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1
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Liu XC, Yan HH, Wei W, Du Q. Idiopathic portal hypertension misdiagnosed as hepatitis B cirrhosis: A case report and review of the literature. World J Hepatol 2025; 17:100923. [PMID: 40027578 PMCID: PMC11866141 DOI: 10.4254/wjh.v17.i2.100923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 01/10/2025] [Accepted: 01/23/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND Idiopathic portal hypertension (IPH) is a subtype of portal hypertension that arises in the absence of cirrhosis. IPH frequently manifests with clinical features typical of portal hypertension, including splenomegaly and esophagogastric fundal varices, along with other associated symptoms. Imaging studies may indicate portal hypertension; however, they typically do not provide evidence of cirrhosis. There are no standardized diagnostic criteria for IPH, and diagnosis is often established by excluding other hepatic diseases. Liver biopsy remains the most reliable approach to verify the diagnosis of IPH. CASE SUMMARY A patient previously diagnosed with "hepatitis B cirrhosis" at an external hospital presented to our facility with gastrointestinal bleeding. Initial assessment revealed minor liver injury, splenomegaly, esophagogastric varices, and portal hypertension. Imaging studies did not indicate cirrhosis and repeated hepatitis B serology tests yielded negative results. After excluding various causes of cirrhosis and other non-cirrhotic etiologies of portal hypertension, liver biopsy confirmed the diagnosis of IPH. The patient was managed with regular endoscopic therapy and long-term carvedilol administration. CONCLUSION Currently, there are no standardized diagnostic criteria for IPH, and its diagnosis is generally established by excluding other conditions. Liver biopsy remains the most reliable method for IPH diagnosis.
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Affiliation(s)
- Xiao-Chen Liu
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Hui-Hui Yan
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Wei Wei
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Qin Du
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China.
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2
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Bartow BB, Dhall D, Lee G, Garapati M, Patel CR, Al Diffalha S. Nodular regenerative hyperplasia: The role of the CK7 immunohistochemistry pattern of expression in diagnosis. Am J Clin Pathol 2025; 163:196-204. [PMID: 39213447 DOI: 10.1093/ajcp/aqae110] [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: 04/18/2024] [Accepted: 08/07/2024] [Indexed: 09/04/2024] Open
Abstract
OBJECTIVES Nodular regenerative hyperplasia (NRH) is a rare vascular disorder of the liver. Clinically, patients present with portal hypertension with or without a cholestatic pattern of injury. Histologically, the liver parenchyma is composed of small nodules of hypertrophic hepatocytes surrounded by atrophic hepatocytes without significant fibrosis. Nodular regenerative hyperplasia is a difficult diagnosis on biopsy specimens, but biopsy remains the gold standard for diagnosis. In this retrospective review, cytokeratin 7 (CK7) immunohistochemistry (IHC) was used to aid in the diagnosis and further characterization of NRH and NRH-like changes. METHODS The H&E-stained slides, reticulin, and CK IHC were reviewed for 22 cases. The percentage of hepatocytes staining for CK7 (0%-100%), the location of staining (centrilobular hepatic progenitor cells vs periportal/bile ductular reaction), and the pattern of staining distribution (patchy or diffuse) were recorded for comparison. RESULTS Of the 22 cases, 9 were CK7 positive. Cases of NRH, however, expressed various degrees of CK7 positivity in centrilobular hepatic progenitor cells, unlike NRH-like changes, which were either CK7 negative or CK7 positive in periportal hepatocytes or in areas of bile ductular reaction. CONCLUSIONS In cases with the appropriate clinical history and histology, CK7 immunohistochemistry can be performed to distinguish nodular regenerative hyperplasia (primary) and NRH-like changes (secondary). In difficult cases, CK7 positivity in centrilobular hepatic progenitor cells can help confirm the diagnosis of NRH. These data support NRH as a true entity with a distinct pathophysiology from NRH-like changes.
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Affiliation(s)
- Brooke B Bartow
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, US
| | - Deepti Dhall
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, US
| | - Goo Lee
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, US
| | - Manjula Garapati
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, US
| | - Chirag R Patel
- Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, AZ, US
| | - Sameer Al Diffalha
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, US
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3
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Shukla A, Rockey DC, Kamath PS, Kleiner DE, Singh A, Vaidya A, Koshy A, Goel A, Dökmeci AK, Meena B, Philips CA, Sharma CB, Payawal DA, Kim DJ, Lo GH, Han G, Qureshi H, Wanless IR, Jia J, Sollano JD, Al Mahtab M, Muthiah MD, Sonderup MW, Nahum MS, Merican MIB, Ormeci N, Kawada N, Reddy R, Dhiman RK, Gani R, Hameed SS, Harindranath S, Jafri W, Qi X, Chawla YK, Furuichi Y, Zheng MH, Sarin SK. Non-cirrhotic portal fibrosis/idiopathic portal hypertension: APASL recommendations for diagnosis and management. Hepatol Int 2024; 18:1684-1711. [PMID: 39546143 DOI: 10.1007/s12072-024-10739-6] [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: 06/17/2024] [Accepted: 09/28/2024] [Indexed: 11/17/2024]
Abstract
Since the Asian Pacific Association for the Study of the Liver (APASL) published guidelines on non-cirrhotic portal fibrosis/idiopathic portal hypertension in 2007, there has been a surge in new information, especially with the introduction of the term porto-sinusoidal vascular disorder (PSVD). Non-cirrhotic intra-hepatic causes of portal hypertension include disorders with a clearly identifiable etiology, such as schistosomiasis, as well as disorders with an unclear etiology such as non-cirrhotic portal fibrosis (NCPF), also termed idiopathic portal hypertension (IPH). This entity is being increasingly recognized as being associated with systemic disease and drug therapy, especially cancer therapy. An international working group with extensive expertise in portal hypertension was assigned with formulating consensus guidelines to clarify the definition, diagnosis, histological features, natural history, and management of NCPF/IPH, especially in the context of PSVD. The guidelines were prepared based on evidence from existing published literature. Whenever there was paucity of evidence, expert opinion was included after detailed deliberation. The goal of this manuscript, therefore, is to enhance the current understanding and help create global consensus on the issues surrounding NCPF/IPH.
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Affiliation(s)
- Akash Shukla
- Department of Gastroenterology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India
| | - Don C Rockey
- Digestive Disease Research Center, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 803, MSC 623, Charleston, SC, 29425, USA
| | | | | | - Ankita Singh
- Department of Gastroenterology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India
| | - Arun Vaidya
- Department of Gastroenterology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India
| | - Abraham Koshy
- Department of Gastroenterology, VPS Lakeshore Hospital, Kochi, Kerala, India
| | - Ashish Goel
- Department of Hepatology, CMC, Vellore, India
| | - A Kadir Dökmeci
- Department of Medicine, Ankara University School of Medicine, Ankara, Turkey
| | - Babulal Meena
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Cyriac Abby Philips
- Department of Clinical and Translational Hepatology, The Liver Institute, Rajagiri Hospital, Aluva, Kerala, India
| | - Chhagan Bihari Sharma
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Diana A Payawal
- Fatima University Medical Center Manila, Manila, Philippines
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Seoul, South Korea
| | - Gin-Ho Lo
- Department of Medical Research, E-Da Hospital, Kaohsiung, School of Medicine for International Students, I-Shou University, 1, Yi-Da Road, Kaohsiung, 824, Taiwan
| | - Guohong Han
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | | | - Ian R Wanless
- Department of Pathology, Dalhousie University, Halifax, Canada
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Beijing, Mainland, China
| | - Jose D Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Mark Dhinesh Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Mark W Sonderup
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Mendez Sanchez Nahum
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | | | - Necati Ormeci
- İstanbul Health and Technology University, Istanbul, Turkey
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan
| | - Rajender Reddy
- Division of Gastroenterology and Hepatology, 2 Dulles, Liver Transplant Office, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
| | - R K Dhiman
- Department of Hepatology, PGIMER, Chandigarh, India
| | - Rino Gani
- Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Saeed S Hameed
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - Sidharth Harindranath
- Department of Gastroenterology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India
| | - Wasim Jafri
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - Xiaolong Qi
- Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China
| | - Yogesh Kumar Chawla
- Department of Hepatology and Gastroenterology, Kalinga Institute of MedicalSciences, KIIT University, Bhubaneshwar, India
| | - Yoshihiro Furuichi
- Department of Clinical Laboratory and Endoscopy, Tokyo Women's Medical University, Adachi Medical Center, Tokyo, Japan
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
- Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, 325000, China
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
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Liu J, Zhang Q, Liu Y, Ma HX, Han X, Ma Y, Zhao LL, Li J. Porto-Sinusoidal Vascular Disease: A New Nomenclature Different from Idiopathic Non-Cirrhotic Portal Hypertension. Diagnostics (Basel) 2024; 14:2053. [PMID: 39335732 PMCID: PMC11431266 DOI: 10.3390/diagnostics14182053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 09/10/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND AND AIMS Porto-sinusoidal vascular disease (PSVD) as a novel clinical conception was modified on the basis of idiopathic non-cirrhotic portal hypertension (INCPH). This study aimed to compare the clinical, biochemical histological features and prognosis between the diagnostic criteria for PSVD and that of INCPH. METHODS A total of 65 patients who underwent liver biopsies were analyzed retrospectively. The clinical, pathological and prognosis date were reviewed and screened according to the latest diagnostic criteria of PSVD and INCPH. RESULTS A total of 65 patients were diagnosed with PSVD, of which 31 (47.69%) also fulfilled INCPH criteria. Specific histological and specific clinical portal hypertension (PH) signs were found in 34 (52.31%) and 30 (46.15%) of the patients, respectively. PSVD patients showed higher LSM levels (11.45 (6.38, 18.08) vs. 7.90 (6.70, 13.00), p = 0.039) than the INCPH patients. INCPH patients had a higher cumulative incidence of liver-related complications than the PSVD patients (86.95% vs. 35.71%, log-rank p < 0.001). CONCLUSION Novel PSVD criteria facilitate early diagnosis. PSVD patients with other liver diseases may have higher LSM values. Disease progression and survival outcomes are correlated with PH in PSVD patients.
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Affiliation(s)
- Jie Liu
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
| | - Qian Zhang
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Yao Liu
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin 300070, China
| | - Hai-Xia Ma
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
| | - Xu Han
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
| | - Ying Ma
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
| | - Li-Li Zhao
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
| | - Jia Li
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
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Tonutti A, Pugliese N, Ceribelli A, Isailovic N, De Santis M, Colapietro F, De Nicola S, Polverini D, Selmi C, Aghemo A. The autoimmune landscape of Porto-sinusoidal vascular disorder: What the rheumatologist needs to know. Semin Arthritis Rheum 2024; 67:152467. [PMID: 38805899 DOI: 10.1016/j.semarthrit.2024.152467] [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: 02/22/2024] [Revised: 04/23/2024] [Accepted: 04/29/2024] [Indexed: 05/30/2024]
Abstract
Porto-sinusoidal vascular disorder (PSVD) encompasses a group of vascular disorders characterized by lesions of the portal venules and sinusoids with clinical manifestations ranging from non-specific abnormalities in serum liver enzymes to clinically overt portal hypertension and related complications. Several reports have documented cases of PSVD in patients with systemic autoimmune conditions, such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. It is of note that these diseases share specific pathophysiological features with PSVD, including endothelial dysfunction, vascular inflammation, and molecular signatures. This narrative review aims to summarize the current knowledge on the association between PSVD and systemic autoimmune diseases, emphasizing the importance of promptly recognizing this condition in the rheumatological practice, and highlighting the key aspects where further research is necessary from both pathogenic and clinical perspectives.
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Affiliation(s)
- Antonio Tonutti
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Angela Ceribelli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Natasa Isailovic
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Maria De Santis
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Francesca Colapietro
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Stella De Nicola
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Davide Polverini
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Carlo Selmi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy.
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
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6
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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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Martín CA, Cuevas CM, Rubiales BM, Ruiz MV, Antolín GS. Hipertensión portal no cirrótica. MEDICINE - PROGRAMA DE FORMACIÓN MÉDICA CONTINUADA ACREDITADO 2024; 14:660-671. [DOI: 10.1016/j.med.2024.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Hirose K, Toshima T, Tobo T, Kai S, Hirakawa M, Higuchi S, Ofuchi T, Hosoda K, Yonemura Y, Hisamatsu Y, Masuda T, Aishima S, Mimori K. A rare case of liver regenerative and non-neoplastic lesion resembling a well-differentiated hepatocellular carcinoma. Surg Case Rep 2024; 10:30. [PMID: 38300348 PMCID: PMC10834926 DOI: 10.1186/s40792-024-01820-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 01/11/2024] [Indexed: 02/02/2024] Open
Abstract
BACKGROUND Nodular regenerative hyperplasia (NRH) is a rare disease that presents pathologically as diffuse hepatic nodules without fibrous septa. It is believed to be caused by vasculopathy against a background of various systemic diseases, such as hematologic, autoimmune, and drug-induced diseases, with various symptoms. In spite of the recent imaging advances, various atypical cases of nodular lesions are observed in daily clinical practice. Cases that do not completely meet these criteria are referred to as -like or -similar lesions in clinical situations, making it difficult to understand their pathogenesis. We present a case in which two hepatic nodular lesions were noted and difficult to differentiate from malignancy preoperatively. The lesions were laparoscopically resected and a pathological diagnosis with non-neoplastic liver regenerative nodules resembling NRH was made. CASE PRESENTATION A 49-year-old man with no alcohol or drug intake and no past medical history was identified as having liver tumors on screening examination without any symptoms. Contrast-enhanced computed tomography (CT) showed two hepatic tumors; approximately 2-cm tumors at S7 and S8. Gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) revealed fat inclusions in their contents. Ethoxybenzyl (EOB) uptake was also observed during the hepatobiliary phase. Based on preoperative examinations, we suspected well-differentiated hepatocellular carcinoma (HCC) and performed laparoscopic S7/8 partial resection for these lesions. Macroscopically, the resected specimens showed a non-cirrhotic yellowish-cut surface containing brownish, ill-defined lesions with irregular borders. Microscopically, these lesions showed zonal necrosis, congestion, and aggregation of hemosiderin-laden macrophages around the central vein. In these areas, the fatty deposition of hepatocytes was lower than that in the surrounding background hepatocytes. Histopathologically, neither neoplastic nor hyperplastic lesions were observed, and he was diagnosed as regenerative hepatic change with centrilobular necrosis. CONCLUSIONS Considering the pathological results, these lesions were thought to be a type of NRH-like lesion with possible hepatic vessel disorder. However, the lesion's cause and classification was difficult to determine. The accumulation of these regenerative changes accompanying fatty liver is needed to clarify the mechanism and its clinical significance.
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Affiliation(s)
- Kosuke Hirose
- Department of Surgery, Kyushu University Beppu Hospital, 4546, Shoen, Beppu-Shi, Oita-Ken, 874-0838, Japan
| | - Takeo Toshima
- Department of Surgery, Kyushu University Beppu Hospital, 4546, Shoen, Beppu-Shi, Oita-Ken, 874-0838, Japan
| | - Taro Tobo
- Department of Pathology, Kyushu University Beppu Hospital, 4546, Shoen, Beppu-Shi, Oita-Ken, 874-0838, Japan
| | - Satohiro Kai
- Department of Radiology, Kyushu University Beppu Hospital, 4546, Shoen, Beppu-Shi, Oita-Ken, 874-0838, Japan
| | - Masakazu Hirakawa
- Department of Radiology, Kyushu University Beppu Hospital, 4546, Shoen, Beppu-Shi, Oita-Ken, 874-0838, Japan
| | - Satoshi Higuchi
- Department of Surgery, Kyushu University Beppu Hospital, 4546, Shoen, Beppu-Shi, Oita-Ken, 874-0838, Japan
| | - Takashi Ofuchi
- Department of Surgery, Kyushu University Beppu Hospital, 4546, Shoen, Beppu-Shi, Oita-Ken, 874-0838, Japan
| | - Kiyotaka Hosoda
- Department of Surgery, Kyushu University Beppu Hospital, 4546, Shoen, Beppu-Shi, Oita-Ken, 874-0838, Japan
| | - Yusuke Yonemura
- Department of Surgery, Kyushu University Beppu Hospital, 4546, Shoen, Beppu-Shi, Oita-Ken, 874-0838, Japan
| | - Yuichi Hisamatsu
- Department of Surgery, Kyushu University Beppu Hospital, 4546, Shoen, Beppu-Shi, Oita-Ken, 874-0838, Japan
| | - Takaaki Masuda
- Department of Surgery, Kyushu University Beppu Hospital, 4546, Shoen, Beppu-Shi, Oita-Ken, 874-0838, Japan
| | - Shinichi Aishima
- Department of Pathology and Microbiology, Saga University, Nabeshima 5-1-1, Saga, 849-8501, Japan
| | - Koshi Mimori
- Department of Surgery, Kyushu University Beppu Hospital, 4546, Shoen, Beppu-Shi, Oita-Ken, 874-0838, Japan.
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9
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Fiordaliso M, Marincola G, Pala B, Muraro R, Mazzone M, Di Marcantonio MC, Mincione G. A Narrative Review on Non-Cirrohotic Portal Hypertension: Not All Portal Hypertensions Mean Cirrhosis. Diagnostics (Basel) 2023; 13:3263. [PMID: 37892084 PMCID: PMC10606323 DOI: 10.3390/diagnostics13203263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 10/17/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
Non-cirrhotic portal hypertension (NCPH), also known as idiopathic non-cirrhotic portal hypertension (INCPH) and porto-sinusoidal vascular disorder (PSVD), is a rare disease characterized by intrahepatic portal hypertension (IPH) in the absence of cirrhosis. The precise etiopathogenesis of IPH is an area of ongoing research. NCPH diagnosis is challenging, as there are no specific tests available to confirm the disease, and a high-quality liver biopsy, detailed clinical information, and an expert pathologist are necessary for diagnosis. Currently, the treatment of NCPH relies on the prevention of complications related to portal hypertension, following current guidelines of cirrhotic portal hypertension. No treatment has been studied that aimed to modify the natural history of the disease; however, transjugular intrahepatic porto-systemic shunt (TIPS) placement, shunt and liver transplantation are considerable symptomatic options. In this review, we discuss the heterogeneity of NCPH as well as its etiopathogenesis, clinical presentation and management issues. Starting from the assumption that portal hypertension does not always mean cirrhosis, cooperative studies are probably needed to clarify the issues of etiology and the possible genetic background of this rare disease. This knowledge might lead to better treatment and perhaps better prevention.
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Affiliation(s)
- Michele Fiordaliso
- Department of Medicine and Ageing Sciences, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy;
| | - Giuseppe Marincola
- Bariatric and Metabolic Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy;
| | - Barbara Pala
- Division of Cardiology, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Via di Grottarossa, 1035/1039, 00189 Rome, Italy;
| | - Raffaella Muraro
- Department of Innovative Technologies in Medicine & Dentistry, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (R.M.); (M.M.); (M.C.D.M.)
| | - Mariangela Mazzone
- Department of Innovative Technologies in Medicine & Dentistry, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (R.M.); (M.M.); (M.C.D.M.)
| | - Maria Carmela Di Marcantonio
- Department of Innovative Technologies in Medicine & Dentistry, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (R.M.); (M.M.); (M.C.D.M.)
| | - Gabriella Mincione
- Department of Innovative Technologies in Medicine & Dentistry, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (R.M.); (M.M.); (M.C.D.M.)
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10
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Biesterveld BE, Schroder PM, Hitchcock ME, Bolognese A, Kim SC, Al-Adra DP. Nodular regenerative hyperplasia and liver transplantation: a systematic review. FRONTIERS IN TRANSPLANTATION 2023; 2:1221765. [PMID: 38993905 PMCID: PMC11235372 DOI: 10.3389/frtra.2023.1221765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 08/17/2023] [Indexed: 07/13/2024]
Abstract
Nodular regenerative hyperplasia (NRH) is a primary disease of the liver that may cause noncirrhotic portal hypertension. Common causes include autoimmune, hematologic, immune deficiency, and myeloproliferative disorders. Given the limited data regarding the development of NRH in contemporary immunosuppressive protocols and the occurrence of NRH post-liver transplantation, we systematically reviewed NRH as it pertains to liver transplantation. We performed a comprehensive search for NRH and transplantation. Nineteen studies were identified with relevant data for NRH as an indication for a liver transplant. Thirteen studies were identified with relevant data pertaining to NRH development after liver transplant. Pooled analysis revealed 0.9% of liver transplant recipients had NRH. A total of 113 patients identified with NRH underwent liver transplantation. Most series report transplants done after the failure of endoscopic banding and TIPS management of portal hypertension. Reported 5-year graft and patient survival ranged from 73%-78% and 73%-90%. The pooled incidence of NRH after liver transplant for all indications was 2.9% and caused complications of portal hypertension. Complications related to portal hypertension secondary to NRH are a rare indication for a liver transplant. NRH can develop at any time after liver transplantation often without an identifiable cause, which may lead to portal hypertension requiring treatment or even re-transplantation.
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Affiliation(s)
- Ben E. Biesterveld
- Department of Transplant Surgery, University of Wisconsin, Madison, WI, United States
| | - Paul M. Schroder
- Department of Transplant Surgery, University of Wisconsin, Madison, WI, United States
| | | | - Alexandra Bolognese
- Division of Abdominal Organ Transplantation, Oregon Health & Science University School of Medicine, Portland, OR, United States
| | - Steven C. Kim
- Department of Surgery, Division of Transplantation, Emory University, Atlanta, GA, United States
| | - David P. Al-Adra
- Department of Transplant Surgery, University of Wisconsin, Madison, WI, United States
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11
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Massive splenomegaly and thrombocytopenia in pregnancy. Pathology 2022; 55:576-578. [PMID: 36503637 DOI: 10.1016/j.pathol.2022.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 09/20/2022] [Accepted: 09/28/2022] [Indexed: 11/24/2022]
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12
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Lima FMS, Toledo-Barros M, Alves VAF, Duarte MIS, Takakura C, Bernardes-Silva CF, Marinho AKBB, Grecco O, Kalil J, Kokron CM. Liver disease accompanied by enteropathy in common variable immunodeficiency: Common pathophysiological mechanisms. Front Immunol 2022; 13:933463. [PMID: 36341360 PMCID: PMC9632424 DOI: 10.3389/fimmu.2022.933463] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 09/29/2022] [Indexed: 11/16/2022] Open
Abstract
Common variable immunodeficiency (CVID) is one of the inborn errors of immunity that have the greatest clinical impact. Rates of morbidity and mortality are higher in patients with CVID who develop liver disease than in those who do not. The main liver disorder in CVID is nodular regenerative hyperplasia (NRH), the cause of which remains unclear and for which there is as yet no treatment. The etiology of liver disease in CVID is determined by analyzing the liver injury and the associated conditions. The objective of this study was to compare CVID patients with and without liver–spleen axis abnormalities in terms of clinical characteristics, as well as to analyze liver and duodenal biopsies from those with portal hypertension (PH), to elucidate the pathophysiology of liver injury. Patients were divided into three groups: Those with liver disease/PH, those with isolated splenomegaly, and those without liver–spleen axis abnormalities. Clinical and biochemical data were collected. Among 141 CVID patients, 46 (32.6%) had liver disease/PH; 27 (19.1%) had isolated splenomegaly; and 68 (48.2%) had no liver–spleen axis abnormalities. Among the liver disease/PH group, patients, even those with mild or no biochemical changes, had clinical manifestations of PH, mainly splenomegaly, thrombocytopenia, and esophageal varices. Duodenal celiac pattern was found to correlate with PH (p < 0.001). We identified NRH in the livers of all patients with PH (n = 11). Lymphocytic infiltration into the duodenal mucosa also correlated with PH. Electron microscopy of liver biopsy specimens showed varying degrees of lymphocytic infiltration and hepatocyte degeneration, which is a probable mechanism of lymphocyte-mediated cytotoxicity against hepatocytes and enterocytes. In comparison with the CVID patients without PH, those with PH were more likely to have lymphadenopathy (p < 0.001), elevated β2-microglobulin (p < 0.001), low B-lymphocyte counts (p < 0.05), and low natural killer-lymphocyte counts (p < 0.05). In CVID patients, liver disease/PH is common and regular imaging follow-up is necessary. These patients have a distinct immunological phenotype that may predispose to liver and duodenal injury from lymphocyte-mediated cytotoxicity. Further studies could elucidate the cause of this immune-mediated mechanism and its treatment options.
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Affiliation(s)
- Fabiana Mascarenhas Souza Lima
- Division of Clinical Immunology and Allergy, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- *Correspondence: Fabiana Mascarenhas Souza Lima,
| | - Myrthes Toledo-Barros
- Division of Clinical Immunology and Allergy, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Maria Irma Seixas Duarte
- Laboratory of the Discipline of Pathology of Transmissible Diseases, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Cleusa Takakura
- Laboratory of the Discipline of Pathology of Transmissible Diseases, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Carlos Felipe Bernardes-Silva
- Department of Gastroenterology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Octavio Grecco
- Division of Clinical Immunology and Allergy, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Jorge Kalil
- Division of Clinical Immunology and Allergy, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- iii-Institute for Investigation in Immunology, Instituto Nacional de Ciência e Tecnologia (INCT), Sao Paulo, Brazil
| | - Cristina Maria Kokron
- Division of Clinical Immunology and Allergy, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
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13
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Özcan HN, Karçaaltıncaba M, Seber T, Yalçın B, Oğuz B, Akyüz C, Haliloğlu M. Hepatocyte-specific contrast-enhanced MRI findings of focal nodular hyperplasia-like nodules in the liver following chemotherapy in pediatric cancer patients. ACTA ACUST UNITED AC 2021; 26:370-376. [PMID: 32490830 DOI: 10.5152/dir.2019.19398] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
PURPOSE We aimed to assess the MRI findings and follow-up of multiple focal nodular hyperplasia (FNH)- like lesions in pediatric cancer patients diagnosed by imaging findings. METHODS We retrospectively analyzed clinical data and MRI examinations of 16 pediatric patients, who had been scanned using gadoxetate disodium (n=13) and gadobenate dimeglumine (n=3). Hepatic nodules were reviewed according to their number, size, contour, T1- and T2-weighted signal intensities, arterial, portal, delayed and hepatobiliary phase enhancement patterns. Follow-up images were evaluated for nodule size, number, and appearance. RESULTS All 16 patients received chemotherapy in due course. Time interval between the initial diagnosis of cancer and detection of the hepatic nodule was 2-14 years. Three patients had a single lesion, 13 patients had multiple nodules. The median size of the largest nodules was 19.5 mm (range, 8-41 mm). Among 16 patients that received hepatocyte-specific agents, FNH-like nodules appeared hyperintense in 11 and isointense in 5 on the hepatobiliary phase. During follow-up, increased number and size of the nodules were seen in 4 patients. The nodules showed growth between 6-15 mm. CONCLUSION Liver MRI using hepatocyte-specific agents is a significant imaging method for the diagnosis of FNH-like lesions, which can occur in a variety of diseases. Lesions can increase in size and number in pediatric patients.
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Affiliation(s)
- H Nursun Özcan
- Department of Radiology, Hacettepe University School of Medicine, Ankara, Turkey
| | | | - Turgut Seber
- Department of Radiology, Kayseri City Hospital, Kayseri, Turkey
| | - Bilgehan Yalçın
- Department of Pediatrics, Division of Pediatric Oncology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Berna Oğuz
- Department of Radiology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Canan Akyüz
- Department of Pediatrics, Division of Pediatric Oncology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Mithat Haliloğlu
- Department of Radiology, Hacettepe University School of Medicine, Ankara, Turkey
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14
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Benguerfi S, Diéras V, Campone M, Mosnier JF, Robert M. Regenerative nodular hyperplasia after T-DM1: consequences from sinusoidal endothelium damages. Acta Oncol 2020; 59:306-309. [PMID: 31556755 DOI: 10.1080/0284186x.2019.1670860] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Affiliation(s)
- Soraya Benguerfi
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
| | - Véronique Diéras
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
| | - Mario Campone
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest - René Gauducheau, Saint Herblain, France
| | | | - Marie Robert
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest - René Gauducheau, Saint Herblain, France
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15
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Bayoumy AB, Simsek M, Seinen ML, Mulder CJJ, Ansari A, Peters GJ, De Boer NK. The continuous rediscovery and the benefit-risk ratio of thioguanine, a comprehensive review. Expert Opin Drug Metab Toxicol 2020; 16:111-123. [PMID: 32090622 DOI: 10.1080/17425255.2020.1719996] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Introduction: In the 1950s, thioguanine (TG), a thiopurine-derivative together with azathioprine (AZA) and mercaptopurine (MP), were developed for the treatment of childhood leukemia. Over the years, the use of TG was also explored for other, mainly immune-mediated and inflammatory, diseases such as in the field of dermatology and rheumatology (e.g. psoriasis, systemic lupus erythematosus (SLE)) and gastroenterology and hepatology (e.g. inflammatory bowel diseases (IBD), autoimmune hepatitis).Areas covered: This review provides a comprehensive overview of all the clinical uses of TG and describes its mechanism of action, pharmacokinetic/pharmacodynamic features, and toxicity.Expert opinion: Thioguanine has shown beneficial clinical effects in hematological (particularly leukemia) and several immune-inflammatory diseases including psoriasis, SLE, polycythemia vera, Churg-Strauss syndrome, IBD, collagenous sprue, refractory celiac disease, and autoimmune hepatitis. Thioguanine is not effective in treating solid-cancers. At relatively low dosages, i.e. 0.2- 0.3mg/kg/day or 20 mg/day, TG has a favorable risk-benefit ratio and is a safe and effective drug in the long-term treatment of amongst other IBD patients. Thioguanine toxicity, especially myelotoxicity, and hepatotoxicity, including nodular regenerative hyperplasia (NRH) of the liver, is limited when dosed adequately. The occurrence of NRH appears dose-dependent and has been especially described during high dose TG above 40 mg/day.
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Affiliation(s)
- Ahmed B Bayoumy
- Amsterdam UMC, Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, Netherlands
| | - Melek Simsek
- Amsterdam UMC, Department of Gastroenterology and Hepatology, VU University Medical Center, AG&M Research Institute, Amsterdam, Netherlands
| | - Margien L Seinen
- Amsterdam UMC, Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, Netherlands
| | - Chris J J Mulder
- Amsterdam UMC, Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, Netherlands
| | - Azhar Ansari
- Department of Gastroenterology, Surrey and Sussex NHS, Easy Surrey Hospital, Surrey, UK
| | - Godefridus J Peters
- Amsterdam UMC, VU University Medical Center, Laboratory Medical Oncology, Cancer Center Amsterdam, Amsterdam, Netherlands.,Department of Biochemistry, Medical University of Gdansk, Gdansk, Poland
| | - Nanne K De Boer
- Amsterdam UMC, Department of Gastroenterology and Hepatology, VU University Medical Center, AG&M Research Institute, Amsterdam, Netherlands
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16
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Bakshi N, Gulati N, Rastogi A, Chougule A, Bihari C, Jindal A. Nodular regenerative hyperplasia - An under-recognized vascular disorder of liver. Pathol Res Pract 2020; 216:152833. [PMID: 32164988 DOI: 10.1016/j.prp.2020.152833] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 12/24/2019] [Accepted: 01/18/2020] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Nodular regenerative hyperplasia (NRH) is a rare hepatic vascular disorder which is often associated with wide variety of systemic diseases. Intrahepatic microvascular injury and subsequent altered perfusion state leads to development of non-cirrhotic portal hypertension in many of these patients. Diagnosis of NRH often remains unsuspected clinically and liver biopsy is essential for the diagnosis and exclusion of fibrosis. We herein, present clinicopathological features of 22 NRH cases. In addition we assessed CK7 and CD34 expression in hepatocytes and sinusoidal endothelial cells respectively. RESULTS Most of the cases were associated with systemic disorders, predominantly immunological, inflammatory and drug-related injuries. Signs and symptoms of portal hypertension were found in 86.4 % patients. Majority of the patients showed a predominant mild cholestatic pattern of liver function tests. Nearly all the (21/22) cases showed CK7 positivity in centrizonal hepatocytes which ranged from <10 % cells to diffuse perivenular positivity extending into the midzonal areas. CD34 positivity in sinusoidal endothelial cells was seen in all the cases, which was prominent in periportal areas in all cases; while perivenular (n = 20) and midzonal (n = 14) areas also showed CD34 positive sinusoidal endothelial cells. CONCLUSION This study highlights the role of pathologist in the diagnosis of NRH and stresses upon the need for awareness of NRH as a cause of unexplained portal hypertension in patients with underlying systemic diseases. The altered perfusion state in NRH leads to phenotypic shift in centrizonal atrophic hepatocytes and sinusoidal endothelial cells (as depicted by IHC) which may be responsible for development of portal hypertension.
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Affiliation(s)
- Neha Bakshi
- Department of Pathology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India.
| | - Natasha Gulati
- Department of Pathology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India.
| | - Abhijit Chougule
- Department of Pathology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India
| | - Chhagan Bihari
- Department of Pathology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India.
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India
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17
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Simsek M, Meijer B, Ramsoekh D, Bouma G, van der Wouden EJ, den Hartog B, de Vries AC, Hoentjen F, Dijkstra G, de Boer SY, Jansen JM, van der Meulen AE, Beukers R, Brink MA, Steinhauser T, Oldenburg B, Gilissen LP, Naber TH, Verhagen MA, de Boer NKH, Mulder CJJ. Clinical Course of Nodular Regenerative Hyperplasia in Thiopurine Treated Inflammatory Bowel Disease Patients. Clin Gastroenterol Hepatol 2019; 17:568-570. [PMID: 29775790 DOI: 10.1016/j.cgh.2018.05.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Revised: 04/04/2018] [Accepted: 05/07/2018] [Indexed: 02/07/2023]
Abstract
Nodular regenerative hyperplasia (NRH) is a poorly understood liver condition, which is increasingly recognized in thiopurine-treated patients with inflammatory bowel disease (IBD).1 It is difficult to establish an optimal approach to NRH patients, because its manifestations are highly variable (from asymptomatic to symptoms of noncirrhotic portal hypertension [NCPH]) and the prognosis is unknown.2 The aim of this study was to identify NRH cases in IBD patients treated with azathioprine, mercaptopurine, and/or thioguanine, and to describe its clinical course.
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Affiliation(s)
- Melek Simsek
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
| | - Berrie Meijer
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands
| | - Dewkoemar Ramsoekh
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands
| | - Gerd Bouma
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands
| | | | - Bert den Hartog
- Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, The Netherlands
| | - Annemarie C de Vries
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Frank Hoentjen
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University Medical Center and University of Groningen, Groningen, The Netherlands
| | - Sybrand Y de Boer
- Department of Gastroenterology and Hepatology, Slingeland Hospital, Doetinchem, The Netherlands
| | - Jeroen M Jansen
- Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - Andrea E van der Meulen
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Ruud Beukers
- Department of Gastroenterology and Hepatology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - Menno A Brink
- Department of Gastroenterology and Hepatology, Meander Medical Center, Amersfoort, The Netherlands
| | - Toos Steinhauser
- Department of Gastroenterology and Hepatology, Bravis Hospital, Roosendaal, The Netherlands
| | - Bas Oldenburg
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Lennard P Gilissen
- Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, The Netherlands
| | - Ton H Naber
- Department of Gastroenterology and Hepatology, Tergooi Hospital, Hilversum, The Netherlands
| | - Marc A Verhagen
- Department of Gastroenterology and Hepatology, Diakonessen Hospital, Utrecht, The Netherlands
| | - Nanne K H de Boer
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands
| | - Chris J J Mulder
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands
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18
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Refractory Hepatic Hydrothorax: A Rare Complication of Systemic Sclerosis and Presinusoidal Portal Hypertension. Case Reports Hepatol 2018; 2018:2704949. [PMID: 29854501 PMCID: PMC5952433 DOI: 10.1155/2018/2704949] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 03/22/2018] [Indexed: 01/15/2023] Open
Abstract
We report on a rare case of refractory hepatic hydrothorax in an individual with Scleroderma/CREST syndrome and noncirrhotic portal hypertension. Portal pressure measurements revealed a normal transjugular hepatic venous portal pressure gradient, mild pulmonary hypertension, and an unremarkable liver biopsy except for mild sinusoidal dilation. Pulmonary hypertension, cardiac diastolic dysfunction, and chronic kidney disease were determined to be the causes of his refractory pleural effusions and ascites. Over the year, he underwent 50 thoracenteses and 20 paracenteses averaging 10-12 liters/week. Repeat pulmonary evaluation determined his pulmonary pressures to be normal and a secondary review of the "unremarkable" liver biopsy noted mild venous outflow obstruction and possibly Nodular Regenerative Hyperplasia (NRH). Repeat portal pressures indirectly and directly confirmed the existence of presinusoidal portal hypertension that has been associated with NRH. A transjugular intrahepatic portal systemic shunt (TIPS) was placed and he has not required thoracentesis or paracentesis over the past 18 months.
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19
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Abstract
The evaluation of liver biopsies in suspected drug-induced liver injury (DILI) can be complex. The biopsy may be approached systematically, by identification of histologic lesions and then identification of the overall pattern of injury. Potential DILI must be separated from concomitant non-DILI liver disease. The findings can be analyzed with respect to the various prescription and nonprescription medications and dietary supplements under suspicion to provide a complete interpretation of the findings. The pathologic findings, the histologic differential diagnosis, and expert interpretation are part of a complete biopsy assessment and provide information that is of greatest value in patient management.
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Affiliation(s)
- David E Kleiner
- Laboratory of Pathology, National Cancer Institute, 10 Center Drive, Building 10, Room 2S235, MSC 1500, Bethesda, MD 20892, USA.
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20
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Lee M, Izzy M, Akki A, Tanaka K, Kalia H. Nodular Regenerative Hyperplasia: A Case of Rare Prognosis. J Investig Med High Impact Case Rep 2017; 5:2324709617690742. [PMID: 28491877 PMCID: PMC5405903 DOI: 10.1177/2324709617690742] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2016] [Revised: 11/23/2016] [Accepted: 12/05/2016] [Indexed: 11/17/2022] Open
Abstract
Introduction: Nodular regenerative hyperplasia (NRH) is a known etiology of noncirrhotic portal hypertension. Cases of biopsy-proven NRH in human immunodeficiency virus (HIV)-positive patients have been described. While these patients often have normal synthetic liver function, several reports described disease progression to liver failure. Case: We here present a 26-year-old woman with history of congenital HIV on antiretroviral therapy complicated by Pneumocystis carinii pneumonia at age 14. CD4 counts have been >300 with undetectable viral load. She was referred to our Hepatology service for evaluation of splenomegaly, elevated liver tests, and thrombocytopenia. On initial presentation, she reported easy bruising and gingival bleeding, and abdominal imaging showed evidence of portal hypertension without associated cirrhosis. Upper endoscopy was significant for large esophageal varices without bleeding stigmata. Liver biopsy showed minimal fibrosis around the portal areas without significant inflammation. The lobules showed focal zones of thin hepatocyte plates on reticulin stain with adjacent areas showing mild regenerative changes. The diagnosis of NRH was made and patient was placed on propranolol for variceal bleeding prophylaxis. Two years later, the patient presented with bleeding gastric varices warranting transjugular intrahepatic portosystemic shunt. Postprocedure course was complicated by mild encephalopathy. Subsequent magnetic resonance imaging showed a 1.7 × 1.3 cm lesion suggestive of hepatocellular carcinoma (HCC). The patient was deemed to be a candidate for liver transplantation, and she is now delisted due to ongoing pregnancy. Conclusion: This report describes the first case of HCC in an HIV patient with NRH. The possible association of NRH with HCC warrants further investigation.
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Affiliation(s)
- Mindy Lee
- Division of Gastroenterology and Liver diseases, Montefiore Medical Center, The Albert Einstein College of Medicine Bronx, NY, USA
| | - Manhal Izzy
- Division of Gastroenterology and Liver diseases, Montefiore Medical Center, The Albert Einstein College of Medicine Bronx, NY, USA
| | - Ashwin Akki
- Division of Surgical Pathology, Montefiore Medical Center, The Albert Einstein College of Medicine Bronx, NY, USA
| | - Kathryn Tanaka
- Division of Surgical Pathology, Montefiore Medical Center, The Albert Einstein College of Medicine Bronx, NY, USA
| | - Harmit Kalia
- Division of Gastroenterology and Liver diseases, Montefiore Medical Center, The Albert Einstein College of Medicine Bronx, NY, USA
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21
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Milligan KL, Schirm K, Leonard S, Hussey AA, Agharahimi A, Kleiner DE, Fuss I, Lingala S, Heller T, Rosenzweig SD. Ataxia telangiectasia associated with nodular regenerative hyperplasia. J Clin Immunol 2016; 36:739-742. [PMID: 27671921 DOI: 10.1007/s10875-016-0334-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Accepted: 09/05/2016] [Indexed: 01/22/2023]
Affiliation(s)
- Ki L Milligan
- Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, MD, USA.,Primary Immunodeficiency Clinic, NIAID, NIH, Building 10, Room 2C410, 10 Center Drive, Bethesda, MD, 20892, USA
| | - Karen Schirm
- Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, MD, USA
| | - Stephanie Leonard
- Division of Allergy and Immunology, University of California, San Diego, Rady Children's Hospital, San Diego, CA, USA
| | - Ashleigh A Hussey
- Primary Immunodeficiency Clinic, NIAID, NIH, Building 10, Room 2C410, 10 Center Drive, Bethesda, MD, 20892, USA
| | - Anahita Agharahimi
- Primary Immunodeficiency Clinic, NIAID, NIH, Building 10, Room 2C410, 10 Center Drive, Bethesda, MD, 20892, USA
| | | | - Ivan Fuss
- Mucosal Immunity Section, NIAID NIH, Bethesda, MD, USA
| | | | - Theo Heller
- Liver Diseases Branch, NIDDK, NIH, Bethesda, MD, USA
| | - Sergio D Rosenzweig
- Primary Immunodeficiency Clinic, NIAID, NIH, Building 10, Room 2C410, 10 Center Drive, Bethesda, MD, 20892, USA. .,Immunology Service, Department of Laboratory Medicine, Clinical Center, NIH, Building 10, Room 2C410, 10 Center Drive, Bethesda, MD, 20892, USA.
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22
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Riggio O, Gioia S, Pentassuglio I, Nicoletti V, Valente M, d’Amati G. Idiopathic noncirrhotic portal hypertension: current perspectives. Hepat Med 2016; 8:81-8. [PMID: 27555800 PMCID: PMC4968980 DOI: 10.2147/hmer.s85544] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
The term idiopathic noncirrhotic portal hypertension (INCPH) has been recently proposed to replace terms, such as hepatoportal sclerosis, idiopathic portal hypertension, incomplete septal cirrhosis, and nodular regenerative hyperplasia, used to describe patients with a hepatic presinusoidal cause of portal hypertension of unknown etiology, characterized by features of portal hypertension (esophageal varices, nonmalignant ascites, porto-venous collaterals), splenomegaly, patent portal, and hepatic veins and no clinical and histological signs of cirrhosis. Physicians should learn to look for this condition in a number of clinical settings, including cryptogenic cirrhosis, a disease known to be associated with INCPH, drug administration, and even chronic alterations in liver function tests. Once INCPH is clinically suspected, liver histology becomes mandatory for the correct diagnosis. However, pathologists should be familiar with the histological features of INCPH, especially in cases in which histology is not only requested to exclude liver cirrhosis.
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Affiliation(s)
- Oliviero Riggio
- Department of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension
| | - Stefania Gioia
- Department of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension
| | - Ilaria Pentassuglio
- Department of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension
| | - Valeria Nicoletti
- Department of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension
| | - Michele Valente
- Department of Radiological, Oncological, and Pathological Sciences, Sapienza University of Rome, Rome, Italy
| | - Giulia d’Amati
- Department of Radiological, Oncological, and Pathological Sciences, Sapienza University of Rome, Rome, Italy
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23
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Feld JJ, Kato GJ, Koh C, Shields T, Hildesheim M, Kleiner DE, Taylor JG, Sandler NG, Douek D, Haynes-Williams V, Nichols JS, Hoofnagle JH, Liang TJ, Gladwin MT, Heller T. Liver injury is associated with mortality in sickle cell disease. Aliment Pharmacol Ther 2015; 42:912-21. [PMID: 26235444 PMCID: PMC6478018 DOI: 10.1111/apt.13347] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 06/25/2015] [Accepted: 07/15/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Increased life expectancy in sickle cell disease (SCD) has resulted in greater recognition of the consequences of repeated intravascular vaso-occlusion and chronic haemolysis to multiple organ systems. AIM To report the long-term consequences of liver dysfunction in SCD. METHODS A cohort of SCD patients was prospectively evaluated at the National Institutes of Health (NIH) Clinical Center. The association of mortality with liver enzymes, parameters of liver synthetic function and iron overload was evaluated using Cox regression. RESULTS Exactly, 247 SCD patients were followed up for 30 months of whom 22 (9%) died. After controlling for predictors, increased direct bilirubin (DB), ferritin, alkaline phosphatase and decreased albumin were independently associated with mortality. In a multivariable model, only high DB and ferritin remained significant. Ferritin correlated with hepatic iron content and total blood transfusions but not haemolysis markers. Forty patients underwent liver biopsies and 11 (28%) had fibrosis. Twelve of 26 patients (48%) had portal hypertension by hepatic venous pressure gradient (HVPG) measurements. All patients with advanced liver fibrosis had iron overload; however, most patients (69%) with iron overload were without significant hepatic fibrosis. Ferritin did not correlate with left ventricular dysfunction by echocardiography. DB correlated with bile acid levels suggesting liver pathology. Platelet count and soluble CD14 correlated with HVPG indicating portal hypertension. CONCLUSIONS Ferritin and direct bilirubin are independently associated with mortality in sickle cell disease. Ferritin likely relates to transfusional iron overload, while direct bilirubin suggests impairment of hepatic function, possibly impairing patients' ability to tolerate systemic insults.
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Affiliation(s)
- Jordan J. Feld
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH),Toronto Centre for Liver Disease, Sandra Rotman Center for Global Health, University of Toronto
| | - Gregory J. Kato
- National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH),Vascular Medicine Institute, University of Pittsburgh Medical Center
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)
| | - Tammy Shields
- National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)
| | - Mariana Hildesheim
- National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)
| | - David E. Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health (NIH)
| | - James G Taylor
- National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)
| | - Netanya G. Sandler
- Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
| | - Daniel Douek
- Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
| | - Vanessa Haynes-Williams
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)
| | - James S. Nichols
- National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH)
| | - Jay H. Hoofnagle
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)
| | - T. Jake Liang
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)
| | - Mark T. Gladwin
- National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH),Vascular Medicine Institute, University of Pittsburgh Medical Center
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)
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24
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Yasuda M, Erwin AL, Liu LU, Balwani M, Chen B, Kadirvel S, Gan L, Fiel MI, Gordon RE, Yu C, Clavero S, Arvelakis A, Naik H, Martin LD, Phillips JD, Anderson KE, Sadagoparamanujam VM, Florman SS, Desnick RJ. Liver Transplantation for Acute Intermittent Porphyria: Biochemical and Pathologic Studies of the Explanted Liver. Mol Med 2015; 21:487-95. [PMID: 26062020 DOI: 10.2119/molmed.2015.00099] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Accepted: 06/04/2015] [Indexed: 12/25/2022] Open
Abstract
Acute intermittent porphyria (AIP) is an autosomal-dominant hepatic disorder caused by the half-normal activity of hydroxymethylbilane (HMB) synthase. Symptomatic individuals experience life-threatening acute neurovisceral attacks that are precipitated by factors that induce the hepatic expression of 5-aminolevulinic acid synthase 1 (ALAS1), resulting in the marked accumulation of the putative neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG). Here, we provide the first detailed description of the biochemical and pathologic alterations in the explanted liver of an AIP patient who underwent orthotopic liver transplantation (OLT) due to untreatable and debilitating chronic attacks. After OLT, the recipient's plasma and urinary ALA and PBG rapidly normalized, and her attacks immediately stopped. In the explanted liver, (a) ALAS1 mRNA and activity were elevated approximately ~3- and 5-fold, and ALA and PBG concentrations were increased ~3- and 1,760-fold, respectively; (b) uroporphyrin III concentration was elevated; (c) microsomal heme content was sufficient, and representative cytochrome P450 activities were essentially normal; (d) HMB synthase activity was approximately half-normal (~42%); (e) iron concentration was slightly elevated; and (f) heme oxygenase I mRNA was increased approximately three-fold. Notable pathologic findings included nodular regenerative hyperplasia, previously not reported in AIP livers, and minimal iron deposition, despite the large number of hemin infusions received before OLT. These findings suggest that the neurovisceral symptoms of AIP are not associated with generalized hepatic heme deficiency and support the neurotoxicity of ALA and/or PBG. Additionally, they indicate that substrate inhibition of hepatic HMB synthase activity by PBG is not a pathogenic mechanism in acute attacks.
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Affiliation(s)
- Makiko Yasuda
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Angelika L Erwin
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Lawrence U Liu
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Manisha Balwani
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.,Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Brenden Chen
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Senkottuvelan Kadirvel
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Lin Gan
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - M Isabel Fiel
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Ronald E Gordon
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Chunli Yu
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Sonia Clavero
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Antonios Arvelakis
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Hetanshi Naik
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - L David Martin
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - John D Phillips
- Department of Internal Medicine, University of Utah, Salt Lake City, Utah
| | - Karl E Anderson
- Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas
| | | | - Sander S Florman
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.,Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Robert J Desnick
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
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25
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Viganò L, Rubbia-Brandt L, De Rosa G, Majno P, Langella S, Toso C, Mentha G, Capussotti L. Nodular Regenerative Hyperplasia in Patients Undergoing Liver Resection for Colorectal Metastases After Chemotherapy: Risk Factors, Preoperative Assessment and Clinical Impact. Ann Surg Oncol 2015; 22:4149-57. [DOI: 10.1245/s10434-015-4533-0] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2014] [Indexed: 12/15/2022]
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Abstract
Background Benign liver tumors are common. They do not spread to other areas of the body, and they usually do not pose a serious health risk. In fact, in most cases, benign liver tumors are not diagnosed because patients are asymptomatic. When they are detected, it’s usually because the person has had medical imaging tests, such as an ultrasound (US), computed tomography (CT) scan, or magnetic resonance imaging (MRI), for another condition. Materials and methods A search of the literature was made using cancer literature and the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: “hepatic benign tumors”, “hepatic cystic tumors”, “polycystic liver disease”, “liver macroregenerative nodules”, “hepatic mesenchymal hamartoma”, “hepatic angiomyolipoma”, “biliary cystadenoma”, and “nodular regenerative hyperplasia”. Discussion and conclusion Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world; there is an increasing incidence worldwide. Approximately 750,000 new cases are reported per year. More than 75 % of cases occur in the Asia-Pacific region, largely in association with chronic hepatitis B virus (HBV) infection. The incidence of HCC is increasing in the USA and Europe because of the increased incidence of hepatitis C virus (HCV) infection. Unlike the liver HCC, benign tumors are less frequent. However, they represent a chapter always more interesting of liver disease. In fact, a careful differential diagnosis with the forms of malignant tumor is often required in such a way so as to direct the patient to the correct therapy. In conclusion, many of these tumors present with typical features in various imaging studies. On occasions, biopsies are required, and/or surgical removal is needed. In the majority of cases of benign hepatic tumors, no treatment is indicated. The main indication for treatment is the presence of significant clinical symptoms or suspicion of malignancy or fear of malignant transformation.
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27
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Schwarz L, Faitot F, Soubrane O, Scatton O. Splenic artery ligation for severe oxaliplatin induced portal hypertension: A way to improve postoperative course and allow adjuvant chemotherapy for colorectal liver metastases. Eur J Surg Oncol 2014; 40:787-8. [DOI: 10.1016/j.ejso.2014.01.018] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2014] [Accepted: 01/07/2014] [Indexed: 01/20/2023] Open
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28
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Rothweiler S, Terracciano L, Tornillo L, Dill MT, Heim MH, Semela D. Downregulation of the endothelial genes Notch1 and ephrinB2 in patients with nodular regenerative hyperplasia. Liver Int 2014; 34:594-603. [PMID: 23870033 DOI: 10.1111/liv.12261] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2013] [Accepted: 06/12/2013] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Nodular regenerative hyperplasia (NRH) is a rare liver disease characterized by small regenerative nodules without fibrosis and can cause portal hypertension. Aetiology and pathogenesis of NRH remain unclear. We have recently shown that Notch1 knockout induces NRH with portal hypertension through vascular remodelling in mice. The aim of this study was to analyse histological and clinical data of NRH patients and to explore if the endothelial pathways identified in our NRH mouse model are also regulated in human NRH. METHODS Patients were identified retrospectively from the pathology database. Clinical and laboratory patient data were retrieved. mRNA expression was measured in liver biopsies from a subset of NRH patients. RESULTS Diagnosis of NRH was confirmed in needle biopsies of 51 patients, including 31 patients with grade 1, 12 patients with grade 2 and 8 patients with grade 3 NRH. Grade 3 nodularity significantly correlated with the presence of portal hypertension: 50% of the patients with grade 3 NRH vs. 6.5% with grade 1 (P = 0.0105). mRNA expression analysis in liver biopsies from 14 NRH patients and in primary human sinusoidal endothelial cells revealed downregulation of identical genes as in the murine NRH model, which are implicated in vascular differentiation: Notch1, delta-like 4 (Dll4) and ephrinB2. CONCLUSIONS In this large NRH needle biopsy cohort, we demonstrated that advanced nodularity correlates with presence of portal hypertension. Downregulation of the endothelial signalling pathways Dll4/Notch1 and ephrinB2/EphB4 supports the hypothesis that human NRH is caused by a sinusoidal injury providing first insights into the molecular pathogenesis of this liver condition.
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Affiliation(s)
- Sonja Rothweiler
- Department of Biomedicine, University Hospital Basel, University Basel, Basel, Switzerland
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29
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Chentoufi AA, Serov YA, Alazmi M, Baba K. Immune Components of Liver Damage Associated with Connective Tissue Diseases. J Clin Transl Hepatol 2014; 2:37-44. [PMID: 26357616 PMCID: PMC4521253 DOI: 10.14218/jcth.2014.00001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2013] [Revised: 02/02/2014] [Accepted: 02/04/2014] [Indexed: 12/16/2022] Open
Abstract
Autoimmune connective tissue diseases are associated with liver abnormalities and often have overlapping pathological and clinical manifestations. As a result, they can present great clinical challenges and evoke questions about diagnostic criteria for liver diseases. Moreover, discriminating between liver involvement as a manifestation of connective tissue disease and primary liver disease can be challenging since they share a similar immunological mechanism. Most patients with connective tissue diseases exhibit liver test abnormalities that likely result from coexisting, primary liver diseases, such as fatty liver disease, viral hepatitis, primary biliary cirrhosis, autoimmune hepatitis, and drug-related liver toxicity. Liver damage can be progressive, leading to cirrhosis, complications of portal hypertension, and liver-related death, and, therefore, must be accurately identified. In this review, we highlight the challenges facing the diagnosis of liver damage associated with connective tissue disease and identify immune mechanisms involved in liver damage associated with connective tissue diseases.
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Affiliation(s)
- Aziz A. Chentoufi
- Department of Immunology, Pathology and Clinical Laboratory Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
- Faculty of Medicine, King Saud Ben AbdulAziz University-Health Sciences, King Fahad Medical City, Riyadh
| | - Youri A. Serov
- Laboratory of Clinical Genetic, Research Institute of Gerontology, Ministry of Health, Leonova 16, Moscow, Russia
| | - Mansour Alazmi
- Department of Immunology, Pathology and Clinical Laboratory Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Kamaldeen Baba
- Department of Microbiology, Pathology and Clinical Laboratory Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
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30
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Sood A, Castrejón M, Saab S. Human immunodeficiency virus and nodular regenerative hyperplasia of liver: A systematic review. World J Hepatol 2014; 6:55-63. [PMID: 24653794 PMCID: PMC3953810 DOI: 10.4254/wjh.v6.i1.55] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2013] [Accepted: 12/13/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the diagnosis, pathogenesis, natural history, and management of nodular regenerative hyperplasia (NRH) in patients with human immunodeficiency virus (HIV).
METHODS: We performed a systematic review of the medical literature regarding NRH in patients with HIV. Inclusion criteria include reports with biopsy proven NRH. We studied the clinical features of NRH, in particular, related to its presenting manifestation and laboratory values. Combinations of the following keywords were implemented: “nodular regenerative hyperplasia”, “human immunodeficiency virus”, “noncirrhotic portal hypertension”, “idiopathic portal hypertension”, “cryptogenic liver disease”, “highly active antiretroviral therapy” and “didanosine”. The bibliographies of these studies were subsequently searched for any additional relevant publications.
RESULTS: The clinical presentation of patients with NRH varies from patients being completely asymptomatic to the development of portal hypertension – namely esophageal variceal bleeding and ascites. Liver associated enzymes are generally normal and synthetic function well preserved. There is a strong association between the occurrence of NRH and the use of antiviral therapies such as didanosine. The management of NRH revolves around treating the manifestations of portal hypertension. The prognosis of NRH is generally good since liver function is preserved. A high index of suspicion is required to make a identify NRH.
CONCLUSION: The appropriate management of HIV-infected persons with suspected NRH is yet to be outlined. However, NRH is a clinically subtle condition that is difficult to diagnose, and it is important to be able to manage it according to the best available evidence.
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32
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Fernando KA, Bhaduri S, Hubscher S, Radcliffe KW. Non-cirrhotic portal hypertension in the HIV-infected individual. J R Soc Med 2013; 106:105-7. [PMID: 23481432 DOI: 10.1177/0141076813479194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- K A Fernando
- Department of Sexual Health & HIV Medicine, Southend University Hospital NHS Foundation Trust, Prittlewell Chase, Essex SS0 0RY, UK.
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Abstract
Nodular regenerative hyperplasia (NRH) of liver may be one of the leading causes of non-cirrhotic intrahepatic portal hypertension (NCIPH), although the exact relationship is currently unknown. Diagnosis of NRH is relatively difficult and involves surgical pathology, and thus it is necessary to improve the preoperative recognition of NRH. Here, we analyze 15 cases of NRH to better understand this disease. All the liver specimens were microscopically examined by hematoxylin-eosin staining and reticulin and Masson trichrome staining. Diagnoses of NRH were confirmed by pathological examination. Clinically, NRH presents as diffused liver lesions with mildly increased liver enzymes. Portal hypertension is the most common clinical manifestation presenting prominently as splenomegaly, hypersplenism, and esophageal varices bleeding. NRH is often associated with autoimmune or collagen vascular diseases, and such patients often present with a variety of positive autoantibodies and increased erythrocyte sedimentation rate (ESR), Ig and γ %. Pathological examination of the liver showed diffuse small regenerative nodules without fibrous septa and obstructive portal venopathy. For those patients with portal hypertension of unknown cause and preserved liver function, especially, those combined with autoimmune diseases, NRH should be considered.
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34
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Granulomatous Disease in CVID: Retrospective Analysis of Clinical Characteristics and Treatment Efficacy in a Cohort of 59 Patients. J Clin Immunol 2012; 33:84-95. [DOI: 10.1007/s10875-012-9778-9] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2012] [Accepted: 08/21/2012] [Indexed: 10/27/2022]
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35
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Greene J, DiPasco P, Koshenkov V, Livingstone A. Portal hypertension from nodular regenerative hyperplasia of the liver treated with distal splenorenal shunt. J Surg Case Rep 2012; 2012:2. [PMID: 24960727 PMCID: PMC3649562 DOI: 10.1093/jscr/2012.7.2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Portal hypertension (PH) is a devastating sequelae of several pathologic entities, with alcoholic cirrhosis being the most common cause in the western world and endemic schistosomiasis worldwide. A much less common aetiology of non-cirrhotic PH is nodular regenerative hyperplasia (NRH) of the liver. The hallmark of NRH is a benign remodeling of the hepatic parenchyma into regenerative nodules in the absence of fibrosis (1). A Warren-Zeppa Distal Splenorenal Shunt (DSRS) was performed in a young patient with NRH of the liver to alleviate PH. This procedure was chosen due to its low postoperative rates of hepatic insufficiency and high durability.
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Abstract
The differential diagnosis of a liver mass is large and requires understanding of the clinical and imaging features of liver lesions. A detailed history, physical examination, hepatic biochemical tests, and imaging studies are all essential in making the diagnosis. Decisions regarding specific imaging modalities for diagnoses, the use of liver biopsy, therapeutic options, and appropriate follow-up are all determined by the presentation of the lesion and associated patient characteristics.
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Affiliation(s)
- Alan Bonder
- Department of Medicine, Liver Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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37
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Manzia TM, Gravante G, Di Paolo D, Orlando G, Toti L, Bellini MI, Ciano P, Angelico M, Tisone G. Liver transplantation for the treatment of nodular regenerative hyperplasia. Dig Liver Dis 2011; 43:929-34. [PMID: 21601542 DOI: 10.1016/j.dld.2011.04.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2010] [Revised: 03/28/2011] [Accepted: 04/04/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND Nodular regenerative hyperplasia (NRH) is the leading cause of non-cirrhotic portal hypertension in Western countries. Although some patients are successfully managed medically or with shunting procedures, others require liver transplantation. The aim of this review was to assess the overall results obtained with liver transplantation and to better define its role in this setting. METHODS Systematic review of all published studies on liver transplantation for NRH without language restrictions, in Medline, Embase and Cochrane Library databases through March 2010. RESULTS 17 studies including a total of 73 patients were identified; 47 (64.3%) were excluded due to lacking inclusion criteria or clinical data and 26 (35.7%) were analysed. Before liver transplantation, the most frequent clinical presentation was gastroesophageal bleeding (65.3%) followed by ascites (61.5%), hepatic encephalopathy (30.7%) and liver failure (11.5%). The mean follow-up reported after liver transplantation was 30.6±27.6 months and patient and graft survival rate was 78.3%. Only one case reported a NRH recurrence 7 years after liver transplantation (LT). CONCLUSIONS Although there are no hard data supporting the role of liver transplantation in symptomatic NRH, onset of severe portal hypertension in this setting may represent a valid indication.
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Under pressure: where's the cirrhosis? Am J Med 2011; 124:818-20. [PMID: 21854890 DOI: 10.1016/j.amjmed.2011.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2011] [Revised: 05/11/2011] [Accepted: 05/11/2011] [Indexed: 11/22/2022]
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Caturelli E, Ghittoni G, Ranalli TV, Gomes VV. Nodular regenerative hyperplasia of the liver: coral atoll-like lesions on ultrasound are characteristic in predisposed patients. Br J Radiol 2011; 84:e129-34. [PMID: 21697407 DOI: 10.1259/bjr/17975057] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Nodular regenerative hyperplasia (NRH) is an uncommon liver disease characterised histologically by numerous small hyperplastic nodules that are not separated by fibrotic tissue. It is thought to be the result of obliterative vasculopathy, and it has been associated with chronic use of medications, toxic substances and a wide variety of systemic diseases. Imaging diagnosis of early-stage NRH remains problematic. The nodules are rarely discerned and their appearance and behaviour before and after contrast medium administration are heterogeneous and not specific. A review of the literature shows that ultrasound has succeeded on occasion in revealing small focal liver lesions in patients with NRH. To our knowledge, there has been no published data on the performance in this setting of last-generation ultrasound scanners and techniques such as contrast-enhanced ultrasound (CEUS). The question is an important one because abdominal ultrasound is widely used as a first-line imaging technique for the evaluation of liver disease, and this makes it particularly suitable as a potential tool for the early diagnosis of NRH. Owing to the prolonged subclinical period and the limited help provided by imaging, the diagnosis in vivo of NRH is currently frequently missed, and it is still made exclusively on the basis of liver biopsy. In conclusion, this report describes 4 cases of biopsy-proven NRH that have been diagnosed over the past 2 years by our group. All were characterised by known comorbidities that confer a predisposition to NRH and by a peculiar parenchymal ultrasound pattern that we refer to as the "atoll sign".
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Affiliation(s)
- E Caturelli
- Unità Operativa di Gastroenterologia, Ospedale Belcolle, Viterbo, Italy
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40
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Biologic and clinical features of benign solid and cystic lesions of the liver. Clin Gastroenterol Hepatol 2011; 9:547-62.e1-4. [PMID: 21397723 DOI: 10.1016/j.cgh.2011.03.007] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2010] [Revised: 02/24/2011] [Accepted: 03/02/2011] [Indexed: 02/07/2023]
Abstract
The widespread use of imaging analyses, either routinely or to evaluate symptomatic patients, has increased the detection of liver lesions (tumors and cysts) in otherwise healthy individuals. Although some of these incidentally discovered masses are malignant, most are benign and must be included in the differential diagnosis. The management of benign hepatic tumors ranges from conservative to aggressive, depending on the nature of the lesions. New imaging modalities, increased experience of radiologists, improved definition of radiologic characteristics, and a better understanding of the clinical features of these lesions have increased the accuracy of diagnoses and reduced the need for invasive diagnostic tests. These advances have led to constant adjustments in management approaches to benign hepatic lesions. We review the biologic and clinical features of some common hepatic lesions, to guide diagnosis and management strategies.
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Abstract
Recent advances in multidetector-row computed tomography, magnetic resonance imaging, and ultrasonography have led to the detection of incidental hepatic lesions in both the oncology and nononcology patient population that in the past remained undiscovered. These incidental hepatic lesions have created a management dilemma for both clinicians and radiologists. In this review, guidelines concerning the diagnosis and management of some of the more common hepatic incidentalomas are presented.
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Hartleb M, Gutkowski K, Milkiewicz P. Nodular regenerative hyperplasia: Evolving concepts on underdiagnosed cause of portal hypertension. World J Gastroenterol 2011; 17:1400-9. [PMID: 21472097 PMCID: PMC3070012 DOI: 10.3748/wjg.v17.i11.1400] [Citation(s) in RCA: 105] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2010] [Revised: 12/22/2010] [Accepted: 12/29/2010] [Indexed: 02/06/2023] Open
Abstract
Nodular regenerative hyperplasia (NRH) is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules. NRH may lead to the development of non-cirrhotic portal hypertension. There are no published systematic population studies on NRH and our current knowledge is limited to case reports and case series. NRH may develop via autoimmune, hematological, infectious, neoplastic, or drug-related causes. The disease is usually asymptomatic, slowly or non-progressive unless complications of portal hypertension develop. Accurate diagnosis is made by histopathology, which demonstrates diffuse micronodular transformation without fibrous septa. Lack of perinuclear collagen tissue distinguishes NRH from typical regenerative nodules in the cirrhotic liver. While the initial treatment is to address the underlying disease, ultimately the therapy is directed to the management of portal hypertension. The prognosis of NRH depends on both the severity of the underlying illness and the prevention of secondary complications of portal hypertension. In this review we detail the epidemiology, pathogenesis, diagnosis, management, and prognosis of NRH.
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Ueda T, Starkey J, Mori K, Fukunaga K, Shimofusa R, Motoori K, Minami M, Kondo F. A pictorial review of benign hepatocellular nodular lesions: comprehensive radiological assessment incorporating the concept of anomalous portal tract syndrome. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2010; 18:386-96. [DOI: 10.1007/s00534-010-0342-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Takuya Ueda
- Department of Radiology; Chiba University Hospital; 1-8-1 Inohana, Chou-ku Chiba Chiba 260-8677 Japan
| | - Jay Starkey
- Department of Internal Medicine; University of California; San Diego, 9500 Gilman Dr. La Jolla CA 92093 USA
| | - Kensaku Mori
- Department of Radiology, Institute of Clinical Medicine; University of Tsukuba; 1-1-1 Ten-noudai Tsukuba Ibaraki 305-8575 Japan
| | - Kiyoshi Fukunaga
- Department of Surgery, Institute of Clinical Medicine; University of Tsukuba; 1-1-1 Ten-noudai Tsukuba Ibaraki 305-8575 Japan
| | - Ryota Shimofusa
- Department of Radiology; Chiba University Hospital; 1-8-1 Inohana, Chou-ku Chiba Chiba 260-8677 Japan
| | - Ken Motoori
- Department of Radiology; Chiba University Hospital; 1-8-1 Inohana, Chou-ku Chiba Chiba 260-8677 Japan
| | - Manabu Minami
- Department of Radiology, Institute of Clinical Medicine; University of Tsukuba; 1-1-1 Ten-noudai Tsukuba Ibaraki 305-8575 Japan
| | - Fukuo Kondo
- Department of Pathology; Teikyo University School of Medicine; 2-11-1 Kaga, Itabashi-ku Tokyo 173-8605 Japan
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Abstract
Sinusoidal obstruction syndrome (SOS), formerly named venoocclusive disease, is a well-known complication of hematopoietic stem cell transplantation and ingestion of food or drinks contaminated by pyrrolizidine alkaloids. Many other drugs and toxins have been associated with SOS, including several chemotherapeutic agents and immunosuppressors. SOS contributes to significant morbidity and mortality in all these settings. This review describes the histologic lesions of SOS, details its pathogenesis as it is understood today, specifies the recent data on its causes and how it may influence clinical management of colorectal liver metastases, and discusses the current knowledge on diagnosis and preventive options.
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Pilz JB, Portmann S, Peter S, Beglinger C, Degen L. Colon Capsule Endoscopy compared to Conventional Colonoscopy under routine screening conditions. BMC Gastroenterol 2010; 10:6. [PMID: 20082713 PMCID: PMC2836274 DOI: 10.1186/1471-230x-10-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2009] [Accepted: 01/18/2010] [Indexed: 12/20/2022] Open
Abstract
Background Nodular regenerative hyperplasia (NRH) has been recently recognized as an emergent cause of liver disease in HIV-infected patients. NRH may cause non-cirrhotic portal hypertension with potentially severe consequences such as refractory ascites, variceal bleeding and hypersplenism. Obliteration of the small intrahepatic portal veins in association with prothrombotic disorders linked to HIV infection itself or anti-retroviral therapy seem to be the causes of NRH and thus the term HIV-associated obliterative portopathy has been proposed. Case Presentation Here we describe a case of a HIV-infected patient with biopsy-proven NRH and listed for liver transplantation (LT) because of refractory ascites and repeated upper gastrointestinal bleedings. A transjugular intrahepatic portosystemic shunt was placed as a bridge to LT and did not improve liver function. However, anticoagulant therapy with low-molecular-weight heparin (LMWH) was associated with rapid improvement in the liver condition and allowed to avoid LT in this patient. Conclusions Thus, this case underscores the relation between thrombophilia and HIV-associated NRH and emphasizes anticoagulant therapy as possible treatment.
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Affiliation(s)
- Julia B Pilz
- Department of Gastroenterology and Hepatology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
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Abstract
BACKGROUND The only way to diagnose nodular regenerative hyperplasia (NRH) is liver biopsy. AIM To evaluate in a prospective study the performance of noninvasive liver investigations in patients with NRH. METHODS All consecutive patients with NRH who were being followed up in our unit from 2004 to 2007 were included. All biopsy specimens were reanalysed independently to confirm the diagnosis of NRH (classified as certain or probable) and to assess portal or sinusoidal associated fibrosis. All patients had liver stiffness (using FibroScan) and FibroTest measurements. Magnetic resonance imaging (MRI) was performed using two contrast agents (gadolinium-chelate and ferucarbotran). RESULTS Thirty patients were included (mean age: 53 years). Median liver stiffness value was 7.9 kPa (range: 3.5-16.8), with 63% of the patients having more than 7.1 kPa. No relationship was found between NRH with or without portal hypertension and liver stiffness or Fibrotest. No correlation was found between liver stiffness and portal and/or sinusoidal fibrosis. In patients studied with MRI, 55% had portal hypertension and 9% a diffuse fine-nodular loss of iron uptake after ferucarbotran injection. CONCLUSION Liver stiffness and FibroTest values may be increased in NRH patients, with no correlation with portal hypertension or portal and sinusoidal fibrosis. Contrast-enhanced MRI is disappointing in NRH.
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Rubbia-Brandt L, Lauwers GY, Wang H, Majno PE, Tanabe K, Zhu AX, Brezault C, Soubrane O, Abdalla EK, Vauthey JN, Mentha G, Terris B. Sinusoidal obstruction syndrome and nodular regenerative hyperplasia are frequent oxaliplatin-associated liver lesions and partially prevented by bevacizumab in patients with hepatic colorectal metastasis. Histopathology 2010; 56:430-9. [PMID: 20459550 DOI: 10.1111/j.1365-2559.2010.03511.x] [Citation(s) in RCA: 217] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
AIMS Because of its efficacy, oxaliplatin (OX) is increasingly used as a chemotherapeutic agent in the treatment of colorectal liver metastases (CRLM). Oxaliplatin-associated liver toxicity has been reported and can affect clinical practice, but studies on its prevalence and a full pathological description are lacking. The aims of this study were to fill this gap by providing, from a pathologist's perspective, a detailed assessment of the spectrum of hepatic lesions associated with OX, to suggest a scoring system to quantify them, and to investigate the protective effect of bevacizumab against OX-associated damage. METHODS AND RESULTS The spectrum of oxaliplatin-associated liver lesions was investigated in a multi-institutional series of surgically resected CRLM (n = 385). Among 274 patients treated by OX, 54% had moderate/severe sinusoidal obstruction syndrome (SOS). Peliosis, centrilobular perisinusoidal/venular fibrosis and nodular regenerative hyperplasia (NRH) developed in 10.6%, 47% and 24.5%, respectively. The 111 patients treated by surgery alone had no lesions. Hepatic lesions were less severe in patients treated with OX/bevacizumab (n = 70) compared with the group treated by OX alone (n = 204), with an incidence of moderate/severe SOS (31.4% versus 62.2%), peliosis (4.3% versus 14.6%), NRH (11.4% versus 28.9%, respectively) and centrilobular/venular fibrosis (31.4% versus 52%, respectively) (P < 0.001). CONCLUSIONS Pathologists should be aware of the distinctive lesions associated with OX and of their high prevalence. OX-related lesions are less frequent in patients treated with bevacizumab, suggesting that this drug has a preventive effect. Uniform criteria for diagnosis and grading of OX-associated lesions should help to include histological data in the optimal multidisciplinary management of CRLM.
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Abstract
Nodular regenerative hyperplasia (NRH) of the liver is a rare disease that is characterized by multiple regenerative nodules in the hepatic parenchyma that may lead to noncirrhotic portal hypertension. The exact pathogenesis of NRH has not been established, but it has been suggested that a primary vascular abnormality causing local ischemia may initiate the nodular transformation. It is also known that this condition is associated with autoimmune disease, hematological disease, and some chemotherapy agents in which vasculopathy is a prominent feature. The patients with NRH are usually asymptomatic unless they develop complications related to portal hypertension. We report a case of a middle-aged female patient with florid carcinoid syndrome, speculating that vasoactive hormones including serotonin secreted by the tumor caused intrahepatic microcirculatory disturbances that eventually induced NRH. This association has not been reported earlier.
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Assy N, Nasser G, Djibre A, Beniashvili Z, Elias S, Zidan J. Characteristics of common solid liver lesions and recommendations for diagnostic workup. World J Gastroenterol 2009; 15:3217-27. [PMID: 19598296 PMCID: PMC2710776 DOI: 10.3748/wjg.15.3217] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Due to the widespread clinical use of imaging modalities such as ultrasonography, computed tomography and magnetic resonance imaging (MRI), previously unsuspected liver masses are increasingly being found in asymptomatic patients. This review discusses the various characteristics of the most common solid liver lesions and recommends a practical approach for diagnostic workup. Likely diagnoses include hepatocellular carcinoma (the most likely; a solid liver lesion in a cirrhotic liver) and hemangioma (generally presenting as a mass in a non-cirrhotic liver). Focal nodular hyperplasia and hepatic adenoma should be ruled out in young women. In 70% of cases, MRI with gadolinium differentiates between these lesions. Fine needle core biopsy or aspiration, or both, might be required in doubtful cases. If uncertainty persists as to the nature of the lesion, surgical resection is recommended. If the patient is known to have a primary malignancy and the lesion was found at tumor staging or follow up, histology is required only when the nature of the liver lesion is doubtful.
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Silva AC, Evans JM, McCullough AE, Jatoi MA, Vargas HE, Hara AK. MR imaging of hypervascular liver masses: a review of current techniques. Radiographics 2009; 29:385-402. [PMID: 19325055 DOI: 10.1148/rg.292085123] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Major technologic advances in magnetic resonance (MR) imaging, including the advent of novel pulse sequences (eg, diffusion-weighted and steady-state free precession sequences) and the use of hepatocyte-specific contrast agents, have led to better image quality and shorter acquisition times, resulting in dramatic improvements in the noninvasive detection and characterization of hepatic lesions, particularly hypervascular neoplasms. However, as the role of MR imaging in clinical evaluation of the liver continues to evolve, keeping abreast of new developments can be daunting as well as confusing. A systematic approach that makes use of a simple decision algorithm can help differentiate hypervascular hepatic lesions on the basis of their distinguishing MR imaging characteristics and related clinical information.
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Affiliation(s)
- Alvin C Silva
- Department of Radiology, Mayo Clinic, Scottsdale, AZ 85259, USA.
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