAs were validated in the entire cohort. Results: In the validation phase, at baseline and in patients treated for 12 weeks, miR-28-5p was confirmed to be more highly expressed in the HCC group compared to the non-HCC group. In all of the patients treated for 12 weeks, at end of the treatment we found a significant downregulation in miR-132-3p, miR-133b-3p, miR-221-3p and miR-324-3p. In the HCC group, miR-28-5p was significantly downregulated after DAA therapy as well as in HCC patients treated for 24 weeks. Conclusion: In the HCC group, miR28-5p was differently expressed both at baseline and at the end of therapy with DAAs. This difference in expression should suggest its involvement in HCC development.
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Affiliation(s)
- Antonietta Romano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, 35128 Padova, Italy
| | - Alessandra Brocca
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, 35128 Padova, Italy
| | - Zoe Mariño
- Liver Unit, Hospital Clinic Barcelona, Universitat de Barcelona, IDIBAPS, CIBEREHD, 08036 Barcelona, Spain
| | - Sofía Pérez-del-Pulgar
- Liver Unit, Hospital Clinic Barcelona, Universitat de Barcelona, IDIBAPS, CIBEREHD, 08036 Barcelona, Spain
| | - Sabela Lens
- Liver Unit, Hospital Clinic Barcelona, Universitat de Barcelona, IDIBAPS, CIBEREHD, 08036 Barcelona, Spain
| | - Loreto Boix
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, Universitat de Barcelona, IDIBAPS, CIBEREHD, 08036 Barcelona, Spain
| | - María Reig
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, Universitat de Barcelona, IDIBAPS, CIBEREHD, 08036 Barcelona, Spain
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, Universitat de Barcelona, IDIBAPS, CIBEREHD, 08036 Barcelona, Spain
| | - Giulio Ceolotto
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, 35128 Padova, Italy
| | - Valeria Calvino
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, 35128 Padova, Italy
| | - Gianluca Zilio
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, 35128 Padova, Italy
| | | | - Ranka Vukotic
- Department of Medical and Surgical Sciences, DIMEC, University of Bologna, 40138 Bologna, Italy
| | - Valeria Guarneri
- Department of Medical and Surgical Sciences, DIMEC, University of Bologna, 40138 Bologna, Italy
| | - Pietro Andreone
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | | | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, University of Padova, 35121 Padova, Italy
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, 35128 Padova, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Center, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, 35128 Padova, Italy
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Sonderup MW, Kamath PS, Awuku YA, Desalegn H, Gogela N, Katsidzira L, Tzeuton C, Bobat B, Kassianides C, Spearman CW. Managing cirrhosis with limited resources: perspectives from sub-Saharan Africa. Lancet Gastroenterol Hepatol 2024; 9:170-184. [PMID: 38215781 DOI: 10.1016/s2468-1253(23)00279-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 08/05/2023] [Accepted: 08/14/2023] [Indexed: 01/14/2024]
Abstract
Cirrhosis represents the end stage of chronic liver disease. Sub-Saharan Africa, a resource-constrained region, has a high burden of chronic liver disease, with causes including chronic viral hepatitis, excessive alcohol use, and metabolic dysfunction-associated steatotic liver disease (MASLD), the risk of which is burgeoning. The development of liver cirrhosis predicts for morbidity and mortality, driven by both liver dysfunction and the consequences of portal hypertension. Compensated cirrhosis portends a better prognosis than decompensated cirrhosis, highlighting the need for the early diagnosis of cirrhosis and its causes. With resource challenges, the diagnosis and management of cirrhosis is demanding, but less costly and less invasive interventions with substantial benefits, ranging from simple blood tests to transient elastography, are feasible in such settings. Simple interventions are also available to manage the complex manifestations of decompensation, such as β blockers in variceal bleeding prophylaxis, salt restriction and appropriate diuretic use in ascites, and lactulose and generic rifaximin in hepatic encephalopathy. Ultimately, managing the underlying causative factors of liver disease is key in improving prognosis. Management demands expanded policy interventions to increase screening and treatment for hepatitis B and C and reduce alcohol use and the metabolic factors driving MASLD. Furthermore, the skills needed for more specialised interventions, such as transjugular intrahepatic portosystemic shunt procedures and even liver transplantation, warrant planning, increased capacity, and support for regional centres of excellence. Such centres are already being developed in sub-Saharan Africa, demonstrating what can be achieved with dedicated initiatives and individuals.
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Affiliation(s)
- Mark W Sonderup
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
| | | | - Yaw A Awuku
- Department of Medicine, School of Medicine, University of Health and Allied Sciences, Ho, Ghana
| | - Hailemichael Desalegn
- Department of Internal Medicine, St Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Neliswa Gogela
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa
| | - Leolin Katsidzira
- Internal Medicine Unit, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe
| | - Christian Tzeuton
- Faculty of Medicine and Pharmaceutical Sciences of Douala, University of Douala, Douala, Cameroon
| | - Bilal Bobat
- Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand and Wits Donald Gordon Medical Centre, Johannesburg, South Africa
| | - Chris Kassianides
- Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - C Wendy Spearman
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa
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7
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Velarde-Ruiz Velasco J, Tapia Calderón D, Llop Herrera E, Castro Narro G, García Jiménez E, Cerda Reyes E, Higuera de la Tijera F, Cano Contreras A, Moreno Alcántar R, Chávez Ramírez R, Calleja Panero J. Más allá de la exploración física convencional en hepatología: POCUS. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2023; 88:381-391. [DOI: 10.1016/j.rgmx.2023.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/21/2025]
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8
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Velarde-Ruiz Velasco JA, Tapia Calderón DK, Llop Herrera E, Castro Narro G, García Jiménez ES, Cerda Reyes E, Higuera de la Tijera F, Cano Contreras AD, Moreno Alcántar R, Chávez Ramírez RM, Calleja Panero JL. Beyond conventional physical examination in hepatology: POCUS. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2023; 88:381-391. [PMID: 37833134 DOI: 10.1016/j.rgmxen.2023.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 07/26/2023] [Indexed: 10/15/2023]
Abstract
Point-of-care ultrasound (POCUS) refers to the use of ultrasound imaging through pocket-sized sonographic devices at the patient's bedside, to make a diagnosis or direct a procedure and immediately answer a clinical question. Its goal is to broaden the physical examination, not to replace conventional ultrasound studies. POCUS has evolved as a complement to physical examination and has been adopted by different medical specialties, including hepatology. A narrative synthesis of the evidence on the applications of POCUS in hepatology was carried out, describing its usefulness in the diagnosis of cirrhosis of the liver, metabolic dysfunction-associated steatotic liver disease (MASLD), decompensated cirrhosis, and portal hypertension. The review also encompasses more recent applications in the hemodynamic evaluation of the critically ill patient with cirrhosis of the liver, patients with other liver diseases, as well as in the ultrasound guidance of procedures. POCUS could make up part of the daily clinical practice of gastroenterologists and hepatologists, simplifying the initial evaluation of patients and optimizing clinical management. Its accessibility, ease of use, and low adverse event profile make POCUS a useful tool for the properly trained physician in the adequate clinical setting. The aim of this review was to describe the available evidence on the usefulness of POCUS in the daily clinical practice of gastroenterologists and hepatologists.
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Affiliation(s)
- J A Velarde-Ruiz Velasco
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico; Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico
| | - D K Tapia Calderón
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Puerta de Hierro, IDIPHISA, Ciberhd, Majadahonda, Madrid, Spain.
| | - E Llop Herrera
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Puerta de Hierro, IDIPHISA, Ciberhd, Majadahonda, Madrid, Spain
| | - G Castro Narro
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - E S García Jiménez
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - E Cerda Reyes
- Servicio de Gineco-Obstetricia, Hospital Central Militar, Mexico City, Mexico
| | - F Higuera de la Tijera
- Servicio de Gastroenterología, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico
| | - A D Cano Contreras
- Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - R Moreno Alcántar
- Unidad Médica de Alta Especialidad Hospital de Especialidades CMN SXXI, Mexico City, Mexico
| | - R M Chávez Ramírez
- Unidad de Cuidados Intensivos, Hospital de Ginecoobstetricia, UMAE CMNO IMSS, Guadalajara, Jalisco, Mexico
| | - J L Calleja Panero
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Puerta de Hierro, IDIPHISA, Ciberhd, Majadahonda, Madrid, Spain
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9
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Maternal and perinatal outcome in pregnancies complicated with portal hypertension: a systematic review and meta-analysis. Hepatol Int 2023; 17:170-179. [PMID: 35802227 DOI: 10.1007/s12072-022-10385-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 06/15/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Portal hypertension is secondary to either cirrhotic or non-cirrhotic causes, and complicating pregnancy poses a challenge to the treating team. A systematic review was performed to determine maternal and perinatal outcomes in women with portal hypertension. Outcomes were compared among those with cirrhotic (CPH) with non-cirrhotic portal hypertension (NCPH) as well as non-cirrhotic portal fibrosis (NCPF) with extra-hepatic portal vein obstruction (EHPVO). METHODS Medline and EMBASE databases were searched for studies reporting outcomes among pregnant women with portal hypertension. Reference lists from relevant papers and reviews were hand-searched for appropriate citations. Data were extracted to describe maternal complications, obstetric and neonatal outcomes. A random-effects model was used to derive pooled estimates of various outcomes, and final estimates were reported as percentages with a 95% confidence interval (CI). Cumulative, sequential and sensitivity analysis was studied to assess the temporal trends of outcomes over the period. RESULTS Information on 895 pregnancies among 581 patients with portal hypertension was included from 26 studies. Portal hypertension was diagnosed during pregnancy in 10% (95% CI 4-24%). There were 22 maternal deaths (0%, 95% CI 0-1%), mostly following complications from variceal bleeding or hepatic decompensation. Variceal bleeding complicated in 14% (95% CI 9-20%), and endoscopic interventions were performed in 12% (95% CI 8-17%) during pregnancy. Decompensation of liver function occurred in 7% (95% CI 3-12%). Thrombocytopenia was the most common complication (41%, 95% CI 23-60%). Miscarriages occurred in 14% (95% CI 8-20%), preterm birth in 27% (95% CI 19-37%), and low birth weights in 22% (95% CI 15-30%). Risk of postpartum hemorrhage was higher (RR 5.09, 95% CI 1.84-14.12), and variceal bleeding was lower (RR 0.51, 95% CI 0.30-0.86) among those with CPH compared to NCPH. Risk of various outcomes was comparable between NCPF and EHPVO. CONCLUSION One in ten pregnancies complicated with portal hypertension is diagnosed during pregnancy, and thrombocytopenia is the most common complication. Hepatic decompensation and variceal bleeding remain the most common cause of maternal deaths, with reduced rates of bleeding and its complications reported following the introduction of endoscopic procedures during pregnancy. CPH increases the risk of postpartum hemorrhage, whereas variceal bleeding is higher among NCPH.
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10
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Maruyama H, Tobari M, Nagamatsu H, Shiina S, Yamaguchi T. Contrast-enhanced ultrasonography for the management of portal hypertension in cirrhosis. Front Med (Lausanne) 2022; 9:1057045. [PMID: 36590972 PMCID: PMC9794740 DOI: 10.3389/fmed.2022.1057045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 11/16/2022] [Indexed: 12/15/2022] Open
Abstract
Portal hypertension is a major pathophysiological condition in patients with cirrhosis. This accounts for the occurrence and severity of the various manifestations. The degree is determined by the portal pressure or hepatic venous pressure gradients, both of which are obtained by invasive interventional radiological procedures. Ultrasound (US) is a simple and minimally invasive imaging modality for the diagnosis of liver diseases. Owing to the availability of microbubble-based contrast agents and the development of imaging modes corresponding to contrast effects, contrast-enhanced US (CEUS) has become popular worldwide for the detailed evaluation of hepatic hemodynamics, diffuse liver disease, and focal hepatic lesions. Recent advancements in digital technology have enabled contrast-based demonstrations with improved resolution, leading to a wider range of applications. This review article describes the current role, benefits, and limitations of CEUS in the management of portal hypertension.
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Affiliation(s)
- Hitoshi Maruyama
- Department of Gastroenterology, Juntendo University, Tokyo, Japan,*Correspondence: Hitoshi Maruyama
| | - Maki Tobari
- Department of Gastroenterology, Juntendo University, Tokyo, Japan
| | | | - Suichiro Shiina
- Department of Gastroenterology, Juntendo University, Tokyo, Japan
| | - Tadashi Yamaguchi
- Center for Frontier Medical Engineering, Chiba University, Chiba, Japan
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11
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Wieczorek M, Weston A, Ledenko M, Thomas JN, Carter R, Patel T. A deep learning approach for detecting liver cirrhosis from volatolomic analysis of exhaled breath. Front Med (Lausanne) 2022; 9:992703. [PMID: 36250077 PMCID: PMC9556819 DOI: 10.3389/fmed.2022.992703] [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: 07/12/2022] [Accepted: 09/08/2022] [Indexed: 11/21/2022] Open
Abstract
Liver disease such as cirrhosis is known to cause changes in the composition of volatile organic compounds (VOC) present in patient breath samples. Previous studies have demonstrated the diagnosis of liver cirrhosis from these breath samples, but studies are limited to a handful of discrete, well-characterized compounds. We utilized VOC profiles from breath samples from 46 individuals, 35 with cirrhosis and 11 healthy controls. A deep-neural network was optimized to discriminate between healthy controls and individuals with cirrhosis. A 1D convolutional neural network (CNN) was accurate in predicting which patients had cirrhosis with an AUC of 0.90 (95% CI: 0.75, 0.99). Shapley Additive Explanations characterized the presence of discrete, observable peaks which were implicated in prediction, and the top peaks (based on the average SHAP profiles on the test dataset) were noted. CNNs demonstrate the ability to predict the presence of cirrhosis based on a full volatolomics profile of patient breath samples. SHAP values indicate the presence of discrete, detectable peaks in the VOC signal.
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Affiliation(s)
- Mikolaj Wieczorek
- Digital Innovation Lab, Mayo Clinic, Jacksonville, FL, United States
| | - Alexander Weston
- Digital Innovation Lab, Mayo Clinic, Jacksonville, FL, United States
| | - Matthew Ledenko
- Department of Transplant, Mayo Clinic, Jacksonville, FL, United States
| | | | - Rickey Carter
- Digital Innovation Lab, Mayo Clinic, Jacksonville, FL, United States
| | - Tushar Patel
- Department of Transplant, Mayo Clinic, Jacksonville, FL, United States
- *Correspondence: Tushar Patel,
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12
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Han SK, Kim MY, Kang SH, Baik SK. Application of ultrasound for the diagnosis of cirrhosis/portal hypertension. J Med Ultrason (2001) 2022; 49:321-331. [PMID: 35179669 DOI: 10.1007/s10396-022-01191-w] [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: 10/29/2021] [Accepted: 12/03/2021] [Indexed: 11/28/2022]
Abstract
With advances in technologic approaches in patients with cirrhosis, including the improvement of management, a simple, one-step approach for advanced fibrotic state of the liver is clinically useful. Although refining the diagnosis of cirrhosis to reflect disease heterogeneity is essential, current diagnostic tests have not kept pace with the progression of this new paradigm. There are unmet needs in primary care centers with respect to patients with cirrhosis. Liver biopsy and measurement of hepatic venous pressure gradient in patients with cirrhosis are the gold standards for the estimation of hepatic fibrosis, and they have diagnostic and prognostic value. However, both approaches are invasive and cannot be used repeatedly in clinical practice. Ultrasonography (US) is safe, easy to perform, inexpensive, and yields numerical and accurate results. Conventionally, the size of the liver and spleen, bluntness of the liver edge, nodularity of the liver surface, and coarseness of the liver parenchyma have been known as useful parameters for hepatic fibrosis or portal hypertension (PHT) in chronic liver disease. Additionally, some functional US indices including Doppler and CEUS-based examination have been suggested as promising markers for diagnosing cirrhosis and PHT. Identification of the reproducibility and long-term prognostic value through further investigations can demonstrate the clinical usefulness of functional US indices, which are characterized as quantitative parameters for hepatic fibrosis and PHT.
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Affiliation(s)
- Seul Ki Han
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20 Ilsanro, Wonju, 220-701, Republic of Korea
| | - Moon Young Kim
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20 Ilsanro, Wonju, 220-701, Republic of Korea.,Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.,Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Seong Hee Kang
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20 Ilsanro, Wonju, 220-701, Republic of Korea.,Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Soon Koo Baik
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20 Ilsanro, Wonju, 220-701, Republic of Korea. .,Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. .,Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
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13
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Mandavdhare HS, Shah J, Kakadiya R, Kumar-M P, Gupta P, Singh H, Sharma V, Dutta U. A pilot randomized trial to study the success rate of early precut fistulotomy and its effect on radiation dose in patients with difficult biliary cannulation. Acta Gastroenterol Belg 2021; 84:557-561. [PMID: 34965035 DOI: 10.51821/84.4.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
BACKGROUND Role of precut fistulotomy in reducing fluoroscopy time and the radiation dose in difficult selective biliary cannulation is unknown. METHODS We performed a randomized trial where patients with difficult biliary cannulation were randomized into 2 groups: early precut fistulotomy (precut five minutes after failed standard biliary cannulation) or late precut fistulotomy (precut fifteen minutes after failed standard biliary cannulation). We compared the success rates of selective biliary cannulation, fluoroscopy time, radiation dose, complication rates, need for repeat endoscopic retrograde cholangiography (ERC) and need for other interventions. RESULTS Of the 130 eligible patients screened, 40 patients were randomized. The technical success was comparable between early and late group. The fluoroscopy time and radiation dose were significantly less in the early group [4 minutes (3, 6) vs 15 minutes (8, 28), p=0.001] and [1.35 mGy (0.90, 1.63) vs 2.40 mGy (1.58, 3.25), p=0.010] respectively. In the late group, 60% required need for rescue precut fistulotomy. One patient from late group developed post ERC pancreatitis while 1 from early group developed perforation. Three needed other interventions due to failed second attempt. CONCLUSION Early precut fistulotomy has comparable technical success and reduces the radiation dose as compared to late precut fistulotomy for difficult biliary cannulation.
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Affiliation(s)
- H S Mandavdhare
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - J Shah
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - R Kakadiya
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - P Kumar-M
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - P Gupta
- Department of Radiodiagnosis, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - H Singh
- Department of Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - V Sharma
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - U Dutta
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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14
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Baratta F, Ferro D, Pastori D, Colantoni A, Cocomello N, Coronati M, Angelico F, Del Ben M. Open Issues in the Transition from NAFLD to MAFLD: The Experience of the Plinio Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:8993. [PMID: 34501590 PMCID: PMC8430687 DOI: 10.3390/ijerph18178993] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 08/19/2021] [Accepted: 08/23/2021] [Indexed: 12/15/2022]
Abstract
Metabolic associated fatty liver diseases (MAFLD) definition was proposed to identify fatty liver condition associated to metabolic disorders and to replace non-alcoholic fatty liver disease (NAFLD). We aimed to explore the effect of the application of the new MAFLD criteria on a pre-existing cohort of NAFLD patients. The consequences of the reclassification were investigated by applying the MAFLD criteria to a prospective cohort (The Plinio Study) of dysmetabolic patients examined for the presence of NAFLD. In the Plinio cohort, 795 patients had NAFLD and 767 of them (96.5%) were reclassified as MAFLD patients. Out of these, 94.9% had overweight/obesity or diabetes, while the remaining were lean and had metabolic dysregulation defined by the presence of at least two metabolic risk abnormalities. By contrast, 3.5% of the NAFLD patients were reclassified as no-MAFLD due to the absence of overweight/obesity, diabetes, or metabolic risk abnormalities. The only significant difference between the NAFLD and MAFLD groups was the higher prevalence of subjects with BMI ≥ 25 kg/m2 in the latter (88.6% vs. 92%; p = 0.018). In the cohort, 68 subjects were defined as "lean NAFLD". Of these, 40 were reclassified as MAFLD and 28 as no-MAFLD. In conclusion, when applying MAFLD criteria to the Plinio cohort, there is a substantial overlap between NAFLD and MAFLD diagnosis. However, some specific subgroups of patients, such as those currently defined as lean NAFLD, were excluded by the new MAFLD definition.
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Affiliation(s)
- Francesco Baratta
- I Clinica Medica, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy; (F.B.); (D.F.); (A.C.); (N.C.); (M.C.); (M.D.B.)
| | - Domenico Ferro
- I Clinica Medica, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy; (F.B.); (D.F.); (A.C.); (N.C.); (M.C.); (M.D.B.)
| | - Daniele Pastori
- Emergency Medicine Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy
| | - Alessandra Colantoni
- I Clinica Medica, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy; (F.B.); (D.F.); (A.C.); (N.C.); (M.C.); (M.D.B.)
| | - Nicholas Cocomello
- I Clinica Medica, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy; (F.B.); (D.F.); (A.C.); (N.C.); (M.C.); (M.D.B.)
| | - Mattia Coronati
- I Clinica Medica, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy; (F.B.); (D.F.); (A.C.); (N.C.); (M.C.); (M.D.B.)
| | - Francesco Angelico
- Department of Public Health and Infectious Diseases, Sapienza University, 00161 Rome, Italy;
| | - Maria Del Ben
- I Clinica Medica, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy; (F.B.); (D.F.); (A.C.); (N.C.); (M.C.); (M.D.B.)
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15
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Bai XP, Fan YM, Zhang L, Yang GH, Li X. Influence of Liver Cirrhosis on Blood Glucose, Insulin Sensitivity and Islet Function in Mice. Am J Med Sci 2021; 362:403-417. [PMID: 34274322 DOI: 10.1016/j.amjms.2021.07.005] [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: 05/26/2020] [Revised: 02/27/2021] [Accepted: 07/09/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The relationship between cirrhosis and diabetes is controversial. We studied the influence of cirrhosis on glucose levels and islet function and explored its possible mechanisms. MATERIALS AND METHODS Cirrhosis was induced in male C57BL/6 mice by bile duct ligation (BDL). Serum biochemical parameters were determined, and oral glucose tolerance tests (OGTT) were performed at 4 and 8 weeks after BDL. Histopathology and phospho-NF-κB-p65/I-kappa B α immunohistochemical staining of the liver and islet were observed. The protein levels of the insulin signaling system and the gene expression of insulin-degrading enzyme (IDE) in the liver and muscle were determined. The activity of glucokinase (GCK) and glucose 6-phosphatase (G6P) and glycogen levels in liver homogenates were measured. RESULTS After BDL, the mice developed cirrhosis, and fasting glucose decreased significantly, but 2 h postprandial glucose increased, and the insulin areas under the curves increased. At 4 weeks of BDL, the ratios of phospho-NF-κB-p65/I-kappa B α accumulation in the liver and islet increased, the activity of G6P and the glycogen content in liver homogenates decreased, the insulin signaling system and the gene expression of IDE in the liver was downregulated, and the islet areas were decreased. After 8 weeks, these changes were more severe. CONCLUSIONS In different periods of cirrhosis, the levels of fasting glucose and 2 h postprandial glucose changed in different amplitudes. Glycogen concentrations and the activity of G6P in the liver were decreased. The mice developed insulin resistance and the islet areas were decreased. The NF-κB pathway may play a role in the process.
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Affiliation(s)
- Xiu-Ping Bai
- Endocrinology Division, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China.
| | - Yong-Mei Fan
- Endocrinology Division, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China
| | - Lei Zhang
- Endocrinology Division, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China
| | - Guo-Hua Yang
- Central Laboratory, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China
| | - Xing Li
- Endocrinology Division, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China
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16
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Ji JH, Park SY, Son WJ, Shin HJ, Lee H, Lee HW, Lee JS, Kim SU, Park JY, Kim DY, Ahn SH, Kim BK. External validation of CAGE-B and SAGE-B scores for Asian chronic hepatitis B patients with well-controlled viremia by antivirals. J Viral Hepat 2021; 28:951-958. [PMID: 33763928 DOI: 10.1111/jvh.13506] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 02/24/2021] [Accepted: 03/15/2021] [Indexed: 12/11/2022]
Abstract
CAGE-B and SAGE-B scores, consisting of age and fibrotic burden as cirrhosis and/or liver stiffness, were recently proposed to predict hepatocellular carcinoma (HCC) risk among Caucasian chronic hepatitis B (CHB) patients undergoing long-term antiviral therapy. We externally validated their predictive performances among an independent cohort from Asia, compared to other conventional prediction models. We consecutively recruited CHB patients with well-controlled viremia (serum HBV DNA < 2000 IU/mL) receiving antiviral therapy. Patients with decompensated cirrhosis or HCC at baseline were excluded. Among 1763 patients, CAGE-B score provided the highest Heagerty's integrated area under the curve (iAUC) (0.820), followed by SAGE-B (0.804), mREACH-B (0.800), CAMD (0.786), mPAGE-B (0.748) and PAGE-B (0.721) scores. CAGE-B score showed a significantly better performance than SAGE-B, CAMD, PAGE-B and mPAGE-B scores, but was similar to mREACH-B. SAGE-B score also showed significantly better performance than mPAGE-B and PAGE-B, but was similar to CAMD and mREACH-B. According to CAGE-B score 0-5, 6-10 and ≥11, the annual HCC incidences were 0.18, 1.34 and 6.03 per 100 person-years, respectively (all p < 0.001 between each pair). Likewise, by SAGE-B score 0-5, 6-10 and ≥11, those were 0.31, 1.49 and 8.96 per 100 person-years, respectively (all p < 0.001 between each pair). Hence, CAGE-B and SAGE-B scores showed acceptable predictive performances for Asian CHB patients undergoing antiviral therapy, with the higher performance by CAGE-B score. They show a trend towards better prognostic capability to predict HCC risk than previous models.
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Affiliation(s)
- Jung Hyun Ji
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Soo Young Park
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea
| | - Won Jeong Son
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea
| | - Hye Jung Shin
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea
| | - Hyein Lee
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
| | - Hye Won Lee
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Seung Lee
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Do Young Kim
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Beom Kyung Kim
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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17
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Zhang M, Huang S, Ye N, Wang X. Clinical characteristics and risk factors of patients with flupirtine-induced liver cirrhosis complicated with upper gastrointestinal bleeding. Am J Transl Res 2021; 13:5582-5588. [PMID: 34150161 PMCID: PMC8205751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 02/09/2021] [Indexed: 06/12/2023]
Abstract
OBJECTIVE To investigate clinical characteristics and risk factors of patients with Flupirtine-induced liver cirrhosis complicated with upper gastrointestinal bleeding. METHODS A total of 116 patients with liver cirrhosis admitted to our hospital from July 2018 to July 2019 were selected and divided into bleeding group (liver cirrhosis complicated with upper gastrointestinal bleeding, n = 71) and non-bleeding group (liver cirrhosis, n = 45). The clinical data of patients in the two groups were collected, including general data, liver function, urinalysis, coagulation function and imaging data. Univariate analysis and multivariate logistic regression analysis were utilized to find the influencing factors of liver cirrhosis complicated with upper gastrointestinal bleeding. RESULTS Of the 116 patients, 45 patients had upper gastrointestinal bleeding, with an incidence rate of 38.79%, including 18 patients (40.00%) with rupture of esophageal varices, 9 (20.00%) with rupture of gastric varices, 9 (20.00%) of portal hypertensive gastropathy, 8 (17.78%) with peptic ulcer, 1 (2.22%) with acute erosive hemorrhagic gastritis; 14 (31.11%) experienced recurrent hemorrhage within 72 hours after treatment, but no death occurred. There were 45 cases (38.79%) in the bleeding group, and 71 (61.21%) in the non-bleeding group, and the differences in the course of liver cirrhosis, the degree of esophageal varices, peptic ulcer, portal hypertension, non-steroidal drug medication and TP between the bleeding group and non-bleeding group were significant (P < 0.05). Severe esophageal varices, liver cirrhosis, peptic ulcer, portal hypertension, non-steroidal drug medication, and TP ≥ 16 s were found to be risk factors of liver cirrhosis complicated with upper gastrointestinal bleeding by logistic regression analysis. CONCLUSION Clinically, it is necessary to take corresponding intervention measures to reduce the incidence of upper gastrointestinal bleeding in patients with liver cirrhosis and improve the prognosis of patients with liver cirrhosis.
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Affiliation(s)
- Mengjun Zhang
- Department of Gastroenterology, Qinghai University Affiliated HospitalQinghai, China
| | - Si Huang
- The First People’s Hospital of Changde CityChangde, China
| | - Na Ye
- People’s Hospital of WuLan CountyWulan, Hainan, China
| | - Xuehong Wang
- Department of Gastroenterology, Qinghai University Affiliated HospitalQinghai, China
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18
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Shen ZF, Liang X. Current status of radical laparoscopy for treating hepatocellular carcinoma with portal hypertension. World J Clin Cases 2021; 9:2419-2432. [PMID: 33889608 PMCID: PMC8040172 DOI: 10.12998/wjcc.v9.i11.2419] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 12/31/2020] [Accepted: 02/01/2021] [Indexed: 02/06/2023] Open
Abstract
The laparoscopic technique is clinically effective in treating hepatocellular carcinoma (HCC) with portal hypertension (PHT). However, existing studies lack systematic arrangement and induction. Here, we review the latest research advancement in laparoscopic technique for treatment of HCC with PHT, based on published literature and our single-institution experience. Our single-center experience reveals no statistical difference in both short- and long-term prognosis of HCC patients after laparoscopic liver resection (LLR), regardless of whether they suffer from PHT, which is consistent with previous studies on the use of LLR for HCC with PHT. Retrieval outcomes indicate existence of short- and long-term prognostic superiority, following laparoscopic treatment, relative to non-laparoscopic treatment. Besides that, LLR offers long-term prognostic advantage compared to laparoscopic radiofrequency ablation. In addition, we review the previous literature and propose corresponding perspectives on the therapy of hypersplenism, the utilization of Pringle maneuver, and the adoption of anatomical hepatectomy during radical laparoscopic treatment. HCC with PHT is not the "forbidden zone" of radical laparoscopic treatment. However, patients’ preoperative liver function should be adequately estimated.
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Affiliation(s)
- Ze-Feng Shen
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Xiao Liang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
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19
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Kim BK. The cutoff of transient elastography for the evaluation of portal hypertension should be different according to the etiology? Clin Mol Hepatol 2021; 27:91-93. [PMID: 33317235 PMCID: PMC7820203 DOI: 10.3350/cmh.2020.0311] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 11/10/2020] [Accepted: 11/10/2020] [Indexed: 12/13/2022] Open
Affiliation(s)
- Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
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Validation and Refinement of the Baveno VI Criteria for Ruling Out High-Risk Varices. Gastroenterol Res Pract 2020; 2020:4217512. [PMID: 33376483 PMCID: PMC7744238 DOI: 10.1155/2020/4217512] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 11/02/2020] [Accepted: 11/17/2020] [Indexed: 12/14/2022] Open
Abstract
In the past decade, numerous studies have evaluated the roles of noninvasive methods for diagnosing or excluding varices and high-risk varices in patients with liver cirrhosis. The Baveno VI criteria recommend the use of a simple algorithm based on a liver stiffness measurement < 20 kPa through transient elastography and a platelet count > 150 × 109/L for ruling out high-risk varices in patients with compensated advanced chronic liver disease. A large number of studies have validated the clinical usefulness of Baveno VI criteria for excluding high-risk varices. Several strategies have been proposed to refine the Baveno VI criteria; however, currently there is no review to summarize the diagnostic accuracy and limitations of the Baveno VI criteria after extensive validation. In this review, we summarize the diagnostic accuracy and limitations of the Baveno VI criteria after extensive validation. We also discuss methods to refine these criteria.
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Baratta F, Pastori D, Angelico F, Balla A, Paganini AM, Cocomello N, Ferro D, Violi F, Sanyal AJ, Del Ben M. Nonalcoholic Fatty Liver Disease and Fibrosis Associated With Increased Risk of Cardiovascular Events in a Prospective Study. Clin Gastroenterol Hepatol 2020; 18:2324-2331.e4. [PMID: 31887443 DOI: 10.1016/j.cgh.2019.12.026] [Citation(s) in RCA: 146] [Impact Index Per Article: 29.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 11/30/2019] [Accepted: 12/23/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with non-alcoholic fatty liver disease (NAFLD) are at increased chance for cardiovascular events (CVEs). Severity of liver fibrosis is used to determine prognoses for patients with NAFLD, but little is known about the relationship between liver fibrosis and CVEs in the real world. METHODS We analyzed data from the prospective observational progression of liver damage and cardiometabolic disorders in non-alcoholic fatty liver disease study, comprising 898 consecutive outpatients (mean age, 56.4 ± 12.7 years; 37.5% women) screened for liver steatosis by ultrasound according to Hamagughi criteria. Liver fibrosis was defined as FIB-4 score greater than 2.67 and NAFLD fibrosis score greater than 0.676. After enrolment, patients were interviewed by phone every 6 months and examined every 12 months in the outpatient clinic, and CVEs were recorded (fatal or nonfatal ischemic stroke and myocardial infarction, cardiac or peripheral revascularization, new-onset arterial fibrillation and cardiovascular death). The primary outcomes were incidence rate of CVEs in patients with vs without NAFLD and factors associated with CVEs in patients with NAFLD. RESULTS Over a median follow-up time of 41.4 months (3044.4 patient-years), 58 CVEs (1.9%/year) were registered. The rate of CVEs was higher in patients with (n = 643, 2.1%/year) vs without NAFLD (n = 255, 1.0%/year) (P = .066). In multivariable Cox proportional regression analysis, NAFLD increased risk for CVEs (hazard ratio [HR], 2.41; 95% CI, 1.06-5.47; P = .036), after adjustment for metabolic syndrome. Among patients with NAFLD, male sex, previous CVEs, metabolic syndrome and FIB-4 scores greater than 2.67 (HR, 4.02; 95% CI, 1.21-13.38; P = .023) were independently associated with risk of incident CVEs. NFS scores greater than 0.676 were also independently associated with risk of incident CVEs (HR, 2.35; 95% CI, 1.05-5.27; P = .038). CONCLUSIONS In an analysis of data from a study of patients screened for NAFLD and followed, individuals with NAFLD had more than a 2-fold increase in risk of CVEs, and those with liver fibrosis had a 4-fold increase in risk. In patients with NAFLD, liver fibrosis indexes were independently associated with risk of incident CVEs. ClinicalTrials.gov no:NCT04036357.
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Affiliation(s)
- Francesco Baratta
- I Clinica Medica, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Daniele Pastori
- I Clinica Medica, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
| | - Francesco Angelico
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Andrea Balla
- Department of General Surgery and Surgical Specialties "Paride Stefanini", Sapienza University of Rome, Rome, Italy
| | - Alessandro Maria Paganini
- Department of General Surgery and Surgical Specialties "Paride Stefanini", Sapienza University of Rome, Rome, Italy
| | - Nicholas Cocomello
- I Clinica Medica, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Domenico Ferro
- I Clinica Medica, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Francesco Violi
- I Clinica Medica, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy; Mediterranea Cardiocentro, Naples, Italy
| | - Arun J Sanyal
- Division of Gastroenterology, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Maria Del Ben
- I Clinica Medica, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
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Kreisel W, Schaffner D, Lazaro A, Trebicka J, Merfort I, Schmitt-Graeff A, Deibert P. Phosphodiesterases in the Liver as Potential Therapeutic Targets of Cirrhotic Portal Hypertension. Int J Mol Sci 2020; 21:6223. [PMID: 32872119 PMCID: PMC7503357 DOI: 10.3390/ijms21176223] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 08/23/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
Liver cirrhosis is a frequent condition with high impact on patients' life expectancy and health care systems. Cirrhotic portal hypertension (PH) gradually develops with deteriorating liver function and can lead to life-threatening complications. Other than an increase in intrahepatic flow resistance due to morphological remodeling of the organ, a functional dysregulation of the sinusoids, the smallest functional units of liver vasculature, plays a pivotal role. Vascular tone is primarily regulated by the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, wherein soluble guanylate cyclase (sGC) and phosphodiesterase-5 (PDE-5) are key enzymes. Recent data showed characteristic alterations in the expression of these regulatory enzymes or metabolite levels in liver cirrhosis. Additionally, a disturbed zonation of the components of this pathway along the sinusoids was detected. This review describes current knowledge of the pathophysiology of PH with focus on the enzymes regulating cGMP availability, i.e., sGC and PDE-5. The results have primarily been obtained in animal models of liver cirrhosis. However, clinical and histochemical data suggest that the new biochemical model we propose can be applied to human liver cirrhosis. The role of PDE-5 as potential target for medical therapy of PH is discussed.
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Affiliation(s)
- Wolfgang Kreisel
- Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany
| | - Denise Schaffner
- Institute for Exercise and Occupational Medicine, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany; (D.S.); (A.L.); (P.D.)
- Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, 79104 Freiburg, Germany;
- Department of Radiology–Medical Physics, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany
| | - Adhara Lazaro
- Institute for Exercise and Occupational Medicine, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany; (D.S.); (A.L.); (P.D.)
| | - Jonel Trebicka
- Translational Hepatology, Department of Internal Medicine I, Goethe University Clinic Frankfurt, 60590 Frankfurt, Germany;
| | - Irmgard Merfort
- Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, 79104 Freiburg, Germany;
| | | | - Peter Deibert
- Institute for Exercise and Occupational Medicine, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany; (D.S.); (A.L.); (P.D.)
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Lee HW, Park SY, Lee M, Lee EJ, Lee J, Kim SU, Park JY, Kim DY, Ahn SH, Kim BK. An optimized hepatocellular carcinoma prediction model for chronic hepatitis B with well-controlled viremia. Liver Int 2020; 40:1736-1743. [PMID: 32239602 DOI: 10.1111/liv.14451] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 03/04/2020] [Accepted: 03/17/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) substantially decreased in the era of potent antiviral therapy. We developed an optimized HCC risk prediction model for CHB with well-controlled viremia by nucelos(t)ide analogs (NUCs). METHOD We analysed those who achieved virological response (VR; serum HBV-DNA < 2000 IU/mL on two consecutive assessments) by NUCs. Liver stiffness by transient elastography, ultrasonography and laboratory tests was performed at the time of confirmed VR. Patients with decompensated cirrhosis or HCC at baseline were excluded. Multivariate Cox-regression analysis was used to determine key variables to construct a novel risk-scoring model. RESULTS Among 1511 patients, 9.5% developed HCC. Cirrhosis on ultrasonography (adjusted HR [aHR] 2.47), age (aHR 1.04), male (aHR 1.90), platelet count <135 000/uL (aHR 1.57), albumin <4.5 g/dL (aHR 1.77) and liver stiffness ≥11 kPa (aHR 6.09) were independently associated with HCC. Using these, CAMPAS model was developed with c-index of 0.874. The predicted and observed HCC probabilities were calibrated with a reliable agreement. Such results were reproduced from internal validation and external validation among the independent cohort (n = 252). The intermediate-risk (CAMPAS model score 75 ~ 161) and high-risk (score >161) groups were more likely to develop HCC compared with the low-risk group (score ≤75) with statistical significances (HRs; 4.43 and 47.693 respectively; both P < .001). CONCLUSION CAMPAS model derived through comprehensive clinical evaluation of liver disease allowed the more delicate HCC prediction for CHB patients with well-controlled viremia by NUCs.
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Affiliation(s)
- Hye W Lee
- Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Soo Y Park
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Myeongjee Lee
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Eun J Lee
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jinae Lee
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung U Kim
- Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Jun Y Park
- Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Do Y Kim
- Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Sang H Ahn
- Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Beom K Kim
- Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
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Baratta F, Pastori D, Bartimoccia S, Cammisotto V, Cocomello N, Colantoni A, Nocella C, Carnevale R, Ferro D, Angelico F, Violi F, Del Ben M. Poor Adherence to Mediterranean Diet and Serum Lipopolysaccharide are Associated with Oxidative Stress in Patients with Non-Alcoholic Fatty Liver Disease. Nutrients 2020; 12:1732. [PMID: 32531941 PMCID: PMC7352324 DOI: 10.3390/nu12061732] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 06/05/2020] [Accepted: 06/07/2020] [Indexed: 12/17/2022] Open
Abstract
Oxidative stress plays a pivotal role in non-alcoholic fatty liver disease (NAFLD). Factors inducing oxidative stress in NAFLD may be several; however, a relationship with the adherence to Mediterranean Diet (Med-diet) and with serum lipopolysaccharide (LPS) has been poorly investigated in this setting. The aim was to investigate factors associated with impaired oxidative stress in NAFLD, focusing on the potential role of LPS and Med-diet. We enrolled 238 consecutive outpatients from the PLINIO study, in whom we measured the soluble Nox2-derived peptide (sNox2-dp), a marker of systemic oxidative stress, and serum LPS. Adherence to Med-diet was investigated by a nine-item validated dietary questionnaire. Serum sNox2-dp and LPS were higher in patients with NAFLD compared to those without (25.0 vs. 9.0 pg/mL, p < 0.001 and 62.0 vs. 44.9 pg/mL, p < 0.001, respectively). In patients with NAFLD, the highest sNox2-dp tertile was associated with the top serum LPS tertile (Odds Ratio (OR): 4.71; p < 0.001), APRI > 0.7 (OR: 6.96; p = 0.005) and Med-diet-score > 6 (OR: 0.14; p = 0.026). Analyzing individual foods, the daily consumption of wine (OR: 0.29, p = 0.046) and the adequate weekly consumption of fish (OR: 0.32, p = 0.030) inversely correlated with the top sNox2-dp tertile. In conclusion, patients with NAFLD showed impaired oxidative stress. Levels of sNox2 correlated with serum LPS and with low adherence to Med-Diet.
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Affiliation(s)
- Francesco Baratta
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Daniele Pastori
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Simona Bartimoccia
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Vittoria Cammisotto
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Nicholas Cocomello
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Alessandra Colantoni
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Cristina Nocella
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Roberto Carnevale
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04015 Latina, Italy;
- Mediterranea Cardio Centro, 80122 Napoli, Italy
| | - Domenico Ferro
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
| | - Francesco Angelico
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Roma, Italy
| | - Francesco Violi
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
- Mediterranea Cardio Centro, 80122 Napoli, Italy
| | - Maria Del Ben
- I Clinica Medica, Department of Clinical Internal, Anestesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Roma, Italy; (F.B.); (D.P.); (S.B.); (V.C.); (N.C.); (A.C.); (C.N.); (D.F.); (F.V.); (M.D.B.)
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Dercle L, Ma J, Xie C, Chen AP, Wang D, Luk L, Revel-Mouroz P, Otal P, Peron JM, Rousseau H, Lu L, Schwartz LH, Mokrane FZ, Zhao B. Using a single abdominal computed tomography image to differentiate five contrast-enhancement phases: A machine-learning algorithm for radiomics-based precision medicine. Eur J Radiol 2020; 125:108850. [PMID: 32070870 DOI: 10.1016/j.ejrad.2020.108850] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 01/25/2020] [Indexed: 11/29/2022]
Abstract
PURPOSE The clinical adoption of quantitative imaging biomarkers (radiomics) has established the need for high quality contrast-enhancement in medical images. We aimed to develop a machine-learning algorithm for Quality Control of Contrast-Enhancement on CT-scan (CECT-QC). METHOD Multicenter data from four independent cohorts [A, B, C, D] of patients with measurable liver lesions were analyzed retrospectively (patients:time-points; 503:3397): [A] dynamic CTs from primary liver cancer (60:2359); [B] triphasic CTs from primary liver cancer (31:93); [C] triphasic CTs from hepatocellular carcinoma (121:363); [D] portal venous phase CTs of liver metastasis from colorectal cancer (291:582). Patients from cohort A were randomized to training-set (48:1884) and test-set (12:475). A random forest classifier was trained and tested to identify five contrast-enhancement phases. The input was the mean intensity of the abdominal aorta and the portal vein measured on a single abdominal CT scan image at a single time-point. The output to be predicted was: non-contrast [NCP], early-arterial [E-AP], optimal-arterial [O-AP], optimal-portal [O-PVP], and late-portal [L-PVP]. Clinical utility was assessed in cohorts B, C, and D. RESULTS The CECT-QC algorithm showed performances of 98 %, 90 %, and 84 % for predicting NCP, O-AP, and O-PVP, respectively. O-PVP was reached in half of patients and was associated with a peak in liver malignancy density. Contrast-enhancement quality significantly influenced radiomics features deciphering the phenotype of liver neoplasms. CONCLUSIONS A single CT-image can be used to differentiate five contrast-enhancement phases for radiomics-based precision medicine in the most common liver neoplasms occurring in patients with or without liver cirrhosis.
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Affiliation(s)
- Laurent Dercle
- Columbia University Vagellos College of Physicians and Surgeons, Department of Radiology, New York, New York City, USA; Department of Radiology New York Presbyterian Hospital, USA.
| | - Jingchen Ma
- Columbia University Vagellos College of Physicians and Surgeons, Department of Radiology, New York, New York City, USA; Department of Radiology New York Presbyterian Hospital, USA
| | - Chuanmiao Xie
- Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Ai-Ping Chen
- Columbia University Vagellos College of Physicians and Surgeons, Department of Radiology, New York, New York City, USA; Department of Radiology New York Presbyterian Hospital, USA
| | - Deling Wang
- Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Lyndon Luk
- Columbia University Vagellos College of Physicians and Surgeons, Department of Radiology, New York, New York City, USA; Department of Radiology New York Presbyterian Hospital, USA
| | - Paul Revel-Mouroz
- Radiology Department, Rangueil University Hospital, Toulouse, France
| | - Philippe Otal
- Radiology Department, Rangueil University Hospital, Toulouse, France
| | - Jean-Marie Peron
- Hepatology Department, Purpan University Hospital, Toulouse, France
| | - Hervé Rousseau
- Radiology Department, Rangueil University Hospital, Toulouse, France
| | - Lin Lu
- Columbia University Vagellos College of Physicians and Surgeons, Department of Radiology, New York, New York City, USA; Department of Radiology New York Presbyterian Hospital, USA
| | - Lawrence H Schwartz
- Columbia University Vagellos College of Physicians and Surgeons, Department of Radiology, New York, New York City, USA; Department of Radiology New York Presbyterian Hospital, USA
| | - Fatima-Zohra Mokrane
- Columbia University Vagellos College of Physicians and Surgeons, Department of Radiology, New York, New York City, USA; Department of Radiology New York Presbyterian Hospital, USA; Radiology Department, Rangueil University Hospital, Toulouse, France
| | - Binsheng Zhao
- Columbia University Vagellos College of Physicians and Surgeons, Department of Radiology, New York, New York City, USA; Department of Radiology New York Presbyterian Hospital, USA
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Baratta F, Pastori D, Tozzi G, D'Erasmo L, Di Costanzo A, Arca M, Ettorre E, Ginanni Corradini S, Violi F, Angelico F, Del Ben M. Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non-alcoholic fatty liver disease. Liver Int 2019; 39:2301-2308. [PMID: 31392821 DOI: 10.1111/liv.14206] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 07/15/2019] [Accepted: 07/26/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Recent evidence showed a reduced activity of the lysosomal acid lipase (LAL) in patients with non-alcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC). However, the relationship between LAL activity and liver fibrosis has never been investigated. METHODS Cross-sectional study including 575 outpatients referred for the management of cardio-metabolic and liver disease. The absence of liver fibrosis was defined by a FIB-4 < 1.30 and NAFLD fibrosis score (NFS) <-1.455. LAL activity was measured with dried blood spot technique. RESULTS Overall, 515 patients had a diagnosis of NAFLD (454 NAFL and 61 biopsy-proven NASH) and 60 of CC. The value of LAL activity progressively decreased from healthy subjects to NAFL/NASH patients to CC (P < .001). LAL activity was reduced by 10% in patients with NAFL, by 20% in NASH and by 50% in CC. The prevalence of CC decreased across the tertiles of LAL activity: 22.2% in the lowest, 4.6% in the intermediate and 0.5% in the highest tertile. In NAFLD patients, 69.9% had a FIB4 < 1.30, and 43.1% a NFS <-1.455. Multivariate logistic regression analysis showed that Log (LAL activity) was associated with FIB-4 < 1.30 (Odds ratio [OR] 2.19 95% confidence interval [CI] 1.33-3.62, P = .002) and NFS < -1.455 (OR 2.43, 95% CI 1.51-3.91, P < .001) after adjustment for confounding factors. CONCLUSIONS We found a progressive reduction of LAL activity according to liver disease severity. LAL activity was inversely associated with markers of liver fibrosis in patients with NAFLD.
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Affiliation(s)
- Francesco Baratta
- I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
- Department of Anatomical Sciences, Histological, Legal Medical and Locomotor, Sapienza University of Rome, Rome, Italy
| | - Daniele Pastori
- I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Giulia Tozzi
- Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy
| | - Laura D'Erasmo
- I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Alessia Di Costanzo
- I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Marcello Arca
- I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Evaristo Ettorre
- Division of Gerontology, Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, Sapienza University, Rome, Italy
| | | | - Francesco Violi
- I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
- Mediterranea Cardiocentro, Naples, Italy
| | - Francesco Angelico
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Maria Del Ben
- I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
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Rana R, Wang S, Li J, Basnet S, Zheng L, Yang C. Diagnostic accuracy of non-invasive methods detecting clinically significant portal hypertension in liver cirrhosis: a systematic review and meta-analysis. Minerva Med 2019; 111:266-280. [PMID: 31638361 DOI: 10.23736/s0026-4806.19.06143-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
INTRODUCTION We attempted to investigate non-invasive techniques and their diagnostic performances for evaluating clinically significant portal hypertension. EVIDENCE ACQUISITION The systematic search was performed on PubMed, Embase, Scopus, and Web of Science TM core index databases before 13 December 2018 restricted to English language and human studies. EVIDENCE SYNTHESIS Thirty-two studies were included, with total populations of 3,987. The overall pooled analysis was performed by bivariate random effect model, which revealed significantly higher sensitivity and specificity of 77.1% (95% confidence interval, 76.8-78.5%) and 80.1% (95% confidence interval, 78.2-81.9%), respectively; positive likelihood ratio (3.67), negative likelihood ratio (0.26); and diagnostic odd ratio (16.24). Additionally, the area under curve exhibited significant diagnostic accuracy of 0.871. However, notable heterogeneity existed in between studies (I2=87.1%), therefore, further subgroup analysis was performed. It demonstrated ultrasonography, elastography, biomarker, and computed tomography scan had a significant overall summary sensitivity (specificity) of 89.6% (78.9%), 81.7% (83.2%), 72.2% (76.8%), and 77.2% (81.2%), respectively. Moreover, the areas under curve values were significantly higher in elastography (0.906), followed by computed tomography scan (0.847), biomarker (0.825), and ultrasonography (0.803). CONCLUSIONS In future, non-invasive techniques could be the future choice of investigations for screening and diagnosis of clinically significant portal hypertension in cirrhosis. However, standardization of diagnostic indices and their cut-off values in each non-invasive method needs to be addressed.
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Affiliation(s)
- Ramesh Rana
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China.,Department of Internal Medicine, Gautam Buddha Community Heart Hospital, Butwal, Nepal
| | - Shenglan Wang
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jing Li
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Shiva Basnet
- Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Liang Zheng
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Changqing Yang
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China -
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Sun J, Zhang T, Wang J, Li W, Zhang A, He W, Zhang D, Li D, Ding J, Duan X. Biologically effective dose (BED) of stereotactic body radiation therapy (SBRT) was an important factor of therapeutic efficacy in patients with hepatocellular carcinoma (≤5 cm). BMC Cancer 2019; 19:846. [PMID: 31455251 PMCID: PMC6712687 DOI: 10.1186/s12885-019-6063-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 08/19/2019] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND To explore the association between biologically effective dose (BED) and survival rates in Child-Pugh A classification (CP-A) small hepatocellular carcinoma (HCC) patients treated with stereotactic body radiation therapy (SBRT). METHODS This retrospective study included 108 small HCC patients who were treated with SBRT between 2011 and 2014. The prescribed dose delivered to the tumor were 48Gy/8f, 49Gy/7f, 50Gy/5f and 54Gy/6f. The median biologically effective dose (BED10) of the total prescribed dose was 100Gy (76.8-102.6Gy). Factors associated with the survival rate were examined using the Cox proportion hazards model, and the factors associated with radiation-induced liver injury (RILD) were examined by logistic regression analysis. RESULTS For these patients, the median follow-up time was 42 months (6-77 months), and the 1-, 2- and 3-year overall survival (OS) rates were 96.3, 89.8 and 80.6%, respectively. The 1-, 2- and 3-year progression-free survival (PFS) rates were 85.2, 70.1 and 60.6%, respectively. The 1-, 2- and 3-year local control (LC) rates were 98.1, 96.2 and 95.1%, respectively. The 1-, 2- and 3-year distant metastasis- free survival (DMFS) rates were 86.1, 72.8 and 61.2%. The OS, PFS and DMFS were significantly higher in the BED10 ≥ 100Gy group than in the BED10 < 100Gy group (OS: p = 0.020; PFS: p = 0.017; DMFS: p = 0.012). The PLT count was a predictive factor of RILD. CONCLUSIONS SBRT is a safe and effective option for CP-A HCC patients. A BED10 value greater than 100Gy and lower CP score are associated with improved OS and PFS. Additionally, the peripheral PLT count are predictive factors of RILD.
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Affiliation(s)
- Jing Sun
- Radiation Oncology Center, The Fifth Medical Center of PLA General Hospital (Beijing 302 Hospital), No. 100 Xi Si Huan Middle Road, Fengtai District, Beijing, 100039 China
| | - Tao Zhang
- Radiation Oncology Center, The Fifth Medical Center of PLA General Hospital (Beijing 302 Hospital), No. 100 Xi Si Huan Middle Road, Fengtai District, Beijing, 100039 China
| | - Jia Wang
- Radiation Oncology Center, The Fifth Medical Center of PLA General Hospital (Beijing 302 Hospital), No. 100 Xi Si Huan Middle Road, Fengtai District, Beijing, 100039 China
| | - Wengang Li
- Radiation Oncology Center, The Fifth Medical Center of PLA General Hospital (Beijing 302 Hospital), No. 100 Xi Si Huan Middle Road, Fengtai District, Beijing, 100039 China
| | - Aimin Zhang
- Radiation Oncology Center, The Fifth Medical Center of PLA General Hospital (Beijing 302 Hospital), No. 100 Xi Si Huan Middle Road, Fengtai District, Beijing, 100039 China
| | - Weiping He
- Radiation Oncology Center, The Fifth Medical Center of PLA General Hospital (Beijing 302 Hospital), No. 100 Xi Si Huan Middle Road, Fengtai District, Beijing, 100039 China
| | - Dan Zhang
- Radiation Oncology Center, The Fifth Medical Center of PLA General Hospital (Beijing 302 Hospital), No. 100 Xi Si Huan Middle Road, Fengtai District, Beijing, 100039 China
| | - Dong Li
- Radiation Oncology Center, The Fifth Medical Center of PLA General Hospital (Beijing 302 Hospital), No. 100 Xi Si Huan Middle Road, Fengtai District, Beijing, 100039 China
| | - Junqiang Ding
- Radiation Oncology Center, The Fifth Medical Center of PLA General Hospital (Beijing 302 Hospital), No. 100 Xi Si Huan Middle Road, Fengtai District, Beijing, 100039 China
| | - Xuezhang Duan
- Radiation Oncology Center, The Fifth Medical Center of PLA General Hospital (Beijing 302 Hospital), No. 100 Xi Si Huan Middle Road, Fengtai District, Beijing, 100039 China
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Aller MA, Blanco-Rivero J, Arias N, Santamaria L, Arias J. The Lymphatic Headmaster of the Mast Cell-Related Splanchnic Inflammation in Portal Hypertension. Cells 2019; 8:cells8070658. [PMID: 31261968 PMCID: PMC6678304 DOI: 10.3390/cells8070658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 06/24/2019] [Accepted: 06/25/2019] [Indexed: 11/16/2022] Open
Abstract
Portal hypertension is a common complication of liver disease, either acute or chronic. Consequently, in chronic liver disease, such as the hypertensive mesenteric venous pathology, the coexisting inflammatory response is classically characterized by the splanchnic blood circulation. However, a vascular lymphatic pathology is produced simultaneously with the splanchnic arterio-venous impairments. The pathological increase of the mesenteric venous pressure, by mechanotransduction of the venous endothelium hyperpressure, causes an inflammatory response involving the subendothelial mast cells and the lymphatic endothelium of the intestinal villi lacteal. In portal hypertension, the intestinal lymphatic inflammatory response through the development of mesenteric-systemic lymphatic collateral vessels favors the systemic diffusion of substances with a molecular pattern associated with damage and pathogens of intestinal origin. When the chronic hepatic insufficiency worsens the portal hypertensive inflammatory response, the splanchnic lymphatic system transports the hyperplasied intestinal mast cells to the mesenteric lymphatic complex. Then, an acquired immune response regulating a new hepato-intestinal metabolic scenario is activated. Therefore, reduction of the hepatic metabolism would reduce its key centralized functions, such as the metabolic, detoxifying and antioxidant functions which would try to be substituted by their peroxisome activity, among other functions of the mast cells.
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Affiliation(s)
- Maria-Angeles Aller
- Department of Surgery, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
| | - Javier Blanco-Rivero
- Department of Physiology, School of Medicine, Autonomous University of Madrid, 28049 Madrid, Spain
- Instituto de Investigación Biomédica La Paz (IdIPAZ), 28046 Madrid, Spain
- Centro de Investigación Biomédica en Red (Ciber) de Enfermedades Cardiovasculares, 28029 Madrid, Spain
| | - Natalia Arias
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK
- INEUROPA (Instituto de Neurociencias del Principado de Asturias), 33003 Oviedo, Spain
| | - Luis Santamaria
- Department of Anatomy, Histology and Neuroscience, School of Medicine, Autonoma University of Madrid, 28029 Madrid, Spain
| | - Jaime Arias
- Department of Surgery, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain
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Yu J, He JQ, Chen DY, Pan QL, Yang JF, Cao HC, Li LJ. Dynamic changes of key metabolites during liver fibrosis in rats. World J Gastroenterol 2019; 25:941-954. [PMID: 30833800 PMCID: PMC6397726 DOI: 10.3748/wjg.v25.i8.941] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 01/10/2019] [Accepted: 01/28/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Fibrosis is the single most important predictor of significant morbidity and mortality in patients with chronic liver disease. Established non-invasive tests for monitoring fibrosis are lacking, and new biomarkers of liver fibrosis and function are needed. AIM To depict the process of liver fibrosis and look for novel biomarkers for diagnosis and monitoring fibrosis progression. METHODS CCl4 was used to establish the rat liver fibrosis model. Liver fibrosis process was measured by liver chemical tests, liver histopathology, and Masson's trichrome staining. The expression levels of two fibrotic markers including α-smooth muscle actin and transforming growth factor β1 were assessed using immunohistochemistry and real-time polymerase chain reaction. Dynamic changes in metabolic profiles and biomarker concentrations in rat serum during liver fibrosis progression were investigated using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The discriminatory capability of potential biomarkers was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS To investigate the dynamic changes of metabolites during the process of liver fibrosis, sera from control and fibrosis model rats based on pathological results were analyzed at five different time points. We investigated the association of liver fibrosis with 21 metabolites including hydroxyethyl glycine, L-threonine, indoleacrylic acid, β-muricholic acid (β-MCA), cervonoyl ethanolamide (CEA), phosphatidylcholines, and lysophosphatidylcholines. Two metabolites, CEA and β-MCA, differed significantly in the fibrosis model rats compared to controls (P < 0.05) and showed prognostic value for fibrosis. ROC curve analyses performed to calculate the area under the curve (AUC) revealed that CEA and β-MCA differed significantly in the fibrosis group compared to controls with AUC values exceeding 0.8, and can clearly differentiate early stage from late stage fibrosis or cirrhosis. CONCLUSION This study identified two novel biomarkers of fibrosis, CEA and β-MCA, which were effective for diagnosing fibrosis in an animal model.
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Affiliation(s)
- Jiong Yu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Jian-Qin He
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
| | - De-Ying Chen
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Qiao-Ling Pan
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Jin-Feng Yang
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Hong-Cui Cao
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Lan-Juan Li
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
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Maruyama H, Kato N. Advances in ultrasound diagnosis in chronic liver diseases. Clin Mol Hepatol 2019; 25:160-167. [PMID: 30773001 PMCID: PMC6589854 DOI: 10.3350/cmh.2018.1013] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 12/25/2018] [Indexed: 02/07/2023] Open
Abstract
Chronic liver disease is a major disorder worldwide. A better understanding of anatomy, blood flow, and pathophysiology may be a key issue for their proper management. Ultrasound (US) is a simple and non-invasive diagnostic tool in the abdominal field. Doppler mode offers real-time hemodynamic evaluation, and the contrast-enhanced US is one of the most frequently used modalities for the detailed assessment. Further development in digital technology enables threedimensional (3D) visualization of target images with high resolution. This article reviews the wide ranges of application in the abdominal US and describes the recent progress in the diagnosis of chronic liver diseases.
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Affiliation(s)
- Hitoshi Maruyama
- Department of Gastroenterology, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Naoya Kato
- Department of Gastroenterology, Chiba University Graduate School of Medicine, Chiba, Japan
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Salman MA, Mansour DA, Balamoun HA, Elbarmelgi MY, Hadad KEE, Abo Taleb ME, Salman A. Portal venous pressure as a predictor of mortality in cirrhotic patients undergoing emergency surgery. Asian J Surg 2019; 42:338-342. [PMID: 30316666 DOI: 10.1016/j.asjsur.2018.09.007] [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: 08/04/2018] [Revised: 09/03/2018] [Accepted: 09/17/2018] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE Emergency surgery is a risk factor for mortality in cirrhotic patients. Portal hypertension is an essential feature of decompensated cirrhosis. This study aimed to assess the value of portal venous pressure (PVP) measurement in prediction of 1-month mortality in cirrhotic patients undergoing emergency laparotomy. METHODS This prospective study included 121 adults with liver cirrhosis subjected to an emergency laparotomy. Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score were used for preoperative patient evaluation. PVP was measured directly at the beginning of surgery. Portal hypertension (PHT) is diagnosed when PVP is greater than 12 mmHg. The primary outcome measure was the risk of mortality within one month after surgery. RESULTS PVP ranged from 5 to 27 mmHg; 82 patients (67.8%) had PHT. Fifty-five patients (45.5%) died within 1 month. Mortality was significantly associated with increasing CTP Class, MELD score and PHT (p < 0.001 for all). PHT predicts mortality with a sensitivity of 83.6% and specificity of 92.8%. PHT was the only independent predictor of mortality (OR: 23.0, 95%CI: 8.9-59.4). CONCLUSION In patients with liver cirrhosis, emergency laparotomy carries a substantial risk of mortality within one month. Portal hypertension is an independent predictor of risk of mortality in these patients.
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Affiliation(s)
| | - Doaa Ahmed Mansour
- General Surgery Department, Kasralainy School of Medicine, Cairo University, Egypt.
| | - Hany Armia Balamoun
- General Surgery Department, Kasralainy School of Medicine, Cairo University, Egypt.
| | | | | | | | - Ahmed Salman
- Internal Medicine Department, Kasralainy School of Medicine, Cairo University, Egypt.
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Kang SH, Jeong WK, Baik SK, Cha SH, Kim MY. Impact of sarcopenia on prognostic value of cirrhosis: going beyond the hepatic venous pressure gradient and MELD score. J Cachexia Sarcopenia Muscle 2018; 9:860-870. [PMID: 30371017 PMCID: PMC6204582 DOI: 10.1002/jcsm.12333] [Citation(s) in RCA: 95] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Revised: 06/03/2018] [Accepted: 06/21/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Sarcopenia has been reported as a prognostic factor. We evaluated the impact of sarcopenia to the conventional prognostic factors [Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, hepatic venous pressure gradient (HVPG)] in cirrhosis. METHODS Overall, 452 patients with cirrhosis were stratified by MELD score (low < 15, high ≥ 15), CTP class, and HVPG [non-clinically significant portal hypertension (CSPH), 6-9 mmHg; CSPH, 10-19 mmHg; extremely severe PH, ≥20 mmHg]. L3 skeletal muscle index as marker of sarcopenia was subdivided into quartiles (47.01-52.25-58.22 cm2 /m2 ). RESULTS Among the patients, 42% (190/452) presented with sarcopenia. During a median follow-up period of 21.2 months, sarcopenia was associated with mortality (adjusted hazard ratio = 2.253, P < 0.001) and specifically with compensated and early decompensated stages of cirrhosis, but not with advanced decompensated stages; low (P < 0.001) and high (P = 0.095) MELD scores; CTP classes A (P = 0.034), B (P < 0.001), and C (P = 0.205); and non-CSPH (P = 0.018), CSPH (P < 0.001), and extremely severe PH (P = 0.846). In quartiles of sarcopenia, MELD score, CTP class, and HVPG were independent predictors of mortality in non-sarcopenia, but not in severe sarcopenia (MELD, P = 0.182; CTP, P = 0.187; HVPG, P = 0.077). CONCLUSIONS Sarcopenia is associated with mortality in compensated and early decompensated cirrhosis, and existing conventional prognostic factors had limited value in severe sarcopenia. Therefore, incorporating sarcopenia in the conventional prognostic factors had added value, particularly in compensated and early decompensated cirrhosis. Subclassification of prognostic factors according to sarcopenia may help to better assess the prognosis of cirrhosis.
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Affiliation(s)
- Seong Hee Kang
- Department of Internal MedicineYonsei University Wonju College of MedicineWonjuKorea
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging ScienceSungkyunkwan University School of MedicineSeoulKorea
| | - Soon Koo Baik
- Department of Internal MedicineYonsei University Wonju College of MedicineWonjuKorea
- Cell Therapy and Tissue Engineering CenterYonsei University Wonju College of MedicineWonjuKorea
- Institute of Evidence Based MedicineYonsei University Wonju College of MedicineWonjuKorea
| | - Seung Hwan Cha
- Department of RadiologyYonsei University Wonju College of MedicineWonjuKorea
| | - Moon Young Kim
- Department of Internal MedicineYonsei University Wonju College of MedicineWonjuKorea
- Cell Therapy and Tissue Engineering CenterYonsei University Wonju College of MedicineWonjuKorea
- Institute of Evidence Based MedicineYonsei University Wonju College of MedicineWonjuKorea
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Hematological Indices in Portal Hypertension: Cirrhosis versus Noncirrhotic Portal Hypertension. J Clin Med 2018; 7:jcm7080196. [PMID: 30072589 PMCID: PMC6112015 DOI: 10.3390/jcm7080196] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 07/26/2018] [Accepted: 07/31/2018] [Indexed: 12/14/2022] Open
Abstract
Portal hypertension (PHT) leads to several alterations on hematological indices (HI). The aim of the study is to investigate the differences in HI between cirrhotic subjects and subjects who have noncirrhotic PHT (NCPHT). This retrospective study included 328 patients with PHT (239 cirrhosis and 89 NCPHT). Demographic and clinical features, endoscopic and radiological findings, and HI including neutrophil to lymphocyte ratio (NLR) at the time of PHT diagnosis were recorded. Severity of cirrhosis was assessed according to the Child–Turcotte–Pugh (CTP) classification and Model for End-Stage Liver Disease (MELD) scores. Hematological abnormalities were found in 92.5% of cirrhotic patients and in 55.1% of patients with NCPHT (p < 0.001). While thrombocytopenia was the most common HI in patients with cirrhosis, anemia was the most prevalent HI in NCPHT group. In the cirrhotic group, the NLR was the only parameter to differentiate each CTP group from two others. The NLR value increased with the severity of cirrhosis (2.28 ± 0.14 in CTP-A, 2.85 ± 0.19 in CTP-B and 3.26 ± 0.37 in CTP-C). The AUROC of NLR was 0.692 for differentiating compensated cirrhotic patients from decompensated. Hematological abnormalities are more prevalent and more severe in cirrhotic patients compared to patients with NCPHT. NLR may be used to assess the severity of cirrhosis.
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Jiang H, Zheng T, Duan T, Chen J, Song B. Non-invasive in vivo Imaging Grading of Liver Fibrosis. J Clin Transl Hepatol 2018; 6:198-207. [PMID: 29951365 PMCID: PMC6018309 DOI: 10.14218/jcth.2017.00038] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 10/25/2017] [Accepted: 11/29/2017] [Indexed: 02/05/2023] Open
Abstract
Liver fibrosis (LF), a common consequence of chronic liver diseases with various etiologies, is characterized by excessive accumulation of macromolecules, including collagen, glycoproteins and proteoglycans, in the liver. LF can result in hepatic dysfunction, cirrhosis, portal hypertension and, in some cases, hepatocellular carcinoma. As the current gold standard for diagnosing LF, liver biopsy, however, is invasive and prone to sampling errors and procedure-related complications. Therefore, developing noninvasive, precise and reproducible imaging tests for diagnosing and staging LF is of great significance. Conventional ultrasound (US), computed tomography (CT) and magnetic resonance (MR) imaging can depict morphological alterations of advanced LF, but have relatively limited capability characterizing early-stage LF. In order to optimize the diagnostic performances of noninvasive imaging techniques for LF across its entire spectrum of severity, a number of novel methods, including US elastography, CT perfusion imaging and various MR imaging-based techniques, have been established and introduced to clinical practice. In this review, we intended to summarize current noninvasive imaging techniques for LF, with special emphasis on the possible roles, advantages and limitations of the new emerging imaging modalities.
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Affiliation(s)
- Hanyu Jiang
- Department of Radiology, Sichuan University West China Hospital, Chengdu, China
| | - Tianying Zheng
- Department of Radiology, Sichuan University West China Hospital, Chengdu, China
| | - Ting Duan
- Department of Radiology, Sichuan University West China Hospital, Chengdu, China
| | - Jie Chen
- Department of Radiology, Sichuan University West China Hospital, Chengdu, China
| | - Bin Song
- Department of Radiology, Sichuan University West China Hospital, Chengdu, China
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Ravaioli F, Montagnani M, Lisotti A, Festi D, Mazzella G, Azzaroli F. Noninvasive Assessment of Portal Hypertension in Advanced Chronic Liver Disease: An Update. Gastroenterol Res Pract 2018; 2018:4202091. [PMID: 29977287 PMCID: PMC6011072 DOI: 10.1155/2018/4202091] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 04/30/2018] [Indexed: 12/14/2022] Open
Abstract
The assessment of portal hypertension is a relevant step in the evaluation of newly diagnosed advanced chronic liver disease (ACLD). The current gold standard includes the invasive evaluation of hepatic venous pressure gradient (HVPG) and endoscopy. However, noninvasive or minimally invasive techniques to assess portal hypertension have been proposed and well established. In the present manuscript, we review clinical studies on the use of noninvasive or minimally invasive techniques to assess portal hypertension in ACLD patients.
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Affiliation(s)
- Federico Ravaioli
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Marco Montagnani
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Andrea Lisotti
- Gastroenterology Unit, Ospedale S. Maria della Scaletta, Imola, Italy
| | - Davide Festi
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Giuseppe Mazzella
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Francesco Azzaroli
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
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Kelly EMM, Feldstein VA, Parks M, Hudock R, Etheridge D, Peters MG. An Assessment of the Clinical Accuracy of Ultrasound in Diagnosing Cirrhosis in the Absence of Portal Hypertension. Gastroenterol Hepatol (N Y) 2018; 14:367-373. [PMID: 30166950 PMCID: PMC6111505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Ultrasound is an invaluable tool for the diagnosis of hepatocellular carcinoma and portal hypertension. However, the accuracy of ultrasound in diagnosing cirrhosis in the absence of portal hypertension has not been well studied. Using the specific terms cirrhosis or nodular(ity), a retrospective evaluation was conducted on abdominal ultrasounds performed between 2008 and 2013. Patients with evidence of portal hypertension were excluded from the evaluation. Charts were reviewed for evidence of cirrhosis on liver biopsy performed within 1 year of the ultrasound. Of the 69 patients whose ultrasound findings reported cirrhosis without portal hypertension who underwent liver biopsy, 47 (68%) had histologic evidence of cirrhosis. When patients with advanced fibrosis (F3 or F4) on liver biopsy were included, the sensitivity of the ultrasound improved to 80%. One in 5 biopsies showed only mild to moderate or no fibrosis (F0-F2). Sonographic assessment by experts may falsely suggest or overestimate cirrhosis. In the absence of objective evidence of portal hypertension, caution should be taken in diagnosing cirrhosis based on sonographic interpretation alone.
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Affiliation(s)
- Erin M M Kelly
- Dr Kelly is an assistant professor of medicine in the Division of Gastroenterology and Hepatology at the University of Ottawa in Ottawa, Canada
- Dr Feldstein is a professor of clinical radiology in the Department of Radiology & Biomedical Imaging at the University of California, San Francisco in San Francisco, California
- Ms Parks is a medical student at the University of California, San Francisco
- Ms Hudock is a pharmacy student in the Division of Pharmacy at the University of California, San Francisco
- Mr Etheridge is an independent statistician in Ottawa, Canada
- Dr Peters is a professor of medicine in the Division of Gastroenterology and Hepatology at the University of California, San Francisco
| | - Vickie A Feldstein
- Dr Kelly is an assistant professor of medicine in the Division of Gastroenterology and Hepatology at the University of Ottawa in Ottawa, Canada
- Dr Feldstein is a professor of clinical radiology in the Department of Radiology & Biomedical Imaging at the University of California, San Francisco in San Francisco, California
- Ms Parks is a medical student at the University of California, San Francisco
- Ms Hudock is a pharmacy student in the Division of Pharmacy at the University of California, San Francisco
- Mr Etheridge is an independent statistician in Ottawa, Canada
- Dr Peters is a professor of medicine in the Division of Gastroenterology and Hepatology at the University of California, San Francisco
| | - Monica Parks
- Dr Kelly is an assistant professor of medicine in the Division of Gastroenterology and Hepatology at the University of Ottawa in Ottawa, Canada
- Dr Feldstein is a professor of clinical radiology in the Department of Radiology & Biomedical Imaging at the University of California, San Francisco in San Francisco, California
- Ms Parks is a medical student at the University of California, San Francisco
- Ms Hudock is a pharmacy student in the Division of Pharmacy at the University of California, San Francisco
- Mr Etheridge is an independent statistician in Ottawa, Canada
- Dr Peters is a professor of medicine in the Division of Gastroenterology and Hepatology at the University of California, San Francisco
| | - Rebecca Hudock
- Dr Kelly is an assistant professor of medicine in the Division of Gastroenterology and Hepatology at the University of Ottawa in Ottawa, Canada
- Dr Feldstein is a professor of clinical radiology in the Department of Radiology & Biomedical Imaging at the University of California, San Francisco in San Francisco, California
- Ms Parks is a medical student at the University of California, San Francisco
- Ms Hudock is a pharmacy student in the Division of Pharmacy at the University of California, San Francisco
- Mr Etheridge is an independent statistician in Ottawa, Canada
- Dr Peters is a professor of medicine in the Division of Gastroenterology and Hepatology at the University of California, San Francisco
| | - Dustin Etheridge
- Dr Kelly is an assistant professor of medicine in the Division of Gastroenterology and Hepatology at the University of Ottawa in Ottawa, Canada
- Dr Feldstein is a professor of clinical radiology in the Department of Radiology & Biomedical Imaging at the University of California, San Francisco in San Francisco, California
- Ms Parks is a medical student at the University of California, San Francisco
- Ms Hudock is a pharmacy student in the Division of Pharmacy at the University of California, San Francisco
- Mr Etheridge is an independent statistician in Ottawa, Canada
- Dr Peters is a professor of medicine in the Division of Gastroenterology and Hepatology at the University of California, San Francisco
| | - Marion G Peters
- Dr Kelly is an assistant professor of medicine in the Division of Gastroenterology and Hepatology at the University of Ottawa in Ottawa, Canada
- Dr Feldstein is a professor of clinical radiology in the Department of Radiology & Biomedical Imaging at the University of California, San Francisco in San Francisco, California
- Ms Parks is a medical student at the University of California, San Francisco
- Ms Hudock is a pharmacy student in the Division of Pharmacy at the University of California, San Francisco
- Mr Etheridge is an independent statistician in Ottawa, Canada
- Dr Peters is a professor of medicine in the Division of Gastroenterology and Hepatology at the University of California, San Francisco
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Hashem S, Esmat G, Elakel W, Habashy S, Raouf SA, Elhefnawi M, Eladawy M, ElHefnawi M. Comparison of Machine Learning Approaches for Prediction of Advanced Liver Fibrosis in Chronic Hepatitis C Patients. IEEE/ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS 2018; 15:861-868. [PMID: 28391204 DOI: 10.1109/tcbb.2017.2690848] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
BACKGROUND/AIM Using machine learning approaches as non-invasive methods have been used recently as an alternative method in staging chronic liver diseases for avoiding the drawbacks of biopsy. This study aims to evaluate different machine learning techniques in prediction of advanced fibrosis by combining the serum bio-markers and clinical information to develop the classification models. METHODS A prospective cohort of 39,567 patients with chronic hepatitis C was divided into two sets-one categorized as mild to moderate fibrosis (F0-F2), and the other categorized as advanced fibrosis (F3-F4) according to METAVIR score. Decision tree, genetic algorithm, particle swarm optimization, and multi-linear regression models for advanced fibrosis risk prediction were developed. Receiver operating characteristic curve analysis was performed to evaluate the performance of the proposed models. RESULTS Age, platelet count, AST, and albumin were found to be statistically significant to advanced fibrosis. The machine learning algorithms under study were able to predict advanced fibrosis in patients with HCC with AUROC ranging between 0.73 and 0.76 and accuracy between 66.3 and 84.4 percent. CONCLUSIONS Machine-learning approaches could be used as alternative methods in prediction of the risk of advanced liver fibrosis due to chronic hepatitis C.
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Maruyama H, Yokosuka O. Ultrasonography for Noninvasive Assessment of Portal Hypertension. Gut Liver 2018; 11:464-473. [PMID: 28267700 PMCID: PMC5491080 DOI: 10.5009/gnl16078] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Revised: 06/07/2016] [Accepted: 06/18/2016] [Indexed: 12/12/2022] Open
Abstract
Portal hypertension is a major pathophysiology in patients with cirrhosis. Portal pressure is the gold standard to evaluate the severity of portal hypertension, and radiological intervention is the only procedure for pressure measurement. Ultrasound (US) is a simple and noninvasive imaging modality available worldwide. B-mode imaging allows broad applications for patients to detect and characterize chronic liver diseases and focal hepatic lesions. The Doppler technique offers real-time observation of blood flow with qualitative and quantitative assessments, and the application of microbubble-based contrast agents has improved the detectability of peripheral blood flow. In addition, elastography for the liver and spleen covers a wider field beyond the original purpose of fibrosis assessment. These developments enhance the practical use of US in the evaluation of portal hemodynamic abnormalities. This article reviews the recent progress of US in the assessment of portal hypertension.
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Affiliation(s)
- Hitoshi Maruyama
- Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan
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Origins of Portal Hypertension in Nonalcoholic Fatty Liver Disease. Dig Dis Sci 2018; 63:563-576. [PMID: 29368124 DOI: 10.1007/s10620-017-4903-5] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 12/26/2017] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) advanced to cirrhosis is often complicated by clinically significant portal hypertension, which is primarily caused by increased intrahepatic vascular resistance. Liver fibrosis has been identified as a critical determinant of this process. However, there is evidence that portal venous pressure may begin to rise in the earliest stages of NAFLD when fibrosis is far less advanced or absent. The biological and clinical significance of these early changes in sinusoidal homeostasis remains unclear. Experimental and human observations indicate that sinusoidal space restriction due to hepatocellular lipid accumulation and ballooning may impair sinusoidal flow and generate shear stress, increasingly disrupting sinusoidal microcirculation. Sinusoidal endothelial cells, hepatic stellate cells, and Kupffer cells are key partners of hepatocytes affected by NAFLD in promoting endothelial dysfunction through enhanced contractility, capillarization, adhesion and entrapment of blood cells, extracellular matrix deposition, and neovascularization. These biomechanical and rheological changes are aggravated by a dysfunctional gut-liver axis and splanchnic vasoregulation, culminating in fibrosis and clinically significant portal hypertension. We may speculate that increased portal venous pressure is an essential element of the pathogenesis across the entire spectrum of NAFLD. Improved methods of noninvasive portal venous pressure monitoring will hopefully give new insights into the pathobiology of NAFLD and help efforts to identify patients at increased risk for adverse outcomes. In addition, novel drug candidates targeting reversible components of aberrant sinusoidal circulation may prevent progression in NAFLD.
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Tseng Y, Ma L, Luo T, Zeng X, Li N, Wei Y, Zhou J, Li F, Chen S. Non-invasive predictive model for hepatic venous pressure gradient based on a 3-dimensional computed tomography volume rendering technology. Exp Ther Med 2018; 15:3329-3335. [PMID: 29545851 PMCID: PMC5841049 DOI: 10.3892/etm.2018.5816] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2017] [Accepted: 11/17/2017] [Indexed: 12/14/2022] Open
Abstract
Portal hypertension secondary to liver cirrhosis may cause a number of life-threatening complications. The rupture of gastroesophageal varices is associated with a high mortality rate of 15–30%. Hepatic venous pressure gradient (HVPG) is an accurate reflection of disease severity, however this can only be assessed via an invasive interventional procedure. The aim of the present study was to explore a non-invasive method based on 3D computed tomography (CT) volume rendering technology to accurately predict HVPG. A total of 77 patients diagnosed with liver cirrhosis underwent HVPG examination in the present study and the appropriate clinical and radiological data were retrospectively reviewed. A 3D liver and spleen volume rendering was constructed for volume measurements. All non-invasive parameters were tested using univariate analysis and the resulting variables that were statistically significant (P<0.20) were used in the multivariate linear regression model. The HVPG predictive model was as follows: HVPG = 18.726 - 0.324 (albumin) + 1.57 (aminotransferase-to-platelet ratio index) + 0.004 (liver volume) (multivariate regression analysis, P=0.006). The corresponding area under receiver operating characteristic curve to identify clinically significant portal hypertension defined as HVPG ≥10 mmHg was 0.810 (95% confidence interval; 0.705–0.891), with an optimal cut-off value of 12.84, yielding a sensitivity of 80.36% a specificity of 76.19%. The results of the present study indicate that 3D CT volume rendering technology may have the potential to be used for non-invasive prediction of HVPG.
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Affiliation(s)
- Yujen Tseng
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Lili Ma
- Department of Endoscopy, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Tiancheng Luo
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Xiaoqing Zeng
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Na Li
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Yichao Wei
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Ji Zhou
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Feng Li
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Shiyao Chen
- Department of Gastroenterology, Endoscopy Center, Evidence-Based Medicine Center, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
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Ronot M, Pommier R, Calame P, Purcell Y, Vilgrain V. Computed Tomography. DIAGNOSTIC METHODS FOR CIRRHOSIS AND PORTAL HYPERTENSION 2018:183-210. [DOI: 10.1007/978-3-319-72628-1_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Polimeni L, Pastori D, Baratta F, Tozzi G, Novo M, Vicinanza R, Troisi G, Pannitteri G, Ceci F, Scardella L, Violi F, Angelico F, Del Ben M. Spleen dimensions are inversely associated with lysosomal acid lipase activity in patients with non-alcoholic fatty liver disease. Intern Emerg Med 2017; 12:1159-1165. [PMID: 28900817 DOI: 10.1007/s11739-017-1746-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Accepted: 09/04/2017] [Indexed: 12/28/2022]
Abstract
Fatty liver and splenomegaly are typical features of genetic lysosomal acid lipase (LAL) deficiency. No data in adult patients with non-genetic reduction of LAL activity are available. We investigate the association between spleen dimensions and LAL activity in non-alcoholic fatty liver disease (NAFLD) patients, in whom a reduced LAL activity has been reported. We include 425 consecutive patients who underwent abdominal ultrasound to evaluate hepatic steatosis and spleen dimensions. LAL activity was measured with dried blood spot method (Lalistat2). NAFLD was present in 74.1% of screened patients. Higher median spleen longitudinal diameter (10.6 vs. 9.9 cm; p < 0.001) and spleen area (SA) (32.7 vs. 27.7 cm2; p < 0.001), together with a higher and proportion of splenomegaly (17.8 vs. 5.5%, p = 0.001), are present in patients with NAFLD compared to those without. In NAFLD patients, median LAL activity is 0.9 nmol/spot/h. LAL activity is lower in 56 patients with splenomegaly, as compared to those without (p = 0.009). At multivariable logistic regression analysis, age (above median, OR 0.344; p = 0.003), LAL activity (below median, OR 2.206, p = 0.028), and platelets (OR 0.101, p = 0.002) are significantly associated with splenomegaly. NAFLD patients disclose a relatively high prevalence of spleen enlargement and splenomegaly, which are significantly associated with a reduced LAL activity, suggesting that LAL may contribute to spleen enlargement in this setting.
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Affiliation(s)
- Licia Polimeni
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - Daniele Pastori
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy.
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University, Rome, Italy.
| | - Francesco Baratta
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University, Rome, Italy
| | - Giulia Tozzi
- Unit for Neuromuscular and Neurodegenerative Diseases, Children's Hospital and Research Institute "Bambino Gesù", Rome, Italy
| | - Marta Novo
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - Roberto Vicinanza
- Department of Cardiovascular, Respiratory Nephrologic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy
| | - Giovanni Troisi
- Department of Cardiovascular, Respiratory Nephrologic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy
| | - Gaetano Pannitteri
- Department of Cardiovascular, Respiratory Nephrologic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy
| | - Fabrizio Ceci
- Department of Cellular Biotechnologies and Hematology, Policlinico Umberto I Hospital, "La Sapienza" University, Rome, Italy
| | - Laura Scardella
- Department of Surgical Sciences, Sapienza University, Rome, Italy
| | - Francesco Violi
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - Francesco Angelico
- Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy
| | - Maria Del Ben
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
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Schaffner D, von Elverfeldt D, Deibert P, Lazaro A, Merfort I, Lutz L, Neubauer J, Baumstark MW, Kreisel W, Reichardt W. Phase-contrast MR flow imaging: A tool to determine hepatic hemodynamics in rats with a healthy, fibrotic, or cirrhotic liver. J Magn Reson Imaging 2017; 46:1526-1534. [PMID: 28240794 DOI: 10.1002/jmri.25677] [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: 11/29/2016] [Accepted: 02/01/2017] [Indexed: 12/14/2022] Open
Abstract
PURPOSE To test a magnetic resonance (MR) scanning protocol as a noninvasive tool to determine hepatic hemodynamics and to assess the degree of liver fibrosis in an animal model of liver fibrosis and cirrhosis. MATERIALS AND METHODS Fifty-four male Wistar rats were studied. Thirty-nine received thioacetamide (TAA) in their drinking water for either 12 or 16 weeks. MR measurements were performed using flow-sensitive 2D phase-contrast MRI and a 9.4T preclinical scanner. The following hemodynamic parameters were investigated: portal cross-sectional area, mean portal flow velocity, and portal and aortic flow volume rate. Therefore, rats (n = 46) were divided into three groups: CON (control, n = 13), FIB (fibrosis, n = 25), and CIR (cirrhosis, n = 8). Furthermore, the degree of liver fibrosis was assessed by a self-established MR score and verified by a standardized histological score (n = 48). RESULTS Portal and aortic flow parameters could be reliably detected. A significant decrease in portal flow velocity was found in FIB (FIB vs. CON: -21%, P = 0.006 and CIR vs. CON: -17%, P = 0.105) and in portal flow volume rate in FIB and CIR (FIB vs. CON: -20%, P = 0.009 and CIR vs. CON: -25%, P = 0.024). If the histological score is taken as standard, the self-established MR score enabled discrimination between healthy and diseased livers (sensitivity to identify diseased livers: 89% and specificity to identify healthy livers: 100%). CONCLUSION This MR scanning protocol presents a noninvasive tool to determine hepatic hemodynamics in healthy and diseased rats. LEVEL OF EVIDENCE 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1526-1534.
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Affiliation(s)
- Denise Schaffner
- Institute for Exercise- und Occupational Medicine, Medical Center, University of Freiburg, Germany
- Faculty of Medicine, University of Freiburg, Germany
- Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Germany
| | - Dominik von Elverfeldt
- Faculty of Medicine, University of Freiburg, Germany
- Department of Radiology, Medical Physics, Medical Center, University of Freiburg, Germany
| | - Peter Deibert
- Institute for Exercise- und Occupational Medicine, Medical Center, University of Freiburg, Germany
- Faculty of Medicine, University of Freiburg, Germany
| | - Adhara Lazaro
- Institute for Exercise- und Occupational Medicine, Medical Center, University of Freiburg, Germany
- Faculty of Medicine, University of Freiburg, Germany
| | - Irmgard Merfort
- Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Germany
| | - Lisa Lutz
- Faculty of Medicine, University of Freiburg, Germany
- Institute of Clinical Pathology, Medical Center, University of Freiburg, Germany
| | - Jakob Neubauer
- Faculty of Medicine, University of Freiburg, Germany
- Department of Radiology, Medical Center, University of Freiburg, Germany
| | - Manfred W Baumstark
- Institute for Exercise- und Occupational Medicine, Medical Center, University of Freiburg, Germany
- Faculty of Medicine, University of Freiburg, Germany
| | - Wolfgang Kreisel
- Faculty of Medicine, University of Freiburg, Germany
- Department of Medicine II, Gastroenterology, Hepatology, Endocrinology and Infectious Diseases, Medical Center, University of Freiburg, Germany
| | - Wilfried Reichardt
- Faculty of Medicine, University of Freiburg, Germany
- Department of Radiology, Medical Physics, Medical Center, University of Freiburg, Germany
- German Cancer Consortium (DKTK), Heidelberg, Germany
- German Cancer Research Center (DKFZ), Heidelberg, Germany
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Zerboni G, Capurso G, Di Pietropaolo M, Carbonetti F, Iannicelli E, Marignani M, Delle Fave G. The prevalence of pancreatic cystic lesions in patients with liver cirrhosis is double that in controls. United European Gastroenterol J 2017; 5:1007-1014. [PMID: 29163967 PMCID: PMC5676548 DOI: 10.1177/2050640617694576] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Accepted: 01/26/2017] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND AND AIMS Pancreatic cystic lesions (PCLs) are commonly diagnosed incidentally and are often preneoplastic. Their presence may influence the management of patients with chronic diseases such as liver cirrhosis (LC). This study evaluated the prevalence and nature of PCLs in LC patients. METHODS The images of 192 LC patients and 192 controls who underwent either computed tomography scan or nuclear magnetic resonance were reviewed for the presence and nature of PCLs. The prevalence of PCLs in both groups and differences between LC patients with and without PCLs were analysed. Multiple logistic regression analysis was used to investigate factors associated with PCLs. RESULTS Thirty-five of 192 LC patients (18%) and 19/192 controls (10%) had PCLs (p = .027). The prevalence of presumptive intraductal pancreatic mucinous neoplasm (IPMN) was double in LC patients compared with controls (14% vs 7%; p = .065). In multivariate analysis, age, LC and having undergone a magnetic resonance cholangiopancreatography were factors associated with PCLs and IPMNs. LC patients with PCLs were older at the time of imaging and had a longer history of liver disease (67 vs. 43 months; p = 0.039) compared with LC patients without PCLs. CONCLUSIONS PCLs are more common in LC patients than in controls, and most are IPMNs. The occurrence of PCLs in LC patients seems to be related to age and disease duration.
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Affiliation(s)
- Giulia Zerboni
- Digestive and Liver Disease Unit, Sant’Andrea Hospital, Faculty of Medicine and Psychology, ‘Sapienza’ University of Rome, Rome, Italy
| | - Gabriele Capurso
- Digestive and Liver Disease Unit, Sant’Andrea Hospital, Faculty of Medicine and Psychology, ‘Sapienza’ University of Rome, Rome, Italy
| | - Marco Di Pietropaolo
- Radiology Unit, Sant’Andrea Hospital, Faculty of Medicine and Psychology, ‘Sapienza’ University of Rome, Rome, Italy
| | - Francesco Carbonetti
- Radiology Unit, Sant’Andrea Hospital, Faculty of Medicine and Psychology, ‘Sapienza’ University of Rome, Rome, Italy
| | - Elsa Iannicelli
- Radiology Unit, Sant’Andrea Hospital, Faculty of Medicine and Psychology, ‘Sapienza’ University of Rome, Rome, Italy
| | - Massimo Marignani
- Digestive and Liver Disease Unit, Sant’Andrea Hospital, Faculty of Medicine and Psychology, ‘Sapienza’ University of Rome, Rome, Italy
| | - Gianfranco Delle Fave
- Digestive and Liver Disease Unit, Sant’Andrea Hospital, Faculty of Medicine and Psychology, ‘Sapienza’ University of Rome, Rome, Italy
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Hepatic venous pressure gradient correlates with advanced hepatic fibrosis: a retrospective review. Abdom Radiol (NY) 2017; 42:2609-2614. [PMID: 28474176 DOI: 10.1007/s00261-017-1171-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE To determine if hepatic venous pressure gradient (HVPG) correlates with advanced hepatic fibrosis, as a complement to transjugular (transvenous) core needle liver biopsy. MATERIALS AND METHODS After institutional review board approval, a retrospective review was conducted on 340 patients who underwent transjugular (transvenous) core needle liver biopsy with concurrent pressure measurements between 6/1/2007 and 6/1/2013. Spearman correlation and linear regression were performed. A receiver operating characteristic (ROC) curve was created and sensitivity, specificity, predictive values and likelihood ratios were calculated. RESULTS Indications included hepatitis C, abnormal liver function tests, non-alcoholic steatohepatitis, autoimmune hepatitis, and cirrhosis, among others. Biopsies showed stage 1 or 2 fibrosis in 15.6% each, stage 3 fibrosis in 21.6%, stage 4 fibrosis in 40.7%, and no fibrosis in 6.5%. Mean HVPG was 6.5 mm Hg (SD 5.0) with a range of 0-26 mm Hg. Spearman correlation coefficient for association between HVPG and fibrosis stage was 0.561 (p < 0.001). R2 on linear regression was 0.247 (p < 0.001). ROC curve for the prediction of stage 4 fibrosis had an area under the curve of 0.79 (95% CI 0.73-0.85). HVPG of ≥6 mm Hg had a sensitivity of 71.3%, specificity of 79.6%, positive predictive value of 70.5%, negative predictive value of 80.2%, positive likelihood ratio of 3.49 (95% CI 2.45-4.97) and negative likelihood ratio of 0.36 (95% CI 0.26-0.50) for diagnosis of stage 4 fibrosis. CONCLUSIONS HVPG correlates with stage 4 (advanced) hepatic fibrosis.
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Kim G, Shim KY, Baik SK. Diagnostic Accuracy of Hepatic Vein Arrival Time Performed with Contrast-Enhanced Ultrasonography for Cirrhosis: A Systematic Review and Meta-Analysis. Gut Liver 2017; 11:93-101. [PMID: 27538445 PMCID: PMC5221866 DOI: 10.5009/gnl16031] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Revised: 03/07/2016] [Accepted: 03/14/2016] [Indexed: 12/15/2022] Open
Abstract
Background/Aims We identified reports in the literature regarding the diagnostic accuracy of hepatic vein arrival time (HVAT) measured by contrast-enhanced ultrasonography (CEUS) to assess hepatic fibrosis in cirrhosis. Methods The Ovid MEDLINE, Embase, and Cochrane databases were searched for all studies published up to 23 July 2015 that evaluated liver status using CEUS and liver biopsy (LB). The QUADAS-II (quality assessment of diagnostic accuracy studies-II) was applied to assess the internal validity of the diagnostic studies. Selected studies were subjected to a meta-analysis with MetaDisc 1.4 and RevMan 5.3. Results A total of 12 studies including 844 patients with chronic liver disease met our inclusion criteria. The overall summary sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of the HVAT measured by CEUS for the detection of cirrhosis compared to LB were 0.83 (95% confidence interval [CI], 0.77 to 0.89), 0.75 (95% CI, 0.69 to 0.79), 3.45 (95% CI, 1.60 to 7.43), and 0.28 (95% CI, 0.10 to 0.74), respectively. The summary diagnostic odds ratio (random effects model) was 15.23 (95% CI, 3.07 to 75.47), the summary receiver operator characteristics area under the curve was 0.74 (standard error [SE]=0.14), and the index Q was 0.69 (SE=0.11). Conclusions Based on a systematic review, the measurement of HVAT by CEUS exhibited an increased accuracy and correlation for the detection of cirrhosis.
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Affiliation(s)
- Gaeun Kim
- Department of Nursing, Keimyung University College of Nursing, Daegu, Korea
| | - Kwang Yong Shim
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Soon Koo Baik
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
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48
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Kim G, Kim MY, Baik SK. Transient elastography versus hepatic venous pressure gradient for diagnosing portal hypertension: a systematic review and meta-analysis. Clin Mol Hepatol 2017; 23:34-41. [PMID: 28263953 PMCID: PMC5381827 DOI: 10.3350/cmh.2016.0059] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Revised: 11/02/2016] [Accepted: 11/09/2016] [Indexed: 02/07/2023] Open
Abstract
Background/Aims Transient elastography (TE) has been proposed as a promising noninvasive alternative to hepatic venous pressure gradient (HVPG) for detecting portal hypertension (PH). However, previous studies have yielded conflicting results. We gathered evidence from literature on the clinical usefulness of TE versus HVPG for assessing PH. Methods We conducted a systematic review by searching databases for relevant literature evaluating the clinical usefulness of non-invasive TE for assessing PH in patients with cirrhosis. A literature search in Ovid Medline, EMBASE and the Cochrane Library was performed for all studies published prior to December 30, 2015. Results Eight studies (1,356 patients) met our inclusion criteria. For the detection of PH (HVPG ≥6 mmHg), the summary sensitivity and specificity were 0.88 (95% confidence interval [CI] 0.86-0.90) and 0.74 (95% CI 0.67-0.81), respectively. Regarding clinically significant PH (HVPG ≥10 mmHg), the summary sensitivity and specificity were 0.85 (95% CI 0.63-0.97) and 0.71 (95% CI 0.50-0.93), respectively. The overall correlation estimate of TE and HVPG was large (0.75, 95% CI: 0.65; 0.82, P<0.0001). Conclusions TE showed high accuracy and correlation for detecting the severity of PH. Therefore, TE shows promise as a reliable and non-invasive procedure for the evaluation of PH that should be integrated into clinical practice.
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Affiliation(s)
- Gaeun Kim
- Research Institute for Nursing Science, College of Nursing, Keimyung University, Daegu, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Soon Koo Baik
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.,Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea.,Institute of Evidence-based Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
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Kim BK. Transient elastography can be integrated into routine clinical practice for the evaluation of portal hypertension? Clin Mol Hepatol 2017; 23:27-30. [PMID: 28349679 PMCID: PMC5381837 DOI: 10.3350/cmh.2017.0101] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 02/20/2017] [Indexed: 12/15/2022] Open
Affiliation(s)
- Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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Bolognesi M, Di Pascoli M, Sacerdoti D. Clinical role of non-invasive assessment of portal hypertension. World J Gastroenterol 2017; 23:1-10. [PMID: 28104976 PMCID: PMC5221271 DOI: 10.3748/wjg.v23.i1.1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Revised: 09/27/2016] [Accepted: 10/31/2016] [Indexed: 02/06/2023] Open
Abstract
Measurement of portal pressure is pivotal in the evaluation of patients with liver cirrhosis. The measurement of the hepatic venous pressure gradient represents the reference method by which portal pressure is estimated. However, it is an invasive procedure that requires significant hospital resources, including experienced staff, and is associated with considerable cost. Non-invasive methods that can be reliably used to estimate the presence and the degree of portal hypertension are urgently needed in clinical practice. Biochemical and morphological parameters have been proposed for this purpose, but have shown disappointing results overall. Splanchnic Doppler ultrasonography and the analysis of microbubble contrast agent kinetics with contrast-enhanced ultrasonography have shown better accuracy for the evaluation of patients with portal hypertension. A key advancement in the non-invasive evaluation of portal hypertension has been the introduction in clinical practice of methods able to measure stiffness in the liver, as well as stiffness/congestion in the spleen. According to the data published to date, it appears to be possible to rule out clinically significant portal hypertension in patients with cirrhosis (i.e., hepatic venous pressure gradient ≥ 10 mmHg) with a level of clinically-acceptable accuracy by combining measurements of liver stiffness and spleen stiffness along with Doppler ultrasound evaluation. It is probable that the combination of these methods may also allow for the identification of patients with the most serious degree of portal hypertension, and ongoing research is helping to ensure progress in this field.
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