Diagnosing nodular regenerative hyperplasia of the liver is thwarted by low interobserver agreement

Background and Aims: Nodular regenerative hyperplasia (NRH) of the liver is associated with several diseases and drugs. Clinical symptoms of NRH may vary from absence of symptoms to full-blown (noncirrhotic) portal hypertension. However, diagnosing NRH is challenging. The objective of this study was to determine inter- and intraobserver agreement on the histopathologic diagnosis of NRH. Methods: Liver specimens (n=48) previously diagnosed as NRH, were reviewed for the presence of NRH by seven pathologists without prior knowledge of the original diagnosis or clinical background. The majority of the liver specimens were from thiopurine using inflammatory bowel disease patients. Histopathologic features contributing to NRH were also assessed. Criteria for NRH were modified by consensus and subsequently validated. Interobserver agreement was evaluated by using the standard kappa index. Results: After review, definite NRH, inconclusive NRH and no NRH were found in 35% (23-40%), 21% (13-27%) and 44% (38-56%), respectively (median, IQR). The median interobserver agreement for NRH was poor (κ = 0.20, IQR 0.14-0.28). The intraobserver variability on NRH ranged between 14% and 71%. After modification of the criteria and exclusion of biopsies with technical shortcomings, the interobserver agreement on the diagnosis NRH was fair (κ = 0.45). Conclusions: The interobserver agreement on the histopathologic diagnosis of NRH was poor, even when assessed by well-experienced liver pathologists. Modification of the criteria of NRH based on consensus effort and exclusion of biopsies of poor quality led to a fairly increased interobserver agreement. The main conclusion of this study is that NRH is a clinicopathologic diagnosis that cannot reliably be based on histopathology alone

Diagnostic performance of FibroTest, SteatoTest and ActiTest in patients with NAFLD using the SAF score as histological reference

BACKGROUND: Blood tests of liver injury are less well validated in non‐alcoholic fatty liver disease (NAFLD) than in patients with chronic viral hepatitis. AIMS: To improve the validation of three blood tests used in NAFLD patients, FibroTest for fibrosis staging, SteatoTest for steatosis grading and ActiTest for inflammation activity grading. METHODS: We pre‐included new NAFLD patients with biopsy and blood tests from a single‐centre cohort (FibroFrance) and from the multicentre FLIP consortium. Contemporaneous biopsies were blindly assessed using the new steatosis, activity and fibrosis (SAF) score, which provides a reliable and reproducible diagnosis and grading/staging of the three elementary features of NAFLD (steatosis, inflammatory activity) and fibrosis with reduced interobserver variability. We used nonbinary‐ROC (NonBinAUROC) as the main endpoint to prevent spectrum effect and multiple testing. RESULTS: A total of 600 patients with reliable tests and biopsies were included. The mean NonBinAUROCs (95% CI) of tests were all significant (P < 0.0001): 0.878 (0.864–0.892) for FibroTest and fibrosis stages, 0.846 (0.830–0.862) for ActiTest and activity grades, and 0.822 (0.804–0.840) for SteatoTest and steatosis grades. FibroTest had a higher NonBinAUROC than BARD (0.836; 0.820–0.852; P = 0.0001), FIB4 (0.845; 0.829–0.861; P = 0.007) but not significantly different than the NAFLD score (0.866; 0.850–0.882; P = 0.26). FibroTest had a significant difference in median values between adjacent stage F2 and stage F1 contrarily to BARD, FIB4 and NAFLD scores (Bonferroni test P < 0.05). CONCLUSIONS: In patients with NAFLD, SteatoTest, ActiTest and FibroTest are non‐invasive tests that offer an alternative to biopsy, and they correlate with the simple grading/staging of the SAF scoring system across the three elementary features of NAFLD: steatosis, inflammatory activity and fibrosis

Follicular large-cell lymphoma treated with intensive chemotherapy: An analysis of 89 cases included in the LNH87 trial and comparison with the outcome of diffuse large B-cell lymphoma

Purpose: The aims of this study were as follows: (1) to analyze clinical, histopathologic characteristics, treatment outcome, and prognostic factors of patients with follicular large-cell lymphoma (FLCL); and (2) to compare them with those of patients with diffuse large B-cell lymphoma (DLCL) treated in the same therapeutic trial. Patients and Methods: Eighty-wine FLCL patients who were histologically reviewed and who received an intensive chemotherapy regimen according to the LNH 87 protocol were analyzed and compared with 1,096 B-cell DLCL patients included in the same protocol. Results: After intensive induction treatment 59 patients (67%) achieved a complete remission (CR), Estimated 5-year survival was 59%, and estimated 5-year freedom from progression (FFP) was 39%. Prognostic factors associated with shorter FFP were age greater than 60 years (P = .02), advanced clinical stage (P = .01), abnormal lactic dehydrogenase (LDH) revel (P = .02), abnormal beta-2 microglobulin (P = .02), B symptoms (P = .03), bone marrow involvement (P = .04), and high expression of bcl-2 protein (P = .05). When compared with B-cell DLCL patients, FLCL patients were younger (P = .02), had a better Eastern Cooperative Oncology Group (ECOG) status (P = .05), less bulky mass (P = .04), more advanced clinical stages (P < .001), and more bone marrow involvment (P = .02). No significant difference was observed between FLCL and DLCL patients for response to therapy (67% v 67% of: CR), 5-year overall survival (58% v 51%), 5-year disease-free survival (53% v 57%), or FFP survival (39% v 43%). Conclusion: FLCL patients have a favorable response rate and survival when treated with intensive chemotherapy. Their outcome is similar to that of B-cell DLCL patients, and a long-term FFP is observed for a substantial number of patients. Some adverse prognostic Factors (including those of the International Prognostic Index, bone marrow involvement, and beta-2 mitroglobulin) have been identified to define a subset of patients who require other therapeutic approach. (C) 1997 by American Society of Clinical Oncology

Validation of the Prognostic Value of Histologic Scoring Systems in Primary Sclerosing Cholangitis:An international cohort study

Histologic scoring systems specific for primary sclerosing cholangitis (PSC) are not validated. We recently determined the applicability and prognostic value of three histological scoring systems in a single PSC cohort. The aim of this study was to validate their prognostic use and reproducibility across a multicenter PSC cohort. Liver biopsies from PSC patients were collected from seven European institutions. Histologic scoring was performed using the Nakanuma, Ishak, and Ludwig scoring systems. Biopsies were independently scored by six liver pathologists for interobserver agreement. The prognostic value of clinical, biochemical, and all three histologic scoring systems on predicting composite endpoints 1 (PSCrelated death and liver transplantation), 2 (liver transplantation), and 3 (liver-related events), was assessed using univariable and multivariable Cox proportional hazards modeling. A total of 119 PSC patients were identified, and the median follow-up was 142 months. During follow-up, 31 patients died (20 PSC-related deaths), 31 patients underwent liver transplantation, and 35 patients experienced one or more liver-related events. All three staging systems were independent predictors of endpoints 2 and 3 (Nakanuma system: hazard ratio [HR], 3.16 [95% confidence interval (CI), 1.49-6.68] for endpoint 2 and HR, 2.05 [95% CI, 1.17-3.57] for endpoint 3; Ishak system: HR, 1.55 [95% CI, 1.10-2.18] for endpoint 2 and HR, 1.43 [95% CI, 1.10-1.85] for endpoint 3; Ludwig system: HR, 2.62 [95% CI, 1.19-5.80] for endpoint 2 and HR, 2.06 [95% CI, 1.09-3.89] for endpoint 3). Only the Nakanuma staging system was independently associated with endpoint 1: HR, 2.14 (95% CI, 1.22-3.77). Interobserver agreement was moderate for Nakanuma stage (k = 0.56) and substantial for Nakanuma component fibrosis (k = 0.67), Ishak stage (k = 0.64), and Ludwig stage (k = 0.62). Conclusion: We confirm the independent prognostic value and demonstrate for the first time the reproducibility of staging disease progression in PSC using the Nakanuma, Ishak, and Ludwig staging systems. The Nakanuma staging system-incorporating features of chronic biliary disease-again showed the strongest predictive value

Impact of nutrition on phenotype in CFTR-deficient mice.

To elucidate the impact of nutrition in cystic fibrosis (CF), we compared the phenotypic traits of Cftr -/- mice fed either a lipid-enriched liquid diet (Peptamen) or a standard chow combined with polyethylenglycol osmotic laxative (PEG), two strategies commonly used to prevent intestinal obstruction in CF mice. Survival, growth, liver, and ventilatory status were determined in Cftr -/- and Cftr +/+ mice, followed-up until 120 d. Ventilation was recorded in conscious animals using whole-body plethysmography. We found that the survival rate was similar in Peptamen and PEG Cftr -/- mice. Cftr -/- mice had lower minute ventilation than Cftr +/+ mice, whatever the diet. Both Cftr -/- and Cftr +/+ mice fed Peptamen displayed preadult growth delay compared with PEG-treated animals. Despite subsequent growth catch-up, Cftr -/- mice remained smaller than Cftr +/+ mice, whatever the diet. All Peptamen fed Cftr -/- mice showed hepatomegaly and liver steatosis, which also occurred but to a lesser extent in Peptamen fed Cftr +/+ animals. Therefore, while both treatment strategies are similarly efficient to avoid high mortality at weaning, Peptamen induces preadult growth delay and liver steatosis. These effects of diet are important to consider in future animal studies and also prompt to evaluate high-energy diets in CF patients.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Cannabis Use and Reduced Risk of Insulin Resistance in HIV-HCV Infected Patients: A Longitudinal Analysis (ANRS CO13 HEPAVIH)

International audienceDiabetes and insulin resistance (IR) is common in human immunodeficiency virus-hepatitis C virus (HIV-HCV)-coinfected patients, a population also concerned with elevated cannabis use. Cannabis has been associated with reduced IR risk in some population-based surveys. We determined whether cannabis use was consistently associated with reduced IR risk in HEPAVIH, a French nationwide cohort of HIV-HCV-coinfected patients.Methods: HEPAVIH medical and sociobehavioral data were collected (using annual self-administered questionnaires). We used 60 months of follow-up data for patients with at least 1 medical visit where IR (using homeostatic model assessment of insulin resistance [HOMA-IR]) and cannabis use were assessed. A mixed logistic regression model was used to evaluate the association between IR risk (HOMA-IR > 2.77) and cannabis use (occasional, regular, daily).Results: Among the 703 patients included in the study (1287 visits), 323 (46%) had HOMA-IR > 2.77 for at least 1 follow-up visit and 319 (45%) reported cannabis use in the 6 months before the first available visit. Cannabis users (irrespective of frequency) were less likely to have HOMA-IR > 2.77 (odds ratio [95% confidence interval], 0.4 [.2-.5]) after adjustment for known correlates/confounders. Two sensitivity analyses with HOMA-IR values as a continuous variable and a cutoff value of 3.8 confirmed the association between reduced IR risk and cannabis use.Conclusions: Cannabis use is associated with a lower IR risk in HIV-HCV-coinfected patients. The benefits of cannabis-based pharmacotherapies for patients concerned with increased risk of IR and diabetes need to be evaluated in clinical research and practice

Post‐HCV cure self‐reported changes in physical activity, eating behaviours, and fatigue in people living with HIV (ANRS CO13 HEPAVIH)

International audienc