|
1
|
Masood M, Siddique A, Krishnamoorthi R, Kozarek RA. Liver Dysfunction in Adult Hemophagocytic Lymphohistiocytosis: A Narrative Review. Adv Ther 2024; 41:553-566. [PMID: 38145441 DOI: 10.1007/s12325-023-02768-8] [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: 11/07/2023] [Accepted: 12/08/2023] [Indexed: 12/26/2023]
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition that has been increasingly recognized in adults and is characterized by a hyperinflammatory state due to immune dysregulation. Its nonspecific presentation, the lack of clinician familiarity given its rarity, and shared clinical features with sepsis and other syndromes can lead to a delay in diagnosis and a poor prognosis. Significant liver function abnormalities as the initial manifestation of HLH are uncommon and can range from mild elevation of aminotransferases to fulminant hepatic failure with high mortality rates. The authors encountered a case of adult HLH mimicking acute viral hepatitis in which a markedly elevated ferritin level led to a prompt diagnosis, early initiation of treatment, and a successful outcome. Clinicians, including gastroenterologists and hepatologists, are often called upon to evaluate patients with abnormal liver tests and may lack experience in the early diagnosis and management of liver dysfunction in the context of HLH. Thus, we expand our reporting to a narrative review of literature which explores the pathogenesis of HLH, challenges associated with its diagnosis, previous reports of liver disease associated with the syndrome, recommended treatments for the familial and adult variations including the role of liver transplantation, and the outcomes of these treatments.
Collapse
Affiliation(s)
- Muaaz Masood
- Division of Gastroenterology and Hepatology, Center for Digestive Health, Virginia Mason Franciscan Health, Seattle, WA, USA
| | - Asma Siddique
- Division of Gastroenterology and Hepatology, Center for Digestive Health, Virginia Mason Franciscan Health, Seattle, WA, USA
| | - Rajesh Krishnamoorthi
- Division of Gastroenterology and Hepatology, Center for Digestive Health, Virginia Mason Franciscan Health, Seattle, WA, USA
| | - Richard A Kozarek
- Division of Gastroenterology and Hepatology, Center for Digestive Health, Virginia Mason Franciscan Health, Seattle, WA, USA.
- Center for Interventional Immunology, Benaroya Research Institute, Virginia Mason Franciscan Health, 1201 Ninth Ave, Seattle, WA, 98101, USA.
| |
Collapse
|
|
2
|
Bao Q, Xu Z, Yang F, Lu J. Clinical Features of Hepatic Manifestations among Adult Patients with Hemophagocytic Lymphohistiocytosis: A Retrospective Study. Acta Haematol 2024; 147:525-533. [PMID: 38228103 DOI: 10.1159/000535535] [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: 03/03/2023] [Accepted: 11/24/2023] [Indexed: 01/18/2024]
Abstract
INTRODUCTION Liver dysfunction is common in patients with hemophagocytic lymphohistiocytosis (HLH). However, whether the severity of liver injury is associated with the prognosis of patients with HLH remains to be determined. This study aims to assess the association of the severity of liver involvement with short-term prognosis among adult patients with HLH. METHODS A retrospective study was performed from January 2012 to December 2020, including 150 patients with newly diagnosed HLH and liver injury. RESULTS The majority of our cohort suffered from mild to moderate hepatic damage, presenting with Child-Turcotte-Pugh (CTP) class A (55, 36.7%) or B (74, 49.3%). The prevalence of acute liver failure (ALF) was 9.3% in our cohort. The overall 30-day mortality rate was 49.3% among the study population. HLH patients with ALF showed an extremely adverse prognosis, with a mortality rate as high as 92.9%. In a multivariate analysis, age ≥60 years (p = 0.016), blood urea nitrogen (BUN) ≥7 μmol/L (p < 0.001), and malignancy-associated HLH (p < 0.001) at the diagnosis of HLH were identified as being strongly correlated with 30-day prognosis. An excellent predictive power was found. Among the predictive scores used to assess early death of HLH patients with liver injury, the prognostic efficiency of chronic liver failure-sequential organ failure assessment (CLIF-SOFA) (AUROC: 0.936 ± 0.0211) and SOFA score (0.901 ± 0.026) were significantly better than those of the APACHE II (p < 0.001), model for end-stage liver disease score (p < 0.001) and CTP scores (p < 0.001). CONCLUSION Patients with old age, elevated BUN, and malignancy had inferior survival. CLIF-SOFA and SOFA enable more accurate prediction of early death in HLH patients with liver injury than other liver-specific and general prognostic models.
Collapse
Affiliation(s)
- Qiongling Bao
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| | - Zhengqing Xu
- Department of Respiratory Medicine, Anji County People's Hospital, PR, Huzhou, China
| | - Fengling Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| | - Juan Lu
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| |
Collapse
|
|
3
|
Premec H, Živko M, Mijić M, Jelić-Puškarić B, Lalovac M, Filipec Kanižaj T, Sobočan N. Acute Liver Failure Caused by Secondary Hemophagocytic Lymphohistiocytosis After COVID-19 Vaccination - Case Report and Literature Review. Int Med Case Rep J 2023; 16:449-455. [PMID: 37577009 PMCID: PMC10416787 DOI: 10.2147/imcrj.s417347] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Accepted: 07/22/2023] [Indexed: 08/15/2023] Open
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a congenital or acquired hyperinflammatory syndrome, in some cases accompanied by acute liver failure. We present a case report of acute liver failure associated with HLH after COVID-19 vaccination and bring a literature review of the connection between HLH and COVID-19 vaccination. HLH has significant mortality rate, and liver transplantation is not a therapeutic option. Therefore, early recognition and timely conservative treatment are corner stones in reducing HLH-related morbidity and mortality.
Collapse
Affiliation(s)
- Hrvoje Premec
- Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia
| | - Matea Živko
- School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Maja Mijić
- Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia
| | - Biljana Jelić-Puškarić
- Department of Pathology and Cytology, University Hospital Merkur, Zagreb, Croatia
- School of Medicine, Catholic University of Croatia, Zagreb, Croatia
| | - Miloš Lalovac
- Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia
- University of Dubrovnik, Dubrovnik, Croatia
| | - Tajana Filipec Kanižaj
- Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia
- School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Nikola Sobočan
- Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia
- School of Medicine, University of Zagreb, Zagreb, Croatia
| |
Collapse
|
|
4
|
Awan RU, Rashid S, Nabeel A, Samant H. COVID-19 vaccination-related hemophagocytic lymphohistiocytosis presenting as acute liver failure. Proc (Bayl Univ Med Cent) 2022; 36:78-80. [PMID: 36578589 PMCID: PMC9762805 DOI: 10.1080/08998280.2022.2123665] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Acute liver failure following COVID-19 infection and/or vaccination is very rare and can be secondary to hemophagocytic lymphohistiocytosis (HLH). Liver injury in such cases appears to be extrinsic and thus treatment hinges on prompt diagnosis and reversal of the primary disease. We describe a patient who developed acute liver failure secondary to HLH after receiving a second dose of the Pfizer COVID-19 vaccine. Persistently elevated liver function tests, fevers, and cytopenia following COVID-19 vaccination should prompt clinicians to calculate an H-score to evaluate for the presence of HLH.
Collapse
Affiliation(s)
- Rehmat Ullah Awan
- Department of Medicine, Ochsner Rush Health, Meridian, Mississippi,Corresponding author: Rehmat Ullah Awan, MD, Department of Medicine, Ochsner Rush Health, 1314 19th Ave., Meridian, MS39305 (e-mail: )
| | - Shazia Rashid
- Division of Gastroenterology, Department of Medicine, Ochsner Health System, Shreveport, Louisiana
| | - Ambreen Nabeel
- Department of Medicine, Ochsner Rush Health, Meridian, Mississippi
| | - Hrishikesh Samant
- Division of Gastroenterology, Department of Medicine, Ochsner Health System, Gonzales, Louisiana
| |
Collapse
|
|
5
|
Cappell MS, Hader I, Amin M. Acute liver failure secondary to severe systemic disease from fatal hemophagocytic lymphohistiocytosis: Case report and systematic literature review. World J Hepatol 2018; 10:629-636. [PMID: 30310541 PMCID: PMC6177573 DOI: 10.4254/wjh.v10.i9.629] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 07/20/2018] [Accepted: 08/28/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To systematically review liver disease associated with hemophagocytic lymphohistiocytosis (HLH), propose reasonable contraindications for liver transplantation for liver failure in HLH, and report an illustrative case.
METHODS Systematic review according to PRISMA guidelines of hepatic manifestations of HLH using computerized literature search via PubMed of articles published since 1980 with keywords (“hemophagocytic lymphohistiocytosis” or “HLH”) AND (“liver” or “hepatic”). Two authors independently performed literature search and incorporated articles into this review by consensus. Illustrative case report presented based on review of medical chart, and expert re-review of endoscopic photographs, radiologic images, and pathologic slides.
RESULTS A 47-year-old Caucasian male, was hospitalized with high-grade pyrexia, rash, total bilirubin = 45 g/dL, moderately elevated hepatic transaminases, ferritin of 3300 ng/dL, leukopenia, and profound neutropenia (absolute neutrophil count < 100 cells/mm³). Viral serologies for hepatitis A, B, and C were negative. Abdominal computed tomography scan and magnetic resonance imaging revealed no hepatic or biliary abnormalities. Pathologic analysis of liver biopsy revealed relatively well-preserved hepatic parenchyma without lymphocytic infiltrates or macrophage invasion, except for sparse, focal hepatocyte necrosis. Bone marrow biopsy and aspirate revealed foamy macrophages engulfing mature and precursor erythrocytes, consistent with HLH. Interleukin-2 receptor (CD25) was highly elevated, confirming diagnosis of HLH according to Histiocytic Society criteria. Patient initially improved after high-dose prednisone therapy. Patient was judged not to be a liver transplant candidate despite model for end stage liver disease (MELD) score = 33 because liver failure was secondary to severe systemic disease from HLH, including septic shock, focal centrilobular hepatocyte necrosis from hypotension, bone marrow failure, and explosive immune activation from HLH. The patient eventually succumbed to overwhelming sepsis, progressive liver failure, and disseminated intravascular coagulopathy. Systematic review reveals liver injury is very common in HLH, and liver failure can sometimes occur. Data on liver transplantation for patients with HLH are very limited, and so far the results have shown a generally much worse prognosis than for other liver transplant indications. Liver transplantation should not be guided solely by MELD score, but should include liver biopsy results and determination whether liver failure is from intrinsic liver injury vs multisystem (extrahepatic) organ failure from HLH.
CONCLUSION This case report illustrates that liver transplantation may not be warranted when liver failure associated with HLH is primarily from multisystem failure from HLH. Liver biopsy may be very helpful in determining the severity and pathophysiology of the liver disease.
Collapse
Affiliation(s)
- Mitchell S Cappell
- Division of Gastroenterology and Hepatology, William Beaumont Hospital, Royal Oak, MI 48073, United States
- Department of Medicine, Oakland University William Beaumont School of Medicine, Royal Oak, MI 48073, United States
| | - Ismail Hader
- Department of Medicine, William Beaumont Hospital, Royal Oak, MI 48073, United States
| | - Mitual Amin
- Department of Pathology, William Beaumont Hospital, Royal Oak, MI 48073, United States
- Department of Pathology, Oakland University William Beaumont School of Medicine, Royal Oak, MI 48073, United States
| |
Collapse
|
|
6
|
Acute Liver Failure Secondary to Hemophagocytic Lymphohistiocytosis during Pregnancy. ACG Case Rep J 2016; 3:e162. [PMID: 27921061 PMCID: PMC5126497 DOI: 10.14309/crj.2016.135] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Accepted: 05/25/2016] [Indexed: 11/17/2022] Open
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive immune activation that mimics and occurs with other systemic diseases. A 35-year-old female presented with signs of viral illness at 13 weeks of pregnancy and progressed to acute liver failure (ALF). We discuss the diagnosis of HLH and Kikuchi-Fujimoto (KF) lymphadenitis in the context of pregnancy and ALF. HLH may respond to comorbid disease-specific therapy, and more toxic treatment can be avoided.
Collapse
|
|
7
|
Lin S, Li Y, Long J, Liu Q, Yang F, He Y. Acute liver failure caused by hemophagocytic lymphohistiocytosis in adults: A case report and review of the literature. Medicine (Baltimore) 2016; 95:e5431. [PMID: 27893685 PMCID: PMC5134878 DOI: 10.1097/md.0000000000005431] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Revised: 10/13/2016] [Accepted: 10/28/2016] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) is a rare condition that can be caused by a primary or acquired disorder of uncontrolled immune response. Liver injury is a common complication of HLH; however, HLH presenting as acute liver failure (ALF) has rarely been reported in adults. CASE SUMMARY A 34-year-old man was admitted to our hospital with nausea and fatigue persisting for 2 weeks and jaundice for 1 week. He had hyperthermia at the onset of disease. At admission, he had severe liver injury with unknown etiology. The laboratory data showed that he had hyperferritinemia, thrombocytopenia, anemia, hypertriglyceridemia, and hypofibrinogenemia. Finally, a bone marrow biopsy revealed hemophagocytic cells, and he was diagnosed with HLH. The patient was treated with prednisone and plasma exchange. However, the liver function of the patient deteriorated, and he finally died of multiorgan failure. CONCLUSIONS Reports of adult patients with ALF caused by HLH have increased, and HLH should be suspected in patients with ALF of indeterminate cause. Although the efficacy of the treatment strategy recommended by the HLH 2004 remains to be confirmed in adult patients with ALF caused by HLH, early diagnosis and prompt combined treatment with steroids and cyclosporin A or etoposide should be emphasized.
Collapse
|
|
8
|
Álvarez Artero E, Campo Núñez A, Albarrán Severo B, Pardo-Lledias J. Severe liver disease as first sign of a haemophagocytic syndrome. GASTROENTEROLOGIA Y HEPATOLOGIA 2016; 40:348-349. [PMID: 27260631 DOI: 10.1016/j.gastrohep.2016.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Revised: 04/01/2016] [Accepted: 04/04/2016] [Indexed: 11/28/2022]
Affiliation(s)
- Elisa Álvarez Artero
- Servicio de Medicina Interna, Hospital General Río Carrión, Complejo Asistencial Universitario de Palencia (CAUPA), Palencia, España.
| | - Amaia Campo Núñez
- Servicio de Medicina Interna, Hospital General Río Carrión, Complejo Asistencial Universitario de Palencia (CAUPA), Palencia, España
| | - Beatriz Albarrán Severo
- Servicio de Hematología, Hospital General Río Carrión, Complejo Asistencial Universitario de Palencia (CAUPA), Palencia, España
| | - Javier Pardo-Lledias
- Servicio de Medicina Interna, Hospital General Río Carrión, Complejo Asistencial Universitario de Palencia (CAUPA), Palencia, España
| |
Collapse
|
|
9
|
Abstract
Hemophagocytic lymphohistiocytosis (HLH) covers a wide array of related life-threatening conditions featuring ineffective immunity characterized by an uncontrolled hyperinflammatory response. HLH is often triggered by infection. Familial forms result from genetic defects in natural killer cells and cytotoxic T-cells, typically affecting perforin and intracellular vesicles. HLH is likely under-recognized, which contributes to its high morbidity and mortality. Early recognition is crucial for any reasonable attempt at curative therapy to be made. Current treatment regimens include immunosuppression, immune modulation, chemotherapy, and biological response modification, followed by hematopoietic stem-cell transplant (bone marrow transplant). A number of recent studies have contributed to the understanding of HLH pathophysiology, leading to alternate treatment options; however, much work remains to raise awareness and improve the high morbidity and mortality of these complex conditions.
Collapse
Affiliation(s)
- Melissa R George
- Department of Pathology, Penn State Milton S Hershey Medical Center, Hershey, PA, USA
| |
Collapse
|
|
10
|
Amin N, Shah I, Bhatnagar S. Hemophagocytic Lymphohistiocytosis (HLH) in Children Presenting as Liver Disease. J Clin Exp Hepatol 2014; 4:175-7. [PMID: 25755554 PMCID: PMC4116702 DOI: 10.1016/j.jceh.2013.06.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2013] [Accepted: 06/16/2013] [Indexed: 12/12/2022] Open
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a rare acute hyperinflammatory condition presenting with high fever, pancytopenia, splenomegaly with the pathologic finding of hemophagocytic lymphohistiocytosis in bone marrow and other tissues. Predominant hepatic manifestations at presentation are rare. We report a series of three cases which showcase the spectrum of liver disease as presentation in hemophagocytic lymphohistiocytosis.
Collapse
Affiliation(s)
| | - Ira Shah
- Address for correspondence: Ira Shah, Co-Incharge, 1/B Saguna, 271/B St Francis Road, Vile Parle (W), Mumbai 400056, India.
| | | |
Collapse
|
|
11
|
Pieri G, Theocharidou E, Burroughs AK. Liver in haematological disorders. Best Pract Res Clin Gastroenterol 2013; 27:513-30. [PMID: 24090939 DOI: 10.1016/j.bpg.2013.06.012] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2013] [Accepted: 06/28/2013] [Indexed: 01/31/2023]
Abstract
Prothrombotic haematological disorders, in particular myeloproliferative disorders, are identified in a significant proportion of patients with Budd-Chiari syndrome and portal vein thrombosis (PVT). Multiple prothrombotic disorders may coexist. PVT is diagnosed in one fourth of patients with cirrhosis and is more common with advanced liver disease and hepatocellular carcinoma. PVT in cirrhosis can precipitate decompensation. Intrahepatic microthrombosis may play a role in the pathogenesis of hepatic fibrosis. Sinusoidal obstruction syndrome is usually a complication of myeloablative treatment before haematopoietic stem cell transplantation. Post-transplant lymphoproliferative disorders can complicate liver transplantation and are related to Epstein-Barr virus infection. Hepatitis B reactivation in patients receiving chemotherapy for haematological malignancies is very common without pre-emptive treatment, and can lead to liver failure. Liver involvement is common in primary haematological diseases, such as haemolytic anaemias, lymphomas and leukaemia.
Collapse
Affiliation(s)
- Giulia Pieri
- The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, Royal Free Hampstead NHS Trust and Institute of Liver and Digestive Health, University College London, Pond Street, NW3 2QG London, United Kingdom
| | | | | |
Collapse
|