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.

Background: In spite of the introduction of peroral endoscopic myotomy (POEM), Heller myotomy (HM) remains the mainstay of treatment and the role of pneumatic dilatation (PD) is being debated. The aim of this study was to present a single-center experience in the diagnostic approach and treatment of esophageal achalasia (EA), including the long-term assessment of the QoL. Methods: Data collection was based on the retrospective analysis of clinical notes and prospective interviews with patients and their parents. Results: The study group consisted of 60 patients with EA (F: 26, M: 34), with a median age of 12.0 (1–17) years at diagnosis. The time from the first symptoms until the diagnosis was 1.0 year (0.5–2.0) and the most common were: regurgitation (91.3%), dysphagia (84.8%), and chest pain (47.8%). The diagnostic approach showed a high sensitivity for barium X-ray follow through, esophageal manometry, and endoscopy. Overall, a long-term good outcome of HM was achieved in 27 out of 37 patients (73%) and it was negatively affected by the time between the first symptoms and the diagnosis. Out of the 16 patients who underwent PD before HM, a good outcome was achieved in 14 patients (87.5%), compared to 13 out of 21 patients (62%) who only underwent HM (p = 0.22). Concomitant fundoplication was routinely performed, and 18% required post-operative endoscopic dilatation. At the end of the 12.1 (0.7–26.6)-year follow up, most patients had a good QoL, which significantly corresponded with the treatment outcomes. Conclusions: Patients suspected of EA should undergo a thorough clinical evaluation including a manometry, a barium X-ray, and an endoscopy. HM is a safe and effective treatment for achalasia and the outcome is not worsened by a preceding endoscopic PD. In most patients, HM alleviates symptoms, although an impaired QoL is common in long-term follow ups.

Functioning farnesoid X receptor (FXR; encoded by NR1H4) is key to normal bile acid homeostasis. Biallelic mutations in NR1H4 are reported in a few children with intrahepatic cholestasis. We describe a boy with progressive familial intrahepatic cholestasis and homozygous mutation in NR1H4. A boy had severe neonatal cholestasis with moderate hypercholanemia and persistently elevated alpha-fetoprotein. Despite medical treatment, coagulopathy was uncontrollable, prompting liver transplantation at age 8 mo with incidental splenectomy. The patient experienced catch-up growth with good liver function and did not develop allograft steatosis. However, 1 year after transplant, he died from an acute infection, considered secondary to immunosuppression and asplenia. A homozygous protein-truncating mutation, c.547C > T, p.(Arg183Ter), was subsequently identified in NR1H4, and both parents were shown to be heterozygous carriers. Absence of FXR and of bile salt export pump expression was confirmed by immunostaining of explanted liver. Severe cholestasis with persistently high alpha-fetoprotein and modest elevation of serum bile acid levels may suggest FXR deficiency. Some patients with FXR deficiency may not develop allograft steatosis and may respond well to liver transplantation.

Chronic kidney disease (CKD) is a common complication after liver transplantation (LT). Its prevalence with modern immunosuppression regimens, especially in children, is variable depending on the transplantation era. The study included 61 pediatric patients with at least 10 years of follow-up after liver transplantation remaining under constant care of the Department of Pediatric Surgery and Organ Transplantation. The analysis included several tests: estimated glomerular function (eGFR), results of screening for renal tubular defects and blood concentrations of basic immunosuppressive drug-tacrolimus. CKD was diagnosed in 3% of children at 12 years after LT. The maintaining of tacrolimus concentrations >4 ng/mL in long-term observation was associated with a significant increase of microalbuminuria. The presence of microalbuminuria, regarded as a risk factor of CKD, confirmed the necessity of regular comprehensive assessment of patients in long-term follow-up.

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.

Liver transplantation has become a routine treatment for children with end stage liver failure. Recently, the long term survival of pediatric patients after liver transplantation has improved, with a life expectancy much longer than that of adult recipients, but also with longer exposition of the graft to various injuries, including immunological, inflammatory and others. Biochemical tests, although important, do not always reflect graft injury. The aim of our study was to analyze the histopathology of the graft in late protocol biopsies and correlate it with the clinical and biochemical status of these patients. We analyzed 61 protocol liver biopsies taken from 61 patients. Biopsies were taken 9.03–17.09 years (mean 12.68, median 11.74 years) after transplantation. Liver specimens were examined particularly for the presence and stage of liver fibrosis, inflammation, steatosis, and acute or chronic cellular and humoral rejection. We did not find any abnormalities in 26 (42.6%) liver specimens. None of the patients had signs of cellular or antibody mediated rejection or chronic rejection. In 23 liver biopsies (37.7%), we found non-specific lymphoid infiltrates. Another problem was fibrosis (equal to or more than three on the Ishak scale)—we found it in 17 patients, including seven liver specimens (11.5%) with severe fibrosis (Ishak 5–6). Conclusions: Various pathomorphological abnormalities were found in more than half of patients with a median 11.74 years post-transplant follow-up. Most of them presented normal laboratory liver tests at the same time, suggesting a slow subclinical process leading to pathomorphological abnormalities. No single factor for the development of these abnormalities was found, but our study supports the need for protocol liver biopsies even in patients with normal/almost normal biochemical liver tests.