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Arora A, Sharma P, Kumar A, Acharya S, Sarin SK, Duseja A, Puri P, Shah S, Chawla Y, Rao P, Saraya A, Mohanka R, Singh S, Saighal S, Rela M, Vij V, Asthana S, Shukla A, Bhangui P, Saraf N, Maiwall R, Mandot A, Saraswat V, Madan K, Shalimar, Kapoor D, Anand AC, Gupta S, Varghese J, Mehta N. Indian National Association for the Study of Liver (INASL) Guidance Statements for Determining Futility in Liver Transplantation. J Clin Exp Hepatol 2025; 15:102539. [PMID: 40343081 PMCID: PMC12056968 DOI: 10.1016/j.jceh.2025.102539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 02/24/2025] [Indexed: 05/10/2025] Open
Abstract
Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver disease; however, with the growing shortage of organ donors, the need to identify futile transplants has become increasingly urgent. Futility in liver transplantation refers to situations where the expected post-transplant survival or quality of life is poor, making the procedure unlikely to yield a meaningful benefit. Various definitions of futility are used across different countries and transplant centers, with criteria often based on clinical factors such as age, comorbidities, MELD score, and functional status. For hepatologists and transplant surgeons, clearer guidelines are essential to make informed decisions and avoid unnecessary transplants that may place patients at risk without improving their prognosis. While some studies have proposed futility scores, there is currently no universal consensus on a standardized definition or set of criteria. This highlights the need for further prospective trials to evaluate the predictors of futility in liver transplantation, aiming to refine decision-making processes, optimize organ allocation, and improve patient outcomes. Future research should focus on the development of universally accepted futility criteria and explore interventions to mitigate the factors contributing to transplant futility.
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Affiliation(s)
- Anil Arora
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - Praveen Sharma
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - Ashish Kumar
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - S.K. Acharya
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | - Shiv K. Sarin
- Institute of Liver and Biliary Sciences, Delhi, India
| | - Ajay Duseja
- Post Institute of Medical Sciences, Chandigarh, India
| | | | - Samir Shah
- Institute of Liver Disease, HPB Surgery and Transplant, Global Hospitals, Dr E Borges Road, Parel, Mumbai, 400012, India
| | - Y.K. Chawla
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | - P.N. Rao
- Asian Institute of Gsstroenterology, Hyderabad, India
| | - Anoop Saraya
- All India Institute of Medical Sciences, New Delhi, India
| | - Ravi Mohanka
- Sir HN Reliance Foundation Hospital, Mumbai, India
| | | | | | - Mohamed Rela
- Dr. Rela Institute & Medical Centre, #7, CLC Works Road, Chromepet, Chennai, 600044, India
| | - Vivek Vij
- Fortis Hospital, Noida, Delhi, India
| | - Sonal Asthana
- Aster CMI Bangalore, Aster RV Bangalore, Aster Whitefield, Bangalore, India
| | - Akash Shukla
- Reliance Foundation Hospital and Research Centre, Mumbai, India
- Seth GSMC & KEM Hospital, Mumbai, 400022, India
| | | | | | - Rakhi Maiwall
- Institute of Liver and Biliary Sciences, Delhi, India
| | - Amit Mandot
- Institute of Liver Disease, HPB Surgery and Transplant, Global Hospitals, Dr E Borges Road, Parel, Mumbai, 400012, India
| | | | | | - Shalimar
- All India Institute of Medical Sciences, New Delhi, India
| | - Dharmesh Kapoor
- Mahatma Gandhi Medical College and Hospital, RIICO Institutional Area, Sitapura, Tonk Road, Jaipur, 302022, Rajasthan, India
- Yashoda Hospital, Hyderabad, India
| | - Anil C. Anand
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | | | - Joy Varghese
- Gleneagles Global Health City, 439, Cheran Nagar, Perumbakkam, Chennai, Tamil Nadu, 600100, India
| | - Naimish Mehta
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
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Galasso L, Esposto G, Mignini I, Ainora ME, Zocco MA. Decoding prognosis in dengue-induced hepatitis: Model for end-stage liver disease vs albumin-bilirubin for predicting liver failure and survival. World J Gastroenterol 2025; 31:102778. [PMID: 40308803 PMCID: PMC12038526 DOI: 10.3748/wjg.v31.i16.102778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 03/09/2025] [Accepted: 03/17/2025] [Indexed: 04/27/2025] Open
Abstract
In this editorial, we comment on the article by Teerasarntipan et al published in a recent issue of the World Journal of Gastroenterology. Dengue infection is a major mosquito-borne disease with global significance. Dengue-induced severe hepatitis (DISH) is a rare complication though severe, as it can lead to acute liver failure (ALF) with an incidence rate between 0.7% and 2.0% and mortality rates from 47.0% to 58.8%. In this context, the identification of patients at risk of ALF could improve prognosis in DISH patients. Teerasarntipan et al retrospectively enrolled 2532 dengue patients, counting 193 DISH and 20 ALF. The authors explored the prognostic role of liver-specific scores, as the model for end-stage liver disease (MELD) score, albumin-bilirubin (ALBI) score, easy (EZ)-ALBI score, and platelet-ALBI (PALBI) score. Univariate analysis identified international normalized ratio (INR), total bilirubin, albumin, and creatinine as independent laboratory factors associated with ALF, while age, gender, and liver comorbidities were not linked to in-hospital mortality. The presence of dengue shock syndrome significantly increased mortality, with an odds ratio (OR) of 28.05 (95%CI: 7.21-109.18, P < 0.001). High INR and low albumin were laboratory markers associated with death from DISH, with ORs of 5.83 (95%CI: 2.59-13.12, P < 0.001) and 0.15 (95%CI: 0.05-0.44, P < 0.001), respectively. Multivariate analysis confirmed that INR remained the only significant predictor of both ALF and death, with adjusted ORs of 19.54 (95%CI: 3.37-113.38, P < 0.001) and 3.86 (95%CI: 1.13-13.18, P = 0.031), respectively. Among prognostic models, the MELD score performed best in predicting ALF, with a very high accuracy [area under the receiver operating characteristic curve (AUROC) of 0.929, 87.5% sensitivity, 89.3% specificity at a cutoff of 16], followed by the EZ-ALBI, ALBI, and PALBI scores, with AUROCs of 0.865, 0.832, and 0.797, respectively. As MELD remains the best scoring system for predicting poor outcomes in DISH-related ALF, EZ-ALBI is a valid adjunct tool that could improve medical care in these patients.
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Affiliation(s)
- Linda Galasso
- Centro Malattie Apparato Digerente, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Giorgio Esposto
- Centro Malattie Apparato Digerente, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Irene Mignini
- Centro Malattie Apparato Digerente, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Maria Elena Ainora
- Centro Malattie Apparato Digerente, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Maria Assunta Zocco
- Centro Malattie Apparato Digerente, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
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Almeida FJ, Sáfadi MAP. Additional questions regarding transfusion-transmitted dengue virus in Brazil - Authors' reply. THE LANCET. INFECTIOUS DISEASES 2025; 25:e67. [PMID: 39788142 DOI: 10.1016/s1473-3099(24)00836-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Accepted: 12/16/2024] [Indexed: 01/12/2025]
Affiliation(s)
- Flávia Jacqueline Almeida
- Department of Pediatrics, Santa Casa de São Paulo School of Medical Sciences, 01221-020 São Paulo, Brazil; Department of Infectious Diseases and Pediatric Cardiovascular Intensive Care Units, Beneficência Portuguesa de São Paulo Hospital, São Paulo, Brazil.
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Yuan Y, Chen Q, Li Z, Cai F, Li D, Wang W. Single-cell sequencing reveals the features of adaptive immune responses in the liver of a mouse model of dengue fever. Animal Model Exp Med 2025; 8:30-43. [PMID: 38988280 PMCID: PMC11798745 DOI: 10.1002/ame2.12454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 05/29/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND Dengue fever, an acute insect-borne infectious disease caused by the dengue virus (DENV), poses a great challenge to global public health. Hepatic involvement is the most common complication of severe dengue and is closely related to the occurrence and development of disease. However, the features of adaptive immune responses associated with liver injury in severe dengue are not clear. METHODS We used single-cell sequencing to examine the liver tissues of mild or severe dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection, and the immune interaction between macrophages and T cells. Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing results. RESULTS Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was down-regulated. The reason may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type, and the macrophages then inhibit T cell immunity through the TGF-β signaling pathway. In addition, the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice. CONCLUSIONS In this study, single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice. Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.
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Affiliation(s)
- Yizhen Yuan
- National Center of Technology Innovation for Animal Model, State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, NHC Key Laboratory of Comparative MedicineInstitute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC)BeijingChina
| | - Qian Chen
- National Center of Technology Innovation for Animal Model, State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, NHC Key Laboratory of Comparative MedicineInstitute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC)BeijingChina
| | - Zhe Li
- National Center of Technology Innovation for Animal Model, State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, NHC Key Laboratory of Comparative MedicineInstitute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC)BeijingChina
| | - Fangzhou Cai
- National Center of Technology Innovation for Animal Model, State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, NHC Key Laboratory of Comparative MedicineInstitute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC)BeijingChina
| | - Dan Li
- National Center of Technology Innovation for Animal Model, State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, NHC Key Laboratory of Comparative MedicineInstitute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC)BeijingChina
| | - Wei Wang
- National Center of Technology Innovation for Animal Model, State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, NHC Key Laboratory of Comparative MedicineInstitute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC)BeijingChina
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Nguyen TT, Ngo PTM, Vo LT. Predicting the risk of mortality in children with dengue-induced hepatitis admitted to the paediatric intensive care unit. World J Crit Care Med 2024; 13:98862. [PMID: 39655306 PMCID: PMC11577541 DOI: 10.5492/wjccm.v13.i4.98862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 09/26/2024] [Accepted: 10/20/2024] [Indexed: 10/31/2024] Open
Abstract
BACKGROUND Dengue-associated acute liver failure (PALF) accounts for a high mortality rate in children admitted to the pediatric intensive care unit (PICU). To date, there is a lack of data on clinical algorithms for estimating the risk of mortality in pediatric patients with dengue-induced severe hepatitis (DISH). AIM To determine the prevalence of PALF and identify the predictors of mortality among patients with DISH. METHODS This single-institution retrospective study was performed at a tertiary pediatric hospital in Vietnam between 2013 and 2022. The primary outcome was in-hospital mortality in pediatric patients with DISH, which was defined as either aspartate aminotransferase > 350 IU/L or alanine aminotransferase > 400 IU/L. Prognostic models for estimating the risk of death among patients with DISH were developed using a predefined set of clinical covariables and hepatic biomarkers on PICU admission and during the first 72 hours of admission. Area under the curve, multivariable logistic regression, and multiple imputation using the chained equation for missing values were performed. Backward stepwise model selection based on the Akaike information criterion was employed. Bootstrapping, calibration slope, and Brier score were used to assess the final models. RESULTS A total of 459 children with DISH were included in the analysis. The median patient age was 7.7 years (interquartile range: 4.3-10.1 years). The prevalence of dengue-associated PALF in children with DISH was 18.3%. Thirty-nine DISH patients developing PALF (8.5%) died. Hepatic biomarkers, including the international normalized ratio (INR) ≥ 2.11 and total serum bilirubin (≥ 1.7 mg/dL), showed high predictive values for mortality (all P values < 0.001). Multivariable models showed the significant clinical predictors of death from dengue-induced PALF in patients with DISH, including reduced level of consciousness (pain and unresponsive levels on the Alert, Verbal, Pain, Unresponsive scale), high vasoactive-inotropic score (> 30), and elevated levels of blood lactate, INR, and serum bilirubin. The final prognostic model demonstrated high discrimination, Brier score, and an acceptable calibration slope. CONCLUSION The prevalence of PALF in children with DISH is 18.3%. We developed robust prognostic models to estimate the risk of death in hospitalized children with severe dengue-induced hepatitis.
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Affiliation(s)
- Thanh Tat Nguyen
- Department of Tuberculosis, Woolcock Institute of Medical Research, Ho Chi Minh 700000, Viet Nam
- Department of Infectious Diseases, The Children’s Hospital 2, Ho Chi Minh 700000, Viet Nam
| | - Phuong Thi-Mai Ngo
- Department of Infectious Diseases, The Children’s Hospital 2, Ho Chi Minh 700000, Viet Nam
| | - Luan Thanh Vo
- Department of Infectious Diseases, The Children’s Hospital 2, Ho Chi Minh 700000, Viet Nam
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Teerasarntipan T, Thanapirom K, Chaiteerakij R, Komolmit P, Treeprasertsuk S. Validation of prognostic scores for predicting acute liver failure and in-hospital death in patients with dengue-induced severe hepatitis. World J Gastroenterol 2024; 30:4781-4790. [PMID: 39649552 PMCID: PMC11606377 DOI: 10.3748/wjg.v30.i45.4781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 09/10/2024] [Accepted: 10/14/2024] [Indexed: 11/13/2024] Open
Abstract
BACKGROUND Acute liver failure (ALF) in dengue is rare but fatal. Early identification of patients who are at risk of ALF is the key strategy to improve survival. AIM To validate prognostic scores for predicting ALF and in-hospital mortality in dengue-induced severe hepatitis (DISH). METHODS We retrospectively reviewed 2532 dengue patients over a period of 16 years (2007-2022). Patients with DISH, defined as transaminases > 10 times the normal reference level and DISH with subsequent ALF, were included. Univariate regression analysis was used to identify factors associated with outcomes. Youden's index in conjunction with receiver operating characteristic (ROC) analysis was used to determine optimal cut-off values for prognostic scores in predicting ALF and in-hospital death. Area under the ROC (AUROC) curve values were compared using paired data nonparametric ROC curve estimation. RESULTS Of 193 DISH patients, 20 developed ALF (0.79%), with a mortality rate of 60.0%. International normalized ratio, bilirubin, albumin, and creatinine were independent predictors associated with ALF and death. Prognostic scores showed excellent performance: Model for end-stage liver disease (MELD) score ≥ 15 predicted ALF (AUROC 0.917, sensitivity 90.0%, specificity 88.4%) and ≥ 18 predicted death (AUROC 0.823, sensitivity 86.9%, specificity 89.1%); easy albumin-bilirubin (ALBI) score ≥ -30 predicted ALF and death (ALF: AUROC 0.835, sensitivity80.0%, specificity 72.2%; death: AUROC 0.808, sensitivity 76.9%, specificity 69.3%); ALBI score ≥ -2 predicted ALF and death (ALF: AUROC 0.806, sensitivity 80.0%, specificity 77.4%; death: AUROC 0.799, sensitivity 76.9%, specificity 74.3%). Platelet-ALBI score also showed good performance in predicting ALF and death (AUROC = 0.786 and 0.699, respectively). MELD and EZ-ALBI scores had similar performance in predicting ALF (Z = 1.688, P = 0.091) and death (Z = 0.322, P = 0.747). CONCLUSION MELD score is the best predictor of ALF and death in DISH patients. EZ-ALBI score, a simpler yet effective score, shows promise as an alternative prognostic tool in dengue patients.
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Affiliation(s)
- Tongluk Teerasarntipan
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
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Rajakumar A, Gupta P, Rammohan A, Devarajan V, Jothimani D, Shanmugam N, Kaliamoorthy I, Rela M. Liver Transplantation for Dengue-induced Acute Liver Failure. J Clin Exp Hepatol 2024; 14:101405. [PMID: 38660561 PMCID: PMC11035359 DOI: 10.1016/j.jceh.2024.101405] [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: 01/02/2024] [Accepted: 03/24/2024] [Indexed: 04/26/2024] Open
Abstract
Although liver involvement has been observed in over two-third cases of dengue viral infection, less than 1% cases progress to dengue-related acute liver failure (D-ALF). Various aspects of management of this disease remain debated including the need and timing of liver transplantation (LT). Moreover, the outcomes of LT for D-ALF have been suboptimal. We present four contrasting cases of D-ALF, two managed with LT and the other two conservatively to highlight the management dilemmas concerning LT in D-ALF. Based on our 4 cases, we would consider dengue shock syndrome, multisystem involvement and neurological deficit not completely accounted for by the ALF as potential contraindications for LT. These would need to be revisited on a case-to-case basis till larger studies define objective selection criteria for LT in D-ALF.
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Affiliation(s)
- Akila Rajakumar
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education & Research, Chennai, India
| | - Prateek Gupta
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education & Research, Chennai, India
| | - Ashwin Rammohan
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education & Research, Chennai, India
| | - Vidya Devarajan
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education & Research, Chennai, India
| | - Dinesh Jothimani
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education & Research, Chennai, India
| | - Naresh Shanmugam
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education & Research, Chennai, India
| | - Ilankumaran Kaliamoorthy
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education & Research, Chennai, India
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education & Research, Chennai, India
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Wongtrakul W, Charatcharoenwitthaya K, Karaketklang K, Charatcharoenwitthaya P. Incidence of acute liver failure and its associated mortality in patients with dengue infection: A systematic review and meta-analysis. J Infect Public Health 2024; 17:102497. [PMID: 39024894 DOI: 10.1016/j.jiph.2024.102497] [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: 05/07/2024] [Revised: 06/27/2024] [Accepted: 07/09/2024] [Indexed: 07/20/2024] Open
Abstract
Acute liver failure (ALF) is a devastating consequence of dengue infection. This systematic review and meta-analysis assessed the incidence of ALF in dengue infection and its associated mortality. We systematically searched the EMBASE and MEDLINE databases from inception to December 2023 for observational studies reporting ALF incidence and mortality in dengue patients. Twenty-one studies encompassing 26,839 dengue-infected patients were included. Meta-analysis revealed a pooled incidence of ALF in cases of general dengue infection of 2.0 % (95 % CI, 1.2-3.0 %), with 1.2 % (95 % CI, 0.6-2.1 %) in adults and 5.0 % (95 % CI, 1.5-10.2 %) in children. ALF incidence was 17.3 % (95 % CI, 6.5 %-31.5 %) in severe dengue and 7.4 % (95 % CI, 0.8-18.5 %) in dengue shock syndrome. The pooled mortality rate of dengue-associated ALF was 47.0 % (95 % CI, 32.9-61.2 %). These findings underscore the detrimental impact of dengue infection on the development of the relatively uncommon, albeit life-threatening, condition of ALF.
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Affiliation(s)
- Wasit Wongtrakul
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | | | - Khemajira Karaketklang
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Phunchai Charatcharoenwitthaya
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
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Cherie TJJ, Choong CSH, Abid MB, Weber MW, Yap ES, Seneviratne SL, Abeysuriya V, de Mel S. Immuno-Haematologic Aspects of Dengue Infection: Biologic Insights and Clinical Implications. Viruses 2024; 16:1090. [PMID: 39066252 PMCID: PMC11281699 DOI: 10.3390/v16071090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 06/26/2024] [Accepted: 07/01/2024] [Indexed: 07/28/2024] Open
Abstract
Dengue infection is caused by the dengue virus (DENV) and is transmitted to humans by infected female Aedes aegypti and Aedes albopictus mosquitoes. There are nearly 100 million new dengue cases yearly in more than 120 countries, with a five-fold increase in incidence over the past four decades. While many patients experience a mild illness, a subset suffer from severe disease, which can be fatal. Dysregulated immune responses are central to the pathogenesis of dengue, and haematologic manifestations are a prominent feature of severe disease. While thrombocytopaenia and coagulopathy are major causes of bleeding in severe dengue, leucocyte abnormalities are emerging as important markers of prognosis. In this review, we provide our perspective on the clinical aspects and pathophysiology of haematologic manifestations in dengue. We also discuss the key gaps in our current practice and areas to be addressed by future research.
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Affiliation(s)
- Tan Jiao Jie Cherie
- Department of Medicine, National University Health System, Singapore 119228, Singapore;
| | - Clarice Shi Hui Choong
- Department of Haematology Oncology, National University Cancer Institute, National University Health System, Singapore 119228, Singapore;
| | - Muhammad Bilal Abid
- Division of Haematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA; (M.B.A.); (M.W.W.)
| | - Matthew W. Weber
- Division of Haematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA; (M.B.A.); (M.W.W.)
| | - Eng Soo Yap
- Department of Laboratory Medicine, National University Health System, Singapore 119228, Singapore;
| | - Suranjith L. Seneviratne
- Institute of Immunity and Transplantation, Royal Free Hospital and University College London, London NW3 2PP, UK
- Nawaloka Hospital Research and Educational Foundation, Nawaloka Hospitals PLC, Colombo 00200, Sri Lanka
| | - Visula Abeysuriya
- Department of Immunology, Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo 00300, Sri Lanka;
| | - Sanjay de Mel
- Department of Haematology Oncology, National University Cancer Institute, National University Health System, Singapore 119228, Singapore;
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Copaja-Corzo C, Flores-Cohaila J, Tapia-Sequeiros G, Vilchez-Cornejo J, Hueda-Zavaleta M, Vilcarromero S, Santana-Téllez T, Parodi JF, Gomez-Colque S, Benites-Zapata VA. Risk factors associated with dengue complications and death: A cohort study in Peru. PLoS One 2024; 19:e0305689. [PMID: 38917093 PMCID: PMC11198833 DOI: 10.1371/journal.pone.0305689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 06/04/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Dengue has emerged as an unprecedented epidemic in Peru, and it is anticipated that this issue will escalate further owing to climate change. This study aimed to determine the risk factors associated with death from dengue in patients treated at Hospital II in Pucallpa, Peru. METHODOLOGY This retrospective cohort study collected information from the medical records of patients with a diagnosis of dengue treated at Hospital II Pucallpa-Peru between January 2019 and March 2023. The primary outcome was death, and the secondary outcome was death, development of severe dengue, or Intensive Care Unit (ICU) admission. Cox regression models were used to determine risk factors. FINDINGS The clinical records of 152 patients were evaluated, with a median age of 27.5 years (interquartile range, 11-45). Among all patients, 29 (19.1%) developed severe dengue, 31 (20.4%) were admitted to the ICU, and 13 (8.6%) died during follow-up. In the survival analysis, bilirubin >1.2 mg/dL was associated with a higher risk of death aHR: 11.38 (95% CI: 1.2 106.8). Additionally, factors associated with poor prognosis included having 1 to 3 comorbidities aRR: 1.92 (1.2 to 3.2), AST ≥251 U/L aRR: 6.79 (2.2 to 21.4), history of previous dengue aRR: 1.84 (1.0 to 3.3), and fibrinogen ≥400 mg/dL aRR: 2.23 (1.2 to 4.1). SIGNIFICANCE Elevated bilirubin was associated with death from dengue, whereas an increase in comorbidities and a history of previous dengue were related to a poor prognosis of the disease. Early identification of severe dengue would be more feasible with improved access to laboratory testing, particularly in tropical areas with a high dengue incidence.
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Affiliation(s)
- Cesar Copaja-Corzo
- Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima, Perú
- Servicio de Infectología, Hospital Nacional Edgardo Rebagliati Martins, EsSalud, Lima, Perú
| | | | - Gustavo Tapia-Sequeiros
- Diagnóstico, Tratamiento e Investigación de Enfermedades Infecciosas y Tropicales, Universidad Privada de Tacna, Tacna, Perú
| | - Jennifer Vilchez-Cornejo
- Facultad de Salud Pública y Administración, Unidad de Investigación de Enfermedades Emergentes y Cambio Climático, Universidad Peruana Cayetano Heredia, Lima, Perú
| | - Miguel Hueda-Zavaleta
- Diagnóstico, Tratamiento e Investigación de Enfermedades Infecciosas y Tropicales, Universidad Privada de Tacna, Tacna, Perú
| | - Stalin Vilcarromero
- Servicio de Infectología, Hospital Nacional Edgardo Rebagliati Martins, EsSalud, Lima, Perú
| | - Tomas Santana-Téllez
- Hospital II Pucallpa, EsSalud, Ucayali, Perú
- Facultad de Ciencias de la Salud, Universidad Nacional de Ucayali, Ucayali, Perú
| | - José F. Parodi
- Facultad de Medicina Humana, Centro de Investigación del Envejecimiento (CIEN), Universidad de San Martín de Porres, Lima, Perú
| | - Sujey Gomez-Colque
- Facultad de Ciencias de la Salud, Universidad Nacional Jorge Basadre Grohmann, Tacna, Perú
| | - Vicente A. Benites-Zapata
- Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima, Perú
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Riaz M, Harun SNB, Mallhi TH, Khan YH, Butt MH, Husain A, Khan MM, Khan AH. Evaluation of clinical and laboratory characteristics of dengue viral infection and risk factors of dengue hemorrhagic fever: a multi-center retrospective analysis. BMC Infect Dis 2024; 24:500. [PMID: 38760732 PMCID: PMC11102246 DOI: 10.1186/s12879-024-09384-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 05/07/2024] [Indexed: 05/19/2024] Open
Abstract
BACKGROUND Dengue Viral Infection (DVI) has become endemic in Pakistan since the first major outbreak in Karachi in 1996. Despite aggressive measures taken by relevant authorities, Pakistan has been dealing with a worsening dengue crisis for the past two decades. DHF is severe form of dengue infection which is linked with significant morbidity and mortality. Early identification of severe dengue infections can reduce the morbidity and mortality. In this context we planned current study in which we find out the different factors related with DHF as well as clinical laboratory features of DHF and compare them to DF so that patients can be best evaluated for DHF and managed accordingly at admission. METHODS Retrospective study conducted over a period of 6 years (2013-2018) in two tertiary care hospitals in Pakistan. Data were collected by using a pre-structured data collection form. Data were statistically analyzed to determine the clinical and laboratory characteristics of DVI and risk factors of dengue hemorrhagic fever (DHF). RESULTS A total 512 dengue cases (34.05 ± 15.08 years; Male 69.53%) were reviewed. Most common clinical manifestations of DVI were fever (99.60%), headache (89.1%), chills (86.5%), rigors (86.5%), myalgia (72.3%). Less common clinical manifestations were vomiting (52.5%), arthralgia (50.2%) and skin rashes (47.5%). Furthermore, nasal bleeding (44.1%), gum bleeding (32.6%), pleural effusion (13.9%) and hematuria (13.1%) were more profound clinical presentations among DHF patients. Mortality rate was 1.5% in this study. Logistic regression analysis indicated that delayed hospitalization (OR: 2.30) and diabetes mellitus (OR:2.71), shortness of breath (OR:2.21), association with risk groups i.e., living near stagnant water, travelling to endemic areas, living in endemic regions (OR:1.95), and presence of warning signs (OR:2.18) were identified as risk factors of DHF. Statistically we found that there is strong association of diabetes mellitus (DM) with DHF while the patient suffering from DM individually had higher odds (2.71) of developing DHF than patients without disease. CONCLUSIONS The current study demonstrated that the clinical and laboratory profiles of DF and DHF are significantly distinct. Significant predictors of DHF were advanced age, diabetes mellitus, ascites, pleural effusion, thick gallbladder and delayed hospitalization. The identification of these factors at early stage provides opportunities for the clinicians to identify high risk patients and to reduce dengue-related morbidity and mortality.
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Affiliation(s)
- Muhammad Riaz
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, University Sains Malaysia, Palau Penang, Malaysia
- Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Sabriah Noor Binti Harun
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, University Sains Malaysia, Palau Penang, Malaysia
| | - Tauqeer Hussain Mallhi
- Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakakah, Al-Jouf, Kingdom of Saudi Arabia
| | - Yusra Habib Khan
- Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakakah, Al-Jouf, Kingdom of Saudi Arabia
| | - Muhammad Hammad Butt
- Department of Medicinal Chemistry, Faculty of Pharmacy, Uppsala University, Uppsala, 75123, Sweden.
| | - Aamir Husain
- Department of Medicine, Faisalabad Medical University, Faisalabad, Pakistan
| | - Muhammad Mujeeb Khan
- Department of Infectious Diseases, Rawalpindi Medical University, Rawalpindi, Pakistan
| | - Amer Hayat Khan
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, University Sains Malaysia, Palau Penang, Malaysia
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Jamil Z, Khalid S, Khan HMMH, Waheed I, Ehsan A, Alissa M, Muhammad K, Munawar N, Waheed Y. Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) as a Novel Score in Early Detection of Complicated Dengue Fever. J Multidiscip Healthc 2024; 17:2321-2330. [PMID: 38770172 PMCID: PMC11104365 DOI: 10.2147/jmdh.s459929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 05/03/2024] [Indexed: 05/22/2024] Open
Abstract
INTRODUCTION The occurrence of dengue fever presents a considerable burden for public health care in developing countries. This study aims to validate APRI as predictor score for severity of dengue fever so that catastrophic events could be prevented, and early triage can save lives. METHODS The retrospective cross-sectional study was done on dengue positive patients from August to November 2023. APRI score was calculated for every patient at the time of admission. The primary end-point was non-complicated disease (Simple dengue fever) vs complicated disease (dengue hemorrhagic fever and dengue shock syndrome). ROC curve was used to identify the role of APRI in prediction of dengue complication. Youden index was used to find the cut-off value of APRI along with sensitivity, specificity, positive and negative likelihood ratios. To further evaluate the role of APRI score, patients were divided into two groups, patients with APRI score greater and lesser than cut-off value. The qualitative variables among two groups were compared by chi-square testing. The predictors of complicated dengue were first determined by univariate regression analysis and then confirmed by multivariate regression analysis. RESULTS The mean APRI score of 135 patients was 20.06 ± 6.31. AUC for APRI score was 0.93 (p < 0.0001) indicating that APRI score calculated at the time of admission is an excellent marker in determining the complicated dengue. The cut-off value for APRI score was 9.04 (sensitivity 84.91%, specificity 89.02%, p < 0.0001). The patients with APRI <9.04 mostly developed simple dengue fever (54.1%) vs DHF (4.4%) and DSS (1.5%), while patients with APRI >9.04 had more DHF (20.7%) and DSS (12.6%) vs simple dengue fever (6.7%). None of the patient died with APRI <9.04 while the mortality rate was 3.7% in patients with APRI >9.04. CONCLUSION The APRI score, calculated at the time of admission, is an excellent marker in determining the severe dengue.
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Affiliation(s)
- Zubia Jamil
- Department of Medicine, Foundation University School of Health Sciences, Foundation University, Islamabad, 44000, Pakistan
| | - Samreen Khalid
- Department of Medicine, Foundation University School of Health Sciences, Foundation University, Islamabad, 44000, Pakistan
| | | | - Ikram Waheed
- Department of Medicine, Foundation University School of Health Sciences, Foundation University, Islamabad, 44000, Pakistan
- Department of Medicine, Fauji Foundation Hospital, Rawalpindi, 43600, Pakistan
| | - Amna Ehsan
- Department of Medicine, Foundation University School of Health Sciences, Foundation University, Islamabad, 44000, Pakistan
- Department of Medicine, Fauji Foundation Hospital, Rawalpindi, 43600, Pakistan
| | - Mohammed Alissa
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Khalid Muhammad
- Department of Biology, College of Science, UAE University, Al Ain, 15551, United Arab Emirates
| | - Nayla Munawar
- Department of Chemistry, College of Science, UAE University, Al Ain, 15551, United Arab Emirates
| | - Yasir Waheed
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, 1401, Lebanon
- MEU Research Unit, Middle East University, Amman, 11831, Jordan
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Giri S, Anirvan P, Vaidya A, Praharaj DL. Dengue-related acute liver failure-A scoping review. Indian J Gastroenterol 2024; 43:407-424. [PMID: 38687431 DOI: 10.1007/s12664-024-01570-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 03/09/2024] [Indexed: 05/02/2024]
Abstract
Infection by dengue virus is common in tropical countries. Hepatic involvement in dengue can range from asymptomatic elevation of transaminases to life-threatening acute liver failure (ALF). Dengue-related ALF (DALF) is responsible for significant morbidity and mortality, especially in Southeast Asia. However, there is a scarcity of literature on DALF, necessitating a thorough examination of its clinical determinants and management strategies. All relevant studies related to DALF were reviewed until December 2023. Case reports, case series and studies reporting ALF in dengue infection were included. Demographics, clinical profiles, management and outcomes of DALF cases were analyzed, which revealed a predominance of DALF incidence in pediatric patients (1.1% to 15.8%) and an upward trend over the years, particularly in India. The proportion of ALF cases attributable to dengue was also higher among pediatric ALF patients (6.7% to 34.3%). Age ≤ 40 years, persistent nausea, vomiting and elevated serum bilirubin and alkaline phosphatase (ALP) with aspartate aminotransferase (AST) > 1000 IU/mL within the first five days of illness, more than 10% of atypical lymphocytes in peripheral blood, platelet count of < 50,000/cu·mm, severe hepatitis at presentation and baseline model for end-stage liver disease (MELD) > 15 were the risk factors for the development of DALF. Histopathological features of DALF included multi-lobular hepatic necrosis, steatosis and occasional cholestasis. Mortality in DALF ranged from 0% to 80%; admission pH and lactate strongly predicted mortality, while mortality was found to be significantly higher in patients with cirrhosis. N-Acetyl cysteine (NAC) has been used as a treatment modality with varying results. There is limited evidence regarding the use of extra-corporeal support systems, while candidate selection for liver transplantation (LT) in DALF remains poorly defined.
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Affiliation(s)
- Suprabhat Giri
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, 751 024, India
| | - Prajna Anirvan
- Kalinga Gastroenterology Foundation, Cuttack, 753 001, India
| | - Arun Vaidya
- Department of Gastroenterology, Seth G S Medical College and K E M Hospital, Mumbai, 400 012, India
| | - Dibya Lochan Praharaj
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, 751 024, India.
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Juneja D, Jain R, Nasa P. Dengue induced acute liver failure: A meta summary of case reports. World J Virol 2024; 13:91457. [PMID: 38616857 PMCID: PMC11008400 DOI: 10.5501/wjv.v13.i1.91457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 01/19/2024] [Accepted: 02/20/2024] [Indexed: 03/11/2024] Open
Abstract
BACKGROUND Dengue fever is the most common cause of viral hemorrhagic fever, with more than 400 million cases being reported annually, worldwide. Even though hepatic involvement is common, acute liver failure (ALF) is a rare complication of dengue fever. AIM To analyze the demographic profile, symptomology, hospital course and outcomes of patients presenting with ALF secondary to dengue infection by reviewing the published case reports. METHODS A systematic search was performed from multiple databases including PubMed, Reference Citation Analysis, Science Direct, and Google Scholar. The search terms used were "dengue" OR "severe dengue" OR "dengue shock syndrome" OR "dengue haemorrhagic syndrome" OR "dengue fever" AND "acute liver failure" OR "hepatic failure" OR "liver injury". The inclusion criteria were: (1) Case reports or case series with individual patient details; (2) Reported acute liver failure secondary to dengue infection; and (3) Published in English language and on adult humans. The data were extracted for patient demographics, clinical symptomatology, clinical interventions, hospital and intensive care unit course, need for organ support and clinical outcomes. RESULTS Data from 19 case reports fulfilling the predefined inclusion criteria were included. The median age of patients was 38 years (inter quartile range: Q3-Q1 26.5 years) with a female preponderance (52.6%). The median days from diagnosis of dengue to development of ALF was 4.5 d. The increase in aspartate aminotransferase was higher than that in alanine aminotransferase (median 4625 U/L vs 3100 U/L). All the patients had one or more organ failure, with neurological failure present in 73.7% cases. 42.1% patients required vasopressor support and hepatic encephalopathy was the most reported complication in 13 (68.4%) cases. Most of the patients were managed conservatively and 2 patients were taken up for liver transplantation. Only 1 death was reported (5.3%). CONCLUSION Dengue infection may rarely lead to ALF. These patients may frequently require intensive care and organ support. Even though most of these patients may improve with supportive care, liver transplantation may be a therapeutic option in refractory cases.
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Affiliation(s)
- Deven Juneja
- Department of Critical Care Medicine, Max Super Speciality Hospital, New Delhi 110017, India
| | - Ravi Jain
- Department of Critical Care Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur 302022, Rajasthan, India
| | - Prashant Nasa
- Department of Critical Care Medicine, NMC Specialty Hospital, Dubai 7832, United Arab Emirates
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15
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Gautam N, Shrestha N, Bhandari S, Thapaliya S. Severe dengue infection unmasking drug-induced liver injury: Successful management with N-acetylcysteine. Clin Case Rep 2024; 12:e8578. [PMID: 38469128 PMCID: PMC10925800 DOI: 10.1002/ccr3.8578] [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: 12/12/2023] [Revised: 02/19/2024] [Accepted: 02/23/2024] [Indexed: 03/13/2024] Open
Abstract
Key Clinical Message Clinicians in tuberculosis and dengue endemic regions should have heightened vigilance for drug-induced liver injury (DILI) overlapping with active infections, enabling prompt recognition and life-saving conservative management. Abstract Severe dengue and drug-induced liver injury (DILI) are significant independent risk factors for acute liver failure. The co-occurrence of these conditions significantly complicates clinical management. Here, we describe the case of a 21-year-old Nepali female who developed acute liver failure during antitubercular therapy (ATT). The patient, presenting with fever and nausea after 3 weeks of ATT, subsequently received a diagnosis of severe dengue. Laboratory evidence indicated markedly elevated transaminases (AST 4335 U/L, ALT 1958 U/L), total bilirubin (72 μmol/L), and INR (>5). Prompt discontinuation of first-line ATT, initiation of a modified ATT regimen, and N-acetylcysteine (NAC) infusion facilitated the patient's recovery after a week of intensive care. This case underscores the potential for synergistic hepatotoxicity in regions where multiple endemic illnesses coincide. Early recognition of DILI, cessation of offending agents, and comprehensive intensive care are crucial interventions. While the definitive efficacy of NAC remains under investigation, its timely administration in these complex cases warrants exploration for its potential lifesaving benefits.
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Affiliation(s)
| | | | - Sanjeev Bhandari
- Department of Internal MedicineTribhuvan University Teaching HospitalKathmanduNepal
| | - Sabin Thapaliya
- Department of Internal MedicineTribhuvan University Teaching HospitalKathmanduNepal
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16
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Dinkar A, Singh J, Kumar N, Kumar K, Singh SK, Singh AK. Impact of secondary infections on dengue presentation: A cross-sectional study in a tertiary care hospital in Uttar Pradesh, India. J Infect Public Health 2023; 16:1925-1932. [PMID: 37866270 DOI: 10.1016/j.jiph.2023.10.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 09/14/2023] [Accepted: 10/02/2023] [Indexed: 10/24/2023] Open
Abstract
BACKGROUND Recently, a wide range variety of manifestations, including a self‑limiting to severe illness, has been increasingly reported in dengue. Few studies attract attention to severe dengue, mainly observed in secondary infection. With this background, this study aims to provide a comprehensive overview to differentiate primary from secondary dengue using serology (IgG) and the possible association of severity of illness in secondary dengue. METHODS Present retrospective cross-sectional study was conducted at a North Indian tertiary care center from September 2021 to January 2022. Clinical data of confirmed dengue patients from the medicine department were collected and assigned as primary and secondary dengue. RESULTS Of the 220 dengue patients, 22 (10 %) had secondary dengue infection. Hemorrhagic manifestations were reported in 58/220 (26.4 %) cases while 7/22 (31.8 %) in secondary dengue. Prevalent hemorrhagic manifestations in secondary dengue include purpura (27.3 %), vaginal bleeding (4.5 %), melaena (9.1 %), and epistaxis (4.5 %). In addition, 42 (19.1 %) patients had pancytopenia, and 8 (36.6 %) cases were of secondary dengue. Hepatic dysfunction was noted in 164 (74.5 %) cases. Notably, all secondary dengue cases (22;100 %) had hepatic dysfunction and severe in 9 (40.9 %) cases. In addition, in secondary dengue patients, evidence of plasma leakages such as hypoproteinemia 7 (31.8 %) and ascites (35 %) were statistically more frequent. Overall, two deaths (0.9 %) were reported, and were one in each group. CONCLUSIONS Many parameters, including hemorrhagic manifestation (melaena), hematological characteristic (pancytopenia), evidence of plasma leakage (hypoproteinemia and ascites), gastrointestinal (GB wall thickening and hepatic dysfunction) and reduction in mean hemoglobin and platelet count were found to be statistically significant in secondary dengue infection. Additionally, early classification of secondary dengue may help to anticipate its severity and allow for early strategic intervention/management to lower morbidity and mortality.
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Affiliation(s)
- Anju Dinkar
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Jitendra Singh
- Department of General Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
| | - Nilesh Kumar
- Department of General Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Kailash Kumar
- Department of General Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Santosh Kumar Singh
- Department of General Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Arun Kumar Singh
- Department of General Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
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Vento S, Cainelli F. Acute liver failure in low-income and middle-income countries. Lancet Gastroenterol Hepatol 2023; 8:1035-1045. [PMID: 37837969 DOI: 10.1016/s2468-1253(23)00142-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 04/28/2023] [Accepted: 05/03/2023] [Indexed: 10/16/2023]
Abstract
Acute liver failure is a rare condition involving the rapid development, progression, and worsening of liver dysfunction, characterised by coagulopathy and encephalopathy, and has a high mortality unless liver transplantation is performed. Population-based studies are scarce, and most published data are from high-income countries, where the main cause of acute liver failure is paracetamol overdose. This Review provides an overview of the scanty literature on acute liver failure in low-income and middle-income countries, where patients are often admitted to primary care hospitals and viral hepatitis (especially hepatitis E), tropical infections (eg, dengue), traditional medicines, and drugs (especially anti-tuberculosis drugs) have an important role. We discuss incidence, cause, occurrence in children and pregnant women, prognostic factors and scores, treatment, and mortality. To conclude, we advocate for international collaboration, the establishment of central registries for the condition, and better diagnostics.
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Affiliation(s)
- Sandro Vento
- Faculty of Medicine, University of Puthisastra, Phnom Penh, Cambodia.
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Vo LT, Do VC, Trinh TH, Vu T, Nguyen TT. Combined Therapeutic Plasma Exchange and Continuous Renal Replacement Therapy in Children With Dengue-Associated Acute Liver Failure and Shock Syndrome: Single-Center Cohort From Vietnam. Pediatr Crit Care Med 2023; 24:818-828. [PMID: 37310173 PMCID: PMC10540756 DOI: 10.1097/pcc.0000000000003304] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
OBJECTIVES Pediatric acute liver failure (PALF) is a fatal complication in patients with severe dengue. To date, clinical data on the combination of therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT) for managing dengue-associated PALF concomitant with shock syndrome are limited. DESIGN Retrospective cohort study (January 2013 to June 2022). PATIENTS Thirty-four children. SETTING PICU of tertiary Children's Hospital No. 2 in Vietnam. INTERVENTIONS We assessed a before-versus-after practice change at our center of using combined TPE and CRRT (2018 to 2022) versus CRRT alone (2013 to 2017) in managing children with dengue-associated acute liver failure and shock syndrome. Clinical and laboratory data were reviewed from PICU admission, before and 24 h after CRRT and TPE treatments. The main study outcomes were 28-day in-hospital mortality, hemodynamics, clinical hepatoencephalopathy, and liver function normalization. MEASUREMENTS AND MAIN RESULTS A total of 34 children with a median age of 10 years (interquartile range: 7-11 yr) underwent standard-volume TPE and/or CRRT treatments. Combined TPE and CRRT ( n = 19), versus CRRT alone ( n = 15), was associated with lower proportion of mortality 7 of 19 (37%) versus 13 of 15 (87%), difference 50% (95% CI, 22-78; p < 0.01). Use of combined TPE and CRRT was associated with substantial advancements in clinical hepatoencephalopathy, liver transaminases, coagulation profiles, and blood lactate and ammonia levels (all p values < 0.001). CONCLUSIONS In our experience of children with dengue-associated PALF and shock syndrome, combined use of TPE and CRRT, versus CRRT alone, is associated with better outcomes. Such combination intervention was associated with normalization of liver function, neurological status, and biochemistry. In our center we continue to use combined TPE and CRRT rather than CRRT alone.
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Affiliation(s)
- Luan Thanh Vo
- Infectious Disease Department, Children Hospital 2, Ho Chi Minh City, Vietnam
| | - Viet Chau Do
- Infectious Disease Department, Children Hospital 2, Ho Chi Minh City, Vietnam
| | - Tung Huu Trinh
- Infectious Disease Department, Children Hospital 2, Ho Chi Minh City, Vietnam
| | - Thien Vu
- NCD Epidemiology Research Center, Shiga University of Medical Science, Otsu, Shiga, Japan
- AI Nutrition Project, National Institutes of Biomedical Innovation, Health and Nutrition, (NIBIOHN), Ibaraki, Osaka, Japan
| | - Thanh Tat Nguyen
- Infectious Disease Department, Children Hospital 2, Ho Chi Minh City, Vietnam
- Woolcock Institute of Medical Research, Ho Chi Minh City, Vietnam
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Lee IK, Lee NY, Huang WC, Hsu JC, Tai CH, Yang CH, Huang CH, Lin CY, Chang K, Chen YH. In-hospital mortality predictors among hospitalized adults and those with chronic kidney disease with dengue. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2023; 56:996-1006. [PMID: 37604758 DOI: 10.1016/j.jmii.2023.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 07/27/2023] [Accepted: 08/06/2023] [Indexed: 08/23/2023]
Abstract
BACKGROUND Accurately identifying risk factors that predict fatality in dengue is crucial for patient triage and clinical management. Our objective was to identify predictors of death associated with dengue and investigate the clinical characteristics and risk factors among patients with chronic kidney disease (CKD) who died from dengue. METHODS A multicenter longitudinal observation study conducted from 2008 to 2019. RESULTS A total of 1272 patients (113 who died and 1186 who recovered) diagnosed with dengue were included. Old age, CKD, and an elevated white blood cell count at hospital presentation were identified as independent predictors of in-hospital mortality among individuals infected with the dengue virus. In a subgroup analysis of 138 patients with CKD infected with dengue virus, 64 (46.3%) patients died, with 46 (33.3%) patients dying within 7 days after symptom onset. Among 64 fatal dengue patients with CKD, 34.4% were in stages 2 and 3 of kidney disease, 51.5% were in stages 4 and 5, and 14.1% had end stage renal disease as per the classification by Kidney Disease Improving Global Outcomes. Multivariate analysis revealed that initial altered consciousness, pulmonary edema, and leukocytosis during hospitalization were independently associated with in-hospital mortality in CKD patients infected with the dengue virus. Leukocytosis during hospitalization and severe hepatitis were independent risk factors for death within 7 days after dengue illness onset in CKD patients. CONCLUSIONS This study offers valuable insights into predictors linked to fatality in dengue and reinforces the importance of optimizing patient triage to improve the quality of care.
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Affiliation(s)
- Ing-Kit Lee
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| | - Nan-Yao Lee
- Division of Infectious Diseases, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Wen-Chi Huang
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jui-Chi Hsu
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chien-Hsiang Tai
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Cheng Hsun Yang
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chung-Hao Huang
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chun-Yu Lin
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ko Chang
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yen-Hsu Chen
- Division of Infectious Diseases, Department of Internal Medicine, Center for Tropical Medicine and Infectious Disease Research, School of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan; College of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
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Alam R, Rukunuzzaman M, Nahid KL. Hepatic involvement in childhood dengue infection. EGYPTIAN LIVER JOURNAL 2023; 13:45. [DOI: 10.1186/s43066-023-00281-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 09/01/2023] [Indexed: 01/04/2025] Open
Abstract
AbstractDengue or breakbone fever is one of the most important causes of febrile illness in children residing in tropical and subtropical regions. This mosquito-borne viral disease is mediated by the bite of the infected Aedes mosquito. Dengue infection has been expanding rapidly throughout the globe in the past few decades. The virus has hepatotoxic effects. However, the pathophysiology of liver involvement in dengue is still not entirely clear. The reported clinical spectrum of dengue hepatitis ranges from mild asymptomatic elevation in transaminaselevels to acute liver failure in children. This review focuses on hepatic manifestation, the pathogenesis of liver injury, and treatment option of the effects of dengue on the liver in the pediatric population.
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Cai X, Chong Y, Gan W, Li X. Progress on clinical prognosis assessment in liver failure. LIVER RESEARCH (BEIJING, CHINA) 2023; 7:101-107. [PMID: 39958953 PMCID: PMC11791918 DOI: 10.1016/j.livres.2023.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 04/01/2023] [Accepted: 05/30/2023] [Indexed: 09/02/2024]
Abstract
Liver failure is a group of clinical syndromes with a mortality rate of >50%. The accurate evaluation of severity in patients with liver failure has been a meaningful and hot topic in clinical research and an important guide for liver transplantation. Numerous prognosis studies have emerged in recent years with high accuracy and adequate validity. Nonetheless, different models utilize distinct parameters and have unequal efficiencies, leading to a specific value and unique application situations for each model. This review focused on the progress in recent prognostic studies including the model for end-stage liver disease, sequential organ failure assessment and its derivative models, the Chinese Group on the Study of Severe Hepatitis B Acute-on-Chronic Liver Failure, the Tongji prognostic predictor model, and other emerging prognostic models and predictors. This review aims to assist clinicians understand the framework of recent models and choose the appropriate model and treatment.
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Affiliation(s)
- Xianghao Cai
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yutian Chong
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Weiqiang Gan
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xinhua Li
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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Chiu YY, Lin CY, Yu LS, Wang WH, Huang CH, Chen YH. The association of obesity and dengue severity in hospitalized adult patients. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2023; 56:267-273. [PMID: 36055945 DOI: 10.1016/j.jmii.2022.08.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 08/03/2022] [Accepted: 08/09/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND Obesity is associated with unfavorable outcomes for infectious diseases. Most researches exploring the association between nutritional status and dengue severity have focused on pediatric populations, with only few studies assessing adult patients. METHODS Adult patients with laboratory-confirmed dengue admitted to a tertiary hospital in southern Taiwan between 2014 and 2015 were enrolled retrospectively. Demographics, comorbidities, clinical presentation, laboratory findings, and outcomes were obtained from case-record forms. Patients were categorized into obese group and nonobese group. The obese group comprised patients with a body mass index of ≥27.5 kg/m2. RESULTS A total of 1417 hospitalized patients with dengue were evaluated. The mean age was 57.9 years (range: 18-92 years). The obese and nonobese groups comprised 333 (23.5%) and 1084 (76.5%) patients, respectively. The obese group included more patients with hypertension (85%, p < 0.001), diabetes mellitus (33%, p < 0.001), and congestive heart failure (6.3%, p = 0.049). Multivariate analysis revealed that the obese group had more petechiae (AOR: 1.353, 95% CI: 1.025-1.786, p = 0.033), more dyspnea (AOR: 1.380, 95% CI: 1.015-1.876, p = 0.040), and more severe hepatitis (AOR: 2.061, 95% CI: 1.050-4.048, p = 0.036). The obese group also had higher peak hematocrit values (44.1%, p < 0.001) and lower nadir platelet count (45.3 × 103/μL, p = 0.049) than the nonobese group. CONCLUSION In adult patients with dengue, obese group had more petechiae, dyspnea, severe hepatitis, lower nadir of platelet count, and higher peak hematocrit level. We observed no difference in severe dengue or mortality between obese and nonobese group.
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Affiliation(s)
- Yu-Yao Chiu
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, Graduate Institute of Medicine, College of Medicine, Sepsis Research Center, Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chun-Yu Lin
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, Graduate Institute of Medicine, College of Medicine, Sepsis Research Center, Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Biochemistry and Microbiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan
| | - Ling-Shan Yu
- Institute of BioPharmaceutical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Wen-Hung Wang
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, Graduate Institute of Medicine, College of Medicine, Sepsis Research Center, Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Hao Huang
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, Graduate Institute of Medicine, College of Medicine, Sepsis Research Center, Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Yen-Hsu Chen
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, Graduate Institute of Medicine, College of Medicine, Sepsis Research Center, Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Biological Science and Technology, College of Biological Science and Technology, National Yang Ming Chiao Tung University, HsinChu, Taiwan; Institute of Medical Science and Technology, School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
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23
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Thanh NT, Dat NT, Thinh TN, Phuong NTM, Thanh MTH, Bao NT, Son PT, Viet DC, Tung TH, Thien V, Luan VT. Therapeutic plasma exchange and continuous renal replacement therapy in pediatric dengue-associated acute liver failure: A case series from Vietnam. Transfus Apher Sci 2023; 62:103617. [PMID: 36522271 DOI: 10.1016/j.transci.2022.103617] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 11/04/2022] [Accepted: 11/23/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND OBJECTIVES Paediatric dengue-associated acute liver failure (PALF) is a rare and fatal complication. To date, clinical data regarding the combination of therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT) for the treatment of dengue-associated PALF are limited. METHODS We conducted a single-center, retrospective study of all children with dengue-associated PALF admitted to the paediatric intensive care unit of Children Hospital No.2, Vietnam, who were treated with TPE+CRRT between January 2021 and March 2022. The main study outcomes were in-hospital survival, normalisation of hepatic function, and hepatic encephalopathy improvement. RESULTS Twelve patients aged from 06 to 12 years underwent TPE+CRRT procedures. Among them, three (25 %) patients died of severe sepsis and septic shock confirmed by Enterobacteriaceae spp. haemocultures (stable on maintenance treatment of COVID-19-associated MIS-C with low dose of oral steroids on hospital admission), acute respiratory distress syndrome (ARDS), and clinically apparent intracranial haemorrhage. Nine patients (75 %) survived. The paediatric mortality risk score improved significantly at discharge compared with PICU admission (P < 0.01). Markedly, all twelve patients were diagnosed with hepatoencephalopathy of grades III and IV on PICU admission. After the combined TPE+CRRT interventions, there were substantial improvements in liver transaminases levels, coagulation profiles, and metabolic biomarkers. Normal neurological functions were observed in nine alive patients at hospital discharge. Only one patient experienced an adverse event of slightly low blood pressure, which rapidly self-resolved. INTERPRETATION AND CONCLUSIONS Combined TPE+CRRT significantly improved survival outcome, neurological status, and rapid normalisation of liver functions in dengue-associated PALF.
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Affiliation(s)
- Nguyen Tat Thanh
- Children Hospital 2, Ho Chi Minh City, Viet Nam; Woolcock Institute of Medical Research, Viet Nam
| | - Nguyen Tat Dat
- University of Medicine and Pharmacy, Ho Chi Minh City, Viet Nam
| | | | - Ngo Thi Mai Phuong
- Children Hospital 2, Ho Chi Minh City, Viet Nam; University of Medicine and Pharmacy, Ho Chi Minh City, Viet Nam.
| | | | | | | | - Do Chau Viet
- Children Hospital 2, Ho Chi Minh City, Viet Nam.
| | | | - Vu Thien
- Shiga University of Medical Science, Otsu City, Shiga, Japan.
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Exotic viral hepatitis: A review on epidemiology, pathogenesis, and treatment. J Hepatol 2022; 77:1431-1443. [PMID: 35817222 DOI: 10.1016/j.jhep.2022.06.031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/14/2022] [Accepted: 06/19/2022] [Indexed: 12/04/2022]
Abstract
Certain "exotic" viruses are known to cause clinical diseases with potential liver involvement. These include viruses, beyond regular hepatotropic viruses (hepatitis A, -B(D), -C, -E, cytomegalovirus, Epstein-Barr virus), that can be found in (sub)tropical areas and can cause "exotic viral hepatitis". Transmission routes typically involve arthropods (Crimean Congo haemorrhagic fever, dengue, Rift Valley fever, yellow fever). However, some of these viruses are transmitted by the aerosolised excreta of rodents (Hantavirus, Lassa fever), or via direct contact or contact with bodily fluids (Ebola). Although some exotic viruses are associated with high fatality rates, such as Ebola for example, the clinical presentation of most exotic viruses can range from mild flu-like symptoms, in most cases, right through to being potentially fatal. A smaller percentage of people develop severe disease with haemorrhagic fever, possibly with (fulminant) hepatitis. Liver involvement is often caused by direct tropism for hepatocytes and Kupffer cells, resulting in virus-mediated and/or immune-mediated necrosis. In all exotic hepatitis viruses, PCR is the most sensitive diagnostic method. The determination of IgM/IgG antibodies is a reasonable alternative, but cross-reactivity can be a problem in the case of flaviviruses. Licenced vaccines are available for yellow fever and Ebola, and they are currently under development for dengue. Therapy for exotic viral hepatitis is predominantly supportive. To ensure that preventive measures can be introduced to control possible outbreaks, the timely detection of these viruses is very important.
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Zheng W, Yan Q, Li Z, Wang X, Wu P, Liao F, Lao Z, Jiang Y, Liu X, Zhan S, Li G. Liver transcriptomics reveals features of the host response in a mouse model of dengue virus infection. Front Immunol 2022; 13:892469. [PMID: 36091000 PMCID: PMC9459046 DOI: 10.3389/fimmu.2022.892469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 07/27/2022] [Indexed: 11/13/2022] Open
Abstract
Background Dengue virus (DENV) infection induces various clinical manifestations and even causes organ injuries, leading to severe dengue haemorrhagic fever and dengue shock syndrome. Hepatic dysfunction was identified as a risk predictor of progression to severe disease during the febrile phase of dengue. However, the underlying mechanisms of hepatic injury remain unclear. Methods A model of dengue disease was established in IFNAR−/− C57BL/6 mice by challenge with DENV-2. Body weight, symptoms, haematological parameters and liver pathological observations in mice were used to determine the effects of DENV infection. Liver transcriptome sequencing was performed to evaluate the features of the host response in IFNAR−/− mice challenged with DENV. Functional enrichment analysis and analysis of significantly differentially expressed genes (DEGs) were used to determine the critical molecular mechanism of hepatic injury. Results We observed haemoconcentration, leukopenia and liver pathologies in mice, consistent with findings in clinical dengue patients. Some differences in gene expression and biological processes were identified in this study. Transcriptional patterns in the liver indicated that antiviral responses to DENV and tissue damage via abnormal expression of proinflammatory cytokines were induced. Further analysis showed that the upregulated DEGs were significantly enriched in the leukocyte transendothelial migration, complement and coagulation cascades, and cytokine-cytokine receptor interactions signalling pathways, which are considered to be closely associated with the pathogenic mechanism of dengue. IL6, IL 10, ICAM-1, VCAM-1, MMP9 and NLRP3 were identified as biomarkers of progression to severe disease. Conclusions The interactions of these cytokines, which activate inflammatory signalling, may lead to organ injury and haemoconcentration and even to vascular leakage in tissues, including the mouse liver. Our study identifies candidate host targets that could be used for further functional verification.
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Affiliation(s)
- Wenjiang Zheng
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
- Animal Experiment Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qian Yan
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zonghui Li
- Animal Experiment Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xianyang Wang
- Animal Experiment Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Peng Wu
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Feng Liao
- Animal Experiment Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zizhao Lao
- Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China
| | - Yong Jiang
- Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China
| | - Xiaohong Liu
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
- *Correspondence: Xiaohong Liu, ; Shaofeng Zhan, ; Geng Li,
| | - Shaofeng Zhan
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
- *Correspondence: Xiaohong Liu, ; Shaofeng Zhan, ; Geng Li,
| | - Geng Li
- Animal Experiment Center, Guangzhou University of Chinese Medicine, Guangzhou, China
- *Correspondence: Xiaohong Liu, ; Shaofeng Zhan, ; Geng Li,
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Jindal A, Sarin SK. Epidemiology of liver failure in Asia-Pacific region. Liver Int 2022; 42:2093-2109. [PMID: 35635298 DOI: 10.1111/liv.15328] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/26/2022] [Accepted: 05/27/2022] [Indexed: 02/13/2023]
Abstract
The global burden of deaths caused by liver failure is substantial. The Asia-Pacific region is home to more than half of the global population and accounted for 62.6% of global deaths because of liver diseases in 2015. The aetiology of liver failure varies in different countries at different times. Viruses (Hepatitis A, B and E), drugs (herbs and anti-tuberculous drugs), toxins (alcohol use) and autoimmune flares are mainly responsible of majority of liver failure in individuals with normal liver (acute liver failure; ALF); else these may precipitate liver failure in those with chronic liver disease (acute-on-chronic liver failure; ACLF). Concomitant increases in alcohol misuse and metabolic syndrome in recent years are concerning. Ongoing efforts to address liver failure-related morbidity and mortality require accurate contemporary estimates of epidemiology and outcomes. In light of the ever-changing nature of liver disease epidemiology, accurate estimates for the burden of liver failure across the countries are vital for setting clinical, research and policy priorities. In this review, we aimed to describe the current as well as changing epidemiological trends of common liver failure syndromes, ALF and ACLF in the Asia-Pacific region.
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Affiliation(s)
- Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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27
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Huy BV, Toàn NV. Prognostic indicators associated with progresses of severe dengue. PLoS One 2022; 17:e0262096. [PMID: 34986174 PMCID: PMC8730386 DOI: 10.1371/journal.pone.0262096] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 12/17/2021] [Indexed: 12/29/2022] Open
Abstract
Background Dengue usually progress abnormally, especially in the critical phase. The main causes of death were shock, severe bleeding and organ failure. The aim of our study was to evaluate prognostic indicators of severe dengue according to the phases of the disease progression. Methods A cross-sectional study was conducted from July to December 2017 at the National Hospital for Tropical Diseases and the Hospital for Tropical Diseases of Ho Chi Minh City. 326 patients, aged 6 years and over, including 99/326 patients with severe dengue and 227/326 patients with non-severe dengue, hospitalized in the first 3 days of illness, confirmed Dengue virus by the RT-PCR assay have been registered for the study. Clinical manifestations were monitored daily. The hematocrit, white blood cells, platelet, serum albumin, ALT, AST, bilirubin, prothrombin time (PT%, PTs), fibrinogen, aPTT, INR and creatinine were evaluated at two times: febrile phase and critical phase. Results Independent factors associated with severe dengue were identified on multivariate logistic regression models. During the first 3 days of the disease, the prognostic indicators were platelet count ≤ 100 G/L (OR = 2.2; 95%CI: 1.2–3.9), or serum albumin < 35 g/L (OR = 3.3; 95%CI: 1.8–6.1). From day 4–6, the indicator were AST > 400 U/L (OR = 3.0; 95%CI: 1.1–7.9), ALT > 400 U/L (OR = 6.6; 95%CI: 1.7–24.6), albumin < 35 g/L (OR = 3.0; 95%CI: 1.5–5.9), and bilirubin total >17 μmol/L (OR = 4.6; 95%CI: 2.0–10.4). Conclusion To predict the risk of patients with severe dengue, prognostic laboratory indicators should be indicated consistent with the progression of the disease. During the first 3 days of illness, prognostic indicators should be platelet count, or serum albumin. From the 4th - 6th day of illness, prognostic indicators should be AST, ALT, albumin, or bilirubin total.
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Affiliation(s)
- Bùi Vũ Huy
- Department of Infectious Diseases, Hanoi Medical University, Hanoi, Vietnam.,Department of Pediatrics, National Hospital for Tropical Diseases, Hanoi, Vietnam
| | - Ngô Văn Toàn
- Department of Environmental Health, Hanoi Medical University, Hanoi, Vietnam
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Shrestha DB, Budhathoki P, Sedhai YR, Adhikari A, Poudel A, Aryal B, Baniya R. N-acetyl cysteine versus standard of care for non-acetaminophen induced acute liver injury: a systematic review and meta-analysis. Ann Hepatol 2022; 24:100340. [PMID: 33722689 DOI: 10.1016/j.aohep.2021.100340] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/17/2021] [Accepted: 02/18/2021] [Indexed: 02/04/2023]
Abstract
The role of N-acetylcysteine (NAC) in the treatment of acetaminophen induced acute liver injury (ALI) is well established but its role in non-acetaminophen induced ALI is still elusive. We conducted this meta-analysis to evaluate the role of NAC in non-acetaminophen induced ALI. We searched electronic databases for studies published till Oct 25, 2020. We used RevMan v5.4 software to analyze the data extracted from selected studies by using Covidence systematic review software. Outcome estimation was done using Odds Ratio (OR) with 95% confidence interval (CI). The heterogeneity in various studies was determined using the I2 test. A total of 11 studies were included in quantitative analysis. Use of NAC in non-acetaminophen induced ALI showed 53% reduction in mortality compared to standard of care (OR, 0.47; CI, 0.29-0.75) and reduced mean duration of hospital stay by 6.52 days (95% CI, -12.91 to -0.13). Similarly, the rate of encephalopathy was 59% lower in the treatment group (OR, 0.41; CI, 0.20-0.83). However, the risk of developing nausea and vomiting (OR, 3.99; CI, 1.42-11.19), and the need for mechanical ventilation (OR 3.88; CI, 1.14-13.29) were significantly higher in the treatment group. These findings conclude use of NAC decreases mortality and hepatic encephalopathy compared to standard of care in patients with non-acetaminophen induced ALI. Although there is an increased risk of nausea and vomiting with the use of NAC, the majority of adverse events are transient and minor.
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Affiliation(s)
| | - Pravash Budhathoki
- Department of Emergency Medicine, Dr. Iwamura Memorial Hospital, Bhaktapur 44800, Nepal
| | - Yub Raj Sedhai
- Department of Internal Medicine, Division of Hospital Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.
| | - Anurag Adhikari
- Department of Emergency Medicine, Nepal National Hospital, Kathmandu, Nepal
| | - Ayusha Poudel
- Department of Emergency Medicine, Alka Hospital, Kathmandu, Nepal
| | - Barun Aryal
- Nepalese Army Institute of Health Sciences, Kathmandu, Nepal
| | - Ramkaji Baniya
- Our Lady of the Lake Regional Medical Center, Baton Rouge, LA, USA
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Leowattana W, Leowattana T. Dengue hemorrhagic fever and the liver. World J Hepatol 2021; 13:1968-1976. [PMID: 35070001 PMCID: PMC8727196 DOI: 10.4254/wjh.v13.i12.1968] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 03/30/2021] [Accepted: 11/13/2021] [Indexed: 02/06/2023] Open
Abstract
Dengue hemorrhagic fever (DHF) is one of the most rapidly emerging infections of tropical and subtropical regions worldwide. It affects more rural and urban areas due to many factors, including climate change. Although most people with dengue viral infection are asymptomatic, approximately 25% experience a self-limited febrile illness with mild to moderate biochemical abnormalities. Severe dengue diseases develop in a small proportion of these patients, and the common organ involvement is the liver. The hepatocellular injury was found in 60%-90% of DHF patients manifested as hepatomegaly, jaundice, elevated aminotransferase enzymes, and critical condition as an acute liver failure (ALF). Even the incidence of ALF in DHF is very low (0.31%-1.1%), but it is associated with a relatively high mortality rate (20%-68.3%). The pathophysiology of liver injury in DHF included the direct cytopathic effect of the DENV causing hepatocytes apoptosis, immune-mediated hepatocyte injury induced hepatitis, and cytokine storm. Hepatic hypoperfusion is another contributing factor in dengue shock syndrome. The reduction of morbidity and mortality in DHF with liver involvement is dependent on the early detection of warning signs before the development of ALF.
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Affiliation(s)
- Wattana Leowattana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Bangkok, Thailand.
| | - Tawithep Leowattana
- Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Bangkok, Thailand
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30
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Comments on "characteristics and outcomes of critically ill patients with severe hyperammonemia". J Crit Care 2020; 63:257-258. [PMID: 33272826 DOI: 10.1016/j.jcrc.2020.11.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 11/19/2020] [Indexed: 11/21/2022]
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