Epstein–Barr Virus (EBV) Related Acute Liver Failure: A Case Series from the US Acute Liver Failure Study Group (original) (raw)
Fulminant hepatitis due to Epstein-Barr virus infection
Journal of Hepatology, 1995
Epstein-Barr virus infection is a benign disease, which may occasionally be fatal, particularly in children. Epstein-Barr virus infection is rare in elderly subjects and appears to have a self-limited course. An unusual case of fulminant hepatitis due to primary Epstein-Barr virus infection in a 62-year-old male 18 days after a cardiosurgical operation and blood transfusions is described in the present paper. Post-mortem examination of the liver showed massive hepatic necrosis. The etiology was established by increase in IgM antibodies to Epstein-Barr virus (titer 1:3.120) in serum and by cellular expression of Epstein-Barr virus DNA in liver tissue.
Acute hepatitis induced by Epstein-Barr virus infection: a case report
The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology, 2007
Epstein-Barr virus is a causative agent of infectious mononucleosis syndrome, which is commonly seen in young adults and characterized by fever, sore throat and lymphadenopathy. In adults, Epstein-Barr virus infection can cause liver function test abnormalities without pharyngitis or lymphadenopathy. Liver involvement usually causes mild elevation of transaminases and this abnormality resolves spontaneously. Jaundice might develop rarely during the clinical course of Epstein-Barr virus infection. It reflects either more severe hepatitis or Epstein-Barr virus infection-associated hemolytic anemia. Acute hepatitis with icterus is a rare clinical manifestation in primary Epstein-Barr virus infection. Especially in older patients, Epstein-Barr virus infection can cause cholestasis; the diagnosis can be established by elimination of extrahepatic biliary obstruction. Here we report an acute hepatitis in a patient who presented with icterus and was diagnosed as acute Epstein-Barr virus inf...
Acute hepatitis: a rare complication of Epstein-Barr virus (EBV) infection
The Journal of Infection in Developing Countries, 2010
Infectious Mononucleosis (IM), a benign lymphoproliferative disease, is the best known clinical syndrome caused by Epstein-Barr Virus (EBV). It usually resolves over a period of weeks or months without sequelae but may occasionally be complicated by a wide variety of neurologic, hematologic, hepatic, respiratory, and psychological complications. In this report we describe a patient with acute hepatitis following EBV-IM in a previously healthy woman. A 26-year-old woman who presented with fever, generalized weakness, nausea, sore throat, yellowing of skin, and a generalized skin rash was admitted to our clinic. Tonsillar enlargement, pharyngeal erythema, palatal petechiae, lymphadenopathy, and jaundice were noted. Significant atypical lymphocytes ( > 10%) were seen on the peripheral blood smear. Liver function tests such as ALT: 303 U/L, AST: 172 U/L, ALP: 193 U/L and total bilirubin: 7.3 mg/dl were elevated. Serological tests for EBV infection were consistent with acute infection (EBV virus capsid antigen was reactive with IgM and IgG antibodies). The Monospot test was also positive. On the seventh day, liver function tests and bilirubin had risen to peak level and platelets were decreased. The patient was managed supportively and her critical condition improved and was finally stabilized. Although the prognosis for IM is very favorable, a variety of acute complications may occur.
The role of Epstein–Barr virus in acute and chronic hepatitis
Journal of Hepatology, 2006
Background/Aims: Epstein-Barr virus has a seroprevalence of more than 80% world wide and is known to be associated with hepatitis. However, little is known about the underlying pathogenesis and immunmechanisms and no standard diagnostic criteria to diagnose EBV-hepatitis are available.
European Journal of Internal Medicine, 2011
Objectives: Epstein-Barr Virus (EBV) infection has the potential to establish life-long, benign infections in their hosts. Although biochemical evidence of hepatocellular damage is common, jaundice is uncommon and complete recovery is the rule. The present study describes clinical characteristics and changes of liver function tests during the course of infectious mononucleosis. Patients and methods: All immunocompetent patients with hepatic dysfunction associated with acute EBV infection, cared for at the University Hospital of Heraklion, over a 6-year period, were identified and retrospectively studied. Results: The study included 41 patients with a median age of 18.5 (15-51) years. Aspartate-aminotrasferase (AST) and alanine-aminotrasferase (ALT) were increased in an average maximum of 5-fold. Both transaminase levels started to rise 2 days after the clinical onset of the disease, and returned to normal after a period of 20 days. Alkaline-phosphatase (ALP), γ-glutamyltransferase (γ-GT) and bilirubin levels also increased above the normal values during the course of the disease and returned to normal after a period of 20, 30 and 22 days respectively. The changes of mean AST and ALT levels over time were statistically significant, while those of mean ALP, γ-GT and bilirubin levels over time were not. Anicteric cholestatic liver disease was observed in 24 patients (59%), while icteric only in 2 (6%). Conclusion: Liver involvement in acute EBV infection represents mild and self-limited hepatitis with predominantly cholestatic features.
Author's personal copy Epstein Barr Virus hepatitis
Objectives: Epstein-Barr Virus (EBV) infection has the potential to establish lifelong , benign infections in their hosts. Although biochemical evidence of hepatocellular damage is common, jaundice is uncommon and complete recovery is the rule. The present study describes clinical characteristics and changes of liver function tests during the course of infectious mononucleosis. Patients and methods: All immunocompetent patients with hepatic dysfunction associated with acute EBV infection, cared for at the University Hospital of Heraklion, over a 6-year period, were identified and retrospectively studied. Results: The study included 41 patients with a median age of 18.5 (15-51) years. Aspartate-aminotrasferase (AST) and alanine-aminotrasferase (ALT) were increased in an average maximum of 5-fold. Both transaminase levels started to rise 2 days after the clinical onset of the disease, and returned to normal after a period of 20 days. Alkaline-phosphatase (ALP), γ-glutamyltransferase (γ-GT) and bilirubin levels also increased above the normal values during the course of the disease and returned to normal after a period of 20, 30 and 22 days respectively. The changes of mean AST and ALT levels over time were statistically significant, while those of mean ALP, γ-GT and bilirubin levels over time were not. Anicteric cholestatic liver disease was observed in 24 patients (59%), while icteric only in 2 (6%). Conclusion: Liver involvement in acute EBV infection represents mild and self-limited hepatitis with predominantly cholestatic features.
Etiology and outcome of patients with viral-induced acute liver failure
International Journal of Research in Medical Sciences
Background: Acute liver failure (ALF) is a rare medical emergency and devastating clinical syndrome associated with high mortality in the absence of immediate intensive supportive care, specific treatment, or liver transplantation. Viral hepatitis is still one of the main causes of ALF in the India as well in world. We aimed to determine the etiology of Viral-ALF and to compare the outcome and clinical and biochemical variables in patients with hepatitis E and non HEV group in this prospective study.Methods: A total of 37 patients with a diagnosis of viral-ALF were included in the study. The variables evaluated were demographic, signs and symptoms, biochemical parameters, severity of liver injury, outcome, complications and duration of hospital stay.Results: Out of 37 Viral-ALF patients, Acute HEV-induced ALF (48.6%) was most common followed by HBV (24.3%) and HAV (21.6%). There were significantly more females in HEV group (61.1%) than non HEV group (21.1%) (P = 0.014). Overall mort...
Epstein-Barr virus: Silent companion or causative agent of chronic liver disease?
World Journal of Gastroenterology, 2010
The Epstein-Barr virus (EBV) has an important and multifaceted role in liver pathology. As a member of the herpes virus family, EBV establishes a persistent infection in more than 90% of adults. Besides acute hepatitis during primary infection, many clinical syndromes of interest for the hepatologist are associated with EBV infection. The role of EBV in the evolution of chronic hepatitis from hepatotropic viruses is considered. Chronic EBVassociated hepatitis is suspected in immunocompetent adults with compatible serology, suggestive histology and detection of the viral genome in the liver and/or increase of specific circulating cytotoxic T-lymphocytes. EBV is the main cause of post-transplant lymphoproliferative disorders which occur in up to 30% of cases. EBV-driven lymphoproliferative diseases are also recognized in non-immunocompromised patients and liver is involved in up to a third of the cases. Directly implicated in the pathogenesis of different tumors, EBV has a disputable role in hepatocellular carcinoma carcinogenesis. Further research is required in order to establish or reject the role of EBV in human liver cancer. This paper attempts to discuss the range of EBV-associated chronic liver diseases in immunocompetent patients, from mild, self-limiting mononuclear hepatitis to liver cancer.
Liver Failure due to Acute Viral Hepatitis (A-E)
Visceral medicine, 2016
Background: Viral hepatitis is still one of the key causes of acute liver failure (ALF) in the world. Methods: A selective literature search of the PubMed database was conducted, including current studies, reviews, metaanalyses, and guidelines. We obtained an overview of ALF due to viral hepatitis in terms of epidemiology, course, and treatment options. Results: Most fulminant viral courses are reported after infection with hepatitis A, B, and B/D, but not with hepatitis C. Hepatitis E is also known to cause ALF but has not gained much attention in recent years. However, more and more autochthonous hepatitis E virus infections have been recently observed in Europe. Reactivation of hepatitis B virus (HBV) under immunosuppressive conditions, such as after intensive chemotherapy, is also an increasing problem. For most viral-induced cases of ALF, liver transplantation represented the only therapeutic option in the past. Today, immediate treatment of HBV-induced ALF with nucleotide or nucleoside analogs is well tolerated and beneficially affects the course of the disease. Conclusion: Although numbers in Western European countries are decreasing rapidly, reliable diagnostic screening for hepatitis A-E is necessary to identify the etiology and to determine those most at risk of developing ALF.
Chronic Epstein-Barr virus-related hepatitis in immunocompetent patients
World journal of gastroenterology : WJG, 2006
To investigate reactivated Epstein-Barr virus (EBV) infection as a cause for chronic hepatitis. Patients with occasionally established elevated serum aminotransferases were studied. HIV, HBV and HCV-infections were excluded as well as any other immunosuppressive factors, metabolic or toxic disorders. EBV viral capsid antigen (VCA) IgG and IgM, EA-R and EA-D IgG and Epstein-Barr nuclear antigen (EBNA) were measured using IFA kits. Immunophenotyping of whole blood was performed by multicolor flow cytometry. CD8(+) T cell responses to EBV and PHA were determined according to the intracellular expression of IFN-gamma. The mean alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (GGTP) values exceeded twice the upper normal limit, AST/ALT ratio < 1. Serology tests showed reactivated EBV infection in all patients. Absolute number and percentages of T, B and NK cells were within the reference ranges. Fine subset analysis, in comparison to EBV(+) healthy carriers, revealed a...
Viral Hepatitis-Related Acute Liver Failure
Amer J Gastroenterol, 2003
OBJECTIVES: Viral hepatitis has previously been the major cause of acute liver failure (ALF) in the United States. We aimed to determine the incidence of viral hepatitis-related ALF and to compare the outcome and clinical and biochemical variables in patients with hepatitis A and B. METHODS: A total of 354 patients with ALF from multiple centers were screened for possible acute viral etiology. RESULTS: Forty-three patients (12.1% of all ALF cases) had acute viral hepatitis: hepatitis A (n ϭ 16), hepatitis B (n ϭ 26), and herpes simplex virus infection (n ϭ 1). There was no difference between groups with regard to age, gender, body mass index, admission or peak coma grade, symptom duration, admission mean arterial pressure, temperature, or biochemical liver tests, creatinine, arterial pH, or rate of infections. Platelet count was significantly higher in hepatitis A patients than in hepatitis B patients. The transplantation-free (spontaneous) survival rate was significantly higher for hepatitis A patients (69%) than for hepatitis B patients (19%, p ϭ 0.007), whereas the liver transplantation rate was higher in hepatitis B patients (62%) than in hepatitis A patients (19%, p ϭ 0.017). Spontaneous survivors had significantly higher mean arterial pressure, higher platelet count, and lower AST/ALT ratio than patients who did not survive spontaneously. CONCLUSIONS: Viral hepatitis now comprises only oneeighth of all ALF cases in the United States. The marked difference in spontaneous survival between hepatitis A and B cannot be explained by the severity of hepatic dysfunction on admission but may rather be an inherent feature of the infections or a bias toward transplanting patients with hepatitis B.
Acute liver failure: Established and putative hepatitis viruses and therapeutic implications
Journal of Gastroenterology and Hepatology, 2000
liver, such as the hepatitis viruses A to E, and those in which liver involvement may occur as part of disseminated infection, as with Epstein-Barr virus, cytomegalovirus (CMV), Varicella zoster virus, adenovirus and herpes simplex virus (HSV).The latter occur mainly, although not exclusively, in the immunosuppressed and in children. 1,2 Fulminant hepatitis has also been reported with infection with Toga virus-like particles, papilloma virus, paramyxoviruses and haemorrhagic fever viruses. 1,3 Although decreasing as a cause of ALF in Western countries, where hepatotoxicity due to acetaminophen in particular is increasingly recognized 4,5 (J Burnuau, pers. comm., 1999), viral hepatitis remains the major aetiological factor in a large part of the world, including Asia, the Western Pacific region, the Middle East, Africa, South America and some European centres.
Annals of clinical microbiology and antimicrobials, 2014
Few data can be available regarding acute liver failure (ALF) caused by severe acute hepatitis B up to now. This study aims to report such cases from China. We conducted a multi-center investigation on ALF from 7 tertiary hospitals in different areas of China. A total of 11 patients with ALF caused by severe acute hepatitis B were finally identified. In these patients, there were 10 male and 1 female patients. As a serious complication, apparent hemorrhage occurred in 9 patients. Eventually, in these 11 patients, 4 survived and 7 died. 4 died of heavy bleeding, 2 died of systemic inflammatory response syndrome and 1 died of irreversible coma. No patients received liver transplantation. ALF caused by severe acute hepatitis B is worthy of formal studies based on its rarity and severity.
Hepatology, 2012
; and the Acute Liver Failure Study Group Hepatitis B virus (HBV)-related acute liver failure (HBV-ALF) may occur after acute HBV infection (AHBV-ALF) or during an exacerbation of chronic HBV infection (CHBV-ALF). Clinical differentiation of the two is often difficult if a previous history of HBV is not available. Quantitative measurements of immunoglobulin M (IgM) anti-hepatitis B core antibody (anti-HBc) titers and of HBV viral loads (VLs) might allow the separation of AHBV-ALF from CHBV-ALF. Of 1,602 patients with ALF, 60 met clinical criteria for AHBV-ALF and 27 for CHBV-ALF. Sera were available on 47 and 23 patients, respectively. A quantitative immunoassay was used to determine IgM anti-HBc levels, and real-time polymerase chain reaction (rtPCR) was used to determine HBV VLs. AHBV-ALFs had much higher IgM anti-HBc titers than CHBV-ALFs (signal-to-noise [S/N] ratio median: 88.5; range, 0-1,120 versus 1.3, 0-750; P < 0.001); a cut point for a S/N ratio of 5.0 correctly identified 44 of 46 (96%) AHBV-ALFs and 16 of 23 (70%) CHBV-ALFs; the area under the receiver operator characteristic curve was 0.86 (P < 0.001). AHBV-ALF median admission VL was 3.9 (0-8.1) log10 IU/mL versus 5.2 (2.0-8.7) log10 IU/mL for CHBV-ALF (P < 0.025). Twenty percent (12 of 60) of the AHBV-ALF group had no hepatitis B surface antigen (HBsAg) detectable on admission to study, wheras no CHBV-ALF patients experienced HBsAg clearance. Rates of transplant-free survival were 33% (20 of 60) for AHBV-ALF versus 11% (3 of 27) for CHBV-ALF (P 5 0.030). Conclusions: AHBV-ALF and CHBV-ALF differ markedly in IgM anti-HBc titers, in HBV VLs, and in prognosis, suggesting that the two forms are, indeed, different entities that might each have a unique pathogenesis. (HEPATOLOGY 2012;55:676-684) H epatitis B virus (HBV)-related acute liver failure (ALF) constitutes 1% of those experiencing acute or chronic HBV (AHBV-ALF and CHBV-ALF, respectively). 1,2 Patients who have AHBV-ALF, as well as those with an acute exacerbation (i.e., disease flare) of CHBV-ALF, cannot be distinguished on clinical grounds without historical or histological evidence for chronicity, which may be lacking in acutely ill patients. CHBV-ALF may occur spontaneously or as a result of the effect of immunosuppression on viral replication and immunity. 1,2 We postulated that serological or virological factors might better separate acute
Clinical Manifestations and Laboratory Tests of AECHB and Severe Hepatitis (Liver Failure)
Acute Exacerbation of Chronic Hepatitis B, 2019
This chapter describes the clinical symptoms and signs of AECHB and HBV ACLF, classification, grading of HBV ACLF and their features, diagnostic principles and standards in liver pathology, biochemistry, and virology of HBV ACLF. Liver failure is defined as serious damage to the liver cause by a variety of etiologies, leading to liver function disorder or even decompensation, and clinical syndromes with coagulopathy, jaundice, hepatic encephalopathy, and ascites. Severe hepatitis B can be indicated pathologically by apparent hepatocellular necrosis, including extensive multifocal, confluent, bridging, sub-massive or massive necrosis. Laboratory tests during the course of severe exacerbation of chronic hepatitis B can reflect pathological changes and liver function in a timely manner, providing objective and informative reference data for evaluation of disease severity and treatment efficacy. Among the most important laboratory tests are those for prothrombin activity, international ...
Hepatitis B infection in patients with acute liver failure in the United States
Hepatology, 2001
Occult hepatitis B virus (HBV) infection has been reported in 30% to 50% of patients with acute liver failure (ALF) in small case series. The aim of this study was to determine the prevalence of occult HBV infection in a large series of ALF patients in the United States and the prevalence of precore and core promoter variants in patients with ALF caused by hepatitis B. Sera from patients in the US ALF study and liver, when available, were tested using nested polymerase chain reaction (PCR) with primers in the HBV S and precore regions. PCR-positive samples were sequenced. Sera and/or liver from 139 patients (39 males, 100 females; mean age, 42 years) enrolled between January 1998 and December 1999 were studied. Twelve patients were diagnosed with hepatitis B, 1 with hepatitis B؉C؉D coinfection, and 22 had indeterminate etiology. HBV DNA was detected in the sera of 9 (6%) patients; all 9 had ALF caused by hepatitis B. HBV genotypes A, B, C, and D were present in 4, 3, 1, and 1 patients, respectively. Seven of these 9 patients had precore and/or core promoter variants. Liver from 19 patients were examined. HBV DNA was detected in the liver of 3 patients with ALF caused by hepatitis B, but in none of the remaining 16 patients with non-B ALF. Contrary to earlier reports, occult HBV infection was not present in this large series of ALF patients in the United States. HBV precore and/or core promoter variants were common among US patients with ALF caused by hepatitis B.
Journal of gastroenterology and hepatology, 2008
Background and Aim: Hepatitis E virus (HEV) has recently been implicated in episodes of acute decompensation in patients having underlying chronic liver disease (CLD) of varying etiology. However, HEV as a cause of acute exacerbation of previously asymptomatic and unrecognized hepatitis B virus (HBV)-infected patients is less well described. The aim of the present study was to investigate the etiology of acute exacerbation of previously asymptomatic and unrecognized HBV-infected patients and to evaluate the relative role of HEV. We also investigated the effect of superinfection on the clinical spectrum of underlying HBV infection. Methods: Forty-three patients presented with the following were retrospectively analyzed: (i) clinical features suggestive of acute hepatitis; (ii) with hepatitis B surface antigen (HBsAg) (+); (iii) IgM hepatitis B core antibody (IgM anti-HBc) (-); (iv) no previous history of liver disease; (v) no features suggestive of CLD at presentation; (vi) HBsAg remaining (+) for at least 12 months on follow up; and (vii) having a follow-up biopsy during the convalescent phase showing evidence of chronic hepatitis B. Results: Of the 43 patients, 21 were hepatitis e antigen (HBeAg) (+) (Gr.1) and 22 HBeAg (-) (Gr.2) at presentation. In Gr.1, only two (9.5%) had superinfection (both with hepatitis A virus), whereas in Gr.2, 11 (50%) had superinfection (27.3% hepatitis E, 13.6% hepatitis A and 9.1% both) (P = 0.007). In Gr.1, the remaining 19 (90.5%) patients had spontaneous exacerbation (immune clearance with spontaneous seroconversion) whereas in Gr.2, the remaining 11 (50%) had spontaneous exacerbation (due to reactivation). Overall, HEV superinfection contributed to 20% of acute exacerbation episodes and, in particular, 36% of episodes in initially HBeAg (-) patients. Time to alanine aminotransferase normalization was longer in patients with superinfection (n = 13) as compared to spontaneous exacerbation (n = 30) (median [range] 36 vs 16 [6-36] weeks, P = 0.001). During convalescence, there was no significant difference between histological activity index score (median [range] 8 [4-11] vs 8 [4-16] weeks, P = 0.629) and fibrosis scores (median [range] 3.5 [1-4] vs 2 [1-4] weeks, P = 0.099] on liver biopsy after recovery among patients with acute exacerbation due to superinfection and spontaneous exacerbation. Conclusions: Acute exacerbations in HBeAg (+) patients are most often due to spontaneous viral activation, while in HBeAg (-) patients, superinfection with non-B hepatitis viruses and spontaneous viral activation are equally common. HEV is an important cause of acute exacerbation in previously asymptomatic and unrecognized patients with HBVrelated CLD.
Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology, 2015
Acute viral hepatitis (AVH) is mostly caused by hepatitis E (HEV) and hepatitis A (HAV) viruses in India. This study was undertaken to find out the incidence of various hepatotropic and non-hepatotropic viruses in AVH and acute-on-chronic liver failure (ACLF) patients. Six-hundred and seventy-three adult patients of AVH and ACLF were screened for acute serological markers of hepatotropic (A, B, C, D, and E) and the non-hepatotropic cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Viral etiology profile in 295 samples with confirmed etiology were HEV in 155 (52.5 %); HAV in 43 (14.5 %); HBV in 35 (11.8 %); HCV in 1 (0.3 %); mixed viral etiology in 30 (10.1 %); and non-hepatotropic viruses, cytomegalovirus, and Epstein-Barr virus in 31 (10.5 %). Two-hundred and six patients (69.8 %) were AVH and 89 (30.1 %) ACLF. HEV was the commonest cause of infection in both the groups AVH (n = 95, 46.1 %) and ACLF (n = 60, 67.4 %). Twenty-nine (9.8 %) patients died on follow up; mortality was h...