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Dalekos GN, Gatselis NK. Variant and Specific Forms of Autoimmune Cholestatic Liver Diseases. Arch Immunol Ther Exp (Warsz) 2019; 67:197-211. [PMID: 31165900 DOI: 10.1007/s00005-019-00550-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Accepted: 05/31/2019] [Indexed: 12/12/2022]
Abstract
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the main autoimmune cholestatic liver diseases. IgG4-associated sclerosing cholangitis is another distinct immune-mediated cholestatic disorder of unknown aetiology that is frequently associated with autoimmune pancreatitis or other IgG4-related diseases. Although the majority of PBC and PSC patients have a typical presentation, there are common and uncommon important variants or specific subgroups that observed in everyday routine clinical practice. In this updated review, we summarize the published data giving also our own experience on the variants and specific groups of autoimmune cholestatic liver diseases. Actually, we give in detail the underlining difficulties and the rising dilemmas concerning the diagnosis and management of these special conditions in the clinical spectrum of autoimmune cholestatic liver diseases including the IgG4-associated sclerosing cholangitis highlighting also the uncertainties and the potential new eras of the research agenda.
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Affiliation(s)
- George N Dalekos
- Institute of Internal Medicine and Hepatology, Larissa, Greece.
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, 41110, Larissa, Greece.
| | - Nikolaos K Gatselis
- Institute of Internal Medicine and Hepatology, Larissa, Greece
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, 41110, Larissa, Greece
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Hata N, Song SE, Olubiyi O, Arimitsu Y, Fujimoto K, Kato T, Tuncali K, Tani S, Tokuda J. Body-mounted robotic instrument guide for image-guided cryotherapy of renal cancer. Med Phys 2016; 43:843-53. [PMID: 26843245 PMCID: PMC4723400 DOI: 10.1118/1.4939875] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Revised: 12/10/2015] [Accepted: 01/02/2016] [Indexed: 01/26/2023] Open
Abstract
PURPOSE Image-guided cryotherapy of renal cancer is an emerging alternative to surgical nephrectomy, particularly for those who cannot sustain the physical burden of surgery. It is well known that the outcome of this therapy depends on the accurate placement of the cryotherapy probe. Therefore, a robotic instrument guide may help physicians aim the cryotherapy probe precisely to maximize the efficacy of the treatment and avoid damage to critical surrounding structures. The objective of this paper was to propose a robotic instrument guide for orienting cryotherapy probes in image-guided cryotherapy of renal cancers. The authors propose a body-mounted robotic guide that is expected to be less susceptible to guidance errors caused by the patient's whole body motion. METHODS Keeping the device's minimal footprint in mind, the authors developed and validated a body-mounted, robotic instrument guide that can maintain the geometrical relationship between the device and the patient's body, even in the presence of the patient's frequent body motions. The guide can orient the cryotherapy probe with the skin incision point as the remote-center-of-motion. The authors' validation studies included an evaluation of the mechanical accuracy and position repeatability of the robotic instrument guide. The authors also performed a mock MRI-guided cryotherapy procedure with a phantom to compare the advantage of robotically assisted probe replacements over a free-hand approach, by introducing organ motions to investigate their effects on the accurate placement of the cryotherapy probe. Measurements collected for performance analysis included accuracy and time taken for probe placements. Multivariate analysis was performed to assess if either or both organ motion and the robotic guide impacted these measurements. RESULTS The mechanical accuracy and position repeatability of the probe placement using the robotic instrument guide were 0.3 and 0.1 mm, respectively, at a depth of 80 mm. The phantom test indicated that the accuracy of probe placement was significantly better with the robotic instrument guide (4.1 mm) than without the guide (6.3 mm, p<0.001), even in the presence of body motion. When independent organ motion was artificially added, in addition to body motion, the advantage of accurate probe placement using the robotic instrument guide disappeared statistically [i.e., 6.0 mm with the robotic guide and 5.9 mm without the robotic guide (p = 0.906)]. When the robotic instrument guide was used, the total time required to complete the procedure was reduced from 19.6 to 12.7 min (p<0.001). Multivariable analysis indicated that the robotic instrument guide, not the organ motion, was the cause of statistical significance. The statistical power the authors obtained was 88% in accuracy assessment and 99% higher in duration measurement. CONCLUSIONS The body-mounted robotic instrument guide allows positioning of the probe during image-guided cryotherapy of renal cancer and was done in fewer attempts and in less time than the free-hand approach. The accuracy of the placement of the cryotherapy probe was better using the robotic instrument guide than without the guide when no organ motion was present. The accuracy between the robotic and free-hand approach becomes comparable when organ motion was present.
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Affiliation(s)
- Nobuhiko Hata
- National Center for Image Guided Therapy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
| | - Sang-Eun Song
- National Center for Image Guided Therapy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
| | - Olutayo Olubiyi
- National Center for Image Guided Therapy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
| | | | | | - Takahisa Kato
- Healthcare Optics Research Laboratory, Canon U.S.A., Cambridge, Massachusetts 02144
| | - Kemal Tuncali
- National Center for Image Guided Therapy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
| | - Soichiro Tani
- National Center for Image Guided Therapy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
| | - Junichi Tokuda
- National Center for Image Guided Therapy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
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Pokorska-Śpiewak M, Kowalik-Mikołajewska B, Aniszewska M, Pluta M, Marczyńska M. Is liver biopsy still needed in children with chronic viral hepatitis? World J Gastroenterol 2015; 21:12141-12149. [PMID: 26576098 PMCID: PMC4641131 DOI: 10.3748/wjg.v21.i42.12141] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 09/23/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Liver biopsy is a standard method used for obtaining liver tissue for histopathological evaluation. Since reliable serological and virological tests are currently available, liver biopsy is no longer needed for the etiological diagnosis of chronic hepatitis B and C. However, liver histology remains the gold standard as a prognostic tool, providing information about the liver disease progression (grading of necroinflammatory activity and staging of fibrosis) and serving clinicians in the management and therapeutic decisions. In general, histopathological evaluation is indicated before starting the antiviral treatment. Main limitations of the liver biopsy include its invasive and painful procedure, sampling errors and the inter- and intra-observer variability. In addition, indications for the liver biopsy in pediatric patients with chronic viral hepatitis were questioned recently, and efforts have been made toward the development of non-invasive methods as an alternative to the liver biopsy. The most commonly used methods are novel imaging studies (elastography) and combinations of biomarkers. However, to date, none of these tests was validated in children with chronic viral hepatitis. In this review, we present the current status of the liver biopsy in the management of chronic viral hepatitis B and C in pediatric population, including specific indications, complications, contraindications, problems, limitations, and alternative non-invasive methods.
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Erturk A, Cure E, Ozkurt Z, Parlak E, Cure MC. Serum fibronectin levels in acute and chronic viral hepatitis patients. Malays J Med Sci 2014; 21:29-36. [PMID: 24639609 DOI: pmid/24639609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2013] [Accepted: 11/08/2013] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The aim of this study was to investigate the serum fibronectin (FN) levels and liver enzyme activities in patients with acute hepatitis (A, B, C) and chronic viral hepatitis (B, C); determine whether the virus types correlated with disease severity; and assess whether FN could be used as a marker of virus type or disease severity in patients. METHODS A total of 60 subjects were enrolled in the study, including 20 patients with acute hepatitis (A, B, C), 20 with chronic hepatitis (B, C), and 20 healthy controls. Serum fibronectin (FN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and albumin were measured in all patients from blood samples. RESULTS Serum FN levels were significantly lower in acute (122.9 μg/mL (SD 43.1), P < 0.001) and chronic hepatitis patients (135.7 μg/mL (SD 46.0), P < 0 .001) compared to controls 221.4 μg/mL (SD 32.5). A negative correlation was found between serum FN and AST (r(2) = 0.528, P < 0.001), ALT (r(2) = 0.425, P < 0.001), and GGT (r(2) = 0.339, P < 0.001). Additionally, high serum GGT levels (β = -0.375, P = 0.010), and low serum albumin levels (β = -0.305, P = 0.008) were associated with low serum FN levels. CONCLUSION Serum FN levels were lower in both acute and chronic hepatitis patients, and an inverse relationship between serum FN and serum AST, ALT, and GGT levels was found. A decrease in serum FN levels may indicate hepatitis severity as AST and ALT represent hepatocyte damage.
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Affiliation(s)
- Ayse Erturk
- Department of Infectious Diseases, School of Medicine, Recep Tayyip Erdogan University, 53100 Rize, Turkey
| | - Erkan Cure
- Department of Internal Medicine, School of Medicine, Recep Tayyip Erdogan University, 53100 Rize, Turkey
| | - Zulal Ozkurt
- Department of Infectious Diseases, School of Medicine, Ataturk University, 25240 Erzurum, Turkey
| | - Emine Parlak
- Department of Infectious Diseases, School of Medicine, Ataturk University, 25240 Erzurum, Turkey
| | - Medine Cumhur Cure
- Department of Biochemistry, School of Medicine, Recep Tayyip Erdogan University, 53100 Rize, Turkey
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Rigopoulou EI, Zachou K, Gatselis NK, Papadamou G, Koukoulis GK, Dalekos GN. Primary biliary cirrhosis in HBV and HCV patients: Clinical characteristics and outcome. World J Hepatol 2013; 5:577-583. [PMID: 24179617 PMCID: PMC3812460 DOI: 10.4254/wjh.v5.i10.577] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2013] [Revised: 09/03/2013] [Accepted: 10/16/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To present the characteristics, management and outcome of patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infections concurrent with primary biliary cirrhosis (PBC).
METHODS: Since January 2001 to September 2009, we retrospectively evaluated the medical records of all HBV (n = 1493) and HCV patients (n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC (8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of PBC.
RESULTS: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients, while one third (5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV (56.1 ± 11.2 vs 68.5 ± 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics (10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency (87.5% vs 33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during follow-up.
CONCLUSION: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC.
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Li N, Puga Yung GL, Pradier A, Toso C, Giostra E, Morard I, Spahr L, Seebach JD. NK cell isolation from liver biopsies: phenotypic and functional analysis of low cell numbers by flow cytometry. Front Immunol 2013; 4:61. [PMID: 23482713 PMCID: PMC3593626 DOI: 10.3389/fimmu.2013.00061] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2012] [Accepted: 02/22/2013] [Indexed: 12/29/2022] Open
Abstract
Natural killer (NK) cells are considered to play a critical role in liver disease. However, the available numbers of intrahepatic lymphocytes (IHL) derived from liver biopsies (LB) for ex vivo analysis of intrahepatic NK cells is very limited; and the isolation method may hamper not only yields and viability, but also phenotype and function of IHL. The aim of the present study was therefore to (1) refine and evaluate the cell yields and viability of a modified isolation protocol from standard size needle LB; and (2) to test the effects of mechanical dissociation and enzymatic tissue digestion, as well as the analysis of very low cell numbers, on the phenotype and function of intrahepatic NK cells. Peripheral blood mononuclear cells (PBMC) and IHL, freshly isolated from the peripheral blood, LB (n = 11) or partial liver resections (n = 5), were used for phenotypic analysis by flow cytometry. NK cell function, i.e., degranulation and cytokine production, was determined by staining of CD107a and intracellular IFN-γ following in vitro stimulation. The mean weight of the LB specimens was 9.1 mg, and a mean number of 7,364 IHL/mg were obtained with a viability of >90%. Exposure of IHL and PBMC to 0.5 mg/ml collagenase IV and 0.02 mg/ml DNase I for 30 min did affect neither the viability, NK cell function, nor the percentages of CD56+, NKp46+, and CD16+ NK cells, whereas the level of CD56 surface expression was reduced. The phenotype of LB-derived NK cells was reliably characterized by acquiring as few as 2,500 IHL per tube for flow cytometry. The functional assay of intrahepatic NK cells was miniaturized by culturing as few as 25,000 IHL in 25 μl (106/ml) using 96-well V-bottom plates with IL-2 and IL-12 overnight, followed by a 4 h stimulation with K562 cells at a NK:K562 ratio of 1:1. In summary, we report reliable phenotypic and functional analyses of small numbers of intrahepatic NK cells isolated from LB specimens providing us with a tool to better address the emerging role of human NK cell immunobiology in liver diseases.
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Affiliation(s)
- Ning Li
- Division of Clinical Immunology and Allergology, Department of Medical Specialties, University Hospital and Medical Faculty Geneva, Switzerland
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Chopra S, Wu MLC. Specimens from biopsies of colorectal polyps often harbor additional diagnoses. PATHOLOGY RESEARCH INTERNATIONAL 2013; 2013:570526. [PMID: 24455417 PMCID: PMC3886612 DOI: 10.1155/2013/570526] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Accepted: 11/13/2013] [Indexed: 12/11/2022]
Abstract
Objectives. The utility of examining specimens from colorectal biopsies of polyps for nonneoplastic diseases is currently unknown. Our objectives were to characterize such additional diagnoses that could be rendered. Methods. We retrospectively and prospectively reviewed specimens from endoscopic biopsies of colorectal polyps obtained during routine screening or surveillance. Results. 17 of 168 specimens (10.1%) contained additional diagnoses, including schistosomiasis, eosinophilic colitis, intestinal spirochetosis, melanosis coli, and other entities. These findings were easily overlooked because they often affected mucosa that was spared by the polyps or were often evident only at high magnification. Schistosomiasis, eosinophilic colitis, and intestinal spirochetosis were clinically occult. Conclusions. Specimens from biopsies of colorectal polyps often harbor other diagnoses, in addition to polyps, and can be simultaneously screened for polyps and examined for nonneoplastic diseases. Detection of other diagnoses in addition to polyps requires awareness, examination at high magnification, and examination of areas spared by the polyps.
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Affiliation(s)
- Shefali Chopra
- Department of Pathology and Laboratory Medicine, University of California Irvine School of Medicine, Irvine, CA 92868, USA
| | - Mark Li-cheng Wu
- Department of Pathology and Laboratory Medicine, University of California Irvine School of Medicine, Irvine, CA 92868, USA
- *Mark Li-cheng Wu:
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Rolls Royce for everybody? Diagnosing liver disease by mini-laparoscopy. J Hepatol 2011; 54:584-5. [PMID: 21159402 DOI: 10.1016/j.jhep.2010.09.033] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2010] [Accepted: 09/29/2010] [Indexed: 12/17/2022]
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Abstract
In chronic viral hepatitis, the role of liver biopsy as a diagnostic test has seen a decline, paralleled by its increasing importance for prognostic purposes. Nowadays, the main indication for liver biopsy in chronic viral hepatitis is to assess the severity of the disease, in terms of both necro-inflammation (grade) and fibrosis (stage), which is important for prognosis and therapeutic management. Several scoring systems have been proposed for grading and staging chronic viral hepatitis and there is no a general consensus on the best system to be used in the daily practice. All scoring systems have their drawbacks and all may be affected by sampling and observer variability. Whatever the system used, a histological score is a reductive approach since damage in chronic viral hepatitis is a complex biological process. Thus, scoring systems are not intended to replace the detailed, descriptive, pathology report. In fact, lesions other than those scored for grading and staging may have clinical relevance and should be assessed and reported. This paper aims to provide a systematic approach to the interpretation of liver biopsies obtained in cases of chronic viral hepatitis, with the hope of helping general pathologists in their diagnostic practice.
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Mubarak M. Non-viral-related pathologic findings in liver needle biopsy specimens from patients with chronic viral hepatitis. Am J Clin Pathol 2010; 134:168-169. [PMID: 20551282 DOI: 10.1309/ajcppo69yirmkhik] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
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