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Xiong A, Li S, Dou X, Yao Y. Cyclophosphamide in refractory autoimmune hepatitis and autoimmune hepatitis coexisting extrahepatic autoimmune disorders. Am J Med Sci 2024; 368:446-454. [PMID: 38876435 DOI: 10.1016/j.amjms.2024.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 12/19/2023] [Accepted: 06/10/2024] [Indexed: 06/16/2024]
Abstract
INTRODUCTION AND OBJECTIVES Despite tacrolimus (TAC) or mycophenolate mofetil (MMF) for alternate approaches, a proportion of patients still required further exploration of other therapeutic options due to uncontrolled autoimmune hepatitis(AIH). The role of cyclophosphamide (CYC) for AIH has been explored in isolated case reports and small series. We present a review of CYC therapy in AIH patients. MATERIALS AND METHODS A search for studies with keywords 'autoimmune hepatitis' and 'cyclophosphamide' was performed. Data recorded included gender, age, laboratory parameters and histological findings at the time of AIH diagnosis and before initiation of CYC therapy. RESULTS We identified 13 patients across 7 studies who met criteria for study inclusion, of whom around 69.2% (9/13) were primary refractory; 30.8% (4/13) patients used CYC as rescue therapy due to their coexisting autoimmune complications. The main findings of the study were that CYC appears to have an acceptable safety profile in difficult-to-treat AIH patients, with an overall remission rate of 88.9% (8/9). The other four patients with AIH accompanied by extrahepatic autoimmune disorders also achieved remission of transaminase levels and stability of liver function after the addition of CYC. A positive response to CYC treatment was seen in 12(92.3%) patients and none of them relapsed during the follow-up. CONCLUSIONS We cautiously recommend that CYC could be a conditioning alternative to starting second-line therapy after unsuccessful intensification of first-line treatment. Pharmacogenetic methods may play a role in guiding cyclophosphamide therapy. Given our small sample size, results should be considered preliminary.
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Affiliation(s)
- AnJi Xiong
- Department of Rheumatology and Immunology, Nanchong Central Hospital, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong Hospital of Bejjing Anzhen Hospital Capital Medical University, Nanchong, Sichuan Province, China; Inflammation and Immunology Key Laboratory of Nanchong City, Nanchong, Sichuan Province, China; Nanchong Central Hospital (Nanchong Clinical Research Center), Nanchong, Sichuan Province, China.
| | - SuTing Li
- Department of Ophthalmology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province 518035, China; Shenzhen University Health Science Center, 3688 Nanhai Avenue, Shenzhen, Guangdong Province 518060, China
| | - XiaoYan Dou
- Department of Ophthalmology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province 518035, China
| | - YuFeng Yao
- Department of Ophthalmology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province 518035, China; Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong Province 515031, China
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Rashad E, Moazam MM, Chaudhry R, El Eraky N, Mirza MSS, Nazmin F. Efficacy of Combination Therapies for Autoimmune Hepatitis: A Systematic Review and Meta-Analysis. Cureus 2024; 16:e60049. [PMID: 38854256 PMCID: PMC11162748 DOI: 10.7759/cureus.60049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/10/2024] [Indexed: 06/11/2024] Open
Abstract
Autoimmune hepatitis (AIH) is a hepatocellular disorder thought to be caused by an immune system that cannot tolerate autoantigens specific to hepatocytes. This study aims to evaluate the efficacy of using corticosteroids (prednisolone and azathioprine) as a combination therapy in treating AIH. This study aims to synthesize and analyze existing evidence to inform clinical practices concerning the overall clinical efficacy of this treatment approach in managing AIH. A comprehensive search was conducted across multiple online databases and search engines, including PubMed, Google Scholar, ScienceDirect, Medline, and Embase. RevMan 5.4 software was used for meta-analysis, with forest plots created for each outcome. Thirteen studies were included in this systematic review and meta-analysis. The results indicate that the combination of prednisolone and azathioprine for treating AIH leads to less recurrence and better disease control.
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Affiliation(s)
- Essam Rashad
- Hospital Medicine, Parkview Regional Medical Center, Fort Wayne, USA
| | - Mustafa M Moazam
- Psychiatry, Texas Tech University Health Sciences Center El Paso, El Paso, USA
| | | | - Noha El Eraky
- Radiology, St Vincent's University Hospital, Dublin, IRL
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Nawalerspanya S, Tantipisit J, Assawasuwannakit S, Kaewdech A, Chamroonkul N, Sripongpun P. Non-Invasive Serum Biomarkers for the Diagnosis of Cirrhosis in Patients with Autoimmune Hepatitis (AIH) and AIH-Primary Biliary Cholangitis Overlap Syndrome (AIH-PBC): Red Cell Distribution Width to Platelet Ratio (RPR) Yielded the Most Promising Result. Diagnostics (Basel) 2024; 14:265. [PMID: 38337781 PMCID: PMC10855432 DOI: 10.3390/diagnostics14030265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 01/15/2024] [Accepted: 01/24/2024] [Indexed: 02/12/2024] Open
Abstract
Several serum biomarkers for fibrosis assessment have been proposed in various liver diseases, but in autoimmune hepatitis (AIH) or overlap with primary biliary cholangitis (PBC; AIH-PBC) patients, the data are scarce. This retrospective cross-sectional study was conducted to validate six non-invasive biomarkers in the diagnosis of cirrhosis (F4 fibrosis) in such patients. We included adult patients diagnosed with AIH or AIH-PBC overlap syndrome who underwent a liver biopsy between 2011 and 2021. Laboratory data were collected to calculate the following scores: red cell distribution width to platelet ratio (RPR), aspartate aminotransferase/platelet ratio index (APRI), Fibrosis-4 index (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-platelet ratio (LPR). A total of 139 patients were eligible (111 AIH and 28 AIH-PBC). The prevalence of cirrhosis was 35.3% (36% in AIH and 32.1% in AIH-PBC). The AUROCs of the RPR, FIB-4, APRI, AAR, LPR, and NLR in all patients were 0.742, 0.724, 0.650, 0.640, 0.609, and 0.585, respectively. RPR was significantly superior to APRI, NLR, and LPR. Moreover, RPR showed the highest AUROC (0.915) in the overlap AIH-PBC subgroup. In conclusion, RPR yielded the highest diagnostic accuracy to predict cirrhosis in AIH and AIH-PBC overlap syndrome patients, while FIB-4 was considerably optimal.
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Affiliation(s)
- Siwanon Nawalerspanya
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (S.N.); (S.A.); (A.K.); (N.C.)
- Department of Internal Medicine, Phaholponpayuhasena Hospital, Kanchanaburi 71000, Thailand
| | - Jarukit Tantipisit
- Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand;
| | - Suraphon Assawasuwannakit
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (S.N.); (S.A.); (A.K.); (N.C.)
- Department of Medicine, Panyananthaphikkhu Chonprathan Medical Center, Srinakharinwirot University, Nonthaburi 11120, Thailand
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (S.N.); (S.A.); (A.K.); (N.C.)
| | - Naichaya Chamroonkul
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (S.N.); (S.A.); (A.K.); (N.C.)
| | - Pimsiri Sripongpun
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (S.N.); (S.A.); (A.K.); (N.C.)
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Lee DU, Schuster K, Bahadur A, Schellhammer S, Ponder R, Mitchell-Sparke E, Fan GH, Lee KJ, Chou H, Lominadze Z. Trends of Costs and Admission Rates Among Patients Admitted With Autoimmune Hepatitis: Analysis of US Hospitals Using the NIS Database. J Clin Exp Hepatol 2024; 14:101279. [PMID: 38076380 PMCID: PMC10709195 DOI: 10.1016/j.jceh.2023.08.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 08/27/2023] [Indexed: 01/05/2025] Open
Abstract
Background and aim Autoimmune hepatitis (AIH) is a prominent cause of chronic liver disease in the United States. This study aims to characterize the incidence, mortality, and cost implications of this condition using a national database. Method The 2016-2019 National Inpatient Sample was used to select patients with AIH. After adjusting for inflation, weighted charge data were used to calculate the admission costs using charge-to-cost ratios. Demographic, socioeconomic status, and comorbidity values were used to build strata to characterize admission incidence, mortality data and aggregate and per-capita cost values. Furthermore, additional sensitivity analysis was performed using a stratified set of patients with AIH as one of the top 10 diagnosis (AIH-specific subsample). Multinomial regression curves were graphed and assessed to derive goodness-of-fit for each trend. R2 and P-values were calculated. Results From 2016 to 2019, the total admissions related to AIH were approximately 20,984, 21,905, 22,055, and 22,680 cases, respectively (R2: 0.93, P-value: 0.03). AIH-related hospitalization aggregate costs came to $338.18, $369.17, $355.98, and $387.25 million dollars (R2: 0.75, P-value: 0.17). Significant admission growth was seen in the Southern region (R2: 0.91, P-value: 0.05). Most notably, increasing trends in total admissions were found across older age, those of White and Hispanic descent, and those with comorbidities. On the other hand, the AIH-specific subsample illustrated decreasing trends in admissions across demographics (i.e., age, gender, and race) and comorbidities; however, those with hepatic complications saw a rise in the admission trends (cirrhosis - R2: 0.98, P-value: 0.009; multiple liver complications - R2: 0.95, P-value: 0.03). Conclusion Among AIH-specific admissions, there was a decreasing trend overall; however, there was an exceptional increase in the admissions among those with hepatic complications.
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Affiliation(s)
- David U. Lee
- Division of Gastroenterology and Hepatology, University of Maryland, 22 S. Greene St, Baltimore, MD, 21201, USA
| | - Kimberly Schuster
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA, 02111, USA
| | - Aneesh Bahadur
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA, 02111, USA
| | | | - Reid Ponder
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA, 02111, USA
| | - Emma Mitchell-Sparke
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA, 02111, USA
| | - Gregory H. Fan
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA, 02111, USA
| | - Ki J. Lee
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA, 02111, USA
| | - Harrison Chou
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA, 02111, USA
| | - Zurabi Lominadze
- Division of Gastroenterology and Hepatology, University of Maryland, 22 S. Greene St, Baltimore, MD, 21201, USA
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Ji W, Peng X, Lou T, Wang J, Qiu W. Total flavonoids from Tetrastigma hemsleyanum ameliorates inflammatory stress in concanavalin A-induced autoimmune hepatitis mice by regulating Treg/Th17 immune homeostasis. Inflammopharmacology 2019; 27:1297-1307. [DOI: 10.1007/s10787-019-00599-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 04/25/2019] [Indexed: 02/08/2023]
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Hanouneh M, Ritchie MM, Ascha M, Ascha MS, Chedid A, Sanguankeo A, Zein NN, Hanouneh IA. A review of the utility of tacrolimus in the management of adults with autoimmune hepatitis. Scand J Gastroenterol 2019; 54:76-80. [PMID: 30650311 DOI: 10.1080/00365521.2018.1551498] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND There is paucity of data on alternative drug therapies for patients with autoimmune hepatitis (AIH). Tacrolimus (TAC) is a promising salvage agent. We present a review of TAC therapy in AIH patients. METHODS A search for studies with keywords 'autoimmune hepatitis' and 'tacrolimus' was performed. Reviews, studies of AIH post-transplant and AIH in children were excluded. Diagnosis of AIH was based on criteria established by the International Autoimmune Hepatitis Group. Complete biochemical response was defined as normalisation of aspartate aminotransferase (AST <45) and alanine aminotransferase (ALT <50). No biochemical response was defined as failure to return to normalisation at the end of follow-up. Demographic information and details of pre- and post-treatment liver biopsy were collected. RESULTS Seven articles achieved the inclusion criteria and reported data for a total of 162 adult patients. The majority of studies reported average ages approximately 35 years old. Treatment duration ranged from 1 to 136 months. Indications for therapy were mostly AIH refractory to steroid treatment or inability to tolerate standard steroid treatment. Eighty-three patients (51.2%) were reported to have pre-therapy liver biopsy. Of 49 patients for whom stage was reported, 6 patients were stage 1, 16 were stage 2, 14 were stage 3 and 13 were stage 4. Of 40 patients for whom grade was reported, 1 patient was grade 0, 3 were grade 1, 9 were grade 2, 14 were grade 3 and 13 were grade 4. Dosing regimens were between 1 and 8 mg/day. Target trough TAC serum concentrations ranged from 0.5 to 10.7 ng/mL TAC was discontinued in 28 (17.3%) patients for various reasons. Renal function remained stable in most patients. One hundred and twenty-one patients (74.7%) demonstrated complete biochemical response to treatment. Post-therapy liver biopsy was obtained for 30 (18.5%) patients, and 25 (15.4%) of these patients were noted to have histological remission according to the grade of inflammation or stage of fibrosis. CONCLUSION TAC is relatively effective in the treatment of AIH refractory to traditional therapy. It appears that liver function can be enhanced at a minimal cost to renal function. Key Points There is a cohort of patients with autoimmune hepatitis (AIH) who do not respond to standard therapy. Alternative treatment options for these patients have been explored, but outcomes have not been comprehensively examined. We report the use and efficacy of tacrolimus (TAC) in patients with AIH. We found that TAC can be safely and effectively used in patients with AIH with minimal side effects. TAC can be a potential treatment option for patients with AIH refractory to standard therapy.
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Affiliation(s)
- Mohamad Hanouneh
- a Department of Internal Medicine, Division of Nephrology , Johns Hopkins University Hospital , Baltimore , MD, USA
| | | | - Mona Ascha
- c School of Medicine , Case Western Reserve University , Cleveland , OH, USA
| | - Mustafa S Ascha
- d Center for Clinical Investigation, Department of Epidemiology and Biostatistics , Case Western Reserve University , Cleveland , OH, USA
| | - Alice Chedid
- a Department of Internal Medicine, Division of Nephrology , Johns Hopkins University Hospital , Baltimore , MD, USA
| | - Anawin Sanguankeo
- a Department of Internal Medicine, Division of Nephrology , Johns Hopkins University Hospital , Baltimore , MD, USA
| | - Nizar N Zein
- e Department of Gastroenterology and Hepatology , Digestive Disease Institute, Cleveland Clinic , Cleveland , OH, USA
| | - Ibrahim A Hanouneh
- b Abbott Northwestern Hospital , Minneapolis , MN, USA.,f Minnesota Gastroenterology , Minneapolis , MN, USA
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Enomoto H, Nishiguchi S. Similarities and Differences in Autoimmune Hepatitis Epidemiology between East and West: Autoimmune Hepatitis in East Asia, Southeast Asia, and South Asia. Inflamm Intest Dis 2017; 1:150-158. [PMID: 29922671 PMCID: PMC5988198 DOI: 10.1159/000454879] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is a relatively rare disease that can develop regardless of age or ethnicity. However, its clinical features differ between eastern and western populations due to several heterogeneous genetic and environmental factors. We herein report the clinical characteristics of AIH patients in East Asia, Southeast Asia, and South Asia. SUMMARY AND KEY MESSAGES The prevalence of AIH in eastern countries is considered to be lower than in western countries. Although a few young patients with type 2 AIH have been observed in South Asia, most patients in Asia are middle-aged women with type 1 AIH who respond well to steroid-based immunosuppressive therapy. Human leukocyte antigen DR4 is suggested to be an influential factor in the genetic background of AIH patients in Asia, particularly in East Asia. Notably, AIH may be induced by some societal- or culture-associated medicines, including herbal medicines. The IAIHG (International Autoimmune Hepatitis Group) scoring systems are generally accepted as the standard diagnostic methods for AIH in Asian countries. The results of repeated nationwide surveys in Japan suggest that the clinical features of AIH patients in East Asia are changing, with IgG levels and rates of anti-nuclear antibody positivity decreasing.
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Affiliation(s)
| | - Shuhei Nishiguchi
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
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Autoimmune Hepatitis: Progress from Global Immunosuppression to Personalised Regulatory T Cell Therapy. Can J Gastroenterol Hepatol 2016; 2016:7181685. [PMID: 27446862 PMCID: PMC4904688 DOI: 10.1155/2016/7181685] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Accepted: 11/20/2015] [Indexed: 12/23/2022] Open
Abstract
Autoimmune hepatitis (AIH) is an immune mediated liver injury. The precise aetiology of AIH is still unknown but current evidence suggests both genetic and environmental factors are involved. Breakdown in peripheral self-tolerance, and impaired functions of FOXP3(+) regulatory T cell along with effector cell resistance to suppression at the tissue level seem to play an important role in AIH immunopathogenesis. AIH is predominantly a T lymphocytes driven disease but B lymphocytes are also involved in the immunopathology. Innate immune cells are crucial in the initial onset of disease and their response is followed by adaptive T (Th1, Th17, and cytotoxic T cells) and B cell responses evidenced by liver histology and peripheral blood serology. Standard treatment regimens involving steroid and immunosuppressive medications lead to global immune suppression requiring life-long therapy with many side effects. Biologic therapies have been attempted but duration of remission is short-lived. Future direction of diagnosis and treatment for AIH should be guided by "omics" and the immunology profile of the individual patient and clinicians should aim to deliver personalised medicine for their patients. Cell therapy such as infusion of autologous, antigen-specific, and liver-homing regulatory T cells to restore hepatic immune tolerance may soon be a potential future treatment for AIH patients.
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Bittencourt PL, Cançado ELR, Couto CA, Levy C, Porta G, Silva AEB, Terrabuio DRB, Carvalho Filho RJD, Chaves DM, Miura IK, Codes L, Faria LC, Evangelista AS, Farias AQ, Gonçalves LL, Harriz M, Lopes Neto EPA, Luz GO, Oliveira P, Oliveira EMGD, Schiavon JLN, Seva-Pereira T, Parise ER, Parise ER. Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver. ARQUIVOS DE GASTROENTEROLOGIA 2015; 52 Suppl 1:15-46. [DOI: 10.1590/s0004-28032015000500002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
ABSTRACT In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology.
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Salvado M, Vargas V, Vidal M, Simon-Talero M, Camacho J, Gamez J. Autoimmune-like hepatitis during masitinib therapy in an amyotrophic lateral sclerosis patient. World J Gastroenterol 2015; 21:10475-10479. [PMID: 26420975 PMCID: PMC4579895 DOI: 10.3748/wjg.v21.i36.10475] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2015] [Revised: 05/07/2015] [Accepted: 07/03/2015] [Indexed: 02/06/2023] Open
Abstract
We report a case of acute severe hepatitis resulting from masitinib in a young amyotrophic lateral sclerosis patient. Hepatotoxicity induced by masitinib, a tyrosine kinase inhibitor, is usually transient with mild elevation of transaminases, although acute hepatitis has been not reported to date. The hepatitis was resolved after masitinib was discontinued and a combination of prednisone and azathioprine was started. The transaminases returned to baseline normal values five months later. This is the first case in the hepatitis literature associated with masitinib. The autoimmune role of this drug-induced liver injury is discussed. Physicians should be aware of this potential complication.
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Wallisch K, Trepanier LA. Incidence, timing, and risk factors of azathioprine hepatotoxicosis in dogs. J Vet Intern Med 2015; 29:513-8. [PMID: 25641386 PMCID: PMC4895519 DOI: 10.1111/jvim.12543] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2014] [Revised: 10/16/2014] [Accepted: 12/17/2014] [Indexed: 01/11/2023] Open
Abstract
Background The use of azathioprine (AZA) in dogs is limited by the development of hepatotoxicosis and cytopenias. Hypothesis and Objectives To characterize the observed incidence, timing, and risk factors for AZA hepatotoxicosis in dogs treated clinically, and to determine the relationship between the development of hepatotoxicosis and cytopenias. Animals Fifty‐two dogs treated with AZA with clinical and biochemical follow‐up, with a subset of 34 dogs available for determination of changes in liver enzyme activities in serum. Methods Retrospective medical record review, from January 2009 through December 2013. Results Hepatotoxicosis (as defined by a >2‐fold increase in serum ALT) was observed in 5 of 34 dogs (15%) within a median onset of 14 days (range, 13–22 days). Dogs had a median 9‐fold increase in ALT and 8‐fold increase in ALP, which stabilized or resolved with drug discontinuation or dose reduction. German shepherds were significantly over‐represented (3 of 5 dogs with hepatotoxicosis; P = .0017). Thrombocytopenia or neutropenia were seen in 4 of 48 dogs with CBC follow‐up (8% of dogs), but occurred significantly later in treatment (median onset, 53 days; range 45–196 days) compared to hepatotoxicosis (P = .016). Conclusions and Clinical Importance These results support the routine monitoring of liver enzymes during the first 1–4 weeks of AZA treatment in dogs, with continued monitoring of the CBC. Additional studies are warranted to characterize the apparently higher risk of AZA hepatotoxicosis in German shepherds.
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Affiliation(s)
- K Wallisch
- Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI
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