Congenital cytomegalovirus infection as an important cause of infantile cholestatic jaundice: a case report.

Infantile cholestasis has numerous causes and diagnosis can be difficult, especially in low-income countries where essential laboratory facilities are not readily available. This is a report of a baby who had severe conjugated neonatal hyperbilirubinaemia and deranged liver function tests, which posed a diagnostic dilemma before a diagnosis of congenital cytomegalovirus (CMV) infection was made. He was treated with Ganciclovir and responded well to treatment. He had no obvious associated neurologic manifestation of the disease and is presently been followed-up. This report highlights the challenges encountered in the diagnosis and management of the baby, as well as the favourable outcome with Ganciclovir therapy. The aim of the report is to increase the awareness of paediatricians and other stakeholders on congenital CMV infection in order to ensure early diagnosis and appropriate treatment of affected babies, with the ultimate aim of improving their prognoses and preventing the associated audiologic and cognitive sequelae.

Presentation of Severe Acute Respiratory Syndrome-Coronavirus 2 Infection as Cholestatic Jaundice in Two Healthy Adolescents.

Liver abnormalities in severe acute respiratory syndrome-coronavirus 2 infection, including hepatitis and cholestasis, have been observed in adults and are associated with worse outcomes. We describe 2 adolescents with cholestasis and hepatitis with mild presentation of severe acute respiratory syndrome-coronavirus 2 lacking typical symptoms. Our intention is to raise index of suspicion for testing and protective equipment use.

Rotavirus Reassortant-Induced Murine Model of Liver Fibrosis Parallels Human Biliary Atresia.

BACKGROUND AND AIMS: Biliary atresia (BA) is a devastating neonatal cholangiopathy that progresses to fibrosis and end-stage liver disease by 2 years of age. Portoenterostomy may reestablish biliary drainage, but, despite drainage, virtually all afflicted patients develop fibrosis and progress to end-stage liver disease requiring liver transplantation for survival. APPROACH AND RESULTS: In the murine model of BA, rhesus rotavirus (RRV) infection of newborn pups results in a cholangiopathy paralleling human BA and has been used to study mechanistic aspects of the disease. Unfortunately, nearly all RRV-infected pups succumb by day of life 14. Thus, in this study we generated an RRV-TUCH rotavirus reassortant (designated as TR(VP2,VP4) ) that when injected into newborn mice causes an obstructive jaundice phenotype with lower mortality rates. Of the mice that survived, 63% developed Ishak stage 3-5 fibrosis with histopathological signs of inflammation/fibrosis and bile duct obstruction. CONCLUSIONS: This model of rotavirus-induced neonatal fibrosis will provide an opportunity to study disease pathogenesis and has potential to be used in preclinical studies with an objective to identify therapeutic targets that may alter the course of BA.

Association between the UGT1A1*28 allele and hyperbilirubinemia in HIV-positive patients receiving atazanavir: a meta-analysis.

Objectives The uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1)*28 allele in HIV-positive patients receiving atazanavir (ATV) might be associated with the risk of hyperbilirubinemia. Owing to mixed and inconclusive results, a meta-analysis was conducted to systematically summarize and clarify this association.Methods Based on a comprehensive search of PubMed, Embase and Web of Science databases, studies investigating the association between UGT1A1 alleles and hyperbilirubinemia was retrieved. We evaluated the strength of this relationship using odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity analysis was performed by removing each study one at a time and calculating the pooled ORs of the remaining studies to test the robustness of the meta-analysis results. The Q statistic and the I2 index statistic were used to assess heterogeneity. Publication bias was evaluated using Orwin's fail-safe N test.Results A total of six individual studies were included in this meta-analysis. A significantly increased risk of hyperbilirubinemia was observed in HIV-positive patients receiving ATV with the UGT1A1*1/*28 or UGT1A1*28/*28 genotype, and the risk was higher with the UGT1A1*28/*28 genotype than with the UGT1A1*1/*28 genotype. (UGT1A1*28/*28 versus UGT1A1*1/*28: OR = 3.69, 95%CI = 1.82-7.49; UGT1A1*1/*28 versus UGT1A1*1/*1: OR = 3.50, 95%CI = 1.35-9.08; UGT1A1*28/*28 versus UGT1A1*1/*1: OR = 10.07, 95%CI = 4.39-23.10). All of the pooled ORs were not significantly affected by the remaining studies and different modeling methods, indicating robust results.Conclusions This meta-analysis suggests that the UGT1A1*28 allele represents a biomarker for an increased risk of hyperbilirubinemia in HIV-positive patients receiving ATV.

Hepatitis C virus intrinsic molecular determinants may contribute to the development of cholestatic hepatitis after liver transplantation.

Cholestatic hepatitis C (CHC) is a severe form of hepatitis C virus (HCV) infection recurrence that leads to high graft loss rates early after liver transplantation (LT). To investigate the pathogenic mechanisms of CHC, we analysed HCV quasispecies in CHC patients compared to a control group (mild hepatitis C recurrence) by deep pyrosequencing. At the time of LT, NS5B quasispecies complexity was similar between the two groups but, after LT, it decreased more sharply in CHC patients than in the control group. Interestingly, the major variant before LT propagated efficiently and remained as the dominant sequence after LT in 62 % of CHC patients versus 11 % of controls (P=0.031). Sequence analysis of the complete non-structural region in a limited number of patients revealed a potential 12 aa signature specific to the CHC group. These data suggest that intrinsic molecular determinants in the circulating HCV quasispecies may provide a fitness advantage, contributing to the development of CHC.

[Occult hepatitis B reactivation in a patient with homozygous sickle cell disease: clinical case and literature review]. / Réactivation d'une hépatite B occulte chez un patient drépanocytaire homozygote: cas clinique et revue de la litérature.

Occult Hepatitis B corresponds to the presence of hepatitis B virus-deoxyribonucleic acid (HBV-DNA) in serum and/or in liver of a patient despite HBsAg negativity. Clinically, it is usually asymptomatic. Its reactivation is rare and commonly occurs in immunosuppressed individuals. We report the case of a 21-year old patient from Senegal, with homozygous sickle cell disease, presenting with cholestatic jaundice. Laboratory tests showed reactivation of occult Hepatitis B. This study emphasizes the need to systematically investigate the presence of occult Hepatitis B in patients with sickle cell disease suffering from acute liver disease.

Biliary atresia: the animal models.

Biliary atresia (BA) is a progressive fibrosing process of the neonatal biliary tree and liver, of unknown origin, and an as-yet unexplained pathologic mechanism. The crucial point is to elucidate the origin of this rare disease to change palliative surgery to etiology-related procedures. Patient-based research can only begin at the time of the Kasai procedure and does not allow retracing of the pathology back to its origin. Basic research has focused on similar diseases in the veterinary literature and started to simulate BA in animal models. Unfortunately, even after 50 years of research, no knowledge has been gained from such models, which has led to a single clinical application. This article reviews BA in the context of the animal models available and discusses whether future studies are promising or futile.

Role of some viral infections in neonatal cholestasis.

Viral infection is one of the postulated causes of neonatal cholestasis. In addition to earlier reports on the association of viral infection and intrahepatic cholestasis (IH), recent studies have suggested a similar link to extra hepatic biliary atresia (EHBA). The aim of this work was to evaluate the role of some viral infections in neonates presenting with cholestasis to the Neonatology Ward of Zagazig University Hospitals. Sixty-two neonates were included in the study (44 cholestatic neonates and 18 apparently healthy neonates as the control group). All neonates were subjected to full history taking and complete physical examination. Laboratory investigations included CBC, liver function tests, bleeding profile, blood cultures, abdominal ultrasound and detection of HBsAg and serum IgM antibodies against certain viruses (CMV, Reovirus III, HSV I, HSV II, Rubella virus) using ELISA. Radionuclide cholescintigraphy was performed for patients only. The study revealed that cholestatic neonates were significantly associated with dark urine, pale stool and hepatomegaly compared with the control (P<0.004, P<0.001, P<0.008, respectively). Quantitation of IgM antibody titre using ELISA revealed significantly higher levels of serum anti-CMV IgM and anti-Reovirus III IgM in cholestatic than in the control groups. No significant differences were found in levels of anti-HSV I, anti-HSV II or anti-rubella antibodies between cholestatic and control groups. HBsAg was negative for all neonates; cholestatic and control. Lastly, no significant differences were found between neonates with EHBA (7 cases) and Intrahepatic cholestasis (37 cases) regarding anti -CMV IgM or anti -Reo III IgM. It can be concluded that CMV and Reovirus type 3 infections of the neonates are associated with the development of cholestatic disorder, not only due to IH cholestasis but also due to the production of EHBA.