scholarly journals P44 Liver injury in children on long-term low dose methotrexate

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_4) ◽  
Author(s):  
Chayarani Kelgeri ◽  
Somashekhar HR ◽  
Rachel Brown ◽  
Eslam Al-Abadi ◽  
Girish Gupte
Keyword(s):  
Risk Factors ◽  
Liver Injury ◽  
Liver Biopsy ◽  
Conflicts Of Interest ◽  
Total Duration ◽  
Patient Characteristics ◽  
Base Line ◽  
Liver Biopsies ◽  
Dose Modifications ◽  
Elevated Transaminases

Abstract Background Liver injury is known in patients on methotrexate (MTX). We retrospectively reviewed records of patients who had liver biopsy for suspected MTX induced liver injury and identify risk factors if any. Methods Children (≤ 16 years) referred to us from 2002 to 2015 with suspected MTX induced liver injury were identified and data related to their underlying diagnosis, biochemical parameters, Body Mass Index (BMI), dose and duration of MTX at the time of liver biopsy, use of concomitant drugs, duration and other causes for elevated transaminases, liver histology including clinical decisions to continue or stop MTX were extracted from the data base. All the liver biopsies were re-analysed for this study and scored using the Roenigk classification by a single histopathologist blinded to patient characteristics. Results Seventeen liver biopsies were performed in 14 children (3 had repeat biopsies) who were referred for frequent/persistent transaminitis (> 2 times upper limit normal). The base line bilirubin, transaminases and synthetic liver function were normal in all prior to MTX therapy. All were on MTX at the time of biopsy except two who had been off the drug for 3 and 8 months following frequent transaminitis. They had liver biopsy to guide reintroduction of MTX in their treatment regime. None of the patients had renal impairment, diabetes or underlying liver disease. Thirteen biopsies (82 %) had none (n = 6) to mild liver injury (n = 7) and were advised to continue MTX. Four biopsies (18%) showed significant liver injury (grade 3b and 4). Of these 3 patients were advised to stop MTX while one was advised to continue and repeat liver biopsy in 6 months. He however, stopped MTX soon thereafter. All biopsies of children (n = 3) with BMI ≥ 91st centile had liver damage. Two of thirteen biopsies with BMI < 91 centile had moderate-severe damage. No correlation was seen between the histologic findings or their severity with dose or duration of MTX, concomitant use of other drugs, severity/highest transaminase peak, total duration of transaminase abnormality, longest single episode of transaminase abnormality or frequency/number of peaks of abnormal transaminases. Of the 3 with repeat biopsies, fibrosis had progressed in 2, necessitating discontinuation of MTX in 1. Conclusion The finding of significant liver injury in our cohort is not entirely in keeping with previous paediatric studies which report non-significant fibrosis or cirrhosis. We could not identify any risk factors though children with BMI ≥ 91st centile seemed more likely to have liver injury. This finding is similar to adult studies implicating obesity as risk factor though it is difficult to draw definitive conclusions given the small size of our cohort. Other limitations include the retrospective nature of the study, bias as MTX dose modifications and referral were at the discretion of the rheumatologist and no information on alcohol intake in the teenagers. This study emphasises the need for careful monitoring to prevent severe fibrosis and cirrhosis. Conflicts of Interest The authors declare no conflicts of interest.

Longitudinal Analysis of Serial Liver Biopsies in Chronically Transfused Sickle Cell Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1052-1052
Author(s):  
Jaime L Wolfe ◽  
Robert Anders ◽  
Shirley Reddoch ◽  
Kathleen Schwarz ◽  
William Savage
Keyword(s):  
Sickle Cell Disease ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Liver Biopsy ◽  
Red Cell ◽  
Cell Disease ◽  
Likelihood Ratios ◽  
Cross Sectional ◽  
Liver Biopsies ◽  
Over Time

Abstract Abstract 1052 Background: Chronic red cell transfusions are commonly used for the treatment and prevention of complications in sickle cell disease (SCD). Liver injury from transfusional iron overload is a recognized morbidity of chronic transfusion therapy, but little is known about the progression of liver injury over time in SCD. Methods: We conducted a retrospective cohort study of all chronically transfused people with SCD who had 2 or more serial liver biopsies at a single academic hospital. Subjects with viral hepatitis were excluded. Serum ferritin, serum ALT, chelation status, and transfusion volumes were extracted from the electronic record and validated against paper records in all subjects. Quantitative liver iron concentration (LIC) was determined at the time of biopsy by inductively coupled plasma-mass spectrometry. Core liver biopsy slides stained for iron and fibrosis were retrieved and scored in a blinded fashion by a hepatopathologist (RA) for total iron score (TIS, Deugnier, 2007) and fibrosis score (Ishak, 1995). Analyses evaluated how liver fibrosis changed over the first 2 biopsies and how changes in biomarkers correlated with changes in fibrosis. Cross sectional analyses assessed the relationship of biomarkers to the presence or absence of fibrosis. Ferritin was analyzed as an average of the 3 closest values ± 6 weeks of liver biopsy. Area under receiver operator characteristic curve (AUC) analysis, likelihood ratios for positive tests (LR+), and summary statistics were calculated using Stata v11.2. Results: 26 people had at least 2 serial core liver biopsies for evaluation (n=70 biopsies total, range 2–7 biopsies per subject). Fibrosis was Ishak grade 0 or 1 in all biopsies. Median age at first biopsy was 13.3 years and median total transfusion duration was 9.4 years. The first 2 biopsies were obtained a median of 2.3 years apart. Evaluation of the first 2 biopsies showed that fibrosis was present in 7/26 initial biopsies and 3/26 second biopsies: fibrosis regressed in 6 subjects, developed in 2 subjects and persisted in 1 subject. Among non-chelated subjects at the time of first biopsy, 2/11 had fibrosis, as compared to 5/15 subjects who had received a mean of 3.7 years of chelation at the time of first biopsy (18% vs 33%, P=0.6). Eleven subjects had 3 or more serial biopsies performed during a median of 9.2 years of chronic transfusion. There was no consistent pattern of fibrosis development, nor was there an apparent association of fibrosis with LIC over time (Figure, asterisks indicate presence of fibrosis). On a cross-sectional basis, ALT performed better than ferritin in classifying fibrosis, with ALT having an AUC of 0.80 (95% CI 0.66–0.94) and ferritin having an AUC of 0.63 (95% CI 0.38–0.87). LIC performed poorly at discriminating fibrosis from no fibrosis (AUC 0.30; 95%CI 0.0–0.82). The highest positive likelihood ratios for fibrosis were for a ferritin cutoff of 5000 ng/mL (LR+ 5.7) and an ALT cutoff of 65 U/L (LR+ 5.2). Longitudinal analysis did not reveal any statistically significant relationship between changes in fibrosis status and changes in ferritin, ALT, LIC, TIS, and cumulative red cell transfusion volume. Summary: Among chronically transfused people with SCD, liver fibrosis most often does not persist or progress, as detected by serial core liver biopsies. On a cross-sectional basis, serum ALT >65 U/L and serum ferritin >5000 ng/mL are cutoffs associated with the highest likelihood of liver fibrosis. Cross-sectional or longitudinal measurements of LIC are not associated with fibrosis. Conclusion: The progression of liver fibrosis is minimal among people with SCD who receive chronic red cell transfusions for up to 17 years. Serum biomarkers may be used to inform when investigations for fibrosis are warranted. Disclosures: No relevant conflicts of interest to declare.

Venous Thrombotic Events (VTEs) in Acute Myeloid Leukemia (AML) Patients During Induction Therapy (IT): Identifying Risk Factors, and Safety of Using Anticoagulation Therapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3148-3148
Author(s):  
Alaa Muslimani ◽  
Aya Rifai ◽  
Mohammad Muhsin Chisti ◽  
Ayham Ashkar ◽  
Kinda Muslemani ◽  
...  
Keyword(s):  
Risk Factors ◽  
Conflicts Of Interest ◽  
Anticoagulation Therapy ◽  
Patient Characteristics ◽  
Risk Groups ◽  
Upper Extremities ◽  
Bleeding Complications ◽  
Hypomethylating Agents ◽  
Flt3 Mutations ◽  
Portal Veins

Abstract Abstract 3148 Background: VTEs are common complications in association with IT which may cause additional morbidity and mortality in AML patients. However, treating patients with AML is challenging because of the cytopenias due to chemotherapy and the high risk for bleeding during IT. This study investigates frequency, risk factors, and safety of using anticoagulation (AC) therapy for VTEs during IT. Method: We retrospectively reviewed the charts of AML patients who received IT between January, 2000-January, 2011 at William Beaumont Health Systems. Exclusion criteria included a documented personal history of inherited thrombophilia. Data retrieved included the following: patient characteristics, leukemia subtype, cytogenetic risk, location of the VTEs, FLT3 mutations, IT regimen used (cytarabine and anthracycline regimens or hypomethylating agents), AC therapy, bleeding complications, mortality related to AC therapy. All patients who received AC were initially treated with regular intravenous unfractionated heparin or subcutaneous low molecular weight heparin. Patients were subsequently started on oral warfarin during the first 10 days of the initial treatment with a targeted INR of 2.0–3.0. Results: We found 48 of 363 (13.2%) AML patients developed VTEs during IT. Of those patients, 56.3 % were female. The VTEs occurred most frequently in upper extremities (58%) and were catheter-related. Other locations for VTEs included lower extremities (21%), pulmonary embolism (15%), and mesenteric or portal veins (6%). We note that 41 patients (87%) received AC therapy. Of these, three patients (7.3%) had bleeding complications and no AC therapy-related deaths were observed. When the three cytogenetic risk groups were compared, there was no difference in the incidence of VTEs (good vs intermediate vs poor). Patients with FLT 3 mutations, however, had a significant higher incidence of VTEs when compared to patients without FLT3 mutations (55.3% vs 12% p <0.001). Finally, patients treated with cytarabine + anthracycline regimen had a higher incidence of VTEs compared to patients treated with hypomethylating agents (81.3% vs 4.2 % p <0.001.) Conclusions: We found that 13% of AML patients developed VTEs during IT, most commonly in upper extremities and were catheter-related. The risk for VTEs was markedly increased in patients with FLT3 mutations. Furthermore, using a cytarabine + anthracycline regimens carried a higher risk for VTEs when compared to regimens using a hypomethylating agents. Finally, using AC therapy during IT is relatively safe and is associated with low risk of bleeding complications. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Implications of Liver Biopsy Results in Patients with Myeloproliferative Neoplasms Being Treated with Ruxolitinib

2019 ◽  
Vol 2019 ◽  
pp. 1-3 ◽  
Author(s):  
Douglas Tremblay ◽  
Juan Putra ◽  
Alexander Vogel ◽  
Adam Winters ◽  
Ronald Hoffman ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Biopsy ◽  
Myeloproliferative Neoplasms ◽  
Extramedullary Hematopoiesis ◽  
Hepatic Toxicity ◽  
Drug Induced ◽  
Significant Treatment ◽  
Drug Induced Liver Injury ◽  
Liver Biopsies ◽  
Obliterative Portal Venopathy

Ruxolitinib is increasingly being utilized for the treatment of myelofibrosis and polycythemia vera, but the potential for hepatic toxicity is poorly understood. We performed a retrospective review of hepatic damage occurring in patients with myeloproliferative neoplasms receiving ruxolitinib. Relevant histologic images of liver biopsies were reviewed by an experienced liver pathologist and reported to a multidisciplinary team including hepatology and hematology. A variety of liver pathology was observed including extramedullary hematopoiesis, obliterative portal venopathy, and drug-induced liver injury. In all cases reviewed, the liver biopsy had significant treatment implications. We conclude that hepatology referral and liver biopsy in patients receiving ruxolitinib therapy with biochemical evidence of liver injury reveals a variety of etiologies which have significant treatment impact. Clinicians should be aware of the potential causes of liver damage in this population and initiate prompt referral and liver biopsy.

scholarly journals A Rare Case of Rivaroxaban Causing Delayed Symptomatic Hepatocellular Injury and Hyperbilirubinemia

2017 ◽  
Vol 2017 ◽  
pp. 1-3 ◽  
Author(s):  
Keith Glenn ◽  
Patrick Chen ◽  
Mustafa Musleh ◽  
Rao Pallivi ◽  
Melissa Grilliot
Keyword(s):  
Liver Injury ◽  
Rare Case ◽  
Inflammatory Infiltrate ◽  
Hepatocellular Injury ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Mixed Inflammatory Infiltrate ◽  
Liver Biopsies ◽  
Elevated Transaminases ◽  
Caucasian Female

Importance. As Rivaroxaban has increased in popularity, it has been accompanied with a growing body of evidence displaying its ability to cause drug induced liver injury (DILI). Observation. A 74-year-old Caucasian female developed Rivaroxaban DILI two weeks after finishing a 14-day course. The patient was symptomatic and jaundiced with elevated transaminases and hyperbilirubinemia with normal lab values two months priorly. Liver biopsies showed mixed inflammatory infiltrate of lymphocytes, neutrophils and eosinophils, rare necrotic hepatocytes, and canalicular and intrahepatocellular cholestasis, all of which are consistent with DILI. Conclusion and Relevance. We present this case to add to the growing evidence that Rivaroxaban can be associated with severe, symptomatic liver injury and to ensure physicians are aware of these possible side effects of novel anticoagulants with their increasing use.

Combined Modality Treatment with Intensified Chemotherapy and Dose-Reduced Involved Field Radiotherapy in Patients with Early Unfavourable Hodgkin Lymphoma (HL): Final Analysis of the German Hodgkin Study Group (GHSG) HD11 Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 717-717 ◽  
Author(s):  
Peter Borchmann ◽  
Volker Diehl ◽  
Helen Goergen ◽  
Horst Mueller ◽  
Rolf Peter Mueller ◽  
...  
Keyword(s):  
Risk Factors ◽  
Conflicts Of Interest ◽  
Remission Rate ◽  
Intensive Therapy ◽  
Final Analysis ◽  
Patient Characteristics ◽  
Combined Modality Treatment ◽  
Combined Modality ◽  
Involved Field ◽  
Involved Field Radiotherapy

Abstract Abstract 717 Purpose: Combined modality treatment consisting of 4 cycles of chemotherapy (CT) followed by involved field radiotherapy (IF-RT) is the standard treatment for early unfavourable HL. In our prior trial for this group of patients (HD8), overall survival (OS) and freedom from treatment failure (FFTF) at 5 years were 91% and 83%, respectively. The HD11 trial thus addressed two major questions: (1) improving outcome by intensifying CT (4xABVD vs. 4xBEACOPPbaseline; Bbas) and (2) defining the best radiation dose (30Gy vs. 20Gy IF-RT). Patients and methods: Between May 1998 and January 2003, 1395 eligible patients aged 16–75 years with untreated early unfavourable stage HL (CS I, IIA with at least one of the risk factors large mediastinal mass (a), extranodal disease (b), elevated ESR (c) or ≥ 3 nodal areas (d); IIB with risk factors c and/or d) were randomized into one of the following 4 treatment arms: 4xABVD + 30Gy (A), 4xABVD + 20Gy (B), 4x Bbas + 30Gy (C) or 4x Bbas + 20Gy (D). Since there are strong indications for an interaction between CT- and RT-doses, a comparison of pooled treatment arms (A+B vs. C+D for comparison of 4×ABVD vs. 4× Bbas and A+C vs. B+D for comparison of 30Gy IF-RT vs. 20Gy IF-RT) would be misleading. Therefore all treatment arms were analysed separately. Results: Patient characteristics were well balanced between the 4 arms (median age 33 years, 49% male, 6% stage I, 29% B-symptoms). CT- and RT-related acute toxicity occurred significantly more often in the arms with the more intensive therapy (CT: 74.1% vs. 51.8%; RT: 12.3% vs. 5.5%). The complete remission rate 3 months after end of therapy was 94.1% for the whole group and did not differ significantly between the 4 arms. The 5-year estimate of FFTF (primary endpoint) is 85.0% (OS 94.5%, PFS 86.0%). Bbas is more effective than ABVD if followed by 20Gy IF-RT (5y-FFTF difference 5.7%, 95%-CI [0.1%; 11.3%]). This effect does not exist in combination with 30Gy IF-RT (5y-FFTF difference 1.6% [-3.6%; 6.9%]). Similar results are observed for the RT-question: After 4 cycles of Bbas, 20Gy is not inferior to 30Gy (5y-FFTF difference -0.1%, 95%-CI [-5.1%; 4.9%]), whereas after 4xABVD, a relevant inferiority of 20Gy cannot be excluded (-4.0% [-9.5%; 1.4%]). Conclusion: A reduction of RT dose from 30Gy to 20Gy IF-RT seems to be justified only in combination with Bbas, but not with a less effective chemotherapy such as 4xABVD. Patients will benefit from an intensified CT such as Bbas only in combination with 20Gy IF-RT but not with 30Gy IF-RT. Disclosures: No relevant conflicts of interest to declare.

TYPE III PRO-COLLAGEN PEPTIDE IN LIVER DISEASE IN HAEMOPHILIA

1987 ◽  
Author(s):  
R S Evely ◽  
F E Preston ◽  
D R Triger ◽  
C R M Hay ◽  
M C Greves ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Biopsy ◽  
Statistical Significance ◽  
Type Iii ◽  
Amino Terminal ◽  
Collagen Peptide ◽  
Collagen Iii ◽  
Liver Biopsies ◽  
Progressive Liver Disease ◽  
Valuable Predictor

During the past 10 years we have carried out liver biopsies on haemophiliacs with biochemical evidence of chronic liver disease (CLD). To date 44 biopsies have been obtained from 35 patients. Histological diagnoses are Chronic Persistent Hepatitis (CPH) 24, Chronic Aggressive Hepatitis (CAH) 11 and Cirrhosis 9. Serial biopsies indicate that progressive liver disease is now a serious problem in haemophilia. Liver biopsy is not without risk and therefore it is important to identify factors which may be of value in predicting the nature of the liver disease or its progression. Since intra-hepatic fibrosis is a feature of CLD we measured Type III amino terminal propeptide of pro-collagen (PC III) by radio-immunoassay on samples taken within a mean of 4.8 months of the liver biopsy. A normal range was established as 4.3 - 15.7ng/ml on healthy subjects (median 7.0). Median values and ranges for patients with CPH (N=13), CAH (N=5) and cirrhosis (N=5) were 8 (5.4 - 23.4), 14.2 (7.2 - 19.8) and 14.2 (11.2 - 23.0)ng/ml respectively. Although pro-collagen III values tended to be higher in progressive liver disease (CAH and cirrhosis) this did not reach statistical significance. It would, therefore, appear that unlike serum IgG, pro-collagen III will not be a valuable predictor of progressive liver disease in haemophilia. A larger study is necessary to clarify this.

scholarly journals Candida infective endocarditis: A retrospective study of patient characteristics and risk factors for death in 703 U.S. cases, 2015-2019

2020 ◽  
Author(s):  
Jonathan P Huggins ◽  
Samuel Hohmann ◽  
Michael Z David
Keyword(s):  
Risk Factors ◽  
Hospital Mortality ◽  
Liver Failure ◽  
Patient Characteristics ◽  
Medication Administration ◽  
Small Sample ◽  
Risk Of Death ◽  
Opiate Abuse ◽  
Small Sample Sizes ◽  
Valve Pathology

Abstract Background Candida endocarditis is a rare, sometimes fatal complication of candidemia. Past investigations of this condition are limited by small sample sizes. We used the Vizient clinical database to report on characteristics of patients with Candida endocarditis and to examine risk factors for in-hospital mortality. Methods This was a multicenter, retrospective cohort study of 703 inpatients admitted to 179 United States hospitals between October 2015 and April 2019. We reviewed demographic, diagnostic, medication administration, and procedural data from each patient’s initial encounter. Univariate and multivariate logistic regression analyses were used to identify predictors of in-hospital mortality. Results Of 703 patients, 114 (16.2%) died during the index encounter. One hundred and fifty-eight (22.5%) underwent an intervention on a cardiac valve. On multivariate analysis, acute and subacute liver failure was the strongest predictor of death (OR 9.2, 95% CI 4.8 –17.7). Female sex (OR 1.9, 95% CI 1.2 – 3.0), transfer from an outside medical facility (OR 1.8, 95% CI 1.1 – 2.8), aortic valve pathology (OR 2.7, 95% CI 1.5 – 4.9), hemodialysis (OR 2.1, 95% CI 1.1 – 4.0), cerebrovascular disease (OR 2.2, 95% CI 1.2 – 3.8), neutropenia (OR 2.5, 95% CI 1.3 – 4.8), and alcohol abuse (OR 2.9, 95% CI 1.3 – 6.7) were also associated with death on adjusted analysis, whereas opiate abuse was associated with a lower odds of death (OR 0.5, 95% CI 0.2 – 0.9). Conclusions We found that the inpatient mortality rate was 16.2% among patients with Candida endocarditis. Acute and subacute liver failure was associated with a high risk of death while opiate abuse was associated with a lower risk of death.

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