Liver stiffness evaluation (LSE) is usually considered as reliable when it fulfills all the following criteria: ≥10 valid measurements, ≥60% success rate, and interquartile range / median ratio (IQR/M) ≤0.30. However, such reliable LSE have never been shown to be more accurate than unreliable LSE. Thus, we aimed to evaluate the relevance of the usual definition for LSE reliability, and to improve reliability by using diagnostic accuracy as a primary outcome in a large population. 1,165 patients with chronic liver disease from 19 French centers were included. All patients had liver biopsy and LSE. 75.7% of LSE were reliable according to the usual definition. However, these reliable LSE were not significantly more accurate than unreliable LSE with, respectively: 85.8% versus 81.5% well‐classified patients for the diagnosis of cirrhosis (P = 0.082). In multivariate analyses with different diagnostic targets, LSE median and IQR/M were independent predictors of fibrosis staging, with no significant influence of ≥10 valid measurements or LSE success rate. These two reliability criteria determined three LSE groups: “very reliable” (IQR/M ≤0.10), “reliable” (0.10< IQR/M ≤0.30, or IQR/M >0.30 with LSE median <7.1 kPa), and “poorly reliable” (IQR/M >0.30 with LSE median ≥7.1 kPa). The rates of well‐classified patients for the diagnosis of cirrhosis were, respectively: 90.4%, 85.8%, and 69.5% (P < 10−3). According to these new reliability criteria, 9.1% of LSE were poorly reliable (versus 24.3% unreliable LSE with the usual definition, P < 10−3), 74.3% were reliable, and 16.6% were very reliable. Conclusion: The usual definition for LSE reliability is not relevant. LSE reliability depends on IQR/M according to liver stiffness median level, defining thus three reliability categories: very reliable, reliable, and poorly reliable LSE. (HEPATOLOGY 2013)

Inter-observer agreement on activity and fibrosis scores used in chronic viral hepatitis has only been studied under selected conditions. The aim of this study was to identify the sources of variability due to specimen characteristics and observers. This study included 254 liver specimens and 15 pathologists and used the Metavir score. In 44 specimens scored by 4 academic pathologists, agreement of Metavir score was good overall, but better for fibrosis ( ‫؍‬ 0.59) than for activity ( ‫؍‬ 0.43) and poor for lobular necrosis ( ‫؍‬ 0.15). The mean agreement was better for senior (0.60 ؎ 0.24) than junior pathologists (0.52 ؎ 0.30, P < .05). Mean intrabserver agreement was better than inter-observer agreement (0.77 ؎ 0.18 vs. 0.58 ؎ 0.26, P < .01). In 157 specimens scored by 2 expert pathologists (one senior, one junior), agreement of Metavir score was only good but greatly improved after consensus reading (fibrosis: ‫؍‬ 0.48 and 0.77, activity: ‫؍‬ 0.44 and 0.70, respectively, before and after consensus). Several causes of disagreement were identified: specimen length, fibrosis class number, observer bias, and putative causes related to Metavir score or specimen. In an intercenter evaluation involving 59 specimens, 1 expert and 10 nonacademic pathologists, agreement was very poor and did not improve over 5 years for activity ( ‫؍‬ 0.22-0.25) or fibrosis ( ‫؍‬ 0.13-0.18). In conclusion, the level of experience (specialization, duration, and location of practice) has more influence on agreement than the characteristics of the specimen (length, fibrosis class number, miscellaneous factors). Agreement can be improved by experienced pathologist or consensus reading. (HEPATOLOGY 2005;41:257-264.)

The objective was to develop new blood tests to characterize different fibrosis parameters in viral and alcoholic chronic liver diseases. Measurements included 51 blood markers and Fibrotest, Fibrospect, ELFG, APRI, and Forns scores. The clinically significant fibrosis was evaluated via Metavir staging (F2-F4), and image analysis was used to determine the area of fibrosis. In an exploratory step in 383 patients with viral hepatitis, the area under the receiving operator characteristic (AUROC) curve for stages F2-F4 in a test termed the "Fibrometer" test combining platelets, prothrombin index, aspartate aminotransferase, ␣2-macroglobulin (A2M), hyaluronate, urea, and age was 0.883 compared with 0.808 for the Fibrotest (P ‫؍‬ .01), 0.820 for the Forns test (P ‫؍‬ .005), and 0.794 for the APRI test (P < 10 ؊4 ). The Fibrometer AUROC curve was 0.892 in the validating step in 120 patients. The AUROC curve for stages F2-F4 in a test combining prothrombin index, A2M, hyaluronate, and age was 0.962 in 95 patients with alcoholic liver diseases. The area of fibrosis was estimated in viral hepatitis by testing for hyaluronate, ␥-glutamyltransferase, bilirubin, platelets, and apolipoprotein A1 ( a R 2 ‫؍‬ 0.645), and in alcoholic liver diseases by testing for hyaluronate, prothrombin index, A2M, and platelets ( a R 2 ‫؍‬ 0.836). In conclusion, the pathological staging and area of liver fibrosis can be estimated using different combinations of blood markers in viral and alcoholic liver diseases. Whereas the Fibrometer has a high diagnostic accuracy for clinically significant fibrosis, blood tests for the area of liver fibrosis provide a quantitative estimation of the amount of fibrosis, which is especially useful in cirrhosis. (HEPATOLOGY 2005;42:1373-1381

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These results show that MC can predict outcome of FL patients and that rituximab is able to circumvent the unfavorable outcome associated with high MC.

Purpose To prospectively assess the clinical impact of expert review of lymphoma diagnosis in France. Materials and Methods From January 2010 to December 2013, 42,145 samples from patients with newly diagnosed or suspected lymphomas were reviewed, according to the 2008 WHO classification, in real time by experts through the Lymphopath Network. Changes in diagnosis between referral and expert review were classified as major or minor according to their potential impact on patient care. Results The 42,145 reviewed samples comprised 36,920 newly diagnosed mature lymphomas, 321 precursor lymphoid neoplasms, 314 myeloid disorders, and 200 nonhematopoietic neoplasms, with 4,390 benign lesions. There were 4,352 cutaneous and 32,568 noncutaneous lymphomas. The most common mature noncutaneous lymphomas were diffuse large B-cell lymphomas (32.4%), follicular lymphomas (15.3%), classic Hodgkin lymphomas (13%), peripheral T-cell lymphomas (6.3%) of which angioimmunoblastic T-cell lymphomas (2.3%) were the most frequent, and mucosa-associated lymphoid tissue lymphomas (5.8%). A diagnostic change between referral and expert review occurred in 19.7% of patients, with an estimated impact on patient care for 17.4% of patients. This rate was significantly higher for patients sent with a provisional diagnosis seeking expert second opinion (37.8%) than for patients sent with a formal diagnosis (3.7%). The most frequent discrepancies were misclassifications in lymphoma subtype (41.3%), with 12.3% being misclassifications among small B-cell lymphoma entities. Fewer than 2% of changes were between benign and malignant lymphoid conditions. Minor changes (2.3%) mostly consisted of follicular lymphoma misgrading and diffuse large B-cell lymphoma subtype misclassification. Conclusion To our knowledge, this study provides the largest ever description of the distribution of lymphoma entities in a western country and highlights how expert review significantly contributes to a precise lymphoma diagnosis and optimal clinical management in a proportion of patients.

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Primary lymphoma of the liver (PLL) is rare. In some cases, the hepatic lymphoma has been diagnosed in patients who were infected by the hepatitis C virus (HCV). It has been suggested that HCV plays a role in the pathogenesis of lymphoma. The aim of our multicentric retrospective study was to assess the characteristics of PLL and to determine the prevalence of HCV infection in PLL. Thirty-one immunocompetent patients (anti-human immunodeficiency virus, anti-human T-cell leukemia/lymphoma virus negative, no history of allograft) with PLL fulfilled the entire selection criteria. The liver biopsy specimens were reassessed by the same pathologist. The non-Hodgkin's lymphomas were classified according to the World Health Organization classification. Blood samples were tested in 28 patients for antibodies to HCV, and HCV RNA was detected by reverse transcription polymerase chain reaction. In the majority of cases, the clinical, biologic, and radiologic data were nonspecific. Twentyseven of 31 patients presented a B-cell lymphoma corresponding to the centroblastic morphologic variant of a diffuse, large B-cell lymphoma (22 cases), a Burkitt's lymphoma (1 case), an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (3 cases), and unclassified, small B-cell lymphoma (1 case). The 4 other cases were T-cell lymphomas. The prevalence of HCV infection was 21% (6 of 28 cases). All of these patients were positive for HCV RNA by polymerase chain reaction in blood. Most of the HCVinfected patients presented a high-grade, B-cell type lymphoma. In conclusion, our study confirms the rarity of PLL and demonstrates an increased prevalence of HCV infection. H epatitis C virus (HCV) is a hepatotropic virus;however, the HCV genome and its replicative intermediate have been detected in peripheral blood mononuclear cells in patients with chronic HCV infection. 1,2 There is a strong association between HCV and type II mixed cryoglobulinemia. [3][4][5] Antibodies to HCV and HCV RNA have been found in up to 98% of patients with mixed cryoglobulinemia, 3 and approximately 36% of patients with chronic HCV infection have mixed cryoglobulinemia. 5 Mixed cryoglobulinemia is considered by some investigators to be a variant of lowgrade, B-cell non-Hodgkin's lymphoma. 6,7 This has prompted several groups to investigate the association between HCV infection and overt B-cell malignancies. Evidence suggesting a direct relationship between HCV infection and development of these tumors have been reported in several Italian studies and in one American study, which demonstrates a high prevalence of chronic HCV infection, 9% to 42%, in patients with B-cell lymphoma. [8][9][10][11] However, data from other countries have not confirmed these findings. [12][13][14][15] Primary lymphoma of the liver (PLL) is rare, with less than 150 cases reported. 16,17 In some cases, the hepatic lymphoma was diagnosed in From the