ABSTRACT
Dengue is a common infectious disease in tropical areas such as Peru. This virus can cause underreported and potentially fatal complications such as acute liver failure. We report the case of a 7-year-old boy who presented with fever, headache, and abdominal pain. On ultrasound, we found hepatomegaly and labs severe thrombocytopenia and elevated transaminases. During hospitalization he was diagnosed with severe dengue and developed acute liver failure, kidney injury, and encephalopathy. Although intensive care management and assisted ventilation, he developed multiple organ dysfunctions with fluid refractoriness and capillary leak. Acute liver failure secondary to severe dengue is a rare complication with an unfavorable outcome.
Subject(s)
Liver Failure, Acute , Severe Dengue , Humans , Male , Liver Failure, Acute/etiology , Liver Failure, Acute/virology , Child , Severe Dengue/complications , Severe Dengue/diagnosis , Fatal OutcomeABSTRACT
Acute severe hepatitis associated with active human herpesvirus 6 (HHV-6) infection is a rare life-threatening condition with unclear clinical course and histopathology. In this study, we retrospectively analyzed 5 patients with indeterminate acute severe hepatitis found to have active hepatic HHV-6 infection during care. All patients were previously healthy children presenting with a nonspecific prodrome. Four developed acute liver failure (ALF) and 3 received liver transplantation. The explanted livers and biopsies demonstrated a centrilobular pattern of necroinflammation characterized by moderate to marked central perivenulitis and confluent centrilobular to panlobular necrosis in 4 cases, accompanied by marked hepatocellular swelling and milder portal inflammation in 3. Central perivenulitis was more prominent in comparison to a control of group of ALF without HHV-6 ( P =0.01). When compared with the children with acute severe hepatitis associated with adenovirus encountered in the recent outbreak, both central perivenulitis and centrilobular necrosis were significant predictors for association with HHV-6 ( P <0.01). Liver immunohistochemistry detected HHV-6 structural protein in biliary epithelium in all cases and a predominance of CD8 + T cells in the perivenular inflammatory infiltrate. Among the 4 patients with ALF, one received early anti-HHV-6 therapy and had transplant-free survival, while the other 3 received either general prophylactic antiviral treatment only (n=2) or late anti-HHV-6 therapy (n=1) and needed liver transplantation. Our findings were similar to those in previously reported cases. In summary, acute severe hepatitis associated with HHV-6 tends to affect children, progress to ALF, and exhibit characteristic centrilobular necroinflammation which likely represents an immune-mediated process.
Subject(s)
Herpesvirus 6, Human , Liver Transplantation , Roseolovirus Infections , Humans , Herpesvirus 6, Human/isolation & purification , Male , Retrospective Studies , Roseolovirus Infections/pathology , Roseolovirus Infections/virology , Roseolovirus Infections/complications , Female , Child, Preschool , Child , Infant , Acute Disease , Hepatitis, Viral, Human/pathology , Hepatitis, Viral, Human/virology , Liver Failure, Acute/virology , Liver Failure, Acute/pathology , Severity of Illness Index , Liver/pathology , Liver/virology , Immunohistochemistry , Biopsy , AdolescentABSTRACT
Hepatitis E virus (HEV) infection in pregnant women is associated with a wide spectrum of adverse consequences for both mother and fetus. The high mortality in this population appears to be associated with hormonal changes and consequent immunological changes. This study conducted an analysis of immune responses in pregnant women infected with HEV manifesting varying severity. Data mining analysis of the GSE79197 was utilized to examine differentially biological functions in pregnant women with HEV infection (P-HEV) versus without HEV infection (P-nHEV), P-HEV progressing to ALF (P-ALF) versus P-HEV, and P-HEV versus non-pregnant women with HEV infection (nP-HEV). We found cellular response to interleukin and immune response-regulating signalings were activated in P-HEV compared with P-nHEV. However, there was a significant decrease of immune responses, such as T cell activation, leukocyte cell-cell adhesion, regulation of lymphocyte activation, and immune response-regulating signaling pathway in P-ALF patient than P-HEV patient. Compared with nP-HEV, MHC protein complex binding function was inhibited in P-HEV. Further microRNA enrichment analysis showed that MAPK and T cell receptor signaling pathways were inhibited in P-HEV compared with nP-HEV. In summary, immune responses were activated during HEV infection while being suppressed when developing ALF during pregnancy, heightening the importance of immune mediation in the pathogenesis of severe outcome in HEV infected pregnant women.
Subject(s)
Hepatitis E virus , Hepatitis E , Pregnancy Complications, Infectious , Humans , Female , Pregnancy , Hepatitis E/immunology , Hepatitis E/virology , Pregnancy Complications, Infectious/virology , Pregnancy Complications, Infectious/immunology , Hepatitis E virus/immunology , Signal Transduction , Liver Failure, Acute/immunology , Liver Failure, Acute/virology , MicroRNAs/genetics , AdultABSTRACT
BACKGROUND AND OBJECTIVES: Hepatitis A virus (HAV)-related hepatitis is witnessing an epidemiological transition with increasing trends in adults. While uncomplicated hepatitis remains common, evidence suggests it to be a growing cause for acute liver failure (ALF). In between the two extremes exists severe acute liver injury (s-ALI) which has a propensity to transition to ALF. We aimed at describing the clinical profile of patients with HAV-related s-ALI and identifying potential predictors of progression to ALF. METHODS: This was a single-center retrospective analysis of adult patients admitted with HAV-related s-ALI between April 2022 and December 2023. Demographic and laboratory parameters were compared between patients with only s-ALI and those with ALF. Predictors of progression from s-ALI to ALF were identified using logistic regression. RESULTS: Forty-three patients satisfied criteria of s-ALI, of which 33 (76.7%) had only s-ALI, while 10 (23.3%) had ALF. Patients with s-ALI had lesser leukocytosis (6.3 ± 3 vs. 13.2 ± 4.8), less incidence of acute kidney injury (9.1% vs. 40%) and lower model for end-stage liver disease (MELD) (20 [18-24.5] vs. 31.5 [26-42]), arterial lactate (2.1 [1.3-3.1] vs. 6.3 [5.2-8.0]), arterial ammonia (94 [72-118] vs. 299 [188-573]), procalcitonin (0.5 [0.28-1.25] vs. 3.2 [1.2-6.1]) and ferritin (482 [213-1633] vs. 5186 [1341-11,053]) compared to HAV-ALF (p < 0.05 for all). Three patients (9.09%) with s-ALI progressed to ALF of whom one (3%) died. Baseline ammonia levels (unadjusted odds ratio [OR] 1.03 [1.01-1.06]) and leukocyte count (OR 1.00 [1.00-1.01]) tended to be associated with ALF progression, although none was significant after multi-variable adjustment. Ammonia levels had an area under receiver operating curve of 0.816 (0.64-0.93) (p = 0.009) (cut-off of 144 µmol/L). Additional comorbidities did not impact overall outcomes. CONCLUSION: HAV presents as s-ALI in young adults, with almost one in 10 progressing to ALF. Baseline ammonia may be an important predictor of progression even in s-ALI, but mandates larger well-designed studies.
Subject(s)
Disease Progression , Hepatitis A , Liver Failure, Acute , Severity of Illness Index , Humans , Male , Hepatitis A/complications , Hepatitis A/epidemiology , Female , Adult , Retrospective Studies , Liver Failure, Acute/etiology , Liver Failure, Acute/virology , Liver Failure, Acute/epidemiology , Middle Aged , Young AdultABSTRACT
Acute liver failure (ALF) is a rare and severe disease, which, despite continuous advances in medicine, is still characterized by high mortality (65-85%). Very often, a liver transplant is the only effective treatment for ALF. Despite the implementation of prophylactic vaccinations in the world, the viral background of ALF is still a problem and leads to many deaths. Depending on the cause of ALF, it is sometimes possible to reverse this condition with appropriate therapies, which is why the search for effective antiviral agents seems to be a very desirable direction of research. Defensins, which are our natural antimicrobial peptides, have a very high potential to be used as therapeutic agents for infectious liver diseases. Previous studies on the expression of human defensins have shown that increased expression of human α and ß-defensins in HCV and HBV infections is associated with a better response to treatment. Unfortunately, conducting clinical trials for ALF is very difficult due to the severity of the disease and the low incidence, therefore animal models are important for the development of new therapeutic strategies. One of the best animal models that has real reference to research on acute liver failure (ALF) is rabbit hemorrhagic disease in rabbits caused by the Lagovirus europaeus virus. So far, there have been no studies on the potential of defensins in rabbits infected with Lagovirus europaeus virus.
Subject(s)
Defensins , Disease Models, Animal , Hemorrhagic Disease Virus, Rabbit , Liver Failure, Acute , Rabbits , Liver Failure, Acute/therapy , Liver Failure, Acute/virology , Defensins/therapeutic use , Animals , Caliciviridae Infections/therapyABSTRACT
Hepatitis E virus (HEV) infection usually results in a self-limiting acute disease; however, in infected pregnant women, it is associated with increased mortality and fulminant hepatic failure. Estrogen is known to be elevated during pregnancy, and estrogen signaling via classical estrogen receptor-ERα is known to regulate hepatocyte function and host innate immune response, including the STAT3 pathway. In this study, we investigated whether the estrogen classical signaling pathway via ERαp66 has any effect on STAT3 activation during HEV replication and HEV-induced IFN response. We first demonstrated that Huh7-S10-3 liver cells expressed the nonfunctional estrogen receptor ERαp36 isoform and lack the functional ERαp66 isoform. We further showed persistent phosphorylated-STAT3 levels in genotype 3 human HEV (Kernow P6 strain) RNA-transfected cells at later time points. In Huh7-S10-3 cells, estrogen at first-to-third trimester concentration (7.3 to 73 nM) did not significantly affect HEV replication; however, blocking of STAT3 activation led to a decrease in the HEV ORF2 protein level. Our mechanistic study revealed that STAT3 differentially regulates SOCS3 and type-III interferon (IFN) levels during HEV replication and the presence of estrogen-ERαp66 signaling stabilizes SOCS3 levels in vitro. We also demonstrate that HEV infection in pregnant and nonpregnant rabbits led to a significant increase in IFN response as measured by increased levels of IFN-stimulated-gene-15 (ISG15) mRNA levels irrespective of pregnancy status. Collectively, the results indicate that estrogen signaling and STAT3 regulate SOCS3 and IFN responses in vitro during HEV replication. The results have important implications for understanding HEV replication and HEV-induced innate immune response in pregnant women. IMPORTANCE Hepatitis E is usually a self-resolving acute disease; however, in pregnant women, HEV infection is associated with high mortality and fulminant hepatic failure. During pregnancy, estrogen levels are elevated, and in the liver, the estrogen receptor ERα is predominant and estrogen signaling is known to regulate hepatocyte metabolism and leptin-induced STAT3 levels. Viruses can module host innate immune response via STAT3. Therefore, in this study, we investigated whether STAT3 and estrogen-classical signaling via the ERαp66 pathway modulate HEV replication and HEV-induced innate immune response. We demonstrated that estrogen signaling did not affect HEV replication in human liver cells, but blocking of STAT3 activation reduced HEV capsid protein levels in human liver cells. We also showed that inhibition of STAT3 activation reduced SOCS3 levels, while the presence of the estrogen-ERαp66 signaling pathway stabilized SOCS3 levels. The results from this study will aid our understanding of the mechanism of HEV pathogenesis and immune response during pregnancy.
Subject(s)
Carcinoma, Hepatocellular , Estrogen Receptor alpha , Hepatitis E , Liver Neoplasms , STAT3 Transcription Factor , Suppressor of Cytokine Signaling 3 Protein , Animals , Capsid Proteins , Carcinoma, Hepatocellular/virology , Estrogen Receptor alpha/metabolism , Estrogens , Female , Hepatitis E/metabolism , Hepatitis E virus/physiology , Humans , Interferons/metabolism , Leptin/metabolism , Liver Failure, Acute/virology , Liver Neoplasms/virology , Pregnancy , RNA , RNA, Messenger , Rabbits , Receptors, Estrogen , STAT3 Transcription Factor/metabolism , Signal Transduction , Suppressor of Cytokine Signaling 3 Protein/metabolism , Virus ReplicationABSTRACT
Hepatitis E virus (HEV) infection in pregnant women has a high incidence of developing fulminant hepatic failure (FHF) with significant mortality. Multiple amino acid changes in genotype 1 HEV (HEV-1) are reportedly linked to FHF clinical cases, but experimental confirmation of the roles of these changes in FHF is lacking. By utilizing the HEV-1 indicator replicon and infectious clone, we generated 11 HEV-1 single mutants, each with an individual mutation, and investigated the effect of these mutations on HEV replication and infection in human liver cells. We demonstrated that most of the mutations actually impaired HEV-1 replication efficiency compared with the wild type (WT), likely due to altered physicochemical properties and structural conformations. However, two mutations, A317T and V1120I, significantly increased HEV-1 replication. Notably, these two mutations simultaneously occurred in 100% of 21 HEV-1 variants from patients with FHF in Bangladesh. We further created an HEV-1 A317T/V1120I double mutant and found that it greatly enhanced HEV replication, which may explain the rapid viral replication and severe disease. Furthermore, we tested the effect of these FHF-associated mutations on genotype 3 HEV (HEV-3) replication and found that all the mutants had a reduced level of replication ability and infectivity, which is not unexpected due to distinct infection patterns between HEV-1 and HEV-3. Additionally, we demonstrated that these FHF-associated mutations do not appear to alter their sensitivity to ribavirin (RBV), suggesting that ribavirin remains a viable option for antiviral therapy for patients with FHF. The results have important implications for understanding the mechanism of HEV-1-associated FHF.
Subject(s)
Hepatitis E virus , Hepatitis E , Liver Failure, Acute , Female , Genotype , Hepatitis E/genetics , Hepatitis E virus/genetics , Humans , Liver Failure, Acute/virology , Mutation , Pregnancy , Ribavirin , Virus ReplicationABSTRACT
Hepatic manifestations of Epstein-Barr virus (EBV) infection are relatively common, mild, and self-limiting. Although fulminant hepatic failure has been reported in a few cases, the contributing factors are unclear. This report discusses a pediatric case of EBV-associated acute liver failure that required urgent liver transplantation; however, liver damage continued to progress post-liver replacement. Monoclonal CD8+ T cells that preferentially infiltrated the native and transplanted liver were positive for EBV-encoded small RNA, suggesting a pathophysiology similar to that of EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection. Therefore, subsequent chemotherapy and hematopoietic cell transplantation was conducted, which led to cure. This is the first case of EBV-associated acute liver failure that relapsed post-liver transplant. As such, it sheds light on an under-recognized clinical entity: liver-restricted hyperinflammation caused by EBV-infected monoclonal CD8+ T cells. This phenomenon needs to be recognized and differentiated from hepatitis/hepatic failure caused by EBV-infected B cells, which has a relatively benign clinical course.
Subject(s)
CD8-Positive T-Lymphocytes/virology , Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/genetics , Liver Failure, Acute/virology , Liver/pathology , Lymphohistiocytosis, Hemophagocytic/virology , Child, Preschool , Epstein-Barr Virus Infections/immunology , Hematopoietic Stem Cell Transplantation , Humans , Liver/diagnostic imaging , Liver Failure, Acute/therapy , Liver Transplantation , Lymphohistiocytosis, Hemophagocytic/therapy , Male , Positron Emission Tomography Computed Tomography , RNA, Viral/analysis , Treatment OutcomeABSTRACT
The complement system (CS) is part of the human immune system, consisting of more than 30 proteins that play a vital role in the protection against various pathogens and diseases, including viral diseases. Activated via three pathways, the classical pathway (CP), the lectin pathway (LP), and the alternative pathway (AP), the complement system leads to the formation of a membrane attack complex (MAC) that disrupts the membrane of target cells, leading to cell lysis and death. Due to the increasing number of reports on its role in viral diseases, which may have implications for research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this review aims to highlight significant progress in understanding and defining the role of the complement system in four groups of diseases of viral etiology: (1) respiratory diseases; (2) acute liver failure (ALF); (3) disseminated intravascular coagulation (DIC); and (4) vector-borne diseases (VBDs). Some of these diseases already present a serious global health problem, while others are a matter of concern and require the collaboration of relevant national services and scientists with the World Health Organization (WHO) to avoid their spread.
Subject(s)
Complement System Proteins , Virus Diseases/etiology , Animals , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/virology , Humans , Liver Failure, Acute/immunology , Liver Failure, Acute/virology , Respiratory Tract Diseases/immunology , Respiratory Tract Diseases/virology , Vector Borne Diseases/immunology , Vector Borne Diseases/virologyABSTRACT
BACKGROUND: Acute liver failure (ALF) is a syndrome of severe hepatocyte injury with high rate of mortality. Hepatitis B virus (HBV) infection is the major cause of ALF worldwide, however, the underlying mechanism by which HBV infection leads to ALF has not been fully disclosed. METHODS: D-GalN-induced hepatocyte injury model and LPS/D-GalN-induced ALF mice model were used to investigate the effects of HBV X protein (HBx) in vitro and in vivo, respectively. Cell viability and the levels of Glutathione (GSH), malondialdehyde (MDA) and iron were measured using commercial kits. The expression of ferroptosis-related molecules were detected by qRT-PCR and western blotting. Epigenetic modification and protein interaction were detected by chromatin immunoprecipitation (ChIP) assay and co-immunoprecipitation (co-IP), respectively. Mouse liver function was assessed by measuring aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The histological changes in liver tissues were monitored by hematoxylin and eosin (H&E) staining, and SLC7A11 immunoreactivity was assessed by immunohistochemistry (IHC) analysis. RESULTS: D-GalN triggered ferroptosis in primary hepatocytes. HBx potentiated D-GalN-induced hepatotoxicity and ferroptosis in vitro, and it suppressed SLC7A11 expression through H3K27me3 modification by EZH2. In addition, EZH2 inhibition or SLC7A11 overexpression attenuated the effects of HBx on D-GalN-induced ferroptosis in primary hepatocytes. The ferroptosis inhibitor ferrostatin-1 (Fer-1) protected against ALF and ferroptosis in vivo. By contrast, HBx exacerbates LPS/D-GalN-induced ALF and ferroptosis in HBx transgenic (HBx-Tg) mice. CONCLUSION: HBx facilitates ferroptosis in ALF via EZH2/H3K27me3-mediated SLC7A11 suppression.
Subject(s)
Ferroptosis/physiology , Liver Failure, Acute/virology , Trans-Activators/genetics , Viral Regulatory and Accessory Proteins/genetics , Amino Acid Transport System y+/metabolism , Animals , Enhancer of Zeste Homolog 2 Protein/metabolism , Male , Mice , Mice, Inbred C57BLABSTRACT
INTRODUCTION: Acute liver failure (ALF) is a life-threatening condition that remains challenging for physicians despite several advances in supportive care. Etiologies vary worldwide, with herpes simplex virus (HSV) hepatitis representing less than 1% of cases. Despite its low incidence, ALF is a lethal cause of acute necrotizing hepatitis and has a high mortality. Early antiviral treatment is beneficial for survival and decreased liver transplantation necessity. However, plasmapheresis, despite its theoretical potential benefit, is scarcely reported. PATIENT CONCERNS: A 25-year-old woman with no known disease presented with painful pharynx ulcers, increased transaminases and impaired liver function. DIAGNOSIS: ALF due to a disseminated HSV-2 primary infection was diagnosed with a positive polymerase chain reaction for HSV-2 in the biopsied liver tissue and blood. INTERVENTIONS: Empiric antiviral treatment was initiated. After clinical deterioration, plasmapheresis was also initiated. OUTCOMES: After 6 cycles of plasmapheresis and supportive care, the patient's condition improved without undergoing liver transplantation. CONCLUSIONS: ALF is a life-threatening condition, and HSV as an etiology must be suspected based on background, clinical manifestation, and laboratory information. The potential role of plasmapheresis in HSV hepatitis should be considered.
Subject(s)
Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , Herpes Simplex/complications , Liver Failure, Acute/virology , Plasmapheresis , Adult , Female , Herpesvirus 2, Human/isolation & purification , Humans , Liver Failure, Acute/diagnostic imaging , Liver Failure, Acute/therapy , Tomography, X-Ray ComputedABSTRACT
Massive cellular necrosis in acute liver failure (ALF) is dominantly immune mediated and innate immune cells are major pathophysiological determinants in liver damage. In fifty ALF and fifteen healthy, immune cells phenotyping by flow-cytometry, DAMPs using ELISA were analysed and correlated with clinical and biochemical parameters. ALF patients (aged 27 ± 9 yr, 56% males, 78% viral aetiology) showed no difference in neutrophils and classical monocytes, but significantly increased intermediate monocytes (CD14+CD16+) (p < 0.01), decreased non-classical monocytes (CD14-CD16+) and CD3-veCD16+CD56+ NK cells compared to HC. ALF patients who survived, showed higher NK cells (9.28 vs. 5.1%, p < 0.001) among lymphocytes and lower serum lactate levels (6.1 vs. 28, Odds ratio 2.23, CI 1.27-3.94) than non- survivors had higher. Logistic regression model predicted the combination of lactate levels with NK cell percentage at admission for survival. In conclusion, Combination of NK cell frequency among lymphocytes and lactate levels at admission can reliably predict survival of ALF patients.
Subject(s)
Killer Cells, Natural/immunology , Lactic Acid/blood , Liver Failure, Acute/blood , Liver Failure, Acute/immunology , Adult , Female , Humans , Liver Failure, Acute/virology , Male , Middle Aged , Prognosis , Virus Diseases/complicationsABSTRACT
The adverse relationship between viral hepatitis and pregnancy in developing countries had been interpreted as a reflection of retrospectively biased hospital-based data collection by the West. However, the discovery of hepatitis E virus (HEV) as the etiological agent of an epidemic of non-A, non-B hepatitis in Kashmir, and the documenting of the increased incidence and severity of hepatitis E in pregnancy via a house-to-house survey, unmasked this unholy alliance. In the Hepeviridae family, HEV-genotype (gt)1 from genus Orthohepevirus A has a unique open reading frame (ORF)4-encoded protein which enhances viral polymerase activity and viral replication. The epidemics caused by HEV-gt1, but not any other Orthohepevirus A genotype, show an adverse relationship with pregnancy in humans. The pathogenesis of the association is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the pregnant women including infection and damage to the maternal-fetal interface by HEV-gt1; vertical transmission of HEV to fetus causing severe fetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the pregnant women, promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of acute liver failure. (ALF). Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.
Subject(s)
Hepatitis E virus/genetics , Hepatitis E/complications , Hepatitis E/epidemiology , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , Female , Genotype , Hepatitis E virus/classification , Humans , India/epidemiology , Infant, Newborn , Infectious Disease Transmission, Vertical , Liver/pathology , Liver/virology , Liver Failure, Acute/virology , Open Reading Frames , Pregnancy , RNA, Viral/genetics , Retrospective Studies , Virus ReplicationSubject(s)
Gastrointestinal Hemorrhage/virology , Hepatitis, Viral, Human/virology , Herpes Genitalis/virology , Herpesvirus 1, Human/pathogenicity , Liver Failure, Acute/virology , Aged , Biopsy , Fatal Outcome , Fever/etiology , Gastrointestinal Hemorrhage/diagnosis , Hepatitis, Viral, Human/diagnosis , Herpes Genitalis/complications , Herpes Genitalis/diagnosis , Humans , Liver Failure, Acute/diagnosis , Male , Multiple Organ Failure/etiologyABSTRACT
Recently, we experienced an outbreak of acute hepatitis A virus (HAV) infection between 2018 and 2020. Herein, we describe this male-dominant HAV infection outbreak observed among non-human immunodeficiency virus (HIV)-infected persons in the northern part of Tokyo, Japan. Clinical information was collected from patient interviews and from medical record descriptions. In the present study, 21 patients were retrospectively analyzed. A total of 90.4 and 33.3% of patients were males, and men who have sex with men (MSM), respectively. The total bilirubin levels and platelet counts tended to be lower in the MSM group than in the non-MSM group. C-reactive protein (CRP) levels tended to be higher in acute liver failure (ALF) patients than in non-ALF patients. Prolonged cholestasis was observed in one patient (4.8%). We also found that 18 HAV isolates belonged to HAV subgenotype IA/subgroup 13 (S13), which clustered with the HAV isolate (KX151459) that was derived from an outbreak of HAV infection among MSM in Taiwan in 2015. Our results suggest that the application of antivirals against HAV, as well as HAV vaccines, would be useful for the treatment and prevention of severe HAV infection.
Subject(s)
Disease Outbreaks , Hepatitis A/epidemiology , Adult , Female , Genotype , Hepatitis A/virology , Hepatitis A virus/classification , Hepatitis A virus/genetics , Hepatitis A virus/isolation & purification , Homosexuality, Male , Humans , Length of Stay , Liver Failure, Acute/epidemiology , Liver Failure, Acute/virology , Male , Middle Aged , Phylogeny , Retrospective Studies , Risk Factors , Sexual and Gender Minorities , Tokyo/epidemiologyABSTRACT
[Figure: see text].
Subject(s)
COVID-19/complications , COVID-19/pathology , Endothelium, Vascular/pathology , Multiple Organ Failure/virology , Thrombosis/virology , Biomarkers/blood , COVID-19/immunology , Complement Activation , Critical Care , Cytokines/blood , Female , Humans , Liver Failure, Acute/virology , Male , Microcirculation , Middle Aged , Nucleosomes/metabolism , Respiratory Insufficiency/virology , SARS-CoV-2ABSTRACT
BACKGROUND: Abnormal liver function has been reported in patients with COVID-19 infection. The aim of our study was to report on the prevalence of liver injury in our cohort, to evaluate the association of mild versus severe liver injury with mortality in COVID-19 patients and to scrutinize the temporal pattern of viral detection and liver injury. METHODS: We present data from a German cohort of 147 SARS-CoV-2 infected patients. The patients were divided into 3 groups according to their liver status during treatment. The first group included patients without elevated alanine aminotransferase or bilirubin, the third group patients meeting the biochemical criteria of acute liver failure (ALF), and the second group all other patients. RESULTS: Liver injury was detected in 75 (50.7%) and 93 (63%) patients by admission and during treatment, respectively. ALF was associated with the male sex, younger age, and higher BMI. Mortality was associated with the presence of ALF (OR = 9.423, 95% CI: 2.410-36.858) in contrast to milder liver injury (OR 1.101, 95% CI: 0.435-2.791). In 30% of patients with mild liver injury and in 50% of ALF patients, peak liver injury was observed at a time point when the virus was no longer detectable in the respiratory tract. CONCLUSION: Mild liver injury was not associated with worse outcome in our cohort, and the pattern of liver injury did not fit well to the theory of SARS-CoV-2 directly causing liver impairment. Instead, severe liver injury in our cohort was associated multiple-organ failure and acute vascular events.
Subject(s)
Alanine Transaminase/blood , Bilirubin/blood , COVID-19 , Liver Failure, Acute , Liver Function Tests , SARS-CoV-2/isolation & purification , Adult , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , Cohort Studies , Correlation of Data , Female , Germany/epidemiology , Hospitalization/statistics & numerical data , Humans , Liver Failure, Acute/blood , Liver Failure, Acute/epidemiology , Liver Failure, Acute/etiology , Liver Failure, Acute/virology , Liver Function Tests/methods , Liver Function Tests/statistics & numerical data , Male , Middle Aged , Prevalence , Severity of Illness IndexABSTRACT
Dengue is a common viral infection, especially in tropical countries, and it is a well-known cause of acute liver failure. The effects on the liver range from a mild illness to acute liver failure. Dengue-related acute liver failure has a high mortality rate, and the role of liver transplant in such cases has been less studied, due to the rapid progression and often associated multiorgan dysfunction in severe cases. Here, we report the first living donor liver transplant for an acute liver failure due to dengue. Although liver transplant is not the choice of treatment for sick patients, timely intervention in specific patients may have a role.
Subject(s)
Dengue , Liver Failure, Acute , Liver Transplantation , Dengue/complications , Dengue/diagnosis , Humans , Liver Failure, Acute/diagnosis , Liver Failure, Acute/surgery , Liver Failure, Acute/virology , Living DonorsABSTRACT
Although several typical manifestation of novel coronavirus disease 2019 (COVID-19) including respiratory symptoms, weakness, fever, and fatigue have been reported, some rare and novel manifestations have also been observed, particularly in children. We report a pediatric case of fulminant hepatic failure associated with COVID-19. Although the patient was treated for acute fulminant hepatic failure in the context of COVID-19, he died following the progression of the disease to stage 4 hepatic failure with encephalopathy and brain death.