Dr Alex Knisely today in JPGN Journal Club is – as usual ! -- speaking with Dr Andreas Jenke, who for discussion has chosen the three articles Budd-Chiari Syndrome – A Single-Centre Experience from the United Kingdom, contributed by the Birmingham paediatric team ; Body Composition and Physical Activity in Pediatric Intestinal Failure, from London’s Great Ormond Street ; and Thiopurines Maintenance Therapy in Children with Ulcerative Colitis, the work of several medical centres in Israel. Budd-Chiari syndrome in children . . . a quarter of a century and 25 cases, but as soon as you think “I’ll never see that” you’ll be called to Accident & Emergency for your first patient with, yes, you guessed it. Good to have this review to read on your mobile telephone as you walk down to A&E. Our London mates remind us that the body-composition shifts-to-fat so usual in intestinal failure do not go away on their own once parenteral feeding no longer is required : One take-home message may be that children who never could develop a habit of exercise when they were catheter-tethered need to be prodded into physical activity (and their parents to learn to see the children as suited for physical activity). Finally, from Israel, a confirmation that the old ways may still be the best ways : Whilst the tendency nowadays is to carpet-bomb ulcerative colitis into submission, calling out the F16s (uhm, those are the biological agents) at presentation, traditional tactics of ground warfare (those are the thiopurines) both regain and hold territory very adequately indeed – less expensively and with far greater knowledge of What To Expect. Happy listening – and reading !

Our todays guest is Prof. Anil Dhawan of King’s College Hospital in London, leader of the paediatric liver service there, about Prof. Dhawan’s lifelong especial interest within paediatric hepatology: Acute liver failure. In May, 2023, at the annual meeting of ESPGHAN, he sketched – from his personal vantage point – the horrorshow with which this clinical diagnosis confronted caregivers thirty-plus years ago; what steps have been taken to improve the prognosis of children with acute liver failure (they’re doing better now); and what remains to be accomplished for these children in both the near term and the longer term. He believes that “bridge transplantation”, using hepatocytes administered intraperitoneally, holds out particular promise for many patients, maintaining them until liver recovery or liver transplantation more definitively resolves the crisis situation that acute liver failure still represents. In this podcast he shares anecdotes, perspectives, and hard data on acute liver failure and what can be, what should be, done for patients with that disorder. This mix is refracted through a unique and commanding personality – both informative and entertaining ? Well, have a listen, see what you think!

Dr Alex Knisely today in JPGN Journal Club is – as usual ! -- speaking with Dr Andreas Jenke, who for discussion has chosen two full-size articles, call them “mains”, and a pair of linked items from among the “starters”, that is, a letter to the editors of the journal and a response from ESPGHAN. The two “mains” are Efficacy and Safety of Teduglutide in Infants and Children With Short Bowel Syndrome Dependent on Parenteral Support, from a coalition of Japanese, British, and Finnish centres supported by Takeda Yakuhin, makers of teduglutide, and, from Boston Children’s Hospital (USA), Gastric Intestinal Metaplasia in Children – Natural History and Clinicopathological Correlation. The “starters” ? Liver Histology Before Treatment Withdrawal in Autoimmune Hepatitis – Is It Time to Review the ESPGHAN Recommendations ?, a Franco-Italian défi, and, réponse à cette provocation, Liver Biopsy is Indicated Before Attempting Treatment Withdrawal in Children with AIH – Commentary by the ESPGHAN HepCom. The mains may leave you wanting a bit more ; the teduglutide data draw on very few patients, the intestinal-metaplasia data yield no very firm conclusions ; but both offer at least reassurance. Mind you, if you are about to spend €100.000,00 on a year of teduglutide for one of your patients, you’ll be well-advised to do it in a manufacturer-supported study with firm guidelines for use and assessment – yes, a registry is needed. And the starters ? Highly spiced ! But, with a J Hepatol article from the Franco-Italian group (summarised in the Commentary, but which you must seek out on your own), they certainly fill the plate. Whose arguments are more convincing ? What will you say to the next teenager with treated AIH and “good numbers” who is desperate to abandon steroids and the like ? Prudence seems in order . . .

Today we are talking to Prof. (and Dr.) Richard Thompson, of London’s King’s College Hospital, who there for twenty-five years has broadened and heightened his leading role in studies of the genetics, physiology, and treatment of forms of intrahepatic cholestasis, disorders that come to clinical attention principally in childhood. Richard and Alex for fifteen years were on the same team at King’s, sometimes shoulder to shoulder, sometimes pushmi-pullyu, but always having fun. Their chat today, after rather a lot of reciprocal congratulation, touches on clinicogenetic correlations in Wilson disease, moving thence to bile salt export pump deficiency – first, with its spectrum of manifestations, as a paradigm of the falsity of Mendelian genetics ; second, with its responses to drugs that inhibit ileal bile acid transport, as a paradigm of how without fixing a programme’s basic code one can apply patches that substantially improve the programme’s utility (that is, how knowledge of clinicogenetic correlations permits patient-tailored choices among surgical and pharmacologic therapies, with earlier and more satisfactory improvements in health). Be warned : You won’t take on board in one hearing what Richard has to share. Make time, then, for a couple of listen-throughs. They will reward you well.

Dr Alex Knisely today is speaking with Dr Andreas Jenke – it’s Journal Club again. Dr Jenke has chosen from the August, 2023, number of JPGN three articles for discussion – from Brisbane (Queensland), Australia, and, in India, Lucknow, Jodhpur, and Rishikesh (a thousand-kilometre span across the centre and north of the subcontinent ! ), Oral Tacrolimus in Steroid-Refractory and - Dependent Pediatric Ulcerative Colitis - a Systematic Review and Meta-Analysis ; from a group in San Diego, California, with contributions from a group at Columbia University in New York City, An Open Label, Randomized, Multicenter Study of Elafibranor in Children with Nonalcoholic Steatohepatitis ; and from Edmonton (Alberta), Canada, Clinical Features of Children with Serology-Negative, Biopsy-Positive Celiac Disease. The Indian / Australian study is a meta-analysis and review rather than primary work ; it concludes that tacrolimus may allow caregivers to temporise, with an initially good response that rather rapidly tails off, and that it may be less effective in the steroid-refractory child. The elafibranor study holds out promise – but that promise is based on findings in only a few children and adolescents. (The study was ended early, with enrolment curtailed when drug- company sponsorship was withdrawn after elafibranor failed to meet expectations in adult patients.) Does seronegative coeliac disease differ clinically from seropositive coeliac disease ? Well, maybe. Hypogammaglobulinaemia A is more frequent in the former, albeit not universally found. But overall no particular feature, no single clinical-laboratory biomarker, emerged as both sensitive and specific for either form of coeliac disease : The search continues.

Today we are talking to Prof. Dr. Tobias Cantz, of Hanover / Hannover, Germany, on a topic that offers the chance to re-work many approaches to both acquired and inborn disease not just of the liver but also of the biliary tree. Prof. Cantz is a regenerative hepatologist, conducting research into how hepatocellular or cholangiocellular organoids – or, more complexly, organoids that include all the components of the differentiated and polarised and vascularised hepatic lobule – can be used to examine and to dissect how gene variants contribute to clinical disease, and how administration of organoids can contribute to repair of hepatobiliary injury. His presentation in Vienna this May, at the annual meeting of ESPGHAN, was a wonder ; the things that can be done already using these “organoids”, these miniature versions of components of an organ, are mind-boggling, and the feats to date really are only the start of what Prof. Cantz envisions. Perhaps his intensity, his devotion, and his determination to take our field forward can be appreciated, at least in part, in this conversation. Not easy listening, better suited for a quarter-hour in a lay-by during which you can concentrate on the abundance of information that he presents than for dodging delivery- van traffic – well, if you have to get to work, then listen to it not just on the way in but also again on the way home, to be sure you grasp it all.

Dr Alex Knisely today is speaking with Dr Andreas Jenke – it’s Journal Club again. Skipping over the June, 2023, number of JPGN, Dr Jenke has chosen from the July number not two but three articles for discussion – from a Scandinavian consortium, Risk Factors of Cancer in Pediatric-Onset Inflammatory Bowel Disease in Denmark and Finland ; from a group in California, Prevalence of Elevated ALT in Adolescents in the US 2011-2018; and from a group in Birmingham, England, Liver Disease inGLIS3 Mutations: Transplant Considerations and Bile Duct Paucity on Explant Histology. Interviewer and interviewee alike consider the Danish / Finnish study a lovely piece of work, the Californian study rather risky in respect of over-medicalisation of a questionably abnormal biomarker value, and the English study as  . . well, as questionable. What will your opinions be?

Today we are talking to Dr. Andreas Jenke — Journal Club again! Two articles of particular interest and significance from the May, 2023, number of JPGN are discussed. From Eva Karbaum and colleagues in Hamburg (Protocol Biopsies in Pediatric Liver Transplantation Recipients Improve Graft Histology and Personalize Immunosuppression) we learn that using protocol-biopsy findings to fine-tune liver transplant recipients’ drug regimens, either increasing them or decreasing them, on follow-up biopsy is demonstratedly safe or even beneficial; from Rachel Levy and colleagues at several Israeli medical centres (Trough Concentration Response in Infliximab and Adalimumab Treated Children With Inflammatory Bowel Disease Following Treatment Adjustment: A Pharmacokinetic Model) we learn that perhaps we need not wait for clinical disease to manifest before fine- tuning drug regimens – to respond to trough drug levels may permit us to intervene proactively. Dr. Jenke assesses the weaknesses and strengths of the studies reported. Will you and he reach the same conclusions? Read the articles, listen to the podcast, and find out! 

Todays guest is Prof. Dr. Christos Tsivinikos of the Al Jalila Children’s Specialty Hospital, Dubai (United Arab Emirates), by way of Liverpool, UK, where he worked long-term. Over the past several years he and his colleagues have built up in Dubai not just a comprehensive paediatric gastroenterology and hepatology service but also an aerodigestive-diseases service, with collaboration from a variety of specialists in coördinated treatment of the complex problems that both underlie and arise from disorders of the organs and tissues of the concerned regions, and he is a powerful advocate for this approach to multisystem disease. For some reason it has not been adopted in Europe so widely as it might be ; Professor Tsivinikos believes and hopes that in this regard progress can be made. At the May, 2023, annual meeting of ESPGHAN, held in Vienna, he discussed the advantages and drawbacks of the aerodigestive-disease paradigm, into which he delves today. If you are not yet convinced that to contribute in aerodigestive-disease clinical work will be of benefit to your patients and their families, perhaps his comments will be of particular interest. Please note : This is the last of three podcasts related to annual- meeting events, a week apart, with a return to Journal Club after another week. Mark your calendars for 15 June Dr Andreas Jenke — Journal Club again – after which the fortnightly rhythm customary to us resumes. 

Dr. Alex Knisely is talking to, or with, or even maybe mostly listening to Prof. Dr. Michael Trauner, of Vienna – Professor Trauner has a lot to say on today’s topic, on which he recently provided the keynote address at the May, 2023, annual meeting of ESPGHAN. The topic is bile acids: They’re paracrine and endocrine hormones, not just lipid solubilisers ; modified versions offer promise in modulating and treating many paediatric and adult hepatobiliary and gastrointestinal processes and disorders ; in short, physiology has no magicks in which they are not involved. They are, taken together, a lapis philosophorum or rather hepatogastroenterologorum. That is, the subject is alchemically complex, and to consult the recent review of the field by Prof. Dr. Trauner and his colleague Dr. Claudia Fuchs (Nat Rev Gastroenterol Hepatol 2022;19:432-50) may help us all get the most from his contribution today. Please note: This is the second of three podcasts related to annual- meeting events, a week apart, with a return to Journal Club after another week. Mark your calendars for Prof Christos Tsivinikos on aerodigestive-disease services to paediatric patients, available on 8 June, and then on 15 June Dr Andreas Jenke — Journal Club again!