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Meena M, Meena DS, Kumar D, Pandit S. Severe Autoimmune Hemolytic Anemia Complicating Treatment-naive Chronic Hepatitis C Infection: A Case Report. Cardiovasc Hematol Disord Drug Targets 2022; 22:CHDDT-EPUB-122646. [PMID: 35440330 DOI: 10.2174/1871529x22666220418105506] [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: 09/17/2021] [Revised: 12/21/2021] [Accepted: 02/10/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Haematological manifestations in Hepatitis C virus (HCV) infection has been uncommon since the advent of direct-acting antiviral drugs (DAAs). However, primary HCV disease can cause significant haematological disease in the form of various autoimmune cytopenias. CASE PRESENTATION We herein discuss a 68-years-old female with chronic HCV infection for the last 15 years (not on the treatment), presented with complaints of progressive fatigue, exertional dyspnea, and increased abdominal distention over the previous 20 days. Coombs-positive autoimmune haemolytic anaemia (AIHA) was diagnosed based on the haematological evaluation (raised lactate dehydrogenase, indirect bilirubinemia, raised reticulocyte count and direct Coombs positive). The patient showed significant improvement in haematological indices with oral prednisolone. However, she eventually succumbed to her illness due to underlying decompensated liver disease. HCV infection may associate with global derangement of the immune system, which is likely to cause AIHA. Diagnosis of autoimmune cytopenias can be easily missed in HCV positive patients due to underlying decompensated liver disease and portal hypertension. CONCLUSION Thus, screening of HCV infection is imperative in every patient of AIHA, especially with the high worldwide prevalence of HCV.
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Affiliation(s)
| | | | | | - Sonu Pandit
- All India Institute of Medical Sciences, Jodhpur
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Diagnosis and Management of Autoimmune Hemolytic Anemia in Patients with Liver and Bowel Disorders. J Clin Med 2021; 10:jcm10030423. [PMID: 33499290 PMCID: PMC7865399 DOI: 10.3390/jcm10030423] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Revised: 01/15/2021] [Accepted: 01/19/2021] [Indexed: 12/12/2022] Open
Abstract
Anemia is a common feature of liver and bowel diseases. Although the main causes of anemia in these conditions are represented by gastrointestinal bleeding and iron deficiency, autoimmune hemolytic anemia should be considered in the differential diagnosis. Due to the epidemiological association, autoimmune hemolytic anemia should particularly be suspected in patients affected by inflammatory and autoimmune diseases, such as autoimmune or acute viral hepatitis, primary biliary cholangitis, and inflammatory bowel disease. In the presence of biochemical indices of hemolysis, the direct antiglobulin test can detect the presence of warm or cold reacting antibodies, allowing for a prompt treatment. Drug-induced, immune-mediated hemolytic anemia should be ruled out. On the other hand, the choice of treatment should consider possible adverse events related to the underlying conditions. Given the adverse impact of anemia on clinical outcomes, maintaining a high clinical suspicion to reach a prompt diagnosis is the key to establishing an adequate treatment.
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Hill QA, Stamps R, Massey E, Grainger JD, Provan D, Hill A. Guidelines on the management of drug-induced immune and secondary autoimmune, haemolytic anaemia. Br J Haematol 2017; 177:208-220. [PMID: 28369704 DOI: 10.1111/bjh.14654] [Citation(s) in RCA: 95] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Quentin A Hill
- Department of Haematology, Leeds Teaching Hospitals, Leeds, UK
| | | | | | - John D Grainger
- Royal Manchester Children's Hospital, University of Manchester, Manchester, UK
| | - Drew Provan
- Barts and The London School of Medicine and Dentistry, London, UK
| | - Anita Hill
- Department of Haematology, Leeds Teaching Hospitals, Leeds, UK
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Rodrigo C, Rajapakse S, Gooneratne L. Rituximab in the treatment of autoimmune haemolytic anaemia. Br J Clin Pharmacol 2016; 79:709-19. [PMID: 25139610 DOI: 10.1111/bcp.12498] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Accepted: 08/13/2014] [Indexed: 11/29/2022] Open
Abstract
Rituximab is a B-cell depleting monoclonal antibody that is gaining popularity as an effective therapy for many autoimmune cytopenias. This article systematically evaluates its therapeutic efficacy in the treatment of different types of autoimmune haemolytic anaemia. We conclude that there is sufficient evidence to recommend it as a second line therapy for warm autoimmune haemolytic anaemia (wAIHA) either as monotherapy or combined therapy. Evidence from a single randomized controlled trial suggests that it may also be more efficacious as first line therapy in combination with steroids than steroids alone. A fewer number of studies have assessed its role in cold autoimmune haemolytic anaemia (cAIHA) and cold agglutinin disease (CAD) with success rates varying from 45-66%. In the absence of alternative definitive therapy, rituximab should be considered for patients with symptomatic CAD and significant haemolysis. Case reports of its efficacy in mixed autoimmune haemolytic anaemias are available but evidence from case series or larger cohorts are nonexistent.
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Affiliation(s)
- Chaturaka Rodrigo
- Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
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Ufearo H, Kambal K, Onojobi GO, Nouraie M, Agbemabiese C, Diaz S, Aggarwal A, Aliyu Z, Taylor RE, Gordeuk VR. Complete blood count, measures of iron status and inflammatory markers in inner-city African Americans with undiagnosed hepatitis C seropositivity. Clin Chim Acta 2010; 411:653-6. [PMID: 20117104 DOI: 10.1016/j.cca.2010.01.028] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2009] [Revised: 12/12/2009] [Accepted: 01/22/2010] [Indexed: 01/11/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection may be associated with thrombocytopenia and increased iron stores in patients receiving medical care. We aimed to determine how often changes in hematologic, iron metabolic and inflammatory markers occur in individuals with undiagnosed HCV in the community. METHODS Inner-city African Americans (n=143) were recruited from the community according to reported ingestion of alcohol. They were divided broadly into those who drank more or less than 56 g alcohol/day as assessed by dietary questionnaire. HCV serology was determined and laboratory values were compared according to HCV seropositivity in analyses that adjusted for alcohol consumption. RESULTS The prevalence of HCV seropositivity was 23% among men and 29% among women. Levels of hepatocellular enzymes were higher with HCV seropositivity (P<0.0001) but hemoglobin concentrations, white blood cell and platelet counts and serum ferritin concentrations did not differ. The globulin fraction of the serum protein concentration (P=0.002) was increased with HCV seropositivity as expected with chronic inflammation. However, erythrocyte sedimentation rate and serum iron and haptoglobin levels did not differ significantly according to HCV status. Furthermore, multivariate analysis revealed that C-reactive protein was decreased and transferrin concentration was increased with both HCV and alcohol consumption (P<0.014). CONCLUSIONS Previously undiagnosed HCV seropositivity has little effect on the complete blood count and body iron stores but appears to perturb the response to an inflammatory stimulus, causing reduced rather than increased circulating CRP concentrations and increased rather than decreased transferrin concentrations.
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Affiliation(s)
- Hilary Ufearo
- Department of Medicine, Howard University College of Medicine, Washington, DC, USA
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Annicchiarico B, Siciliano M, Avolio A, Agnes S, Bombardieri G. Orthotopic Liver Transplantation After Successful Treatment With Anti-CD20 Monoclonal Antibody (Rituximab) for Severe Steroid-Resistant Autoimmune Hemolytic Anemia: A Case Report. Transplant Proc 2009; 41:1380-2. [DOI: 10.1016/j.transproceed.2009.03.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Severe autoimmune cytopenias in treatment-naive hepatitis C virus infection: clinical description of 16 cases. Eur J Gastroenterol Hepatol 2009; 21:245-53. [PMID: 19279468 DOI: 10.1097/meg.0b013e3283249908] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To describe the prevalence, main characteristics, and treatment of severe autoimmune cytopenias [autoimmune hemolytic anemia (AIHA), autoimmune thrombocytopenic purpura (AITP)] in patients with chronic hepatitis C virus (HCV) infection. METHODS Retrospective chart review of patients with chronic HCV infection seen at our institution. Two additional departments contributed eight more patients to assess therapy of HCV-related autoimmune cytopenias. RESULTS Eight patients (seven AITP, one AIHA) fulfilled the inclusion criteria in our population of 4345 HCV-infected patients. The number of patients with AITP was much greater than would be expected by chance (P<0.0001). Patients with HCV-related AITP were older and demonstrated more immunological markers than a group of 40 controls. Eight additional patients (six AITP, two Evans syndrome) were included. We only assessed the response for AITP patients because of the single case of AIHA. Patients with AITP had a poor response to initial corticosteroids [one complete response (CR), three partial response (PR), and four failures]. Intravenous immunoglobulins led to transient efficacy in three of four patients. In second-line therapy, five of seven patients responded to splenectomy. Rituximab proved effective in increasing platelets in two patients. Of eight patients treated with antiviral therapy (IFN-alpha+/-ribavirin), five responded (three CR, two PR). CONCLUSION AITP occurs more commonly in patients with chronic HCV infection than would be expected by chance. HCV-positive AITP requires a treatment strategy different from that used in HCV-negative AITP. On the basis of the results from our study and a literature analysis, we propose an algorithm for treatment of severe HCV-related autoimmune cytopenias.
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Valent P, Lechner K. Diagnosis and treatment of autoimmune haemolytic anaemias in adults: a clinical review. Wien Klin Wochenschr 2008; 120:136-51. [DOI: 10.1007/s00508-008-0945-1] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2007] [Accepted: 02/18/2008] [Indexed: 11/30/2022]
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Chapter 16 Extrahepatic Manifestations in Patients with Chronic Hepatitis C Virus Infection. ACTA ACUST UNITED AC 2008. [DOI: 10.1016/s1571-5078(07)00016-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Fernández AB. An unusual case of autoimmune hemolytic anemia in treatment naïve hepatitis C virus infection. ACTA ACUST UNITED AC 2007; 11:385-7. [PMID: 17607592 DOI: 10.1080/10245330600938596] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Hepatitis C virus (HCV) infection is emerging as a common and insidiously progressive liver condition. In more than one third of the cases, extrahepatic manifestations are seen in the course of the disease. Over the past decade, authors have reported membranous nephropathy, cutaneous vasculitis, idiopathic thrombocytopenic purpura, porphyria cutanea tarda and diabetes mellitus, among other extrahepatic manifestations of HCV infection. Recently, there have been a growing number of reports relating HCV infection to autoimmune cytopenias. Here, we report an unusual case of Coombs'-negative autoimmune hemolytic anemia (AHA) with severe autoimmune leukopenia and neutropenia, occurring simultaneously, in a patient with untreated hepatitis C infection. Mild cytopenias during chronic hepatitis C have been reported widely in the medical literature; however, severe cytopenias are seldom described and are usually seen only after or simultaneously with therapy.
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Affiliation(s)
- Antonio B Fernández
- Department of Internal Medicine, University of Connecticut Health Center, Farmington, CT, USA
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Okada T, Kubota K, Kita J, Kato M, Sawada T. Hepatocellular carcinoma with chronic B-type hepatitis complicated by autoimmune hemolytic anemia: A case report. World J Gastroenterol 2007; 13:4401-4. [PMID: 17708620 PMCID: PMC4250873 DOI: 10.3748/wjg.v13.i32.4401] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
A 57-year-old man consulted a local hospital because of a persistent slight fever. At the age of 37 years he was diagnosed having B-type hepatitis, but left the liver dysfunction untreated. Twenty years later, he was diagnosed having chronic hepatitis B, hepatocellular carcinoma (HCC) and macrocytic anemia, and referred to our hospital for further investigation. A HCC with a maximum diameter of 5.2 cm was detected in segment 8. Results of blood tests included 1.8 mg/dL serum total bilirubin, 0.9 mg/dL bilirubin, less than 10 mg/dL haptoglobin, 7.9 g/dL hemoglobin, 130 fL MCV, and 14.5% reticulocytes. A bone marrow sample showed erythroid hyperplasia. The direct Coombs test gave a positive result. We diagnosed the anemia as autoimmmune hemolytic anemia (AIHA), for which prednisolone could not be administered due to positivity for HBsAg and HBeAg. After preparation of washed blood cells for later transfusion, the patient underwent systematic resection of segment 8. The cut surface of the resected specimen demonstrated an encapsulated yellow-brownish tumor measuring 52 mm × 40 mm which was diagnosed pathologicaly as moderately differentiated HCC. On the 9th postoperative day, the patient’s temperature rose to 38°C, and exacerbated hemolysis was observed. The maximum total bilirubin value was 5.8 mg/dL and minimum hemoglobin level was 4.6 g/dL. He tolerated this period without blood transfusion. Currently he is being followed up as an outpatient, and shows no signs of HCC recurrence or symptoms of anemia. AIHA associated with HBV infection has been described in only three previous cases, and the present case is the first in which surgery was performed for accompanying HCC.
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Affiliation(s)
- Toshie Okada
- Department of Gastroenterological Surgery, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293, Japan
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Butt AA, Evans R, Skanderson M, Shakil AO. Comorbid medical and psychiatric conditions and substance abuse in HCV infected persons on dialysis. J Hepatol 2006; 44:864-8. [PMID: 16516332 DOI: 10.1016/j.jhep.2006.01.024] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2005] [Revised: 01/06/2006] [Accepted: 01/17/2006] [Indexed: 02/06/2023]
Abstract
BACKGROUND/AIMS The burden of comorbidity in the Hepatitis C virus (HCV) infected persons on dialysis is unknown. METHODS We identified all HCV infected and uninfected subjects in the United States Renal Data System in the years 1997-1998 using ICD-9 codes. Controls were matched on the date of first dialysis. ICD-9 codes and claims data was used to identify medical and psychiatric comorbidities. RESULTS We identified 5,737 HCV infected persons and 11,228 HCV uninfected subjects. HCV infected subjects were younger, more likely to be black race and male and more likely to have the following comorbidities: hypertension; hepatitis B; cirrhosis; wasting; anemia; human immunodeficiency virus (HIV) infection; major depression; mild depression; bipolar disorder; schizophrenia; post-traumatic stress disorder; drug use; alcohol use; smoking and less likely to have the following comorbidities: coronary artery disease; stroke; peripheral vascular disease; diabetes; cancer; erythropoietin use. After adjusting for age, gender and race, HCV infected subjects were more likely to have hypertension, hepatitis B, cirrhosis, wasting, anemia and HIV infection and less likely to have coronary artery disease and stroke. CONCLUSIONS HCV infected persons on dialysis are more likely to have psychiatric comorbidities and substance abuse, as well as certain medical comorbidities. These factors should be considered when developing future intervention strategies.
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Affiliation(s)
- Adeel A Butt
- University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
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Ramos-Casals M, Font J. Extrahepatic manifestations in patients with chronic hepatitis C virus infection. Curr Opin Rheumatol 2005; 17:447-55. [PMID: 15956842 DOI: 10.1097/01.bor.0000166386.62851.49] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW Chronic hepatitis C virus infection often has autoimmune clinical and analytic features. This review analyzes recent data on the close association of chronic hepatitis C virus infection with autoimmune and lymphoproliferative processes. RECENT FINDINGS Hepatitis C virus infection has been associated with both organ-specific (thyroiditis, diabetes) and systemic autoimmune diseases. Experimental, virologic, and clinical evidence has demonstrated a close association between hepatitis C virus infection and Sjögren syndrome, with hepatitis C virus-associated Sjögren syndrome being indistinguishable in most cases from the primary form. With respect to rheumatoid arthritis, patients with hepatitis C virus-related polyarthritis and positive rheumatoid factor may fulfill the classification criteria for rheumatoid arthritis. Hepatitis C virus has also been associated with an atypical presentation of antiphospholipid syndrome, as well as with the development of sarcoidosis. A higher prevalence of hematologic processes in patients with hepatitis C virus infection has recently been reported, including cytopenias and lymphoproliferative disorders. Recent data are available on the use of new immunosuppressive and biologic agents (mainly mycophenolate mofetil, anti-tumor necrosis factor agents, and rituximab) in patients with hepatitis C virus infection and autoimmune or lymphoproliferative manifestations. SUMMARY There is increasing evidence of a close association of hepatitis C virus infection with autoimmune and hematologic processes. The sialotropism of hepatitis C virus may explain the close association with Sjögren syndrome, and its lymphotropism links the virus to cryoglobulinemia, autoimmune cytopenias, and lymphoma. The substantial overlap between cryoglobulinemic features and the classification criteria for some systemic autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, and polyarteritis nodosa) make the differentiation between mimicking and coexistence difficult.
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Affiliation(s)
- Manuel Ramos-Casals
- Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer, School of Medicine, University of Barcelona, Hospital Clínic, Barcelona, Spain
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