The Multifaceted Clinical Characteristics of Congenital Cytomegalovirus Infection: From Pregnancy to Long-Term Outcomes

Background@#The aim of this study was to capture multifaceted clinical characteristics of congenital cytomegalovirus (CMV) infection from diagnosis to treatment using a multidisciplinary approach including obstetrics, pediatrics, pathology, and otorhinolaryngology-head and neck surgery. @*Methods@#This is a retrospective study including 30 consecutive cases of congenital CMV infection that were diagnosed at a single tertiary hospital located in Seoul, Korea from January 2009 to December 2020. Congenital CMV infection was defined as a positive result by polymerase chain reaction from urine, saliva or cerebrospinal fluid or positive CMV IgM from neonatal blood sampled within 3 weeks after birth. All cases were analyzed with respect to whole clinical characteristics from diagnosis to treatment of congenital CMV by a multidisciplinary approach including prenatal sonographic findings, maternal immune status regarding CMV infection, detailed placental pathology, neonatal clinical manifestation, auditory brainstem response test, and antiviral treatment (ganciclovir or valganciclovir). Long-term outcomes including developmental delay and hearing loss were also investigated. @*Results@#The total number of births during the study period in our institution was 19,385, with the prevalence of congenital infection estimated to be 0.15%. Among 30 cases of congenital CMV, the median gestational age at delivery was 32.2 weeks [range, 22.6–40.0] and 66.7% of these infants were delivered preterm at less than 37 weeks. Suspected fetal growth restriction was the most common prenatal ultrasound finding (50%) followed by ventriculomegaly (17.9%) and abnormal placenta (17.9%), defined as thick placenta with calcification. No abnormal findings on ultrasound examination were observed in one-third of births. Maternal CMV serology tests were conducted in only 8 cases, and one case each of positive and equivocal IgM were found. The most common placental pathologic findings were chronic villitis (66.7%) and calcification (63.0%), whereas viral inclusions were identified in only 22.2%. The most common neonatal manifestations were jaundice (58.6%) followed by elevation of aspartate aminotransferase (55.2%) and thrombocytopenia (51.7%). After excluding cases for which long-term outcomes were unavailable due to death (n = 4) or subsequent follow up loss (n = 3), developmental delay was confirmed in 43.5% of infants (10/23), and hearing loss was confirmed in 42.9% (9/21) during the follow-up period. In our cohort, 56.7% (17/30) of neonates were treated for congenital CMV with ganciclovir or valganciclovir. @*Conclusion@#Our data show that prenatal findings including maternal serologic tests and ultrasound have limited ability to detect congenital CMV in Korea. Given that CMV is associated with high rates of developmental delay and hearing loss in infants, there is an urgent need to develop specific strategies for the definite diagnosis of congenital CMV infection during the perinatal period by a multidisciplinary approach to decrease the risks of neurologic impairment and hearing loss through early antiviral treatment.

Initial Hematochezia and Kidney Involvement are Important Prognostic Factors of Adult Onset Henoch-Schonlein Purpura in Korea

OBJECTIVE: Henoch-Schonlein purpura (HSP) is a systemic vasculitis, characterized by small-vessel leukocytoclastic vasculitis with the deposition of immune complexes containing IgA. It is the most common acute vasculitic disorder affecting children but is relatively uncommon in adults. We investigated the clinical features and factors affecting the prognosis of adult HSP in Korea. METHODS: From 1996 to 2011 seventy patients over 15 years of age with HSP were retrospectively analyzed. RESULTS: Thirty eight patients (54.3%) were female and the age at disease onset ranged from 15 to 75 years (35.0+/-15.8 years). Purpuric skin rash was observed in all patients and arthralgia was present in 34 patients (48.6%). GI symptoms and kidney involvements were observed in 28 patients (40.0%) and 34 patients (48.6%), respectively. Complete remission was achieved in 46 patients (65.7%). The remission group showed a lower incidence of hematochezia (p=0.044), hematuria (p=0.008), and proteinuria (p=0.011) at diagnosis than the no remission group. About 10% of adult HSP patient progressed to chronic kidney disease (CKD), which showed higher a incidence of nephrotic range proteinuria. Only nephrotic range proteinuria at diagnosis was a significant risk factor for CKD (OR=16.7, p=0.008, 95% CI=2.1~133.1). CONCLUSION: Hematochezia, hematuria and proteinuria at the diagnosis of HSP are important prognostic factors in predicting remission. In addition, HSP patients with nephrotic range proteinuria at diagnosis have an increased risk of renal failure.

G-Protein Beta3 Subunit C825T Polymorphism in Patients With Overlap Syndrome of Functional Dyspepsia and Irritable Bowel Syndrome

BACKGROUND/AIMS: Guanine nucleotide binding protein (G-protein) beta polypeptide 3 (GNB3) C825T polymorphism alters intracellular signal transduction, which may lead to motor or sensory abnormalities of the gastrointestinal tract. The aim of the present study was to evaluate the association of the GNB3 C825T polymorphism with susceptibility to overlap syndrome of functional dyspepsia (FD) and irritable bowel syndrome (IBS) in a Korean population. METHODS: One hundred sixty-seven patients with FD alone, 60 patients with IBS alone, 85 patients with the overlap of FD and IBS, and 434 asymptomatic healthy subjects participated in the study. Genotyping for GNB3 C825T polymorphism was performed using their blood samples. RESULTS: No association of GNB3 genotypes in patients with FD alone, IBS alone or overlap phenotype, when compared to genotypes in controls, was detected. The frequency of CT and TT genotypes relative to the CC genotype for the phenotypes of FD alone, IBS alone and the coexistence of FD and IBS did not significantly differ. Comparison of the TT genotype with the CC/CT genotype showed no significant association for each phenotype group. CONCLUSIONS: There is no apparent association of the GNB3 C825T polymorphism with the susceptibility to FD, IBS or the overlap of FD and IBS. Larger-scale studies and further investigation on other candidate genes are required.

Association between apolipoprotein E genotype, chronic liver disease, and hepatitis B virus

BACKGROUND/AIMS: Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies. METHODS: This hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits. RESULTS: The epsilon3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%, and 9.9% for the epsilon2, epsilon3, and epsilon4 alleles, respectively. Significantly more of those patients carrying the epsilon3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype. CONCLUSIONS: The ApoE epsilon3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls.