Role of Hepatitis E Virus Infection in North American Patients With Severe Acute Liver Injury.
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ABSTRACT:
Methods: Serum samples from 594 consecutive adults enrolled between 2008 and 2018 in the US Acute Liver Failure Study Group ALI registry were tested for anti-HEV IgM and anti-HEV IgG levels. Those with detectable anti-HEV IgM underwent further testing for HEV RNA using real-time polymerase chain reaction.
Results: The median age of patients was 38 years; 41% were men and 72% Caucasian. Etiologies of ALI included acetaminophen hepatotoxicity (50%), autoimmune hepatitis (8.9%), hepatitis B virus (8.9%), and idiosyncratic drug-induced liver injury (7.9%). Overall, 62 patients (10.4%) were negative for anti-HEV IgM but positive for IgG, whereas only 3 men (0.5%) were positive for both anti-HEV IgM and IgG. These 3 cases were initially diagnosed as having indeterminate, HEV, and hepatitis B virus-related ALI. One of these patients had detectable HEV RNA genotype 3, and another anti-HEV IgM+ patient had detectable HEV antigens by immunohistochemistry on liver biopsy. On multivariate modeling, older (odds ratio: 1.99) and non-Caucasian subjects (odds ratio: 2.92) were significantly more likely to have detectable anti-HEV IgG (P < 0.0001).
Discussion: Acute HEV infection is an infrequent cause of ALI in hospitalized North American adults. The anti-HEV IgG+ patients were significantly older and more likely to be non-Caucasian. These data are consistent with other population-based studies that indicate exposure to HEV in the general US population is declining over time and might reflect a cohort effect.
SUBMITTER: Fontana RJ
PROVIDER: S-EPMC7665257 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
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Project description:AimTo examine the incidence of hepatitis E (HepE) in individuals with acute liver injury severe enough to warrant treatment at a transplant unit.MethodsHepatitis E virus (HEV) is an emerging pathogen in developed countries causing severe illness, particularly in immunocompromised patients or those with underlying chronic liver disease. HepE infection is often under diagnosed, as clinicians can be reluctant to test patients who have not travelled to regions traditionally considered hyperendemic for HepE. There are few data regarding the significance of HEV in patients with very severe acute liver injury in developed countries. Eighty patients with acute severe liver injury attending the Scottish Liver Transplant unit were tested for HEV and anti-HEV IgG and IgM. Severe acute liver injury was defined as a sudden deterioration in liver function confirmed by abnormal liver function tests and coagulopathy or presence of hepatic encephalopathy. Eighty percent of these patients were diagnosed with paracetomol overdose. No patients had a history of chronic or decompensated chronic liver disease at time of sampling. IgG positive samples were quantified against the World Health Organization anti-HEV IgG standard. Samples were screened for HEV viral RNA by quantitative reverse transcription polymerase chain reaction.ResultsFour cases of hepatitis E were identified. Three of the four cases were only diagnosed on retrospective testing and were initially erroneously ascribed to drug-induced liver injury and decompensated chronic liver disease, with the cause of the decompensation uncertain. One case was caused by HEV genotype 1 in a traveller returning from Asia, the other three were autochthonous and diagnosed on retrospective testing. In two of these cases (where RNA was detected) HEV was found to be genotype 3, the most prevalent genotype in developed countries. Three patients survived, two of whom had been misdiagnosed as having drug induced liver injury. The fourth patient died from sepsis and liver failure precipitated as a result of hepatitis E infection and previously undiagnosed cirrhosis. Histopathology data to date is limited to mainly that seen for endemic HepE. All patients, with the exception of patient 1, demonstrated characteristics of HepE infection, as seen in previously described locally acquired cases.ConclusionIn patients with acute severe liver injury, HEV testing should be part of the initial diagnostic investigation algorithm irrespective of suspected initial diagnosis, age or travel history.
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Project description:We describe here what is, to the best of our knowledge, the third reported case of severe thrombocytopenia associated with acute hepatitis E virus infection. The patient was a 72-year-old French woman. It seems likely that the cause of the thrombocytopenia was acute hepatitis E virus infection, possibly occurring via an immune mechanism. No complications were noted, in contrast to the two previous reports.
| S-EPMC2446901 | biostudies-literature
Project description: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).
| S-EPMC5115940 | biostudies-literature
Project description:Background:Patients with human immunodeficiency virus (HIV) and/or chronic hepatitis C virus (HCV) infection may be prescribed statins as treatment for metabolic/cardiovascular disease, but it remains unclear if the risk of acute liver injury (ALI) is increased for statin initiators compared to nonusers in groups classified by HIV/HCV status. Methods:We conducted a cohort study to compare rates of ALI in statin initiators vs nonusers among 7686 HIV/HCV-coinfected, 8155 HCV-monoinfected, 17739 HIV-monoinfected, and 36604 uninfected persons in the Veterans Aging Cohort Study (2000-2012). We determined development of (1) liver aminotransferases >200 U/L, (2) severe ALI (coagulopathy with hyperbilirubinemia), and (3) death, all within 18 months. Cox regression was used to determine propensity score-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of outcomes in statin initiators compared to nonusers across the groups. Results:Among HIV/HCV-coinfected patients, statin initiators had lower risks of aminotransferase levels >200 U/L (HR, 0.66 [95% CI, .53-.83]), severe ALI (HR, 0.23 [95% CI, .12-.46]), and death (HR, 0.36 [95% CI, .28-.46]) compared with statin nonusers. In the setting of chronic HCV alone, statin initiators had reduced risks of aminotransferase elevations (HR, 0.57 [95% CI, .45-.72]), severe ALI (HR, 0.15 [95% CI, .06-.37]), and death (HR, 0.42 [95% CI, .32-.54]) than nonusers. Among HIV-monoinfected patients, statin initiators had lower risks of aminotransferase increases (HR, 0.52 [95% CI, .40-.66]), severe ALI (HR, 0.26 [95% CI, .13-.55]), and death (HR, 0.19 [95% CI, .16-.23]) compared with nonusers. Results were similar among uninfected persons. Conclusions:Regardless of HIV and/or chronic HCV status, statin initiators had a lower risk of ALI and death within 18 months compared with statin nonusers.
| S-EPMC5850026 | biostudies-literature
Project description:Background & aimsHepatitis A virus (HAV) is a common cause of enterically transmitted viral hepatitis. In non-immune individuals, infection results in typically transient but occasionally fulminant and fatal inflammatory liver injury. Virus-specific T cell frequencies peak when liver damage is at its zenith, leading to the prevalent notion that T cells exacerbate liver disease, as suspected for other hepatotropic virus infections. However, the overall contribution of T cells to the control of HAV and the pathogenesis of hepatitis A is unclear and has been impeded by a historic lack of small animal models.MethodsIfnar1-/- mice are highly permissive for HAV and develop pathogenesis that recapitulates many features of hepatitis A. Using this model, we identified HAV-specific CD8+ and CD4+ T cells by epitope mapping, and then used tetramers and functional assays to quantify T cells in the liver at multiple times after infection. We assessed the relationships between HAV-specific T cell frequency, viral RNA amounts, and liver pathogenesis.ResultsA large population of virus-specific T cells accumulated within the livers of Ifnar1-/- mice during the first 1-2 weeks of infection and persisted over time. HAV replication was enhanced and liver disease exacerbated when mice were depleted of T cells. Conversely, immunization with a peptide vaccine increased virus-specific CD8+ T cell frequencies in the liver, reduced viral RNA abundance, and lessened liver injury.ConclusionThese data show that T cells protect against HAV-mediated liver injury and can be targeted to improve liver health.Lay summaryHepatitis A virus is a leading cause of acute viral hepatitis worldwide. T cells were thought to contribute to liver injury during acute infection. We now show that virus-specific T cells protect against infection and limit liver injury.
| S-EPMC8604763 | biostudies-literature
Project description:INTRODUCTION:It is difficult to differentiate acute severe hepatitis (AH) with acute on chronic liver failure (ACLF). Aim was to study the role of transient elastography (Fibroscan) in identifying the patients with AH and ACLF. MATERIALS AND METHODS:Consecutive patients of severe AH or ACLF presented within two weeks of jaundice were enrolled. LSM and liver function tests were done at admission, week 1, 4 and at 6 months. Diagnosis of ACLF was based on documenting cirrhotic morphology on imaging and/or liver biopsy and follow-up of these patients for six months. Similarly, AH patients were diagnosed based on serology, no features of cirrhosis on imaging and follow-up of these patients for 6 months documenting reversal of liver stiffness measurement (LSM) to normal. RESULTS:104 patients were included in the final analysis (AH, n = 59, ACLF, n = 45). Out of 59 patients in severe AH group, etiology of acute hepatitis included hepatitis A (HAV, n = 22), hepatitis E (HEV, n = 21), hepatitis B (HBV, n = 4), indeterminate (n = 8) and drug induced liver injury (n = 4). Similarly for ACLF, the causes of chronic liver disease were alcohol (n = 26), hepatitis B (n = 7), hepatitis C (n = 2) and cryptogenic (n = 10). Patients with ACLF were significantly older, had low hemoglobin, low albumin, high bilirubin and lower transaminases level compared to severe AH at admission. LSM was higher in patients with ACLF compared to severe AH (61 ± 18 kPa vs 15 ± 6.4 kPa, P = 0.001) at admission. On multivariate analysis of noninvasive tests only LSM was found to differentiate AH with ACLF significantly. When we took a cutoff of 26 kPa the sensitivity and specificity of diagnosis of ACLF were 96% and 93%, respectively, with area under the curve was 0.98 (0.95-1.005), P = 0.001. CONCLUSION:LSM could differentiate patients with severe AH and ACLF at admission.
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Project description:The diagnosis of drug-induced liver injury relies on exclusion of other causes, including viral hepatitis A, B, and C. Hepatitis E virus (HEV) infection has been proposed as another cause of suspected drug-induced liver disease. We assessed the frequency of HEV infection among patients with drug-induced liver injury in the United States.The Drug-Induced Liver Injury Network (DILIN) is a prospective study of patients with suspected drug-induced liver injury; clinical information and biological samples are collected to investigate pathogenesis and disease progression. We analyzed serum samples, collected from patients enrolled in DILIN, for immunoglobulin (Ig) G and IgM against HEV; selected samples were tested for HEV RNA.Among 318 patients with suspected drug-induced liver injury, 50 (16%) tested positive for anti-HEV IgG and 9 (3%) for anti-HEV IgM. The samples that contained anti-HEV IgM (collected 2 to 24 weeks after onset of symptoms) included 4 that tested positive for HEV RNA genotype 3. Samples from the 6-month follow-up visit were available from 4 patients; they were negative for anti-HEV IgM, but levels of anti-HEV IgG increased with time. Patients who had anti-HEV IgM were mostly older men (89%; mean age, 67 years), and 2 were human immunodeficiency virus positive. Clinical reassessment of the 9 patients with anti-HEV IgM indicated that acute hepatitis E was the most likely diagnosis for 7 and might be the primary diagnosis for 2.HEV infection contributes to a small but important proportion of cases of acute liver injury that are suspected to be drug induced. Serologic testing for HEV infection should be performed, particularly if clinical features are compatible with acute viral hepatitis.
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Project description:Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death.386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)?2.0 and alanine aminotransferase (ALT)?10 × elevated (irrespective of bilirubin level) for acetaminophen (N-acetyl-p-aminophenol, APAP) ALI, or INR?2.0, ALT?10x elevated, and bilirubin?3.0?mg/dl for non-APAP ALI, both groups without any discernible HE. Subjects who progressed to poor outcomes (ALF, death, LT) were compared, by univariate analysis, with those who recovered. A model to predict poor outcome was developed using the random forest (RF) procedure.Progression to a poor outcome occurred in 90/386 (23%), primarily in non-APAP (71/179, 40%) vs. only 14/194 (7.2%) in APAP patients comprising 52% of all cases (13 cases did not have an etiology assigned; 5 of whom had a poor outcome). Of 82 variables entered into the RF procedure: etiology, bilirubin, INR, APAP level and duration of jaundice were the most predictive of progression to ALF, LT, or death.A majority of ALI cases are due to APAP, 93% of whom will improve rapidly and fully recover, while non-APAP patients have a far greater risk of poor outcome and should be targeted for early referral to a liver transplant center.
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Project description:We investigated hepatitis C virus (HCV) epidemiology in populations with liver-related diseases (LRDs) in the Middle East and North Africa. The data source was standardized databases of HCV measures populated through systematic reviews. Random-effects meta-analyses and meta-regressions were performed, and genotype diversity was assessed. Analyses were based on 252 HCV antibody prevalence measures, eight viremic rate measures, and 30 genotype measures on 132,358 subjects. Pooled mean prevalence in LRD populations was 58.8% (95% confidence interval [CI], 51.5%-66.0%) in Egypt and 55.8% (95% CI, 49.1%-62.4%) in Pakistan; these values were higher than in other countries, which had a pooled prevalence of only 15.6% (95% CI, 12.4%-19.0%). Mean prevalence was highest in patients with hepatocellular carcinoma at 56.9% (95% CI, 50.2%-63.5%) and those with cirrhosis at 50.4% (95% CI, 40.8%-60.0%). Type of LRD population and country were the strongest predictors of prevalence, explaining 48.6% of the variation. No evidence for prevalence decline was found, but there was strong evidence for prevalence increase in Pakistan. A strong, positive association was identified between prevalence in the general population and that in LRD populations; the Pearson correlation coefficient ranged between 0.605 and 0.862. The pooled mean viremic rate was 75.5% (95% CI, 61.0%-87.6%). Genotype 4 was most common (44.2%), followed by genotype 3 (34.5%), genotype 1 (17.0%), genotype 2 (3.5%), genotype 6 (0.5%), and genotype 5 (0.3%). Conclusion: HCV appears to play a dominant role in liver diseases in Egypt and Pakistan and has a growing role in Pakistan. Testing and treatment of LRD populations are essential to reduce disease burden and transmission and to reach HCV elimination by 2030.
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