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Nie Q, Liang Q, Li M, Zhu R, Ren J, Jiang K, Li J. Idiopathic non-cirrhotic portal hypertension: A case report. Medicine (Baltimore) 2024; 103:e40642. [PMID: 39705493 PMCID: PMC11666171 DOI: 10.1097/md.0000000000040642] [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] [Received: 07/16/2024] [Revised: 10/24/2024] [Accepted: 11/05/2024] [Indexed: 12/22/2024] Open
Abstract
RATIONALE Idiopathic noncirrhotic portal hypertension (INCPH) is a rare liver disorder with elevated portal pressure without cirrhosis, making diagnosis challenging. This case report presents a 46-year-old Chinese male with INCPH, highlighting the crucial role of liver biopsy. PATIENT CONCERNS A 46-year-old male presented with persistent fatigue that lasted for 2 months and significantly worsened over the last 3 days. The patient described his fatigue as a profound lack of energy that persisted throughout the day, which progressively impaired his ability to perform daily activities and maintain his usual work responsibilities. He reported feeling exhausted even after light physical exertion, such as walking or standing for short periods. The severity of the fatigue also led to frequent short rests during the day, and he experienced difficulty concentrating and carrying out routine tasks. In addition, he noted a loss of appetite and mild discomfort in the upper abdomen. Given his previous history of abnormal liver function tests and a liver biopsy showing mild chronic liver damage, the patient was initially diagnosed with cirrhosis at a local hospital. This initial diagnosis caused significant emotional distress, as the patient experienced a state of panic and anxiety over the implications of having a progressive liver disease. The psychological burden was evident in his reported difficulty sleeping and persistent worry about his health and future. DIAGNOSES Initial imaging suggested portal hypertension and cirrhosis, but a liver biopsy ruled out cirrhotic changes, confirming INCPH by excluding other causes such as chronic hepatitis. INTERVENTIONS The patient received symptomatic treatment (acid suppression, gastric and liver protection) and underwent a liver biopsy. Histological analysis confirmed INCPH, ruling out cirrhosis. OUTCOMES After the definitive diagnosis, the patient's anxiety lessened. Fatigue and weakness improved with ongoing symptomatic treatment, and psychological support enhanced his overall well-being. His follow-up plan includes regular liver function monitoring, imaging for portal pressure changes, and potential anticoagulation therapy for thrombosis risks. LESSONS This case highlights the diagnostic difficulty of INCPH and underscores the importance of liver biopsy. Further research is needed to develop specific diagnostic tools and treatments for INCPH.
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Affiliation(s)
- Qilong Nie
- The Eighth Clinical Medical College, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Qiuyan Liang
- The Eighth Clinical Medical College, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Mingyang Li
- The Eighth Clinical Medical College, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Ronghuo Zhu
- Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Jian Ren
- Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Kaiping Jiang
- Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Jianhong Li
- Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
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Zhang Y, Lai H, Chen J, Lai R, Lin X, Lin S, Liu B, Lin Q, Wang B, Zheng Q. Clinically significant portal hypertension in patients with primary biliary cholangitis: Clinicopathological features and prognostic value. Ann Hepatol 2024; 30:101577. [PMID: 39276989 DOI: 10.1016/j.aohep.2024.101577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 07/26/2024] [Accepted: 08/21/2024] [Indexed: 09/17/2024]
Abstract
INTRODUCTION AND OBJECTIVES Primary biliary cholangitis (PBC) may progress to clinically significant portal hypertension (CSPH) before the development of cirrhosis. This study aimed to investigate CSPH incidence as well as the clinicopathological characteristics and predictive value of these features for the prognosis of patients with PBC, especially at early histologic stage. PATIENTS AND METHODS Patients diagnosed with PBC between January 2013 and April 2022 were retrospectively enrolled. The prognostic value of baseline clinicopathological characteristics for long-term outcomes in PBC patients with CSPH was assessed using Kaplan-Meier survival analysis and COX regression analysis. RESULTS Among 280 patients with PBC, 104 underwent liver biopsy and 68 were at early histologic stage. CSPH was present in 47.2 % of participants with 20.6 % at early histologic stage. CSPH was a risk factor for predicting the liver transplant-free survival in PBC patients (hazard ratio [HR], 6.78; 95 % CI, 2.94-15.63), especially those at early stage. Perisinusoidal fibrosis and nodular regenerative hyperplasia (NRH) were common histopathological features in PBC patients with CSPH at the early stages. Fibrous septa formation in the hepatic lobules (HR, 4.85; 95 % CI, 1.51-15.52) and cholestasis (HR, 7.70; 95 % CI, 2.56-23.18) were independent predictors of adverse outcomes. CONCLUSIONS CSPH indicates an increased risk of adverse outcomes in PBC patients, especially those in early histologic stage. Perisinusoidal fibrosis and NRH are valuable histological features of CSPH in patients with early-stage PBC. Identification of clinicopathological features and assessment of portal hypertension (especially at early stage), contribute to the development of personalized strategies.
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Affiliation(s)
- Ying Zhang
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, PR China; Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, PR China
| | - Huaying Lai
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, PR China; Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, PR China
| | - Jing Chen
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, PR China; Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, PR China
| | - Ruimin Lai
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, PR China; Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, PR China
| | - Xiaoyu Lin
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, PR China; Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, PR China
| | - Shan Lin
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, PR China; Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, PR China
| | - Bingping Liu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, PR China; Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, PR China
| | - Qiuxiang Lin
- DepartmentofHepatology, Mengchao Hepatobiliary hospital of Fujian Medical University, Fuzhou 350025, Fujian Province, PR China
| | - Bin Wang
- Department of Pathology and Institute of Oncology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province, PR China; Diagnostic Pathology Centre, Fujian Medical University, Fuzhou, Fujian Province, PR China; Department of Pathology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, Fujian Province, PR China.
| | - Qi Zheng
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, PR China; Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, PR China.
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Premkumar M, Anand AC. Porto-sinusoidal Vascular Disease: Classification and Clinical Relevance. J Clin Exp Hepatol 2024; 14:101396. [PMID: 38601747 PMCID: PMC11001647 DOI: 10.1016/j.jceh.2024.101396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Accepted: 03/05/2024] [Indexed: 04/12/2024] Open
Abstract
Non-cirrhotic portal hypertension (NCPH) is a well-recognized clinico-pathological entity, which is associated with clinical signs and symptoms, imaging, and endoscopic features of portal hypertension (PHT), in absence of cirrhosis. In patients with NCPH without known risk factors of PHT or extrahepatic portal vein thrombosis, the condition is called idiopathic non-cirrhotic portal hypertension (INCPH). There are multiple infectious, immune related causes, systemic diseases, drug and toxin exposures, haematological disorders, and metabolic risk factors that have been associated with this INCPH. However, the causal pathogenesis is still unclear. The Vascular liver disorders interest group group recently proposed porto-sinusoidal vascular disease (PSVD) as a syndromic entity, which provides definite histopathological criteria for diagnosis of NCPH (table 1). The three classical histo-morphological lesions specific for PSVD include obliterative portal venopathy, nodular regenerative hyperplasia, and incomplete septal fibrosis. The PSVD definition includes patients with portal vein thrombosis, PVT, and even those without PHT, thus broadening the scope of diagnosis to include patients who may have presented early, prior to haemodynamic changes consistent with PHT. However, this new diagnosis has pros and cons. The cons include mandating invasive liver biopsy to assess the PSVD histological triad in all patients with NCPH, an erstwhile clinical diagnosis in Asian patients. In addition, the natural history of the subclinical forms of PSVD without PHT and linear progression to develop PHT is unknown yet. In this review, we discuss the diagnosis and treatment of INCPH/PSVD, fallacies and strengths of the old and new schema, pathobiology of this disease, and clinical correlates in an Asian context. Although formulation of standardised diagnostic criteria is useful for comparison of clinical cohorts with INCPH/PSVD, prospective clinical validation in global cohorts is necessary to avoid misclassification of vascular disorders of the liver.
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Affiliation(s)
- Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Anil C. Anand
- Department of Hepatology, Kalinga Institute of Medical Sciences, Bhubaneshwar, Odisha, India
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Zhang Y, Xiong Q, Zhong Y, Liu D, Liu H, Wang L, Du Z, Chen M, Zheng Y, Yang Y. Clinical characteristics and natural history of porto-sinusoidal vascular disease: A cohort study of 234 patients in China. Liver Int 2024; 44:2329-2340. [PMID: 38828515 DOI: 10.1111/liv.16002] [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: 03/06/2024] [Revised: 05/02/2024] [Accepted: 05/21/2024] [Indexed: 06/05/2024]
Abstract
BACKGROUND AND AIMS Porto-sinusoidal vascular disease (PSVD) is an under-recognized and under-diagnosed disease. The purpose of this study was to investigate the clinical features and prognosis of PSVD. METHODS The patients who underwent liver biopsies were analyzed retrospectively. The clinical and pathological data were reviewed and screened according to the latest diagnostic criteria of PSVD. RESULTS A total of 234 patients were diagnosed as PSVD, including 103 patients presented with portal hypertension (PH) and 131 patients without PH. At baseline, the alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT) levels were higher in the no-PH group. The liver stiffness increased in the PH group. In histological review, obliterative portal venopathy, sinusoidal dilatation and architectural disturbance were more common in the PH group, while portal tract abnormalities were more widely distributed in the no-PH group. After a median follow-up of 43.6 months, the survival rate of patients with baseline liver decompensation was 76.0%, and that of patients at a liver compensated stage in the PH group was 98.7%. First variceal bleeding occurred in 13.8% of patients with gastric-oesophageal varices. None of the patients in the no-PH group developed portal hypertension during follow-up. CONCLUSIONS PSVD can manifest as PH or mild liver enzyme abnormalities. There are significant differences in pathological features among patients with different clinical manifestations. Recurrent ascites are the main cause of death in PSVD patients. However, patients without PH have a slow disease progression, with recurrent elevated GGT levels being their main clinical feature.
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Affiliation(s)
- Yu Zhang
- School of Medicine, Southeast University, Nanjing, China
- The Second Hospital of Nanjing, Teaching Hospital of Southeast University, Nanjing, China
| | - Qingfang Xiong
- Department of Liver Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yandan Zhong
- Department of Liver Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Duxian Liu
- Department of Pathology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Hongli Liu
- School of Medicine, Southeast University, Nanjing, China
| | - Li Wang
- Department of Infectious Disease and Liver Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhixiang Du
- Department of Infectious Disease and Liver Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Miaoyang Chen
- Department of Infectious Disease and Liver Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yufeng Zheng
- Department of Infectious Disease and Liver Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yongfeng Yang
- The Second Hospital of Nanjing, Teaching Hospital of Southeast University, Nanjing, China
- Department of Liver Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
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Malik A, Malik S, Farooq A, Malik MI, Javaid S. Histopathological features of idiopathic portal hypertension: A systematic review and meta-analysis. Sci Prog 2024; 107:368504241264996. [PMID: 39053026 PMCID: PMC11282518 DOI: 10.1177/00368504241264996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/27/2024]
Abstract
BACKGROUND Portal hypertension (PH) is a clinically significant entity that could present with life-threatening gastrointestinal bleeding. Cirrhosis is the most common cause of PH, with well-documented histopathology and etiology. However, in idiopathic portal hypertension (IPH), no single histopathologic finding is associated with PH. Our systematic review aims to identify and summarize the prevalence of the common histological findings of IPH. METHODS We systematically searched PubMed, Cochrane CENTRAL, Web of Science, and Scopus till 1ST March 2022 for studies describing the histopathological features of IPH. Data were extracted from eligible studies and pooled as events rate and 95% confidence interval (CI) using binary random-effects model by open meta-analyst software. RESULTS We included 23 retrospective studies with a total sample size of 813 patients. The overall incidence of nodular regenerative hyperplasia was 38.6%, 59.8% for portal fibrosis, 51.3% for periportal fibrosis, 39.3% for perisinusoidal fibrosis, 89.8% for portal vein sclerosis, 42.2% for portal inflammation, 53.3% for mega-sinusoids, 39.5% for thickening of portal vein branches, 93.8% for narrowing of portal veins, 53.3% for hepatic veins/venous outflow obstruction, 51.4% for aberrant portal/periportal vessels, 42.4% for shunt vessel, 50.9% for ductular proliferation, and 16.3% for steatosis. CONCLUSION Due to the relatively non-pathognomonic and non-specific nature of IPH, a combination of different histological features such as the portal and periportal fibrosis, portal vein sclerosis, mega-sinusoids, narrowing of portal veins, hepatic venous outflow obstruction, aberrant portal or periportal vessels, and ductular proliferation may be of value in diagnosing IPH as the incidence rate of these features was at approximately 50%.
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Affiliation(s)
- Adnan Malik
- Mountain Vista Medical Center, Midwestern University Program, Mesa AZ, USA
| | - Sohira Malik
- Penn State College of Medicine, Hershey, PA, USA
| | - Ahsan Farooq
- Penn State College of Medicine, Hershey, PA, USA
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Büyük M, Berker N, Bakkaloğlu DV, Şenkal İV, Önal Z, Güllüoğlu M. Evaluation of the histologic and immunohistochemical (CD34, glutamine synthetase) findings in idiopathic non-cirrhotic portal hypertension (INCPH). Hepatol Int 2024; 18:1011-1019. [PMID: 38536628 PMCID: PMC11126445 DOI: 10.1007/s12072-024-10654-w] [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: 12/06/2023] [Accepted: 01/26/2024] [Indexed: 05/25/2024]
Abstract
AIM Idiopathic non-cirrhotic portal hypertension (INCPH) is a vascular disorder of uncertain origin. Diagnosis can be challenging on liver biopsy. Despite diverse histomorphologic findings documented in literature, studies on the frequency of these findings are lacking. This study aims to assess both the histomorphologic features and the immunoexpression patterns of CD34 and glutamine synthetase (GS) in liver biopsies and searched for their contribution to the pathologic diagnosis of INCPH. MATERIALS AND METHODS Hematoxylin-eosin, CD34, and GS-stained liver needle biopsy sections of 16 patients clinically diagnosed with INCPH were retrospectively analyzed. Histologic findings such as portal vein narrowing, obliteration, or loss were grouped as major findings, while portal vein herniation, hypervascularized portal tracts, and periportal abnormal vessels were grouped as minor findings, and their frequency were evaluated. Periportal endothelial CD34 stained areas were measured via ocular micrometer. The distribution of GS immunoexpression was evaluated. Eighteen healthy liver donor biopsies were evaluated as controls. RESULTS In INCPH cases, 58% of portal tracts showed major findings, compared to 15% in the control group (p < 0.001). Minor findings were observed in 16% of INCPH cases and 7% of controls (p = 0.014). The number of portal tracts with histologic findings is significantly higher in INCPH than in control liver biopsies. Abnormal portal tract distribution, like being close to each other, was seen in 75% of INCPH cases but not in controls (p < 0.001). Nodular regenerative hyperplasia (NRH) was present in 31% of cases. Periportal CD34 expression was higher in INCPH, and affected areas were larger than in controls (p < 0.001). Irregular GS staining, i.e. GS staining with patchy distribution in zone 3, and/or periportal and zone 2 hepatocytes, was found in 62% of INCPH cases, while controls showed the usual pattern (p < 0.001). CONCLUSION In the biopsy diagnosis of INCPH, in addition to the presence of major histologic findings and the amount of portal tracts displaying these features, the expression of endothelial CD34 in periportal areas, and irregular hepatocellular GS expression can also be considered as supporting feature.
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Affiliation(s)
- Melek Büyük
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Fatih, Istanbul, Turkey.
| | - Neslihan Berker
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Fatih, Istanbul, Turkey
| | - Doğu Vurallı Bakkaloğlu
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Fatih, Istanbul, Turkey
| | - İbrahim Volkan Şenkal
- Department of Gastroenterology and Hepatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Zerrin Önal
- Department of Pediatric Gastroenterology, Hepatology and Nutrition Department, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mine Güllüoğlu
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Fatih, Istanbul, Turkey
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Shan S, Zhao X, Wood-Trageser MA, Hu D, Liu L, Qi B, Jian J, Wang P, Lv W, Hu C. Obliteration of portal venules contributes to portal hypertension in biliary cirrhosis. J Pathol 2024; 263:178-189. [PMID: 38551075 DOI: 10.1002/path.6273] [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: 08/08/2023] [Revised: 01/05/2024] [Accepted: 02/13/2024] [Indexed: 05/12/2024]
Abstract
The effects of the obliteration of portal venules (OPV) in cirrhotic portal hypertension are poorly understood. To investigate its contribution to portal hypertension in biliary cirrhosis and its underlying mechanism, we evaluated OPV using two-dimensional (2D) histopathology in liver explants from patients with biliary atresia (BA, n = 63), primary biliary cholangitis (PBC, n = 18), and hepatitis B-related cirrhosis (Hep-B-cirrhosis, n = 35). Then, three-dimensional (3D) OPV was measured by X-ray phase-contrast CT in two parallel models in rats following bile duct ligation (BDL) or carbon tetrachloride (CCl4) administration, representing biliary cirrhosis and post-necrotic cirrhosis, respectively. The portal pressure was also measured in the two models. Finally, the effects of proliferative bile ducts on OPV were investigated. We found that OPV was significantly more frequent in patients with biliary cirrhosis, including BA (78.57 ± 16.45%) and PBC (60.00 ± 17.15%), than that in Hep-B-cirrhotic patients (29.43 ± 14.94%, p < 0.001). OPV occurred earlier, evidenced by the paired liver biopsy at a Kasai procedure (KP), and was irreversible even after a successful KP in the patients with BA. OPV was also significantly more frequent in the BDL models than in the CCl4 models, as shown by 2D and 3D quantitative analysis. Portal pressure was significantly higher in the BDL model than that in the CCl4 model. With the proliferation of bile ducts, portal venules were compressed and irreversibly occluded, contributing to the earlier and higher portal pressure in biliary cirrhosis. OPV, as a pre-sinusoidal component, plays a key role in the pathogenesis of portal hypertension in biliary cirrhosis. The proliferated bile ducts and ductules gradually take up the 'territory' originally attributed to portal venules and compress the portal venules, which may lead to OPV in biliary cirrhosis. © 2024 The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Shan Shan
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China
- Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Disease, Beijing, PR China
| | - Xinyan Zhao
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China
- Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Disease, Beijing, PR China
| | | | - Doudou Hu
- The Second Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong, PR China
| | - Liwei Liu
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China
| | - Beining Qi
- School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, PR China
| | - Jianbo Jian
- Department of Radiation Oncology, Tianjin Medical University General Hospital, Tianjin, PR China
| | - Ping Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China
| | - Wenjuan Lv
- School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, PR China
| | - Chunhong Hu
- School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, PR China
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Bellamy COC, O'Leary JG, Adeyi O, Baddour N, Batal I, Bucuvalas J, Del Bello A, El Hag M, El-Monayeri M, Farris AB, Feng S, Fiel MI, Fischer SE, Fung J, Grzyb K, Guimei M, Haga H, Hart J, Jackson AM, Jaeckel E, Khurram NA, Knechtle SJ, Lesniak D, Levitsky J, McCaughan G, McKenzie C, Mescoli C, Miquel R, Minervini MI, Nasser IA, Neil D, O'Neil MF, Pappo O, Randhawa P, Ruiz P, Fueyo AS, Schady D, Schiano T, Sebagh M, Smith M, Stevenson HL, Taner T, Taubert R, Thung S, Trunecka P, Wang HL, Wood-Trageser M, Yilmaz F, Zen Y, Zeevi A, Demetris AJ. Banff 2022 Liver Group Meeting report: Monitoring long-term allograft health. Am J Transplant 2024; 24:905-917. [PMID: 38461883 DOI: 10.1016/j.ajt.2024.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 02/27/2024] [Accepted: 03/06/2024] [Indexed: 03/12/2024]
Abstract
The Banff Working Group on Liver Allograft Pathology met in September 2022. Participants included hepatologists, surgeons, pathologists, immunologists, and histocompatibility specialists. Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimization, and long-term structural changes. Potential revision of the rejection classification scheme to better accommodate and communicate late T cell-mediated rejection patterns and related structural changes, such as nodular regenerative hyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression to match the heterogeneity of patient settings will be central to improving long-term patient survival. Such personalized therapeutics are in turn contingent on a better understanding and monitoring of allograft status within a rational decision-making approach, likely to be facilitated in implementation with emerging decision-support tools. Proposed revisions to rejection classification emerging from the meeting include the incorporation of interface hepatitis and fibrosis staging. These will be opened to online testing, modified accordingly, and subject to consensus discussion leading up to the next Banff conference.
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Affiliation(s)
- Christopher O C Bellamy
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, Scotland and Department of Pathology, Edinburgh Royal Infirmary, Edinburgh, Scotland.
| | - Jacqueline G O'Leary
- Dallas VA Medical Center & University of Texas, Southwestern, Department of Medicine, Dallas Texas, USA
| | - Oyedele Adeyi
- University of Minnesota Medical School, Department of Pathology, Minneapolis, Minnesota, USA
| | - Nahed Baddour
- Faculty of Medicine, University of Alexandria, Egypt
| | - Ibrahim Batal
- Pathology, Columbia University Irving Medical Center, New York, New York, USA
| | | | | | | | | | - Alton B Farris
- Pathology, Emory University Hospital, Atlanta, Georgia, USA
| | - Sandy Feng
- UCSF Health, Department of Surgery, San Francisco, California, USA
| | - Maria Isabel Fiel
- Pathology, Icahn School of Medicine, Mount Sinai, New York, New York, USA
| | | | - John Fung
- Uchicago Medicine, Department of Surgery, Chicago, Illinois, USA
| | | | - Maha Guimei
- Armed Forces College of Medicine, Cairo, Egypt
| | | | - John Hart
- Uchicago Medicine, Department of Pathology, Chicago, Illinois, USA
| | | | | | - Nigar A Khurram
- University of Pittsburgh Medical Center, Department of Pathology, Pittsburgh, Pennsylvania, USA
| | | | - Drew Lesniak
- University of Pittsburgh Medical Center, Department of Pathology, Pittsburgh, Pennsylvania, USA
| | | | | | | | | | - Rosa Miquel
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Marta I Minervini
- University of Pittsburgh Medical Center, Department of Pathology, Pittsburgh, Pennsylvania, USA
| | - Imad Ahmad Nasser
- Beth Israel Deaconess Medical Center, Harvard, Boston, Massachusetts, USA
| | - Desley Neil
- University Hospitals Birmingham NHS Foundation Trust, United Kingdom
| | - Maura F O'Neil
- University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Orit Pappo
- Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Parmjeet Randhawa
- University of Pittsburgh Medical Center, Department of Pathology, Pittsburgh, Pennsylvania, USA
| | - Phillip Ruiz
- University of Miami Hospital, Miami, Florida, USA
| | | | | | - Thomas Schiano
- Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, New York, USA
| | | | - Maxwell Smith
- Pathology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | | | - Timucin Taner
- Division of Transplantation Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Richard Taubert
- Dept. of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Swan Thung
- Pathology, Icahn School of Medicine, Mount Sinai, New York, New York, USA
| | - Pavel Trunecka
- Institute for Clinical and Experimental Medicine (IKEM), Prague, Czechia
| | - Hanlin L Wang
- Pathology, UCLA Health, Los Angeles, California, USA
| | - Michelle Wood-Trageser
- University of Pittsburgh Medical Center, Department of Pathology, Pittsburgh, Pennsylvania, USA
| | - Funda Yilmaz
- Pathology, University of Ege, Imir, Bornova, Turkey
| | - Yoh Zen
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Adriana Zeevi
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
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10
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Zhang X, Durham KM, Garza AA, Murali AR. Portal vein thrombosis, hepatic decompensation, and survival in patients with porto-sinusoidal vascular disease and portal hypertension. J Gastroenterol 2023; 58:268-276. [PMID: 36692825 DOI: 10.1007/s00535-023-01957-0] [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] [Received: 11/30/2022] [Accepted: 01/07/2023] [Indexed: 01/25/2023]
Abstract
BACKGROUND Porto-sinusoidal vascular disease (PSVD) is a novel nomenclature to describe non-cirrhotic portal hypertension and characteristic histology without portal vein thrombosis (PVT). It is a more inclusive definition than the previously well-recognized entity idiopathic non-cirrhotic portal hypertension. There is a paucity of data on PSVD patients. METHODS A total of 33 patients diagnosed with PSVD and portal hypertension (PH) between 2005 and 2021 were included. Data were retrieved from electronic medical record system and analyzed. RESULTS Of the 33 patients, 6 (18%) occurred in post-transplant allograft liver. After a median follow-up of 96 months (interquartile range, IQR [52, 139]), 14 deaths occurred (42%), 4 directly related to decompensated liver disease. The Kaplan-Meier survival estimates at 1, 5, and 10 years were 94%, 87% and 58%. PVT occurred in 10 patients (30%). The Nelson-Aalen cumulative risk estimate for PVT at 1, 5 and 10 years were 16%, 25% and 48%. The median model for end-stage liver disease and Child-Pugh score at initial presentation were 8 (IQR [7-12]) and 5 [5-6], and increased to 13 [8, 18] and 7 [5, 8], respectively, at the end of follow-up. Of the 11 patients who presented with splenomegaly and no specific sign of PH, 7 (64%) developed varices and 3 (27%) ascites at a median follow-up of 100 months. CONCLUSIONS PSVD with PH is not a benign entity. Mortality, PVT and hepatic decompensation are common. Patients with PSVD must be closely monitored, including those who only have non-specific clinical signs (e.g., splenomegaly) of PH.
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Affiliation(s)
- Xiaocen Zhang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, USA
| | - Katelin Marie Durham
- Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, USA
| | - Alexander Austin Garza
- Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, USA
| | - Arvind R Murali
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, USA.
- Liver Center, Orlando Health Digestive Health Institute, 89 W. Copeland Dr., Orlando, FL, USA.
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11
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Wöran K, Semmler G, Jachs M, Simbrunner B, Bauer DJM, Binter T, Pomej K, Stättermayer AF, Schwabl P, Bucsics T, Paternostro R, Lampichler K, Pinter M, Trauner M, Mandorfer M, Stift J, Reiberger T, Scheiner B. Clinical Course of Porto-Sinusoidal Vascular Disease Is Distinct From Idiopathic Noncirrhotic Portal Hypertension. Clin Gastroenterol Hepatol 2022; 20:e251-e266. [PMID: 33279774 DOI: 10.1016/j.cgh.2020.11.039] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 11/08/2020] [Accepted: 11/25/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Porto-sinusoidal vascular disease (PSVD) was recently proposed as novel clinical entity characterized by typical histological changes with or without portal hypertension (PH) in the absence of cirrhosis. Thus, we aimed to describe clinical characteristics and the outcome of PSVD patients and to compare these to patients meeting traditional idiopathic non-cirrhotic portal hypertension (INCPH) criteria. METHODS Patients undergoing liver biopsy (baseline) ±hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital between 2000-2019 were screened for PSVD and INCPH criteria. RESULTS 91 patients were diagnosed with PSVD of which 28 (30.8%) also fulfilled INCPH criteria (INCPH+/PSVD+). Specific histological and specific clinical PH signs were found in 72 (79.1%) and 54 (59.3%) patients, respectively. INCPH+/PSVD+ showed higher Child-Pugh-scores (7±2 vs 6±1 points; P = .002) and a higher prevalence of decompensation (57.1% vs 28.6%; P = .009) than INCPH-/PSVD+ patients. Importantly, hepatic decompensation after three years (3Y) occurred in 11.2% of PSVD patients with specific clinical signs of PH, while no decompensation occurred in patients with only specific histological or with unspecific clinical/histological signs (P = .002). When categorizing by INCPH definition, 3Y decompensation was 13.4% in INCPH+/PSVD+ and 3.8% in INCPH-/PSVD+ (P = .120). While overall mortality was similar in INCPH+/PSVD+ (n = 6; 21.4%) and INCPH-/PSVD+ (n = 10; 15.9%) patients (P = .558), liver-related mortality tended to be higher in INCPH+/PSVD+ (6.9%) than in INCPH-/PSVD+ (0%; P = .078). CONCLUSION Novel PSVD criteria facilitate diagnosis. Compared to INCPH, clinical course of PSVD patients is more favorable. Importantly, specific signs of PH including varices and collaterals are associated with hepatic decompensation and mortality.
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Affiliation(s)
- Katharina Wöran
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - David Josef Maria Bauer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Teresa Binter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Katharina Pomej
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Albert Friedrich Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Theresa Bucsics
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Rafael Paternostro
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Katharina Lampichler
- Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Matthias Pinter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Judith Stift
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Rare Liver Disease Center of the European Reference Network RARE-LIVER, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
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Microcirculatory changes in the liver of patients with refractory ascites and their relationship with diabetes and alcohol. Eur J Gastroenterol Hepatol 2021; 33:e145-e152. [PMID: 33208687 DOI: 10.1097/meg.0000000000001990] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES The determinants of refractory ascites have not been fully characterized. The aims of this study were to assess liver histopathological alterations associated with refractory ascites and their relationship with comorbidities. METHODS Consecutive patients with cirrhosis who underwent liver transplantation were retrospectively included. Patients' characteristics at the time of listing were analysed. The native livers were reviewed and lesions associated with refractory ascites were examined. RESULTS Out of the 89 patients included, 30 had refractory ascites and 59 did not (including 35 without ascites and 24 with diuretic-sensitive ascites). Patients with and without refractory ascites had a similar amount of fibrous tissue and features of fatty liver disease. By contrast, microvascular changes, namely sinusoidal dilatation (P < 0.001), diffuse perisinusoidal fibrosis (P = 0.001), hepatic venous thromboses (P = 0.004) and vascular proliferation (P = 0.01) were more frequently observed in the livers of patients with refractory ascites. Diabetes (57% vs. 31%, P = 0.02) and alcohol as a causal factor for cirrhosis (80% vs. 42%, P = 0.001) were more frequent in patients with refractory ascites than in those without. By multivariate analysis, refractory ascites was independently associated with diabetes mellitus [odds ratio (OR) (95% confidence interval, CI) 6.15 (1.47-25.71); P = 0.01], alcohol as a causal factor for cirrhosis [OR (95% CI) 4.63 (1.07-20.02); P = 0.04], higher Model For End Stage Liver Diseases [OR (95% CI) 1.21 (1.05-1.38); P = 0.008] and lower serum sodium [OR (95% CI) 0.87 (0.78-0.98); P = 0.03]. CONCLUSION Liver microcirculatory changes are associated with refractory ascites. Diabetes and alcohol may explain refractory ascites by causing microangiopathy.
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Araújo C, Nunes VS, Santos G, Freitas LARD, Schinoni MI, Paraná R. HISTOPATHOLOGICAL, CLINICAL AND EPIDEMIOLOGICAL FEATURES OF HEPATOPORTAL SCLEROSIS IN A REFERRAL CENTER FOR LIVER DISEASE IN NORTHEASTERN BRAZIL. ARQUIVOS DE GASTROENTEROLOGIA 2021; 58:276-280. [PMID: 34705959 DOI: 10.1590/s0004-2803.202100000-48] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 02/09/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Hepatoportal sclerosis HPS or obliterative portal venopathy (OPV), one of the differential diagnoses for non-cirrohtic portal hypertension, is characterized by the disappearance of the portal branches, portal and septal fibrosis, perisinusoidal fibrosis and regenerative nodular hyperplasia (RNH). It is a spectral disease that may progress to severe portal hypertension. Its etiopathogenesis is still little understood, especially in Brazil, it has been probably misdiagnosed due to its histopatological similarities with the hepatosplenic form of schistosomiasis. OBJECTIVE To analyze the profile of patients with HPS in Northeastern Brazil and to demonstrate the pathological characteristics of HPS. METHODS We retrospectively analyzed cases of OPV in liver biopsies and explants from a referral center for liver in Bahia - Brazil. The qualitative and quantitative analysis of the portal tracts and liver parenchyma was made so that comparisons could be done among the HPS findings of our population and the findings described by other authors. RESULTS From the 62 patients identified with HPS, 42% were male, while 58% were female. The average age at diagnosis was 48.3 years. From this group, we analyzed the liver biopsy of 10 patients whose diagnosis of schistosomiasis could be ruled out. From these 100% (10/10) presented dense portal fibrosis and portal venous obliteration. Liver parenchymal atrophy was present in 60% (6/10) of the patients, sinusoidal dilation was present in 30% (3/10), the presence of portal septa occurred in 50% (5/10) and dense portal fibrosis in all patients analyzed. Nodular regenerative hyperplasia was found in 30% (3/10) of the patients. CONCLUSION HPS seems to be neglected and misdiagnosed in Brazil, due to its similarities with schistossomiasis. In our study dense portal fibrosis, obliteration of the portal vein branches, parenchymal atrophy, sinusoidal dilatation and parenchymal nodular hyperplasia were the main histopathological findings and were similar to that described in other countries.
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Affiliation(s)
- Caio Araújo
- Universidade Federal da Bahia, Faculdade de Medicina, Salvador, BA, Brasil
| | - Vinícius Santos Nunes
- Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, BA, Brasil
| | - Genario Santos
- Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, BA, Brasil
| | - Luiz Antônio Rodrigues de Freitas
- Universidade Federal da Bahia, Faculdade de Medicina, Salvador, BA, Brasil.,Instituto Gonçalo Moniz - Fundação Oswaldo Cruz, Departamento de Patologia, Salvador, BA, Brasil
| | | | - Raymundo Paraná
- Universidade Federal da Bahia, Faculdade de Medicina, Salvador, BA, Brasil
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14
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Kmeid M, Liu X, Ballentine S, Lee H. Idiopathic Non-Cirrhotic Portal Hypertension and Porto-Sinusoidal Vascular Disease: Review of Current Data. Gastroenterology Res 2021; 14:49-65. [PMID: 34007347 PMCID: PMC8110235 DOI: 10.14740/gr1376] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Accepted: 03/30/2021] [Indexed: 12/29/2022] Open
Abstract
Idiopathic non-cirrhotic portal hypertension (INCPH) is a clinicopathologic disease entity characterized by the presence of clinical signs and symptoms of portal hypertension (PH) in the absence of liver cirrhosis or known risk factors accountable for PH. Multiple hematologic, immune-related, infectious, hereditary and metabolic risk factors have been associated with this disorder. Still, the exact etiopathogenesis is largely unknown. The recently proposed porto-sinusoidal vascular disease (PSVD) scheme broadens the spectrum of the disease by also including patients without clinical PH who are found to have similar histopathologic findings on core liver biopsies. Three histomorphologic lesions have been identified as specific for PSVD to include obliterative portal venopathy, nodular regenerative hyperplasia and incomplete septal cirrhosis/fibrosis. However, these findings are often subtle, under-recognized and subjective with low interobserver agreement among pathologists. Additionally, the natural history of the subclinical forms of the disease remains unexplored. The clinical course is more favorable compared to cirrhosis patients, especially in the absence of clinical PH or liver dysfunction. There are no universally accepted guidelines in regard to diagnosis and treatment of INCPH/PSVD. Hence, this review emphasizes the need to raise awareness of this entity by highlighting its complex pathophysiology and clinicopathologic associations. Lastly, formulation of standardized diagnostic criteria with clinical validation is necessary to avoid misclassifying vascular diseases of the liver and to develop and implement targeted therapeutic strategies.
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Affiliation(s)
- Michel Kmeid
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA
| | - Xiuli Liu
- Department of Pathology and Laboratory Medicine, University of Florida at Gainesville, FL, USA
| | - Samuel Ballentine
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
| | - Hwajeong Lee
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA
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15
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Gao E, Hercun J, Heller T, Vilarinho S. Undiagnosed liver diseases. Transl Gastroenterol Hepatol 2021; 6:28. [PMID: 33824932 DOI: 10.21037/tgh.2020.04.04] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 03/19/2020] [Indexed: 02/06/2023] Open
Abstract
The landscape of chronic liver disease has drastically changed over the past 20 years, largely due to advances in antiviral therapy and the rise of metabolic syndrome and associated non-alcoholic fatty liver disease (NAFLD). Despite advances in the diagnosis and treatment of a variety of liver diseases, the burden of chronic liver disease is increasing worldwide. The first step to addressing any disease is accurate diagnosis. Here, we discuss liver diseases that remain undiagnosed, either because they are difficult to diagnose or due to hepatic manifestations of an unrecognized systemic disease. Additionally, their underlying etiology may remain unknown or they represent previously uncharacterized and therefore novel liver diseases. Our goal is to provide a framework for approaching undiagnosed liver diseases which elude standard hepatic diagnostic work-up and whose patterns of disease are often overlooked.
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Affiliation(s)
- Emily Gao
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
| | - Julian Hercun
- Translational Hepatology Section, National Institute of Diabetes & Digestive & Kidney Diseases, National Institute of Health, Bethesda, MD, USA
| | - Theo Heller
- Translational Hepatology Section, National Institute of Diabetes & Digestive & Kidney Diseases, National Institute of Health, Bethesda, MD, USA
| | - Sílvia Vilarinho
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA.,Department of Pathology, Yale School of Medicine, New Haven, CT, USA
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Liang J, Shi C, Dupont WD, Salaria SN, Huh WJ, Correa H, Roland JT, Perri RE, Washington MK. Key histopathologic features in idiopathic noncirrhotic portal hypertension: an interobserver agreement study and proposal for diagnostic criteria. Mod Pathol 2021; 34:592-602. [PMID: 32958831 DOI: 10.1038/s41379-020-00676-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 08/21/2020] [Accepted: 08/25/2020] [Indexed: 12/16/2022]
Abstract
Histologic features of idiopathic noncirrhotic portal hypertension (INCPH), loosely termed as obliterative portal venopathy (OPV), are heterogenous, often subtle, and overlap with other entities. To this date, no consensus histopathologic diagnostic criteria have been established for INCPH. For these reasons, rendering a reproducible consensus histologic diagnosis of OPV on a liver biopsy may often be challenging even for experienced hepatopathologists. We report herein a two-phase interobserver agreement study on the diagnosis of OPV and assessed the relative value of histologic features in 104 liver biopsies in distinguishing between INCPH and non-INCPH with the goal to obtain a consensus on specific practical diagnostic criteria. Six hepatopathologists blinded to clinical information and original pathologic diagnosis reviewed internet-based case study sets with high-resolution whole-slide images. The initial interobserver agreement on OPV was expectedly low, but significantly improved (moderate agreement in most categories) upon adopting a consensus view recognizing portal vein sclerosis as the only strong independent histologic predictor for INCPH, and that contrary to the conventional view, aberrant portal/periportal vessels does not significantly contribute to the positive assignment of OPV status. We propose a three-tiered classification with diagnostic criteria to facilitate the histologic assignment of OPV status for the evaluation of INCPH. Furthermore, we have validated the performance of the proposed criteria either based on histology alone or coupled with clinicopathologic correlation. This classification may aid in practical histologic assessment of liver biopsies with or without portal hypertension and help to improve diagnostic consistency and accuracy.
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Affiliation(s)
- Jiancong Liang
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Chanjuan Shi
- Department of Pathology, Duke University Medical Center, Durham, NC, USA
| | - William D Dupont
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Safia N Salaria
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Won Jae Huh
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Hernan Correa
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Joseph T Roland
- Epithelial Biology Center and Department of Surgery, Vanderbilt University School of Medicine and the Nashville VA Medical Center, Nashville, TN, USA
| | - Roman E Perri
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Mary Kay Washington
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
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Vallonthaiel AG, Baloda V, Singh L, Yadav R, Kilambi R, Battu S, Sreenivas V, Pal S, Acharya SK, DattaGupta S, Shalimar, Das P. Histological analyses of trucut liver biopsies from patients with noncirrhotic portal fibrosis and extra-hepatic portal vein obstruction. INDIAN J PATHOL MICR 2021; 64:S127-S135. [PMID: 34135154 DOI: 10.4103/ijpm.ijpm_387_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Background Both noncirrhotic portal fibrosis (NCPF) and extrahepatic portal venous obstruction (EHPVO) are important causes of noncirrhotic portal hypertension (PH) in the Asian region. In this study, we analyzed the histopathological changes of liver needle-core biopsies from patients with NCPF and EHPVO. Patients and Methods The patients were diagnosed as per the Asia Pacific Association for the Study of Liver (APASL) criteria. Minimum adequacy criteria for liver core biopsies were defined, and finally, 69 liver biopsies from patients with NCPF and 100 liver biopsies from patients with EHPVO were analyzed. All histological parameters were predefined, and three experienced pathologists analyzed the biopsies after reaching consensus. Institute ethics committee clearance was taken. Results Although some histological features were overlapping, phlebosclerosis of intra-hepatic branches of the portal vein (PV), periportal aberrant vascular channels, remnant portal tracts, and hepatic fibrosis beyond the portal tracts without the formation of complete hepatic nodules (P < 0.001 for all) were common histological characteristics of NCPF on core-needle liver biopsies; while maintained lobular architecture, nonspecific dilatation of PV branches, absence of intra-hepatic PV phlebosclerosis, aberrant vascular channels, and significant fibrosis were characteristics of EHPVO. Conclusions Despite the considerable histological overlap between NCPF and EHPVO, careful histological evaluation, supplemented by clinical features, radiological and biochemical findings can help in making a conclusive diagnosis. Patients with NCPF and EHPVO with clinical jaundice show transaminitis, high serum alkaline phosphatase level, more variceal bleed, and histological evidences of nodular regenerative hyperplasia.
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Affiliation(s)
| | - Vandana Baloda
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Lavleen Singh
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Rajni Yadav
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Ragini Kilambi
- Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Sudha Battu
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | | | - Sujoy Pal
- Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Subrat K Acharya
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | | | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
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18
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Kmeid M, Zuo C, Lagana SM, Choi WT, Lin J, Yang Z, Liu X, Westerhoff M, Fiel MI, Affolter K, Choi EYK, Lee H. Interobserver study on histologic features of idiopathic non-cirrhotic portal hypertension. Diagn Pathol 2020; 15:129. [PMID: 33097074 PMCID: PMC7583235 DOI: 10.1186/s13000-020-01049-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 10/15/2020] [Indexed: 02/08/2023] Open
Abstract
Background Histologic features of idiopathic non-cirrhotic portal hypertension (INCPH) may overlap with those without INCPH. Recently, these features have been recognized as part of the larger spectrum of porto-sinusoidal vascular disease (PSVD). We assessed interobserver agreement on histologic features that are commonly associated with INCPH and studied whether a provision of relevant clinical history improves interobserver agreement. Methods The examined histologic features include lobular (such as anisocytosis, nodular regeneration, sinusoidal dilatation, increased parenchymal draining veins, and incomplete fibrous septa) and portal tract changes (such as paraportal shunting vessel(s), portal tract remnant, increased number of portal vessels, and obliterative portal venopathy). Thirty-four archived liver samples from patients with (group A) and without (group B) INCPH were retrieved. A total of 90 representative images of lobules (L) and portal tracts (P) were distributed among 9 liver pathologists blinded to true clinical history. Each pathologist answered multiple choice questions based on the absence (Q1) or presence (Q2) of clinical history of portal hypertension. Fleiss’ kappa coefficient analysis (unweighted) was performed to assess interobserver agreement on normal versus abnormal diagnosis, in L and P, based on Q1 and Q2. Results The kappa values regarding normal versus abnormal diagnosis were 0.24, 0.24, 0.18 and 0.18 for L-Q1, L-Q2, P-Q1, and P-Q2, respectively. With true clinical history provided, the kappa values were L- 0.32, P-0.17 for group A and L-0.12, P-0.14 for group B. Four pathologists changed their assessments based on the provided history. Interobserver agreement on the interpretation of L and P as normal versus abnormal was slight to fair regardless of provision of clinical history. Conclusions Our findings indicate that the histologic features of INCPH/PSVD are not limited to patients with portal hypertension and are subject to significant interobserver variation. Supplementary information The online version contains supplementary material available at 10.1186/s13000-020-01049-0.
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Affiliation(s)
- Michel Kmeid
- Department of Pathology, Albany Medical Center, 47 New Scotland Ave., MC81, Albany, NY, 12208, USA
| | - Chunlai Zuo
- Department of Pathology, Albany Medical Center, 47 New Scotland Ave., MC81, Albany, NY, 12208, USA
| | - Stephen M Lagana
- Department of Pathology, Columbia University, New York, NY, 10032, USA
| | - Won-Tak Choi
- Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA
| | - Jingmei Lin
- Department of Pathology, Indiana University, Indianapolis, IN, 46202, USA
| | - Zhaohai Yang
- Department of Pathology, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Xiuli Liu
- Department of Pathology, University of Florida at Gainesville, Gainesville, FL, 32608, USA
| | - Maria Westerhoff
- Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - M Isabel Fiel
- Department of Pathology, Mount Sinai Medical Center, New York, NY, 10029, USA
| | - Kajsa Affolter
- Department of Pathology, University of Utah, Salt Lake City, UT, 84132, USA
| | - Eun-Young K Choi
- Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Hwajeong Lee
- Department of Pathology, Albany Medical Center, 47 New Scotland Ave., MC81, Albany, NY, 12208, USA.
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19
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Nicoară-Farcău O, Rusu I, Stefănescu H, Tanțău M, Badea RI, Procopeț B. Diagnostic challenges in non-cirrhotic portal hypertension - porto sinusoidal vascular disease. World J Gastroenterol 2020; 26:3000-3011. [PMID: 32587444 PMCID: PMC7304099 DOI: 10.3748/wjg.v26.i22.3000] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 03/31/2020] [Accepted: 05/27/2020] [Indexed: 02/06/2023] Open
Abstract
Non-cirrhotic portal hypertension consists of a group of diseases characterized by signs and complications of portal hypertension, which differ from cirrhosis through histological alterations, hemodynamic characterization and, clinical outcome. Because of the similarities in clinical presentation and imaging signs, frequently these patients, and particularly those with porto-sinusoidal vascular disease (PSVD), are misdiagnosed as having liver cirrhosis and thus raising difficulties in their diagnosis. The most challenging differentiation to be considered is between PSVD and cirrhosis and, although not pathognomonic, liver biopsy is still the standard of diagnosis. Although they still require extended validation before being broadly used, new non-invasive methods for the diagnosis of porto-sinusoidal vascular disease, like transient elastography, contrast-enhanced ultrasound or metabolomic profiling, have shown promising results. Another issue is the differentiation between PSVD and chronic extrahepatic portal vein obstruction, especially now when it is known that 40% of patients suffering from PSVD develop portal vein thrombosis. In this particular case, once the portal vein thrombosis occurred, the diagnosis of PSVD is impossible according to the current guidelines. Moreover, so far, the differentiation between PSVD and sinusoidal obstruction syndrome has not been clear so far in particular circumstances. In this review we highlighted the diagnostic challenges regarding the PSVD, as well as the current techniques used in the evaluation of these patients.
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Affiliation(s)
- Oana Nicoară-Farcău
- University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca 400000, Romania
- Gastroenterology Department, Regional Institute of Gastroenterology and Hepatology “O. Fodor”, Cluj-Napoca 400000, Romania
| | - Ioana Rusu
- University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca 400000, Romania
- Pathology Department, Regional Institute of Gastroenterology and Hepatology “O. Fodor”, Cluj-Napoca 400000, Romania
| | - Horia Stefănescu
- Gastroenterology Department, Regional Institute of Gastroenterology and Hepatology “O. Fodor”, Cluj-Napoca 400000, Romania
| | - Marcel Tanțău
- University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca 400000, Romania
- Gastroenterology Department, Regional Institute of Gastroenterology and Hepatology “O. Fodor”, Cluj-Napoca 400000, Romania
| | - Radu Ion Badea
- University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca 400000, Romania
- Imagistic Department, Regional Institute of Gastroenterology and Hepatology “O. Fodor”, Cluj-Napoca 400000, Romania
| | - Bogdan Procopeț
- University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca 400000, Romania
- Gastroenterology Department, Regional Institute of Gastroenterology and Hepatology “O. Fodor”, Cluj-Napoca 400000, Romania
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20
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Zhang X, Thomas C, Schiano TD, Thung SN, Ward SC, Fiel MI. Aberrant von Willebrand factor expression of sinusoidal endothelial cells and quiescence of hepatic stellate cells in nodular regenerative hyperplasia and obliterative portal venopathy. Histopathology 2020; 76:959-967. [PMID: 31994248 DOI: 10.1111/his.14083] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 01/20/2020] [Accepted: 01/25/2020] [Indexed: 02/06/2023]
Abstract
AIMS Nodular regenerative hyperplasia (NRH) and obliterative portal venopathy (OPV), entities that comprise idiopathic non-cirrhotic portal hypertension (INCPH), are under-recognised diseases of uncertain aetiology and the diagnosis can be easily missed on liver biopsy. The expression of CD34 and von Willebrand factor (vWF) in liver sinusoidal endothelial cells (LSEC) and alpha-smooth muscle actin (ASMA) in hepatic stellate cells (HSCs) is unknown in NRH and OPV. We sought to investigate the pathogenesis and potential immunomarkers that might aid in making the diagnosis of NRH and OPV. METHODS AND RESULTS Immunohistochemical (IHC) staining for CD34, vWF and ASMA was performed in clinically and histologically well-characterised NRH (n = 15) and OPV (n = 47) liver specimens. Among the 47 OPV cases, 37 (78.7%) had concurrent features of NRH. CD34 positive staining was mainly confined to small vessels in the portal tracts and LSECs in periportal areas, a finding similar to that in non-NRH/OPV livers. However, expression of vWF in LSECs was positive in the compressed sinusoids of NRH and in a patchy or geographic pattern, particularly prominent in the perivenular areas and dilated sinusoids of OPV cases. HSCs were negative for ASMA in all NRH and OPV cases. CONCLUSION Our findings indicate that NRH may be a subtle but common concurrent morphological feature in OPV. The aberrant expression of vWF in LSECs suggests that endothelial injury may play a role in the pathogenesis, which may thus aid in the recognition and diagnosis of NRH and OPV, particularly when confronted with otherwise apparent normal liver histology on needle biopsy.
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Affiliation(s)
- Xuchen Zhang
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
| | - Courtney Thomas
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
| | - Thomas D Schiano
- Department of Medicine - Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Swan N Thung
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Stephen C Ward
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - M Isabel Fiel
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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21
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El Jabbour T, McHugh KE, Patil DT, Zuo C, Koo BH, Kim S, Lee H. Histologic Lesions of Porto-Sinusoidal Vascular Disease Following Phlebotomy in Hemochromatosis. Gastroenterology Res 2020; 13:32-39. [PMID: 32095171 PMCID: PMC7011912 DOI: 10.14740/gr1236] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Accepted: 11/12/2019] [Indexed: 12/19/2022] Open
Abstract
Background Phlebotomy induces regression of liver fibrosis in genetic hemochromatosis. We assessed the histologic changes in pre-phlebotomy and post-phlebotomy liver biopsies from patients with HFE mutation as a model to study regression of fibrosis. We aimed to show that phlebotomy-induced histologic lesions overlap with porto-sinusoidal vascular disease (PSVD, also known as idiopathic non-cirrhotic portal hypertension), histologically. Methods A total of 51 biopsies (22 pre-phlebotomy and 29 post-phlebotomy) were reviewed, and three variables were studied: iron index indicative of the amount of accumulated iron (range 0 to 18), the combined score of vascular changes reflecting the presence of histological lesions that are described in PSVD (range 0 to 9) and the high-grade shunt vessel by calculating the proportion of portal tracts with shunt vessels, with a cutoff of 50%. Two-tailed Student's t-test and Fisher's exact test were performed to compare the means of two variables and frequencies of the histologic lesions in two groups, respectively. A P-value < 0.05 was considered statistically significant. Results The iron index was higher in the pre-phlebotomy compared to post-phlebotomy group (P = 0.01). Compared to the pre-phlebotomy group, the combined score was higher in the post-phlebotomy group when the cases of advanced fibrosis were excluded (P = 0.023) and remained higher when patients with risk factors for PSVD were further excluded (P = 0.034). The high-grade shunt vessel tended to be more common in the post-phlebotomy group when advanced fibrosis was excluded; however, the statistical significance was marginal (P = 0.056). Conclusions Phlebotomy reduces hepatic iron load and induces histologic lesions of PSVD in patients with HFE mutation. Our data support a postulation that some of the histologic lesions of PSVD represent vascular remodeling following a regression of fibrosis and may not be reflective of risk factors or etiopathogenesis of PSVD. Regressed fibrosis and PSVD may not be reliably distinguished in a limited sample, therefore warranting cautious interpretation in the right clinical context.
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Affiliation(s)
| | | | - Deepa T Patil
- Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA.,Pathology, Brigham and Women's hospital, Boston, MA, USA
| | - Chunlai Zuo
- Anatomic Pathology, Albany Medical College, Albany, NY, USA
| | | | - Sungeun Kim
- Anatomic Pathology, Albany Medical College, Albany, NY, USA
| | - Hwajeong Lee
- Anatomic Pathology, Albany Medical College, Albany, NY, USA
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22
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23
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Gioia S, Nardelli S, Ridola L, d'Amati G, Riggio O. Is porto sinusoidal vascular disease to be actively searched in patients with portal vein thrombosis? World J Hepatol 2019; 11:613-618. [PMID: 31528244 PMCID: PMC6717715 DOI: 10.4254/wjh.v11.i8.613] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 07/03/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023] Open
Abstract
Porto sinusoidal vascular liver disease (PSVD) and portal vein thrombosis (PVT) are distinct vascular liver diseases characterized, respectively, by an intrahepatic and a prehepatic obstacle to the flow in the liver portal system. PVT may also occur as a complication of the natural history of PSVD, especially if a prothrombotic condition coexists. In other cases, it is associated to local and systemic pro-thrombotic conditions, even if its cause remains unknown in up to 25% despite an active search. In our opinion, the presence of PSVD should be suspected in patients with PVT especially in those with PVT "sine causa" and the active search of this condition should be included in their diagnostic work-out. However, sometimes the diagnosis of pre-existing PSVD is very hard. Biopsy cannot be fully discriminant as similar histological data have been described in both conditions. Liver stiffness may help as it has been shown to be higher in PSVD than in "pure" PVT, due to the presence of sclerosis in the portal venous radicles observable in PSVD patients. Nevertheless, comparing liver stiffness between PVT and PSVD has until now been restricted to very limited series of patients. In conclusion, even if it is still totally hypothetical, our point of view may have clinical consequences, especially when deciding to perform a liver biopsy in patients with a higher liver stiffness and suspending the anticoagulation in patients with PVT and no detectable prothrombotic factors.
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Affiliation(s)
- Stefania Gioia
- Dipartimento di Medicina Traslazionale e di Precisione, "Sapienza" Università di Roma, Roma 00185, Italy,
| | - Silvia Nardelli
- Dipartimento di Medicina Traslazionale e di Precisione, "Sapienza" Università di Roma, Roma 00185, Italy
| | - Lorenzo Ridola
- Dipartimento di Medicina Traslazionale e di Precisione, "Sapienza" Università di Roma, Roma 00185, Italy
| | - Giulia d'Amati
- Dipartimento di Scienze Radiologiche, Oncologiche e Anatomo Patologiche, "Sapienza" Università di Roma, Roma 00185, Italy
| | - Oliviero Riggio
- Dipartimento di Medicina Traslazionale e di Precisione, "Sapienza" Università di Roma, Roma 00185, Italy
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24
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Sun Y, Lan X, Shao C, Wang T, Yang Z. Clinical features of idiopathic portal hypertension in China: A retrospective study of 338 patients and literature review. J Gastroenterol Hepatol 2019; 34:1417-1423. [PMID: 30462857 DOI: 10.1111/jgh.14552] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 11/03/2018] [Accepted: 11/09/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Idiopathic portal hypertension (IPH) refers to a relatively rare condition characterized by intrahepatic portal hypertension in the absence of underlying disease such as liver cirrhosis. METHODS We retrospectively reviewed 338 patients with IPH that were diagnosed at the pathological consultation center of our hospital. RESULTS The ratio of male to female patients was 1:1. Mean age at onset was 35.1 ± 16.5 years; male patients on average were 12 years younger than female patients at onset. The median duration from onset to IPH diagnosis was 12 months. In 50 patients, medication use may have been an etiological factor. The most common clinical manifestations were splenomegaly (91.3%) and hypersplenism (68.9%); 57.0% patients presented varicosis, while 25.1% patients had a history of variceal bleeding. Nodular regenerative hyperplasia was found in 22.2% liver biopsies. Among patients for whom laboratory data were available, 65.0%, 50.3%, and 71.4% patients presented leukopenia, anemia, and thrombocytopenia due to hypersplenism. Liver function was mostly in the compensated stage. Female patients showed worse leukopenia and anemia, while male patients were more likely to have abnormal serum transaminase and bilirubin levels. Sixty-seven patients received surgical or interventional treatment. CONCLUSIONS High-quality liver biopsy, detailed clinical information, and expert pathologist are necessary for diagnosis of IPH. IPH can occur concurrently with other liver disease such as hepatitis and drug-induced liver injury. Medication appears to be an important etiological factor for IPH in China. Management approach was largely focused on treatment of portal hypertension and its complications.
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Affiliation(s)
- Yongliang Sun
- Department of General Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Xu Lan
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Chen Shao
- Department of Pathology, Beijing You'an Hospital affiliated with Capital Medical University, Beijing, China
| | - Tailing Wang
- Department of Pathology, China-Japan Friendship Hospital, Beijing, China
| | - Zhiying Yang
- Department of General Surgery, China-Japan Friendship Hospital, Beijing, China
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25
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Vuppalanchi R, Chalasani N. Reply. Hepatology 2019; 70:445-446. [PMID: 30951197 DOI: 10.1002/hep.30640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Affiliation(s)
- Raj Vuppalanchi
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN
| | - Naga Chalasani
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN
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26
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Gioia S, Nardelli S, Riggio O. Letter to the Editor: Liver Stiffness in Noncirrhotic Portal Hypertension: The Devil Is in the Diagnosis. Hepatology 2019; 70:444-445. [PMID: 30506573 DOI: 10.1002/hep.30367] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Stefania Gioia
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Silvia Nardelli
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Oliviero Riggio
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
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27
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Oikonomou KG, Tsai E, Sarpel D, Dieterich DT. Liver Disease in Human Immunodeficiency Virus Infection. Clin Liver Dis 2019; 23:309-329. [PMID: 30947879 DOI: 10.1016/j.cld.2018.12.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver disease in human immunodeficiency virus (HIV) remains a main cause of morbidity and mortality. Liver-related morbidity and mortality can be caused by multiple etiologic factors, including opportunistic infections, direct and indirect effects of antiretrovirals, direct and indirect effects of HIV, and viral hepatitides. These factors present with varied liver pathophysiologic mechanisms that lead to abnormalities in liver enzymes and synthetic function test, followed by distinct clinical presentations. This article elucidates the direct effects on HIV in the liver and explores the diagnostic and management challenges in patients with HIV in the era of highly active antiretroviral treatment.
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Affiliation(s)
- Katerina G Oikonomou
- Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, New York, NY 10029-6574, USA.
| | - Eugenia Tsai
- Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, New York, NY 10029-6574, USA
| | - Dost Sarpel
- Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, New York, NY 10029-6574, USA
| | - Douglas T Dieterich
- Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, New York, NY 10029-6574, USA
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28
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Lv Y, Li K, He C, Luo B, Zhang B, Liu H, Wang Z, Guo W, Wang Q, Chen H, Bai W, Yuan X, Yu T, Li X, Yuan J, Han N, Zhu Y, Niu J, Xie H, Wang J, Chen L, Yin Z, Fan D, Li Z, Han G. TIPSS for variceal bleeding in patients with idiopathic non-cirrhotic portal hypertension: comparison with patients who have cirrhosis. Aliment Pharmacol Ther 2019; 49:926-939. [PMID: 30820990 DOI: 10.1111/apt.15186] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Revised: 11/23/2018] [Accepted: 01/18/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND In patients with idiopathic non-cirrhotic portal hypertension (INCPH), the usual recommended strategy for management of variceal bleeding is the same as that in cirrhosis. However, this policy has been challenged by the different natural history between INCPH and cirrhosis. AIM To compare outcomes after transjugular intrahepatic portosystemic shunt (TIPSS) between INCPH and cirrhotic patients admitted for variceal bleeding. METHODS Between March 2001 and September 2015, 76 consecutive patients with biopsy-proven INCPH undergoing TIPSS for variceal bleeding in a tertiary-care centre were included. 76 patients with cirrhotic portal hypertension receiving TIPSS for variceal bleeding, and matched for age, sex, Child-Pugh class, stent type and index year of TIPSS creation served as controls. RESULTS Patients with INCPH, compared to those with cirrhosis, had significantly lower mortality (11% vs 36% at 5 years, adjusted HR, 0.37; 95% CI 0.15-0.87, P = 0.022), overt hepatic encephalopathy (16% vs 33% at 5 years, adjusted HR, 0.35; 95% CI 0.16-0.75, P = 0.007) and hepatic impairment, despite similar rates of further bleeding (33% vs 32% at 5 years, adjusted HR, 0.72; 95% CI 0.36-1.44, P = 0.358), and shunt dysfunction (35% vs 36% at 5 years, adjusted HR, 0.84; 95% CI 0.41-1.72, P = 0.627). These findings were consistent across different relevant subgroups. CONCLUSIONS Patients with INCPH treated with TIPSS for variceal bleeding had similar progression of portal hypertension (further bleeding and shunt dysfunction) but fewer complications of liver disease (overt hepatic encephalopathy and hepatic insufficiency) and lower mortality rate compared with cirrhotic patients with comparable liver function.
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Affiliation(s)
- Yong Lv
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Kai Li
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Chuangye He
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Bohan Luo
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Bojing Zhang
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Haibo Liu
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Zhengyu Wang
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Wengang Guo
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Qiuhe Wang
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Hui Chen
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Wei Bai
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Xulong Yuan
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Tianlei Yu
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Xiaomei Li
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Jie Yuan
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Na Han
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Ying Zhu
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Jing Niu
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Huahong Xie
- Department of Digestive Endoscopy, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Jianhong Wang
- Department of Ultrasound, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Ling Chen
- Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zhanxin Yin
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Daiming Fan
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Zengshan Li
- Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Guohong Han
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
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Lejealle C, Paradis V, Bruno O, de Raucourt E, Francoz C, Soubrane O, Lebrec D, Bedossa P, Valla D, Mal H, Vilgrain V, Durand F, Rautou PE. Evidence for an Association Between Intrahepatic Vascular Changes and the Development of Hepatopulmonary Syndrome. Chest 2019; 155:123-136. [DOI: 10.1016/j.chest.2018.09.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2018] [Revised: 08/21/2018] [Accepted: 09/05/2018] [Indexed: 02/06/2023] Open
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Hernández-Gea V, Baiges A, Turon F, Garcia-Pagán JC. Idiopathic Portal Hypertension. Hepatology 2018; 68:2413-2423. [PMID: 30066417 DOI: 10.1002/hep.30132] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 05/16/2018] [Indexed: 12/12/2022]
Abstract
Idiopathic portal hypertension (IPH) is a rare disorder characterized by clinical portal hypertension in the absence of a recognizable cause such as cirrhosis. Laboratory tests often reveal a preserved liver function with anemia, leukopenia, and thrombocytopenia due to splenomegaly. Imaging studies reveal signs of portal hypertension, whereas liver stiffness and portal pressure values are usually normal or slightly elevated. Liver biopsy is considered mandatory in order to rule out other causes of portal hypertension, mainly cirrhosis. Liver histology may only show subtle or mild changes, and the definite diagnosis of IPH often requires an expert pathologist and a high-quality specimen. The most frequent clinical presentation is variceal bleeding. Ascites is rarely observed initially, although it may occasionally appear during follow-up. Typical histological findings associated with IPH have been described in patients without portal hypertension, probably representing early stages of the disease. Although the pathophysiology of this entity remains largely unknown, it is frequently associated with underlying immunological disorders, bacterial infections, trace metal poisoning, medications, liver circulatory disturbances, and thrombotic events. The long-term prognosis of patients with IPH, where ascites and the underlying condition are important prognostic factors, is better than in patients with cirrhosis. Treatments that modify the natural history of the disease remain an unmet need, and management of IPH is frequently restricted to control of portal hypertension-related complications.
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Affiliation(s)
- Virginia Hernández-Gea
- Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clinic, Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Anna Baiges
- Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clinic, Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Fanny Turon
- Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clinic, Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Juan Carlos Garcia-Pagán
- Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clinic, Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.,University of Barcelona, Barcelona, Spain
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Guido M, Alves VAF, Balabaud C, Bathal PS, Bioulac-Sage P, Colombari R, Crawford JM, Dhillon AP, Ferrell LD, Gill RM, Hytiroglou P, Nakanuma Y, Paradis V, Quaglia A, Rautou PE, Theise ND, Thung S, Tsui WMS, Sempoux C, Snover D, van Leeuwen DJ. Histology of portal vascular changes associated with idiopathic non-cirrhotic portal hypertension: nomenclature and definition. Histopathology 2018; 74:219-226. [DOI: 10.1111/his.13738] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 06/07/2018] [Accepted: 08/18/2018] [Indexed: 12/19/2022]
Affiliation(s)
- Maria Guido
- Department of Medicine-DIMED; Pathology Unit; University of Padova; Padova Italy
| | - Venancio A F Alves
- Department of Pathology; University of Sao Paulo School of Medicine; Sao Paulo Brazil
| | | | - Prithi S Bathal
- Department of Pathology; University of Melbourne; Melbourne Vic. Australia
| | - Paulette Bioulac-Sage
- Department of Pathology; CHU Bordeaux, and Inserm U1053; Bordeaux University; Bordeaux France
| | | | - James M Crawford
- Department of Pathology and Laboratory Medicine; Donald and Barbara School of Medicine at Hofstra/Northwell; New York NY USA
| | - Amar P Dhillon
- Department of Cellular Pathology; UCL Medical School; London UK
| | - Linda D Ferrell
- Department of Pathology; University of California; San Francisco CA USA
| | - Ryan M Gill
- Department of Pathology; University of California; San Francisco CA USA
| | - Prodromos Hytiroglou
- Department of Pathology; Aristotle University Medical School; Thessaloniki Greece
| | - Yasuni Nakanuma
- Department of Diagnostic Pathology; Shizuoka Cancer Centre; Shizuoka Japan
| | | | - Alberto Quaglia
- Institute of Liver Studies; King's College Hospital and King's College; London UK
| | - Pierre E Rautou
- Department of Hepatology; Hopital Beaujon; University of Paris; Paris France
| | - Neil D Theise
- Department of Pathology; New York University School of Medicine; New York NY USA
| | - Swan Thung
- Department of Pathology; Icahn School of Medicine at Mount Sinai; New York NY USA
| | | | - Christine Sempoux
- Service of Clinical Pathology; Lausanne University Hospital; Institute of Pathology; Lausanne Switzerland
| | - Dale Snover
- Department of Pathology; Fairview Southdale Hospital; Edina MN USA
| | - Dirk J van Leeuwen
- Section of Gastroenterology and Hepatology; Geisel School of Medicine at Dartmouth College; Hanover NH USA
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Guido M, Sarcognato S, Russo FP, Cardin R, Piciocchi M, Colloredo G, Farinati F. Focus on histological abnormalities of intrahepatic vasculature in chronic viral hepatitis. Liver Int 2018; 38:1770-1776. [PMID: 29427537 DOI: 10.1111/liv.13718] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 01/30/2018] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS The histological intrahepatic microvasculature lesions have not been deeply investigated outside the setting of portal hypertension. The aim of this study was to analyse the type and the prevalence of microvasculature abnormalities and their correlation with inflammatory activity, fibrosis stage and tissue markers of fibrogenesis, angiogenesis and oxidative DNA damage in liver biopsies obtained from patients with chronic viral hepatitis. METHODS Seventy-four liver biopsies from untreated patients affected by hepatitis B (22 cases) and C (52 cases) were included. The presence of microvascular changes was correlated with (i) the severity of the activity and fibrosis; (ii) immunohistochemical markers of angiogenesis (CD34) and hepatic stellate cells activation (alpha-smooth muscle actin); (iii) a tissue marker of oxidative damage (8-OHdG adducts). RESULTS Sixty-five out of 74 biopsies (87.8%) showed vascular lesions. Portal angiomatosis was the most prevalent (62.2%) and it was associated with, on 1 side, the fibrosis stage at both univariate (P < .0001) and multivariate analysis (P = .01, OR = 9.4 [1.6-54]) and, on the other, with angiogenesis (P = .05) and hepatic stellate cells activation (P = .002). Interestingly, 36/46 cases with portal angiomatosis were at early/intermediate fibrosis stage. The hepatic stellate cells activation was also associated with the presence of aberrant periportal vessels (P = .01). CONCLUSIONS The histological alterations of intrahepatic microvasculature, usually seen in cirrhosis and portal hypertension, occur in chronic viral hepatitis even at early/intermediate fibrosis stages. Their correlation with angiogenesis and fibrogenesis supports a possible involvement in disease progression.
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Affiliation(s)
- Maria Guido
- Surgical Pathology & Cytopathology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy
| | - Samantha Sarcognato
- Surgical Pathology & Cytopathology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy
| | - Francesco P Russo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology-DISCOG, University Hospital of Padova, Padova, Italy
| | - Romilda Cardin
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology-DISCOG, University Hospital of Padova, Padova, Italy
| | - Marika Piciocchi
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology-DISCOG, University Hospital of Padova, Padova, Italy
| | - Guido Colloredo
- Department of Internal Medicine, San Pietro Hospital, Ponte San Pietro, Italy
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology-DISCOG, University Hospital of Padova, Padova, Italy
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Gioia S, Nardelli S, Pasquale C, Pentassuglio I, Nicoletti V, Aprile F, Merli M, Riggio O. Natural history of patients with non cirrhotic portal hypertension: Comparison with patients with compensated cirrhosis. Dig Liver Dis 2018; 50:839-844. [PMID: 29429910 DOI: 10.1016/j.dld.2018.01.132] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 01/15/2018] [Accepted: 01/17/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND The knowledge of natural history of patients with portal hypertension (PH) not due to cirrhosis is less well known than that of cirrhotic patients. AIM To describe the clinical presentation and the outcomes of 89 patients with non-cirrhotic PH (25 with non-cirrhotic portal hypertension, INCPH, and 64 with chronic portal vein thrombosis, PVT) in comparison with 77 patients with Child A cirrhosis. METHODS The patients were submitted to a standardized clinical, laboratory, ultrasonographic and endoscopic follow-up. Variceal progression, incidence of variceal bleeding, portal vein thrombosis, ascites and survival were recorded. RESULTS At presentation, the prevalence of varices, variceal bleeding and ascites was similar in the 3 groups. During follow-up, the rate of progression to varices at risk of bleeding (p < 0.0001) and the incidence of first variceal bleeding (p = 0.02) were significantly higher in non-cirrhotic then in cirrhotic patients. A PVT developed in 32% of INCPH patients and in 18% of cirrhotics (p = 0.02). CONCLUSIONS In the patients with non-cirrhotic PH variceal progression is more rapid and bleeding more frequent than in cirrhotics. Patients with INCPH are particularly prompt to develop PVT. This observational study suggests that the management of patients with non-cirrhotic PH should take into consideration the natural history of portal hypertension in these patients and cannot be simply derived by the observation of cirrhotic patients.
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Affiliation(s)
- Stefania Gioia
- Dept. of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension, Rome, Italy.
| | - Silvia Nardelli
- Dept. of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension, Rome, Italy.
| | - Chiara Pasquale
- Dept. of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension, Rome, Italy.
| | - Ilaria Pentassuglio
- Dept. of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension, Rome, Italy
| | - Valeria Nicoletti
- Dept. of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension, Rome, Italy
| | - Francesca Aprile
- Dept. of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension, Rome, Italy.
| | - Manuela Merli
- Dept. of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension, Rome, Italy
| | - Oliviero Riggio
- Dept. of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension, Rome, Italy
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34
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Pathology of idiopathic non-cirrhotic portal hypertension. Virchows Arch 2018; 473:23-31. [DOI: 10.1007/s00428-018-2355-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Revised: 03/29/2018] [Accepted: 04/02/2018] [Indexed: 12/15/2022]
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35
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Spectrum of histopathological changes in patients with non-cirrhotic portal fibrosis. Hepatol Int 2018; 12:158-166. [DOI: 10.1007/s12072-018-9857-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 03/15/2018] [Indexed: 12/13/2022]
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36
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Vascular liver diseases on the clinical side: definitions and diagnosis, new concepts. Virchows Arch 2018; 473:3-13. [PMID: 29572606 DOI: 10.1007/s00428-018-2331-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 02/21/2018] [Accepted: 02/27/2018] [Indexed: 12/17/2022]
Abstract
The components of the hepatic vascular system (hepatic arteries, portal and hepatic veins, sinusoids, and lymphatics) can be damaged by various types of injury. Each of the resulting conditions is rare, which has limited knowledge and awareness. In the last two decades, international collaborations have allowed to reach critical masses of data, which has driven significant progresses in understanding and management of vascular disorders of the liver. The present paper discusses definitions, denominations, and diagnosis of such vascular disorders with the exception of those affecting hepatic arteries. Evolving pathogenic or pathophysiologic views relevant to the clinical aspects are also overviewed.
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37
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Pathology of idiopathic non-cirrhotic portal hypertension. Hepatol Int 2017; 11:409-411. [DOI: 10.1007/s12072-017-9823-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 09/06/2017] [Indexed: 01/27/2023]
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38
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Witters P, Libbrecht L, Roskams T, De Boeck K, Dupont L, Proesmans M, Vermeulen F, Maleux G, Monbaliu D, Pirenne J, Cassiman D. Liver disease in cystic fibrosis presents as non-cirrhotic portal hypertension. J Cyst Fibros 2017; 16:e11-e13. [DOI: 10.1016/j.jcf.2017.03.006] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Accepted: 03/06/2017] [Indexed: 10/19/2022]
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Zuo C, Chumbalkar V, Ells PF, Bonville DJ, Lee H. Prevalence of histological features of idiopathic noncirrhotic portal hypertension in general population: a retrospective study of incidental liver biopsies. Hepatol Int 2017; 11:452-460. [PMID: 28597108 DOI: 10.1007/s12072-017-9801-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 05/16/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Idiopathic noncirrhotic portal hypertension (INCPH) is associated with histologic changes secondary to obliterative portal venopathy without cirrhosis. We studied the prevalence of individual histological features of INCPH in liver biopsies obtained incidentally during unrelated elective procedures and in elective liver biopsies with the diagnosis of fatty liver disease. METHODS A total of 53 incidental liver biopsies obtained intraoperatively during unrelated elective procedures and an additional 28 elective biopsies with the diagnosis of fatty liver disease without portal hypertension and cirrhosis were studied. Various histologic features of INCPH were evaluated. RESULTS Shunt vessel (30%), phlebosclerosis (27%), increased number of portal vessels (19%) and incomplete septa (17%) were common in these liver biopsies after confounding factors such as co-existing fatty liver disease or fibrosis were excluded. At least one feature of INCPH was noted in 90% of the biopsies. Eight (10%) biopsies showed 5-6 features of INCPH. In total, 11 (14%) of 81 patients had risk factors associated with INCPH, including hypercoagulability, autoimmune disease, exposure to drugs, and infections. No patient had portal hypertension at the end of the follow-up. CONCLUSION The histologic features of INCPH are seen in incidental liver biopsies and fatty liver disease without portal hypertension. Ten percent of the biopsies show 5-6 features of INCPH without portal hypertension. Interpreting histologic features in the right clinical context is important for proper patient care.
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Affiliation(s)
- Chunlai Zuo
- Pathology and Laboratory Medicine, Albany Medical College, 47 New Scotland Ave., MC81, Albany, NY, 12208, USA
| | - Vaibhav Chumbalkar
- Pathology and Laboratory Medicine, Albany Medical College, 47 New Scotland Ave., MC81, Albany, NY, 12208, USA
| | - Peter F Ells
- Division of Gastroenterology, Albany Medical College, 47 New Scotland Ave., a405, Albany, NY, 12208, USA
| | - Daniel J Bonville
- General Surgery, Houston Methodist Hospital, 6550 Fannin St., Suite 1661, Houston, TX, 77030, USA
| | - Hwajeong Lee
- Pathology and Laboratory Medicine, Albany Medical College, 47 New Scotland Ave., MC81, Albany, NY, 12208, USA.
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García‐Tsao G. ¿Qué es la hipertensión portal no cirrótica idiopática? Clin Liver Dis (Hoboken) 2016; 8:S39-S42. [PMID: 31041095 PMCID: PMC6490228 DOI: 10.1002/cld.600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- Guadalupe García‐Tsao
- De Yale University School of Medicine, Section of Digestive Diseases, New Haven, CT, y VA‐CT Healthcare System, Section of Digestive DiseasesWest HavenCT, EE. UU
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Hepatic encephalopathy in patients with non-cirrhotic portal hypertension: Description, prevalence and risk factors. Dig Liver Dis 2016; 48:1072-7. [PMID: 27448844 DOI: 10.1016/j.dld.2016.06.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Revised: 06/06/2016] [Accepted: 06/14/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatic encephalopathy (HE) is a common complication of cirrhosis but it is less studied in patients with non-cirrhotic portal hypertension (NCPH). AIMS To describe the prevalence of cognitive impairment (overt and covert HE) in NCPH patients and to identify the risk factors for its development. METHODS 51 patients with NCPH, 35 with chronic portal vein thrombosis (PVT) and 16 with idiopathic non-cirrhotic portal hypertension (INCPH), were evaluated for the presence of previous or present overt HE (OHE). The psychometric hepatic encephalopathy score and the SCAN battery were used to detect the presence of covert HE (CHE). 34 compensated cirrhotic patients were used as control. In NCPH patients, abdominal scans were performed to detect the presence of shunts. RESULTS None of the patients experienced OHE at evaluation while 5.7% of PVT and 12.5% of INCPH patients referred at least one documented episode of previous OHE, similarly to patients with cirrhosis (14.7%). Even if lower than in patients with cirrhosis (64.7%), a considerable proportion of patients with chronic PVT (34.3%) and INCPH (25%) had CHE (p=0.008). The presence of a large portal-systemic shunt was the only factor significantly correlated to cognitive impairment in NCPH patients. CONCLUSION HE is a tangible complication of NCPH and is mainly related to the presence of portal-systemic shunts.
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Noncirrhotic Portal Hypertension in Perinatally HIV-infected Adolescents Treated With Didanosine-containing Antiretroviral Regimens in Childhood. Pediatr Infect Dis J 2016; 35:e248-52. [PMID: 27167116 DOI: 10.1097/inf.0000000000001202] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Noncirrhotic portal hypertension (NCPH) has been reported in HIV-infected adults. Antiretroviral drugs, as well as genetic and thrombophilic predisposition, have been suggested as possible etiologic factors. METHODS Clinical data were collected from 6 HIV-infected patients attending the Infectious Diseases Departments at respectively Emma Children's Hospital Academic Medical Centre in Amsterdam, The Thai Red Cross AIDS Research Centre, Bangkok, Imperial College Healthcare NHS Trust, London who were diagnosed with NCPH. All underwent extensive blood analysis, liver ultrasound, liver elastography, esophagogastroduodenoscopy and percutaneous needle liver biopsy for histological evaluation. RESULTS We describe 6 perinatally HIV-infected adolescents, all female, who developed NCPH after prolonged exposure during childhood to a didanosine-containing antiretroviral regimen. Histology and electron microscopy showed periportal fibrosis and mitochondrial damage as key findings in their liver biopsies. One of these 6 patients required surgical intervention, the remainder have been managed conservatively to date. CONCLUSIONS Thus, symptomatic NCPH may present in adolescence after perinatally acquired HIV-1 infection. In this case series, risk factors included female sex and prolonged exposure to antiretroviral regimens that included the nucleoside-analogue didanosine in childhood.
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43
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Barge S, Grando V, Nault JC, Broudin C, Beaugrand M, Ganne-Carrié N, Roulot D, Ziol M. Prevalence and clinical significance of nodular regenerative hyperplasia in liver biopsies. Liver Int 2016; 36:1059-66. [PMID: 26415006 DOI: 10.1111/liv.12974] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Accepted: 09/17/2015] [Indexed: 02/13/2023]
Abstract
BACKGROUND Nodular regenerative hyperplasia (NRH) is a rare histological disorder associated with a wide variety of systemic diseases. AIMS We aimed (i) to report the prevalence of NRH in a database of liver biopsies (LBs) and the frequency of portal hypertension (PHT) at diagnosis, and (ii) to investigate whether associated diseases and/or specific histological lesions, including abnormalities of the microvasculature, were related to PHT. METHODS Patients with a histological diagnosis of NRH, referred by seven clinical departments, were retrospectively selected. Clinical, biological, radiological, haemodynamic and endoscopic data at diagnosis were recorded. LBs were reassessed for microvascular abnormalities. RESULTS NRH was diagnosed in 4.4% of LBs (n = 159, male: 52%, mean age: 54). Among patients referred for unexplained liver enzyme abnormalities, 15% had NRH. PHT was present at diagnosis in 45 patients (38%), including 13 with portal thrombosis; 65% of patients had an associated disorder. Obliteration of portal vein branches, observed in the LBs of 17 patients (11%), was significantly associated with PHT (P = 0.02). Periportal angiomatosis, observed in 101 patients (63%), was associated with the absence of PHT (P < 10(-4) ). CONCLUSION We suggest that NRH is a frequent histological lesion in the setting of unexplained liver enzyme abnormalities. PHT is present at the time of diagnosis in 1/3 of patients regardless of the presence of associated disease. The frequency of periportal angiomatosis in NRH without obliteration of portal vein branches, and its association with the absence of PHT suggest that obstructive portal venopathy would not represent the most frequent mechanism involved in NRH.
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Affiliation(s)
- Sandrine Barge
- Service d'Hépato-Gastro-entérologie, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, France et Université Paris 13, Bobigny, France
| | - Véronique Grando
- Service d'Hépato-Gastro-entérologie, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, France et Université Paris 13, Bobigny, France
| | - Jean-Charles Nault
- Service d'Hépato-Gastro-entérologie, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, France et Université Paris 13, Bobigny, France.,Faculté de Médecine, INSERM UMR-1162, Génomique fonctionnelle des Tumeurs solides, IUH, France Université Paris Descartes, Paris, France
| | - Chloé Broudin
- Service d'Anatomie pathologique et Centre de Ressources biologiques, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, France et Université Paris 13, Bobigny, France
| | - Michel Beaugrand
- Service d'Hépato-Gastro-entérologie, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, France et Université Paris 13, Bobigny, France
| | - Nathalie Ganne-Carrié
- Service d'Hépato-Gastro-entérologie, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, France et Université Paris 13, Bobigny, France.,Faculté de Médecine, INSERM UMR-1162, Génomique fonctionnelle des Tumeurs solides, IUH, France Université Paris Descartes, Paris, France
| | - Dominique Roulot
- UF Hépatologie, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Avicenne, AP-HP, France et Université Paris 13, Bobigny, France
| | - Marianne Ziol
- Faculté de Médecine, INSERM UMR-1162, Génomique fonctionnelle des Tumeurs solides, IUH, France Université Paris Descartes, Paris, France.,Service d'Anatomie pathologique et Centre de Ressources biologiques, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, France et Université Paris 13, Bobigny, France
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Hepatic arterial buffer response: pathologic evidence in non-cirrhotic human liver with extrahepatic portal vein thrombosis. Mod Pathol 2016; 29:489-99. [PMID: 26916069 DOI: 10.1038/modpathol.2016.43] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Revised: 01/13/2016] [Accepted: 01/22/2016] [Indexed: 02/07/2023]
Abstract
Increase in hepatic arterial flow in response to reduced portal flow (hepatic arterial buffer response) has been demonstrated experimentally and surgically. We provide pathologic evidence for hepatic arterial buffer response in non-cirrhotic patients with extrahepatic portal vein thrombosis and elucidate the histopathologic spectrum of non-cirrhotic portal vein thrombosis. Liver biopsies and resections from non-cirrhotic patients with extra-hepatic portal vein thrombosis were retrieved. Morphologic features, extent of CD34 staining, outer diameters, luminal diameters and wall thickness of hepatic arteries cut in cross-section and outer diameters of cross-sectioned paired bile ducts were compared with age- and gender-matched controls. There were 12 male and 9 female patients. Measurements of 280 and 193 arteries from patients and controls, respectively, demonstrated statistically significant (P<0.05) arterial dilatation (increase in percentage of arterial lumen to outer diameter) and arterial wall thinning in resection specimens of non-cirrhotic patients with extra-hepatic portal vein thrombosis. Subtle and/or focal dilatation of central veins, portal veins and sinusoids; focal trabecular thinning/thickening and mild ductular reaction were common findings in both the patient and control groups. Diffuse and obvious changes, and portal vein absence or attenuation were seen only in the patient group. Capillarization of sinusoids was not seen on CD34 stain. Two patients showed significant ductular reaction, one of who developed biliary strictures on follow-up. Hepatic arterial dilatation and wall thinning in non-cirrhotic patients with portal vein thrombosis provide pathologic evidence of hepatic arterial buffer response in the human liver. Obvious and diffuse sinusoidal dilatation and absence or attenuation of portal veins are highly suggestive of extrahepatic portal vein thrombosis in non-cirrhotic patients with portal hypertension. Periportal shunt vessels, hypervascular portal tracts, muscularized portal veins, large thick-walled or dilated arteries aid diagnosis but are rare findings. Normal or near-normal biopsies do not rule out portal vein thrombosis.
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45
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Gómez Alonso M, Goñi Esarte S, Bolado Concejo F, Urman Fernández JM, Basterra Ederra M, Kutz Leoz M, Zozaya Urmeneta JM. Idiopathic non-cirrhotic portal hypertension and portal vein thrombosis in a patient with HIV infection. GASTROENTEROLOGIA Y HEPATOLOGIA 2016; 40:353-354. [PMID: 27084670 DOI: 10.1016/j.gastrohep.2016.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Revised: 03/01/2016] [Accepted: 03/07/2016] [Indexed: 11/15/2022]
Affiliation(s)
- Marta Gómez Alonso
- Servicio de Aparato Digestivo, Hospital de Zumárraga, Zumárraga, Guipúzcoa, España
| | - Silvia Goñi Esarte
- Servicio de Aparato Digestivo, Complejo Hospitalario de Navarra, Pamplona, Navarra, España.
| | | | | | | | - Marcos Kutz Leoz
- Servicio de Aparato Digestivo, Hospital Reina Sofía, Tudela, Navarra, España
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Guido M, Sarcognato S, Sonzogni A, Lucà MG, Senzolo M, Fagiuoli S, Ferrarese A, Pizzi M, Giacomelli L, Colloredo G. Obliterative portal venopathy without portal hypertension: an underestimated condition. Liver Int 2016; 36:454-460. [PMID: 26264219 DOI: 10.1111/liv.12936] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Accepted: 07/30/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Obliterative portal venopathy without portal hypertension has been described by a single study in a limited number of patients, thus very little is known about this clinical condition. This study aimed to investigate the prevalence of obliterative portal venopathy and its clinical-pathological correlations in patients with cryptogenic chronic liver test abnormalities without clinical signs of portal hypertension. METHODS We analysed 482 liver biopsies from adults with non-cirrhotic cryptogenic chronic liver disorders and without any clinical signs of portal hypertension, consecutively enrolled in a 5-year period. Twenty cases of idiopathic non-cirrhotic portal hypertension diagnosed in the same period, were included for comparison. Histological findings were matched with clinical and laboratory features. RESULTS Obliterative portal venopathy was identified in 94 (19.5%) of 482 subjects and in all 20 cases of idiopathic non-cirrhotic portal hypertension: both groups shared the entire spectrum of histological changes described in the latter condition. The prevalence of incomplete fibrous septa and nodular regenerative hyperplasia was higher in the biopsies of idiopathic non-cirrhotic portal hypertension (P = 0.006 and P = 0.002), a possible hint of a more advanced stage of the disease. The two groups also shared several clinical laboratory features, including a similar liver function test profile, concomitant prothrombotic conditions and extrahepatic autoimmune disorders. CONCLUSION Obliterative portal venopathy occurs in a substantial proportion of patients with unexplained chronic abnormal liver function tests without portal hypertension. The clinical-pathological profile of these subjects suggests that they may be in an early (non-symptomatic) stage of idiopathic non-cirrhotic portal hypertension.
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Affiliation(s)
- Maria Guido
- Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy
| | - Samantha Sarcognato
- Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy
| | - Aurelio Sonzogni
- Pathology Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Maria Grazia Lucà
- Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Department of Surgical and Gastroenterological Sciences, University Hospital of Padova, Padova, Italy
| | - Stefano Fagiuoli
- Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgical and Gastroenterological Sciences, University Hospital of Padova, Padova, Italy
| | - Marco Pizzi
- Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy
| | - Luciano Giacomelli
- Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy
| | - Guido Colloredo
- Department of Internal Medicine, San Pietro Hospital, Ponte San Pietro, Italy
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47
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EASL Clinical Practice Guidelines: Vascular diseases of the liver. J Hepatol 2016; 64:179-202. [PMID: 26516032 DOI: 10.1016/j.jhep.2015.07.040] [Citation(s) in RCA: 522] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Accepted: 07/20/2015] [Indexed: 12/11/2022]
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48
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Sato Y, Harada K, Sasaki M, Nakanuma Y. Altered intrahepatic microcirculation of idiopathic portal hypertension in relation to glutamine synthetase expression. Hepatol Res 2015; 45:1323-30. [PMID: 25692330 DOI: 10.1111/hepr.12506] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2014] [Revised: 02/09/2015] [Accepted: 02/09/2015] [Indexed: 01/02/2023]
Abstract
AIM Alteration in intrahepatic microcirculation of idiopathic portal hypertension (IPH) has been poorly understood. This study aimed to characterize altered intrahepatic microcirculation of IPH focusing on the expression pattern of glutamine synthetase (GS). METHODS Immunohistochemical staining of GS was performed using liver sections of IPH (n = 28). Serial section analysis was performed to determine microcirculatory disturbances of IPH. RESULTS Paraportal shunt vessels were observed in 20 cases of IPH, and they were divided into two types according to the GS staining pattern; hepatocytes surrounding the vessels were negative for GS (type 1) and positive for GS (type 2). All 20 cases had one or more type 1 vessels within a section, and 10 cases were further associated with type 2 vessels. The cases with type 2 vessels showed infrequent symptoms of esophageal varices. Regarding the GS staining as an indicator of hepatic veins, some type 2 vessels were supposed to represent portovenous shunts. Isolated arteries in hepatic parenchyma were present in 21 cases, and they were located around terminal hepatic venules in six cases, corresponding to centrizonal arteries. Broad hepatocellular GS staining in hyperplastic lesions was noted in five cases, whereas nodular regenerative hyperplasia lacked GS expression. CONCLUSION GS immunostaining revealed microcirculatory disturbances of IPH that were associated with abnormalities in both venous and arterial vessels.
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Affiliation(s)
- Yasunori Sato
- Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
| | - Kenichi Harada
- Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
| | - Motoko Sasaki
- Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
| | - Yasuni Nakanuma
- Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.,Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan
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Lee H, Rehman AU, Fiel MI. Idiopathic Noncirrhotic Portal Hypertension: An Appraisal. J Pathol Transl Med 2015; 50:17-25. [PMID: 26563701 PMCID: PMC4734966 DOI: 10.4132/jptm.2015.09.23] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 09/23/2015] [Indexed: 02/07/2023] Open
Abstract
Idiopathic noncirrhotic portal hypertension is a poorly defined clinical condition of unknown etiology. Patients present with signs and symptoms of portal hypertension without evidence of cirrhosis. The disease course appears to be indolent and benign with an overall better outcome than cirrhosis, as long as the complications of portal hypertension are properly managed. This condition has been recognized in different parts of the world in diverse ethnic groups with variable risk factors, resulting in numerous terminologies and lack of standardized diagnostic criteria. Therefore, although the diagnosis of idiopathic noncirrhotic portal hypertension requires clinical exclusion of other conditions that can cause portal hypertension and histopathologic confirmation, this entity is under-recognized clinically as well as pathologically. Recent studies have demonstrated that variable histopathologic entities with different terms likely represent a histologic spectrum of a single entity of which obliterative portal venopathy might be an underlying pathogenesis. This perception calls for standardization of the nomenclature and formulation of widely accepted diagnostic criteria, which will facilitate easier recognition of this disorder and will highlight awareness of this entity.
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Affiliation(s)
- Hwajeong Lee
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA
| | - Aseeb Ur Rehman
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA
| | - M Isabel Fiel
- Department of Pathology, The Mount Sinai Medical Center, New York, NY, USA
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50
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Sarin SK, Philips CA, Khanna R. Noncirrhotic portal hypertension: Medical and endoscopic management. Clin Liver Dis (Hoboken) 2015; 6:107-111. [PMID: 31041002 PMCID: PMC6490692 DOI: 10.1002/cld.511] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2015] [Accepted: 10/22/2015] [Indexed: 02/04/2023] Open
Affiliation(s)
- S K Sarin
- Department of Hepatology and Transplant Medicine Institute of Liver and Biliary Sciences New Delhi India
| | - Cyriac Abby Philips
- Department of Hepatology and Transplant Medicine Institute of Liver and Biliary Sciences New Delhi India
| | - Rajeev Khanna
- Department of Hepatology and Transplant Medicine Institute of Liver and Biliary Sciences New Delhi India
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