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Background: Erythropoietic protoporphyria (EPP) is a rare inherited disease of heme biosynthesis resulting in the accumulation of protoporphyrin, characterized by liver failure in a minority of cases. Although liver transplant (LT) is the therapeutic strategy for advanced hepatic disease, it does not correct the primary defect, which leads to recurrence in liver graft. Thus, hematopoietic stem cell transplantation (HSCT) is an approach for treating EPP., Methods: We aim to describe the first sequential LT and HSCT for EPP performed in Latin America, besides reviewing the present-day literature., Results: The patient, a 13-year-old female with a history of photosensitivity, presented with symptoms of cholestatic and hepatopulmonary syndrome and was diagnosed with EPP. Liver biopsy demonstrated cirrhosis. She was submitted to a successful LT and showed improvement of respiratory symptoms. However, she had disease recurrence on the liver graft. She underwent a myeloablative HSCT using a matched unrelated donor, conditioning with BuCy (busulfan and cyclophosphamide), and GvHD (graft vs. host disease) prophylaxis with ATG (thymoglobulin), tacrolimus and methotrexate. Neutrophil engraftment occurred on D+18. She has presented mixed chimerism, but normalization of PP levels, being 300 days after HSCT, in good state of health and normal liver function., Conclusions: Consecutive LT and HSCT for EPP is a procedure that has been described in 10 cases in the literature and, even though these patients are a highly diversified population, studies have shown favorable results. This concept of treatment should be considered in patients with established liver disease., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The objective of this article is to evaluate the response to 6000 IU oral cholecalciferol (OC) treatment in children with chronic liver disease (CLD) and 25(OH)D deficiency., Methods: This historical cohort included non-transplanted CLD patients younger than 18 years old, which were analyzed for serum 25(OH)D, liver function, bone metabolism, Child-Pugh classification, and anthropometry. Patients with 25(OH)D deficiency (defined as 25(OH)D < 20 ng/mL) who received 6000 IU/day of OC were analyzed pre- and post-intervention, and considered responders if 25(OH)D > 20 ng/mL after at least 60 days. We compared clinical and laboratory data from patients with and without 25(OH)D deficiency, responders and nonresponders., Results: We studied 96 patients, of which 57.2% had biliary atresia. The prevalence of 25(OH)D deficiency was 67.7% (65/96). These patients were younger ( P < 0.001), had higher Child-Pugh scores ( P < 0.001), higher levels of total bilirubin (TB) ( P < 0.001), gamma-glutamyl transferase ( P < 0.001), and alkaline phosphatase ( P = 0.002), as well as lower levels of phosphorus ( P = 0.009) compared with patients without 25(OH)D deficiency. The median treatment length was 126 days (70-307 days). At the end of treatment, we observed a higher median of 25(OH)D ( P < 0.001), and lower median of parathyroid hormone (PTH) ( P = 0.023). Nine patients (29%) restored 25(OH)D to normal range; they had lower Child-Pugh score ( P = 0.001), lower TB levels ( P = 0.001), and higher level of phosphorus ( P = 0.003) after treatment., Conclusion: Despite an increase in 25(OH)D and decrease in PTH levels, 6000 IU/day of OC was not sufficient to restore 25(OH)D deficiency in most of the patients in this study., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

IL-17 is an important cytokine in the physiopathology of rheumatoid arthritis (RA). However, its participation in the genesis of nociception during RA remains undetermined. In this study, we evaluated the role of IL-17 in the genesis of articular nociception in a model of antigen (mBSA)-induced arthritis. We found that mBSA challenge in the femur-tibial joint of immunized mice induced a dose- and time-dependent mechanical hypernociception. The local IL-17 concentration within the mBSA-injected joints increased significantly over time. Moreover, co-treatment of mBSA challenged mice with an antibody against IL-17 inhibited hypernociception and neutrophil recruitment. In agreement, intraarticular injection of IL-17 induced hypernociception and neutrophil migration, which were reduced by the pre-treatment with fucoidin, a leukocyte adhesion inhibitor. The hypernociceptive effect of IL-17 was also reduced in TNFR1(-/-) mice and by pre-treatment with infliximab (anti-TNF antibody), a CXCR1/2 antagonist or by an IL-1 receptor antagonist. Consistent with these findings, we found that IL-17 injection into joints increased the production of TNF-alpha, IL-1beta and CXCL1/KC. Treatment with doxycycline (non-specific MMPs inhibitor), bosentan (ET(A)/ET(B) antagonist), indomethacin (COX inhibitor) or guanethidine (sympathetic blocker) inhibited IL-17-induced hypernociception. IL-17 injection also increased PGE(2) production, MMP-9 activity and COX-2, MMP-9 and PPET-1 mRNA expression in synovial membrane. These results suggest that IL-17 is a novel pro-nociceptive cytokine in mBSA-induced arthritis, whose effect depends on both neutrophil migration and various pro-inflammatory mediators, as TNF-alpha, IL-1beta, CXCR1/2 chemokines ligands, MMPs, endothelins, prostaglandins and sympathetic amines. Therefore, it is reasonable to propose IL-17 targeting therapies to control this important RA symptom.

Objective: To evaluate 16S ribosomal RNA (rRNA) gene amplification to diagnose spontaneous bacterial peritonitis (SBP)., Patients and Methods: According to a retrospective protocol, 31 patients with portal hypertensive ascites (serum to ascites albumin gradient > or = 1.1 g/dL) were studied. Ascitic fluid was analyzed as follows: Gram stain, aerobic and anaerobic cultures, polymorphonuclear cell count, and biochemical tests. Bacterial DNA was detected by polymerase chain reaction., Results: There were 8 episodes of SBP and 4 episodes of bacterascites (BA). Culture was positive in 4 of 8 cases of SBP and bacterial DNA was positive in 7 of 8 cases of SBP. Bacterial DNA was positive in 3 of 4 cases of BA and in 8 of 28 cases of culture-negative non-neutrocytic ascites (CNNNA). The PELD score, serum to albumin ascites gradient, and mortality showed no statistical difference between patients with CNNNA and the result of the bacterial DNA analysis., Conclusions: Although the 16S rRNA gene amplification was better than culture to diagnose SBP, bacterial DNA does not seem to allow a distinction between ascites infection and ascites colonization.

Objectives: To determine the prevalence of spontaneous bacterial peritonitis, ascites with bacterial infection and noninfected ascites in pediatric patients with portal hypertensive ascites and to compare the clinical and laboratory features of infected and noninfected ascites., Methods: Forty-one episodes of portal hypertensive ascites (serum-ascites albumin gradient >1.1 g/dL) in 31 patients were studied. Median age was 2.9 years. Twenty-four (77.4%) patients were cirrhotic and 20 (83.3%) were classified as Child-Pugh C. Median pediatric end-stage liver disease score was 18.5. The following ascites features were assessed: polymorphonuclear neutrophil cell count, cytology, pH, concentration of glucose, lactic dehydrogenase, total protein and albumin, Gram stain and bacteriological culture. Blood was sampled for complete blood count, coagulation studies, liver and renal function tests. Groups were compared by Mann-Whitney and chi tests (P < 0.05)., Results: Noninfected ascites were observed in 29 of 41 samples, spontaneous bacterial peritonitis in eight of 41 and ascites with bacterial infection in four of 41. The most prevalent clinical features were fever, voluminous ascites and encephalopathy, but there were no significant differences in the clinical features of the groups. All patients with infected ascites were cirrhotic. There was no statistical difference in Child-Pugh or pediatric end-stage liver disease status between patients with infected and noninfected ascites. Culture of ascetic fluid was positive in four of eight cases of spontaneous bacterial peritonitis. Gram-negative rods were the most prevalent bacteria cultured. Except for serum albumin, no statistical differences in biochemical markers were observed between patients with infected and noninfected ascites., Conclusions: The prevalence of infected ascites was 29.2%. With the exception of serum albumin, there were no differences in the clinical and biochemical features of patients with infected ascites and noninfected ascites.

Objectives: Hepatitis A vaccine has not been investigated in children with Down syndrome. The aim of this study was to evaluate immunogenicity and safety of an inactivated hepatitis A vaccine in noninstitutionalized children with Down syndrome and compare their responses to those of healthy control children., Methods: An open, prospective, controlled trial of 127 children ages 1 to 12 years, 63 with Down syndrome and 64 healthy control subjects, was conducted at a single hospital. Inactivated hepatitis A virus (HAV) vaccine containing 720 enzyme-linked immunosorbent assay units of alum-adsorbed HAV was administered intramuscularly in a two-dose schedule at 0 and 6 months. Seroconversion and anti-HAV titers were measured at months 1 and 7., Results: Seroconversion rates at month 1 were 92% and 94% and geometric mean titers (GMT) were 164.02 and 160.77 mIU/mL in the Down syndrome (DS) and control groups, respectively. At month 7, seroconversion rates were 100% in both groups, with GMT of 1,719.86 and 2,344.90 mIU/mL in the DS and control groups, respectively (P = 0.117). Both doses were well tolerated and no significant adverse events observed. Local reaction at the injection site was the most common adverse event reported in both groups (15% in DS and 11% in controls)., Conclusions: The authors' data demonstrate a good response to HAV vaccination in children with DS living at home, with GMT not statistically different from that of healthy control children. HAV vaccine is well tolerated and highly immunogenic in children with DS.

Background: Acute hepatitis A superimposed on chronic liver disease has been associated with a more severe course of disease and development of fulminant hepatitis. The aim of this study was to evaluate the immunogenicity and safety of an inactivated hepatitis A virus vaccine in children with chronic liver disease., Patients and Methods: This was an open, prospective, and controlled trial with 89 anti-HAV negative children between 1 and 16 years of age studied at a pediatric liver disease and transplantation referral center. Inactivated HAV vaccine (Havrix), from GlaxoSmithKline Biologicals containing 720 Elisa units of alum-adsorbed hepatitis A antigen per 0.5 ml dose was used. Thirty-four pediatric patients with chronic liver disease (mean age: 7.0 +/- 4.86 years) and 55 healthy controls (mean age: 4.8 +/- 2.7 years) received two doses of Havrix vaccine in months zero and six. Seroconversion and anti-HAV titers expressed as geometric mean titers (GMT) in mIU/ml were measured at months one and seven, by a modified Hepatitis A virus antibodies (HAVAB) assay., Results: Seroconversion rates at four weeks after primary immunization were 76% and 94% and the GMT 107.77 and 160.77 mIU/ml in the patient and control groups, respectively. One month after second dose the seroconversion rates were 97% and 100% in the groups with GMT of 812.40 and 2,344.90 mIU/ml. Both doses were well tolerated with no significant adverse events observed. Local injection-site symptoms were the most common reactions reported in both groups., Conclusion: Although GMTs were significantly lower in children with chronic liver disease compared to healthy controls, the overall seroconversion rates were not different. Hepatitis A virus vaccine was safe, well-tolerated, and immunogenic in children with chronic liver disease.