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Yoshimura R, Tanaka M, Kurokawa M, Nakamura N, Goya T, Imoto K, Kohjima M, Fujiu K, Iwami S, Ogawa Y. Stratifying and predicting progression to acute liver failure during the early phase of acute liver injury. PNAS NEXUS 2025; 4:pgaf004. [PMID: 39917257 PMCID: PMC11801268 DOI: 10.1093/pnasnexus/pgaf004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 12/03/2024] [Indexed: 02/09/2025]
Abstract
Acute liver failure (ALF) is a serious disease that progresses from acute liver injury (ALI) and that often leads to multiorgan failure and ultimately death. Currently, effective treatment strategies for ALF, aside from transplantation, remain elusive, partly because ALI is highly heterogeneous. Furthermore, clinicians lack a quantitative indicator that they can use to predict which patients hospitalized with ALI will progress to ALF and the need for liver transplantation. In our study, we retrospectively analyzed data from 319 patients admitted to the hospital with ALI. By applying a machine-learning approach and by using the SHapley Additive exPlanations (SHAP) algorithm to analyze time-course blood test data, we identified prothrombin time activity percentage (PT%) as a biomarker reflecting individual ALI status. Unlike previous studies predicting the need for liver transplantation in patients with ALF, our study focused on PT% dynamics. Use of this variable allowed us to stratify the patients with highly heterogeneous ALI into six groups with distinct clinical courses and prognoses, i.e. self-limited, intensive care-responsive, or intensive care-refractory patterns. Notably, these groups were well predicted by clinical data collected at the time of admission. Additionally, utilizing mathematical modeling and machine learning, we assessed the predictability of individual PT% dynamics during the early phase of ALI. Our findings may allow for optimizing medical resource allocation and early introduction of tailored individualized treatment, which may result in improving ALF prognosis.
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Affiliation(s)
- Raiki Yoshimura
- Interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Aichi 464-8602, Japan
| | - Masatake Tanaka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Miho Kurokawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Naotoshi Nakamura
- Interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Aichi 464-8602, Japan
| | - Takeshi Goya
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Koji Imoto
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Motoyuki Kohjima
- Department of Gastroenterology, NHO Kyushu Medical Center, Fukuoka 810-8563, Japan
| | - Katsuhito Fujiu
- Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
| | - Shingo Iwami
- Interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Aichi 464-8602, Japan
- Institute of Mathematics for Industry, Kyushu University, Fukuoka 819-0395, Japan
- Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan
- Interdisciplinary Theoretical and Mathematical Sciences Program (iTHEMS), RIKEN, Saitama 351-0198, Japan
- NEXT-Ganken Program, Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan
- International Research Center for Neurointelligence, The University of Tokyo Institutes for Advanced Study, The University of Tokyo, Tokyo 113-0033, Japan
- Science Groove Inc., Fukuoka 810-0041, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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Siraz MMM, Reza A, Khan M, Alam MS, Al Mahmud J, Rashid MB, Begum M, Sultana N, Khandaker MU, Osman H, Yeasmin S. Pioneering study of radioactivity in soil near the Payra 1320 MW Thermal Power Plant, the largest coal-fired thermal power plant in Bangladesh. INTERNATIONAL JOURNAL OF ENVIRONMENTAL ANALYTICAL CHEMISTRY 2024:1-19. [DOI: 10.1080/03067319.2024.2404526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 09/06/2024] [Indexed: 10/12/2024]
Affiliation(s)
| | - Ashik Reza
- Department of Nuclear Engineering, University of Dhaka, Dhaka, Bangladesh
| | - Mohammad Khan
- Department of Nuclear Engineering, University of Dhaka, Dhaka, Bangladesh
| | - Mohammad Shafiqul Alam
- Department of Nuclear Engineering, Chittagong University of Engineering & Technology, Chattogram, Bangladesh
| | - Jubair Al Mahmud
- Department of Nuclear Engineering, University of Dhaka, Dhaka, Bangladesh
| | - Md. Bazlar Rashid
- Coastal and Marine Geology Branch, Geological Survey of Bangladesh, Dhaka, Bangladesh
| | - Mahbuba Begum
- Health Physics Division, Atomic Energy Centre, Dhaka, Bangladesh
| | - Nazneen Sultana
- Health Physics Division, Atomic Energy Centre, Dhaka, Bangladesh
| | - Mayeen Uddin Khandaker
- Applied Physics and Radiation Technologies Group, CCDCU, School of Engineering and Technology, Sunway University, Bandar, Selangor, Malaysia
- Faculty of Graduate Studies, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, Bangladesh
| | - Hamid Osman
- Department of Radiological Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia
| | - S. Yeasmin
- Health Physics Division, Atomic Energy Centre, Dhaka, Bangladesh
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Kurokawa M, Goya T, Kohjima M, Tanaka M, Iwabuchi S, Shichino S, Ueha S, Hioki T, Aoyagi T, Takahashi M, Imoto K, Tashiro S, Suzuki H, Kato M, Hashimoto S, Matsuda H, Matsushima K, Ogawa Y. Microcirculatory disturbance in acute liver injury is triggered by IFNγ-CD40 axis. J Inflamm (Lond) 2024; 21:23. [PMID: 38907339 PMCID: PMC11191181 DOI: 10.1186/s12950-024-00387-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 04/15/2024] [Indexed: 06/23/2024] Open
Abstract
BACKGROUND Acute liver failure (ALF) is a life-threatening disorder that progresses from self-limiting acute liver injury (ALI). Microcirculatory disturbance characterized by sinusoidal hypercoagulation and subsequent massive hypoxic hepatocyte damage have been proposed to be the mechanism by which ALI deteriorates to ALF; however, the precise molecular pathway of the sinusoidal hypercoagulation remains unknown. Here, we analyzed ALI patients and mice models to uncover the pathogenesis of ALI with microcirculatory disturbance. METHODS We conducted a single-center retrospective study for ALI and blood samples and liver tissues were analyzed to evaluate the microcirculatory disturbance in ALI patients (n = 120). Single-cell RNA sequencing analysis (scRNA-seq) was applied to the liver from the concanavalin A (Con A)‑induced mouse model of ALI. Interferon-gamma (IFNγ) and tumor necrosis factor-alpha knockout mice, and primary human liver sinusoidal endothelial cells (LSECs) were used to assess the mechanism of microcirculatory disturbance. RESULTS The serum IFNγ concentrations were significantly higher in ALI patients with microcirculatory disturbance than in patients without microcirculatory disturbance, and the IFNγ was upregulated in the Con A mouse model which presented microcirculatory disturbance. Hepatic IFNγ expression was increased as early as 1 hour after Con A treatment prior to sinusoidal hypercoagulation and hypoxic liver damage. scRNA-seq revealed that IFNγ was upregulated in innate lymphoid cells and stimulated hepatic vascular endothelial cells at the early stage of liver injury. In IFNγ knockout mice treated with Con A, the sinusoidal hypercoagulation and liver damage were remarkably attenuated, concomitant with the complete inhibition of CD40 and tissue factor (TF) upregulation in vascular endothelial cells. By ligand-receptor analysis, CD40-CD40 ligand interaction was identified in vascular endothelial cells. In human LSECs, IFNγ upregulated CD40 expression and TF was further induced by increased CD40-CD40 ligand interaction. Consistent with these findings, hepatic CD40 expression was significantly elevated in human ALI patients with microcirculatory disturbance. CONCLUSION We identified the critical role of the IFNγ-CD40 axis as the molecular mechanism of microcirculatory disturbance in ALI. This finding may provide novel insights into the pathogenesis of ALI and potentially contribute to the emergence of new therapeutic strategies for ALI patients.
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Affiliation(s)
- Miho Kurokawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
- Department of Gastroenterology and Hepatology, NHO Fukuokahigashi Medical Center, 1-1-1 Chidori, Koga, 811-3195, Japan
| | - Takeshi Goya
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Motoyuki Kohjima
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
- Department of Gastroenterology, NHO Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka, 810-8563, Japan.
| | - Masatake Tanaka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Sadahiro Iwabuchi
- Department of Molecular Pathophysiology, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama-shi, 641-8509, Japan
| | - Shigeyuki Shichino
- Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Japan
| | - Satoshi Ueha
- Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Japan
| | - Tomonobu Hioki
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Tomomi Aoyagi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Motoi Takahashi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Koji Imoto
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Shigeki Tashiro
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Hideo Suzuki
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Masaki Kato
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
- Graduate School of Nutritional Sciences, Nakamura Gakuen University, 5-7-1 Befu, Jounan-ku, Fukuoka, 814-0198, Japan
| | - Shinichi Hashimoto
- Department of Molecular Pathophysiology, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama-shi, 641-8509, Japan
| | - Hideo Matsuda
- Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita-shi, 565-0871, Japan
| | - Kouji Matsushima
- Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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Oliveira EMG, Amaral ACDC, Oliveira PMC, Lanzoni VP, Perez RM, Narciso-Schiavon JL, Whale RC, Carvalho-Filho RJ, Silva AEB, Ferraz MLCG. Clinical Characteristics of Genuine Acute Autoimmune Hepatitis. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024; 31:173-181. [PMID: 38757065 PMCID: PMC11095594 DOI: 10.1159/000531018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 04/17/2023] [Indexed: 05/18/2024]
Abstract
INTRODUCTION Autoimmune hepatitis (AIH) has a spectrum of symptoms ranging from asymptomatic disease to acute severe hepatitis, chronic hepatitis, and decompensated cirrhosis. The acute presentation is not rare and could represent genuine acute AIH (GAAIH) or acute exacerbation of chronic autoimmune hepatitis. We aimed to identify the prevalence, clinical features, and prognostic factors associated with GAAIH and compare these cases with acute exacerbation of chronic AIH. METHODS This cross-sectional observational study evaluated patients with acute AIH presentation, defined as total bilirubin >5 times the upper limit of normality (xULN) and/or alanine aminotransferase >10 xULN, and no prior history of liver disease. Histology findings of acute disease defined GAAIH. Bivariate analyses were performed to identify factors associated with the GAAIH, when compared with acute exacerbation of chronic AIH. RESULTS Seventy-two patients with acute presentation of AIH were included and six (8.3%) of them presented GAAIH. Comparative analysis between patients with GAAIH and patients with acute exacerbation of chronic AIH revealed that prothrombin activity (96% [74-100] vs. 61% [10-100]; p = 0.003) and albumin levels (3.9 ± 0.2 g/dL vs. 3.4 ± 0.5 g/dL; p < 0.001) were higher in patients with GAAIH. The International Autoimmune Hepatitis Group score was higher in patients with acute exacerbation of chronic AIH (18.5 [8-23] vs. 16.5 [15-17]; p = 0.010). Compared to 15.2% of acute exacerbation of chronic AIH, complete therapeutic response to treatment was achieved in 67.7% of cases with GAAIH (p = 0.018). CONCLUSIONS GAAIH was rare (8.3%), and patients with this presentation exhibited more preserved liver function tests, suggesting that most cases presenting with loss of function are acute exacerbation of chronic AIH. Additionally, patients with GAAIH had a better complete therapeutic response, suggesting a more preserved liver function at presentation, and early diagnosis has a positive therapeutic implication.
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Affiliation(s)
- Elze Maria Gomes Oliveira
- Division of Gastroenterology, Federal University of Sao Paulo, Sao Paulo, Brazil
- Centro Universitário Lusíada, Santos, Brazil
| | | | | | | | - Renata Mello Perez
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Janaína Luz Narciso-Schiavon
- Division of Gastroenterology, Department of Internal Medicine, Federal University of Santa Catarina, Florianópolis, Brazil
| | - Raul Carlos Whale
- Division of Gastroenterology, Federal University of Sao Paulo, Sao Paulo, Brazil
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Siraz MMM, A. M. J, Alam MS, Rashid MB, Hossain Z, Khandaker MU, Bradley DA, Yeasmin S. Measurement of radioactivity in soils of Karamjal and Harbaria mangrove forest of Sundarbans for establishment of radiological database. PLoS One 2023; 18:e0289113. [PMID: 37856554 PMCID: PMC10586596 DOI: 10.1371/journal.pone.0289113] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 07/09/2023] [Indexed: 10/21/2023] Open
Abstract
This work presents the first in-depth study of soil radioactivity in the mangrove forest of Bangladesh part of the Sundarbans. It used HPGe gamma-ray spectrometry to measure the amount of natural radioactivity in soil samples from Karamjal and Harbaria sites of the world's largest mangrove forest. The activity concentrations of most of the 226Ra (14±2 Bqkg-1 to 35±4 Bqkg-1) and 232Th (30±5 Bqkg-1 to 50±9 Bqkg-1) lie within the world average values, but the 40K concentration (370± 44 Bqkg-1 to 660±72 Bqkg-1) was found to have exceeded the world average value. The evaluation of radiological hazard parameters revealed that the outdoor absorbed dose rate (maximum 73.25 nGyh-1) and outdoor annual effective dose (maximum 0.09 mSvy-1) for most samples exceeded the corresponding world average values. The elevated concentration of 40K is mainly due to the salinity intrusion, usage of fertilizers and agricultural runoff, and migration of waste effluents along the riverbanks. Being the pioneering comprehensive research on the Bangladesh side of the Sundarbans, this study forms a baseline radioactivity for the Sundarbans before the commissioning of the Rooppur Nuclear Power Plant in Bangladesh.
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Affiliation(s)
| | - Jubair A. M.
- Department of Nuclear Engineering, University of Dhaka, Dhaka, Bangladesh
| | - M. S. Alam
- Department of Nuclear Engineering, University of Dhaka, Dhaka, Bangladesh
| | | | - Z. Hossain
- Health Physics Division, Atomic Energy Centre, Dhaka, Bangladesh
| | - Mayeen Uddin Khandaker
- Department of General Educational Development, Faculty of Science and Information Technology, Daffodil International University, Dhaka, Bangladesh
- Centre for Applied Physics and Radiation Technologies, School of Engineering and Technology, Sunway University, Bandar Sunway, Petaling Jaya, Selangor, Malaysia
| | - D. A. Bradley
- Centre for Applied Physics and Radiation Technologies, School of Engineering and Technology, Sunway University, Bandar Sunway, Petaling Jaya, Selangor, Malaysia
- Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford, Surrey, United Kingdom
| | - S. Yeasmin
- Health Physics Division, Atomic Energy Centre, Dhaka, Bangladesh
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Siraz MMM, Kamal MH, Khan ZH, Alam MS, Al Mahmud J, Rashid MB, Khandaker MU, Osman H, Yeasmin S. Evaluation of radioactivity in soil and rock samples from an undiscovered sea beach in the southeastern coastline of Bangladesh and associated health risk. ENVIRONMENTAL MONITORING AND ASSESSMENT 2023; 195:1028. [PMID: 37558890 DOI: 10.1007/s10661-023-11636-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 07/24/2023] [Indexed: 08/11/2023]
Abstract
This study marks the first-ever assessment of radiological hazards linked to the sands and rocks of Patuartek Sea Beach, situated along one of the world's longest sea beaches in Cox' Bazar of Bangladesh. Through the utilization of an HPGe detector, a comprehensive analysis of the activity concentrations of 226Ra, 232Th, and 40 K was conducted, and their activity ranged from 7 to 23 Bq/kg, 9-58 Bq/kg, and 172-340 Bq/kg, respectively, in soils, and 19-24 Bq/kg, 27-39 Bq/kg, and 340-410 Bq/kg, respectively, in rocks. Some sand samples exhibited elevated levels of 232Th, while the rock samples displayed higher levels of 40 K compared to the global average. The radiological hazard parameters were assessed, and no values surpassed the recommended limits set by several international organizations. Hence, the sands and rocks of Patuartek sea beach pose no significant radiological risk to the residents or tourists. The findings of this study provide crucial insights for the development of a radiological baseline map in the country, which is important due to the commissioning of the country's first nuclear power plant Rooppur Nuclear Power Plant. The data may also stimulate interest in the rare-earth minerals present in the area, which is important for the electronics industry, thorium-based nuclear fuel cycles.
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Affiliation(s)
- M M Mahfuz Siraz
- Health Physics Division, Atomic Energy Centre, Dhaka, 1000, Bangladesh
| | - Md Hossain Kamal
- Department of Physics, University of Dhaka, Dhaka, 1000, Bangladesh
| | | | - M S Alam
- Department of Nuclear Engineering, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Jubair Al Mahmud
- Department of Nuclear Engineering, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Md Bazlar Rashid
- Geological Survey of Bangladesh, Segunbaghicha, Dhaka, 1000, Bangladesh
| | - Mayeen Uddin Khandaker
- Centre for Applied Physics and Radiation Technologies, School of Engineering and Technology, Sunway University, Selangor, 47500, Bandar Sunway, Malaysia
- Department of General Educational Development, Faculty of Science and Information Technology, Daffodil International University, DIU Rd, Dhaka, 1341, Bangladesh
| | - Hamid Osman
- Department of Radiological Sciences, College of Applied Medical Sciences, Taif University, 21944, Taif, Saudi Arabia
| | - S Yeasmin
- Health Physics Division, Atomic Energy Centre, Dhaka, 1000, Bangladesh.
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Kuwano A, Okui T, Kohjima M, Kurokawa M, Goya T, Tanaka M, Aoyagi T, Takahashi M, Imoto K, Tashiro S, Suzuki H, Fujita N, Ushijima Y, Ishigami K, Tokunaga S, Kato M, Ogawa Y. Transcatheter arterial steroid injection therapy improves the prognosis of patients with acute liver failure. Medicine (Baltimore) 2023; 102:e33090. [PMID: 36897684 PMCID: PMC9997803 DOI: 10.1097/md.0000000000033090] [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: 11/11/2022] [Accepted: 02/03/2023] [Indexed: 03/11/2023] Open
Abstract
Acute liver failure (ALF) is a disorder defined by coagulopathy and encephalopathy with a poor prognosis. No effective therapies have been established except for liver transplantation. We previously reported a subgroup of patients with acute liver injury who developed microcirculatory disturbance. We also established and reported transcatheter arterial steroid injection therapy (TASIT) as a new treatment of ALF. Here, we analyze the effectiveness of TASIT in a larger cohort and evaluate the impact on ALF patients with or without microcirculatory disturbance. We conducted a single-center retrospective study to evaluate the effectiveness of TASIT in patients with ALF admitted at Kyushu University Hospital between January 2005 and March 2018. TASIT is performed by injecting methylprednisolone via the proper hepatic artery for 3 days. One hundred ninety-4 patients with ALF were enrolled and analyzed in this study. Of the 87 patients given TASIT, 71 (81.6%) recovered without any complications and 16 (18.4%) died or underwent liver transplantation. Of the 107 patients not administered TASIT, 77 (72.0%) recovered and 30 (28.0%) progressed to irreversible liver failure. In the high-lactate dehydrogenase subgroup, 52 (86.7%) of the 60 patients with TASIT recovered, and the survival rate was significantly higher than that in patients who did not receive TASIT. Multivariate regression analysis revealed that the TASIT procedure was one of the significant prognostic factors in the high-lactate dehydrogenase subgroup and was significantly associated with prothrombin activity percentage improvement. TASIT is an effective treatment for patients with ALF, especially in those with microcirculatory disturbance.
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Affiliation(s)
- Akifumi Kuwano
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Tasuku Okui
- Medical Information Center, Kyushu University Hospital, Higashi-ku, Fukuoka, Japan
| | - Motoyuki Kohjima
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Miho Kurokawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Takeshi Goya
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Masatake Tanaka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Tomomi Aoyagi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Motoi Takahashi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Koji Imoto
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Shigeki Tashiro
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Hideo Suzuki
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Nobuhiro Fujita
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Yasuhiro Ushijima
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Kousei Ishigami
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Shoji Tokunaga
- Medical Information Center, Kyushu University Hospital, Higashi-ku, Fukuoka, Japan
| | - Masaki Kato
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
- Graduate School of Nutritional Sciences, Nakamura Gakuen University, Jounan-ku, Fukuoka, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
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Kim JD. [Acute Liver Failure: Current Updates and Management]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 81:17-28. [PMID: 36695063 DOI: 10.4166/kjg.2022.148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Revised: 12/25/2022] [Accepted: 12/29/2022] [Indexed: 01/26/2023]
Abstract
Acute liver failure (ALF) is a rare disease condition with a dynamic clinical course and catastrophic outcomes. Several etiologies are involved in ALF. Hepatitis A and B infections and indiscriminate use of untested herbs or supplemental agents are the most common causes of ALF in Korea. Noninvasive neurological monitoring tools have been used in patients with ALF in recent times. Ongoing improvements in intensive care, including continuous renal replacement therapy, therapeutic plasma exchange, vasopressor, and extracorporeal membrane oxygenation, have reduced the mortality rate of patients with ALF. However, liver transplantation is still the most effective treatment for patients with intractable ALF. There is a need for further research in the areas of better prognostication and precise selection of patients for emergency transplantation.
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Affiliation(s)
- Jin Dong Kim
- Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea
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Mizota T, Hishiki T, Shinoda M, Naito Y, Hirukawa K, Masugi Y, Itano O, Obara H, Kitago M, Yagi H, Abe Y, Matsubara K, Suematsu M, Kitagawa Y. The hypotaurine-taurine pathway as an antioxidative mechanism in patients with acute liver failure. J Clin Biochem Nutr 2022; 70:54-63. [PMID: 35068682 PMCID: PMC8764102 DOI: 10.3164/jcbn.21-50] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 04/19/2021] [Indexed: 12/02/2022] Open
Abstract
The liver has been thought to protect against oxidative stress through mechanisms involving reduced glutathione (GSH) that consumes high-energy phosphor-nucleotides on its synthesis. However, hepatoprotective mechanisms in acute liver failure (ALF) where the phosphor-nucleotides are decreased in remain to be solved. Liver tissues were collected from patients with ALF and liver cirrhosis (LC) and living donors (HD) who had undergone liver transplantation. Tissues were used for metabolomic analyses to determine metabolites belonging to the central carbon metabolism, and to determine sulfur-containing metabolites. ALF and LC exhibited a significant decline in metabolites of glycolysis and pentose phosphate pathways and high-energy phosphor-nucleotides such as adenosine triphosphate as compared with HD. Conversely, methionine, S-adenosyl-l-methionine, and the ratio of serine to 3-phosphoglycerate were elevated significantly in ALF as compared with LC and HD, suggesting a metabolic boost from glycolysis towards trans-sulfuration. Notably in ALF, the increases in hypotaurine (HTU) + taurine (TU) coincided with decreases in the total amounts of reduced and oxidized glutathione (GSH + 2GSSG). Plasma NH3 levels correlated with the ratio of HTU + TU to GSH + 2GSSG. Increased tissue levels of HTU + TU vs total glutathione appear to serve as a biomarker correlating with hyperammonemia, suggesting putative roles of the HTU-TU pathway in anti-oxidative protective mechanisms.
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Affiliation(s)
| | - Takako Hishiki
- Department of Biochemistry, Keio University School of Medicine
| | | | - Yoshiko Naito
- Department of Biochemistry, Keio University School of Medicine
| | | | - Yohei Masugi
- Department of Pathology, Keio University School of Medicine
| | - Osamu Itano
- Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare School of Medicine
| | - Hideaki Obara
- Department of Surgery, Keio University School of Medicine
| | - Minoru Kitago
- Department of Surgery, Keio University School of Medicine
| | - Hiroshi Yagi
- Department of Surgery, Keio University School of Medicine
| | - Yuta Abe
- Department of Surgery, Keio University School of Medicine
| | | | - Makoto Suematsu
- Department of Biochemistry, Keio University School of Medicine
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine
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10
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Shammout R, Alhassoun T, Rayya F. Acute Liver Failure due to Hepatitis A Virus. Case Rep Gastroenterol 2021; 15:927-932. [PMID: 34949977 PMCID: PMC8647103 DOI: 10.1159/000514393] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 01/12/2021] [Indexed: 12/02/2022] Open
Abstract
Acute liver failure (ALF) is a syndrome, rather than a specific disease, with several possible causes, and viral hepatitis is a major cause. The relationship between self-limited and ALF hepatitis A is still poorly understood. A 45-year-old woman presented to our hospital with ALF diagnosis (from another hospital). She suffered from hospital-acquired pneumonia. The patient recovered within 4 weeks and returned to her normal life after 6 months of follow-up.
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Affiliation(s)
- Reem Shammout
- Faculty of Medicine, Damascus University, Damascus, Syrian Arab Republic
| | - Turki Alhassoun
- Department of General Surgery, Faculty of Medicine, Damascus University, Damascus, Syrian Arab Republic
| | - Fadi Rayya
- Department of General Surgery, Al Assad University Hospital, Faculty of Medicine, Damascus University, Damascus, Syrian Arab Republic
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11
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MacDonald AJ, Speiser JL, Ganger DR, Nilles KM, Orandi BJ, Larson AM, Lee WM, Karvellas CJ. Clinical and Neurologic Outcomes in Acetaminophen-Induced Acute Liver Failure: A 21-Year Multicenter Cohort Study. Clin Gastroenterol Hepatol 2021; 19:2615-2625.e3. [PMID: 32920216 PMCID: PMC10656032 DOI: 10.1016/j.cgh.2020.09.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 08/25/2020] [Accepted: 09/04/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND & AIMS Acetaminophen (APAP)-induced acute liver failure (ALF) is a rare disease associated with high mortality rates. This study aimed to evaluate changes in interventions, psychosocial profile, and clinical outcomes over a 21-year period using data from the ALF Study Group registry. METHODS A retrospective review of this prospective, multicenter cohort study of all APAP-ALF patients enrolled during the study period (1998-2018) was completed. Primary outcomes evaluated were the 21-day transplant-free survival (TFS) and neurologic complications. Covariates evaluated included enrollment cohort (early, 1998-2007; recent, 2008-2018), intentionality, psychiatric comorbidity, and use of organ support including continuous renal replacement therapy (CRRT). RESULTS Of 1190 APAP-ALF patients, recent cohort patients (n = 608) had significantly improved TFS (recent, 69.8% vs early, 61.7%; P = .005). Recent cohort patients were more likely to receive CRRT (22.2% vs 7.6%; P < .001), and less likely to develop intracranial hypertension (29.9% vs 51.5%; P < .001) or die by day 21 from cerebral edema (4.5% vs 11.6%; P < .001). Grouped by TFS status (non-TFS, n = 365 vs TFS, n = 704), there were no differences in psychiatric comorbidity (51.5% vs 55.0%; P = .28) or intentionality (intentional, 39.7% vs 41.6%; P = .58). On multivariable logistic regression adjusting for vasopressor support, development of grade 3/4 hepatic encephalopathy, King's College criteria, and MELD score, the use of CRRT (odds ratio, 1.62; P = .023) was associated with significantly increased TFS (c-statistic, 0.86). In a second model adjusting for the same covariates, recent enrollment was associated significantly with TFS (odds ratio, 1.42; P = .034; c-statistic, 0.86). CONCLUSIONS TFS in APAP-ALF has improved in recent years and rates of intracranial hypertension/cerebral edema have decreased, possibly related to increased CRRT use.
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Affiliation(s)
- Andrew J MacDonald
- Department of Surgery, Division of General Surgery, Edmonton, Alberta, Canada
| | - Jaime L Speiser
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Daniel R Ganger
- Department of Gastroenterology and Hepatology, Northwestern University, Chicago, Illinois
| | - Kathleen M Nilles
- MedStar Georgetown Transplant Institute, Division of Gastroenterology and Hepatology, Georgetown University School of Medicine, Washington, District of Columbia
| | - Babak J Orandi
- Division of Transplantation, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
| | - Anne M Larson
- Department of Internal Medicine, Division of Gastroenterology, University of Washington Medical Center, Seattle, Washington
| | - William M Lee
- Department of Internal Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Constantine J Karvellas
- Liver Unit, Division of Gastroenterology, Department of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada.
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12
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Liver transplantation in acute liver failure due to Hepatitis B. Two clinical cases. Ann Hepatol 2021; 21:100107. [PMID: 31623992 DOI: 10.1016/j.aohep.2019.06.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 05/30/2019] [Accepted: 06/03/2019] [Indexed: 02/04/2023]
Abstract
Hepatitis B virus (HBV) related acute liver failure (ALF) is uncommon in our region, and there is limited HBV literature regarding the optimal management of these cases. In this article, we report two clinical cases of young men who have sex with men (MSM), both developed severe acute hepatitis caused by HBV, progressed to ALF and afterward required liver transplantation. Antiviral post-transplant treatment included entecavir without Hepatitis B Immunoglobulin (HBIG), and immunosuppression therapy with steroids, tacrolimus, and mycophenolate. Serologic follow-up showed early Hepatitis B surface Antigen (HBsAg) seroconversion, undetectable HBV viral load, and positive Anti-HBs titers. During later follow-up, Anti-HBs titers gradually fell (<10mUI/L after six months), with normal liver function. DISCUSSION: In cases of HBV-related ALF, the liver develops a robust immune response, leading to, an early undetectable viral load and seroconversion, with loss of HBsAg, and the appearance of Anti-HBs as a result of the inflammatory response. The management varies depending on whether this is a de novo acute infection or a reactivation of a previous chronic infection. In both cases, the use of antiviral therapy is recommended, with entecavir or tenofovir, among others, but the use of specific HBIG is supported only in ALF related to chronic HBV infection. The optimal length of the antiviral therapy after liver transplantation is still under discussion. CONCLUSION: These cases of HBV related ALF with an early HBsAg seroconversion demonstrates the relevance of requesting IgM antibody against hepatitis B core antigen (anti-HBc IgM) for the etiological study of ALF with negative HBsAg. Usage of HBIG does not seem essential during the post-transplantation period in these cases.
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13
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Rodríguez-Orozco AR. Considerations about the use of antivirals in patients with primary biliary cholangitis and hepatitis B virus early infection. Med Clin (Barc) 2021; 157:262-263. [PMID: 32854952 DOI: 10.1016/j.medcli.2020.06.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/22/2020] [Accepted: 06/24/2020] [Indexed: 11/28/2022]
Affiliation(s)
- Alain R Rodríguez-Orozco
- Faculty of Medicine and Biological Sciences "Dr. Ignacio Chávez", University of San Nicolás de Hidalgo, Morelia, Mexico; Instituto de Investigación Científica en Temas de Familia, Alergia e Inmunología, Morelia, Mexico.
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14
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Indication of Liver Transplantation in the Treatment of Newly Categorized Acute-on-Chronic Liver Failure In Japan. Transplant Proc 2021; 53:1611-1615. [PMID: 33965241 DOI: 10.1016/j.transproceed.2021.03.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 03/04/2021] [Accepted: 03/17/2021] [Indexed: 11/23/2022]
Abstract
AIM This study aims to validate Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) and confirm the feasibility of performing transplantation. METHODS We included 60 patients with acute liver injury. Demographic and clinical features were retrospectively collected, and the primary outcome was compared among 4 types: acute liver failure (ALF) with hepatic coma (n = 23), ALF without hepatic coma (n = 12), acute liver injury (n = 20), and ACLF (n = 5). Moreover, 80 transplanted patients were enrolled to compare the difficulty of transplantation between ALF (n = 8) vs non-ALF (n = 72) patients. RESULTS Seven patients in the ALF with hepatic coma group and 1 patient in the ACLF with hepatic coma group were transplanted. Ten patients who could not be registered for transplantation died. In univariate analysis, liver failure type (P < .0001), total bilirubin level (P = .05), and prothrombin time internationalized ratio (P < .0001) were associated with patient survival. In multivariate analysis, liver failure type was associated with patient survival (P < .0001). The respective 1-, 3-, and 5-year patient survival rates were 45.9%, 45.9%, and 45.9% for ALF patients with hepatic coma; 100.0%, 100.0%, and 100.0% for ALF patients without hepatic coma and acute liver injury; and 80.0%, 80.0%, and 80.0% for ACLF patients (P < .0001). Chronic liver disease did not affect operation time (P = .46) and bleeding volume (P = .49). CONCLUSION Patients diagnosed with ACLF via Japanese criteria presented significantly higher survival rates than ALF patients with hepatic coma.
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15
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Kuwano A, Kurokawa M, Kohjima M, Imoto K, Tashiro S, Suzuki H, Tanaka M, Okada S, Kato M, Ogawa Y. Microcirculatory disturbance in acute liver injury. Exp Ther Med 2021; 21:596. [PMID: 33884034 PMCID: PMC8056117 DOI: 10.3892/etm.2021.10028] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Accepted: 10/19/2020] [Indexed: 12/23/2022] Open
Abstract
Microcirculatory disturbance is thought to be involved in the pathogenesis of acute liver injury (ALI). The current study examined the pathophysiologic role of hepatic microcirculatory disturbance in patients with ALI and in mouse models of ALI. Using serum aminotransferase (ALT)/lactate dehydrogenase (LDH) ratio as a hypoxic marker, 279 patients with ALI were classified into the low ALT/LDH ratio (ALT/LDH ≤1.5) and high ALT/LDH ratio group (ALT/LDH >1.5). In the low ALT/LDH ratio group, serum ALT, LDH, fibrinogen degradation products and prothrombin time-international normalized ratio were increased relative to the high ALT/LDH ratio group. Histologically, hepatic expression of tissue factor (TF) and hypoxia-related proteins was enhanced in the low ALT/LDH ratio group, and this was accompanied by sinusoidal fibrin deposition. Sinusoidal hypercoagulation and intrahepatic hypoxia was also analyzed in two different mouse models of ALI; Concanavalin A (ConA) mice and Galactosamine/tumor necrosis factor (TNF)-α (G/T) mice. Serum ALT/LDH ratio in ConA mice was significantly lower compared with G/T mice. Pimonidazole staining revealed the upregulation of hypoxia-related proteins in ConA mice. Recombinant human soluble thrombomodulin improved liver damage in ConA mice in association with reduced sinusoidal hypercoagulation and intrahepatic hypoxia. The present study provides evidence that serum ALT/LDH ratio aids in the identification of patients with ALI and intrahepatic hypoxia as a result of microcirculatory disturbance. The results facilitate the improved understanding of the pathogenesis of ALI, thereby offering a novel therapeutic strategy against ALI, which arises from sinusoidal hypercoagulation.
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Affiliation(s)
- Akifumi Kuwano
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
| | - Miho Kurokawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
| | - Motoyuki Kohjima
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
| | - Koji Imoto
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
| | - Shigeki Tashiro
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
| | - Hideo Suzuki
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
| | - Masatake Tanaka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.,Department of Pathophysiology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
| | - Seiji Okada
- Department of Pathophysiology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
| | - Masaki Kato
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.,Core Research for Evolutionary Science and Technology (CREST), Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo 100-0004, Japan
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16
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LCR based quick detection of hotspot G1896A mutation in patients with different spectrum of hepatitis B. J Infect Public Health 2021; 14:651-654. [PMID: 33857724 DOI: 10.1016/j.jiph.2021.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 01/12/2021] [Accepted: 01/16/2021] [Indexed: 11/24/2022] Open
Abstract
G1896A switch is one of the hotspots in subjects affected with hepatitis B. This hotspot mutation is observed in all the different spectrum of hepatitis B, and it has a very dangerous and a long lasting effect. The major purpose of the study was to screen G1986A mutations at a large scale and also to establish ligase chain reaction as a mutation testing tool. Polymerase chain reaction (PCR) and Nucleotide Sequencing was done to identify the G1896A mutation in the precore region of the genome. All the 331 HBV positive patients were screened. Almost 29% (24/82) of the cases remarkably had the presence of G1896A mutation confirmed by LCR and direct sequencing. The precore G1896A mutation is responsible for one third of the patients suffering from precore stop codon mutation. It clearly exhibits that LCR is 100% in sync with direct sequencing and is extremely reliable and the results are highly reproducible.
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17
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Fujiwara K, Nakayama N, Kato N, Yokosuka O, Tsubouchi H, Takikawa H, Mochida S. Infectious complications and timing for liver transplantation in autoimmune acute liver failure in Japan: a subanalysis based on nationwide surveys between 2010 and 2015. J Gastroenterol 2020; 55:888-898. [PMID: 32556645 DOI: 10.1007/s00535-020-01699-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 06/08/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND The prognosis of autoimmune acute liver failure (ALF) without liver transplantation (LT) is poor worldwide. We subanalyzed infectious complications of autoimmune ALF using data of nationwide surveys between 2010 and 2015 retrospectively and tried to determine when to evaluate the efficacy of corticosteroid (CS) treatment or abandon it for LT based on objective data. METHODS One hundred and forty-four patients with autoimmune ALF, comprising 79 ALF with coma ≤ I, 52 ALF with coma ≥ II and 13 late onset hepatic failure (LOHF), were analyzed. RESULTS CS was administered to 140 (97%) patients. Thirty-seven (26%) patients had infectious complications. Patients with infection revealed more advanced disease type (p < 0.001) and poorer spontaneous survival (p < 0.001) than those without infection. Median (interquartile range) duration between diagnosis of ALF and onset of infection was 18.5 (11-36) days, and that between introduction of CS and onset of infection was 17 (10.5-36) days. Seventy-nine (55%) recovered without LT, 14 (10%) received LT and 51 (35%) died without LT. Dead or transplanted patients were older (p = 0.0057), and revealed more advanced liver failure (p < 0.001) and more occurrence of infection (p < 0.001). CONCLUSIONS A critical point for evaluating the efficacy of CS treatment and switching to LT is at most 2-week after diagnosis of ALF and introduction of CS. More important, we should accelerate the point and prepare for LT in cases of ALF with coma ≥ II and LOHF, and we should have performed LT by then at the latest in case of failure to improve.
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Affiliation(s)
- Keiichi Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan.
- Faculty of Healthcare Sciences, Chiba Prefectural University of Health Sciences, Chiba, Japan.
| | - Nobuaki Nakayama
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | | | - Hajime Takikawa
- Faculty of Medical Technology, Teikyo University, Tokyo, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama, Japan
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18
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Sano T, Akuta N, Suzuki Y, Kasuya K, Fujiyama S, Kawamura Y, Sezaki H, Hosaka T, Saitoh S, Kobayashi M, Suzuki F, Kobayashi M, Arase Y, Ikeda K, Kumada H. Fulminant Hepatitis due to de novo Hepatitis B after Cord Blood Transplantation Rescued by Medical Treatment. Intern Med 2020; 59:1519-1524. [PMID: 32536678 PMCID: PMC7364250 DOI: 10.2169/internalmedicine.4190-19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
A 53-year-old man presented with fulminant hepatitis due to de novo hepatitis B. He had been diagnosed previously with adult T-cell leukemia (ATL) and previously resolved hepatitis B virus infection. The ATL had been treated with cord blood transplantation (CBT). He developed fulminant hepatitis 18 months after CBT, 15 months after the withdrawal of immunosuppressants, and 10 months after vitreous injections of methotrexate for ATL-related retinal infiltration. The aggressive medical protocol included entecavir, prednisolone, plasma exchange, hemodialysis, and bilirubin adsorption. We herein report successful medical treatment for fulminant de novo hepatitis B in a patient considered unsuitable for liver transplantation.
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Affiliation(s)
- Tomoya Sano
- Department of Hepatology, Toranomon Hospital, Japan
| | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Japan
| | | | | | | | | | | | | | | | | | | | | | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Japan
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19
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Padmanabhan A, Connelly-Smith L, Aqui N, Balogun RA, Klingel R, Meyer E, Pham HP, Schneiderman J, Witt V, Wu Y, Zantek ND, Dunbar NM, Schwartz GEJ. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher 2019; 34:171-354. [PMID: 31180581 DOI: 10.1002/jca.21705] [Citation(s) in RCA: 864] [Impact Index Per Article: 144.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Eighth Edition of the JCA Special Issue continues to maintain this methodology and rigor in order to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Eighth Edition, like its predecessor, continues to apply the category and grading system definitions in fact sheets. The general layout and concept of a fact sheet that was introduced in the Fourth Edition, has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease entity or medical condition. The Eighth Edition comprises 84 fact sheets for relevant diseases and medical conditions, with 157 graded and categorized indications and/or TA modalities. The Eighth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.
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Affiliation(s)
- Anand Padmanabhan
- Medical Sciences Institute & Blood Research Institute, Versiti & Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Laura Connelly-Smith
- Department of Medicine, Seattle Cancer Care Alliance & University of Washington, Seattle, Washington
| | - Nicole Aqui
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Rasheed A Balogun
- Department of Medicine, University of Virginia, Charlottesville, Virginia
| | - Reinhard Klingel
- Apheresis Research Institute, Cologne, Germany & First Department of Internal Medicine, University of Mainz, Mainz, Germany
| | - Erin Meyer
- Department of Hematology/Oncology/BMT/Pathology, Nationwide Children's Hospital, Columbus, Ohio
| | - Huy P Pham
- Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Jennifer Schneiderman
- Department of Pediatric Hematology/Oncology/Neuro-oncology/Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, Illinois
| | - Volker Witt
- Department for Pediatrics, St. Anna Kinderspital, Medical University of Vienna, Vienna, Austria
| | - Yanyun Wu
- Bloodworks NW & Department of Laboratory Medicine, University of Washington, Seattle, Washington, Yale University School of Medicine, New Haven, Connecticut
| | - Nicole D Zantek
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota
| | - Nancy M Dunbar
- Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
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20
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Nakao M, Nakayama N, Uchida Y, Tomiya T, Oketani M, Ido A, Tsubouchi H, Takikawa H, Mochida S. Deteriorated outcome of recent patients with acute liver failure and late-onset hepatic failure caused by infection with hepatitis A virus: A subanalysis of patients seen between 1998 and 2015 and enrolled in nationwide surveys in Japan. Hepatol Res 2019; 49:844-852. [PMID: 30957325 DOI: 10.1111/hepr.13345] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 02/20/2019] [Accepted: 03/25/2019] [Indexed: 02/08/2023]
Abstract
AIM A nationwide survey of acute liver failure (ALF) and late-onset hepatic failure (LOHF) has revealed that the outcomes of recent patients whose diseases were caused by infection with hepatitis A virus (HAV) have worsened, compared with those of previously reported patients. The factors associated with this deterioration were evaluated. METHODS A total of 83 patients with HAV infection seen between 1998 and 2015 were enrolled. All the patients had a prothrombin time-international normalized ratio of 1.5 or more and hepatic encephalopathy of grade 2 or more severe. The demographic and clinical features of 45 patients seen prior to 2003 (cohort 1) and 38 patients seen during 2004 and thereafter (cohort 2) were compared. RESULTS Three and four patients in cohort 1 and cohort 2, respectively, received liver transplantations; the survival rates among the remaining patients were 56% for cohort 2 and 79% for cohort 1 (P < 0.05). The mean age (±standard deviation) of the patients was higher in cohort 2 than in cohort 1 (58 ± 11 vs. 48 ± 13 years; P < 0.01). The percentages of patients with underlying metabolic diseases were 22% in cohort 1 and 61% in cohort 2 (P < 0.01). Diabetic mellitus was more common among deceased patients than among rescued patients (29% vs. 8%; P < 0.05) among patients who did not receive liver transplantations, and a multivariate analysis revealed that patient age and disease type were significantly and independently associated with the outcome. CONCLUSION The outcomes of recent patients with ALF or LOHF caused by HAV infection have recently worsened mainly because of an increase in underlying metabolic diseases as a consequence of aging.
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Affiliation(s)
- Masamitsu Nakao
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Nobuaki Nakayama
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Yoshihito Uchida
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Tomoaki Tomiya
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Makoto Oketani
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.,Department of Medicine, Yoshinohigashi Home Clinic, Kagoshima, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Hirohito Tsubouchi
- Department of Gastroenterology and Hepatology, Kagoshima City Hospital, Kagoshima, Japan
| | - Hajime Takikawa
- Faculty of Medical Technology, Teikyo University, Tokyo, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
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21
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Warrillow S, Bailey M, Pilcher D, Kazemi A, McArthur C, Young P, Bellomo R. Characteristics and outcomes of patients with acute liver failure admitted to Australian and New Zealand intensive care units. Intern Med J 2019; 49:874-885. [PMID: 30479057 DOI: 10.1111/imj.14167] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2018] [Revised: 11/20/2018] [Accepted: 11/20/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND Knowledge about patients with acute liver failure (ALF) in Australia and New Zealand (ANZ) is lacking. AIMS To evaluate whether the pattern of ALF would be similar to previous studies and whether, despite potentially low transplantation rates, mortality would be comparable. METHODS We obtained data from the ANZ Intensive Care Society Adult Patient Database and the ANZ Liver Transplant Registry for 10 years commencing 2005 and analysed for patient outcomes. RESULTS During the study period, 1 022 698 adults were admitted to intensive care units across ANZ, of which 723 had ALF. The estimated annual incidence of ALF over this period was 3.4/million people and increased over time (P = 0.001). ALF patients had high illness severity (Acute Physiology And Chronic Health Evaluation III 79.8 vs 50.1 in non-ALF patients; P < 0.0001) and were more likely to be younger, female, pregnant and immunosuppressed. ALF was an independent predictor of mortality (odds ratio 1.5 (1.26-1.79); P < 0.0001). At less than 23%, the use of liver transplantation was low, but the mortality of 39% was similar to previous studies. CONCLUSIONS ALF is a rare but increasing diagnosis in ANZ intensive care units. Low transplantation rates in ANZ for ALF do not appear to be associated with higher mortality rates than reported in the literature.
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Affiliation(s)
- Stephen Warrillow
- Department of Intensive Care, Austin Health, Melbourne, Australia
- School of Medicine, University of Melbourne, Melbourne, Australia
| | - Michael Bailey
- Australian and New Zealand Intensive Care Research Centre, Monash University School of Public Health and Preventive Medicine, Melbourne, Australia
| | - David Pilcher
- Australian and New Zealand Intensive Care Research Centre, Monash University School of Public Health and Preventive Medicine, Melbourne, Australia
- Department of Intensive Care, Alfred Health, Melbourne, Australia
| | - Alex Kazemi
- Intensive Care Unit, Middlemore Hospital, Auckland, New Zealand
| | - Colin McArthur
- Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand
- Medical Research Institute of New Zealand, Auckland, New Zealand
| | - Paul Young
- Medical Research Institute of New Zealand, Auckland, New Zealand
- Intensive Care Unit, Wellington Hospital, Wellington, New Zealand
| | - Rinaldo Bellomo
- Department of Intensive Care, Austin Health, Melbourne, Australia
- School of Medicine, University of Melbourne, Melbourne, Australia
- Department of Intensive Care, Alfred Health, Melbourne, Australia
- Department of Intensive Care Royal Melbourne Hospital, Melbourne, Australia
- Data Analytics Research and Evaluation (DARE) Centre, Austin Hospital and University of Melbourne, Melbourne, Australia
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22
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Kuwano A, Kohjima M, Suzuki H, Yamasaki A, Ohashi T, Imoto K, Kurokawa M, Morita Y, Kato M, Ogawa Y. Recombinant human soluble thrombomodulin ameliorates acetaminophen-induced liver toxicity in mice. Exp Ther Med 2019; 18:1323-1330. [PMID: 31316624 DOI: 10.3892/etm.2019.7665] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Accepted: 05/21/2019] [Indexed: 12/13/2022] Open
Abstract
Recombinant human soluble thrombomodulin alpha (rhTM) has been developed as an anticoagulant with anti-inflammatory activity. Notably, acetaminophen (APAP) -induced liver disease (AILI) is caused by direct metabolite-induced hepatotoxicity as well as hepatic hyper-coagulation. To evaluate the utility of anticoagulant for the treatment of AILI, rhTM was administered in a mouse AILI model and liver damage was analyzed. AILI was induced in 8-week-old mice by intraperitoneal injection of APAP. rhTM (20 mg/kg) or placebo was injected at the same time as APAP administration. Serum alanine aminotransferase, fibrin degradation products and high-mobility group box 1 levels were significantly decreased in the rhTM-treated group compared with the control group. Furthermore, rhTM reduced the necrotic area and fibrin deposition in liver sections. rhTM suppressed the mRNA expression of heme oxygenase-1, plasminogen activator inhibitor type-1, tissue factors, and inflammatory cytokines compared with the control group. rhTM did not change the hepatic GSH content at 2 h after APAP injection, but restored them at 4 h after the insult. rhTM ameliorated liver damage in mice with AILI, probably via the improvement in liver perfusion induced by it's anticoagulant acitivity, which can lead to the suppression of secondary liver damage.
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Affiliation(s)
- Akifumi Kuwano
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Motoyuki Kohjima
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Hideo Suzuki
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Akihiro Yamasaki
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Tomoko Ohashi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Koji Imoto
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Miho Kurokawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Yusuke Morita
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Masaki Kato
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.,Department of Molecular and Cellular Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.,CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan
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23
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Aljumah AA, Al-Ashgar H, Fallatah H, Albenmousa A. Acute onset autoimmune hepatitis: Clinical presentation and treatment outcomes. Ann Hepatol 2019; 18:439-444. [PMID: 31040094 DOI: 10.1016/j.aohep.2018.09.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Revised: 09/10/2018] [Accepted: 09/13/2018] [Indexed: 02/07/2023]
Abstract
INTRODUCTION AND AIM Autoimmune hepatitis (AIH) may present acutely, which can rapidly progress to fulminant type. This pattern has been described worldwide but is generally under-reported. We aim to describe the clinical presentation and treatment outcomes of patients with acute onset AIH. MATERIALS AND METHODS A multicenter retrospective cohort study of patients with acute onset AIH. Clinical, biochemical, and histological data were analyzed and the outcomes were reported. RESULTS Seventy patients were included. The mean age was 33.8±1.5 years and 58.6% were female. Upon initial presentation, 94% had jaundice, 44% had fatigue, 31% had pruritus, and 29% had abdominal pain. Biochemical analysis revealed elevated alanine transaminase (733±463.6), aspartate transaminase (699±423), and total bilirubin (210±181.8). Antinuclear antibody (ANA) was positive in 61% of patients, anti-smooth muscle antibody (ASMA) in 69%, and both in 31%; immunoglobulin G (IgG) was elevated in 86% of patients. Advanced fibrosis was found in 39%. Complete remission was achieved in 74.3%, two patients required liver transplants and six died. No specific biomarkers were identified as predictive of remission; however, advanced age was associated with poor prognosis. CONCLUSION Acute onset AIH is a disease that requires early diagnosis and management. We confirmed that elevated transaminases are the hallmark of biochemical presentation of acute AIH. High IgG, ANA and ASMA are typically present in such patients upon presentation, however, their absence does not totally exclude the diagnosis. Initial response to treatment was excellent; however, the long-term mortality was higher than the general patient population.
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Affiliation(s)
- Abdulrahman A Aljumah
- Hepatology Division, Department of Hepatobiliary Sciences and Organ Transplant Center, King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
| | - Hamad Al-Ashgar
- Section of Gastroenterology, Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Hind Fallatah
- Division of Gastroenterology and Hepatology, Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ali Albenmousa
- Department of Gastroenterology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
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24
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Abstract
Extracorporeal liver support (ECLS) emerged from the need stabilize high-acuity liver failure patients with the highest risk of death. The goal is to optimize the hemodynamic, neurologic, and biochemical parameters in preparation for transplantation or to facilitate spontaneous recovery. Patients with acute liver failure and acute-on-chronic liver failure stand to benefit from these devices, especially because they have lost many of the primary functions of the liver, including detoxifying the blood of various endogenous and exogenous substances, manufacturing circulating proteins, secreting bile, and storing energy. Existing ECLS devices are designed to mimic some of these functions.
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Affiliation(s)
- Prem A Kandiah
- Division of Neuro Critical Care & co appt. in 5E Surgical/Transplant Critical Care, Department of Neurosurgery, Emory University Hospital, 1364 Clifton Road Northeast, 2nd Floor, 2D ICU- D264, Atlanta, GA 30322, USA; Department of Neurology, Emory University Hospital, 1364 Clifton Road Northeast, 2nd Floor, 2D ICU- D264, Atlanta, GA 30322, USA
| | - Ram M Subramanian
- Critical Care and Hepatology, Emory University, 1364 Clifton Road Northeast, 2nd Floor, 2D ICU- D264, Atlanta, GA 30322, USA.
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25
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Asgari S, Chaturvedi N, Scepanovic P, Hammer C, Semmo N, Giostra E, Müllhaupt B, Angus P, Thompson AJ, Moradpour D, Fellay J. Human genomics of acute liver failure due to hepatitis B virus infection: An exome sequencing study in liver transplant recipients. J Viral Hepat 2019; 26:271-277. [PMID: 30315682 DOI: 10.1111/jvh.13019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Revised: 09/05/2018] [Accepted: 09/10/2018] [Indexed: 12/12/2022]
Abstract
Acute liver failure (ALF) or fulminant hepatitis is a rare, yet severe outcome of infection with hepatitis B virus (HBV) that carries a high mortality rate. The occurrence of a life-threatening condition upon infection with a prevalent virus in individuals without known risk factors is suggestive of pathogen-specific immune dysregulation. In the absence of established differences in HBV virulence, we hypothesized that ALF upon primary infection with HBV could be due to rare deleterious variants in the human genome. To search for such variants, we performed exome sequencing in 21 previously healthy adults who required liver transplantation upon fulminant HBV infection and 172 controls that were positive for anti-HBc and anti-HBs but had no clinical history of jaundice or liver disease. After a series of hypothesis-driven filtering steps, we searched for putatively pathogenic variants that were significantly associated with case-control status. We did not find any causal variant or gene, a result that does not support the hypothesis of a shared monogenic basis for human susceptibility to HBV-related ALF in adults. This study represents a first attempt at deciphering the human genetic contribution to the most severe clinical presentation of acute HBV infection in previously healthy individuals.
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Affiliation(s)
- Samira Asgari
- School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.,Swiss Institute of Bioinformatics, Lausanne, Switzerland.,Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Nimisha Chaturvedi
- School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.,Swiss Institute of Bioinformatics, Lausanne, Switzerland
| | - Petar Scepanovic
- School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.,Swiss Institute of Bioinformatics, Lausanne, Switzerland
| | - Christian Hammer
- School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.,Swiss Institute of Bioinformatics, Lausanne, Switzerland
| | - Nasser Semmo
- Department for BioMedical Research, Hepatology, University of Bern, Bern, Switzerland
| | - Emiliano Giostra
- Department of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland
| | - Beat Müllhaupt
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
| | - Peter Angus
- Gastroenterology and Hepatology Department, Austin Health and the University of Melbourne, Melbourne, Victoria, Australia
| | - Alexander J Thompson
- Department of Gastroenterology, St Vincent's Hospital, University of Melbourne, Melbourne, Australia
| | - Darius Moradpour
- Service of Gastroenterology and Hepatology, Lausanne University Hospital, Lausanne, Switzerland
| | - Jacques Fellay
- School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.,Swiss Institute of Bioinformatics, Lausanne, Switzerland.,Precision Medicine Unit, Lausanne University Hospital, Lausanne, Switzerland
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26
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Fujiwara K, Abe R, Yasui S, Yokosuka O, Kato N, Oda S. High recovery rate of consciousness by high-volume filtrate hemodiafiltration for fulminant hepatitis. Hepatol Res 2019; 49:224-231. [PMID: 30277289 DOI: 10.1111/hepr.13255] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 09/23/2018] [Accepted: 09/26/2018] [Indexed: 12/12/2022]
Abstract
AIM An artificial liver support (ALS) system sustaining patients with acute liver failure (ALF) in good condition until recovery of the native liver or performance of liver transplantation (LT), is essential for the improvement of the poor prognosis of ALF despite the lack of survival benefit. We aimed to investigate the efficacy of various ALS systems for fulminant hepatitis (FH) carried out in our liver unit so far, focusing on the restoration of consciousness from hepatic encephalopathy. METHODS One hundred and ten consecutive adult Japanese patients with FH admitted to Chiba University Hospital (Chiba, Japan) between 1988 and 2016 who received ALS were analyzed. RESULTS Recovery rate of consciousness improved with the increased dialysate flow rate and filtrate rate: 37.5% by plasma exchange (PE), 51.9% by PE + continuous hemodiafiltration (CHDF), 57.7% by slow PE (sPE) + high-flow CHDF (HFCHDF) (QD = 300 mL/min), 88.6% by HFCHDF (QD = 500 mL/min) (+ sPE), and 92.9% by on-line HDF (OLHDF) (+ sPE). All patients except one, who could not be fully treated because of circulatory failure, recovered consciousness by OLHDF, including those whose liver function were completely abolished. Superiority of HFCHDF (QD = 500 mL/min) and OLHDF was also shown in patients who died without LT or received LT. CONCLUSIONS More effective ALS should be recognized considering the extremely high recovery rate of consciousness. In particular, OLHDF with predilution reduces the cost of substitution fluid by supplying an unlimited amount of dialysate as substitution fluid prepared using an on-line system, and simplifies the procedure for the management.
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Affiliation(s)
- Keiichi Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Ryuzo Abe
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shin Yasui
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shigeto Oda
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
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27
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Nakao M, Nakayama N, Uchida Y, Tomiya T, Ido A, Sakaida I, Yokosuka O, Takikawa Y, Inoue K, Genda T, Shimizu M, Terai S, Tsubouchi H, Takikawa H, Mochida S. Nationwide survey for acute liver failure and late-onset hepatic failure in Japan. J Gastroenterol 2018; 53:752-769. [PMID: 29030713 DOI: 10.1007/s00535-017-1394-2] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Accepted: 09/21/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND A nationwide survey was performed to clarify the recent status of acute liver failure (ALF) and late-onset hepatic failure (LOHF) in Japan. METHODS Two-step surveys for patients with ALF and LOHF meeting the Japanese diagnostic criteria were performed annually in 782 hospitals. The clinical features of the patients were then compared to those reported in previous surveys. RESULTS In total, 1554 and 49 patients with ALF and LOHF, respectively, who were seen between 2010 and 2015 were enrolled. The subjects were classified into 1280 patients with hepatitis (642 non-comatose and 638 comatose) and 323 patients without hepatitis (190 non-comatose and 133 comatose). Compared with patients seen between 1998 and 2009, an older patient age and a higher percentage of underlying extrahepatic disease were observed. Although hepatitis virus infection was the most frequent etiology, the percentage of patients with this etiology had decreased, compared with previous cohorts, while the percentages of patients with drug-induced liver injuries, autoimmune hepatitis, and an indeterminate etiology had increased. Liver transplantation was performed in 170 patients (10.6%), whereas artificial liver support with plasmapheresis and/or hemodiafiltration were performed for most of the comatose patients. The outcomes of comatose patients were unfavorable, similar to previous surveys, especially the outcomes of hepatitis B virus carriers, including those with de novo hepatitis B (survival rate of 5.4% without liver transplantation). CONCLUSION Although the clinical features, including the etiologies, of patients with ALF and LOHF have changed, the outcomes of patients have not improved in recent years.
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Affiliation(s)
- Masamitsu Nakao
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-Cho, Iruma-Gun, Saitama, 350-0495, Japan
| | - Nobuaki Nakayama
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-Cho, Iruma-Gun, Saitama, 350-0495, Japan
| | - Yoshihito Uchida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-Cho, Iruma-Gun, Saitama, 350-0495, Japan
| | - Tomoaki Tomiya
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-Cho, Iruma-Gun, Saitama, 350-0495, Japan
| | - Akio Ido
- Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Isao Sakaida
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | | | - Yasuhiro Takikawa
- Department of Gastroenterology and Hepatology, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Kazuaki Inoue
- Department of Gastroenterology, Showa University Fujigaoka Hospital, Yokohama, Japan
| | - Takuya Genda
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Masahito Shimizu
- Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata, Japan
| | | | - Hajime Takikawa
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-Cho, Iruma-Gun, Saitama, 350-0495, Japan.
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28
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Fujiwara K, Yasui S, Haga Y, Nakamura M, Yonemitsu Y, Arai M, Kanda T, Oda S, Yokosuka O, Kato N. Early Combination Therapy with Corticosteroid and Nucleoside Analogue Induces Rapid Resolution of Inflammation in Acute Liver Failure due to Transient Hepatitis B Virus Infection. Intern Med 2018; 57:1543-1552. [PMID: 29321429 PMCID: PMC6028684 DOI: 10.2169/internalmedicine.9670-17] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Objective Patients with acute hepatitis B sometimes develop acute liver failure (ALF), which has a poor prognosis. The efficacy of nucleoside analogue (NA) monotherapy for ALF due to transient hepatitis B virus infection (HBV-ALF) remains controversial. Further investigations are necessary in nations with a shortage of donor livers for liver transplantation. In the present study, we aimed to clarify the efficacy of combination therapy with corticosteroid (CS) and NA in the treatment HBV-ALF. Patients We examined the clinical and biochemical features of 19 patients with HBV-ALF who were treated in the early stage of the disease between 2000 and 2015. Results Fourteen patients received CS and NA (CS + NA group) and 5 received NA monotherapy (NA group). Eleven patients (58%) survived and 8 (42%) died. The survival rates in the CS + NA and NA groups were 64% and 40%, respectively (p=0.60). The mean alanine aminotransferase (ALT) levels declined significantly at week 2 in both groups. The mean PT activities improved significantly at weeks 1 and 2 in the CS + NA group (p<0.05) but not in the NA group. None of the surviving patients developed persistent infection. Conclusion Combination therapy with CS and NA induces the rapid resolution of inflammation leading to a rapid recovery of the liver function. When it is administered at a sufficiently early stage, it would have a survival benefit and prevent persistent infection in HBV-ALF.
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Affiliation(s)
- Keiichi Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Shin Yasui
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Yuuki Haga
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Masato Nakamura
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Yutaka Yonemitsu
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Makoto Arai
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Shigeto Oda
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
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29
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Fujiwara K, Hida S, Yasui S, Yokosuka O, Oda S. Corticosteroid might reduce serum levels of pro-inflammatory cytokines in fulminant hepatitis: A case series. Hepatol Res 2018; 48:106-112. [PMID: 28422386 DOI: 10.1111/hepr.12906] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 04/06/2017] [Accepted: 04/15/2017] [Indexed: 01/11/2023]
Abstract
AIM There are no beneficial therapies except for emergency liver transplantation for acute liver failure (ALF). However, in Japan, which has a serious problem in the shortage of donor livers, therapies other than transplantation must be further investigated for patients with ALF. Pro-inflammatory cytokines promoting tissue destruction are predominant at an early phase of ALF. Corticosteroid (CS) influences monocyte/macrophage differentiation, by suppressing pro-inflammatory genes, indicating CS treatment might be beneficial during the early phase of ALF. Our aim was to elucidate the efficacy of CS pulse therapy in decreasing pro-inflammatory cytokine levels in the early stage of ALF. METHODS Ten consecutive adult Japanese patients with fulminant hepatitis in the early stage, three treated with artificial liver support (ALS) and CS pulse therapy (ALS + CS group) and seven treated with ALS (ALS group), were enrolled. Clinical and biochemical data on admission were matched between the groups and retrospectively analyzed for serum concentrations of interleukin-6, tumor necrosis factor-α, and interleukin-1β over a 2-week period. RESULTS Mean cytokine levels on admission were not different between the two groups. Tumor necrosis factor-α was significantly reduced on day 7 in patients with CS. Serum levels of pro-inflammatory cytokines tended to be reduced in patients with CS compared to those without during the observation period, although the differences were not significant. CONCLUSIONS It might be possible that introduction of CS pulse therapy in the early stage of ALF could reduce levels of pro-inflammatory cytokines, which might inhibit the cascade of progression of ALF.
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Affiliation(s)
- Keiichi Fujiwara
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Seiji Hida
- Department of Anesthesiology, Niigata Tokamachi Hospital, Tokamachi, Japan
| | - Shin Yasui
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shigeto Oda
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
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30
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Fujiwara K, Yasui S, Yokosuka O, Oda S, Kato N. Diagnostic utility of radiological heterogeneity in acute severe (fulminant) autoimmune hepatitis. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2017; 24:485-491. [PMID: 28660716 DOI: 10.1002/jhbp.487] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND Histological examination is useful for the diagnosis of acute severe (fulminant) autoimmune hepatitis (AIH), but it is sometimes difficult to perform liver biopsy due to the complicated coagulopathy and ascites. We have shown that heterogeneous hypoattenuation on unenhanced computed tomography (CT) is a characteristic imaging feature of acute severe (fulminant) AIH. In the present study, we examined the utility of the imaging feature by applying the score to diagnose acute severe (fulminant) AIH. METHODS Twenty-three patients with acute severe (fulminant) AIH were analyzed retrospectively. Modified AIH score was created by adding three points to AIH score with/without histological points in case of the presence of heterogeneous hypoattenuation on unenhanced CT. RESULTS Areas of hypoattenuation were present in 15 (65%) patients, all of which were heterogeneous pattern. Five (22%) patients were diagnosed as "definite" AIH, 16 (69%) as "probable" and two (9%) as "non-diagnosis" by the revised original score without histological score. By adding three points, two of "non-diagnosis" changed to "probable" AIH, and all patients were diagnosed as AIH. CONCLUSIONS Modified AIH score using heterogeneous CT image finding would be beneficial especially for patients in whom histological examinations cannot be performed because of complications.
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Affiliation(s)
- Keiichi Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
| | - Shin Yasui
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
| | - Shigeto Oda
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
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31
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Moini M, Pahlevan-Sabagh MR, Dehghani SM. Acute Liver Failure, Etiology, and Outcome: An Experience in a Referral Liver Transplant Center. HEPATITIS MONTHLY 2017; 17. [DOI: 10.5812/hepatmon.14086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Tadokoro T, Morishita A, Sakamoto T, Fujihara S, Fujita K, Mimura S, Oura K, Nomura T, Tani J, Yoneyama H, Iwama H, Himoto T, Niki T, Hirashima M, Masaki T. Galectin‑9 ameliorates fulminant liver injury. Mol Med Rep 2017; 16:36-42. [PMID: 28534962 PMCID: PMC5482106 DOI: 10.3892/mmr.2017.6606] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Accepted: 03/16/2017] [Indexed: 01/21/2023] Open
Abstract
Fulminant hepatitis is a severe liver disease resulting in hepatocyte necrosis. Galectin-9 (Gal-9) is a tandem-repeat-type galectin that has been evaluated as a potential therapeutic agent for various diseases that regulate the host immune system. Concanavalin A (ConA) injection into mice results in serious, immune-mediated liver injury similar to human viral, autoimmune and fulminant hepatitis. The present study investigated the effects of Gal-9 treatment on fulminant hepatitis in vivo and the effect on the expression of microRNAs (miRNAs), in order to identify specific miRNAs associated with the immune effects of Gal-9. A ConA-induced mouse hepatitis model was used to investigate the effects of Gal-9 treatment on overall survival rates, liver enzymes, histopathology and miRNA expression levels. Histological analyses, TUNEL assay, immunohistochemistry and miRNA expression characterization, were used to investigate the degree of necrosis, fibrosis, apoptosis and infiltration of neutrophils and macrophages. Overall survival rates following ConA administration were significantly higher in Gal-9-treated mice compared with control mice treated with ConA + PBS. Histological examination revealed that Gal-9 attenuated hepatocellular damage, reduced local neutrophil infiltration and prevented the local accumulation of macrophages and liver cell apoptosis in ConA-treated mice. In addition, various miRNAs induced by Gal-9 may contribute to its anti-apoptotic, anti-inflammatory and pro-proliferative effects on hepatocytes. The results of the present study demonstrate that Gal-9 may be a candidate therapeutic target for the treatment of fulminant hepatitis.
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Affiliation(s)
- Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761‑0793, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761‑0793, Japan
| | - Teppei Sakamoto
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761‑0793, Japan
| | - Shintaro Fujihara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761‑0793, Japan
| | - Koji Fujita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761‑0793, Japan
| | - Shima Mimura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761‑0793, Japan
| | - Kyoko Oura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761‑0793, Japan
| | - Takako Nomura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761‑0793, Japan
| | - Joji Tani
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761‑0793, Japan
| | - Hirohito Yoneyama
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761‑0793, Japan
| | - Hisakazu Iwama
- Life Science Research Center, Faculty of Medicine, Kagawa University, Kagawa 761‑0793, Japan
| | - Takashi Himoto
- Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Kagawa 761‑0123, Japan
| | - Toshiro Niki
- Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Kagawa 761‑0793, Japan
| | - Mitsuomi Hirashima
- Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Kagawa 761‑0793, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761‑0793, Japan
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Schwartz J, Padmanabhan A, Aqui N, Balogun RA, Connelly-Smith L, Delaney M, Dunbar NM, Witt V, Wu Y, Shaz BH. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue. J Clin Apher 2017; 31:149-62. [PMID: 27322218 DOI: 10.1002/jca.21470] [Citation(s) in RCA: 276] [Impact Index Per Article: 34.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Joseph Schwartz
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York
| | - Anand Padmanabhan
- Blood Center of Wisconsin, Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Nicole Aqui
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Rasheed A Balogun
- Division of Nephrology, University of Virginia, Charlottesville, Virginia
| | - Laura Connelly-Smith
- Department of Medicine, Seattle Cancer Care Alliance and University of Washington, Seattle, Washington
| | - Meghan Delaney
- Bloodworks Northwest, Department of Laboratory Medicine, University of Washington, Seattle, Washington
| | - Nancy M Dunbar
- Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
| | - Volker Witt
- Department for Pediatrics, St. Anna Kinderspital, Medical University of Vienna, Vienna, Austria
| | - Yanyun Wu
- Bloodworks Northwest, Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut
| | - Beth H Shaz
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.,New York Blood Center, Department of Pathology.,Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia
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Uehara S, Fukuzawa Y, Matuyama T, Gotoh K. Role of Tyro3, Axl, and Mer Receptors and Their Ligands (Gas6, and Protein S) in Patients with Hepatocellular Carcinoma. ACTA ACUST UNITED AC 2017. [DOI: 10.4236/jct.2017.82010] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Yasui S, Fujiwara K, Haga Y, Nakamura M, Mikata R, Arai M, Kanda T, Oda S, Yokosuka O. Infectious complications, steroid use and timing for emergency liver transplantation in acute liver failure: analysis in a Japanese center. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2016; 23:756-762. [PMID: 27629813 DOI: 10.1002/jhbp.399] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 09/12/2016] [Indexed: 12/31/2022]
Abstract
BACKGROUND Corticosteroid (CS) has been introduced in most acute liver failure (ALF) patients for the purpose of suppressing pro-inflammatory cytokines in Japan where a shortage of donor livers exists, whereas CS use is evaluated to be no benefit in Western countries. In the present study, we aimed to clarify the association between infectious complications and CS use in ALF, and determine when to evaluate treatment response and consider the timing for switching to liver transplantation (LT). METHODS Corticosteroid was administered to patients in the early stage prospectively. Clinical and biochemical features of 110 adult patients were analyzed. RESULTS Corticosteroids were administered to 78 (71%) patients. The duration between start of CS and onset of infection was 17 ± 10 days. Multivariate analysis revealed that infection was associated with age >50 years (P = 0.034) and T-BIL >15 mg/dl (P < 0.001), and not with CS use (P = 0.10). Accumulative incidence of infection was not different between patients with and without CS (P = 0.18). CONCLUSIONS Corticosteroid use did not significantly increase the incidence of infection. Two weeks after introduction of CS is a critical point for evaluating treatment response, avoiding infectious complications and switching to LT.
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Affiliation(s)
- Shin Yasui
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Keiichi Fujiwara
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Yuuki Haga
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Masato Nakamura
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Rintaro Mikata
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Makoto Arai
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Shigeto Oda
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
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Mochida S, Nakao M, Nakayama N, Uchida Y, Nagoshi S, Ido A, Mimura T, Harigai M, Kaneko H, Kobayashi H, Tsuchida T, Suzuki H, Ura N, Nakamura Y, Bessho M, Dan K, Kusumoto S, Sasaki Y, Fujii H, Suzuki F, Ikeda K, Yamamoto K, Takikawa H, Tsubouchi H, Mizokami M. Nationwide prospective and retrospective surveys for hepatitis B virus reactivation during immunosuppressive therapies. J Gastroenterol 2016; 51:999-1010. [PMID: 26831356 DOI: 10.1007/s00535-016-1168-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Accepted: 01/07/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND The significance of HBV reactivation during immunosuppressive therapy was evaluated in three nationwide cohorts including patients with previously resolved HBV (prHBV) infection. METHODS The clinical features of 1061 patients with acute liver failure (ALF) or late-onset hepatic failure (LOHF) were retrospectively examined, focusing on those who experienced HBV reactivation. Additionally, 420 patients with prHBV infection were prospectively enrolled: 203 received immunosuppressive therapies immediately after enrollment, while the remaining 217 were enrolled after having received immunosuppressive therapies without the occurrence of HBV reactivation. The serum HBV-DNA levels were prospectively monitored every month, and the incidences of HBV reactivation, defined as a serum HBV-DNA level of 1.3 log IU/ml or more, were evaluated. RESULTS In the retrospective study, persistent HBV infection was found in 90 patients, and HBV reactivation was responsible for liver injuries in 50 patients including 23 receiving immunosuppressive therapies (26 with HBs-antigen positivity, 7 with prHBV infection). None of seven patients with prHBV infection were rescued. In the prospective studies, HBV reactivation occurred in ten patients, but preemptive entecavir administration prevented liver injury. The cumulative reactivation rate was 3.2 % at 6 months, and the increase of the rate compared to that at 6 months was +1.5 % at 48 months. CONCLUSIONS HBV reactivation during immunosuppression was responsible for liver injuries in a quarter of the ALF/LOHF patients with persistent HBV infection. Early serum HBV-DNA monitoring may improve patient prognosis, since HBV reactivation typically occurs within 6 months of the start of immunosuppressive therapies in patients with prHBV infection.
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Affiliation(s)
- Satoshi Mochida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan.
| | - Masamitsu Nakao
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Nobuaki Nakayama
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Yoshihito Uchida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Sumiko Nagoshi
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan
| | - Akio Ido
- Department of Digestive and Lifestyle Related Diseases, Human and Enviromental Sciences, Health Research, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan
| | - Toshihide Mimura
- Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama, Japan
| | - Masayoshi Harigai
- Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hiroshi Kaneko
- Division of Rheumatic Diseases, National Center for Global Health and Medicine, Tokyo, Japan
| | - Hiroko Kobayashi
- Department of Gastroenterology and Rheumatology, School of Medicine, Fukushima Medical University, Fukushima, Japan
| | - Tetsuya Tsuchida
- Department of Dermatology, Saitama Medical University, Saitama, Japan
| | - Hiromichi Suzuki
- Department of Nephrology, Saitama Medical University, Saitama, Japan
| | - Nobuyuki Ura
- Department of Nephrology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Yuichi Nakamura
- Department of Hematology, Saitama Medical University, Saitama, Japan
| | - Masami Bessho
- Department of Hematology, Saitama Medical University, Saitama, Japan
| | - Kazuo Dan
- Department of Hematology, Nippon Medical School, Tokyo, Japan
| | - Shigeru Kusumoto
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Science, Nagoya, Japan
| | - Yasutsuna Sasaki
- Department of Medical Oncology, International Medical Cnter/Comprehensive Cancer Center, Saitama Medical University, Saitama, Japan
| | - Hirofumi Fujii
- Department of Clinical Oncology, Jichi Medical University, Shimotsuke, Japan
| | | | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Kazuhiko Yamamoto
- Department of Allergy and Pheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Hajime Takikawa
- Department of Medicine, Teikyo University of School of Medicine, Tokyo, Japan
| | - Hirohito Tsubouchi
- Department of Digestive and Lifestyle Related Diseases, Human and Enviromental Sciences, Health Research, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan
| | - Masashi Mizokami
- The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan
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Acute Disseminated Encephalomyelitis. J Clin Apher 2016; 31:163-202. [PMID: 27322219 DOI: 10.1002/jca.21474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Mochida S, Nakayama N, Ido A, Takikawa Y, Yokosuka O, Sakaida I, Moriwaki H, Genda T, Takikawa H. Revised criteria for classification of the etiologies of acute liver failure and late-onset hepatic failure in Japan: A report by the Intractable Hepato-biliary Diseases Study Group of Japan in 2015. Hepatol Res 2016; 46:369-71. [PMID: 26615003 DOI: 10.1111/hepr.12626] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 11/17/2015] [Indexed: 02/08/2023]
Abstract
In 2011, the Intractable Liver Diseases Study Group of Japan, established novel diagnostic criteria for "acute liver failure ", and published the classification criteria for the etiologies of acute liver failure and late-onset hepatic failure (LOHF) in 2013. According to this classification, HBV carriers showing acute hepatitis exacerbation were divided into 3 subgroups; asymptomatic or inactive HBV carriers without drug exposure, asymptomatic or inactive HBV carriers developing HBV reactivation during and after immunosuppressive therapies and/or antineoplastic chemotherapies and those with previously resolved HBV infection showing iatrogenic HBV reactivation. In an annual nationwide survey in 2013, however, a patient with previously resolved HBV infection was enrolled, in whom LOHF developed as a result of HBV reactivation despite in the absence of immunosuppressive therapies and/or antineoplastic chemotherapies. Thus, the study group revised the classification criteria in 2015; HBV carriers developing acute hepatitis exacerbation were classified into asymptomatic or inactive HBV carriers and patients with previously resolved HBV infection, and both groups were further sub-classified into those receiving immunosuppressive therapies and/or antineoplastic chemotherapies and those without such drugs exposure.
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Affiliation(s)
- Satoshi Mochida
- Department of Gastroenterology and Hepatology, Saitama Medical University, Moroyama-Machi, Japan
| | - Nobuaki Nakayama
- Department of Gastroenterology and Hepatology, Saitama Medical University, Moroyama-Machi, Japan
| | - Akio Ido
- Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Yasuhiro Takikawa
- Department of Gastroenterology and Hepatology, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Isao Sakaida
- Department of Gastroenterology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Hisataka Moriwaki
- Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Takuya Genda
- Department of Gastroenterology, Shizuoka Hospital, Juntendo University, Izunokuni, Japan
| | - Hajime Takikawa
- Department of Medicine, School of Medicine, Teikyo University, Tokyo, Japan
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Fujiwara K, Yasui S, Yonemitsu Y, Arai M, Kanda T, Fukuda Y, Nakano M, Oda S, Yokosuka O. Analysis of infectious complications and timing for emergency liver transplantation in autoimmune acute liver failure. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2016; 23:212-9. [PMID: 26808231 DOI: 10.1002/jhbp.326] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Accepted: 01/20/2016] [Indexed: 12/20/2022]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is one of major etiologies of acute liver failure (ALF), and the survival rate without liver transplantation (LT) of patients with fulminant AIH is especially poor worldwide. We investigated the clinicopathological features of infectious complications in autoimmune ALF retrospectively and tried to determine when to continue corticosteroid (CS) treatment or abandon it for LT. METHODS Twenty patients with autoimmune ALF, comprising five severe hepatitis, 13 fulminant hepatitis and two late onset hepatic failure, were analyzed. RESULTS Corticosteroids were administered to 19 patients. Seventeen infectious complications were observed in 12 patients. The median (range) duration between the introduction of CS and onset of infection was 15 (10–41) days. There were no significant differences in clinicobiochemical features between patients with and without infection. Of 20 patients, eight (40%) recovered without LT, four (20%) received LT and eight (40%) died without LT. Dead or transplanted patients had more advanced liver failure on admission than recovered ones (P < 0.01). CONCLUSIONS Two-week after the introduction of CS is a critical point for avoiding infectious complications. Therefore, we should have evaluated efficacy of CS and performed LT by then at the latest in case of failure to improve.
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Affiliation(s)
- Keiichi Fujiwara
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
| | - Shin Yasui
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Yutaka Yonemitsu
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Makoto Arai
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Yoshihiro Fukuda
- Department of Gastroenterology, Seikeikai Chiba Medical Center, Chiba, Japan
| | - Masayuki Nakano
- Division of Pathology, Shonan Fujisawa Tokushukai Hospital, Fujisawa, Japan
| | - Shigeto Oda
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
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Tanaka H, Sasaki H, Arita M. An elderly female with rib osteolytic lesion after recovery from fulminant liver failure induced by acute‐onset autoimmune hepatitis. Clin Case Rep 2016; 4:186-91. [PMID: 26862420 PMCID: PMC4736527 DOI: 10.1002/ccr3.452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Revised: 10/04/2015] [Accepted: 10/22/2015] [Indexed: 11/13/2022] Open
Abstract
This report highlights an interesting case of an osteolytic lesion (actinomycosis) after fulminant liver failure induced by autoimmune hepatitis (AIH). When treating patients with fulminant liver failure due to AIH using immunosuppressive drugs, such as steroids, the possibility of such rare occurrences should be kept in mind.
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Affiliation(s)
- Hiroto Tanaka
- The Department of Internal Medicine Kihoku Hospital Wakayama Medical University Japan
| | - Hideyuki Sasaki
- The Department of Internal Medicine Kihoku Hospital Wakayama Medical University Japan
| | - Mikio Arita
- The Department of Internal Medicine Kihoku Hospital Wakayama Medical University Japan
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Fujiwara K, Yokosuka O, Inoue K, Yasui S, Abe R, Oda S, Arata S, Takikawa Y, Ido A, Mochida S, Tsubouchi H, Takikawa H. Distribution of core hospitals for patients with fulminant hepatitis and late onset hepatic failure in Japan. Hepatol Res 2016; 46:10-12. [PMID: 26096326 DOI: 10.1111/hepr.12543] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Revised: 06/01/2015] [Accepted: 06/05/2015] [Indexed: 02/08/2023]
Affiliation(s)
- Keiichi Fujiwara
- Departments of Gastroenterology and Nephrology, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Departments of Gastroenterology and Nephrology, Chiba University, Chiba, Japan
| | - Kazuaki Inoue
- Division of Gastroenterology, Showa University Fujigaoka Hospital, Yokohama, Japan
| | - Shin Yasui
- Departments of Gastroenterology and Nephrology, Chiba University, Chiba, Japan
| | - Ryuzo Abe
- Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shigeto Oda
- Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shinju Arata
- Yokohama City University School of Medicine, Yokohama, Japan
| | - Yasuhiro Takikawa
- Department of Gastroenterology and Hepatology, Iwate Medical University, Morioka, Japan
| | - Akio Ido
- Department of Digestive and Lifestyle Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Satoshi Mochida
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Saitama Medical University, Moroyama, Japan
| | | | - Hajime Takikawa
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
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Fujiwara K, Yasui S, Nakano M, Yonemitsu Y, Arai M, Kanda T, Fukuda Y, Oda S, Yokosuka O. Severe and fulminant hepatitis of indeterminate etiology in a Japanese center. Hepatol Res 2015; 45:E141-9. [PMID: 25582192 DOI: 10.1111/hepr.12483] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Revised: 12/22/2014] [Accepted: 01/05/2015] [Indexed: 02/08/2023]
Abstract
AIM The outcome of acute liver failure (ALF) is influenced by its etiology, making etiological consideration of ALF important. However, specific etiology could not be identified in 30-40% of adult patients in a Japanese nationwide survey. We examined our patients with severe (SH) and fulminant hepatitis (FH) of indeterminate etiology for the better understanding of ALF. METHODS We investigated 106 adult patients with SH or FH including 24 of indeterminate etiology between 2000 and 2013, retrospectively. RESULTS Of 24 patients, 12 were men. Seventeen were SH and seven FH (three FH acute type and four FH subacute type). Eighty-three percent of patients were positive for antinuclear antibody. Seventeen recovered without liver transplantation (LT), two received LT and five died without LT. Histology of 15 patients showed a pattern of acute hepatitis (massive necrosis in four, submassive necrosis in one, severe acute hepatitis in two and acute hepatitis in eight). The involvement of immune-mediated liver injury was histologically suggested in some patients. CONCLUSION There was no large cluster of etiology in our patients with indeterminate cause. The causes of ALF of indeterminate etiology were the mixture of various minor or rare ones, if precise diagnosis of acute AIH was done. Outcome of our patients with indeterminate cause was not poor if they were treated as early as possible after the diagnosis of severe disease. Careful examination of unknown viral infection, drugs, toxins, undefined metabolic disorders and histology may help detect some of these etiologies.
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Affiliation(s)
| | - Shin Yasui
- Departments of Gastroenterology and Nephrology
| | - Masayuki Nakano
- Division of Pathology, Shonan Fujisawa Tokushukai Hospital, Fujisawa, Japan
| | | | - Makoto Arai
- Departments of Gastroenterology and Nephrology
| | | | - Yoshihiro Fukuda
- Department of Gastroenterology, Seikeikai Chiba Medical Center, Chiba
| | - Shigeto Oda
- Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University
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Fujiwara K, Yasui S, Yonemitsu Y, Arai M, Kanda T, Nakano M, Oda S, Yokosuka O. Importance of the poor prognosis of severe and fulminant hepatitis in the elderly in an era of a highly aging society: Analysis in a Japanese center. Hepatol Res 2015; 45:863-71. [PMID: 25238570 DOI: 10.1111/hepr.12426] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2014] [Revised: 08/22/2014] [Accepted: 09/12/2014] [Indexed: 01/11/2023]
Abstract
AIM Older age has been widely believed to be associated with a poor prognosis of acute liver failure. We aimed to evaluate the impact of older age on outcomes of Japanese patients with severe and fulminant hepatitis in an era of a highly aging society. METHODS We investigated 105 consecutive adult patients with fulminant hepatitis (FH) or severe hepatitis (SH) admitted to our liver unit between 2000 and 2013, consisting of 14 elderly patients (≥65 years) and 91 younger ones (<65 years). RESULTS In elderly patients, the proportion of women was greater (P < 0.001), the levels of aspartate aminotransferase and lactate dehydrogenase on admission were lower (P = 0.011 and P = 0.010, respectively), and the survival rate without liver transplantation was lower (P = 0.024) than younger ones. Two of seven SH and all seven FH elderly patients died, whereas all 45 SH and 16 of 46 FH younger patients recovered. Seventy-one percent of elderly patients had underlying diseases with medications, and 57% had additional complications after the start of treatment for acute liver failure. Patients aged 70 years or more showed even poorer prognoses than younger ones and those aged 65-69 years (P = 0.0052 and P = 0.036, respectively). CONCLUSION Older age was associated with a poor prognosis of patients with SH and FH. One of the reasons other than complications and loss of organ reserve by aging would be that elderly patients consulted us at a more advanced stage of illness than younger ones.
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Affiliation(s)
- Keiichi Fujiwara
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shin Yasui
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yutaka Yonemitsu
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Makoto Arai
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | | | - Shigeto Oda
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
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Kurokohchi K, Imataki O, Kubo F. Anti-inflammatory effect of recombinant thrombomodulin for fulminant hepatic failure. World J Gastroenterol 2015; 21:8203-8207. [PMID: 26185395 PMCID: PMC4499366 DOI: 10.3748/wjg.v21.i26.8203] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2014] [Revised: 03/01/2015] [Accepted: 03/19/2015] [Indexed: 02/06/2023] Open
Abstract
Fulminant hepatic failure (FHF) is a critical illness that can be comorbid to primary liver damage. FHF shows a high mortality rate, and patients with FHF require intensive therapy, including plasma apheresis. However, intensive care at the present is not enough to restore the severe liver damage or promote hepatocellular reproduction, and a standard therapy for the treatment of FHF has not been established. An 86-year-old female with FHF was admitted to our hospital. Her manifestation demonstrated a clinical situation of systemic inflammatory response syndrome (SIRS) and disseminated intravascular coagulation. A diagnosis of fulminant hepatitis was made according to the definition given in the position paper of the American Association for the Study of Liver Diseases. Her serum hepatocyte growth factor (HGF) level had increased to 11.84 ng/mL. The HGF level indicated massive liver damage as seen in FHF. Recombinant thrombomodulin (rTM) was administered daily from the admission day for 1 wk at 380 U/kg. The patient’s white blood cells and C-reactive protein responded to the rTM treatment within a few days. The HGF level and PT recovered to the normal range. The levels of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) were suppressed by the administration of rTM. The patient’s hepatic function (e.g., PT and albumin) completely recovered without plasma exchange. rTM may modulate the over-response of SIRS with the improvement of proinflammatory cytokines. The underlying mechanism is thought to be the inhibitory effect of rTM on high-mobility group box 1 (HMBG1). The pathogenesis of HMBG1 protein in fulminant hepatic failure has been already known. A novel favorable effect of rTM for SIRS would be promising for FHF, and the wide application of rTM for SIRS should be considered.
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Kuroda H, Kakisaka K, Oikawa T, Onodera M, Miyamoto Y, Sawara K, Endo R, Suzuki K, Takikawa Y. Liver stiffness measured by acoustic radiation force impulse elastography reflects the severity of liver damage and prognosis in patients with acute liver failure. Hepatol Res 2015; 45:571-7. [PMID: 25041122 DOI: 10.1111/hepr.12389] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2014] [Revised: 07/02/2014] [Accepted: 07/06/2014] [Indexed: 02/01/2023]
Abstract
AIM We measured liver stiffness (LS) in patients with acute liver failure (ALF) using acoustic radiation force impulse (ARFI) elastography and investigated the usefulness of measuring LS for predicting the prognosis of ALF patients. METHODS From April 2010 to December 2013, we evaluated 63 patients with acute liver disease. The subjects included 41 patients with acute hepatitis (AH), 16 patients with severe AH (SAH), who had no hepatic encephalopathy despite plasma prothrombin time of 40% or less, and six patients with fulminant hepatitis (FH) diagnosed according to the criteria of the Japanese Study Group. The relationships among shear wave velocity (SWV), clinical diagnosis, liver function tests and prognosis were evaluated. Receiver-operator curve (ROC) analysis was performed to investigate whether ARFI elastography exhibits potential usefulness for the prediction of FH. RESULTS The mean SWV on admission were 1.98 ± 0.55, 2.61 ± 0.58 and 3.66 ± 0.86 m/s in the AH, SAH and FH groups, respectively. The SWV was significantly higher in the FH group than in the other groups (P < 0.001), and in the SAH group than in the AH group (P = 0.002). The area under the ROC for predicting FH was 0.924 (sensitivity, 83.3%; specificity, 93.0%). The SWV was significantly increased in non-survivors, while remaining decreased in survivors (P = 0.002). CONCLUSION The SWV measured by ARFI elastography reflects severity of liver damage, and serial changes in SWV predict the prognosis of ALF patients. The SWV is an early and precise biomarker of FH.
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Affiliation(s)
- Hidekatsu Kuroda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
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Minami S, Shibata M, Matsuhashi T, Hiura M, Abe S, Harada M. Acute Liver Failure Complicated with Severe Heart Failure. Intern Med 2015; 54:2443-7. [PMID: 26424300 DOI: 10.2169/internalmedicine.54.2913] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
A young pregnant woman was hospitalized due to hepatitis B virus (HBV)-related acute liver failure (ALF). The cardiac function was normal on admission. However, she developed ALF concurrently with a coma and severe cardiac failure. The patient was diagnosed with severe acute cardiomyopathy due to diffuse hypokinesis of the left ventricle wall on ultrasound cardiography. Following intensive treatment, both the liver and cardiac function dramatically recovered. Although some factors, such as HBV, pregnancy and systemic inflammatory response syndrome, are possible causes of acute cardiomyopathy in the present case, ALF itself may be a risk factor for heart failure.
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Affiliation(s)
- Sota Minami
- The Third Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Japan
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Fujiwara K, Yasui S, Yonemitsu Y, Arai M, Kanda T, Nakano M, Oda S, Yokosuka O. Fixed point observation of etiology of acute liver failure according to the novel Japanese diagnostic criteria. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2014; 22:225-9. [PMID: 25339364 DOI: 10.1002/jhbp.178] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
BACKGROUND There has existed important differences in the definition of acute liver failure (ALF) between Japanese criteria and those of other countries. The novel diagnostic criteria for ALF in Japanese patients were established by the Intractable Hepato-Biliary Diseases Study Group of Japan, in order to correspond to those for ALF in Europe and the USA. We prospectively diagnosed our ALF patients based on this novel criteria, and discussed the etiology by a fixed point observation. METHODS We investigated the etiology of 54 adult inpatients and outpatients with ALF between 2010 and 2012. RESULTS Of 54 patients, 36 were ALF without coma, 17 ALF with coma and one late onset hepatic failure. The etiology was due to viral infections in 38.9%, autoimmune hepatitis in 11.1%, drug-induced liver injury in 13.0%, etiologies without hepatitis in 29.6% (circulatory disturbance in 18.5%, infiltration of the liver by malignant cells in 7.4%, and metabolic diseases in 3.7%) and indeterminate causes in 7.4%. CONCLUSIONS Circulatory disturbance was the most frequent etiology according to the novel criteria. Indeterminate etiology was less observed in our study than the nation-wide survey with significance (P = 0.0014).
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Affiliation(s)
- Keiichi Fujiwara
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
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Uchida Y, Kouyama JI, Naiki K, Sugawara K, Inao M, Nakayama N, Mochida S. Novel hepatitis B virus strain developing due to recombination between genotypes H and B strains isolated from a Japanese patient. Hepatol Res 2014; 44:1130-1141. [PMID: 24020990 DOI: 10.1111/hepr.12238] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Revised: 09/04/2013] [Accepted: 09/04/2013] [Indexed: 02/08/2023]
Abstract
AIM In Japan, genotypes B and C are the predominant genotypes isolated from patients with chronic hepatitis B, while genotype A predominates in patients with acute hepatitis B. Globalization, however, appears to have changed the distribution of the hepatitis B virus (HBV) genotypes. Thus, the viral characteristics of HBV genotypes other than genotypes A, B and C were examined. METHODS Screening of genotypes was performed by enzyme immunoassay and/or polymerase chain reaction INVADER method in 222 patients with HBV. The full-length nucleotide sequences of unusual strains were compared to those in the database, followed by construction of a phylogenetic tree. RESULTS Unusual HBV strains were isolated from two patients: a 27-year-old Japanese bisexual man with acute hepatitis B with HIV co-infection and a 52-year-old Japanese man with chronic hepatitis B. The former strain was classified as genotype H, showing an overall identity of 99.8% to the Thailand strain (EU498228), while the nucleotide sequence of the latter strain showed similarity to the genotype B strains isolated in Malaysia (JQ027316) and Indonesia (JQ429079) between DR2 and DR1 in the X region, with identities of 96.9%. However, this strain was classified as genotype H by full-length sequence analysis, and the sequence between nt2023 and nt2262 showed no similarity to that in any previously reported strains. CONCLUSION HBV strains showing recombination between genotype B and H strains were found even in chronic hepatitis patients in Japan. Globalization may yield HBV strains of possible novel genotypes containing novel nucleotide sequences in the precore/core region.
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Affiliation(s)
- Yoshihito Uchida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Moroyamacho, Japan
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Harigai M, Mochida S, Mimura T, Koike T, Miyasaka N. A proposal for management of rheumatic disease patients with hepatitis B virus infection receiving immunosuppressive therapy. Mod Rheumatol 2014; 24:1-7. [PMID: 24261752 DOI: 10.3109/14397595.2013.852834] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Reactivation of hepatitis B virus (HBV) and de novo HBV hepatitis in patients with rheumatic diseases given intensive and long-term immunosuppressive therapy with or without biological disease-modifying antirheumatic drugs is of great concern, especially in regions where the virus is endemic, including Japan. To ascertain a better benefit-risk balance for immunosuppressive therapy for patients with rheumatic diseases, the Japan College of Rheumatology developed this proposal. All patients with rheumatic diseases commencing immunosuppressive therapy should be screened for hepatitis B surface antigen (HBsAg); those who are negative for HBsAg should be screened for hepatitis B core antibody (HBcAb) and hepatitis B surface antibody (HBsAb) as well. HBV carriers and serum HBV DNA positive patients with resolved infection should receive nucleoside analog as soon as possible, prior to commencing immunosuppressive therapy. For serum HBV DNA negative patients with resolved infection, careful monthly monitoring using serum levels of aspartate and alanine aminotransferases and HBV DNA is recommended during and at least 12 months after withdrawal of immunosuppressive therapy. If serum HBV DNA becomes positive, patients should receive nucleoside analog treatment as soon as possible, while ongoing immunosuppressive therapy should be continued to avoid severe or fulminant hepatitis development. To facilitate proper management of patients with HBV infection, collaboration between rheumatologists and hepatologists is strongly encouraged.
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Affiliation(s)
- Masayoshi Harigai
- Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 , Japan
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Zhu B, You SL, Wan ZH, Liu HL, Rong YH, Zang H, Xin SJ. Clinical characteristics and corticosteroid therapy in patients with autoimmune-hepatitis-induced liver failure. World J Gastroenterol 2014; 20:7473-7479. [PMID: 24966618 PMCID: PMC4064093 DOI: 10.3748/wjg.v20.i23.7473] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 01/15/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the clinical features, response to corticosteroids, and prognosis of autoimmune hepatitis (AIH)-induced liver failure in China.
METHODS: A total of 22 patients (19 female and 3 male; average age 51 ± 15 years) with AIH-induced liver failure treated in our hospital from 2004 to 2012 were retrospectively analyzed. Clinical, biochemical and pathological characteristics of the 22 patients and responses to corticosteroid treatment in seven patients were examined retrospectively. The patients were divided into survivor and non-survivor groups, and the clinical characteristics and prognosis were compared between the two groups. The t test was used for data analysis of all categorical variables, and overall survival was calculated by the Kaplan-Meier method.
RESULTS: At the time of diagnosis, mean IgG was 2473 ± 983 mg/dL, with three (18.8%) patients showing normal levels. All of the patients had elevated serum levels of antinuclear antibody (≥ 1:640). Liver histology from one patient showed diagnostic pathological changes, including massive necrosis and plasma cell infiltration. Four patients survived (18.2%) and 18 died (81.8%) without liver transplantation. The results showed that patients with low admission Model for End-Stage Liver Disease (MELD) scores (21.50 ± 2.08 vs 30.61 ± 6.70, P < 0.05) and corticosteroid therapy (100% vs 16.7%, P < 0.05) had better prognosis. A total of seven patients received corticosteroid therapy, of whom, four responded and survived, and the other three died. Survivors showed young age, shorter duration from diagnosis to corticosteroid therapy, low MELD score, and absence of hepatic encephalopathy at the time of corticosteroid administration. Six patients who were administered corticosteroids acquired fungal infections but recovered after antifungal therapy.
CONCLUSION: Early diagnosis and corticosteroid therapy are essential for improving the prognosis of patients with AIH-induced liver failure without liver transplantation.
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