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Mikko P. Pakarinen - One of the best experts on this subject based on the ideXlab platform.

  • divergent expression of liver transforming growth factor superfamily cytokines after successful Portoenterostomy in biliary atresia
    Surgery, 2019
    Co-Authors: Anna Kerola, Päivi Heikkilä, Jouko Lohi, Hannu Jalanko, Annika Mutanen, Mikko P. Pakarinen
    Abstract:

    Background Pathogenesis of progressive liver fibrosis in biliary atresia after successful Portoenterostomy remains unclear. We related hepatic expression of transforming growth factor beta (TGF-β) superfamily cytokines to histologic liver injury after successful Portoenterostomy. Methods Enrolled in our study were 28 patients with biliary atresia who had liver biopsies obtained during and after successful Portoenterostomy, which normalized serum bilirubin ( Results After median follow-up of 3.0 years, histologic cholestasis resolved, whereas fibrosis had progressed only in isolated biliary atresia. Liver protein expression of transforming growth factor beta 1 and connective tissue growth factor (P Conclusion These findings support a central role of transforming growth factor beta superfamily in mediating continuing liver fibrogenesis after successful Portoenterostomy. Transforming growth factor beta pathway cytokines responded divergently to clearance of jaundice, which was reflected by differential progression of fibrosis between syndromic and isolated patients.

  • very low bilirubin after Portoenterostomy improves survival of the native liver in patients with biliary atresia by deferring liver fibrogenesis
    Surgery, 2019
    Co-Authors: Maria Hukkinen, Päivi Heikkilä, Jouko Lohi, Anna Kerola, Timo Jahnukainen, Mikko P. Pakarinen
    Abstract:

    Background Progression of fibrosis and ensuing complications determine the postoperative course of patients operated on for biliary atresia. We evaluated predictors of the progression of fibrosis in the native liver after operative treatment. Methods Among patients whose bilirubin decreased to Results After median follow-up of 5.2 years (interquartile range 1.6–10.2) after Portoenterostomy, liver biopsies showed cirrhosis in 53% of patients, and the Metavir stage remained stable or decreased in 38%. The development of cirrhosis was predicted by total or conjugated bilirubin ≥170/120 µmol/L at the time of Portoenterostomy (P ≤ .009); normalization of bilirubin within 1.9 months (P = .002); total or conjugated bilirubin ≥ 12.5/7.5 µmol/L (P = .002) and aspartate aminotransferase-to-platelet ratio ≥ 0.55 at 3 months postoperatively (P = .001); and total or conjugated bilirubin ≥ 7.5/2.5 µmol/L (P ≤ .001), aspartate aminotransferase-to-platelet ratio ≥ 0.63 (P = .004), and gamma glutamyl transferase ≥ 266 U/L (P = .007) at 6 months postoperatively. In multiple regression analysis, conjugated bilirubin ≥ 2.5 µmol/L at 6 months increased the risk of cirrhosis 35-fold (P = .020), and other predictors were not predictive. Total or conjugated bilirubin Conclusion Among patients whose serum bilirubin normalizes after Portoenterostomy, its rapid decrease to very low levels prolongs the survival of their native liver by delaying the progression of fibrosis.

  • noninvasive evaluation of liver fibrosis and portal hypertension after successful Portoenterostomy for biliary atresia
    Hepatology Communications, 2019
    Co-Authors: Maria Hukkinen, Päivi Heikkilä, Jouko Lohi, Hannu Jalanko, Timo Jahnukainen, Reetta Kivisaari, Mikko P. Pakarinen
    Abstract:

    We investigated noninvasive follow-up markers for histologic liver fibrosis and portal hypertension (PH) in patients with biliary atresia after successful Portoenterostomy (PE). Among children with bilirubin 11 µmol/L in the youngest tertile (AUROC, 0.91; P 80 µmol/L in the middle tertile (AUROC, 0.81; P = 0.009), and liver stiffness was >24 kPa in the oldest age tertile (AUROC, 0.96; P = 0.002). Conclusion: After successful PE, development of PH associates with progression of liver fibrosis and can be accurately detected by APRI and stiffness. Liver stiffness most accurately identified cirrhosis in older children, whereas biochemical markers of cholestasis closely reflected histologic cirrhosis in younger children.

  • molecular signature of active fibrogenesis prevails in biliary atresia after successful Portoenterostomy
    Surgery, 2017
    Co-Authors: Anna Kerola, Hanna Lampela, Päivi Heikkilä, Jouko Lohi, Hannu Jalanko, Annika Mutanen, Mikko P. Pakarinen
    Abstract:

    Background In biliary atresia mechanisms of progressive liver injury leading to need of liver transplantation after successful Portoenterostomy remain unknown. A better understanding is a prerequisite for development of novel therapies to extend native liver survival, and we aimed to unravel molecular characteristics of liver injury after successful Portoenterostomy. Methods Liver biopsies obtained from 28 biliary atresia children during successful Portoenterostomy and at median age 3.0 years were studied. Biopsies were analyzed for histology and immunohistochemical expression of collagen 1, myofibroblast marker α-smooth muscle actin, and cytokeratin-7 positive ductal reactions. Hepatic ribonucleic acid (RNA) expression of growth factors and inflammatory cytokines was evaluated. Intestinal failure patients with comparable liver fibrosis and nonfibrotic gallstone patients and donor livers were controls. Results After successful Portoenterostomy, histologic cholestasis resolved and portal inflammation reduced, while fibrosis along with ductal reactions and overexpression of collagen and α-smooth muscle actin persisted. At follow-up, liver RNA expression of collagen and platelet-derived growth factor was increased, whereas RNA expression of various inflammatory cytokines remained low. Disappearance of periductal α-smooth muscle actin expression after successful Portoenterostomy (36% of patients) associated with contracted ductal reactions and reduced progression of fibrosis, collagen accumulation, platelet-derived growth factor RNA expression, and serum levels of bile acids and bilirubin. Fibrosis progressed less rapidly in syndromic than in isolated biliary atresia patients. Conclusion These findings suggest that instead of inflammation, molecular signature of active fibrogenesis in association with ductal reactions prevails in long-term native liver survivors with biliary atresia. Patients should be stratified for isolated and syndromic disease forms in interventional studies.

  • Native liver histology after successful Portoenterostomy in biliary atresia.
    Journal of Clinical Gastroenterology, 2014
    Co-Authors: Hanna Lampela, Silja Kosola, Päivi Heikkilä, Jouko Lohi, Hannu Jalanko, Mikko P. Pakarinen
    Abstract:

    Background:Biliary atresia is the most common indication for childhood liver transplantation. The effects of successful Portoenterostomy (PE) on native liver histology remain unclear.Aims:We assessed changes in native liver histology after a successful PE in relation to liver function and clinical o

Claus Petersen - One of the best experts on this subject based on the ideXlab platform.

Benno M Ure - One of the best experts on this subject based on the ideXlab platform.

Mark Davenport - One of the best experts on this subject based on the ideXlab platform.

  • glucocorticosteroids for infants with biliary atresia following kasai Portoenterostomy
    Cochrane Database of Systematic Reviews, 2016
    Co-Authors: Athanasios Tyraskis, Christopher Parsons, Mark Davenport
    Abstract:

    Background Biliary atresia is a life-threatening disease characterised by progressive destruction of both intra- and extra-hepatic biliary ducts. The mainstay of treatment is Kasai Portoenterostomy, as soon as the disease has been confirmed. Glucocorticosteroids are steroid hormones which act on the glucocorticoid receptor and have a range of metabolic and immunomodulatory effects. Glucocorticosteroids are used to improve the postoperative outcomes in infants who have undergone Kasai Portoenterostomy. Objectives To assess the beneficial and harmful effects of glucocorticosteroid administration versus placebo or no intervention following Kasai Portoenterostomy in infants with biliary atresia. Search methods We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE Ovid, Embase Ovid, Science Citation Index Expanded (Web of Science), and online trial registries (last search: 20 December 2017) for randomised controlled trials. Selection criteria We included randomised clinical trials which assessed glucocorticosteroids for infants who have undergone Kasai Portoenterostomy. For harm, we also considered quasi-randomised studies, observational studies, and case-control studies that were identified amongst the search results. Data collection and analysis We used standard methodological procedures expected by Cochrane. We assessed the risk of bias for each trial according to prespecified domains. We analysed data using both random-effects and fixed-effect models. We performed the analyses using Review Manager 5.3 and Trial Sequental Analysis software. We considered a P value of 0.025 or less, two-tailed, as statistically significant. We planned to calculate risk ratios (RRs) for dichotomous outcomes, and the mean difference (MD) for continuous outcomes. For all association measures, we planned to use 95% confidence intervals (CIs) as well as Trial Sequential Analysis-adjusted CIs. We used Trial Sequential Analyisis to control the risks of random errors; however, we were often unable to implement this beyond calculating the required information size as there were few trials and data. We assessed the certainty of the evidence using GRADE. Main results We found two randomised controlled trials fulfilling the inclusion criteria of our review. The trials provided data for meta-analysis. We judged the two trials as trials at low risk of bias. The two trials randomised a total of 213 infants to glucocorticosteroids versus placebo. In our Trial Sequential Analysis, the required information size (that is, the meta-analytic sample size) was not reached for any outcome. Trials were funded by charities, public organisations, and received support from private sector companies, none of which seemed to have an interest in the outcome of the respective trials. The effect of glucocorticosteroids after Kasai Portoenterostomy on all-cause mortality is uncertain; the confidence interval is consistent with appreciable benefit and harm (RR 1.00; 95% CI 0.14 to 6.90; low-certainty evidence). The results showed little or no difference in adverse effects between the use of glucocorticosteroids or placebo after Kasai Portoenterostomy, however this analysis was based on a single trial and we have low certainty in the result (RR 1.02; 95% CI 0.87 to 1.20;). Available data suggest that the proportions of infants who do not clear their jaundice at six months is similar between the two groups (RR 0.89; 95% CI 0.67 to 1.17; low-certainty evidence). All-cause mortality or liver transplantation did not differ at two years between the two groups (RR 1.00; 95% CI 0.72 to 1.39; low-certainty evidence). There were no data regarding health-related quality of life.Our searches also yielded 19 observational studies, some of them containing limited information on harmful effects of glucocorticosteroid treatment. We presented the extracted information narratively. We identified one further ongoing trial with no currently available results. Authors' conclusions The two meta-analysed randomised clinical trials present insufficient evidence to determine the effects of using glucocorticosteroids versus placebo after Kasai Portoenterostomy in infants with biliary atresia on any of the primary or secondary review outcomes. There is insufficient evidence to support glucocorticosteroid use in the postoperative management of infants with biliary atresia for long-term outcomes of all-cause mortality or liver transplantation. It is also unclear if glucocorticosteroids are able to reduce the numbers of infants who did not clear their jaundice by six months. Further randomised, placebo-controlled trials are required to be able to determine if glucocorticosteroids may be of benefit in the postoperative management of infants with biliary atresia treated with Kasai Portoenterostomy. Such trials need to be conducted as multicentre trials.

  • vitamin d levels in infants with biliary atresia pre and post kasai Portoenterostomy
    Journal of Pediatric Gastroenterology and Nutrition, 2016
    Co-Authors: Anu Paul, Nedim Hadzic, Naomi Wright, Mark Davenport
    Abstract:

    ABSTRACTObjectives:Infants with biliary atresia (BA) are at high risk of vitamin D deficiency. We aimed to determine the prevalence and factors influencing vitamin D levels at presentation and post-Kasai Portoenterostomy (KPE).Methods:Single-centre retrospective review of infants with BA who underwe

  • cytomegalovirus associated biliary atresia an aetiological and prognostic subgroup
    Journal of Pediatric Surgery, 2015
    Co-Authors: Augusto Zani, Alberto Quaglia, Nedim Hadzic, Mark Zuckerman, Mark Davenport
    Abstract:

    Abstract Background and aims Perinatal cytomegalovirus (CMV) infection is a possible cause or trigger of biliary atresia though clinical evidence is scant. We hypothesised that CMV IgM+ve biliary atresia is a separate clinical entity compared to CMV IgM−ve biliary atresia. Methods Prospective single-centre study. 210 infants with histologically confirmed biliary atresia were treated in our institution (Jan. 2004 to Dec. 2011); of these 20 (9.5%) were CMV IgM+ve at presentation. We compared these with 111 infants who were CMV IgM−ve (controls) for clinical features, biochemistry at presentation and outcome following Kasai Portoenterostomy (KPE). A blinded comparison of age-matched liver histology was also performed. Data are quoted as median (interquartile range). A P value ≤0.05 was regarded as significant. Results Infants with CMV IgM+ve biliary atresia were older at Kasai Portoenterostomy (or laparotomy) [70 (60–80) days vs. 56 (44–75)days; P=0.003] and were more jaundiced [175 (147–224) vs. 140 (121–181) μmol/L; P=0.002+ with higher AST*287 (157–403) vs. 180 (133–254) IU/L; P=0.005] and aspartate aminotransferase-to-platelet ratio index [1.1 (0.79–3.0) vs. 0.63 (0.43–0.95)] levels. Liver histology : CMV IgM+ve biliary atresia was characterised by a greater degree of inflammation (P Outcome : CMV IgM+ve biliary atresia had a poorer outcome with a reduced clearance of jaundice (15% vs. 52.2%; P=0.002), native liver survival (P Conclusions CMV IgM+ve biliary atresia is a distinct clinical and pathological entity with a diminished response to Kasai Portoenterostomy.

  • current management of biliary atresia
    Archives of Disease in Childhood, 2007
    Co-Authors: Deirdre Kelly, Mark Davenport
    Abstract:

    Extra-hepatic biliary atresia occurs in approximately 1:15 000 live births leading to about 50 new cases/year in the UK. Presentation is with prolonged jaundice, usually in a term baby who develops signs of obstructive jaundice. Management has been improved by public and professional education to encourage early referral and diagnosis to facilitate initial surgery before 8 weeks of age. Surgical management is complementary and includes an attempt to restore biliary flow (the Kasai Portoenterostomy) and liver transplantation if necessary. Medical management consists of antibiotics, ursodeoxycholic acid to encourage bile flow, fat soluble vitamin supplementation and nutritional support. Centralising surgery to specialised centres has improved survival of this potentially fatal disease to over 90% in the UK. Over half of infants undergoing Portoenterostomy will clear the jaundice and have a greater than 80% chance of a good quality of life, reaching adolescence without transplantation. For those children developing intractable complications of cirrhosis and portal hypertension, liver transplantation provides a 90% chance of achieving normal life.

  • randomized double blind placebo controlled trial of corticosteroids after kasai Portoenterostomy for biliary atresia
    Hepatology, 2007
    Co-Authors: Mark Davenport, Mark D Stringer, Patricia Mcclean, Giorgina Mielivergani, S Tizzard, Nedim Hadzic
    Abstract:

    The objective of this study was to evaluate adjuvant corticosteroids after Kasai Portoenterostomy for biliary atresia. The study consisted of a prospective, 2-center, double-blind, randomized, placebo-controlled trial of post–Kasai Portoenterostomy corticosteroids (oral prednisolone: 2 mg/kg/day from day 7 to day 21 and 1 mg/kg/day from day 22 to day 28). The data were compared with χ2 or Mann-Whitney tests, as appropriate. Seventy-one postoperative infants with type 3 biliary atresia were randomized to receive either oral prednisolone (n = 36) or a placebo (n = 37). At 1 month, the median bilirubin level was lower in the steroid group (66 versus 92 μmol/L, P = 0.06), but no difference was evident at 6 (P = 0.56) or 12 (P = 0.3) months. The proportion of infants with a normal bilirubin level (<20 μmol/L) at 6 (47% versus 49%, P = 0.89) and 12 months (50% versus 40%, P = 0.35) was not significantly different. The need for transplantation by 6 (12% versus 13%, P = 0.99) and 12 months (26% versus 35%, P = 0.47) was not significantly different. The steroid effect was more pronounced in younger infants (less than 70 days at Kasai Portoenterostomy, n = 51), with a reduced bilirubin level at 1 month (64 versus 117 μmol/L, P = 0.01) and with a greater proportion with a normal bilirubin level at 12 months (54% versus 37%, P = 0.22). Conclusion: There was a beneficial effect on the rate of reduction of bilirubin in the early postoperative period (specifically in infants less than 70 days old at surgery), but this steroid regimen did not reduce the need for liver transplantation. (HEPATOLOGY 2007;46:1821–1827.)

Chiyoe Shirota - One of the best experts on this subject based on the ideXlab platform.

  • laparoscopic kasai Portoenterostomy is advantageous over open kasai Portoenterostomy in subsequent liver transplantation
    Surgical Endoscopy and Other Interventional Techniques, 2020
    Co-Authors: Chiyoe Shirota, Takahisa Tainaka, Yujiro Tanaka, Naruhiko Murase, Akinari Hinoki, Yasuhiro Ogura, Masahiro Nakatochi, Hideya Kamei, Nobuhiko Kurata, Wataru Sumida
    Abstract:

    Native liver survival after laparoscopic Kasai Portoenterostomy (Lap-PE) for biliary atresia (BA) is controversial. We examined whether a jaundice-free native liver survival rate is comparable between conventional Kasai Portoenterostomy (Open-PE) and Lap-PE. Then, the impact of the two types of PE on subsequent living-donor liver transplantation (LTx) was addressed in this study. The jaundice-free rate in 1- and 2-year-old patients who underwent Open-PE and Lap-PE from January 2006 to December 2017 was investigated. Additionally, perioperative data (duration from the start of surgery to the completion of hepatectomy and others) of patients aged 2 years or younger who underwent LTx after either Open-PE or Lap-PE from 2006 to 2017 were evaluated. Thirty-one (67%) out of 46 Open-PE patients and 23 (77%) out of 30 Lap-PE patients showed native liver survival with jaundice-free status at 1 year of age (p = 0.384); 29 (63%) out of 46 Open-PE patients and 19 (70%) out of 27 Lap-PE patients showed native liver survival with jaundice-free status at 2 years of age (p = 0.524); there were no significant differences. Additionally, there were 37 LTx cases after PE within 2 years of birth, including 29 Open-PE and 8 Lap-PE cases. The patients in the Lap-PE group had fewer adhesions and significantly shorter durations of surgery up to the completion of the recipient’s hepatectomy and durations of post-LTx hospital stay compared to the Open-PE group. There were no differences in blood loss or duration of stay in intensive care unit between the Lap-PE and Open-PE groups. Jaundice-free native liver survival rate has been comparable between Open-PE and Lap-PE. Lap-PE resulted in fewer adhesions, contributing to better outcomes of subsequent LTx compared to Open-PE.

  • efficacy of and prognosis after steroid pulse therapy in patients with poor reduction of jaundice after laparoscopic kasai Portoenterostomy
    Pediatric Surgery International, 2019
    Co-Authors: Yujiro Tanaka, Takahisa Tainaka, Chiyoe Shirota, Wataru Sumida, Kazuo Oshima, Satoshi Makita, Tomoko Tanaka, Yukiko Tani, Kosuke Chiba, Hiroo Uchida
    Abstract:

    High-dose postoperative steroid therapy after Kasai Portoenterostomy is reported to improve jaundice clearance and a strong anti-inflammatory activity might prevent fibrous tissue formation which is often observed at the porta hepatis in revision surgery. We started steroid pulse therapy for the patients with cessation of decrease in jaundice and aimed to evaluate the efficacy in this study. The demographics and outcomes of patients who underwent laparoscopic Kasai Portoenterostomy and received steroid pulse therapy within 2 months postoperatively between September 2014 and December 2018 were retrospectively reviewed; the therapy was determined successful when the serum total bilirubin level decreased to or below two-thirds of the pre-therapy level after 2 weeks. Patient data in the successful group were compared with those in the unsuccessful group. Steroid pulse therapy was successful in seven of 16 patients (43.8%). The percentage of patients whose serum total bilirubin level decreased to normal was significantly higher in the successful group at 3 months (85.7% vs. 11.1%, P = 0.0028) and after all (100% vs. 33.3%, P = 0.011). Steroid pulse therapy was effective for some patients. Unsuccessful cases may have little chances of jaundice clearance; revision Kasai Portoenterostomy would be a good option.

  • multicenter retrospective comparative study of laparoscopic and open kasai Portoenterostomy in children with biliary atresia from japanese high volume centers
    Journal of Hepato-biliary-pancreatic Sciences, 2019
    Co-Authors: Naruhiko Murase, Masaki Nio, Hideyuki Sasaki, Chiyoe Shirota, Akinari Hinoki, Hirofumi Tomita, Naoki Shimojima, Kazunori Tahara, Yutaka Kanamori, Masato Shinkai
    Abstract:

    Background Multicenter study was undertaken to analyze the results of laparoscopic and open Kasai Portoenterostomy. Methods Subjects were infants with type III biliary atresia who underwent open operation (n = 106) or laparoscopic operation (n = 21) between January 2012 and December 2015. Clinical data were compared between open and laparoscopic operations (2016-0534). Propensity score matching was performed to reduce the effect of treatment selection bias. Multivariate analyses were used to estimate the effect of the surgical approach on the jaundice clearance rate and the native liver survival rate. Results The postoperative jaundice clearance rate and the 1-year native liver survival rate were not significantly different between open and laparoscopic operations. Rates of cholangitis and major complications of laparoscopic operation were comparable to those of open operation. Blood loss, time to resume oral intake, time to drain removal, and duration of analgesic usage of laparoscopic operation were significantly superior to those of open operation. Similar results were observed when analysis was adjusted based on propensity score. Multivariate analyses demonstrated that only age at operation was a poor prognostic factor. Conclusion Laparoscopic Kasai Portoenterostomy was associated with several favorable perioperative outcomes compared with open Kasai Portoenterostomy. The difference of surgical approach was not a significant independent predictor.

  • long term outcomes after revision of kasai Portoenterostomy for biliary atresia
    Journal of Hepato-biliary-pancreatic Sciences, 2016
    Co-Authors: Chiyoe Shirota, Takahisa Tainaka, Yasuyuki Ono, Kazuo Oshima, Hiroo Uchida, Naruhiko Murase, Akinari Hinoki, Kazuki Yokota, Ryo Shirotsuki, Hisami Ando
    Abstract:

    Background The indications for and efficacy of revision of Portoenterostomy (PE) for biliary atresia (BA) needs to be reassessed in an era of liver transplantation. We therefore reviewed the long-term outcomes following revision of PE. Methods This was a retrospective study of the medical records of patients with BA who underwent PE and revision of PE. We investigated the role of revision on outcomes of jaundice-free native liver survival (approval number: 2015–0094). Results Portoenterostomy was performed in 76 patients, among whom 22 underwent revision. Revision for recurrent jaundice was performed for four of 51 patients, who were transiently jaundice free after initial PE, but only one achieved native liver survival. Revision for repeated cholangitis in two patients achieved native liver survival over 10 years. Revision was performed in 16 of the 25 patients in whom initial PE failed; of these, four survived with their native liver (ages 3, 12, 12, and 14 years). The PE revision did not significantly affect liver transplantation duration and survival outcome. Conclusions Revision of PE was suitable for repeated cholangitis. Revision for recurrent jaundice, regardless of whether the initial PE was successful, could have a limited but positive effect in preventing long-term progressive liver failure.

  • hepatolithiasis after hepatic Portoenterostomy for biliary atresia
    Journal of Pediatric Surgery, 2006
    Co-Authors: Takahisa Tainaka, Kenitiro Kaneko, Takahiko Seo, Yasuyuki Ono, Yukio Ogura, Hidemi Wada, Chiyoe Shirota, Hisami Ando
    Abstract:

    Abstract Background Hepatolithiasis after hepatic Portoenterostomy for biliary atresia has been paid little attention, with only 22 reported cases. Patients and Methods Fifteen patients underwent living-related liver transplantation for biliary atresia after hepatic Portoenterostomy in our hospital between 1998 and 2004. The resected livers were examined for the existence and location of hepatolithiasis, composition of the calculi, and bacterial infection of bile. The relation between a history of cholangitis and the presence of hepatolithiasis was analyzed. Results Intrahepatic calculi were found in 8 (53%) of 15 patients. The calculi consisted of almost 100% calcium bilirubinate. Calculi were found in bile lakes in 8 patients. Bacteria were present in the bile in 8 (53%) of the 15 patients. Of the 8 patients, 7 (88%) had a history of ascending cholangitis. Conclusions Hepatolithiasis occurs after hepatic Portoenterostomy for biliary atresia more frequently than previously thought. Bile stasis and possibly bile infection are the main causes of calculi formation.