Prolonged cholestasis after acute viral hepatitis: successfully treated with oral steroid.

Cholestasis is a rare distinct complication of hepatitis A infection. Usually it runs a long indolent course with significant pruritus and malabsorption lasting for few months. A 9-year-old boy presented with yellowish discolouration of eye for 1 month. Liver function test showed conjugated hyperbilirubinaemia. Serology was positive for hepatitis A IgM antibody. Liver biopsy showed features of hepatitis with cholestasis. Child successfully treated with oral steroids.

A Rare Presentation of Epstein-Barr Virus Infection.

BACKGROUND: Epstein-Barr virus (EBV) is a herpesvirus spread by intimate contact. It is known to cause infectious mononucleosis. Complications, including hematologic pathology and splenic rupture, are uncommon. This report is a case of EBV-induced autoimmune hemolytic anemia and biliary stasis. CASE REPORT: An 18-year-old man presented to the emergency department with abdominal pain, nausea, vomiting, and jaundice. He did not have risk factors for liver injury or hepatitis. His vital signs were notable for a fever. On examination, he was obviously jaundiced, but not in distress. Laboratory evaluation showed hemolytic anemia and biliary stasis. Ultimately, his inpatient workup yielded positive EBV serology and a positive direct agglutinin test with cold agglutinins. He made a full recovery with supportive care. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: EBV is a widely disseminated herpesvirus. Infectious mononucleosis is a common presentation of acute infection, and treatment of EBV-related diseases are largely supportive. Complications, such as splenic rupture and hematologic pathology, are uncommon. Biliary stasis and autoimmune hemolytic anemia in the form of cold agglutinin disease secondary to EBV is rare, and typically resolves with supportive care and cold avoidance. More advanced treatment methods are available in the setting of severe hemolysis. Elevated transaminases, direct hyperbilirubinemia, or evidence of hemolytic anemia in the setting of a nonspecific viral syndrome should raise suspicion for EBV infection. Rapid recognition can lead to more prompt prevention and treatment of other EBV-related complications.

[Cytomegalovirus cholestasis in an immunocompetent host]. / Cholestase secondaire à une infection à cytomégalovirus chez une patiente immunocompétente.

Primary infection or reactivation of cytomegalovirus (CMV) can induce in immunocompromised patients a severe disease depending on the type of immuno-suppression, and can affect multiple organs. On the other hand, the infection is benign and mostly asymptomatic in immunocompetent individuals who do not require antiviral treatment. Rare cases of primary infection have been documented. In this article, we report the case of a 21-year-old immunocompetent female patient with CMV cholestatic jaundice. The diagnosis was retained on all clinico-pathologic data after eliminating the autoimmune, surgical and other infectious causes. Resolution of cholestasis has been observed with ganciclovir.

A Rotavirus-Induced Mouse Model to Study Biliary Atresia and Neonatal Cholestasis.

Biliary atresia is a devastating neonatal cholangiopathy that affects both extra- and intrahepatic bile ducts progressing to fibrosis and end-stage liver disease by 2 years of age. Despite re-establishment of biliary drainage following a Kasai portoenterostomy (surgical procedure), many infants develop fibrosis requiring liver transplant. In the murine model of biliary atresia, rhesus rotavirus infection of newborn pups results in a cholangiopathy paralleling human biliary atresia and is used to study mechanistic aspects of the disease. The infected mice displayed histopathological signs similar to human biliary atresia, with bile duct obstruction, bile duct proliferation, and liver inflammation with fibrosis.

Anti-inflammatory consequences of bile acid accumulation in virus-infected bile duct ligated mice.

Cholestatic patients exhibiting high bile acid serum levels were reported to be more susceptible to bacterial and viral infections. Animal studies in bile duct ligated (BDL) mice suggest that cholestasis leads to an aggravation of hepatic bacterial infections. We have investigated the impact of cholestasis on mouse cytomegalovirus (MCMV)-induced immune responses and viral replication. While MCMV did not aggravate BDL-induced liver damage, BDL markedly reduced MCMV-triggered chemokine expression and immune cell recruitment to the liver. MCMV-infected BDL mice showed diminished trafficking of Ly6C+/F4/80+ myeloid cells and NK1.1+ NK cells to the liver compared to MCMV infected control mice. Moreover, virus-driven expression of CCL7, CCL12, CXCL9 and CXCL10 was clearly impaired in BDL- compared to sham-operated mice. Furthermore, production of the anti-inflammatory cytokine IL-10 was massively augmented in infected BDL mice. In contrast, intra- and extrahepatic virus replication was unaltered in BDL-MCMV mice when compared to sham-MCMV mice. Cholestasis in the BDL model severely impaired pathogen-induced chemokine expression in the liver affecting CCR2- and CXCR3-dependent cell trafficking. Cholestasis resulted in reduced recruitment of inflammatory monocytes and NK cells to the liver.

Hepatitis E virus infection mimicking acute graft rejection in a liver transplant recipient.

INTRODUCTION: In liver transplant (LT) patients, hepatitis E virus (HEV) can lead to acute liver failure, chronic hepatitis and graft cirrhosis. Few data on graft rejection associated with HEV are available and are subject to discussion. CASE REPORT: Here we report the case of a 58-year-old male patient who underwent LT in July 2015 for cirrhosis due to NASH and chronic alcohol intake complicated by hepatocellular carcinoma. LT was performed with a deceased donor isogroup and a mismatch CMV (donor+ and recipient-). HEV serology was negative before LT. In February 2016, we noted abnormal liver function, with increased transaminases and cholestasis parameters, without functional complaints. The patient was immunosuppressed by tacrolimus (4mg) and everolimus (2mg). Abdominal ultrasound was normal and liver biopsy showed signs of acute rejection (Banff score 6/9). We dispensed 500mg of methylprednisolone before obtaining positive serological results for HEV genotype 3 infection. Ribavirin (1,200mg per day) for 3 months was started, leading to rapid improvement in liver tests. Viral load became negative one month later. To date, the patient is under LP 5mg tacrolimus with normal liver tests. CONCLUSION: We describe a case of HEV genotype 3 infection mimicking acute cellular rejection, with a favorable outcome due to ribavirin treatment. As intensive immunosuppressive therapy administered for graft rejection may promote viral replication and worsen liver damage, potential HEV infection must be considered in cases of pathological signs of acute cellular rejection, in order to avoid chronic graft hepatitis, cirrhosis and liver decompensation.

Detection of Cytomegalovirus in Liver Tissue by Polymerase Chain Reaction in Infants With Neonatal Cholestasis.

AIM: Cytomegalovirus (CMV) is associated with neonatal cholestasis (NC). Diagnosis of CMV infection is most often based on either positive blood CMV IgM or CMV blood polymerase chain reaction (PCR). Isolation of CMV in liver tissues in patients with NC has rarely been reported. This study was undertaken to see if CMV is present in liver tissues of patients with NC and evaluate the correlation between positive CMV PCR in liver tissue with the serology and blood PCR. METHODS: This study was conducted in 31 infants with NC from June 2015 to December 2016. All patients underwent blood CMV IgM, blood CMV PCR and liver CMV PCR. Prevalence of CMV in NC based on positive liver CMV PCR was calculated. Sensitivity and specificity of the serologic markers and blood CMV PCR to identify CMV infection in the liver was determined. RESULTS: CMV IgM was positive in 13 (42%) patients, CMV IgG was positive in 26 (84%) patients and blood CMV PCR was positive in 23 (74%) patients. Liver CMV PCR was positive in 16 (52%) patients. Fifteen (48%) patients had biliary atresia (BA), 10 (32%) patients had neonatal hepatitis, 5 (16%) had paucity of bile ducts and 1 (3%) had ascending cholangitis. Of the 16 patients with positive liver CMV PCR, 8 (50%) had BA, 4 (25%) had neonatal hepatitis, 3 (19%) had paucity of bile ducts and 1 (6%) had ascending cholangitis. Sensitivity of blood CMV IgM in relation to liver CMV PCR was 69% and specificity was 61%. Sensitivity of blood CMV PCR was 61% and specificity was 71% when compared with liver CMV PCR. CONCLUSION: CMV is present in the liver tissues of more than half the patients with NC. Serology or blood CMV PCR is apparently not an accurate marker of CMV in the liver tissue. Also, CMV infection in children seems to be associated equally with BA or non-BA neonatal hepatitis.

Fibrosing Cholestatic Hepatitis C After Liver Transplantation: Therapeutic Options Before and After Introduction of Direct-Acting Antivirals: Our Experience and Literature Review.

BACKGROUND: Cirrhosis caused by hepatitis C is the most common indication for liver transplantation. The most aggressive form of hepatitis C virus (HCV) relapse after liver transplantation is fibrosing cholestatic hepatitis C, which can be observed in 2% to 15% of recipients. METHODS: Double therapy with peg-interferon and ribavirin was characterized by low antiviral response, rapid fibrosis, and frequent graft failure within 1 year after surgery. RESULTS: Introduction of direct-acting antivirals for HCV treatment allows for more efficient therapy with less adverse reactions, including patients with fibrosing cholestatic hepatitis C. CONCLUSIONS: We present 4 (2.5%) cases of cholestatic viral hepatitis C recurrence in patients undergoing transplantation between 2006 and 2015 at the Transplantation Institute of Warsaw; during this period, 158 liver transplants were performed in patients with cirrhosis caused by HCV infection.

Infección por virus de Epstein-Barr y hepatitis aguda colestásica / Infection with Epstein-Barr virus and acute cholestatic hepatitis

El Virus de Epstein-Barr (VEB) es un herpes virus cuyo medio de transmisión es a través de secreciones de una persona portadora del virus, siendo el hombre el único huésped. La primo infección por lo general es asintomática o puede manifestarse como mononucleosis infecciosa con la triada clásica de fiebre, faringitis y adenopatías. Esta cursa con elevación leve y autolimitada de transaminasas, por lo que solo un 5% de los casos se ha asociado con hepatitis aguda colestásica. Presentamos a un paciente con una infección por virus de Epstein-Barr y hepatitis aguda colestásica con historia de aparición de una masa cervical lateral derecha. Al examen físico evidencia ictericia a nivel de escleras, mucosas y ambos miembros superiores. Niveles de bilirrubina en sangre elevados. Paciente con ultrasonido hepático y vías biliares normal, colangiopancreatografía retrograda endoscópica normal por lo que se procede a realizar pruebas serológicas para VEB siendo esta positiva. Se da tratamiento con ganciclovir, mejorando pruebas de función hepática y disminuyendo ictericia, teniendo así una evolución favorable del paciente...(AU)

Epstein-Barr Virus (EBV) is a herpes virus, whose means of transmission is through secretions of a person carrying the virus, the man being the only host. The cousin infection is usually asymptomatic or may manifest as infectious mononucleosis with the classical triad of fever, pharyngitis and lymphadenopathy. This is a mild and self-limiting elevation of transaminases, which means that only 5% of the cases have been associated with acute cholestasis hepatitis. We present a patient with an Epstein-Barr virus infection and acute cholestasis hepatitis with a history of the appearance of a right lateral cervical mass. Physical examination shows jaundice at the level of sclera, mucosa and both upper limbs. Elevated blood bilirubin levels. Patient with hepatic ultrasound and normal bile ducts, normal endoscopic retrograde cholangiopancreatography, so serological tests for EBV are performed and this is positive. Ganciclovir is given, improving liver function tests and decreasing jaundice, thus having a favorable evolution of the patient...(AU)

Acute cholestatic hepatitis induced by Epstein-Barr virus infection in an adult: a case report.

BACKGROUND: Acute cholestatic hepatitis without features of infectious mononucleosis is a rare presentation of primary Epstein-Barr infection, with only several cases previously reported in the medical literature. Early investigation for Epstein-Barr virus in febrile patients with deranged liver function tests and no demonstrable biliary obstruction on imaging can expedite both diagnosis and treatment, thereby avoiding costly or invasive procedures such as liver biopsy. CASE PRESENTATION: A 59-year-old white woman of Anglo-Saxon descent presenting with a febrile illness was noted to have a cholestatic picture of deranged liver function tests. Over the following week a progressive obstructive jaundice developed, with no evidence of choledocholithiasis on ultrasound or magnetic resonance cholangiopancreatography. Specific immunoglobulin M antibodies against Epstein-Barr virus were detected in her serum and the diagnosis of Epstein-Barr hepatitis was confirmed by polymerase chain reaction testing. Supportive treatment was implemented and her liver function had normalized 3 months after presentation. CONCLUSIONS: Epstein-Barr virus is associated with a wide variety of clinical manifestations and can present as cholestatic hepatitis with or without features of infectious mononucleosis. While the diagnosis is often suggested by serological testing, Epstein-Barr virus polymerase chain reaction is a new non-invasive laboratory study that can help identify infection in cases where the clinical presentation is atypical.

Liver Metabolic Function of Hemodialysis Patients With Surface Antigen-Positive Hepatitis B.

OBJECTIVES: Hepatitis B virus remains a serious problem, particularly for patients with end-stage renal disease on maintenance hemodialysis. This study sought to investigate the levels of serum cholestasis markers in hepatitis B virus-positive patients on maintenance hemodialysis. MATERIALS AND METHODS: This study included 50 hepatitis B virus-positive hemodialysis patients (aged 45.4 ± 4.1 years). All patients had been receiving hemodialysis (because of end-stage renal disease) from 2008 to 2009 at the "MedServis" Private Medical Center in Baku, Azerbaijan. We studied serum gamma-glutamyl transpeptidase and alkaline phosphatase levels after the admission (baseline levels) and after 1, 3, and 6 months of beginning of hemodialysis (or observation for control groups-2). The control groups consisted of hepatitis B virus-negative hemodialysis patients (control group-1) and hepatitis B virus-positive patients with end-stage renal disease not requiring hemodialysis (control group-2). RESULTS: After 1 and 3 months of hemodialysis, serum gamma-glutamyl transpeptidase and alkaline phosphatase levels gradually declined but remained elevated in hepatitis B virus-positive hemodialysis patients compared to control group-1 and control group-2 patients. After 1 month gamma-glutamyl transpeptidase levels in hepatitis B virus-positive hemodialysis patients were 67.9% lower than baseline levels (P0 < .05), were 51.6% higher compared to control group-2 patients (P1 < .05) and did not differ from control group-1 patients (at the same time points). By month 6, serum alkaline phosphatase levels in hepatitis B virus-positive hemodialysis patients had become 53.9% lower than baseline (P < .01), and did not differ from control group-1 and control group-2 patients. CONCLUSIONS: The data obtained in this study suggest that hemodialysis may have a positive effect on cholestasis in end-stage renal disease patients with hepatitis B virus infection, and may increase immune response and improve liver function in this group of patients.

Cholestasis, ascites and pancytopenia in an immunocompetent adult with severe cytomegalovirus hepatitis.

Human cytomegalovirus (CMV) is a herpesvirus, which establishes lifelong latency after primary infection and leads to severe disease in immunocompromised patients. However, CMV infection in immunocompetent patients is usually asymptomatic and severe organ damage is rarely reported. We report a case of severe CMV hepatitis in an immunocompetent patient presenting with cholestasis, portal hypertension-related ascites and pancytopenia. The patient was asymptomatic with normal liver function and negative CMV DNA after two weeks of antiviral therapy. This case is an example of a common infection with an uncommon presentation, and suggests that testing for CMV should be carried out, even in patients with normal immune status, presenting with severe liver damage or cholestasis.

Cholestatic hepatitis C after chemotherapy containing rituximab in diffuse large B cell lymphoma.

Rituximab is a chimeric anti-CD20 monoclonal antibody that is a widely used for the treatment of B cells non-Hodgkin lymphoma. The use of chemotherapy regimens containing rituximab in HCV-positive patients with non-Hodgkin lymphoma has been associated with liver dysfunction, but no cases of cholestatic hepatitis C were described. To our knowledge, this is the first case of cholestatic hepatitis C in an HCV-positive patient with diffuse large B-cell lymphoma describes in the literature. We discuss the pathogenetic mechanisms underlying this severe form of hepatitis and describe its evolution after antiviral treatment.

Telaprevir- and Boceprevir-based Triple Therapy for Hepatitis C in Liver Transplant Recipients With Advanced Recurrent Disease: A Multicenter Study.

BACKGROUND: Antiviral treatment with sustained virologic response (SVR) improves survival in liver transplant (LT) recipients, and is especially relevant to patients with advanced recurrent hepatitis C virus (HCV). We assessed the safety and efficacy of protease inhibitor-based triple therapy in patients with recurrent advanced fibrosis and cholestatic hepatitis. METHODS: The LT recipients with genotype 1 HCV and advanced fibrosis (F3-4/4) or cholestatic hepatitis treated with telaprevir- or boceprevir-based triple therapy at 6 centers (CRUSH-C consortium) were retrospectively assessed. The primary endpoints were SVR at 12 weeks (SVR12) and safety. RESULTS: Forty-five patients with advanced fibrosis and 9 with cholestatic hepatitis (74% men, 57% genotype 1a, 63% previous nonresponders) were included. SVR12 occurred in 51% with advanced fibrosis and 44% with cholestatic hepatitis. Extended rapid virologic response was highly predictive of SVR12. Hispanic ethnicity (odds ratio, 0.16; P = 0.03), previous null/partial response (0.24; P = 0.02), IL28B genotype CC (7.0; P = 0.02), albumin (3.87; P = 0.03), platelet count (1.01; P = 0.02), and steroid use (0.21; P = 0.03) were associated with SVR12. Six (11%) patients died, and hepatic decompensation occurred in 22% with advanced fibrosis and 33% with cholestatic hepatitis. Albumin (0.02; P = 0.001), encephalopathy (12.0; P = 0.04) and Hispanic ethnicity (odds ratio, 6.17; P = 0.01) were associated with death or decompensation. CONCLUSIONS: For LT recipients with recurrent advanced HCV and at greatest need of cure, protease inhibitor-based triple therapy achieved approximately 50% SVR12. However, there is significant risk of serious adverse events, arguing for earlier intervention. The availability of treatments with better efficacy and safety is of particular importance for posttransplant patients with advanced disease.

Prevalence of groups A and C rotavirus antibodies in infants with biliary atresia and cholestatic controls.

OBJECTIVE: To analyze the prevalence of acute asymptomatic group A and C rotavirus (RV-A and RV-C) infection in neonates with cholestasis. STUDY DESIGN: Participants were infants <180 days of age with cholestasis (serum direct or conjugated bilirubin >20% of total and ≥2 mg/dL) enrolled in the Childhood Liver Disease Research and Education Network during RV season (December-May). Forty infants with biliary atresia (BA), age 62 ± 29 days (range, 4.7-13 weeks) and 38 infants with cholestasis, age 67 ± 44 days (range, 3-15.8 weeks) were enrolled. RESULTS: At enrollment, RV-A IgM positivity rates did not differ between infants with BA (10%) vs those without (18%) (P = .349). RV-C IgM was positive in 0% of infants with BA vs 3% in those without BA (P = .49). RV-A IgG was lower in infants with BA: 51 ± 39 vs 56 ± 44 enzyme-linked immunoassay unit, P = .045 but this difference may lack biological relevance as maternal RV-A IgG titers were similar between groups. Infant RV-A IgM titers at 2-6 months follow-up increased markedly vs at presentation in both infants with BA (50 ± 30 vs 9 ± 9) and those without (43 ± 18 vs 16 ± 20 enzyme-linked immunoassay unit) (P < .0001), without differences between groups. CONCLUSIONS: RV-A infection in the first 6 months of life is common in infants with cholestasis of any cause. RV-A could have different pathogenetic effects by initiating different hepatic immune responses in infants with vs without BA or could lack pathogenetic significance.

Hepatic involvement in congenital cytomegalovirus infection - infrequent yet significant.

Congenital cytomegalovirus (cCMV) infection can reside in many organ systems; however, the virus has a particular predilection towards inhabiting the reticuloendothelial system, especially the liver. Specific studies focusing only on hepatic involvement in infants with cCMV are lacking. We report our experience with a large cohort of infants treated in our hospital clinic due to cCMV and hepatic involvement. Hepatic involvement was defined either as hepatitis (elevated alanine transaminases (ALT) >80 units/L without cholestatic disease) or cholestatic disease (elevated ALT >80 units/L combined with direct bilirubin >2 mg/dL). During the study period, 198 infants were diagnosed with symptomatic cCMV in our clinic. Hepatic involvement was observed in 13 infants (6.6%); 7 (3.5%) with hepatitis and 6 (3%) with cholestatic disease. Maternal primary infection with cytomegalovirus during pregnancy was diagnosed in 7 (53.8%) of the 13 infants, nonprimary in 3 (23.1%) and unknown in 3 (23.1%). Among these 13 infants, central nervous system (CNS) involvement was observed in 11 (84.6%) and hearing impairment in 7 (53.8%). Treatment with an antiviral agent was initiated in all cases. Gradual improvement of hepatic enzymes and cholestasis was observed over a prolonged period. We found that the incidence of hepatic involvement in infants with cCMV is much less frequent than previously reported. The hepatic involvement in these infants may manifest in two different ways, and thus, a high index of suspicion and a stepwise approach will help in correctly diagnosing these infants. Antiviral treatment due to CNS involvement is warranted and prognosis is excellent.