Case series
Patients: Male • Male / (siblings)
Final Diagnosis: Progressive intrahepatic familial cholestasis type 1 (PFIC-1)
Symptoms: Jaundice
Medication: —
Clinical Procedure: —
Specialty: ...Transplantology
Hepatocellular carcinoma (HCC) is rare in young children. We attempted to see if immunohistochemical and mutational‐analysis studies could demonstrate that deficiency of the canalicular bile acid ...transporter bile salt export pump (BSEP) and mutation in ABCB11, encoding BSEP, underlay progressive familial intrahepatic cholestasis (PFIC)—or “neonatal hepatitis” suggesting PFIC—that was associated with HCC in young children. We studied 11 cases of pediatric HCC in the setting of PFIC or “neonatal hepatitis” suggesting PFIC. Archival liver were retrieved and immunostained for BSEP. Mutational analysis of ABCB11 was performed in leukocyte DNA from available patients and parents. Among the 11 nonrelated children studied aged 13‐52 months at diagnosis of HCC, 9 (and a full sibling, with neonatal hepatitis suggesting PFIC, of a tenth from whom liver was not available) had immunohistochemical evidence of BSEP deficiency; the eleventh child did not. Mutations in ABCB11 were demonstrated in all patients with BSEP deficiency in whom leukocyte DNA could be studied (n = 7). These mutations were confirmed in the parents (n = 14). With respect to the other 3 children with BSEP deficiency, mutations in ABCB11 were demonstrated in all 5 parents in whom leukocyte DNA could be studied. Thirteen different mutations were found. In conclusion, PFIC associated with BSEP deficiency represents a previously unrecognized risk for HCC in young children. Immunohistochemical evidence of BSEP deficiency correlates well with demonstrable mutation in ABCB11. (HEPATOLOGY 2006;44:478–486.)
The treatment of autoimmune hepatitis (AIH) is based on steroids and azathioprine (AZA). AZA is a pro-drug which is converted among others into 6-thioguanine (6-TG) and 6-methylmercaptopurine ...(6-MMP). The aim of the study was to determine the relationship between the AZA active metabolite 6-TG and both the biochemical and histological remission outcomes.
The authors conducted a retrospective analysis of a single chart review. The sample size consisted of 44 pediatric patients with AIH. Biochemical remission was defined as an alanine aminotransferase (ALT) level below 40 U/l and histological remission was defined as a situation when the control biopsy revealed inflammation grade G1 (or lower) in the Batts-Ludwig score. Statistical analysis was applied to assess the difference in remission outcomes in patients with different levels of 6-TG.
In the benchmark variant of our statistical analysis, we found that the correlation between 6-TG and ALT in the sample was not statistically significant. Moreover, the difference between the mean levels of ALT in the populations in and without remission was not statistically significant (the
-value of the
-test was 0.16).
Our results tend to support the claim that there is no statistically significant relationship between 6-TG concentration and remission (both biochemical and histological) in pediatric patients with AIH.
In adult liver transplant recipients, coronary artery disease and congestive heart failure are significant cause of morbidity and mortality. This may be attributed to the long-term immunosuppressive ...treatment, mostly with calcineurin inhibitors and steroids, which in long-term may be associated with hyperlipidemia, oxidative stress and cardiovascular complications. Since such data for children is sparse, the aim of this study was to assess the lipid and oxidative stress markers after pediatric liver transplantation (LTx).
We performed prospective analysis of 74 children, at the median age of 7.9 (2.8-11.6) years, 3.2 (1.2-4.3) years after LTx. We assessed the BMI Z-scores, cholesterol fractions (LDLc, HDLc, VLDLc), triglicerides, apolipoproteins (ApoAI, ApoB, ApoE), LCAT, insulin resistance by HOMA-IR and markers of oxidative stress and atherosclerosis: glutathione (GSH), glutathione peroxidase (GPx), asymmetrical dimethyl arginine (ADMA) and oxidized low-density lipoprotein (oxyLDL). At baseline, the results were compared with a healthy age-and-sex matched control group. After 3.1±0.3 year follow-up we repeated all investigations and compared them with the baseline results.
At the baseline, we investigated 74 patients 3.2 (1.2-4.3) years after LTx, at the median age of 7.9 (2.8-11.6) years. The prevalence of overweight or obesity (BMI >85
percentile) was 23% and was more common in girls (24% vs 20%). Fourteen patients had TCH >200 mg%, 9 patients had LDLc >130 mg% and TG were at normal levels in all patients. Compared to the controls, there were no significant differences in lipid profiles but we found decreased GSH (p<0.001) and GPx (p<0.001) which play role as an antioxidant defense. OS markers were higher in the study group: ADMA (p<0.001), and oxyLDL (p<0.0001). Insulin resistance by HOMA-IR was increased in the study group (p=0.0002) but fasting glucose remained within normal ranges in all patients. After 3.1-year follow-up, the BMI >95
and >85
percentile was present in 8% and 14% respectively. ADMA and oxyLDL decreased, whilst GSH and GPx increased when compared to the baseline. There was also significant decrease in apoB and Lp(a).
Children after LTx had normal lipid profiles when compared to controls, however there is a tendency for hypercholesterolemia and obesity, which may play a role in cardiovascular complications in the future. Some markers of oxidative stress were increased after LTx, however further investigations are required to establish its clinical significance.
A novel, mechanically interlocked molecular device was obtained from unique supramolecular tectons - pi -deficient tetraazamacrocyclic complexes of copper(ii) and nickel(ii). We present the synthesis ...of the first rotaxanes based on donor-acceptor interactions involving transition metal complexes. While spontaneous shuttling manifests itself in the variability of the NMR spectra, voltammetric experiments reveal a surprising mode of potential-controlled molecular switching, which does not employ common co-conformational changes. Significantly, it relies on reversible folding/unfolding of the rotaxane. The process is driven by the interplay between electrostatic repulsion and cohesive pi - pi interaction - a tug of war with a critical point at 1.31 V. Although rotaxanes with equivalent stations are considered degenerate molecular shuttles, we show that this is not the case when an unusual mechanism of switching is involved.
A new dataset of benthic foraminiferal assemblages from Adventfjorden (tributary fjord of Isfjorden, West Spitsbergen) was compared with the results of a study conducted by Zajączkowski et al. (2010) ...in Hornsund (West Spitsbergen). According to Nilsen et al. (2016), Atlantic water inflow to the Isfjorden Trough occurs more readily than to anywhere else along the shelf of Spitsbergen; thus, we compared the foraminiferal assemblages of the outwash Adventfjorden fjord, located in the Isfjorden system, with glacial Hornsund, located in southwest Spitsbergen. Despite the juxtaposition of Adventfjorden and Hornsund the data revealed varying impacts of shelf-transformed water (STW) on the benthic foraminiferal assemblages. Outer and central Adventfjorden was dominated by Adercotryma glomerata, Recurvoides turbinata and Spiroplectammina sp., reflecting the presence of STW, while abundant Melonis barleeanus in the central area of the fjord indicated a large flux of unaltered organic matter. Only the head of the fjord was dominated by the glaciomarine taxa Cassidulina reniforme and Elphidium clavatum. Foraminiferal fauna characteristic of STW-influenced environments (i.e., Nonionellina labradorica and R. turbinata) were also observed in outer Hornsund. However, the glacier-proximal taxa E. clavatum and C. reniforme were dominant throughout the fjord, demonstrating the impacts of meltwater and high sedimentation. Therefore, it is likely that in Hornsund, glacial impact is a major environmental factor, which is stronger than the influence of STW.
AbstractBackground and rationale for the study. The aim of the study was to determine the prognostic value of histopathological findings with special care to the severity of liver fibrosis at the ...moment of hepatopor-toenterostomy (HPE) in children with biliary atresia (BA). We performed analysis of 142 wedge liver biopsies taken at the time of HPE. All patients were operated by the same surgical team between 1995 and 2007. According to the outcome 6 months after HPE patients were divided into prognostic groups: group 1-bilirubin level < 2 mg% (n = 65), group 2-bilirubin level > 2 mg% (n = 77). Liver biopsies were re-evaluated according to the extended histopathological protocol and then were compared between the prognostic groups. Survival with native liver (SNL) estimates were performed in regard to severity of liver fibrosis. Results. Survival with native liver estimates after 2, 5 and 10 years in patients after successful operation were 96%, 91%, 75% vs. 30%, 11%, and 5% if operation failed (p < 0.001). There was no difference between groups in the following variables: fibrosis (p = 0.69), portal inflammation (p = 0.99), lobular inflammation (p = 0.95), cholangiolitis (p = 0.23), accumulation of bile pigments (zone 1:p = 0.49; zone 2:p = 0.51; zone 3:p = 0.48), bile plugs in canaliculi (p = 0.12), bile plugs in ducts (p = 0.32), bilirubinostasis in hepatocytes (p = 0.45), bile ductular proliferation (p = 0.59), ductal plate malformation (p = 0.12), focal necrosis (p = 0.44), giant cell transformation (p = 0.45), haematopoesis (p = 0.52), ductopenia (p = 0.46), microabscesses (p = 0.49), ballooning of hepatocytes (p = 0.08). The actuarial 5/10-year SNL was not dependent on severity of liver fibrosis (log-rank test p = 0.84). The severity of fibrosis corresponded neither with the age at HPE nor with the laboratory findings before operation but increased the risk of portal hypertension. Conclusion. Liver histology at the time of HPE is of limited value in prognosis making in BA.
Ecosystems of arctic fjords are exposed to various natural and human-induced stressors that shape the taxonomic structure and functioning. Glacial activity and meltwater inflows together with ...advection of sea water masses from shelves form variety of environmental gradients that have been shown to influence marine biota. Some of these stressors like sedimentation of inorganic matter, instabilities of bottom sediments or food supply have been recognized as drivers of benthic species richness and diversity with use of traditional (morphology based) methods (Węsławski et al. 2011, Włodarska-Kowalczuk et al. 2005, Włodarska-Kowalczuk et al. 2012). In this study we aimed to use eDNA metabarcoding based methods to discriminate ecological diversity of benthic Eukaryota along environmental gradient (fjord mouth – glacier) at 6 stations in Hornsund fjord (Svalbard). At each station we collected 9 surface sediment samples. To cover a wide diversity of eukaryotic taxa we sequenced mitochondrial COI and nuclear 18S VIV2 genes to. Computational pipeline (SLIM, Dufresne et al. 2019) was used to de-multiplexed sequences, cluster them into ASVs and then taxonomically assigned. For the COI marker we distinguished 4486 unique ASVs, which in majority (95%) remained unassigned but constituted 51% of all sequences. Among sequences with assigned taxonomy 98% of them belonged to Opisthokonta clade, which consisted of 12 phyla in majority Annelida (80% of seqences) followed by Nemertea (13%) and Echinodermata (6%). In case of 18S marker we obtained 1309 unique ASVs, almost 70% of them were taxonomically assigned, constituting almost 97% of all sequences. Seven clades were assessed with dominance of Opistokonta (44%) followed by Stramenopiles (29%) and Rhizaria (18%) of all sequences. Among Opistokonta we noted 17 phyla, which were dominated by Annelida (54% of sequences) with significant share of Arthropoda (20%), Nematoda (10%) and Nemertea (8%). Analysis of alpha diversity expressed as number of unique ASV and Shannon-Wiener index showed different results for COI and 18S markers. For the first marker we did no notice any trend along fjord except much lower indices at the station nearest to the glacier, while for the second marker we observed a decline of both indices from fjord mouth towards glacier, however when data were limited only to benthic metazoans (e.g. excluding Calanoida or Chaetognatha) the trend was not that evident. Our results show that eDNA metabarcoding based methods may be successfully used for diversity assessments of arctic benthic fauna. Among the two markers we used 18S V1V2 allowed to assign higher number of taxa, however high proportion of sequences belonged to non-benthic and unicellular organism. Nevertheless, using 18S V1V2 data we observer similar biodiversity pattern along fjord (desceasing biodiversity with decreasing distance to glacier) that is known from traditional, morphological studies.
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