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To explore the impacts of cytomegalovirus (CMV) infection and antiviral treatment (AVT) on native liver survival (NLS) in biliary atresia (BA) infants. This retrospective cohort study included infants diagnosed as BA between January 2015 and December 2021 at Hunan Children's Hospital. CMV infection was defined by DNA polymerase chain reaction alone (DNA data set) and combination of DNA and immunoglobulin M (CMV data set). In the DNA data set of 330 patients, 234 patients (70.9%) survived with their native liver in 2 years, with 113 (73.9%) in the DNA- cohort, 70 (65.4%) in the DNA+ and AVT- cohort and 51 (72.9%) in the DNA+ and AVT+ cohort, without significant differences by log-rank tests. In patients administrated between 2015 and March 2019, there were 206 evaluable patients in the DNA data set, with rates of 5-year NLS of 68.3% in the DNA- cohort, similar to that in the DNA+ and AVT+ cohort (62.2%, p = 0.546), but significantly higher than that in the DNA+ and AVT- cohort (51.4%, p = 0.031). Similar trends were also observed in the CMV data set, although statistically insignificant. CMV infection before or on the day of HPE can reduce the rate of 5-year NLS and AVT was recommended for CMV-infected BA infants., (© 2024 Wiley Periodicals LLC.)

Purpose: Patients with biliary atresia (BA) and cytomegalovirus (CMV) infection may have poorer outcomes after Kasai portoenterostomy (KPE) than uninfected patients, suggesting a rationale for antiviral treatment (AVT). We aimed to describe the incidence of CMV infection and of AVT in BA patients, and to detect any differences between infected and uninfected patients to conclude if AVT is of use. Methods: Data on BA patients who underwent KPE 2004–2020 were retrospectively collected, and the outcome was analyzed with regard to CMV status. Results: Fifteen out of forty-six (33%) BA patients had signs of ongoing CMV infection. They did not differ significantly from the CMV-negative patients regarding rate of prematurity, birth weight, or biochemical markers but were slightly older at KPE. All patients received steroids postoperatively and all patients with ongoing CMV infection received AVT with very good effect on viremia and without major side effects. The AVT consisted of oral valganciclovir (10–40 (– 58) mg/kg/d) or intravenous ganciclovir (5.3–11 mg/kg/d). Conclusion: Ongoing CMV infection is common in this group of patients. The viremia can effectively be treated with AVT without any major side effects. Larger, randomized studies are needed to clarify the possible effect on clinical outcome. [ABSTRACT FROM AUTHOR]

Nonsyndromic biliary atresia (BA) is a rare polygenic disease, with autoimmunity, virus infection and inflammation thought to play roles in its pathogenesis. We conducted a genome-wide association study in 336 nonsyndromic BA infants and 8900 controls. Our results validated the association of rs17095355 in ADD3 with BA risk (odds ratio (OR) = 1.70, 95% confidence interval (95% CI) = 1.49–1.99; p = 4.07 × 10−11). An eQTL analysis revealed that the risk allele of rs17095355 was associated with increased expression of ADD3. Single-cell RNA-sequencing data and immunofluorescence analysis revealed that ADD3 was moderately expressed in cholangiocytes and weakly expressed in hepatocytes. Immuno-fluorescent staining showed abnormal deposition of ADD3 in the cytoplasm of BA hepatocytes. No ADD3 auto-antibody was observed in the plasma of BA infants. In the HLA gene region, no variants achieved genome-wide significance. HLA-DQB1 residue Ala57 is the most significant residue in the MHC region (OR = 1.44, 95% CI = 1.20–1.74; p = 1.23 × 10−4), and HLA-DQB1 was aberrantly expressed in the bile duct cells. GWAS stratified by cytomegalovirus (CMV) IgM status in 87 CMV IgM (+) BA cases versus 141 CMV IgM (−) BA cases did not yield genome-wide significant associations. These findings support the notion that common variants of ADD3 account for BA risk. The HLA genes might have a minimal role in the genetic predisposition of BA due to the weak association signal. CMV IgM (+) BA patients might not have different genetic risk factor profiles compared to CMV IgM (−) subtype. [ABSTRACT FROM AUTHOR]

Objective To explore the impact of cytomegalovirus (CMV) infection on the prognosis of Kasai operation in children with biliary atresia (BA). Methods From January 2018 to December 2020, 91 BA children undergoing Kasai operation at Tianjin Children's Hospital and Shanxi Children's Hospital were divided into two groups of CMV positive (n=35) and CMV negative (n=56).CMV positive children were divided into antiviral treatment and non-treated groups. Follow-ups were conducted for (2-34) months until October 10, 2021.The impact of CMV infection on jaundice clearance, cholangitis and autologous liver survival after Kasai operation were examined. Results In CMV positive group, there were 26 cases in treatment group and 9 cases in non-treated group. Operative age was significantly older in positive group. Significant difference existed in proportion of white blood cell (WBC).In positive group, aspartate aminotransferase (AST) spiked sharply[244.00(195.00, 341.00) vs. 185.00(126.25, 281.00), P < 0.05].No significant difference existed in jaundice clearance rate, incidence of cholangitis or survival of autologous liver after Kasai operation. The incidence rate of early cholangitis declined markedly after antiviral treatment(11.54% vs. 55.56%, P < 0.05). Conclusion CMV infection has no significant impact on the prognosis of BA children. And antiviral therapy lowers the incidence of early cholangitis. It hints that antiviral therapy has a positive effect on BA children with CMV infection. [ABSTRACT FROM AUTHOR]

Background and Aim: Biliary atresia is known to have a multifactorial etiology and perinatal infection with hepatotropic viruses such as cytomegalovirus (CMV) is a probable trigger in a subset of patients. The aim of the current study is to evaluate the effects of CMV association of biliary atresia on the initial presentation of patients and their response to Kasai portoenterostomy. Patients and Methods: We conducted a retrospective, single-center study on 20 patients of biliary atresia and classified them into two groups based on their CMV immunoglobulin M (IgM) positivity. We compared the age of initial presentation, the liver biochemistry at presentation, immediate and delayed follow-up, rate of jaundice clearance following Kasai portoenterostomy, and histopathology of liver between the two groups. Data were reported in terms of means, and P < 0.05 was considered significant. Results: Out of 20 cases of biliary atresia, 60% (n = 12) were CMV IgM positive. Infants with CMV-positive status were noted to be older at presentation (88.5 days [65–150 days] vs. 83 days [45–160 days] P < 0.05) were more jaundiced at presentation (total bilirubin – 13.51 mg/dl [9.09–15.99 mg/dl] vs. 11.83 mg/dl [6.5–13.5 mg/dl] P < 0.05), had higher alkaline phosphatase (751.2 IU/L [387–1951 IU/L] vs. 621.75 IU/L [172–857 IU/L] P < 0.05), higher gamma-glutamyl transferase levels (505.58 IU/L [376–1127 IU/L] vs. 376.75 IU/L [186–624 IU/L] P < 0.05), and had higher incidence of splenomegaly. The rate of resolution of jaundice postKasai portoenterostomy was also evidently less in CMV-positive patients. Four out of 12 patients have bilirubin >2 mg/dl at a 6-month follow-up. Conclusion: CMV-associated biliary atresia patients have delayed initial presentation and impaired jaundice clearance postKasai portoenterostomy. The role of antiviral therapy should be studied in this subset of patients. [ABSTRACT FROM AUTHOR]

The pathogenesis of biliary atresia (BA) is still not clear. The aim of this study was to evaluate the expression of selected immunological parameters in liver tissue in BA children based on CMV/EBV infection status. Eight of thirty-one children with newly diagnosed BA were included in this prospective study and assigned to two groups (I with active infection, II without active or past infection). All studies were performed on surgical liver biopsies. To visualize CD8+ T cells and CD56 expression, immunohistochemical staining was performed. The viral genetic material in the studied groups was not found, but CMV infection significantly affected the number of CD8+ lymphocytes in both the portal area and the bile ducts. The average number of CD8+ cells per mm2 of portal area in Groups I and II was 335 and 200 (p = 0.002). The average number of these cellsthat infiltrated the epithelium of the bile duct per mm2 in Group I and II was 0.73 and 0.37 (p = 0.0003), respectively. Expression of CD56 in the bile ducts corresponded to the intensity of the inflammatory infiltrate of CD8+ cells. Our results suggest that active CMV infection induces an increased infiltration of CD8+ lymphocytes, which could play a role in BA immunopathogenesis. Increased CD56 expression can be a sign of a newly formed bile structure often without lumen, suggesting inhibition of the maturation process in BA. [ABSTRACT FROM AUTHOR]

Biliary atresia, a fibro-obliterative disease of the newborn, is usually initially treated by Kasai portoenterostomy, although there are many variations in technique and different options for post-operative adjuvant medical therapy. A questionnaire on such topics (e.g., open vs. laparoscopic; the need for liver mobilisation; use of post-operative steroids; use of post-operative anti-viral therapy, etc.) was circulated to delegates (n = 43) of an international webinar (Biliary Atresia and Related Diseases—BARD) held in June 2021. Respondents were mostly European, but included some from North America, and represented 18 different countries overall. The results of this survey are presented here, together with a commentary and review from an expert panel convened for the meeting on current trends in practice. [ABSTRACT FROM AUTHOR]

Nonsyndromic biliary atresia (BA) is a rare polygenic disease, with autoimmunity, virus infection and inflammation thought to play roles in its pathogenesis. We conducted a genome-wide association study in 336 nonsyndromic BA infants and 8900 controls. Our results validated the association of rs17095355 in ADD3 with BA risk (odds ratio (OR) = 1.70, 95% confidence interval (95% CI) = 1.49–1.99; p = 4.07 × 10−11). An eQTL analysis revealed that the risk allele of rs17095355 was associated with increased expression of ADD3. Single-cell RNA-sequencing data and immunofluorescence analysis revealed that ADD3 was moderately expressed in cholangiocytes and weakly expressed in hepatocytes. Immuno-fluorescent staining showed abnormal deposition of ADD3 in the cytoplasm of BA hepatocytes. No ADD3 auto-antibody was observed in the plasma of BA infants. In the HLA gene region, no variants achieved genome-wide significance. HLA-DQB1 residue Ala57 is the most significant residue in the MHC region (OR = 1.44, 95% CI = 1.20–1.74; p = 1.23 × 10−4), and HLA-DQB1 was aberrantly expressed in the bile duct cells. GWAS stratified by cytomegalovirus (CMV) IgM status in 87 CMV IgM (+) BA cases versus 141 CMV IgM (−) BA cases did not yield genome-wide significant associations. These findings support the notion that common variants of ADD3 account for BA risk. The HLA genes might have a minimal role in the genetic predisposition of BA due to the weak association signal. CMV IgM (+) BA patients might not have different genetic risk factor profiles compared to CMV IgM (−) subtype.

Background: There is limited information on the impact of cytomegalovirus (CMV) infection on clinical outcomes and operative histopathology in children with biliary atresia (BA). We hypothesized that CMV infection is associated with greater histopathological damage and unfavorable short-term clinical outcomes. Materials and Methods: A prospective single-center study was conducted with effect from January 2011–July 2012 including all infants with BA who underwent surgery. Diagnosis of CMV infection was confirmed by serum immunoglobulin M (IgM) positivity or the presence of CMV-deoxyribonucleic acid (DNA) in the liver tissue. Four short-term outcome variables were observed. The cohort was divided into subgroups on the basis of seropositivity (IgM + or IgM−); the presence of CMV-DNA in the liver (polymerase chain reaction [PCR]+ or PCR−); and composite CMV groups (Group 1 – IgM+, PCR+; Group 2 – IgM+, PCR−; Group 3 –- IgM−, PCR+; and Group 4 – IgM−, PCR−). Outcomes and histopathology were compared in these subgroups. Results: A total of 32 infants with BA were operated at a mean age of 3.5 (range: 1–6) months. Serum IgM+ and PCR+ were observed in 50% and 37.5% of the patients. Unfavorable outcomes showed a significant association with IgM+ and not PCR+. Similarly, outcomes were poor for CMV Groups 1 and 2 at 1-month follow-up. Infants with IgM+ and PCR+ showed a greater degree of histopathological damage in terms of bile duct proliferation and severe bile duct fibrosis, respectively. Conclusion: In the present study, there was a high incidence of serum IgM+ (50%) and PCR+ of biopsy specimens (37.5%) in infants with BA. This CMV-infected subgroup was associated with greater histopathological damage and unfavorable short-term outcomes after surgery.

Objectives Biliary atresia (BA) is the most common indication of liver transplantation in children. Several reports attributed BA to both prenatal and perinatal etiologies, including a viral infection-induced autoimmune response that targets the bile ducts. Cytomegalovirus (CMV) remains the most common virus being linked to BA. This meta-analysis aimed to estimate to what extent CMV infection is detected in patients with BA. Methods This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases of MEDLINE, Embase, Scopus, WHO-Virtual Health Library (VHL), ScienceDirect, and Google Scholar were used for the systematic search. The risk of bias was assessed using the Newcastle–Ottawa scale. Random effects model was used to estimate the pooled prevalence estimate with the corresponding 95% confidence interval (CI) using Comprehensive Meta-Analysis Software version 3.3. Results A total of 19 studies that fulfilled the eligibility criteria were included in the meta-analysis. The total number of infants with BA was 630 patients, and the pooled overall prevalence of CMV infection among them was 25.4% (95% CI: 15.9%–38.0%). There was high heterogeneity among studies (I2 = 85.1%, p

Purpose: Perinatal cytomegalovirus (CMV) infection can lead to biliary atresia (BA) in different entities. This study aimed to compare the clinical, hematological, biochemical, and histological features of infants with BA based on their CMV immunoglobulin M (IgM) status at presentation. Methods: This cross-sectional descriptive study was carried out between January 2019 and June 2020 at the Department of Pediatric Gastroenterology and Nutrition at the Bangabandhu Sheikh Mujib Medical University (BSMMU) in Dhaka. Forty-three patients with BA were selected purposively and categorized into either the CMV IgM-positive or CMV IgM-negative BA group. Categorical variables were compared using Fisher's exact test and chi-square tests, while the Student's t-test and Mann-Whitney U-test were used to compare continuous variables. For all statistical tests, a p-value <0.05 was considered statistically significant. Results: Thirty-three (76.7%) of the cases were between 2 and 3 months of age on admission. The clinical, hematological, and biochemical parameters did not differ significantly between the CMV IgM-positive and CMV IgM-negative BA groups. Most (50.0%) of the CMV IgMpositive cases had fibrosis stage F2, while 43.5% of the CMV IgM-negative cases had fibrosis stage F3, with no significant difference between the groups (p=0.391). Conclusion: Our data shows no significant distinction between CMV IgM-positive and CMV IgM-negative BA, suggesting that CMV does not contribute to BA pathogenesis. [ABSTRACT FROM AUTHOR]

Background: There is limited information on the impact of cytomegalovirus (CMV) infection on clinical outcomes and operative histopathology in children with biliary atresia (BA). We hypothesized that CMV infection is associated with greater histopathological damage and unfavorable short-term clinical outcomes. Materials and Methods: A prospective single-center study was conducted with effect from January 2011–July 2012 including all infants with BA who underwent surgery. Diagnosis of CMV infection was confirmed by serum immunoglobulin M (IgM) positivity or the presence of CMV-deoxyribonucleic acid (DNA) in the liver tissue. Four short-term outcome variables were observed. The cohort was divided into subgroups on the basis of seropositivity (IgM + or IgM−); the presence of CMV-DNA in the liver (polymerase chain reaction [PCR]+ or PCR−); and composite CMV groups (Group 1 – IgM+, PCR+; Group 2 – IgM+, PCR−; Group 3 –- IgM−, PCR+; and Group 4 – IgM−, PCR−). Outcomes and histopathology were compared in these subgroups. Results: A total of 32 infants with BA were operated at a mean age of 3.5 (range: 1–6) months. Serum IgM+ and PCR+ were observed in 50% and 37.5% of the patients. Unfavorable outcomes showed a significant association with IgM+ and not PCR+. Similarly, outcomes were poor for CMV Groups 1 and 2 at 1-month follow-up. Infants with IgM+ and PCR+ showed a greater degree of histopathological damage in terms of bile duct proliferation and severe bile duct fibrosis, respectively. Conclusion: In the present study, there was a high incidence of serum IgM+ (50%) and PCR+ of biopsy specimens (37.5%) in infants with BA. This CMV-infected subgroup was associated with greater histopathological damage and unfavorable short-term outcomes after surgery. [ABSTRACT FROM AUTHOR]

The pathogenesis of biliary atresia (BA) is still not clear. The aim of this study was to evaluate the expression of selected immunological parameters in liver tissue in BA children based on CMV/EBV infection status. Eight of thirty-one children with newly diagnosed BA were included in this prospective study and assigned to two groups (I with active infection, II without active or past infection). All studies were performed on surgical liver biopsies. To visualize CD8+ T cells and CD56 expression, immunohistochemical staining was performed. The viral genetic material in the studied groups was not found, but CMV infection significantly affected the number of CD8+ lymphocytes in both the portal area and the bile ducts. The average number of CD8+ cells per mm2 of portal area in Groups I and II was 335 and 200 (p = 0.002). The average number of these cellsthat infiltrated the epithelium of the bile duct per mm2 in Group I and II was 0.73 and 0.37 (p = 0.0003), respectively. Expression of CD56 in the bile ducts corresponded to the intensity of the inflammatory infiltrate of CD8+ cells. Our results suggest that active CMV infection induces an increased infiltration of CD8+ lymphocytes, which could play a role in BA immunopathogenesis. Increased CD56 expression can be a sign of a newly formed bile structure often without lumen, suggesting inhibition of the maturation process in BA.

Biliary atresia, a fibro-obliterative disease of the newborn, is usually initially treated by Kasai portoenterostomy, although there are many variations in technique and different options for post-operative adjuvant medical therapy. A questionnaire on such topics (e.g., open vs. laparoscopic; the need for liver mobilisation; use of post-operative steroids; use of post-operative anti-viral therapy, etc.) was circulated to delegates (n = 43) of an international webinar (Biliary Atresia and Related Diseases—BARD) held in June 2021. Respondents were mostly European, but included some from North America, and represented 18 different countries overall. The results of this survey are presented here, together with a commentary and review from an expert panel convened for the meeting on current trends in practice.

Objective: The etiology of biliary atresia is unclear, but viral infection has been implicated. The aim of the current meta-analysis was to investigate relationships between cytomegalovirus (CMV) and the prognosis of biliary atresia.Methods: PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure database, and Wanfang Data electronic databases were searched for eligible studies. Each relevant text was thoroughly reviewed and examined, including related papers in their reference lists.Results: A total of nine studies including 784 patients were included in the analysis. Biliary atresia patients with CMV exhibited significantly lower jaundice clearance (odds ratio: 0.46, p < 0.0001; I2 = 15%, p = 0.31). There were no significant differences in the rates of cholangitis or native liver survival. CMV-pp65-positive biliary atresia patients had a significantly lower rate of jaundice clearance (odds ratio: 5.87, p = 0.003; I2 = 0%, p = 0.71) and a significantly higher rate of cholangitis (odds ratio: 0.21, p = 0.01; I2 = 0%, p = 0.43) than CMV antibody-positive biliary atresia patients.Conclusion: Biliary atresia patients who were also infected with CMV had a poorer prognosis, particularly with respect to jaundice clearance. CMV status may influence the prognosis of biliary atresia. Clinicians should be able to routinely identify the subset of biliary atresia patients who are also CMV-positive, in order to improve native liver survival.

Introduction and objectives: Differentiating biliary atresia from other causes of neonatal cholestasis is challenging, particularly when cytomegalovirus (CMV) and biliary atresia occur simultaneously. We aimed to elucidate whether CMV infection would affect the differential diagnosis of biliary atresia and intrahepatic cholestasis. Patients and methods: This retrospective study was conducted among patients with neonatal cholestasis admitted to three tertiary hospitals between January 2010 and August 2019. The clinical characteristics, laboratory, and imaging findings were recorded. On the basis of the CMV serology results, the infants were classified into CMV-IgM (+) and CMV-IgM (−) groups. The clinical differences and diagnostic performances of routine predictors between biliary atresia and intrahepatic cholestasis were analyzed in each group. Finally, we compared the diagnostic performances of various tests in the two groups. Results: A total of 705 patients with neonatal cholestasis were enrolled: 215 (30.5%) patients were positive for CMV-IgM, among whom 97 had biliary atresia and 118 had CMV hepatitis; 490 infants were CMV-IgM (−), among whom 240 had biliary atresia and 250 had intrahepatic cholestasis. The diagnostic performances of stool color, direct bilirubin level, γ-glutamyl transpeptidase level, abnormal gallbladder, triangular cord sign, and hepatobiliary scintigraphy between CMV hepatitis and CMV-IgM (+) biliary atresia were similar to those between CMV-IgM (−) biliary atresia and CMV-IgM (−) intrahepatic cholestasis groups. Conclusions: Our large-scale study showed a high prevalence of CMV infection in patients with neonatal cholestasis in China. The presence of CMV infection did not affect the routine predictors to discriminate biliary atresia and intrahepatic cholestasis.

Cytomegalovirus (CMV) infection has been suggested to be of importance for the development and outcome of biliary atresia (BA). However, most data are only available from single centre studies. We retrospectively collected data on rates, outcomes, and treatments for ongoing CMV infection at the time of Kasai portoenterostomy (KPE) from four different tertiary centres in Europe. The rate of ongoing CMV infection varied between 10–32% in the four centres. CMV positive patients were significantly older and had higher levels of several liver biochemistries at the time of KPE (p < 0.05 for all comparisons). In the largest centre, CMV infection was more common in non-Caucasians, and CMV infected patients had poorer long-term survival with native liver than CMV negative patients (p = 0.0001). In contrast, survival with native liver in the subgroup of CMV infected patients who had received antiviral treatment was similar to the CMV negative group. We conclude that ongoing CMV infection at the time of KPE occurs in a significant proportion of BA patients and that these patients seem to differ from CMV negative patients regarding age and biochemistry at the time of KPE as well as long-term survival with native liver. The latter difference may be reduced by antiviral treatment, but randomized, controlled trials are needed before such treatment can be recommended routinely.

Biliary atresia associated with positive cytomegalovirus IgM results is a rare condition characterized by progressive inflammatory obliteration of the intra- or extrahepatic ducts. It is caused by a perinatal autoimmune reaction against cytomegalovirus (CMV). Diagnosis is made based on positive IgM for CMV and liver biopsy with evidence of bile duct atresia. Knowledge and timely identification of this disease leads to early surgical management, considerably improving the prognosis of these patients. This is the clinical case of an 82-day-old female patient with late-onset acholia, choluria, and jaundice, associated with conjugated hyperbilirubinemia, elevated liver function tests and positive CMV IgM results. Intraoperative cholangioresonance confirmed bile duct atresia. The Kasai procedure was performed, and a liver biopsy was taken, confirming the diagnosis. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) is an important cause of neonatal hepatitis. Untreated, though hepatomegaly may spontaneously regress, these children may develop portal hypertension and chronic liver disease. Also, these children can progress to develop biliary atresia. Long term sequelae may be sensorineural deafness and intellectual impairment. Role of ganciclovir and its prodrug valganciclovir for treatment of congenital CMV infection is not completely established. There have been few case series and case reports that have documented resolution of CMV hepatitis on treatment with ganciclovir. However, there is very little literature on role of valganciclovir in neonatal CMV hepatitis. We report for the first time in India, effectiveness of valganciclovir in 3 infants with neonatal hepatitis and CMV. All 3 infants in age group of 2-4 months with neonatal hepatitis and variable CMV viral load were treated with oral valganciclovir (125250 mg/m2/day) for 6 weeks and had clinical improvement and undetectable viral load at the end of therapy. One patient however developed long term sequelae of CMV in form of sensorineural deafness and delayed development. Thus, valganciclovir appears safe and effective in neonatal hepatitis with CMV. However, randomized controlled trials in larger groups are required to determine its efficacy. [ABSTRACT FROM AUTHOR]

Background: The presence of cartilage in extra hepatic biliary tree is an unusual finding. An isolated presence of the cartilage is possibly heterotopic or occurs as a metaplastic response to the inflammatory insult. Material and methods: We had examined the liver biopsy and the resected specimen of a biliary atresia (BA) after Kasai procedure. Results: There was hyaline cartilage around the common hepatic and common bile duct in a 3-months-old male infant with distal obstructive cholangiopathy on liver biopsy and had positive serum IgM for cytomegalovirus (CMV). Similar findings could not be documented in the pericholedochal tissue of any of the 25 other pediatric cases operated for BA or choledochal cyst and three neonatal autopsies performed for liver-related deaths. Conclusion: Peri-bile duct cartilage is a unique finding and could represent an unusual form of heterotopia or connective tissue metaplasia. [ABSTRACT FROM AUTHOR]

CMV-IgM + ve associated biliary atresia (CMV-BA) is a distinct etiological subgroup characterized by older age at presentation and a greater degree of inflammation and hepatic fibrosis, leading to a worse outcome. We report our experience with adjuvant antiviral therapy after Kasai portoenterostomy (KPE). Single-center prospective database identification of CMV-IgM + ve associated BA managed between 2003 and 2017. Since 2011, IV ganciclovir (5 mg/kg b.d.) and/or oral valganciclovir (520 mg/m2 b.d.) were started in the early postoperative period in selected cases and continued until negativity of CMV DNA load [Anti-Viral Therapy (AVT) Group 1]. Clearance of jaundice was defined as achieving a total bilirubin ≤ 20 μmol/L in post-KPE period and tested with a Fisher test; native liver survival (NLS) and overall actuarial survival (OS) were compared with untreated BA CMV IgM + ve patients (Group 2) using a Log-Rank test. A P value of < 0.05 was regarded as significant. Data are quoted as median (IQ range). During the 14-year period, 376 infants with histologically confirmed BA were treated; of those 38(10%) were CMV IgM + ve at presentation. One child was considered too late at presentation for KPE and underwent primary liver transplantation while another only started AVT one month after KPE. Both were excluded from survival analysis. Therefore 36 underwent KPE [AVT Group 1 (n = 8) and Control Group 2 (n = 28)]. Overall age at surgery was 67(53–77) days. There was no difference in age at surgery (P = 0.26); bilirubin (P = 0.12); or AST (P = 0.15) between Group 1 and Group 2. Viral load data were available in 16 with a trend towards higher counts in the AVT group 1 [4935 (2668–18,817) vs. 1296 (253–10,471) c/ml; P = 0.06]. Clearance of jaundice was higher in AVT Group 1 (75% vs 21%, P = 0.009). There was no difference in OS (P = 0.24) but NLS was improved in the AVT Group 1 (75% vs. 25% at 2 years; P = 0.04). Although this finding may be regarded as preliminary, adjuvant antiviral therapy appeared to improve outcome in infants with CMV IgM + ve BA. III. [ABSTRACT FROM AUTHOR]

Biliary atresia (BA) is a common cause of obstructive jaundice in the infantile period, and also a severe hepatobiliary disease leading to liver failure. At present, the research on the etiology and pathogenesis of BA is continuing. But various signs show that perinatal viral infection plays an important role in the occurrence and development of BA, which may be the exact cause of BA. Therefore, this paper mainly discussed the feasibility of preventing BA from the view of virus vaccination, in order to provide a new perspective for reducing the incidence of BA. [ABSTRACT FROM AUTHOR]

The pathogenesis of biliary atresia (BA) is propounded to be an immunological process, but the detailed mechanisms remain unclear. In recent studies with abnormal immunological findings, T cells have drawn attention in the mechanism of BA pathogenesis. Furthermore, cytomegalovirus (CMV) infection in BA patients resulted in elevated levels of helper T cells (Th1 and Th17) and reduction of regulatory T cells. Thus, CMV infection is considered as a cause of BA. We present the case of a 3-month-old boy who presented with intracerebral hemorrhage and finally died of liver failure. BA was diagnosed on autopsy and serum CMV-IgM was positive, but CMV antigen in the liver tissue was negative. Because CMV-associated BA has poor prognosis, compared with BA not associated with CMV, accurate classification of the type of BA is essential. [ABSTRACT FROM AUTHOR]

Cytomegalovirus can affect people of all ages, from all geographical areas, regardless their race or the social status. The severity of infection fluctuates from easy to severe, in most cases being asymptomatic. The antiviral therapy is rarely administered, only in selected cases and consists in ganciclovir or sometimes valganciclovir. Most of the patients do not present long-term sequelae from the infection, but for premature infants and children with very low birth weight, complications may occur more frequently than in the general population. We present the case of an infant of three months, diagnosed with cytomegalovirus hepatitis after corroborating clinical data, laboratory and ultrasound results. Evolution is initially favorable towards healing without suggesting the possibility of long-term organ injuries, but after four months, the infant is readmitted to the hospital and is diagnosed with biliary atresia. [ABSTRACT FROM AUTHOR]

Introduction: Biliary atresia (BA) is a disease characterized by a biliary obstruction of unknown origin. Viral agents have been proposed in the aetiology of BA such as cytomegalovirus (CMV). This virus also considered as a one of agents that can infect the liver and cause hepatitis. The aim of this study was to determine the role of CMV in children with both chronic hepatitis (negative for hepatitis B and C) and have biliary atresia in the same time. Material and Methods: A retrospective study done on 13 liver tissue paraffin blocks of children with chronic hepatitis (negative for hepatitis B and C) and biliary atresia (extra and intra). The diagnosis was based on the presence of HCMV protein (pp65) by using immunohistochemistry. Results: Immunohistochemistry for pp65 showed the liver tissue blocks were positive for 10 cases (76.9%).The mild inflammation and moderate fibrosis were the highest among the cases. Conclusion: CMV is one of the important viruses that can causes hepatitis in infants (whom are negative for hepatitis B and C), also this virus has significant role in pathogenesis of biliary atresia. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection has been suggested to be of importance for the development and outcome of biliary atresia (BA). However, most data are only available from single centre studies. We retrospectively collected data on rates, outcomes, and treatments for ongoing CMV infection at the time of Kasai portoenterostomy (KPE) from four different tertiary centres in Europe. The rate of ongoing CMV infection varied between 10–32% in the four centres. CMV positive patients were significantly older and had higher levels of several liver biochemistries at the time of KPE (p < 0.05 for all comparisons). In the largest centre, CMV infection was more common in non-Caucasians, and CMV infected patients had poorer long-term survival with native liver than CMV negative patients (p = 0.0001). In contrast, survival with native liver in the subgroup of CMV infected patients who had received antiviral treatment was similar to the CMV negative group. We conclude that ongoing CMV infection at the time of KPE occurs in a significant proportion of BA patients and that these patients seem to differ from CMV negative patients regarding age and biochemistry at the time of KPE as well as long-term survival with native liver. The latter difference may be reduced by antiviral treatment, but randomized, controlled trials are needed before such treatment can be recommended routinely. [ABSTRACT FROM AUTHOR]

Abstract: Background/Purpose: A viral origin of biliary atresia (BA) is discussed, and several studies have demonstrated different viral strains in liver biopsies of patients undergoing Kasai portoenterostomy. We hypothesized that the presence of hepatotropic viruses in patients undergoing portoenterostomy contributes to the progression of the disease and negatively affect the outcome. Methods: Liver biopsies were prospectively taken from 70 patients undergoing portoenterostomy in our department from April 1996 to April 2004. Samples were screened by polymerase chain reaction for all common hepatic viruses. Primary outcome parameter was survival with the native liver. Secondary parameters were postoperative serum activity of liver enzymes and serum bilirubin levels at different time points. Patients underwent regular follow-up until October 2008. Results: Twenty-eight patients (40%) were positive for 1 or more hepatotropic viruses. Four patients were lost to follow-up. In the remaining 66 patients, there was no significant difference in survival with their native liver between virus-positive and virus-negative patients. After a mean follow-up of 7.7 years (range, 4.6-16.1 years), 15 (23%) of 66 patients still lived with their native liver. There was no difference in liver enzymes, C-reactive protein, or bilirubin at any time point between both groups. Conclusion: A significant number of our patients tested positive for hepatotropic viruses in liver biopsies at the time of the Kasai procedure, but the presence of virus had no influence on the course of BA. This suggests that the ongoing inflammatory process of BA leading to liver cirrhosis in most Kasai-treated patients is not affected by hepatotropic viruses. Our data question the necessity to aggressively screen for and treat viral infections in patients with BA. [Copyright &y& Elsevier]

Aims. The aims of this study were to detect the infection rates of DNA viruses in liver tissue of biliary atresia and to investigate the effect of perinatal infection of cytomegalovirus in biliary atresia. Methods. A total of 85 liver biopsies (taken during Kasai portoenterostomy) were tested by fluorescence quantitative polymerase chain reaction for DNA viruses (herpes simplex virus [HSV], Epstein–Barr virus [EBV], varicella zoster virus [VZV], cytomegalovirus [HCMV], and adenovirus). Immunocytochemical detection of CMV-pp65 antigenemia assay was used to detect the presence of viral protein in liver samples. Human intrahepatic biliary epithelial cells was infected by the laboratory strain AD169 of HCMV in vitro. Results. Virus DNA was found in the biopsies (51/85 HCMV, 5/85 ADV, 3/85 EBV). The biopsies of 2 patients were tested positive for 2 viruses simultaneously. They include one case of HCMV in combination with ADV and one case of ASV in combination with EBV. CMV-pp65 antigenemia were distributed in hepatocyte, vascular endothelial cell, and biliary duct endothelial cell. The cytopathic effect and apoptosis were observed after HCMVAD169 infected human intrahepatic biliary epithelial cells at 6 days. Conclusion. Human intrahepatic biliary epithelial cell is the target cell of HCMV. The etiology of biliary atresia is probably multifactorial. The perinatal infection of HCMV is one of the important etiologies for biliary atresia in China. [ABSTRACT FROM PUBLISHER]

The etiology of biliary atresia is still unknown. It is generally accepted that virus infection may be one of the important causes that lead to biliary atresia. This study aimed to illustrate the relationship between infection of cytomegalovirus and prognosis of biliary atresia. From January 2002 to March 2004, 27 patients who had undergone Kasai’s procedure because of biliary atresia were investigated for cytomegalovirus-IgG, IgM and pp65, and their mothers were also examined for confirmation of cytomegalovirus infection. The patients were divided into three groups: infection free group, cytomegalovirus positive group and cytomegalovirus infection group. The rate of jaundice disappearance and the incidence of reflux cholangitis were analyzed statistically. The histopathological changes of the liver were also analyzed. The positive expression of cytomegalovirus-IgM and cytomegalovirus-pp65 in the patients was higher than that in their mothers (48% versus 14.81% and 37% versus 3.78%, respectively). Compared with the other two groups (80% in the infection free group, and 82% in the cytomegalovirus positive group), the rate of jaundice disappearance after operation in the cytomegalovirus infection group (36%) was significantly lower ( P<0.05), and the incidence of reflux cholangitis was higher ( P<0.05). Histopathological examination also showed that the degree of liver fibrosis and inflammation was more serious ( P<0.05). There is a strong correlation between cytomegalovirus infection and a lower rate of jaundice disappearance, also a higher post-operational reflux cholangitis. Liver fibrosis seems to be more severe in biliary atresia patients with cytomegalovirus infection. [ABSTRACT FROM AUTHOR]

Purpose The aim of this report was to study the amount and distribution of immunoglobulin deposits in liver biopsies from infants with biliary atresia (BA) and correlate the results to the cytomegalovirus (CMV) infection status. Methods Stored liver biopsies from 18 patients with BA and from 6 control patients without liver disease were immunohistochemically stained to detect IgG and IgM deposits. The intensity of the immunoglobulin staining was evaluated by a semiquantitative scoring scale. Ongoing CMV infection was defined as the detection of CMV-IgM in serum and/or the isolation of CMV in the urine and was noted in 9 of the patients with BA. Results When analyzing the immunoglobulin deposits on the hepatocellular canalicular membrane the intensity score for IgM deposits was significantly higher in biopsies from patients with BA infected with CMV than in those without. No canalicular staining was detected in control biopsies. Conclusions The results support the possibility that immunologic mechanisms are of importance in the pathogenesis of BA and that a CMV infection may trigger such mechanisms. [ABSTRACT FROM AUTHOR]

Biliary atresia has been commonly reported with cytomegalovirus (CMV) infection. CMV positive patients may present with a later onset however long term outcome is similar to non-CMV patients. There are very few case reports of role of antivirals in CMV and biliary atresia. We treated a 2 month old girl with biliary atresia who underwent portoduodenostomy at 2½ months of age but continued to have jaundice (bilirubin = 23.6 mg/dl) even after 1 month of Kasai's surgery and subsequently was treated with valganciclovir for 6 weeks following which her jaundice resolved. [ABSTRACT FROM AUTHOR]

Aim: To study the impact of ongoing cytomegalovirus (CMV) infection at presentation of biliary atresia (BA) on the long-term outcome after Kasai procedure. Methods: Twenty-eight patients with BA born 1988–1997 were included and followed-up until 2007. Eleven patients (group A) had ongoing CMV infection at presentation and were compared to the remaining 17 patients (group B). Median age at Kasai procedure was 75 days in group A and 70 days in group B (p = 0.12). Results: Including all patients, survival with native liver was 50% and 36% at 4 and 10 years of follow-up respectively. At the end of follow-up, it was 25% and overall survival was 68%. When comparing groups A and B, neither difference in survival with native liver (p = 0.67, log-rank test) nor in survival after liver transplantation was detected. Conclusion: Survival with native liver after Kasai procedure is comparable to that of other centres. CMV positive patients may present with a later onset, alternatively the detection of CMV infection could delay the referral of BA patients. No significant differences in long-term outcome were detected with regard to early CMV infection. [ABSTRACT FROM AUTHOR]