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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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2
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Younes S, Suarez CJ, Pogoriler J, Bhatti T, Shenoy A, Saab R, Surrey LF, Tan SY. Congenital Peribronchial Myofibroblastic Tumors Harbor a Recurrent EGFR Kinase Domain Duplication. Mod Pathol 2025; 38:100661. [PMID: 39577666 DOI: 10.1016/j.modpat.2024.100661] [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: 07/13/2024] [Revised: 10/29/2024] [Accepted: 11/11/2024] [Indexed: 11/24/2024]
Abstract
Congenital peribronchial myofibroblastic tumor (CPMT) is a rare benign infantile pulmonary neoplasm that presents prenatally, or early in infancy, and exhibits distinctive histologic features characterized by the presence of cartilaginous islands intermixed with bland spindle cells, not uncommonly displaying prominent mitoses. Despite its benign nature, CPMT can lead to fetal demise, postnatal respiratory distress, or complications from perinatal surgical resection. Although the morphologic and clinical features of CPMT are well described, its molecular features and oncogenesis remain elusive. Following the detection of EGFR kinase domain duplication (KDD) of exons 18 to 25 in an index case, we identified 3 additional cases of morphologically classic and clinically well-characterized CPMTs from the archives and performed targeted RNA- and DNA-based profiling via next-generation sequencing for detection of rearrangements, sequence variants, and copy number variants on all cases. Two cases were detected prenatally, 1 patient presented at birth, and 1 at 8 weeks of life. All tumors were resected, with a follow-up period ranging from 0 days to 10 years. One patient died shortly after surgical resection, and the other 3 had no recurrences. In all cases, EGFR KDD was detected. In 2 out of 4 cases, gains of select whole chromosomes were noted. Our findings establish EGFR KDD as a recurrent oncogenic driver of CPMT. Notably, this alteration is also found in classical congenital mesoblastic nephromas, infantile kidney tumors with which CPMTs share striking morphologic and clinical similarities. This strongly suggests that CPMTs and classical congenital mesoblastic nephromas share common oncogenesis, and represent the same tumor in different locations. EGFR KDDs have also been reported in neonatal soft tissue tumors with infantile fibrosarcoma-like histology and cartilaginous differentiation, raising questions about their relationship. EGFR KDD emerges as a diagnostic marker, a potential therapeutic target, and a window into the oncogenesis of a distinct subset of infantile mesenchymal tumors.
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Affiliation(s)
- Sheren Younes
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - Carlos J Suarez
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - Jennifer Pogoriler
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Tricia Bhatti
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Archana Shenoy
- Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio
| | - Raya Saab
- Department of Pediatrics, Stanford University School of Medicine, Stanford, California
| | - Lea F Surrey
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Serena Y Tan
- Department of Pathology, Stanford University School of Medicine, Stanford, California.
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Nie Q, Liang Q, Li M, Zhu R, Ren J, Jiang K, Li J. Idiopathic non-cirrhotic portal hypertension: A case report. Medicine (Baltimore) 2024; 103:e40642. [PMID: 39705493 PMCID: PMC11666171 DOI: 10.1097/md.0000000000040642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 10/24/2024] [Accepted: 11/05/2024] [Indexed: 12/22/2024] Open
Abstract
RATIONALE Idiopathic noncirrhotic portal hypertension (INCPH) is a rare liver disorder with elevated portal pressure without cirrhosis, making diagnosis challenging. This case report presents a 46-year-old Chinese male with INCPH, highlighting the crucial role of liver biopsy. PATIENT CONCERNS A 46-year-old male presented with persistent fatigue that lasted for 2 months and significantly worsened over the last 3 days. The patient described his fatigue as a profound lack of energy that persisted throughout the day, which progressively impaired his ability to perform daily activities and maintain his usual work responsibilities. He reported feeling exhausted even after light physical exertion, such as walking or standing for short periods. The severity of the fatigue also led to frequent short rests during the day, and he experienced difficulty concentrating and carrying out routine tasks. In addition, he noted a loss of appetite and mild discomfort in the upper abdomen. Given his previous history of abnormal liver function tests and a liver biopsy showing mild chronic liver damage, the patient was initially diagnosed with cirrhosis at a local hospital. This initial diagnosis caused significant emotional distress, as the patient experienced a state of panic and anxiety over the implications of having a progressive liver disease. The psychological burden was evident in his reported difficulty sleeping and persistent worry about his health and future. DIAGNOSES Initial imaging suggested portal hypertension and cirrhosis, but a liver biopsy ruled out cirrhotic changes, confirming INCPH by excluding other causes such as chronic hepatitis. INTERVENTIONS The patient received symptomatic treatment (acid suppression, gastric and liver protection) and underwent a liver biopsy. Histological analysis confirmed INCPH, ruling out cirrhosis. OUTCOMES After the definitive diagnosis, the patient's anxiety lessened. Fatigue and weakness improved with ongoing symptomatic treatment, and psychological support enhanced his overall well-being. His follow-up plan includes regular liver function monitoring, imaging for portal pressure changes, and potential anticoagulation therapy for thrombosis risks. LESSONS This case highlights the diagnostic difficulty of INCPH and underscores the importance of liver biopsy. Further research is needed to develop specific diagnostic tools and treatments for INCPH.
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Affiliation(s)
- Qilong Nie
- The Eighth Clinical Medical College, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Qiuyan Liang
- The Eighth Clinical Medical College, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Mingyang Li
- The Eighth Clinical Medical College, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Ronghuo Zhu
- Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Jian Ren
- Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Kaiping Jiang
- Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Jianhong Li
- Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
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4
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Premkumar M, Anand AC. Porto-sinusoidal Vascular Disease: Classification and Clinical Relevance. J Clin Exp Hepatol 2024; 14:101396. [PMID: 38601747 PMCID: PMC11001647 DOI: 10.1016/j.jceh.2024.101396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Accepted: 03/05/2024] [Indexed: 04/12/2024] Open
Abstract
Non-cirrhotic portal hypertension (NCPH) is a well-recognized clinico-pathological entity, which is associated with clinical signs and symptoms, imaging, and endoscopic features of portal hypertension (PHT), in absence of cirrhosis. In patients with NCPH without known risk factors of PHT or extrahepatic portal vein thrombosis, the condition is called idiopathic non-cirrhotic portal hypertension (INCPH). There are multiple infectious, immune related causes, systemic diseases, drug and toxin exposures, haematological disorders, and metabolic risk factors that have been associated with this INCPH. However, the causal pathogenesis is still unclear. The Vascular liver disorders interest group group recently proposed porto-sinusoidal vascular disease (PSVD) as a syndromic entity, which provides definite histopathological criteria for diagnosis of NCPH (table 1). The three classical histo-morphological lesions specific for PSVD include obliterative portal venopathy, nodular regenerative hyperplasia, and incomplete septal fibrosis. The PSVD definition includes patients with portal vein thrombosis, PVT, and even those without PHT, thus broadening the scope of diagnosis to include patients who may have presented early, prior to haemodynamic changes consistent with PHT. However, this new diagnosis has pros and cons. The cons include mandating invasive liver biopsy to assess the PSVD histological triad in all patients with NCPH, an erstwhile clinical diagnosis in Asian patients. In addition, the natural history of the subclinical forms of PSVD without PHT and linear progression to develop PHT is unknown yet. In this review, we discuss the diagnosis and treatment of INCPH/PSVD, fallacies and strengths of the old and new schema, pathobiology of this disease, and clinical correlates in an Asian context. Although formulation of standardised diagnostic criteria is useful for comparison of clinical cohorts with INCPH/PSVD, prospective clinical validation in global cohorts is necessary to avoid misclassification of vascular disorders of the liver.
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Affiliation(s)
- Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Anil C. Anand
- Department of Hepatology, Kalinga Institute of Medical Sciences, Bhubaneshwar, Odisha, India
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5
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Jafari P, Evaristo G, Du XA, Sharma AE, Marcus V, Liu X, Zhao L, Westerhoff M, Hart J. Portosinusoidal Vascular Disorder: A Heretofore Unrecognized Manifestation of Sickle Cell Disease? Mod Pathol 2024; 37:100351. [PMID: 37820763 DOI: 10.1016/j.modpat.2023.100351] [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: 07/09/2023] [Revised: 09/10/2023] [Accepted: 10/04/2023] [Indexed: 10/13/2023]
Abstract
Portosinusoidal vascular disorder (PSVD) is a recently proposed histopathologic entity that encompasses a spectrum of often subtle hepatic microvascular lesions and related microarchitectural abnormalities. Clinical manifestations may arise years after histologic diagnosis and include extrahepatic portal vein thrombosis and portal hypertension. While the histopathologic features of PSVD have been associated with numerous clinical conditions, most notably prothrombotic/vasculopathic disorders, PSVD has not yet been described in sickle cell disease. This gap is striking given the central role of microvascular dysfunction in sickle cell disease and well-described patterns of hepatic injury and dysfunction in this population. This case series is the first to explore the prevalence and pathogenesis of PSVD in sickle cell disease. Forty-one diagnostically adequate liver biopsies from patients with sickle cell disease were identified across the archives of 5 tertiary medical centers. All biopsies exhibited at least 1 histopathologic feature associated with PSVD (mean 3.8 features/case). Overall, 90.2% of patients met the criteria for a diagnosis of PSVD based on the presence of specific histopathologic and/or clinical findings. Immunohistochemical stains for von Willebrand factor, CD34, and glutamine synthetase were performed on 36 cases (87.8%). Aberrant (centrilobular sinusoidal) CD34 and von Willebrand factor staining was present in 97.2% and 86.1% of cases, respectively. Glutamine synthetase reactivity was at least mildly decreased in zone 3 hepatocytes in 52.8% of cases. We posit that chronic erythrocyte sickling results in dysfunction and remodeling of the portal microvasculature, culminating in regression of zone 3 hepatocytes. The presence of PSVD may explain, at least in part, the hepatic dysfunction observed in this patient population. These patients may also benefit from extended clinical surveillance for portal hypertension and other complications. While subtle and prone to overdiagnosis, the features of PSVD should be carefully considered when interpreting liver biopsies from patients with sickle cell disease.
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Affiliation(s)
- Pari Jafari
- Department of Pathology, University of Chicago Medicine, The University of Chicago, Chicago, Illinois.
| | - Gertruda Evaristo
- Department of Pathology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Xiaotang Alison Du
- Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Aarti E Sharma
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Victoria Marcus
- Department of Pathology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Xiuli Liu
- Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, Missouri
| | - Lei Zhao
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Maria Westerhoff
- Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan
| | - John Hart
- Department of Pathology, University of Chicago Medicine, The University of Chicago, Chicago, Illinois
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Giuli L, Pallozzi M, Venturini G, Gasbarrini A, Ponziani FR, Santopaolo F. Molecular Mechanisms Underlying Vascular Liver Diseases: Focus on Thrombosis. Int J Mol Sci 2023; 24:12754. [PMID: 37628933 PMCID: PMC10454315 DOI: 10.3390/ijms241612754] [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: 07/15/2023] [Revised: 08/07/2023] [Accepted: 08/11/2023] [Indexed: 08/27/2023] Open
Abstract
Vascular liver disorders (VLDs) comprise a wide spectrum of clinical-pathological entities that primarily affect the hepatic vascular system of both cirrhotic and non-cirrhotic patients. VLDs more frequently involve the portal and the hepatic veins, as well as liver sinusoids, resulting in an imbalance of liver homeostasis with serious consequences, such as the development of portal hypertension and liver fibrosis. Surprisingly, many VLDs are characterized by a prothrombotic phenotype. The molecular mechanisms that cause thrombosis in VLD are only partially explained by the alteration in the Virchow's triad (hypercoagulability, blood stasis, and endothelial damage) and nowadays their pathogenesis is incompletely described and understood. Studies about this topic have been hampered by the low incidence of VLDs in the general population and by the absence of suitable animal models. Recently, the role of coagulation imbalance in liver disease has been postulated as one of the main mechanisms linked to fibrogenesis, so a novel interest in vascular alterations of the liver has been renewed. This review provides a detailed analysis of the current knowledge of molecular mechanisms of VLD. We also focus on the promising role of anticoagulation as a strategy to prevent liver complications and to improve the outcome of these patients.
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Affiliation(s)
- Lucia Giuli
- Hepatology Unit, CEMAD Centro Malattie Dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy; (L.G.); (M.P.); (G.V.); (F.R.P.); (F.S.)
| | - Maria Pallozzi
- Hepatology Unit, CEMAD Centro Malattie Dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy; (L.G.); (M.P.); (G.V.); (F.R.P.); (F.S.)
| | - Giulia Venturini
- Hepatology Unit, CEMAD Centro Malattie Dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy; (L.G.); (M.P.); (G.V.); (F.R.P.); (F.S.)
| | - Antonio Gasbarrini
- Hepatology Unit, CEMAD Centro Malattie Dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy; (L.G.); (M.P.); (G.V.); (F.R.P.); (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Hepatology Unit, CEMAD Centro Malattie Dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy; (L.G.); (M.P.); (G.V.); (F.R.P.); (F.S.)
| | - Francesco Santopaolo
- Hepatology Unit, CEMAD Centro Malattie Dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy; (L.G.); (M.P.); (G.V.); (F.R.P.); (F.S.)
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7
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Phrathep DD, Anthony S, Healey KD, Khan H, Herman M. Portal Hypertension Due to Hepatoportal Sclerosis in an HIV-Positive Patient Secondary to Didanosine Use. Cureus 2023; 15:e36364. [PMID: 37082489 PMCID: PMC10112855 DOI: 10.7759/cureus.36364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/19/2023] [Indexed: 03/20/2023] Open
Abstract
Noncirrhotic portal hypertension (NCPH) has recently been found in human immunodeficiency virus (HIV)-infected patients taking didanosine. Here, we describe an HIV-infected patient with portal hypertension due to hepatoportal sclerosis who presented with hematemesis at the emergency department (ED). CT angiography of the abdomen and pelvis with and without contrast revealed a diminutive portal vein with corresponding massive lower esophageal varices and superior mesenteric vein to the right gonadal vein varices. Esophagogastroduodenoscopy (EGD) revealed grade II varices were found in the lower third of the esophagus, for which the patient's symptoms improved with emergency endoscopic band ligation, octreotide and didanosine discontinuation. Our case demonstrates a rare complication that can occur with continued didanosine use in an HIV-positive patient. We highlight the need for a standard diagnostic upper gastrointestinal endoscopy to screen for portal hypertension and high-risk esophageal varices in patients with long-term didanosine use as seen in our patient.
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8
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Zhang X, Durham KM, Garza AA, Murali AR. Portal vein thrombosis, hepatic decompensation, and survival in patients with porto-sinusoidal vascular disease and portal hypertension. J Gastroenterol 2023; 58:268-276. [PMID: 36692825 DOI: 10.1007/s00535-023-01957-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 01/07/2023] [Indexed: 01/25/2023]
Abstract
BACKGROUND Porto-sinusoidal vascular disease (PSVD) is a novel nomenclature to describe non-cirrhotic portal hypertension and characteristic histology without portal vein thrombosis (PVT). It is a more inclusive definition than the previously well-recognized entity idiopathic non-cirrhotic portal hypertension. There is a paucity of data on PSVD patients. METHODS A total of 33 patients diagnosed with PSVD and portal hypertension (PH) between 2005 and 2021 were included. Data were retrieved from electronic medical record system and analyzed. RESULTS Of the 33 patients, 6 (18%) occurred in post-transplant allograft liver. After a median follow-up of 96 months (interquartile range, IQR [52, 139]), 14 deaths occurred (42%), 4 directly related to decompensated liver disease. The Kaplan-Meier survival estimates at 1, 5, and 10 years were 94%, 87% and 58%. PVT occurred in 10 patients (30%). The Nelson-Aalen cumulative risk estimate for PVT at 1, 5 and 10 years were 16%, 25% and 48%. The median model for end-stage liver disease and Child-Pugh score at initial presentation were 8 (IQR [7-12]) and 5 [5-6], and increased to 13 [8, 18] and 7 [5, 8], respectively, at the end of follow-up. Of the 11 patients who presented with splenomegaly and no specific sign of PH, 7 (64%) developed varices and 3 (27%) ascites at a median follow-up of 100 months. CONCLUSIONS PSVD with PH is not a benign entity. Mortality, PVT and hepatic decompensation are common. Patients with PSVD must be closely monitored, including those who only have non-specific clinical signs (e.g., splenomegaly) of PH.
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Affiliation(s)
- Xiaocen Zhang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, USA
| | - Katelin Marie Durham
- Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, USA
| | - Alexander Austin Garza
- Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, USA
| | - Arvind R Murali
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, USA.
- Liver Center, Orlando Health Digestive Health Institute, 89 W. Copeland Dr., Orlando, FL, USA.
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9
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Kablawi D, Alhinai A, Wong P, Deschenes M, Sebastiani G, Benmassaoud A. Splenomegaly is a marker of advanced chronic liver disease and portal hypertension in HIV infection. HIV Med 2023; 24:366-371. [PMID: 36042533 DOI: 10.1111/hiv.13390] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 08/09/2022] [Indexed: 11/27/2022]
Abstract
OBJECTIVES To evaluate the clinical significance of splenomegaly as a marker of underlying liver disease in people with HIV (PWH). METHODS We included consecutive PWH from a prospective cohort from 2010 to 2020 with available liver stiffness measurement (LSM) and liver imaging to define splenomegaly (> 13 cm) within 1 year. Cut-offs of LSM > 10 kPa and > 21 kPa were used to identify advanced chronic liver disease (ACLD) and portal hypertension, respectively. Logistic regression multivariable analysis was employed to identify independent predictors of ACLD. RESULTS In all, 331 PWH were included, 76% of them men, with a median (interquartile range) age of 51.3 (45-58) years, all receiving antiretroviral treatment, and 53% were HIV monoinfected. The PWH with splenomegaly exhibited a higher prevalence of ACLD compared with those with normal spleen size, as per LSM (26% vs. 9%; p = 0.009). Portal hypertension diagnosed by LSM was also more prevalent in PWH with splenomegaly than in those without (15% vs. 2%; p < 0.001). Independent predictors of ACLD were viral hepatitis coinfection [adjusted odds ratio (aOR) = 3.15, 95% confidence interval (CI): 1.65-6.0], lower platelets (aOR = 0.99, 95% CI: 0.99-0.99) and splenomegaly (aOR = 2.41, 95% CI: 1.17-4.99). In patients with available oesophagogastroduodenoscopy, splenomegaly was also associated with higher prevalence of oesophageal varices and other endoscopic findings of portal hypertension (38% vs. 17%; p = 0.027). CONCLUSIONS Splenomegaly identified on routine imaging may have utility as a marker of ACLD and portal hypertension, prompting further investigations.
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Affiliation(s)
- Dana Kablawi
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Québec, Canada
| | - Alshaima Alhinai
- Division of Experimental Medicine, McGill University, Montreal, Québec, Canada
| | - Philip Wong
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Québec, Canada
| | - Marc Deschenes
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Québec, Canada
| | - Giada Sebastiani
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Québec, Canada.,Division of Experimental Medicine, McGill University, Montreal, Québec, Canada
| | - Amine Benmassaoud
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Québec, Canada
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10
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Sarma MS, Seetharaman J. Pediatric non-cirrhotic portal hypertension: Endoscopic outcome and perspectives from developing nations. World J Hepatol 2021; 13:1269-1288. [PMID: 34786165 PMCID: PMC8568571 DOI: 10.4254/wjh.v13.i10.1269] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/27/2021] [Accepted: 09/19/2021] [Indexed: 02/06/2023] Open
Abstract
Non-cirrhotic portal hypertension (NCPH) forms an important subset of portal hypertension in children. Variceal bleed and splenomegaly are their predominant presentation. Laboratory features show cytopenias (hypersplenism) and preserved hepatic synthetic functions. Repeated sessions of endoscopic variceal ligation or endoscopic sclerotherapy eradicate esophageal varices in almost all cases. After variceal eradication, there is an increased risk of other complications like secondary gastric varices, cholangiopathy, colopathy, growth failure, especially in extra-hepatic portal vein obstruction (EHPVO). Massive splenomegaly-related pain and early satiety cause poor quality of life (QoL). Meso-Rex bypass is the definitive therapy when the procedure is anatomically feasible in EHPVO. Other portosystemic shunt surgeries with splenectomy are indicated when patients present late and spleen-related issues predominate. Shunt surgeries prevent rebleed, improve growth and QoL. Non-cirrhotic portal fibrosis (NCPF) is a less common cause of portal hypertension in children in developing nations. Presentation in the second decade, massive splenomegaly and patent portal vein are discriminating features of NCPF. Shunt surgery is required in severe cases when endotherapy is insufficient for the varices. Congenital hepatic fibrosis (CHF) presents with firm palpable liver and splenomegaly. Ductal plate malformation forms the histological hallmark of CHF. CHF is commonly associated with Caroli’s disease, renal cysts, and syndromes associated with neurological defects. Isolated CHF has a favourable prognosis requiring endotherapy. Liver transplantation is required when there is decompensation or recurrent cholangitis, especially in Caroli’s syndrome. Combined liver-kidney transplantation is indicated when both liver and renal issues are present.
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Affiliation(s)
- Moinak Sen Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Jayendra Seetharaman
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
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11
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Larrey D, Meunier L, Valla D, Hillaire S, Hernandez-Gea V, Dutheil D, Plessier A, Bureau C. Drug induced liver injury and vascular liver disease. Clin Res Hepatol Gastroenterol 2020; 44:471-479. [PMID: 32371005 DOI: 10.1016/j.clinre.2020.03.020] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 03/03/2020] [Indexed: 02/04/2023]
Affiliation(s)
- Dominique Larrey
- Department of Gastroenterology and Hepatology, Saint-Éloi Hospital, University Hospital of Montpellier, 80, avenue Augustin-Fliche, 34090 Montpellier, France; French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France.
| | - Lucy Meunier
- Department of Gastroenterology and Hepatology, Saint-Éloi Hospital, University Hospital of Montpellier, 80, avenue Augustin-Fliche, 34090 Montpellier, France; French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France
| | - Dominique Valla
- French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of Hepatology, Beaujon Hospital, AP-HP, 100, boulevard du Général Leclerc, 92118 Clichy, France; Reference center of vascular liver diseases, European Reference Network (ERN) Rare-Liver, Clichy, France
| | - Sophie Hillaire
- Department of Internal Medicine, Foch Hospital, 40, rue Worth, 92150 Suresnes, France
| | - Virginia Hernandez-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona. Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd). Health Care Provider of the European Reference Network onRare Liver Disorders (ERN-Liver), Spain
| | - Danielle Dutheil
- French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Association of patients with vascular liver diseases (AMVF), Department of Hepatology, Beaujon Hospital, 100, boulevard du Général Leclerc, 92118 Clichy, France
| | - Aurélie Plessier
- French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of Hepatology, Beaujon Hospital, AP-HP, 100, boulevard du Général Leclerc, 92118 Clichy, France; Reference center of vascular liver diseases, European Reference Network (ERN) Rare-Liver, Clichy, France
| | - Christophe Bureau
- French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of Gastroenterology and Hepatology, Rangueil Hospital, University Hospital of Toulouse, 1, avenue du Professeur Jean-Poulhès, 31400 Toulouse, France
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12
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De Gottardi A, Rautou PE, Schouten J, Rubbia-Brandt L, Leebeek F, Trebicka J, Murad SD, Vilgrain V, Hernandez-Gea V, Nery F, Plessier A, Berzigotti A, Bioulac-Sage P, Primignani M, Semela D, Elkrief L, Bedossa P, Valla D, Garcia-Pagan JC. Porto-sinusoidal vascular disease: proposal and description of a novel entity. Lancet Gastroenterol Hepatol 2020; 4:399-411. [PMID: 30957754 DOI: 10.1016/s2468-1253(19)30047-0] [Citation(s) in RCA: 167] [Impact Index Per Article: 33.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 01/16/2019] [Accepted: 01/17/2019] [Indexed: 12/14/2022]
Abstract
Portal hypertension in the absence of portal vein thrombosis and without cirrhosis, but with mild or moderate alterations of liver histology (eg, obliterative venopathy, nodular regenerative hyperplasia, or incomplete septal cirrhosis) is being increasingly recognised. Owing to the heterogeneity of causes and histological findings, a substantial number of terms have been used to describe such idiopathic non-cirrhotic portal hypertension. Patients with the same clinical and histological features exist, but without portal hypertension at the time of diagnosis. Therefore, improved criteria are needed to define this form of liver disease. Here, we propose the term porto-sinusoidal vascular disease, since all lesions found involve the portal venules or sinusoids. The definition of this entity is based on the characteristic absence of cirrhosis with or without signs of portal hypertension or histological lesions. The presence of known causes of liver disease does not rule out porto-sinusoidal vascular disease, but specific causes of vascular liver disease are excluded from its definition. The diagnosis of porto-sinusoidal vascular disease is based on liver biopsy and might include signs specific for portal hypertension with normal or mildly elevated liver stiffness values and no complete portal vein thrombosis. We provide simple diagnostic criteria, because agreement on a uniform nomenclature is an essential requirement for future collaborative studies.
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Affiliation(s)
- Andrea De Gottardi
- University Clinic for Visceral Surgery and Medicine, Inselspital, Bern, Switzerland; Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Pierre-Emmanuel Rautou
- Service d'Hépatologie, Hôpital Beaujon, Clichy, France; Centre de Recherche de l'Inflammation, Inserm and Université Paris Diderot, Paris, France
| | | | - Laura Rubbia-Brandt
- Service de Pathologie Clinique, Hôpitaux Universitaires de Genève, Geneva, Switzerland
| | - Frank Leebeek
- Department of Haematology, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Jonel Trebicka
- Department of Internal Medicine I, University of Bonn, Bonn, Germany; European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Sarwa Darwish Murad
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, Netherlands
| | | | - Virginia Hernandez-Gea
- Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain; CIBER Hepatic and Digestive Diseases, Instituto de Salud Carlos III, Madrid, Spain
| | - Filipe Nery
- Centro Hospitalar Universitário and EpiUnit, Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
| | - Aurélie Plessier
- Service d'Hépatologie, Hôpital Beaujon, Clichy, France; Centre de Recherche de l'Inflammation, Inserm and Université Paris Diderot, Paris, France
| | - Annalisa Berzigotti
- University Clinic for Visceral Surgery and Medicine, Inselspital, Bern, Switzerland; Department of Biomedical Research, University of Bern, Bern, Switzerland
| | | | - Massimo Primignani
- Gastroenterologia ed Epatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - David Semela
- Gastroenterology and Hepatology, Kantonsspital, St Gallen, Switzerland
| | - Laure Elkrief
- Hepatology, Hôpitaux Universitaires de Genève, Geneva, Switzerland
| | | | - Dominique Valla
- Service d'Hépatologie, Hôpital Beaujon, Clichy, France; Centre de Recherche de l'Inflammation, Inserm and Université Paris Diderot, Paris, France
| | - Juan Carlos Garcia-Pagan
- Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain; CIBER Hepatic and Digestive Diseases, Instituto de Salud Carlos III, Madrid, Spain.
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13
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Abstract
Idiopathic portal hypertension (IPH) and extrahepatic portal venous obstruction (EHPVO) are prototype noncirrhotic causes of portal hypertension (PHT), characterized by normal hepatic venous pressure gradient, variceal bleeds, and moderate to massive splenomegaly with preserved liver synthetic functions. Infections, toxins, and immunologic, prothrombotic and genetic disorders are possible causes in IPH, whereas prothrombotic and local factors around the portal vein lead to EHPVO. Growth failure, portal biliopathy, and minimal hepatic encephalopathy are long-term concerns in EHPVO. Surgical shunts and transjugular intrahepatic portosystemic shunt resolve the complications secondary to PHT. Meso-Rex shunt is now the standard-of-care surgery in children with EHPVO.
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Affiliation(s)
- Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver & Biliary Sciences (ILBS), D-1, Vasant Kunj, New Delhi 110 070, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver & Biliary Sciences (ILBS), D-1, Vasant Kunj, New Delhi 110 070, India.
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14
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Abstract
: Elevation of liver transaminases is common in patients infected with the HIV. Although this is usually an incidental finding during regular work-up, HIV-infected patients with transaminase elevations require additional visits for laboratory studies and clinical assessments, and often undergo interruptions and changes in antiretroviral therapy (ART). Alanine aminotransferase is present primarily in the liver, thus being a surrogate marker of hepatocellular injury. Aspartate aminotransferase is present in the liver and other organs, namely cardiac and skeletal muscle, kidney and brain. Serum levels of both liver transaminases predict liver-related mortality. Moreover, serum fibrosis biomarkers based on alanine aminotransferase and aspartate aminotransferase predict all-cause mortality. In a busy clinical setting, a diagnostic approach to elevated liver transaminases could be complicated given the frequency and nonspecificity of this finding. Indeed, HIV-infected individuals present multiple risk factors for liver damage and chronic elevation of transaminases, including coinfection with hepatitis B and C viruses, alcohol abuse, hepatotoxicity due to ART, HIV itself and frequent metabolic comorbidities leading to nonalcoholic fatty liver disease. This review provides an update on epidemiology of elevated liver transaminases, summarizes the main etiologic contributors and discusses the prognostic significance and a pragmatic approach to this frequent finding in the clinical practice of HIV medicine. With the aging of the HIV-infected population following the successful implementation of ART in Western countries, liver-related conditions are now a major comorbidity in this setting. As such, clinicians should be aware of the frequency, clinical significance and diagnostic approach to elevated liver transaminases.
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15
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Andrade RJ, Aithal GP, Björnsson ES, Kaplowitz N, Kullak-Ublick GA, Larrey D, Karlsen TH. EASL Clinical Practice Guidelines: Drug-induced liver injury. J Hepatol 2019; 70:1222-1261. [PMID: 30926241 DOI: 10.1016/j.jhep.2019.02.014] [Citation(s) in RCA: 645] [Impact Index Per Article: 107.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 02/14/2019] [Indexed: 02/07/2023]
Abstract
Idiosyncratic (unpredictable) drug-induced liver injury is one of the most challenging liver disorders faced by hepatologists, because of the myriad of drugs used in clinical practice, available herbs and dietary supplements with hepatotoxic potential, the ability of the condition to present with a variety of clinical and pathological phenotypes and the current absence of specific biomarkers. This makes the diagnosis of drug-induced liver injury an uncertain process, requiring a high degree of awareness of the condition and the careful exclusion of alternative aetiologies of liver disease. Idiosyncratic hepatotoxicity can be severe, leading to a particularly serious variety of acute liver failure for which no effective therapy has yet been developed. These Clinical Practice Guidelines summarize the available evidence on risk factors, diagnosis, management and risk minimization strategies for drug-induced liver jury.
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16
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Alexopoulou A, Mani I, Tiniakos DG, Kontopidou F, Tsironi I, Noutsou M, Pantelidaki H, Dourakis SP. Successful treatment of noncirrhotic portal hypertension with eculizumab in paroxysmal nocturnal hemoglobinuria: A case report. World J Hepatol 2019; 11:483-488. [PMID: 31183008 PMCID: PMC6547289 DOI: 10.4254/wjh.v11.i5.483] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 05/15/2019] [Accepted: 05/21/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Idiopathic non-cirrhotic portal hypertension (INCPH) is mainly associated with thrombophilia in Western countries. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease that manifests with hemolytic anemia, thrombosis, and peripheral blood cytopenias. Portal and hepatic venous thrombosis were reported in PNH. A rare case of INCPH complicating PNH is described.
CASE SUMMARY A 63-year old woman with a 2-year past medical history of PNH without treatment was admitted because of jaundice and refractory ascites requiring large volume paracentesis. Liver histology revealed portal venopathy with portal fibrosis and sclerosis, nodular regenerative hyperplasia, parenchymal ischemic changes, and focal sinusoidal and perivenular fibrosis without bridging fibrosis or cirrhosis, all indicative of INCPH. The flow cytometry confirmed PNH diagnosis and eculizumab treatment was initiated. Her condition was improved gradually, bilirubin was normalized 6 months following initiation of eculizumab, and 1 year later diuretics were stopped.
CONCLUSION Eculizumab improved intravascular hemolysis and reversed clinical manifestations of INCPH in a patient with paroxysmal nocturnal hemoglobinuria.
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Affiliation(s)
- Alexandra Alexopoulou
- 2nd Department of Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens 11527, Greece
| | - Iliana Mani
- 2nd Department of Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens 11527, Greece
| | - Dina G Tiniakos
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle NE2 4HH, United Kingdom
- Department of Pathology, Aretaieion Hospital, National and Kapodistrian University of Athens, Athens 11528, Greece
| | - Flora Kontopidou
- 2nd Department of Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens 11527, Greece
| | - Ioanna Tsironi
- 2nd Department of Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens 11527, Greece
| | - Marina Noutsou
- 2nd Department of Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens 11527, Greece
| | - Helen Pantelidaki
- 2nd Department of Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens 11527, Greece
| | - Spyros P Dourakis
- 2nd Department of Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens 11527, Greece
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17
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Jha RC, Khera SS, Kalaria AD. Portal Vein Thrombosis: Imaging the Spectrum of Disease With an Emphasis on MRI Features. AJR Am J Roentgenol 2018; 211:14-24. [PMID: 29792748 DOI: 10.2214/ajr.18.19548] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Affiliation(s)
- Reena C. Jha
- Department of Radiology, MedStar Georgetown University Hospital, 3800 Reservoir Rd, NW, Lombardi, G-184, Washington, DC 20007
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18
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Soriano V, Ramos JM, Barreiro P, Fernandez-Montero JV. AIDS Clinical Research in Spain-Large HIV Population, Geniality of Doctors, and Missing Opportunities. Viruses 2018; 10:v10060293. [PMID: 29848987 PMCID: PMC6024378 DOI: 10.3390/v10060293] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 05/24/2018] [Accepted: 05/25/2018] [Indexed: 02/07/2023] Open
Abstract
The first cases of AIDS in Spain were reported in 1982. Since then over 85,000 persons with AIDS have been cumulated, with 60,000 deaths. Current estimates for people living with HIV are of 145,000, of whom 20% are unaware of it. This explains the still high rate of late HIV presenters. Although the HIV epidemic in Spain was originally driven mostly by injection drug users, since the year 2000 men having sex with men (MSM) account for most new incident HIV cases. Currently, MSM represent over 80% of new yearly HIV diagnoses. In the 80s, a subset of young doctors and nurses working at Internal Medicine hospital wards became deeply engaged in attending HIV-infected persons. Before the introduction of antiretrovirals in the earlier 1990s, diagnosis and treatment of opportunistic infections was their major task. A new wave of infectious diseases specialists was born. Following the wide introduction of triple combination therapy in the late 1990s, drug side effects and antiretroviral resistance led to built a core of highly devoted HIV specialists across the country. Since then, HIV medicine has improved and currently is largely conducted by multidisciplinary teams of health care providers working at hospital-based outclinics, where HIV-positive persons are generally seen every six months. Antiretroviral therapy is currently prescribed to roughly 75,000 persons, almost all attended at clinics belonging to the government health public system. Overall, the impact of HIV/AIDS publications by Spanish teams is the third most important in Europe. HIV research in Spain has classically been funded mostly by national and European public agencies along with pharma companies. Chronologically, some of the major contributions of Spanish HIV research are being in the field of tuberculosis, toxoplasmosis, leishmaniasis, HIV variants including HIV-2, drug resistance, pharmacology, antiretroviral drug-related toxicities, coinfection with viral hepatitis, design and participation in clinical trials with antiretrovirals, immunopathogenesis, ageing, and vaccine development.
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Affiliation(s)
- Vicente Soriano
- Infectious Diseases Unit, La Paz University Hospital, 28046 Madrid, Spain.
- UNIR Health Sciences School, 28040 Madrid, Spain.
| | - José M Ramos
- Department of Internal Medicine, General University Hospital, 03010 Alicante, Spain.
| | - Pablo Barreiro
- Infectious Diseases Unit, La Paz University Hospital, 28046 Madrid, Spain.
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19
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Guerra MAR, Naini BV, Scapa JV, Reed EF, Busuttil RW, Cheng EY, Farmer DG, Vargas JH, Venick RS, McDiarmid SV, Wozniak LJ. Obliterative portal venopathy: A histopathologic finding associated with chronic antibody-mediated rejection in pediatric liver allografts. Pediatr Transplant 2018; 22. [PMID: 29363222 DOI: 10.1111/petr.13124] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/14/2017] [Indexed: 12/11/2022]
Abstract
The significance of post-transplant HLA DSA and chronic AMR in LT is an emerging field of study. Although OPV has previously been described as a histopathologic finding in DSA-positive adult LT recipients, it was not included in the recent Banff criteria for chronic AMR. Our aim was to describe the association between OPV and chronic AMR in pediatric LT recipients. A retrospective review of 67 liver biopsies performed between November 2014 and April 2016 in 45 pediatric LT recipients identified four patients with OPV. Clinical status, liver biochemistry, the presence of DSA, and available non-HLA antibody testing, as well as histopathologic features of chronic AMR, were assessed. All four patients with OPV had class II DSA and histopathologic features of chronic AMR based on the Banff criteria. Two patients were noted to have non-HLA antibodies. Three patients are undergoing treatment with IVIG but have persistent DSA. Two patients have graft failure and are awaiting retransplantation. In conclusion, OPV is a histopathologic finding associated with chronic AMR in pediatric LT recipients. Further studies are needed to elucidate whether OPV is reversible and/or amenable to medical therapy.
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Affiliation(s)
- Marjorie-Anne R Guerra
- Pediatric Gastroenterology, Hepatology, and Nutrition, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Bita V Naini
- Pathology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Jason V Scapa
- Pathology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Elaine F Reed
- Pathology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Ronald W Busuttil
- Transplant Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Elaine Y Cheng
- Transplant Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Douglas G Farmer
- Transplant Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Jorge H Vargas
- Pediatric Gastroenterology, Hepatology, and Nutrition, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Robert S Venick
- Pediatric Gastroenterology, Hepatology, and Nutrition, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.,Transplant Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Sue V McDiarmid
- Pediatric Gastroenterology, Hepatology, and Nutrition, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.,Transplant Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Laura J Wozniak
- Pediatric Gastroenterology, Hepatology, and Nutrition, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
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20
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Khanna R, Sarin SK. Idiopathic portal hypertension and extrahepatic portal venous obstruction. Hepatol Int 2018; 12:148-167. [PMID: 29464506 DOI: 10.1007/s12072-018-9844-3] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 01/19/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Idiopathic portal hypertension (IPH) and extrahepatic portal venous obstruction (EHPVO) are non-cirrhotic vascular causes of portal hypertension (PHT). Variceal bleed and splenomegaly are the commonest presentations. AIM The present review is intended to provide the existing literature on etiopathogenesis, clinical profile, diagnosis, natural history and management of IPH and EHPVO. RESULTS IPH and EHPVO are both characterized by normal hepatic venous pressure gradient, moderate to massive splenomegaly with preserved liver synthetic functions. While the level of block in IPH is presinusoidal, in EHPVO it is at prehepatic level. Infections, autoimmunity, drugs, immunodeficiency and prothrombotic states are possible etiological agents in IPH. Contrastingly in EHPVO, prothrombotic disorders and local factors around the portal vein are the incriminating factors. Diagnosis is often clinical, supported by simple radiological tools. Natural history is defined by episodes of variceal bleed and symptoms related to enlarged spleen. Growth failure, portal biliopathy and minimal hepatic encephalopathy are additional concerns in EHPVO. Long-term survival is reasonably good with endoscopic surveillance; however, parenchymal extinction leading to decompensation is seen in a minority of patients in both the disorders. Surgical shunts revert the complications secondary to PHT. Meso-Rex shunt has become the standard surgery in children with EHPVO. CONCLUSION This review gives a detailed summary of these two vascular conditions of liver-IPH and EHPVO. Further research is needed to understand the pathogenesis and natural history of these disorders.
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Affiliation(s)
- Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
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21
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Kleiner DE. Histopathological challenges in suspected drug-induced liver injury. Liver Int 2018; 38:198-209. [PMID: 28865179 DOI: 10.1111/liv.13584] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Accepted: 08/25/2017] [Indexed: 12/13/2022]
Abstract
When a patient with suspected drug-induced liver injury (DILI) undergoes liver biopsy, the pathologist is confronted with two major challenges. The first and most important is to establish the pattern(s) of injury which are present. Patterns of injury represent stereotypical responses of an organ to injury and relate to specific aetiologies of liver damage. The pattern of injury and the histological details of that injury can then be analysed with respect to the patient's intercurrent diseases and medication history. The specific expertise of the pathologist can be used to weigh the prospect of DILI against the likelihood of other explanations of injury. The second challenge is to characterize specific types of injury and the severity of injury, both of which may have importance for clinical decision-making and prognosis. The pathologist's report should convey both an accurate description of the pathology as well its interpretation.
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Affiliation(s)
- David E Kleiner
- Post-Mortem Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA
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22
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Sonderup MW, Wainwright HC. Human Immunodeficiency Virus Infection, Antiretroviral Therapy, and Liver Pathology. Gastroenterol Clin North Am 2017; 46:327-343. [PMID: 28506368 DOI: 10.1016/j.gtc.2017.01.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
The improvement in antiretroviral therapy has significantly impacted the lives of people living with human immunodeficiency virus (HIV). In high-income countries, HIV deaths are predominated by liver disease consequent to viral hepatitis coinfection, alcohol, and nonalcoholic fatty liver disease. Published liver pathology findings have shifted from being predominated by opportunistic infections to the metabolic effects of HIV and antiretroviral therapy as well as drug-induced liver injuries. Differences remain between high-income and low-income countries, where opportunistic infections and immune reconstitution syndromes, dominate findings.
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Affiliation(s)
- Mark W Sonderup
- Division of Hepatology, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Observatory, Cape Town 7925, South Africa.
| | - Helen Cecilia Wainwright
- Department of Anatomical Pathology, National Health Laboratory Services, D7 Groote Schuur Hospital, University of Cape Town, Observatory, Cape Town 7925, South Africa
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23
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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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24
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Xue Y, Farris AB, Quigley B, Krasinskas A. The Impact of New Technologic and Molecular Advances in the Daily Practice of Gastrointestinal and Hepatobiliary Pathology. Arch Pathol Lab Med 2017; 141:517-527. [PMID: 28157407 DOI: 10.5858/arpa.2016-0261-sa] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The practice of anatomic pathology, and of gastrointestinal pathology in particular, has been dramatically transformed in the past decade. In addition to the multitude of diseases, syndromes, and clinical entities encountered in daily clinical practice, the increasing integration of new technologic and molecular advances into the field of gastroenterology is occurring at a fast pace. Application of these advances has challenged pathologists to correlate newer methodologies with existing morphologic criteria, which in many instances still provide the gold standard for diagnosis. This review describes the impact of new technologic and molecular advances on the daily practice of gastrointestinal and hepatobiliary pathology. We discuss new drugs that can affect the gastrointestinal tract and liver, new endoluminal techniques, new molecular tests that are often performed reflexively, new imaging techniques for evaluating hepatocellular carcinoma, and modified approaches to the gross and histologic assessment of tissues that have been exposed to neoadjuvant therapies.
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Affiliation(s)
| | | | | | - Alyssa Krasinskas
- From the Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia
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Progression of Hepatic Adenoma to Carcinoma in the Setting of Hepatoportal Sclerosis in HIV Patient: Case Report and Review of the Literature. Case Reports Hepatol 2016; 2016:1732069. [PMID: 27812395 PMCID: PMC5080467 DOI: 10.1155/2016/1732069] [Citation(s) in RCA: 4] [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: 08/10/2016] [Accepted: 09/28/2016] [Indexed: 11/17/2022] Open
Abstract
We report a case of hepatic adenoma progression to carcinoma in the setting of hepatoportal sclerosis in an HIV+ patient and provide a review of the scarce literature regarding hepatoportal sclerosis in HIV patients. We describe the clinical presentation, diagnostic workup, and management. This is the first case report in the literature of progression of hepatic adenoma to carcinoma in hepatoportal sclerosis in an HIV patient. This case also highlights the broad differential diagnosis that should always be included in the study of any liver disease in this patient population, including the performance of invasive and aggressive tests to arrive at the final diagnosis.
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Noncirrhotic Portal Hypertension in Perinatally HIV-infected Adolescents Treated With Didanosine-containing Antiretroviral Regimens in Childhood. Pediatr Infect Dis J 2016; 35:e248-52. [PMID: 27167116 DOI: 10.1097/inf.0000000000001202] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Noncirrhotic portal hypertension (NCPH) has been reported in HIV-infected adults. Antiretroviral drugs, as well as genetic and thrombophilic predisposition, have been suggested as possible etiologic factors. METHODS Clinical data were collected from 6 HIV-infected patients attending the Infectious Diseases Departments at respectively Emma Children's Hospital Academic Medical Centre in Amsterdam, The Thai Red Cross AIDS Research Centre, Bangkok, Imperial College Healthcare NHS Trust, London who were diagnosed with NCPH. All underwent extensive blood analysis, liver ultrasound, liver elastography, esophagogastroduodenoscopy and percutaneous needle liver biopsy for histological evaluation. RESULTS We describe 6 perinatally HIV-infected adolescents, all female, who developed NCPH after prolonged exposure during childhood to a didanosine-containing antiretroviral regimen. Histology and electron microscopy showed periportal fibrosis and mitochondrial damage as key findings in their liver biopsies. One of these 6 patients required surgical intervention, the remainder have been managed conservatively to date. CONCLUSIONS Thus, symptomatic NCPH may present in adolescence after perinatally acquired HIV-1 infection. In this case series, risk factors included female sex and prolonged exposure to antiretroviral regimens that included the nucleoside-analogue didanosine in childhood.
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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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Use of antiretroviral therapy and risk of end-stage liver disease and hepatocellular carcinoma in HIV-positive persons. AIDS 2016; 30:1731-43. [PMID: 26752282 DOI: 10.1097/qad.0000000000001018] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVES Although several antiretroviral drugs, including the d-drugs stavudine (d4T) and didanosine (ddI), may cause biomarker-defined hepatotoxicity, their association with clinically defined end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) remains unknown. DESIGN Prospective cohort study. METHODS Data collection on adverse events of anti-HIV drugs study (D:A:D) participants were followed until the first of ESLD (variceal bleeding, hepatic encephalopathy, hepatorenal syndrome or liver transplantation), HCC (histology or α-fetoprotein along with imaging), death, 6 months after last visit or 1 February 2014. Associations between ESLD/HCC and cumulative use of individual antiretrovirals were investigated using Poisson regression adjusting for potential confounders. RESULTS During a median follow-up of 8.4 years, 319 ESLD/HCC cases occurred [incidence 1.01/1000 person-years (95% confidence interval 0.90-1.12)] with a 1-year mortality rate of 62.6%. After adjustment, cumulative (per 5 years) exposure to d4T [relative rate 1.46 (95% confidence interval 1.20-1.77)], ddI [1.32 (1.07-1.63)], tenofovir [TDF, 1.46 (1.11-1.93)] and (fos)amprenavir [APV; 1.47 (1.01-2.15)] was associated with increased ESLD/HCC rates. Longer exposure to emtricitabine [0.51 (0.32-0.83)] and nevirapine [0.76 (0.58-0.98)] were associated with lower ESLD/HCC rates. The ddI/d4T-associated increased ESLD/HCC rate only started to decline 6 years after cessation. CONCLUSION Cumulative use of d4T, ddI, TDF and APV were independently associated with increased ESLD/HCC rates, and intensified monitoring of liver function should hence be considered among all individuals exposed for longer time periods. The use of d-drugs should furthermore be avoided, where there are alternatives available, and focus should be put on those with longer-term d-drugs exposure who remain at increased ESLD/HCC risk. The unexpected, and viral hepatitis-independent, TDF association calls for further investigations.
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Mohite AR, Gambhire PA, Pawar SV, Jain SS, Contractor QQ, Rathi PM. Changing clinical profile and factors associated with liver enzyme abnormalities among HIV-infected persons. Trop Doct 2016; 47:205-211. [PMID: 27342920 DOI: 10.1177/0049475516655068] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The spectrum of liver disease among HIV-infected patients is changing. In the era of antiretroviral therapy, opportunistic infections are diminishing and deranged liver function appears to be due usually to drug-induced liver injury, alcohol, non-alcoholic steatohepatitis (NASH) or chronic hepatitis B. To test this hypothesis, 98 HIV-positive patients with deranged liver function were compared with matched HIV-positive patients with normal liver function and likewise matched HIV-negative patients with normal liver function tests.
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Affiliation(s)
- Ashok R Mohite
- Department of Gastroenterology, TN Medical College and BYL Nair Charitable Hospital, Mumbai, India
| | - Pravir A Gambhire
- Department of Gastroenterology, TN Medical College and BYL Nair Charitable Hospital, Mumbai, India
| | - Sunil V Pawar
- Department of Gastroenterology, TN Medical College and BYL Nair Charitable Hospital, Mumbai, India
| | - Samit S Jain
- Department of Gastroenterology, TN Medical College and BYL Nair Charitable Hospital, Mumbai, India
| | - Qais Q Contractor
- Department of Gastroenterology, TN Medical College and BYL Nair Charitable Hospital, Mumbai, India
| | - Pravin M Rathi
- Department of Gastroenterology, TN Medical College and BYL Nair Charitable Hospital, Mumbai, India
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Bissonnette J, Rautou PE, Valla DC. [Idiopathic non-cirrhotic portal hypertension: An update]. Presse Med 2015; 44:1009-15. [PMID: 26362514 DOI: 10.1016/j.lpm.2015.06.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 05/28/2015] [Accepted: 06/03/2015] [Indexed: 01/16/2023] Open
Abstract
Idiopathic non-cirrhotic portal hypertension is an under-estimated cause of portal hypertension. The diagnosis requires the exclusion of cirrhosis, common causes of chronic liver disease and venous obstruction of the portal and hepatic veins. It has been associated with various extra-hepatic conditions that are most frequently immunologic, prothrombotic, hematologic and toxic. The most frequent clinical complications are variceal hemorrhage and portal vein thrombosis. Complications of portal hypertension should be managed as in patients with cirrhosis.
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Affiliation(s)
- Julien Bissonnette
- AP-HP, hôpital Beaujon, centre de référence des maladies vasculaires du foie, pôle des maladies de l'appareil digestif, service d'hépatologie, DHU unity, 92118 Clichy, France
| | - Pierre-Emmanuel Rautou
- AP-HP, hôpital Beaujon, centre de référence des maladies vasculaires du foie, pôle des maladies de l'appareil digestif, service d'hépatologie, DHU unity, 92118 Clichy, France; Université Paris Diderot, hôpital Bichat, CRI Paris-Montmartre, UMR 1149, PRES SPC, 75018 Paris, France
| | - Dominique-Charles Valla
- AP-HP, hôpital Beaujon, centre de référence des maladies vasculaires du foie, pôle des maladies de l'appareil digestif, service d'hépatologie, DHU unity, 92118 Clichy, France; Université Paris Diderot, hôpital Bichat, CRI Paris-Montmartre, UMR 1149, PRES SPC, 75018 Paris, France; Université Paris Descartes, Paris cardiovascular research center, PARCC, UMR-S970, Inserm, U970, Sorbonne Paris Cité, 75015 Paris, France.
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Schouten JNL, Verheij J, Seijo S. Idiopathic non-cirrhotic portal hypertension: a review. Orphanet J Rare Dis 2015; 10:67. [PMID: 26025214 PMCID: PMC4457997 DOI: 10.1186/s13023-015-0288-8] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Accepted: 05/20/2015] [Indexed: 02/07/2023] Open
Abstract
Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare disease characterized of intrahepatic portal hypertension in the absence of cirrhosis or other causes of liver disease and splanchnic venous thrombosis. The etiology of INCPH can be classified in five categories: 1) immunological disorders (i.e. association with common variable immunodeficiency syndrome, connective tissue diseases, Crohn’s disease, etc.), 2) chronic infections, 3) exposure to medications or toxins (e.g. azathioprine, 6- thioguanine, arsenic), 4) genetic predisposition (i.e. familial aggregation and association with Adams-Oliver syndrome and Turner disease) and 5) prothrombotic conditions (e.g. inherited thrombophilias myeloproliferative neoplasm antiphospholipid syndrome). Roughly, INCPH diagnosis is based on clinical criteria and the formal exclusion of any other causes of portal hypertension. A formal diagnosis is based on the following criteria: 1) presence of unequivocal signs of portal hypertension, 2) absence of cirrhosis, advanced fibrosis or other causes of chronic liver diseases, and 3) absence of thrombosis of the hepatic veins or of the portal vein at imaging. Patients with INCPH usually present with signs or symptoms of portal hypertension such as gastro-esophageal varices, variceal bleeding or splenomegaly. Ascites and/or liver failure can occur in the context of precipitating factors. The development of portal vein thrombosis is common. Survival is manly limited by concomitant disorders. Currently, treatment of INCPH relies on the prevention of complications related to portal hypertension, following current guidelines of cirrhotic portal hypertension. No treatment has been studied aimed to modify the natural history of the disease. Anticoagulation therapy can be considered in patients who develop portal vein thrombosis.
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Affiliation(s)
- Jeoffrey N L Schouten
- Department of Gastroenterology, University Hospital Ghent, De Pintelaan 185, Ghent, Belgium.
| | - Joanne Verheij
- Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
| | - Susana Seijo
- Department of Medicine, CTO, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
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Lee H, Ainechi S, Singh M, Ells PF, Sheehan CE, Lin J. Histological Spectrum of Idiopathic Noncirrhotic Portal Hypertension in Liver Biopsies From Dialysis Patients. Int J Surg Pathol 2015; 23:439-46. [DOI: 10.1177/1066896915582264] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Objectives. Liver biopsy is performed for various indications in dialysis patients. Being a less-common subset, the hepatic pathology in renal dialysis is not well documented. Idiopathic noncirrhotic portal hypertension (INCPH) is a clinical entity associated with unexplained portal hypertension and/or a spectrum of histopathological vascular changes in the liver. After encountering INCPH and vascular changes of INCPH in 2 renal dialysis patients, we sought to further investigate this noteworthy association. Materials and methods. A random search for patients on hemodialysis or peritoneal dialysis with liver biopsy was performed. Hematoxylin and eosin, reticulin, trichrome, and CK7 stains were performed on formalin-fixed, paraffin-embedded tissue sections. Histopathological features were reviewed, and the results were correlated with clinical findings. Results. In all, 13 liver biopsies were retrieved. The mean cumulative duration of dialysis was 50 months (range = 17 months to 11 years). All patients had multiple comorbidities. Indications for biopsy were a combination of abnormal liver function tests (6), portal hypertension (4), ascites (3), and possible cirrhosis (3). Two patients with portal hypertension underwent multiple liver biopsies for diagnostic purposes. All (100%) biopsies showed some histological features of INCPH, including narrowed portal venous lumen (9), increased portal vascular channels (8), shunt vessels (3), dilated sinusoids (9), regenerative nodule (5), and features of venous outflow obstruction (3). No cirrhosis was identified. Conclusion. Liver biopsies from patients on dialysis demonstrate histopathological vascular changes of INCPH. Some (31%) patients present with portal hypertension without cirrhosis. The histological changes may be reflective of underlying risk factors for INCPH in this group.
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Affiliation(s)
| | | | | | | | | | - Jingmei Lin
- Indiana University School of Medicine, Indianapolis, IN, USA
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Matthews GV, Neuhaus J, Bhagani S, Mehta SH, Vlahakis E, Doroana M, Naggie S, Arenas-Pinto A, Peters L, Rockstroh JK. Baseline prevalence and predictors of liver fibrosis among HIV-positive individuals: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med 2015; 16 Suppl 1:129-36. [PMID: 25711331 PMCID: PMC11700561 DOI: 10.1111/hiv.12241] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/21/2014] [Indexed: 11/30/2022]
Abstract
OBJECTIVES Liver disease is increasingly recognized in HIV-positive individuals, even among those without viral hepatitis, partly as a result of the recent availability of noninvasive methods of liver fibrosis assessment. The objective of this substudy is to compare the effects of early versus deferred antiretroviral therapy (ART) on liver fibrosis progression. METHODS Sites in the Strategic Timing of AntiRetroviral Treatment (START) study with access to FibroScan® were invited to participate in the Liver Fibrosis Progression Substudy. All substudy participants underwent FibroScan® at baseline, and two noninvasive serum algorithms, APRI and FIB-4, were calculated. Demographic and liver-related information was collected for all START participants at baseline. RESULTS A total of 230 participants were enrolled in the substudy (11.5% with hepatitis B or C virus coinfection), of whom 221 had a valid transient elastography (TE) result. The median TE score was 4.9 kPa [interquartile range (IQR) 4.3-6.0 kPa]. Seventeen patients (7.8%) [95% confidence interval (CI) 5.1-12.1%] had a TE score of > 7.2 kPa, indicating significant liver fibrosis. Baseline factors associated with higher TE scores in multivariate analysis were higher alanine aminotransferase (ALT) per 10 U/L (P = 0.045), higher log10 HIV RNA (P < 0.001) and Hispanic/Latino ethnicity (P = 0.01). TE correlated weakly with noninvasive markers. CONCLUSIONS At baseline, significant liver fibrosis was observed in approximately 8% of participants, with higher ALT and HIV RNA the only clinical factors associated with increasing TE score. TE will be used annually to monitor fibrosis and evaluate the role of ART in further fibrosis progression.
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Affiliation(s)
- G V Matthews
- Kirby Institute, University of New South Wales, Sydney, Australia
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The efficacy of the ImmuKnow assay for evaluating the immune status in human immunodeficiency virus and hepatitis C virus-coinfected patients. Transplant Proc 2015; 46:733-5. [PMID: 24767336 DOI: 10.1016/j.transproceed.2013.11.119] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Accepted: 11/07/2013] [Indexed: 01/06/2023]
Abstract
BACKGROUND The survival of human immunodeficiency virus (HIV)-infected patients has significantly improved since the introduction of antiretroviral therapy (ART). However, the mortality due to hepatitis C virus (HCV)-related liver disease has not been reduced in HIV/HCV-coinfected patients, and HCV has recently become the most significant cause of death in HIV/HCV-coinfected patients. Liver transplantation might be one of the treatments of choice in such cases, but it is very difficult to evaluate the immune status of these patients due to ART, anti-HCV treatment, and HIV-related immunocompromised state. AIM The aim of this study was to evaluate the immune status in HIV/HCV-coinfected patients using the Cylex ImmuKnow assay, which was designed to monitor the global immune status by measuring the adenosine triphosphate (ATP) levels produced by activated CD4+ T cells. METHODS Twenty-eight HIV/HCV-coinfected patients were included in this study. We evaluated their immune activity using the ImmuKnow assay, and compared the data with those of HCV mono-infected patients indicated for liver transplantation as well as healthy controls. RESULTS The ATP levels of HIV/HCV-coinfected patients were significantly higher than those of HCV mono-infected liver transplant recipients (P < .001), and were significantly lower than those of healthy controls (P = .001). CONCLUSION The ImmuKnow assay was considered to be a useful tool to evaluate the immune status of HIV/HCV-coinfected patients.
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Abstract
There are an estimated 40 million HIV infected individuals worldwide, with chronic liver disease being the 2nd leading cause of mortality in this population. Elevated liver functions are commonly noted in HIV patients and the etiologies are varied. Viral hepatitis B and C, fatty liver and drug induced liver injury are more common. Treatment options for viral hepatitis C are rapidly evolving and are promising, but treatments are limited for the other conditions and is primarily supportive. Opportunistic infections of the liver are now uncommon. Irrespective of etiology, management requires referral to specialized centers and with due diligence mortality can be reduced.
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Strauss E, Valla D. Non-cirrhotic portal hypertension--concept, diagnosis and clinical management. Clin Res Hepatol Gastroenterol 2014; 38:564-9. [PMID: 24581591 DOI: 10.1016/j.clinre.2013.12.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Revised: 12/12/2013] [Accepted: 12/24/2013] [Indexed: 02/08/2023]
Abstract
Non-cirrhotic portal hypertension (NCPH) is mainly related to vascular disorders in the portal system, granuloma formation with periportal fibrosis or genetic alterations affecting the hepatobiliary system. For the diagnosis of the so-called idiopathic NCPH, it is essential to rule out chronic liver diseases associated with progression to cirrhosis as viral hepatitis B and C, alcoholic and non-alcoholic fatty liver, autoimmune disease, hereditary hemochromatosis, Wilson's disease as well as primary biliary cirrhosis and primary sclerosing cholagitis. This mini review will focus on the most common types of NCPH, excluding the idiopathic NCPH. Primary Budd-Chiari syndrome, characterized by obstruction of hepatic venous outflow, must be distinguished from sinusoidal obstruction syndrome, a cause of portal hypertension associated with exposure to toxic plants or therapeutic agents. Noninvasive imaging methods usually help the diagnosis of both Budd-Chiari syndrome and portal thrombosis, the later a relatively frequent cause NCPH. Clinical presentation and management of these vascular disorders are evaluated. Schistosomiasis, a worldwide spread endemic parasitic disease, may evolve to severe forms of the disease with huge spleen and gastroesophageal varices due to presinusoidal portal hypertension. Although management of acute upper gastrointestinal bleeding is similar to that of cirrhosis, prevention of rebleeding differs. Instead of portosystemic shunt procedures, the esophagogastric devascularization with splenectomy is the accepted surgical alternative. Its association with endoscopic therapy is suggested to be the best option for PH due to schistosomiasis. In conclusion, the prompt diagnosis of the disorder leading to non-cirrhotic portal hypertension is essential for its correct management.
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Affiliation(s)
- Edna Strauss
- School of Medicine, University of São Paulo, São Paulo, Brazil.
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Goel A, Elias JE, Eapen CE, Ramakrishna B, Elias E. Idiopathic Non-Cirrhotic Intrahepatic Portal Hypertension (NCIPH)-Newer Insights into Pathogenesis and Emerging Newer Treatment Options. J Clin Exp Hepatol 2014; 4:247-56. [PMID: 25755567 PMCID: PMC4284211 DOI: 10.1016/j.jceh.2014.07.005] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Accepted: 07/05/2014] [Indexed: 12/12/2022] Open
Abstract
Chronic microangiopathy of portal venules results in idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH). Recent data suggest a role for vasoactive factors of portal venous origin in the pathogenesis of this 'pure' vasculopathy of the liver. Enteropathies (often silent), are an important 'driver' of this disease. NCIPH is under-recognized and often mis-labeled as cryptogenic cirrhosis. Liver biopsy is needed to prove the diagnosis of NCIPH. In these patients, with advancing disease and increased porto-systemic shunting, the portal venous vasoactive factors bypass the liver filter and contribute to the development of pulmonary vascular endothelial disorders-porto-pulmonary hypertension and hepato-pulmonary syndrome as well as mesangiocapillary glomerulonephritis. Prognosis in NCIPH patients is determined by presence, recognition and management of associated disorders. With better understanding of the pathogenesis of NCIPH, newer treatment options are being explored. Imbalance in ADAMTS 13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13): vWF (von-Willebrand factor) ratio is documented in NCIPH patients and may have a pathogenic role. Therapeutic interventions to correct this imbalance may prove to be important in the management of NCIPH.
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Key Words
- ADAMTS 13
- CVID, common variable immunodeficiency
- HPS, hepato-pulmonary syndrome
- HVPG, hepatic venous pressure gradient
- IBD, inflammatory bowel disease
- NCIPH, non-cirrhotic intrahepatic portal hypertension
- NRH, nodular regenerative hyperplasia
- OPV, obliterative portal venopathy
- PPH, porto-pulmonary hypertension
- PVT, portal vein thrombosis
- SOS, sinusoidal obstruction syndrome
- endothelial dysfunction
- primary haemostasis
- tTG, Tissue transglutaminase
- von-Willebrand factor (vWF)
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Affiliation(s)
- Ashish Goel
- Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
| | | | | | | | - Elwyn Elias
- Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India,Liver Unit, University Hospital Birmingham, Birmingham, UK,Address for correspondence: Elwyn Elias, Emeritus Professor, Liver Unit, University Hospital Birmingham, Birmingham, UK.
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Abstract
Non-cirrhotic portal hypertension (NCPH) encompasses a wide range of disorders, primarily vascular in origin, presenting with portal hypertension (PHT), but with preserved liver synthetic functions and near normal hepatic venous pressure gradient (HVPG). Non-cirrhotic portal fibrosis/Idiopathic PHT (NCPF/IPH) and extrahepatic portal venous obstruction (EHPVO) are two prototype disorders in the category. Etiopathogenesis in both of them centers on infections and prothrombotic states. Presentation and management strategies focus on repeated well tolerated episodes of variceal bleed and moderate to massive splenomegaly and other features of PHT. While the long-term prognosis is generally good in NCPF, portal biliopathy and parenchymal extinction after prolonged PHT makes outcome somewhat less favorable in EHPVO. While hepatic schistosomiasis, congenital hepatic fibrosis and nodular regenerative hyperplasia have their distinctive features, they often present with NCPH.
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Affiliation(s)
- Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi 110070, India.
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi 110070, India
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Eguchi S, Takatsuki M, Soyama A, Hidaka M, Nakao K, Shirasaka T, Yamamoto M, Tachikawa N, Gatanaga H, Kugiyama Y, Yatsuhashi H, Ichida T, Kokudo N. Analysis of the Hepatic Functional Reserve, Portal Hypertension, and Prognosis of Patients With Human Immunodeficiency Virus/Hepatitis C Virus Coinfection Through Contaminated Blood Products in Japan. Transplant Proc 2014; 46:736-8. [DOI: 10.1016/j.transproceed.2013.11.126] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Accepted: 11/07/2013] [Indexed: 10/25/2022]
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40
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Khanna R, Sarin SK. Non-cirrhotic portal hypertension - diagnosis and management. J Hepatol 2014; 60:421-41. [PMID: 23978714 DOI: 10.1016/j.jhep.2013.08.013] [Citation(s) in RCA: 256] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2013] [Revised: 08/07/2013] [Accepted: 08/19/2013] [Indexed: 02/06/2023]
Abstract
NCPH is a heterogeneous group of liver disorders of vascular origin, leading to PHT with near normal HVPG. NCPF/IPH is a disorder of young adults or middle aged women, whereas EHPVO is a disorder of childhood. Early age acute or recurrent infections in an individual with thrombotic predisposition constitute the likely pathogenesis. Both disorders present with clinically significant PHT with preserved liver functions. Diagnosis is easy and can often be made clinically with support from imaging modalities. Management centers on control and prophylaxis of variceal bleeding. In EHPVO, there are additional concerns of growth faltering, portal biliopathy, MHE and parenchymal dysfunction. Surgical shunts are indicated in patients with failure of endotherapy, bleeding from sites not amenable to endotherapy, symptomatic hypersplenism or symptomatic biliopathy. Persistent growth failure, symptomatic and recurrent hepatic encephalopathy, impaired quality of life or massive splenomegaly that interferes with daily activities are other surgical indications. Rex-shunt or MLPVB is the recommended shunt for EHPVO, but needs proper pre-operative radiological assessment and surgical expertise. Both disorders have otherwise a fairly good prognosis, but need regular and careful surveillance. Hepatic schistosomiasis, CHF and NRH have similar presentation and comparable prognosis.
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Affiliation(s)
- Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
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41
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Lengthy follow-up after liver transplantation for nodular regenerative hyperplasia in human immunodeficiency virus-infected patients: does the disease recur? Transplantation 2014; 96:e79-81. [PMID: 24296606 DOI: 10.1097/01.tp.0000436930.53768.45] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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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: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 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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Sherman KE, Thomas D, Chung RT. Human immunodeficiency virus and liver disease forum 2012. Hepatology 2014; 59:307-17. [PMID: 23904401 PMCID: PMC3849330 DOI: 10.1002/hep.26638] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2013] [Revised: 06/24/2013] [Accepted: 07/13/2013] [Indexed: 02/06/2023]
Abstract
In the United States, more than 1.1 million individuals are infected with the human immunodeficiency virus (HIV). These patients exhibit a high frequency of coinfections with other hepatotropic viruses and ongoing fibrosis, leading to cirrhosis and liver-related mortality. Etiologies of liver disease include viral hepatitis coinfections, drug-related hepatotoxicity, fatty liver disease, and direct and indirect effects from HIV infection, including increased bacterial translocation, immune activation, and presence of soluble proteins, that modulate the hepatic cytokine environment. New treatments for hepatitis C virus (HCV) using direct-acting agents appear viable, though issues related to intrinsic toxicities and drug-drug interactions remain. Recent research suggests that acute HCV infection, unrecognized hepatitis D infection, and hepatitis E may all represent emergent areas of concern. Antiretroviral agents, including those used in recent years, may represent risk factors for hepatic injury and portal hypertension. Key issues in the future include systematic implementation of liver disease management and new treatment in HIV-infected populations with concomitant injection drug use, alcohol use, and low socioeconomic status.
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Affiliation(s)
- Kenneth E. Sherman
- Division of Digestive Diseases; University of Cincinnati College of Medicine; Cincinnati OH
| | - David Thomas
- Division of Infectious Diseases; Johns Hopkins Medical Institute; Baltimore MD
| | - Raymond T. Chung
- Harvard Medical School, Massachusetts General Hospital; Boston MA
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44
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Takatsuki M, Soyama A, Eguchi S. Liver transplantation for HIV/hepatitis C virus co-infected patients. Hepatol Res 2014; 44:17-21. [PMID: 23607831 DOI: 10.1111/hepr.12132] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2013] [Revised: 04/07/2013] [Accepted: 04/07/2013] [Indexed: 12/26/2022]
Abstract
Since the introduction of antiretroviral therapy (ART) in the mid-1990s, AIDS-related death has been dramatically reduced, and hepatitis-C-virus (HCV)-related liver failure or hepatocellular carcinoma has currently become the leading cause of death in HIV/HCV co-infected patients. Liver transplantation may be one of the treatments of choices in such cases, but the indications for transplantation, perioperative management including both HIV and HCV treatments, immunosuppression and the prevention/treatment of infectious complications are all still topics of debate. With the improved understanding of the viral behaviors of both HIV and HCV and the development of novel strategies, especially to avoid drug interactions between ART and immunosuppression, liver transplantation has become a realistic treatment for HIV/HCV co-infected patients.
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Affiliation(s)
- Mitsuhisa Takatsuki
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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45
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Abstract
Drug-induced hepatotoxicity is underrecognized but increasingly identified as causing acute and chronic liver disease. Several prescription drugs, over-the-counter medications, dietary and/or supplementary agents, and herbal products are hepatotoxic. Drug-induced liver injury mimics other primary acute and chronic liver diseases and it should be considered in patients with hepatobiliary disease. Certain drugs result in specific histopathologic patterns of liver injury, which may help in sorting out the responsible drug. The diagnosis of drug-induced hepatotoxicity is challenging. It involves excluding other possible causes, careful medication history, the latent period between drug exposure and symptom onset and/or abnormal liver tests, and histopathologic findings.
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Affiliation(s)
- Xuchen Zhang
- Department of Pathology, VA Connecticut Health System and Yale University School of Medicine, 310 Cedar Street, LH 108, New Haven, CT 06516, USA.
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46
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Aggarwal S, Fiel MI, Schiano TD. Obliterative portal venopathy: a clinical and histopathological review. Dig Dis Sci 2013; 58:2767-76. [PMID: 23812828 DOI: 10.1007/s10620-013-2736-4] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2013] [Accepted: 05/29/2013] [Indexed: 12/12/2022]
Abstract
Non-cirrhotic portal hypertension (NCPH) is characterized by the elevation of the portal pressure in the absence of cirrhosis. Obliterative portal venopathy (OPV) as a cause of NCPH is being increasingly diagnosed, especially after recent reports of its occurrence in patients with HIV using didanosine. Patients usually present with episodes of variceal hemorrhage and other features of portal hypertension including jaundice, ascites, encephalopathy and hepatopulmonary syndrome. Hepatic synthetic function is typically well preserved and the laboratory evaluation in OPV patients typically reveals only mild nonspecific hematological abnormalities chiefly related to hypersplenism. Its diagnosis remains a challenge and patients are often mistakenly diagnosed as having cirrhosis. Despite the increasing recognition of OPV, its etiology and pathogenesis are still unclear. A number of etiologies have been proposed including genetic predisposition, recurrent bacterial infections, HIV infection and highly active antiretroviral therapy, an altered immune response, hypercoagulability, and exposure to chemicals and certain medications. Histopathological evaluation remains critical in excluding cirrhosis and other causes of portal hypertension, and is the only way of definitively establishing the diagnosis of OPV. Clinicians should have a high index of suspicion for OPV in patients who present with variceal bleeding and splenomegaly and who do not have other features of cirrhosis. The purpose of this review is to summarize the known etiologies for OPV and its associated clinical aspects and correlations, and to also provide ample histophotomicrographs of OPV to aid in the diagnosis. It will also help raise awareness of this entity amongst pathologists and clinicians alike.
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Affiliation(s)
- Sourabh Aggarwal
- School of Medicine, Western Michigan University, Kalamazoo, MI, USA
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47
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Cantez MS, Gerenli N, Ertekin V, Güllüoğlu M, Durmaz Ö. Hepatoportal sclerosis in childhood: descriptive analysis of 12 patients. J Korean Med Sci 2013; 28:1507-11. [PMID: 24133357 PMCID: PMC3792606 DOI: 10.3346/jkms.2013.28.10.1507] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Accepted: 07/29/2013] [Indexed: 11/20/2022] Open
Abstract
Hepatoportal sclerosis (HPS) is defined as sclerosis of portal areas in the absence of cirrhosis. There is little information about HPS in children in the literature. The aim of this study was to describe the clinical presentation, associated disorders, laboratory characteristics and outcome of children who were diagnosed as HPS. This study included 12 children diagnosed as HPS by the Pathology Department between 2005 and 2011. Data were collected from the gastroenterology clinic charts retrospectively, including demographics, presentation characteristics, laboratory data and recent status of patients. Twelve patients were enrolled (6 girls, 6 boys). The median age of patients was 13.5 yr. Median age at the time of biopsy was 11 yr. Four patients had splenomegaly, 3 had esophageal varices, one had hepatopulmonary syndrome and had been transplanted. Smooth muscle antibody was found positive in 4 patients, without autoimmune hepatitis findings in liver biopsy. One patient had celiac disease and another patient had positive celiac disease serology but pathology findings. Another patient had Turner's syndrome. Mean follow-up time was 39 months (3.3 yr) after biopsy. Hepatoportal sclerosis does not necessarily present with portal hypertension in children.
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Affiliation(s)
- Mustafa Serdar Cantez
- Istanbul University, Istanbul Faculty of Medicine, Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Istanbul, Turkey
| | - Nelgin Gerenli
- Istanbul University, Istanbul Faculty of Medicine, Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Istanbul, Turkey
| | - Vildan Ertekin
- Istanbul University, Istanbul Faculty of Medicine, Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Istanbul, Turkey
| | - Mine Güllüoğlu
- Istanbul University, Istanbul Faculty of Medicine, Department of Pathology, Istanbul, Turkey
| | - Özlem Durmaz
- Istanbul University, Istanbul Faculty of Medicine, Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Istanbul, Turkey
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Eguchi S, Takatsuki M, Kuroki T. Liver transplantation for patients with human immunodeficiency virus and hepatitis C virus co-infection: update in 2013. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2013; 21:263-8. [PMID: 24027085 DOI: 10.1002/jhbp.31] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Because of the progress of anti-retroviral therapy (ART) for human immunodeficiency virus (HIV), mortality due to opportunistic infection resulting in AIDS has been remarkably reduced. However, meanwhile, half of those patients have died of end-stage liver cirrhosis due to hepatitis C virus (HCV) with liver cirrhosis and early occurrence of hepatocellular carcinoma. Recently, in 2013, non-cirrhotic portal hypertension due to ART drugs or still unknown mechanisms have become problematic with early progression of the disease in this patient population. Liver transplantation (LT) could be one treatment of choice in such cases, but the indications for LT perioperative management, including both HIV and HCV treatments and immunosuppression, are still challenging. In this review, we update the literature on HIV/HCV co-infection and LT as well as recent effort for modifying allocation system for those patients.
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Affiliation(s)
- Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
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49
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Parikh ND, Martel-Laferriere V, Kushner T, Childs K, Vachon ML, Dronamraju D, Taylor C, Fiel MI, Schiano T, Nelson M, Agarwal K, Dieterich DT. Clinical factors that predict noncirrhotic portal hypertension in HIV-infected patients: a proposed diagnostic algorithm. J Infect Dis 2013; 209:734-8. [PMID: 23911709 DOI: 10.1093/infdis/jit412] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Noncirrhotic portal hypertension (NCPH) is a rare but important clinical entity in human immunodeficiency virus (HIV) populations. The purpose of this study was to describe the clinical factors associated with the condition in an effort to formulate a diagnostic algorithm for easy and early diagnosis. We performed a multicenter, retrospective case-control study of 34 patients with NCPH and 68 control HIV patients. The study found that thrombocytopenia, splenomegaly, didanosine use, elevated aminotransferases, and an elevated alkaline phosphatase level were all significantly more prevalent in the NCPH cohort. Using these easily available clinical parameters, we developed an algorithm for early diagnosis of NCPH in HIV.
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Affiliation(s)
- Neil D Parikh
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
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50
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Seijo S, Lozano JJ, Alonso C, Reverter E, Miquel R, Abraldes JG, Martinez-Chantar ML, Garcia-Criado A, Berzigotti A, Castro A, Mato JM, Bosch J, Garcia-Pagan JC. Metabolomics discloses potential biomarkers for the noninvasive diagnosis of idiopathic portal hypertension. Am J Gastroenterol 2013; 108:926-32. [PMID: 23419380 DOI: 10.1038/ajg.2013.11] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Idiopathic portal hypertension (IPH) is a rare cause of portal hypertension that lacks a specific diagnostic test. Requiring ruling-out other causes of portal hypertension it is frequently misdiagnosed. This study evaluates whether using high-throughput techniques there is a metabolomic profile allowing a noninvasive diagnosis of IPH. METHODS Thirty-three IPH patients were included. Matched patients with cirrhosis (CH) and healthy volunteers (HV) were included as controls. Metabolomic analysis of plasma samples was performed using UPLC-time-of-flight-mass spectrometry. We computed Student's P-values, corrected by multiple comparison and VIP score (Variable Importance in the Projection). The metabolites were selected with an adjusted Benjamini Hochberg P value <0.05. We use markers with a greater VIP score, to build partial least squares projection to latent structures regression with discriminant analysis (PLS-DA) representative models to discriminate IPH from CH and from HV. The performance of the PLS-DA model was evaluated using R(2) and Q(2) parameter. An additional internal cross-validation was done. RESULTS PLS-DA analysis showed a clear separation of IPH from CH with a model involving 28 metabolites (Q(2)=0.67, area under the curve (AUC)=0.99) and a clear separation of IPH from healthy subjects with a model including 31 metabolites (Q(2)=0.75, AUC=0.98). After cross-validation, both models showed high rates of sensitivity (94.8 and 97.5), specificity (89.1 and 89.7), and AUC (0.98 and 0.98), reinforcing the strength of our findings. CONCLUSIONS A metabolomic profile clearly differentiating patients with IPH from CH and healthy subjects has been identified using subsets of 28 and 31 metabolites, respectively. Therefore, metabolomic analysis appears to be a valuable tool for the noninvasive diagnosis of IPH.
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Affiliation(s)
- Susana Seijo
- Liver Unit, Hepatic Hemodynamic Laboratory, Institut de Malalties Digestives i Metaboliques, Hospital Clínic-Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
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