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The role of hepatitis E virus infection in adult Americans with acute liver failure.

ABSTRACT: Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western countries. Given that antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV-related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the U.S. Acute Liver Failure Study Group were tested for anti-HEV immunoglobulin (Ig) M and anti-HEV IgG levels. Subjects with a detectable anti-HEV IgM also underwent testing for HEV RNA. Mean patient age was 41.8 years, 32.9% were male, and ALF etiologies included acetaminophen (APAP) hepatotoxicity (29%), indeterminate ALF (23%), idiosyncratic drug-induced liver injury DILI (22%), acute hepatitis B virus infection (12%), autoimmune hepatitis (12%), and pregnancy-related ALF (2%). Three men ages 36, 39, and 70 demonstrated repeatedly detectable anti-HEV IgM, but all were HEV-RNA negative and had other putative diagnoses. The latter 2 subjects died within 3 and 11 days of enrollment whereas the 36-year-old underwent emergency liver transplantation on study day 2. At admission, 294 (43.4%) of the ALF patients were anti-HEV IgG positive with the seroprevalence being highest in those from the Midwest (50%) and lowest in those from the Southeast (28%). Anti-HEV IgG+ subjects were significantly older, less likely to have APAP overdose, and had a lower overall 3-week survival compared to anti-HEV IgG- subjects (63% vs. 70%; P = 0.018).Acute HEV infection is very rare in adult Americans with ALF (i.e., 0.4%) and could not be implicated in any indeterminate, autoimmune, or pregnancy-related ALF cases. Past exposure to HEV with detectable anti-HEV IgG was significantly more common in the ALF patients compared to the general U.S.(Hepatology 2016;64:1870-1880).

SUBMITTER: Fontana RJ

PROVIDER: S-EPMC5115940 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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The role of hepatitis E virus infection in adult Americans with acute liver failure.

Fontana Robert John RJ Engle Ronald E RE Scaglione Steven S Araya Victor V Shaikh Obaid O Tillman Holly H Attar Nahid N Purcell Robert H RH Lee William M WM

Hepatology (Baltimore, Md.) 20160623 6

Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western countries. Given that antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV-related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the U.S. Acute Liver Failure Study Group were tested for anti-HEV immunoglobulin (Ig) M and anti-HEV IgG levels. Subjects ...[more]

PMID: 27215797

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Project description:BACKGROUND:Infection is common in acute-on-chronic liver failure (ACLF), which may worsen the clinical condition and prognosis. However, the characteristics of infection and its influence on prognosis in hepatitis B virus related ACLF (HBV-ACLF) as defined by the European Association for the Study of the Liver (EASL) have not been clarified. We aimed to investigate the characteristics of infection and its influence on mortality in patients with HBV-ACLF defined by EASL in China. METHODS:We performed a retrospective cohort study in patients with HBV-ACLF defined by EASL in a single center from January 2015 to December 2017. These patients were divided into two groups with and without infection. The incidence, sites of infection, isolated strains, and risk factors associated with mortality were evaluated. RESULTS:A total of 289 patients were included, among them 185 (64.0%) were diagnosed with an infection. The most common type of infection was pneumonia (55.7%), followed by spontaneous bacterial peritonitis (47.6%) and others. The gram-negative bacteria were the most frequent (58.3%). Patients with one, two, and three or more infection sites had a gradually increasing incidence of sepsis (P?<?0.01), septic shock (P?<?0.001), and ACLF-3 (P?<?0.05). Also, patients with infection isolated one, two, and three or more strains showed a growing incidence of sepsis (P?<?0.01) and septic shock (P?<?0.001). Patients with infection showed a significantly higher 28-day mortality than those without (P?<?0.01), especially in patients with ACLF-3. Infection was identified as an independent risk factor for 28-day mortality in all HBV-ACLF patients. Pneumonia and sepsis were identified as independent predictors of 28-day mortality for patients with infection. CONCLUSIONS:Infection is associated with severe clinical course and high mortality in HBV-ACLF defined by EASL. The increased number of infection sites or isolated strains was associated with the occurrence of sepsis and septic shock. Pneumonia and sepsis were independent predictors for mortality in HBV-ACLF patients with infection.

Project description:BackgroundAcute-on-chronic liver failure (ACLF) is characterized by an excessive systemic inflammatory response and organ failure and has high mortality. Bacterial infections (BIs) worsen the clinical course of ACLF and carry a poor prognosis in ACLF patients. The efficacy of third-generation cephalosporins has been challenged in recent years. The aim of this study was to characterize the difference between ACLF patients with and without BIs and to provide a reference for medical intervention.MethodsA total of 140 patients with hepatitis B virus-related ACLF (HBV-ACLF) hospitalized at the Department of Infectious Diseases, Huashan Hospital, Fudan University (Shanghai, China) between May 2013 and January 2020 were enrolled. Mann-Whitney U test was used to compare the baseline characteristics of HBV-ACLF patients with and without BIs. Univariate and multivariate analyses were performed to find predictors of BIs. The characteristics of BIs and the role of prophylactic antibiotics were profiled.ResultsA total of 97 episodes of BIs occurred in patients during the course of HBV-ACLF. Patients with and without BIs differed in clinical characteristics. The incidence of BIs showed a positive correlation with the ACLF grade (P = 0.003) and the clinical course (P = 0.003). The 90-day transplant-free survival of patients with BIs was lower than those without BIs (P < 0.0001). Patients administered prophylactic antibiotics showed a lower incidence of BIs and had a higher transplant-free survival probability than those who did not (P = 0.046). No statistical differences in antibiotic efficacy between third-generation and other antibiotics were observed (P = 0.108).ConclusionsBIs affected the clinical course and prognosis of patients with HBV-ACLF. Prophylactic antibiotics were of potential clinical importance in the prevention of BIs and improving the clinical course and prognosis in HBV-ACLF patients. Third-generation cephalosporins were qualified for use in antibiotic prophylaxis.

Project description:BackgroundHepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is an important type of liver failure in Asia. There is a direct relationship between HBV-ACLF and gastrointestinal barrier function. However, the nutritional status of HBV-ACLF patients has been poorly studied.AimTo investigate the nutritional risk and nutritional status of HBV-ACLF patients and evaluated the impact of nutritional support on the gastrointestinal barrier and 28-d mortality.MethodsNutritional risk screening assessment and gastrointestinal barrier biomarkers of patients with HBV-ACLF (n = 234) and patients in the compensatory period of liver cirrhosis (the control group) (n = 234) were compared during the period between 2016 and 2018. Changes were analyzed after nutritional support in HBV-ACLF patients. Valuable biomarkers have been explored to predict 28-d death. The 28-d survival between HBV-ACLF patients with nutritional support (n = 234) or no nutritional support (2014-2016) (n = 207) was compared.ResultsThe nutritional risk of the HBV-ACLF patients was significantly higher than that of the control group. The nutritional intake of the patients with HBV-ACLF was lower than that of the control group. The decrease in skeletal muscle and fat content and the deficiency of fat intake were more obvious (P < 0.001). The coccus-bacillus ratio, secretory immunoglobulin A, and serum D-lactate were significantly increased in HBV-ACLF patients. The survival group had a lower nutritional risk, lower D-lactate, and cytokine levels (endotoxin, tumor necrosis factor alpha, interleukin-10, and interleukin-1). Interleukin-10 may be a potential predictor of death in HBV-ACLF patients. The 28-d survival of the nutritional support group was better than that of the non-nutritional support group (P = 0.016).ConclusionPatients with HBV-ACLF have insufficient nutritional intake and high nutritional risk, and their intestinal barrier function is impaired. Individualized and dynamic nutritional support is associated with a better prognosis of 28-d mortality in HBV-ACLF patients.

Project description:IntroductionThe liver has inherent regenerative capacity via mitotic division of mature hepatocytes or, when the hepatic loss is massive or hepatocyte proliferation is impaired, through activation of hepatic stem/progenitor cells (HSPC). The dramatic clinical course of acute liver failure (ALF) has posed major limitations to investigating the molecular mechanisms of liver regeneration and the role of HSPC in this setting. We investigated the molecular mechanisms of liver regeneration in 4 patients who underwent liver transplantation for hepatitis B virus (HBV)-associated ALF.Methods and findingsGene expression profiling of 17 liver specimens from the 4 ALF cases and individual specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two clusters of ALF that segregated according to histopathological severity massive hepatic necrosis (MHN; 2 patients) and submassive hepatic necrosis (SHN; 2 patients). We found that ALF is characterized by a strong HSPC gene signature, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of stem cell genes (EpCAM, CK19, CK7), whereas the most up-regulated genes in SHN were related to cellular growth and proliferation. The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound-healing process.ConclusionOur data provide evidence for a distinct gene signature in HBV-associated ALF whose intensity is directly correlated with the histopathological severity. HSPC activation and fibrogenesis positively correlated with the extent of liver necrosis. Moreover, we detected a tumorigenesis gene signature in ALF, emphasizing the close relationship between liver regeneration and liver cancer.

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The role of hepatitis E virus infection in adult Americans with acute liver failure.

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The role of hepatitis E virus infection in adult Americans with acute liver failure.

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