Primary liver transplantation vs transplant after Kasai portoenterostomy in children with biliary atresia: A retrospective Brazilian single-center cohort

BACKGROUND Biliary atresia(BA)is the most common indication for pediatric liver transplantation,although portoenterostomy is usually performed first.However,due to the high failure rate of portoenterostomy,liver transplantation has been advocated as the primary procedure for patients with BA.It is still unclear if a previous portoenterostomy has a negative impact on liver transplantation outcomes.AIM To investigate the effect of prior portoenterostomy in infants un-dergoing liver transplantation for BA.METHODS This was a retrospective cohort study of 42 pediatric patients with BA who underwent primary liver transplantation from 2013 to 2023 at a single tertiary center in Brazil.Patients with BA were divided into two groups:Those undergoing primary liver transplantation without portoenterostomy and those undergoing liver transplantation with prior portoenterostomy.Continuous variables were compared using the Student’s t-test or the Kruskal-Wallis test,and categorical variables were compared using theχ2 or Fisher’s exact test,as appropriate.Multivariable Cox regression analysis was performed to determine risk factors for portal vein thrombosis.Patient and graft survival analyses were conducted with the Kaplan–Meier product-limit estimator,and patient subgroups were compared using the two-sided log-rank test.RESULTS Forty-two patients were included in the study(25[60%]girls),23 undergoing liver transplantation without prior portoenterostomy,and 19 undergoing liver transplantation with prior portoenterostomy.Patients with prior portoenterostomy were older(12 vs 8 months;P=0.02)at the time of liver transplantation and had lower Pediatric End-Stage Liver Disease scores(13.2 vs 21.4;P=0.01).The majority of the patients(35/42,83%)underwent livingdonor liver transplantation.The group of patients without prior portoenterostomy appeared to have a higher incidence of portal vein thrombosis(39 vs 11%),but this result did not reach statistical significance.Prior portoenterostomy was not a protective factor against portal vein thrombosis in the multivariable analysis after adjusting for age at liver transplantation,graft-to-recipient weight ratio,and use of vascular grafts.Finally,the groups did not significantly differ in terms of post-transplant survival.CONCLUSION In our study,prior portoenterostomy did not significantly affect the outcomes of liver transplantation.

Tolerance in liver transplantation: Biomarkers and clinical relevance

Transplantation is the optimal treatment for end-stage organ failure,and modern immunosuppression has allowed important progress in short-term outcomes. However,immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus,a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor Fox P3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise,other immune cells,such as dendritic cells,monocyte/macrophages or natural killer cells,have been described as part of the process known as "operational tolerance". However,translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way,a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multicenter clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio.

De novo malignancies after liver transplantation: The effect of immunosuppression-personal data and review of literature

BACKGROUND Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients. AIM To study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients. METHODS A systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy.RESULTS Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences. CONCLUSION The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer.

Biliary complications after pediatric liver transplantation: Risk factors, diagnosis and management

The expanded indications of partial grafts in pediatric liver transplantation have reduced waiting list mortality. However, a higher morbidity is observed, including an increased rate of biliary complications(BCs). Factors such as the type of graft, the preservation methods applied, the donor characteristics, the type of biliary reconstruction, and the number of bile ducts in the liver graft influences the occurrence of these complications. Bile leaks and strictures comprise the majority of posttransplant BCs. Biliary strictures require a high grade of suspicion, and because most children have a bileoenteric anastomosis, its diagnosis and management rely on percutaneous hepatic cholangiography and percutaneous biliary interventions(PBI). The success rates with PBI range from 70% to 90%. Surgery is reserved for patients who have failed PBI. BCs in children after liver transplantation have a prolonged treatment and are associated with a longer length of stay and higher hospital costs. However, with early diagnosis and aggressive treatment, patient and graft survival are not significantly compromised.

Hepatitis B virus recurrence after liver transplantation: An old tale or a clear and present danger?

Hepatitis B virus(HBV) recurrence after liver transplantation(LT) has been described more than 50 years ago. Similarly, to other clinical conditions, in which impairment of host immune defense favors viral replication, early reports described in details recurrence and reactivation of HBV in liver transplant recipients. The evidence of a possible, severe, clinical evolution of HBV reappearance in a significant percentage of these patients, allowed to consider,for some years, HBV positivity a contraindication for LT. Moving from the old to the new millennium this picture has changed dramatically. Several studies contributed to establish efficient prophylactic protocols for HBV recurrence and with the advent of more potent anti-viral drugs an increased control of infection was achieved in transplanted patients as well as in the general immunecompetent HBV population. Success obtained in the last decade led some authors to the conclusion that HBV is now to consider just as a "mere nuisance".However, with regard to HBV and LT, outstanding issues are still on the table:(1)A standard HBV prophylaxis protocol after transplant has not yet been clearly defined;(2) The evidence of HBV resistant strains to the most potent antiviral agents is claiming for a new generation of drugs;and(3) The possibility of prophylaxis withdrawal in some patients has been demonstrated, but reliable methods for their selection are still lacking. The evolution of LT for HBV is examined in detail in this review together with the description of the strategies adopted to prevent HBV recurrence and their pros and cons.

Liver transplantation in acute liver failure:A challengingscenario

Acute liver failure is a critical medical condition defined as rapid development of hepatic dysfunction associated with encephalopathy. The prognosis in these patients is highly variable and depends on the etiology, intervalbetween jaundice and encephalopathy, age, and the degree of coagulopathy. Determining the prognosis for this population is vital. Unfortunately, prognostic models with both high sensitivity and specificity for prediction of death have not been developed. Liver transplantation has dramatically improved survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment. The identification of patients who will eventually require liver transplantation should be carefully addressed through the combination of current prognostic models and continuous medical assessment. The concerns of inaccurate selection for transplantation are significant, exposing the recipient to a complex surgery and lifelong immunosuppression. In this challenging scenario, where organ shortage remains one of the main problems, alternatives to conventional orthotopic liver transplantation, such as living-donor liver transplantation, auxiliary liver transplant, and ABO-incompatible grafts, should be explored. Although overall outcomes after liver transplantation for acute liver failure are improving, they are not yet comparable to elective transplantation.

Production and activity of matrix metalloproteinases during liver fibrosis progression of chronic hepatitis C patients

BACKGROUND Matrix metalloproteinases(MMPs)participate in the degradation of extracellular matrix compounds,maintaining the homeostasis between fibrogenesis and fibrolytic processes in the liver.However,there are few studies on the regulation of liver MMPs in fibrosis progression in humans.AIM To assess the production activity and regulation of matrix metalloproteinases in liver fibrosis stages in chronic hepatitis C(CHC).METHODS A prospective,cross-sectional,multicenter study was conducted.CHC patients were categorized in fibrosis grades through FibroTest®and/or FibroScan®.Serum MMP-2,-7,and-9 were determined by western blot and multiplex suspension array assays.Differences were validated by the Kruskal-Wallis and Mann-Whitney U tests.The Spearman correlation coefficient and area under the receiver operating characteristic curve were calculated.Collagenolytic and gelatinase activity was determined through the Azocoll substrate and zymogram test,whereas tissue inhibitor of metalloproteinase-1 production was determined by dot blot assays.RESULTS Serum concentrations of the MMPs evaluated were higher in CHC patients than in healthy subjects.MMP-7 distinguished early and advanced stages,with a correlation of 0.32(P<0.001),and the area under the receiver operating characteristic displayed moderate sensitivity and specificity for MMP-7 in F4(area under the receiver operating characteristic,0.705;95%confidence interval:0.605-0.805;P<0.001).Collagenolytic activity was detected at F0 and F1,whereas gelatinase activity was not detected at any fibrosis stage.Tissue inhibitor of metalloproteinase-1 determination showed upregulation in F0 and F1 but downregulation in F2(P<0.001).CONCLUSION High concentrations of inactive MMPs were present in the serum of CHC patients,reflecting the impossibility to restrain liver fibrosis progression.MMPs could be good diagnostic candidates and therapeutic targets for improving novel strategies to reverse liver fibrosis in CHC.

Gram-negative bacteria causing infective endocarditis: Rare cardiac complication after liver transplantation

Bacterial endocarditis is a rare complication amongst solid organ transplant recipients and is often linked to bacteremia. Majority of these recipients do not have underlying valvular heart disease or congenital valvular abnormalities. Staphylococoocusaureus and Enterococcus species are the most commonly isolated organisms. There are very few reports of gram-negative bacteria causing endocarditis in liver transplant recipients. We report a 51-yearold male, a liver transplant recipient, who developed bacterial endocarditis of the mitral valve due to extended spectrum of betalactamase producing strain of Escherichia coli and was managed successfully with antibiotics.

Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation

BACKGROUND In a previous paper,we reported a high prevalence of donor-specific antibody(DSA)in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger cohort.AIM To clarify the importance of DSAs on long-term graft survival in a larger cohort of pediatric patients.METHODS We performed a retrospective analysis of 123 pediatric liver transplantation(LT)recipients who participated in yearly follow-ups including Luminex testing for DSA at our center.The cohort was split into two groups according to the DSA status(DSA-positive n=54,DSA-negative n=69).Groups were compared with regard to liver function,biopsy findings,graft survival,need for re-LT and immunosuppressive medication.RESULTS DSA-positive pediatric patients showed a higher prevalence of chronic rejection(P=0.01),fibrosis(P<0.001)and re-transplantation(P=0.018)than DSA-negative patients.Class II DSAs particularly influenced graft survival.Alleles DQ2,DQ7,DQ8 and DQ9 might serve as indicators for the risk of chronic rejection and/or allograft fibrosis.Mean fluorescence intensity levels and DSA number did not impact graft survival.Previous episodes of chronic rejection might lead to DSA development.CONCLUSION DSA prevalence significantly affected long-term liver allograft performance and liver allograft survival in our cohort of pediatric LT.Screening for class II DSAs in combination with assessment of protocol liver biopsies for chronic antibodymediated rejection improved early identification of patients at risk of graft loss.

Lenvatinib as first-line therapy for recurrent hepatocellular carcinoma after liver transplantation:Is the current evidence applicable to these patients?

Liver transplantation(LT)is one of the leading curative therapies for hepatocellular carcinoma(HCC).Despite recent optimization of transplant selection criteria,including alpha-feto protein,HCC recurrence after LT is still the leading cause of death in these patients.During the last decades,effective systemic treatments for HCC,including tyrosine kinase inhibitors and immunotherapy,have been approved.We describe the clinical scenario of a patient with recurrence of HCC five years after LT,who received lenvatinib as first-line systemic therapy to introduce systemic treatment options in this clinical setting.In this opinion review,we detail first and second-line systemic treatment options,focusing on those feasible for patients with recurrent HCC after LT.Several trials have evaluated new drugs to treat HCC patients in first and secondline therapy,but patients with recurrent HCC after LT have been excluded from these trials.Consequently,most of the evidence comes from observational retrospective studies.Whether tyrosine kinase inhibitors will remain the primary therapeutic approach in these patients,due to a relative contraindication for immunotherapy,may be clarified in the near future.

Rectal neuroendocrine tumors:Current advances in management,treatment,and surveillance

Rectal neuroendocrine neoplasms(r-NENs)are considered among the most frequent digestive NENs,together with small bowel NENs.Their incidence has increased over the past few years,and this is probably due to the widespread use of endoscopic screening for colorectal cancer and the advanced endoscopic procedures available nowadays.According to the current European Neuroendocrine Tumor Society(ENETS)guidelines,well-differentiated r-NENs smaller than 10 mm should be endoscopically removed in view of their low risk of local and distant invasion.R-NENs larger than 20 mm are candidates for surgical resection because of their high risk of distant spreading and the involvement of the muscularis propria.There is an area of uncertainty regarding tumors between 10 and 20 mm,in which the metastatic risk is intermediate and the endoscopic treatment can be challenging.Once removed,the indications for surveillance are scarce and poorly codified by international guidelines,therefore in this paper,a possible algorithm is proposed.

Serious drug-induced liver disease secondary to ezetimibe

Ezetimibe is the f irst member of a new family of lipid- lowering drugs that inhibits uptake of dietary and bili- ary cholesterol. It was approved by the FDA in 2002 for hypercholesterolemia alone or in combination with statins. Its use has been spreading over the last years. Ezetimibe was considered a safe drug. We report a case of a woman who developed a serious hepatocellular drug-induced liver disease after 4 mo therapy with 10 mg daily of ezetimibe. After withdrawal of the drug, the patient recovered slowly. Ezetimibe may produce seri- ous toxic hepatitis and prompt withdrawal is mandatory in case of a signif icant abnormality in liver testing after beginning or during treatment with ezetimibe.

Fatty liver disease,an emerging etiology of hepatocellular carcinoma in Argentina

AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma(HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease(NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit.RESULTS A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers(n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC(37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLDHCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015(4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3%(P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups(6.6 ng/m L vs 26 ng/m L; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality.CONCLUSION The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.

Immunosuppressive potency of mechanistic target of rapamycin inhibitors in solid-organ transplantation

Mammalian target of rapamycin, also known as me-chanistic target of rapamycin(m TOR) is a protein kinase that belongs to the PI3K/AKT/m TOR signaling pathway, which is involved in several fundamental cellular functions such as cell growth, proliferation, and survival. This protein and its associated pathway have been implicated in cancer development and the regulation of immune responses, including the rejection response generated following allograft transplantation. Inhibitors of m TOR(m TORi) such as rapamycin and its derivative everolimus are potent immunosuppressive drugs that both maintain similar rates of efficacy and could optimize the renal function and diminish the side effects compared with calcineurin inhibitors. These drugs are used in solid-organ transplantationtoinduceimmunosuppression while also promoting the expansion of CD4+CD25+FOXP3+ regulatory T-cells that could favor a scenery of immu-nological tolerance. In this review, we describe the mechanisms by which inhibitors of m TOR induce sup-pression by regulation of these pathways at different levels of the immune response. In addition, we par-ticularly emphasize about the main methods that are used to assess the potency of immunosuppressive drugs, highlighting the studies carried out about immunosuppressive potency of inhibitors of m TOR.

Gastrinoma and Zollinger Ellison syndrome:A roadmap for the management between new and old therapies

Zollinger-Ellison syndrome(ZES)associated with pancreatic or duodenal gastrinoma is characterized by gastric acid hypersecretion,which typically leads to gastroesophageal reflux disease,recurrent peptic ulcers,and chronic diarrhea.As symptoms of ZES are nonspecific and overlap with other gastrointestinal disorders,the diagnosis is often delayed with an average time between the onset of symptoms and final diagnosis longer than 5 years.The critical step for the diagnosis of ZES is represented by the initial clinical suspicion.Hypergastrinemia is the hallmark of ZES;however,hypergastrinemia might recognize several causes,which should be ruled out in order to make a final diagnosis.Gastrin levels>1000 pg/mL and a gastric pH below 2 are considered to be diagnostic for gastrinoma;some specific tests,including esophageal pH-recording and secretin test,might be useful in selected cases,although they are not widely available.Endoscopic ultrasound is very useful for the diagnosis and the local staging of the primary tumor in patients with ZES,particularly in the setting of multiple endocrine neoplasia type 1.Some controversies about the management of these tumors also exist.For the localized stage,the combination of proton pump inhibitory therapy,which usually resolves symptoms,and surgery,whenever feasible,with curative intent represents the hallmark of gastrinoma treatment.The high expression of somatostatin receptors in gastrinomas makes them highly responsive to somatostatin analogs,supporting their use as anti-proliferative agents in patients not amenable to surgical cure.Other medical options for advanced disease are super-imposable to other neuroendocrine neoplasms,and studies specifically focused on gastrinomas only are scant and often limited to case reports or small retrospective series.The multidisciplinary approach remains the cornerstone for the proper management of this composite disease.Herein,we reviewed available literature about gastrinoma-associated ZES with a specific focus on differential diagnosis,providing potential diagnostic and therapeutic algorithms.

Endoscopic techniques for diagnosis and treatment of gastroentero-pancreatic neuroendocrine neoplasms:Where we are

BACKGROUND The correct localization of the primary tumor site and a complete histological diagnosis represent the milestones for the proper management of gastro-enteropancreatic neuroendocrine neoplasms(GEP-NENs).AIM To analyze current evidence on the role of endoscopy in the diagnosis/treatment of GEP-NENs.METHODS An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature(retrospective and prospective studies,systematic reviews,case series)published in the last 15 years,using both medical subject heading(MeSH)terms and free-language keywords:gastro-enteropancreatic neuroendocrine neoplasms;endoscopy;ultrasound endoscopy;capsule endoscopy;double-balloon enteroscopy;diagnosis;therapy;staging.RESULTS In the diagnostic setting,endoscopic ultrasonography(EUS)represents the diagnostic gold standard for pancreatic NENs and the technique of choice for the locoregional staging of gastric,duodenal and rectal NENs.The diagnosis of small bowel NENs(sbNENs)has been improved with the advent of video capsule endoscopy and double-balloon enteroscopy,which allow for direct visualization of the entire small bowel;however,data regarding the efficacy/safety of these techniques in the detection of sbNENs are scanty and often inconclusive.From a therapeutic point of view,endoscopic removal is the treatment of choice for the majority of gastric NENs(type 1/2),for well-differentiated localized nonmetastatic duodenal NENs<1 cm,confined to the submucosa layer and for<10 mm,stage T1–T2,rectal NENs.EUS-guided pancreatic locoregional ablative treatments have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients.CONCLUSION Standard axial endoscopy and EUS still play a pivotal role in several GEP-NENs.Advanced techniques for increasing the rate of R0 resection should be reserved for high-volume referral centers.

Human leukocyte antigen compatibility and incidence of donorspecific antibodies in pediatric liver transplant recipients

BACKGROUND Antibody-mediated rejection following liver transplantation(LT)has been increasingly recognized,particularly with respect to the emergence of de novo donor-specific antibodies(DSAs)and their impact on graft longevity.While substantial evidence for adult populations exists,research focusing on pediatric LT outcomes remains limited.AIM To investigate the prevalence of human leukocyte antigen(HLA)mismatches and DSA and evaluate their association with rejection episodes after pediatric LT.METHODS A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre,Brazil,between December 2013 and December 2023.Only patients who survived for>30 days after LT with at least one DSA analysis were included.DSA classes I and II and cross-matches were analyzed.The presence of de novo DSA(dnDSA)was evaluated at least 3 months after LT using the Luminex®single antigen bead method,with a positive reaction threshold set at 1000 MFI.Rejection episodes were confirmed by liver biopsy.RESULTS Overall,67 transplanted children were analyzed;61 received grafts from living donors,85%of whom were related to recipients.Pre-transplant DSA(class I or II)was detected in 28.3%of patients,and dnDSA was detected in 48.4%.The median time to DSA detection after LT was 19.7[interquartile range(IQR):4.3-35.6]months.Biopsyproven rejection occurred in 13 patients at follow-up,with C4d positivity observed in 5/13 Liver biopsies.The median time to rejection was 7.8(IQR:5.7-12.8)months.The presence of dnDSA was significantly associated with rejection(36%vs 3%,P<0.001).The rejection-free survival rates at 12 and 24 months were 76%vs 100%and 58%vs 95%for patients with dnDSA anti-DQ vs those without,respectively.CONCLUSION Our findings highlight the importance of incorporating DSA assessment into pre-and post-transplantation protocols for pediatric LT recipients.Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.

Prevention and Treatment of Recurrent Hepatitis B after Liver Transplantation

Chronic hepatitis B is a global health problem that leads to development of various complications,such as cirrhosis,liver cancer,and liver failure requiring liver transplantation.The recurrence of hepatitis B virus (HBV) post-liver transplantation is a major cause of allograft dysfunction,cirrhosis of the allograft,and graft failure.Patients with high viral load at the time of transplantation,hepatitis B e antigen (HBeAg)positivity,or those with a history of anti-viral drug resistance are considered as high-risk for recurrent HBV post-liver transplantation,while patients with low viral load,including HBeAg negative status,acute liver failure,and hepatitis D virus (HDV) co-infection are considered to be at low-risk for recurrent HBV post-liver transplantation.Antivirals for patients awaiting liver transplantation(LT) cause suppression of HBV replication and reduce the risk of recurrent HBV infection of the allograft and,therefore,all HBV patients with decompensated cirrhosis should be treated with potent antivirals with high genetic barrier to resistance (entecavir or tenofovir) prior to liver transplantation.Prevention of post-liver transplantation recurrence should be done using a combination of hepatitis B immunoglobulin (HBIG) and antivirals in patients at high risk of recurrence.Low dose HBIG,HBIG-free protocols,and monoprophylaxis with high potency antivirals can still be considered in patients at low risk of recurrence.Even,marginal grafts from anti-HBc positive donors can be safely used in hepatitis B surface antigen (HBsAg) negative,preferably in anti-hepatitis B core (HBc)/anti-hepatitis B surface (HBs) positive recipients.In this article,we aim to review the mechanisms and risk factors of HBV recurrence post-LT in addition to the various treatment strategies proposed for the prevention of recurrent HBV infection

Gastroesophageal reflux disease in children: What’s new right now?

Gastroesophageal reflux(GER)in children is very common and refers to the involuntary passage of gastric contents into the esophagus.This is often physiological and managed conservatively.In contrast,GER disease(GERD)is a less common pathologic process causing troublesome symptoms,which may need medical management.Apart from abnormal transient relaxations of the lower esophageal sphincter,other factors that play a role in the pathogenesis of GERD include defects in esophageal mucosal defense,impaired esophageal and gastric motility and clearance,as well as anatomical defects of the lower esophageal reflux barrier such as hiatal hernia.The clinical manifestations of GERD in young children are varied and nonspecific prompting the necessity for careful diagnostic evaluation.Management should be targeted to the underlying aetiopathogenesis and to limit complications of GERD.The following review focuses on up-to-date information regarding of the pathogenesis,diagnostic evaluation and management of GERD in children.

Probiotics for gastrointestinal disorders: Proposed recommendations for children of the Asia-Pacific region

Recommendations for probiotics are available in several regions. This paper proposes recommendations for probiotics in pediatric gastrointestinal diseases in the Asia-Pacific region. Epidemiology and clinical patterns of intestinal diseases in Asia-Pacific countries were discussed. Evidence-based recommendations and randomized controlled trials in the region were revised. Cultural aspects,health management issues and economic factors were also considered. Final recommendations were approved by applying the Likert scale and rated using the GRADE system. Saccharomyces boulardii CNCM I-745(Sb) and Lactobacillus rhamnosus GG(LGG) were strongly recommended as adjunct treatment to oral rehydration therapy for gastroenteritis. Lactobacillus reuteri could also be considered. Probiotics may be considered for prevention of(with the indicated strains): antibiotic-associated diarrhea(LGG or Sb); Clostridium difficile-induced diarrhea(Sb); nosocomial diarrhea(LGG); infantile colic(L reuteri) and as adjunct treatment of Helicobacter pylori(Sb and others). Specific probiotics with a history of safe use in preterm and term infants may be considered in infants for prevention of necrotizing enterocolitis. There is insufficient evidence for recommendations in other conditions. Despite a diversity of epidemiological,socioeconomical and health system conditions,similar recommendations apply well to Asia pacific countries. These need to be validated with local randomized-controlled trials.