Liver biopsy in primary biliary cholangitis: is sinusoidal fibrosis the missing key?

2019 ◽  
Vol 72 (10) ◽  
pp. 669-676 ◽  
Author(s):  
Thomas Warnes ◽  
Stephen Roberts ◽  
Alexander Smith ◽  
Najib Haboubi ◽  
Raymond F McMahon
Keyword(s):  
Liver Biopsy ◽  
Clinical Outcomes ◽  
Prognostic Value ◽  
Staging System ◽  
Primary Biliary Cholangitis ◽  
Hepatic Decompensation ◽  
Optimal Method ◽  
Mayo Score ◽  
Serum Aspartate Aminotransferase

AimsThe role of liver biopsy in primary biliary cholangitis (PBC) is controversial, as is the optimal method of histological assessment. We compared the Ludwig and Ishak systems and three components of the Japanese (Nakanuma) staging system to evaluate their clinical and biochemical correlations and prognostic value.MethodsWe reviewed biopsies from 106 patients with PBC, derived from a previous trial of colchicine therapy with 24–34 years’ follow-up, following which five clinical outcomes were evaluated: hepatic decompensation, cholestatic PBC death/liver transplant, portal hypertensive PBC death, all PBC deaths and overall survival.ResultsLudwig and Ishak stages correlated well with prognostically significant parameters, including serum bilirubin, and both Mayo and Child Scores. Serum aspartate aminotransferase correlated with interface hepatitis (IFH), and alkaline phosphatase with orcein deposition, bile duct (BD) loss and cholestasis. Ludwig correlated with all five clinical outcomes, while Ishak stage was only significantly correlated with two. While sinusoidal fibrosis, orcein deposition, BD loss and cholestasis all predicted hepatic death/transplant, after correction for Mayo Score, the only histological parameters predictive of clinical outcomes were IFH (associated with two) and sinusoidal fibrosis (associated with all five).ConclusionLiver biopsy is required in the diagnosis of around 20% of patients with PBC. The Ludwig system is of more prognostic value than both Ishak and any of the three individual components of the Nakanuma staging system, but the major histological parameter providing independent prognostic value beyond the Mayo Score is sinusoidal fibrosis.

PROREPAIR-A: Clinical and molecular characterization study of prostate cancer (PC) patients with and without previously known germline BRCA1/2 mutations.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5511-5511
Author(s):  
Rebeca Lozano ◽  
Elena Castro ◽  
Isabel Aragon ◽  
Heather Thorne ◽  
Fernando López-Campos ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Prognostic Value ◽  
Cox Regression ◽  
Castration Resistance ◽  
Free Survival ◽  
Kaplan Meier ◽  
Characterization Study ◽  
Control Study ◽  
Cause Specific Survival

5511 Background: Germline BRCA1/2 (g BRCA1/2) mutations are associated with poor clinical outcomes in PC. Previous studies showed that g BRCA2 carriers present more CNV in several genes associated with more aggressive disease. These aberrations may explain the poor clinical outcomes of these patients, but larger studies are needed to confirm these findings. Methods: PROREPAIR-A is a multicenter case-control study in which g BRCA2 carriers with available diagnostic timor-tissue were matched 1:2 by Gleason and stage at diagnosis (M0 vs M1) with known non-carriers (NC). A minimum of 120 controls-60 cases were required to prove a 5yr Cause Specific Survival (CSS)-rate of 85% vs 60%. The primary endpoint was to confirm the independent prognostic value of g BRCA2 in PC CSS. In addition, we explored the prognostic role of g BRCA1 and somatic events in BRCA2, RB1, MYC, PTEN and TMPRSS2-ERG by FISH. Χ2, Kaplan-Meier, log-rank and cox-regression models were carried out to identify associations with baseline characteristics and outcomes: Metastases Free Survival (MFS), Time to Castration-Resistance (TTCR) and CSS. Results: A total of 80:160 matched cases-controls were initially included, but tumor tissue and clinical data were only available in 73 g BRCA2 and 127 NC. 14 g BRCA1 were also included. At diagnosis, g BRCA2 were younger (median 62.6 vs 64.5, p = 0.02) and had cT3-4 disease more often than NC (31.5% vs 9.4%, p < 0.01), but no other significant differences were found. Somatic BRCA2-RB1 codeletion (40.8% vs 11.8%, p < 0.01) and MYC amplification (51.4% vs 22.8%, p < 0.01) were more frequent in g BRCA2 compared to NC, but no significant differences in PTEN and TMPRSS2-ERG were observed. g BRCA2 mutations as well as somatic BRCA2-RB1 codel and MYC amplif were significantly associated with shorter CSS, MFS and TTCR (Table). MVA model confirmed the independent prognostic value of g BRCA2 (HR 1.94, p = 0.03), BRCA2-RB1 codel (HR 3.16, p < 0.01), MYC amplif (HR 2.36, p < 0.01), Gleason ≥8 (p < 0.01) and M1 at diagnosis (p < 0.01) for CSS. Conclusions: PROREPAIR-A confirmed the independent prognostic value of g BRCA2 for CSS. Somatic BRCA2, RB1 and MYC aberrations were more frequent in g BRCA2 carriers. Those alterations are associated with shorter CSS, MFS and TTCR, and may contribute to poor clinical outcomes in g BRCA2 and NC. [Table: see text]

scholarly journals Sarcoidosis and Primary Biliary Cholangitis- An Overlap

2021 ◽  
Author(s):  
Akshatha Manohar ◽  
CA Jayashankar ◽  
Nithin Kumar ◽  
Prakash Bhanu ◽  
Prathima Shivaji Rao
Keyword(s):  
Case Report ◽  
Liver Disease ◽  
Liver Biopsy ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Granulomatous Disease ◽  
Granulomatous Lesions ◽  
Histological Confirmation ◽  
Treatment Of Sarcoidosis

Primary Biliary Cholangitis (PBC) is a chronic progressive autoimmune cholestatic liver disease. Sarcoidosis is a multisystem chronic granulomatous disease. Both diseases are known to affect the liver causing granulomas. Sarcoidosis commonly involves the skin while PBC is associated with autoimmune skin disorders. Diagnosis of PBC requires biochemical, serological and histological confirmation. Steroids are used in the treatment of sarcoidosis. The role of steroids in the treatment of PBC is not completely established. In this case report, authors present the case of a 31-years-old female diagnosed as sarcoidosis based on granulomatous lesions in skin biopsy with concurrent PBC diagnosed on basis of serology and liver biopsy.

scholarly journals DNA Repair Expression Profiling to Identify High-Risk Cytogenetically Normal Acute Myeloid Leukemia and Define New Therapeutic Targets

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2874
Author(s):  
Ludovic Gabellier ◽  
Caroline Bret ◽  
Guillaume Bossis ◽  
Guillaume Cartron ◽  
Jérôme Moreaux
Keyword(s):  
Dna Repair ◽  
Clinical Outcomes ◽  
Prognostic Value ◽  
Gene Mutations ◽  
Risk Groups ◽  
Prognostic Information ◽  
Mutational Status ◽  
Cox Analysis ◽  
Acute Myeloid

Cytogenetically normal acute myeloid leukemias (CN-AML) represent about 50% of total adult AML. Despite the well-known prognosis role of gene mutations such as NPM1 mutations of FLT3 internal tandem duplication (FLT3-ITD), clinical outcomes remain heterogeneous in this subset of AML. Given the role of genomic instability in leukemogenesis, expression analysis of DNA repair genes might be relevant to sharpen prognosis evaluation in CN-AML. A publicly available gene expression profile dataset from two independent cohorts of patients with CN-AML were analyzed (GSE12417). We investigated the prognostic value of 175 genes involved in DNA repair. Among these genes, 23 were associated with a prognostic value. The prognostic information provided by these genes was summed in a DNA repair score, allowing to define a group of patients (n = 87; 53.7%) with poor median overall survival (OS) of 233 days (95% CI: 184–260). These results were confirmed in two validation cohorts. In multivariate Cox analysis, the DNA repair score, NPM1, and FLT3-ITD mutational status remained independent prognosis factors in CN-AML. Combining these parameters allowed the identification of three risk groups with different clinical outcomes in both training and validation cohorts. Combined with NPM1 and FLT3 mutational status, our GE-based DNA repair score might be used as a biomarker to predict outcomes for patients with CN-AML. DNA repair score has the potential to identify CN-AML patients whose tumor cells are dependent on specific DNA repair pathways to design new therapeutic avenues.

scholarly journals Prognostic Role of Elevated Myeloperoxidase in Patients with Acute Coronary Syndrome: A Systemic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Andrew R. Kolodziej ◽  
Mohamed Abo-Aly ◽  
Eman Elsawalhy ◽  
Charles Campbell ◽  
Khaled M. Ziada ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Clinical Outcomes ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Systemic Review ◽  
Myocardial Inflammation ◽  
Prognostic Role ◽  
Coronary Syndrome

Background. Myocardial inflammation following acute ischemic injury has been linked to poor cardiac remodeling and heart failure. Many studies have linked myeloperoxidase (MPO), a neutrophil and inflammatory marker, to cardiac inflammation in the setting of acute coronary syndrome (ACS). However, the prognostic role of MPO for adverse clinical outcomes in ACS patients has not been well established. Methods. MEDLINE and Cochrane databases were searched for studies from 1975 to March 2018 that investigated the prognostic value of serum MPO in ACS patients. Studies which have dichotomized patients into a high MPO group and a low MPO group reported clinical outcomes accordingly and followed up patients for at least 30 days to be eligible for enrollment. Data were analyzed using random-effects model. Sensitivity analyses were conducted for quality control. Results. Our meta-analysis included 13 studies with 9090 subjects and a median follow-up of 11.4 months. High MPO level significantly predicted mortality (odds ratio (OR) 2.03; 95% confidence interval (CI): 1.40-2.94; P<0.001), whereas it was not significantly predictive of major adverse cardiac events and recurrent myocardial infarction (MI) (OR 1.28; CI: 0.92-1.77, P=0.14 and OR 1.23; CI: 0.96-1.58, P=0.101, respectively). Hypertension, diabetes mellitus, and age did not affect the prognostic value of MPO for clinical outcomes, whereas female gender and smoking status have a strong influence on the prognostic value of MPO in terms of mortality and recurrent MI (metaregression coefficient -8.616: 95% CI -14.59 to -2.633, P=0.0048 and 4.88: 95% CI 0.756 to 9.0133, P=0.0204, respectively). Conclusions. Our meta-analysis suggests that high MPO levels are associated with the risk of mortality and that MPO can be incorporated in risk stratification models that guide therapy of high-risk ACS patients.

scholarly journals Investigation of the prognostic value of CD4 T cell subsets expanded from tumor-infiltrating lymphocytes of colorectal cancer liver metastases

2020 ◽  
Vol 8 (2) ◽  
pp. e001478
Author(s):  
Marie Kroemer ◽  
Celia Turco ◽  
Laurie Spehner ◽  
Julien Viot ◽  
Idir Idirène ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Liver Metastases ◽  
Clinical Outcomes ◽  
Prognostic Value ◽  
Tumor Infiltrating Lymphocytes ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Infiltrating Lymphocytes

BackgroundThe positive role of CD8+ tumor-infiltrating lymphocytes (TIL) in patients with colorectal cancer (CRC) has been well described but the prognostic value of CD4 T cell subsets remained to be investigated. In this study, we expanded TIL from surgically resected liver metastases of patients with CRC and characterized the phenotype and the prognostic value of expanded-CD4 T cells.MethodsLiver metastases were surgically resected from 23 patients with CRC. Tumors were enzymatically digested and cultured in high dose of interleukin-2 for up to 5 weeks. T cell phenotype and reactivity of cultured-T cells were measured by flow cytometry and correlated with patients’ clinical outcomes.ResultsWe successfully expanded 21 over 23 TIL from liver metastases of patients with CRC. Interestingly, we distinguished two subsets of expanded T cells based on T cell immunoglobulin mucin domain-containing protein 3 (TIM-3) expression. Medians fold expansion of expanded T cells after rapid expansion protocol was higher in CD3+TIM-3low cultures. In an attempt to investigate the correlation between the phenotype of expanded CD4 T cells and clinical outcomes, we observed on one hand that the level of Tregs in culture as well as the expression of both PD1 and TIM-3 by expanded T cells was not correlated to the clinical outcomes. Interestingly, on the other hand, cultures containing high levels of Th17 cells were associated with a poor prognosis (p=0.0007).ConclusionsOur data confirmed the presence of Th17 cells in expanded T cells from liver metastases. Among CD4 T cell characteristics investigated, TIM-3 but not programmed cell death protein 1 predicted the expansion capacity of TIL while only the Th17 phenotype showed correlation with patients’ survival, suggesting a particular role of this T cell subset in CRC immune contexture.Trial registration numberNCT02817178.

scholarly journals Role of Liver Biopsy in Management of Liver Diseases Following End of the Interferon Era: Experience of A Tertiary Referral Centre

2021 ◽  
Author(s):  
Nermine A Ehsan ◽  
Maha M Elsabaawy ◽  
Dina M Sweed ◽  
Esraa A Karman ◽  
Eman Abdelsameea ◽  
...  
Keyword(s):  
Liver Biopsy ◽  
Liver Diseases ◽  
Primary Biliary Cholangitis ◽  
Tertiary Referral Centre ◽  
Drug Induced ◽  
Laboratory Findings ◽  
Alcoholic Fatty Liver ◽  
Drug Induced Liver Injury ◽  
Pathology Reports

Abstract Background: Liver biopsy (LB) is the cornerstone in the management of patients with liver diseases. However, a lot of queries had emerged about its role following the end of the interferon era. The aim of this study was to re-evaluate the current role of LB in the diagnosis of liver diseases. Methods: All patients who had underwent LB at the department of Hepatology, National Liver Institute, from January 2015 through December 2018 were recruited. Indications for LB, pathology reports, and medical records of all cases were retrieved, reviewed and statistically analyzed. Results: A total of 275 liver biopsies were collected, 191 males and 84 females with mean age 41.22±13.36 years. Etiological diagnosis made by histopathological evaluation was 48 drug induced liver injury (DILI), 42 Non-alcoholic fatty liver disease (NAFLD), 34 chronic hepatitis B, or C with cholestasis, 29 autoimmune hepatitis, 34 primary sclerosing cholangitis, 13 primary biliary cholangitis, 7 autoimmune overlap syndrome, 13 active bilharziasis, 10 Wilson’s disease. Minor number of cases were diagnosed by different other etiologies. Initial diagnosis was made by liver biopsy and confirmed by clinical response and laboratory findings. Conclusion: Liver biopsy is still considered as the gold standard diagnostic measure of different liver diseases representing an integral component of management decisions in hepatology.

The Relevance of Noninvasive Tools To Assess Fibrosis in Non-Alcoholic Fatty Liver Disease

2020 ◽  
Vol 26 (32) ◽  
pp. 3928-3938
Author(s):  
Grazia Pennisi ◽  
Ciro Celsa ◽  
Antonina Giammanco ◽  
Federica Spatola ◽  
Salvatore Petta
Keyword(s):  
Liver Disease ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Assessment Tools ◽  
Hepatic Decompensation ◽  
Alcoholic Fatty Liver ◽  
Simple Steatosis ◽  
Life Threatening ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver diseases worldwide, involving about 25% of people. NAFLD incorporates a large spectrum of pathological conditions, from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and its complications include hepatic decompensation and hepatocellular carcinoma (HCC). This progression occurs, over many years, in an asymptomatic way, until advanced fibrosis appears. Thus, the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis are key issues. To date, the histological assessment of fibrosis with liver biopsy is the gold standard, but obviously, invasiveness is the greater threshold. In addition, rare but potentially life-threatening complications, poor acceptability, sampling variability and cost maybe restrict its use. Furthermore, due to the epidemic of NAFLD worldwide and several limitations of liver biopsy evaluation, noninvasive assessment tools to detect fibrosis in NAFLD patients are needed.

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