Case Report: An unusual case of severe autoimmune hemolytic anemia in untreated hepatitis C viral infection

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Autoimmune hemolytic anemia (AIHA) is usually reported with interferon-alpha and/or ribavirin treatment in hepatitis C virus (HCV) infections. We report an unusual case of AIHA occurring in a49-year-old patient with untreated hepatitis C infection who presented with functional anemia syndrome. Monospecific direct antiglobulin test showed the presence of anti-complement (C3d++). Cold agglutinin titer was 1/16 at 4°C. The patient improved following blood transfusion, steroid therapy and direct acting antivirals." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/13-863", "name": "Case Report: An unusual case of severe autoimmune hemolytic anemia..." } } ] } Home Browse Case Report: An unusual case of severe autoimmune hemolytic anemia... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Debbabi H, Chakroun A, Elloumi H et al. Case Report: An unusual case of severe autoimmune hemolytic anemia in untreated hepatitis C viral infection [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2024, 13 :863 ( https://doi.org/10.12688/f1000research.148607.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Case Report Case Report: An unusual case of severe autoimmune hemolytic anemia in untreated hepatitis C viral infection [version 1; peer review: 1 approved, 1 approved with reservations] H Debbabi 1 , A Chakroun 2 , H Elloumi 3 , H Yacoub https://orcid.org/0000-0002-0042-7704 1 , S Ben Azouz https://orcid.org/0000-0002-9628-265X 1 , R Marouani 4 H Debbabi 1 , A Chakroun 2 , [...] H Elloumi 3 , H Yacoub https://orcid.org/0000-0002-0042-7704 1 , S Ben Azouz https://orcid.org/0000-0002-9628-265X 1 , R Marouani 4 PUBLISHED 01 Aug 2024 Author details Author details 1 Gastroeneterology Department, La Rabta Hospital, Tunis, Tunisia 2 Hematology Department, La Rabta Hospital, Tunis, Tunisia 3 Gastroenterology Department, Habib Bougatfa, Bizerte, Tunisia 4 Gastroenterology Department, Kasserine Hospital, Kasserine, Tunisia H Debbabi Roles: Conceptualization, Data Curation, Formal Analysis, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing A Chakroun Roles: Conceptualization, Data Curation, Writing – Original Draft Preparation H Elloumi Roles: Conceptualization, Software, Supervision, Validation, Writing – Original Draft Preparation H Yacoub Roles: Conceptualization, Data Curation, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing S Ben Azouz Roles: Conceptualization, Data Curation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing R Marouani Roles: Conceptualization OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Patients with hepatitis C share a variety of anemia, including bleeding, nutritional deficiencies, and anemia of chronic disease. Autoimmune hemolytic anemia (AIHA) is usually reported with interferon-alpha and/or ribavirin treatment in hepatitis C virus (HCV) infections. We report an unusual case of AIHA occurring in a49-year-old patient with untreated hepatitis C infection who presented with functional anemia syndrome. Monospecific direct antiglobulin test showed the presence of anti-complement (C3d++). Cold agglutinin titer was 1/16 at 4°C. The patient improved following blood transfusion, steroid therapy and direct acting antivirals. READ ALL READ LESS Keywords Cold agglutinin- autoimmune hemolytic anemia- Chronic hepatitis C Corresponding Author(s) H Yacoub ( [email protected] ) Close Corresponding author: H Yacoub Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2024 Debbabi H et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Debbabi H, Chakroun A, Elloumi H et al. Case Report: An unusual case of severe autoimmune hemolytic anemia in untreated hepatitis C viral infection [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2024, 13 :863 ( https://doi.org/10.12688/f1000research.148607.1 ) First published: 01 Aug 2024, 13 :863 ( https://doi.org/10.12688/f1000research.148607.1 ) Latest published: 01 Aug 2024, 13 :863 ( https://doi.org/10.12688/f1000research.148607.1 ) Introduction Chronic hepatitis C virus (HCV) infection is widely recognized as a cause of extrahepatic manifestations, including autoimmune disorders. 1 – 4 Autoimmune hemolytic anemia (AIHA) is rare. Warm AIHA with HCV infection in treatment-naïve patients has been described either during interferon treatment or in treatment-naive patients. 4 – 7 However, the association between AIHA due to cold agglutinin and untreated hepatitis C seems to be a rare situation, to the best of our knowledge only two cases have been reported. 8 , 9 Herein, we present a case of HVC infection complicated by cold AIHA. Case report A 49-year-old man with a history of HVC diagnosed two months ago, presented with dyspnea and pallor. HCV belonged to the type 1a genotype and the viral load was 1.6 10 6 UI/ml. Fibroscan showed F2 hepatic fibrosis stage. No evidence of recent drug use was found. On admission, the patient was pale, polypneic, and tachycardic with mild hepatomegaly. The patient did not have splenomegaly or lymphadenopathy. Laboratory tests showed severe anemia with a low hemoglobin (Hb) level (4.2 g/dl), macrocytosis (MCV 120 fL), reticulocytosis (5.2%), and normal white blood cell and platelet counts. A peripheral blood smear showed anisocytosis and polychromasia with rare schizocytes. Hemolysis workup revealed elevated indirect bilirubin (84 μmol/l), high lactate dehydrogenase (LDH) (580 U/L), and low haptoglobin concentration (0.15 g/l). These findings were consistent with the diagnosis of hemolytic anemia. The presence of anti-complement C3d++ was confirmed using a monospecific direct antiglobulin test (DAT- Low Ionic Strength Solution). Anti-immunoglobulin G antibodies were absent. Screening of the eluate was negative, and the cold agglutinin titer was 1/16 at 4°C. Hemoglobin electrophoresis results were normal. A bone marrow biopsy was performed to elucidate the underlying etiology of the patient’s AIHA and showed erythroid hyperplasia with no evidence of tumor lymphoma. Further investigations, including anti-smooth muscle, antinuclear antibodies, and anti-DNA antibodies, were negative. However, type III mixed cryoglobulinemia was also observed. Thoracic-abdominal computed tomography (CT) indicated that the underlying malignancy was ruled out. Serology results for hepatitis B and human immunodeficiency virus (HIV) were also negative. Based on the above findings, a diagnosis of AIHA due to cold agglutinin complicating untreated chronic hepatitis C was made. The patient required repeated packed RBC transfusions on admission. When the diagnosis of AIHA was confirmed, the patient received corticosteroid therapy (1.5 mg/kg/day) for six weeks. No additional blood transfusion was needed because a remarkable improvement in the Hb level was obtained (9.8 g/dl). After three months, the patient started HCV treatment with oral antiviral therapy. During the follow-up, the patient’s hematologic disorders were completely renormalized. Discussion HCV-related immune disorders are frequent secondary to the activation of the immune system. HCV lymphotropism determines dysregulation of the immune system, facilitating clonal B-lymphocyte expansion and autoantibody production. 10 This state represents a trigger in the pathogenesis of virus-related immune disorders both in systemic autoimmune diseases (Sjögren syndrome, rheumatoid arthritis, etc.) and in organ-specific autoimmune diseases (diabetes mellitus, thyroid disorders, etc.). 11 A wide variety of hematologic disorders associated with HCV, such as anemia, neutropenia, and thrombocytopenia, are well documented and are usually associated with interferon (IFN) and ribavarin therapy. 2 , 12 – 14 It has been suggested that AIHA observed in untreated HCV infection occurs especially in cirrhotic patients, who have a higher prevalence of autoimmune diseases and respond well to corticosteroid therapy. 12 However, HCV-related AIHA is uncommon in treatment-naive patients. 4 Most cases previously reported in the literature describe warm AIHA with no history of autoimmune disorders. 14 – 19 Anemia was not associated with any other hematological disorders with a good response to steroid therapy. However, the association between AIHA due to cold agglutinin and untreated hepatitis C seems rare. To the best of our knowledge, only two cases have been reported. 8 , 9 In the latter, cold agglutinin-mediated hemolytic anemia occurred in 72- and 74-year-old men who were positive for type III mixed cryoglobulinemia, as in our patient. Mixed cryoglobulinemia is the most documented extrahepatic manifestation of HCV infection. 20 A common hypothesis for HCV-related cryoglobulinemia is chronic antigen stimulation of the humoral immune system, with clonal b-lymphocyte expansion producing circulating immunocomplexes. It may also facilitate the development of autoimmune diseases and lymphoproliferative disorders. However, in our patient, as well as in the two published cases, there was no evidence of lymphoproliferative disorder. 9 Our patient was diagnosed with cold agglutinins AIHA, including hemolytic anemia, reticulocytosis, elevated lactate dehydrogenase, hyperbilirubinemia, positive direct antiglobulin test (DAT), monospecific DAT positive for C3d, and negative for IgG and cold agglutinin titers ≥ 64. In our patient, the thermal amplitude, which is the highest temperature at which the antibody reacts with the antigen, at 4°C was useful for diagnosis, considering the cold agglutinin titer < 64. 21 Cold agglutinins can adhere to red blood cells at low temperatures (complement activation). C3b-coated erythrocytes are removed by macrophages. 22 Subsequently, it is imperative to rule out potential etiologies of cold agglutinin-induced AIHA, including medication side effects, systemic lupus erythematosus, and malignancy. In our patient and in two similar published cases, no etiology was found, except for HCV infection. Pathogenesis of AIHA induced by infectious agents is still not well understood. Inflammatory state may explain this rare condition. 23 , 24 Different treatment modalities are available for AIHA: corticosteroids, anti-CD20 (rituximab), Intravenous immunoglobulin (IVIG), and splenectomy. However, in cold AIHA, steroids are less effect in patients with cold AIHA compared with patients with warm AIHA. 14 , 19 , 25 Our patient was a good responder to corticosteroids. Steroids do not seem to show good results in all cases. 8 In this situation, anti-CD20 or IVIG may be considered. 26 However, it is important to note that the concomitant use of HCV antiretroviral drugs could explain the good response to corticosteroid therapy observed in our patient. Conclusions AIHA due to cold agglutinin is a very uncommon hematologic manifestation of HCV infection, particularly in treatment-naive patients. HCV seems to be mysterious, and further research is needed to elucidate the mechanisms of some related HCV autoimmune manifestations. Consent Patient gave an informed written consent to publish details regarding the case summary and its use in medical publications. Data availability All data underlying the results are available as part of the article and no additional source data are required. References 1. Canavese C, Hollò Z, Ciccone G, et al. : Extrahepatic immunological manifestations of hepatitis C virus in dialysis patients. J. Nephrol. 2000; 13 (5): 352–359. PubMed Abstract 2. Bayraktar Y, Bayraktar M, Gurakar A, et al. : A comparison of the prevalence of autoantibodies in individuals with chronic hepatitis C and those with autoimmune hepatitis: the role of interferon in the development of autoimmune diseases. Hepato-Gastroenterology. 1997; 44 (14): 417–425. PubMed Abstract 3. Clifford BD, Donahue D, Smith L, et al. : High prevalence of serological markers of autoimmunity in patients with chronic hepatitis C. Hepatology. 1995; 21 (3): 613–619. PubMed Abstract 4. Bianco C, Coluccio E, Prati D, et al. : Diagnosis and Management of Autoimmune Hemolytic Anemia in Patients with Liver and Bowel Disorders. J. Clin. Med. 2021 22; 10 (3): 423. PubMed Abstract | Publisher Full Text | Free Full Text 5. Basseri RJ, Schmidt MT, Basseri B: Autoimmunehemolyticanemia in treatment-naivechronichepatitis C infection: a case report and review of literature. Clin. J. Gastroenterol. 2010; 3 (5): 237–242. PubMed Abstract | Publisher Full Text 6. Oliveira TL, Caetano AZ, Belem JM, et al. : Interferon-α induced psoriatic arthritis and autoimmune hemolytic anemia during chronic hepatitis C treatment. Acta Reumatol. Port. 2014; 39 (4): 327–330. PubMed Abstract 7. Cauli C, Serra G, Chessa L, et al. : Severe autoimmune hemolytic anemia in a patient with chronic hepatitis C during treatment with peginterferon alfa-2a and ribavirin. Haematologica. 2006; 91 : ECR26. PubMed Abstract 8. Etienne A, Gayet S, Vidal F, et al. : Severe hemolytic anemia due to cold agglutinin complicating untreated chronic hepatitis C: Efficacy and safety of anti-CD20 (rituximab) treatment: Brief Report: Hemolytic Anemia Due to Cold Agglutinin in Untreated Hepatitis C. Am. J. Hematol. 2004 Apr; 75 (4): 243–245. PubMed Abstract | Publisher Full Text 9. Ruivard M, Tridon A, Quainon F, et al. : Agglutinines froides et cryoglobulinémie chez un patient avec une hépatite C [Cold agglutinins and cryoglobulinemia in a patient with hepatitis C]. Presse Med. 1996; 25 (32): 1548–1549. French. PubMed Abstract 10. Zignego AL, Ferri C, Pileri SA, et al. : Extrahepatic manifestations of Hepatitis C Virus infection: a general overview and guidelines for a clinical approach. Dig. Liver Dis. 2007; 39 : 2–17. PubMed Abstract | Publisher Full Text 11. Calvaruso V, Craxì A: Immunological alterations in hepatitis C virus infection. World J. Gastroenterol. 2013; 19 : 8916–8923. Publisher Full Text 12. Reau N, Hadziyannis SJ, Messinger D, et al. : Early predictors of anemia in patients withhepatitis C genotype 1 treated with peginterferon alfa-2a (40KD) plus ribavirin. Am. J. Gastroenterol. 2008; 103 (8): 1981–1988. PubMed Abstract | Publisher Full Text | Free Full Text 13. Davidovitz Y, Halpern Z, Vardi J, et al. : Pure Red Cell Aplasia Responsive to Interferon-α in a Patient with Hepatitis C Virus Infection. Acta Haematol. 1998; 100 (4): 213–215. Publisher Full Text 14. Srinivasan R: Autoimmune Hemolytic Anemia in Treatment-naïve Chronic Hepatitis C Infection. J. Clin. Gastroenterol. 2001; 32 (3): 245–247. PubMed Abstract | Publisher Full Text 15. Ramos-Casals M, García-Carrasco M, López-Medrano F, et al. : Severe Autoimmune Cytopenias in Treatment-naïve Hepatitis C Virus Infection: Clinical Description of 35 Cases. Medicine (Baltimore). 2003; 82 (2): 87–96. PubMed Abstract | Publisher Full Text 16. Elhajj II, Sharara AI, Taher AT: Chronic hepatitis C associated with Coombs-positive hemolytic anemia. Hematol. J. 2004; 5 (4): 364–366. PubMed Abstract | Publisher Full Text 17. Chao TC, Chen CY, Yang YH, et al. : Chronic hepatitis C virus infection associated with primary warm-type autoimmune hemolytic anemia. J. Clin. Gastroenterol. 2001 Sep; 33 (3): 232–233. PubMed Abstract | Publisher Full Text 18. Moccia F, Tognoni E, Boccaccio P: Autoimmune hemolytic anemia in chronic hepatitis C virus infection: an unusual extrahepatic autoimmune manifestation. Ann. Ital. Med. Int. 2001; 16 (4): 256–259. PubMed Abstract 19. Espinosa BerenguelJ L, Muñoz Sánchez JA: Autoimmune hemolytic anemia and post hepatitis-C liver cirrhosis. An. Med. Interna. 1997; 14 (11): 583–584. 20. Ferri C, Greco F, Longombardo G, et al. : Association between hepatitis C virus and mixed cryoglobulinemia [see comment]. Clin. Exp. Rheumatol. 1991; 9 : 621–624. PubMed Abstract 21. Jäger U, Barcellini W, Broome CM, et al. : Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting. Blood Rev. 2019; 41 : 100648. Publisher Full Text 22. Jaffe CJ, Atkinson JP, Frank MM: The role of complement in the clearance of cold agglutinin-sensitized erythrocytes in man. J. Clin. Invest. 1976; 58 : 942–949. PubMed Abstract | Publisher Full Text | Free Full Text 23. Lazarian G, Quinquenel A, Bellal M, et al. : Autoimmune haemolytic anaemia associated with COVID-19 infection. Br. J. Haematol. 2020; 190 : 29–31. PubMed Abstract | Publisher Full Text | Free Full Text 24. Prabhu R, Bhaskaran R, Shenoy V, et al. : Clinical characteristics and treatment outcomes of primary autoimmune hemolytic anemia: a single center study from South India. Blood Res. 2016; 51 (2): 88–94. PubMed Abstract | Publisher Full Text | Free Full Text 25. Berentsen S: How I manage cold agglutinin disease: Review. Br. J. Haematol. 2011; 153 (3): 309–317. PubMed Abstract | Publisher Full Text 26. Berentsen S: New insights in the pathogenesis and therapy of cold agglutinin-mediated autoimmune hemolytic anemia. Front. Immunol. 2020; 11 : 590. PubMed Abstract | Publisher Full Text | Free Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 01 Aug 2024 ADD YOUR COMMENT Comment Author details Author details 1 Gastroeneterology Department, La Rabta Hospital, Tunis, Tunisia 2 Hematology Department, La Rabta Hospital, Tunis, Tunisia 3 Gastroenterology Department, Habib Bougatfa, Bizerte, Tunisia 4 Gastroenterology Department, Kasserine Hospital, Kasserine, Tunisia H Debbabi Roles: Conceptualization, Data Curation, Formal Analysis, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing A Chakroun Roles: Conceptualization, Data Curation, Writing – Original Draft Preparation H Elloumi Roles: Conceptualization, Software, Supervision, Validation, Writing – Original Draft Preparation H Yacoub Roles: Conceptualization, Data Curation, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing S Ben Azouz Roles: Conceptualization, Data Curation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing R Marouani Roles: Conceptualization Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 01 Aug 2024, 13:863 https://doi.org/10.12688/f1000research.148607.1 Copyright © 2024 Debbabi H et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Debbabi H, Chakroun A, Elloumi H et al. Case Report: An unusual case of severe autoimmune hemolytic anemia in untreated hepatitis C viral infection [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2024, 13 :863 ( https://doi.org/10.12688/f1000research.148607.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 01 Aug 2024 Views 0 Cite How to cite this report: Batsaikhan B. Reviewer Report For: Case Report: An unusual case of severe autoimmune hemolytic anemia in untreated hepatitis C viral infection [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2024, 13 :863 ( https://doi.org/10.5256/f1000research.162939.r324838 ) The direct URL for this report is: https://f1000research.com/articles/13-863/v1#referee-response-324838 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 14 Oct 2024 Batbold Batsaikhan , Institute of Medical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia Approved VIEWS 0 https://doi.org/10.5256/f1000research.162939.r324838 This case report is well written and included all necessary patient's condition. Also it is well described extrahepatic manifestations such as cryoglobulinemia. It is informative for practitioners that chronic HCV infection can be related with cold autoimmune hemolytic anemia. Authors ... Continue reading READ ALL This case report is well written and included all necessary patient's condition. Also it is well described extrahepatic manifestations such as cryoglobulinemia. It is informative for practitioners that chronic HCV infection can be related with cold autoimmune hemolytic anemia. Authors may address SVR condition after HCV treatment, it is sure that patient responded the treatment. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: liver fibrosis, HCV, HCC I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Batsaikhan B. Reviewer Report For: Case Report: An unusual case of severe autoimmune hemolytic anemia in untreated hepatitis C viral infection [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2024, 13 :863 ( https://doi.org/10.5256/f1000research.162939.r324838 ) The direct URL for this report is: https://f1000research.com/articles/13-863/v1#referee-response-324838 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Premkumar M. Reviewer Report For: Case Report: An unusual case of severe autoimmune hemolytic anemia in untreated hepatitis C viral infection [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2024, 13 :863 ( https://doi.org/10.5256/f1000research.162939.r324843 ) The direct URL for this report is: https://f1000research.com/articles/13-863/v1#referee-response-324843 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 01 Oct 2024 Madhumita Premkumar , Postgraduate Institute of Medical Education and Research,, Chandigarh, India Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.162939.r324843 The authors present a single report of AIHA occurring in a 49-year-old patient with untreated hepatitis C infection who presented with 'functional' anemia syndrome. 1. Please advise if it was appropriate to start steroids without the cover ... Continue reading READ ALL The authors present a single report of AIHA occurring in a 49-year-old patient with untreated hepatitis C infection who presented with 'functional' anemia syndrome. 1. Please advise if it was appropriate to start steroids without the cover of direct acting antiviral agents (DAAs) given that the patient has f2 fibrosis and could worsen. 2. How were other causes of hemolytic anemia ruled out? What is a functional anemia syndrome? 3. What was the regimen of DAA prescribed? Did the patient attain SVR-12? 4. Was a liver biopsy done? 5. Change the statement 'HCV seems to be mysterious, and further research is needed to elucidate the mechanisms of some related HCV autoimmune manifestations.' There is no new information in this report to suggest mystery. Please see the additional references[ref 1][ref 2] and [ref 3]. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Yes References 1. Chiao EY, Engels EA, Kramer JR, Pietz K, et al.: Risk of immune thrombocytopenic purpura and autoimmune hemolytic anemia among 120 908 US veterans with hepatitis C virus infection. Arch Intern Med . 2009; 169 (4): 357-63 PubMed Abstract | Publisher Full Text 2. Dufour JF, Pradat P, Ruivard M, Hot A, et al.: Severe autoimmune cytopenias in treatment-naive hepatitis C virus infection: clinical description of 16 cases. Eur J Gastroenterol Hepatol . 2009; 21 (3): 245-53 PubMed Abstract | Publisher Full Text 3. Fernández A: An unusual case of autoimmune hemolytic anemia in treatment naïve hepatitis C virus infection. Hematology . 2006; 11 (5-6): 385-387 Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Hepatology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Premkumar M. Reviewer Report For: Case Report: An unusual case of severe autoimmune hemolytic anemia in untreated hepatitis C viral infection [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2024, 13 :863 ( https://doi.org/10.5256/f1000research.162939.r324843 ) The direct URL for this report is: https://f1000research.com/articles/13-863/v1#referee-response-324843 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 01 Aug 2024 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 01 Aug 24 read read Madhumita Premkumar , Postgraduate Institute of Medical Education and Research,, Chandigarh, India Batbold Batsaikhan , Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Batsaikhan B. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 14 Oct 2024 | for Version 1 Batbold Batsaikhan , Institute of Medical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia 0 Views copyright © 2024 Batsaikhan B. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This case report is well written and included all necessary patient's condition. Also it is well described extrahepatic manifestations such as cryoglobulinemia. It is informative for practitioners that chronic HCV infection can be related with cold autoimmune hemolytic anemia. Authors may address SVR condition after HCV treatment, it is sure that patient responded the treatment. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise liver fibrosis, HCV, HCC I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Batsaikhan B. Peer Review Report For: Case Report: An unusual case of severe autoimmune hemolytic anemia in untreated hepatitis C viral infection [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2024, 13 :863 ( https://doi.org/10.5256/f1000research.162939.r324838) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-863/v1#referee-response-324838 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Premkumar M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 01 Oct 2024 | for Version 1 Madhumita Premkumar , Postgraduate Institute of Medical Education and Research,, Chandigarh, India 0 Views copyright © 2024 Premkumar M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors present a single report of AIHA occurring in a 49-year-old patient with untreated hepatitis C infection who presented with 'functional' anemia syndrome. 1. Please advise if it was appropriate to start steroids without the cover of direct acting antiviral agents (DAAs) given that the patient has f2 fibrosis and could worsen. 2. How were other causes of hemolytic anemia ruled out? What is a functional anemia syndrome? 3. What was the regimen of DAA prescribed? Did the patient attain SVR-12? 4. Was a liver biopsy done? 5. Change the statement 'HCV seems to be mysterious, and further research is needed to elucidate the mechanisms of some related HCV autoimmune manifestations.' There is no new information in this report to suggest mystery. Please see the additional references[ref 1][ref 2] and [ref 3]. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Yes References 1. Chiao EY, Engels EA, Kramer JR, Pietz K, et al.: Risk of immune thrombocytopenic purpura and autoimmune hemolytic anemia among 120 908 US veterans with hepatitis C virus infection. Arch Intern Med . 2009; 169 (4): 357-63 PubMed Abstract | Publisher Full Text 2. Dufour JF, Pradat P, Ruivard M, Hot A, et al.: Severe autoimmune cytopenias in treatment-naive hepatitis C virus infection: clinical description of 16 cases. Eur J Gastroenterol Hepatol . 2009; 21 (3): 245-53 PubMed Abstract | Publisher Full Text 3. Fernández A: An unusual case of autoimmune hemolytic anemia in treatment naïve hepatitis C virus infection. Hematology . 2006; 11 (5-6): 385-387 Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Hepatology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Premkumar M. Peer Review Report For: Case Report: An unusual case of severe autoimmune hemolytic anemia in untreated hepatitis C viral infection [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2024, 13 :863 ( https://doi.org/10.5256/f1000research.162939.r324843) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-863/v1#referee-response-324843 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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