• Epstein-Barr virus
• Mediation effects
• Mendelian randomization
• Non-alcoholic fatty liver disease
• Plasma proteins

• Humans
• Non-alcoholic Fatty Liver Disease/genetics
• Non-alcoholic Fatty Liver Disease/blood
• Mendelian Randomization Analysis
• Genome-Wide Association Study
• Polymorphism, Single Nucleotide
• Herpesvirus 4, Human/immunology
• Herpesvirus 4, Human/genetics
• Blood Proteins/genetics
• Antibodies, Viral/blood
• Antibodies, Viral/immunology
• Genetic Predisposition to Disease

• 82170666 National Natural Science Foundation of China

• Acute cholestatic hepatitis
• Case report
• Epstein-Barr virus
• Hyperferritinemia

• ebv- associated hepatitis
• gastroenterology hepatology
• immunosuppression
• primary ebv infection
• ulcerative colitis (uc)

Epstein–Barr virus (EBV) infection may affect all tissues and organs of the body. Little is known about the impact of this entity on its systematic incorporation in patients with gastric cancer (GC). This study enrolled a total of 113 GC patients with EBV infection (EBVaGC) and 167 GC patients without EBV infection (EBVnGC). It was found that the CRP levels (indicative of inflammatory status) were significantly increased in EBVaGC compared with those in EBVnGC (12.11 mg/L vs. 5.72 mg/L, P = 0.008), but WBC and neutrophils counts were similar in both groups (P > 0.05). Consistent elevations in the levels of liver enzymes, ALP and GGT, with incompatible alterations in ALT or AST were observed in EBVaGC. Slightly prolonged coagulation indices, PT and INR, and decreased albumin consistently suggested impaired synthesis capability of the liver in EBVaGC (all P < 0.05). The level of circulating EBV DNA was positively correlated with the level of GGT, tumor marker CA72-4 and the lymphocyte infiltration in tumor tissues (all P < 0.05). Of note, the EBV associated high-lymphocyte infiltrated tissues presented rich CD8 + T cells. Circulating EBV DNA further showed a predictive role in distinguishing EBVaGC from EBVnGC (AUC 0.79, 95% CI 0.73 to 0.85, P < 0.001), and was associated closely with better overall survival (HR 0.45, 95% CI 0.21 to 0.96, P = 0.039). EBV infection in patients with gastric cancer may be linked to hepatic impairment and immune response. Circulating cell-free EBV DNA is not only a biomarker for the screening of an EBV-related GC subtype but is also an independently prognosis factor for the long-term survival benefit in GC patients.

• Epstein-Barr virus
• diagnosis
• gastric cancer
• inflammation
• liver function
• prognosis

More than 300 million people worldwide suffer from hepatitis B or hepatitis C and more than 1 million people die each year from cirrhosis and liver cancer. In some cases, the nature of hepatitis remains unclear. The purpose of this research was to assess the prevalence of human herpesviruses (cytomegalovirus, Epstein–Barr virus, and herpesvirus type 6) in patients with hepatitis, and to examine their effect on the disease severity. In the clinical materials of 377 patients with acute or chronic hepatitis, DNA of these three herpesviruses was detected in the blood in 13.5% of patients with viral hepatitis B or C and in 10.1% of patients with hepatitis of unspecified etiology. The cirrhosis was diagnosed in patients with herpesviruses 3 times more often than in patients without them. In patients with hepatitis C, the incidence of herpesviruses was higher in the tissue samples of liver biopsies (38.7%) than in the blood. Clinical and virological indicators of hepatitis were considerably higher in the patients with coinfection. Since in patients with hepatitis the presence of herpesviruses is associated with a more severe course of the disease, the detection, and herpesvirus DNA monitoring will help to adjust the course of therapy.

Acute and chronic liver diseases are a major global public health problem; nevertheless, the etiology of 12–30% of cases remains obscure. The purpose of this research was to study the incidence of human herpesviruses (HHVs) cytomegalovirus, Epstein–Barr virus (EBV), and HHV-6 in patients with hepatitis and to examine the effect of HHV on the disease severity. We studied the clinical materials of 259 patients with hepatitis treated in Infectious Clinic n.1 (Moscow) and the archived materials of 118 patients with hepatitis C. HHV DNA was detected in the whole blood in 13.5% of patients with hepatitis B or C and in 10.1% of patients with hepatitis of unspecified etiology. EBV demonstrated the highest incidence (58.1%). Cirrhosis was diagnosed in 50% of patients with HHV and in 15.6% of patients without HHV. In patients with hepatitis C, the frequency of HHV was higher in liver biopsy (38.7%) compared to blood. The clinical and virological indicators of hepatitis were considerably higher in patients with coinfection. Conclusion: HHV detected in patients with viral hepatitis has been associated with a significant effect on the severity of the disease, and we suggest monitoring HHV DNA in patients with severe hepatitis and/or poor response to antiviral drugs.

• HCV RNA
• disease severity
• hepatitis C virus
• herpesviruses
• liver cirrhosis
• unspecified hepatitis
• viral DNA
• viral hepatitis

We report a case of a 46-year-old female living with HIV since 2010 who was originally from Malawi and had settled in the UK in 2001. She was admitted to our hospital with confusion and quickly noted to have a decreased Glasgow Coma Scale of 10/15. Her biochemical parameters showed the presence of elevated liver function tests (LFTs), clotting abnormalities, and her ammonia were found to be >400 mmol/L with a severe metabolic acidosis (pH = 7.05). She was treated for HIV with combined antiretroviral therapy, namely tenofovir disoproxil fumarate, emtricitabine (FTC) and cobicistat boosted atazanavir 2 years previously and had normal LFTs at that time. Her HIV-1 viral load was 1400 copies/ml on admission after recently having an undetectable viral load 2 months previously, and her CD4 count was 480. Her relevant past medical history included insulin-dependent diabetes mellitus. Her other medications included insulin, ramipril, sertraline, amitriptyline, and zopiclone. Toxicology and viral hepatitis screen were negative. Epstein Barr virus (EBV) serology showed evidence of previous exposure, but she was found to have a very high EBV viral load of 55,000 copies/ml, which given her serology, was very likely to be a reactivation of EBV infection rather than a primary EBV infection. In the intensive care unit, the patient deteriorated and died very quickly. The postmortem examination showed extensive hepatic necrosis with collapse. To our knowledge, this is the first case report to show an association between EBV reactivation and fulminant hepatic failure in an individual living with HIV.

• Acute liver failure
• Epstein–Barr virus
• HIV

We report a case of 55-year-old female with chief complaints of fever and deranged liver function tests, diagnosed as autoimmune hepatitis (AIH) and under immunosuppressive therapy for two years. Following the failure in clinical improvement, she was started on anti-tubercular therapy (ATT). While investigating the underlying etiology, virological markers for Hepatitis A to E were found to be negative with plasma Epstein-Barr virus (EBV) viral load of 5 log₁₀ copies/ml. Additional investigation of the liver biopsy showed Hodgkin's lymphoma (HL). The patient was initiated on chemotherapy but eventually succumbed to the illness. This case report underlines the dilemma in the initial diagnosis of AIH and the importance of considering hepatic involvement of EBV as one of the differential diagnosis among clinically suspected AIH cases not responding to immunosuppressive medications.

• Chronic active EBV
• Hodgkin's lymphoma
• Immunosuppressive medications

• Cytomegalovirus
• Epstein-Barr virus
• Hepatitis
• Infectious mononucleosis
• Liver
• Transplantation

• Chronic active EBV infection
• EBV-associated hemophagocytic lymphohistiocytosis
• Hepatitis
• Steatohepatitis
• T/NK-cell lymphoma

• Herpesviridae infections
• Epstein-Barr virus infections
• cytomegalovirus
• hepatitis
• herpes simplex virus

• Epstein-Barr virus
• Hepatitis
• Infectious mononucleosis syndrome

Primary Epstein-Barr virus (EBV) infection is usually asymptomatic, although at times it results in the benign lymphoproliferative disease, infectious mononucleosis (IM), during which almost half of patients develop hepatitis. The aims of the present study are to evaluate polymorphisms of EBV genes circulating in IM isolates from this geographic region and to investigate the correlation of viral sequence patterns with the available IM biochemical parameters.

The study included plasma samples from 128 IM patients. The genes EBNA2, LMP1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses.

The presence of EBV DNA in plasma samples showed correlation with patients’ necessity for hospitalization (p=0.034). The majority of EBV isolates was genotype 1. LMP1 variability showed 4 known variants, and two new deletions (27-bp and 147-bp). Of the 3 analyzed attributes of LMP1 isolates, the number of 33-bp repeats less than the reference 4.5 was the only one that absolutely correlated with the elevated levels of transaminases. EBNA1 variability was presented by prototype subtypes. A particular combination of EBNA2, LMP1, and EBNA1 polymorphisms, deleted LMP1/P-thr and non-deleted LMP1/P-ala, as well as genotype 1/ 4.5 33-bp LMP1 repeats or genotype 2/ 4.5 33-bp LMP1 repeats showed correlation with elevated AST (aspartate aminotransferase) and ALT (alanine transaminase).

This is the first study which identified the association between EBV variability and biochemical parameters in IM patients. These results showed a possibility for the identification of hepatic related diagnostic EBV markers.

• EBV
• LMP1
• gene polymorphism
• infectious mononucleosis
• transaminase

• Immunology
• Liver dysfunction
• Liver failure
• Liver function test
• Systemic infection

Viruses other than the classic hepatotropic viruses, hepatitis A through E, may cause hepatic injury [1]. Among these are Epstein–Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV), human herpes viruses (HHV) 6, 7, and 8, human parvovirus B19, and adenoviruses (Table 11.1). The clinical presentation of infections with these viruses may be indistinguishable from that associated with infection with classic hepatotropic viruses. The presentation ranges from mild and transient elevation of aminotransferases to acute hepatitis and can also lead to acute liver failure [1]. These viruses should be considered as possible etiologic agents in patients who have acute liver injury and whose serologic markers for the classic hepatotropic viruses are not indicative of an active infection [1]. In the present chapter, we review the clinical manifestations and the potential for immune-mediated liver injury associated with several of these viruses (see summary Table 11.2).

• Carcinogenesis
• Drug resistance
• Epstein-Barr virus
• Latent membrane proteins 1
• Latent membrane proteins 2A
• Phosphoinositide 3-kinase/protein kinase B

Xenografting primary human solid tumor tissue into immunodeficient mice is a widely used tool in studies of human cancer biology; however, care must be taken to prove that the tumors obtained recapitulate parent tissue. We xenografted primary human hepatocellular carcinoma (HCC) tumor fragments or bulk tumor cell suspensions into immunodeficient mice. We unexpectedly observed that 11 of 21 xenografts generated from 16 independent patient samples resembled lymphoid neoplasms rather than HCC. Immunohistochemistry and flow cytometry analyses revealed that the lymphoid neoplasms were comprised of cells expressing human CD45 and CD19/20, consistent with human B lymphocytes. In situ hybridization was strongly positive for Epstein-Barr virus (EBV) encoded RNA. Genomic analysis revealed unique monoclonal or oligoclonal immunoglobulin heavy chain gene rearrangements in each B-cell neoplasm. These data demonstrate that the lymphoid neoplasms were EBV-associated human B-cell lymphomas. Analogous to EBV-associated lymphoproliferative disorders in immunocompromised humans, the human lymphomas in these HCC xenografts likely developed from reactivation of latent EBV in intratumoral passenger B lymphocytes following their xenotransplantation into immunodeficient recipient mice. Given the high prevalence of latent EBV infection in humans and the universal presence of B lymphocytes in solid tumors, this potentially confounding process represents an important pitfall of human solid tumor xenografting. This phenomenon can be recognized and avoided by routine phenotyping of primary tumors and xenografts with human leukocyte markers, and provides a compelling biological rationale for exclusion of these cells from human solid tumor xenotransplantation assays.

• Aged
• Aged, 80 and over
• Animals
• Cell Transformation, Viral/genetics
• Female
• Gene Rearrangement
• Herpesvirus 4, Human/genetics
• Humans
• Immunoglobulin Heavy Chains/genetics
• Leukocytes/metabolism
• Lymphoma, B-Cell/genetics
• Lymphoma, B-Cell/immunology
• Lymphoma, B-Cell/metabolism
• Lymphoma, B-Cell/virology
• Male
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Microsatellite Repeats
• Middle Aged
• Neoplasms/genetics
• Neoplasms/immunology
• Neoplasms/metabolism
• Neoplasms/virology
• Neoplasms, Second Primary/genetics
• Neoplasms, Second Primary/immunology
• Neoplasms, Second Primary/metabolism
• Neoplasms, Second Primary/virology
• RNA, Viral/genetics
• Transplantation, Heterologous

• Canadian Institutes of Health Research