Liver-Intestinal Involvement in Graft Versus Host Disease in Pediatric Hematopoietic Stem Cell Transplantation Patients: Ten Years of Experience in 2 Centers of Latin America

**Background:** Graft-versus-host disease (GVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (HSCT), with an incidence of 35%–50%. After skin, the gastrointestinal (GI) tract and liver are most frequently affected. GI GVHD typically presents with abdominal pain and diarrhea, while liver GVHD manifests with elevated bilirubin and transaminases. Most available literature is based on adult populations; pediatric data from Latin America are scarce.

**Methods:** This retrospective observational descriptive study included all patients aged ≤18 years with confirmed GI or liver GVHD after HSCT at two centers (Clinical Hospital of Universidad Católica de Chile and Hospital Italiano de Buenos Aires, Argentina) from January 2007 through January 2017. Inclusion criteria were age ≤18 years at transplantation and histologically confirmed GI or liver GVHD. Toxic and infectious causes were excluded. Clinical presentation, endoscopic and histological findings (classified per Correa-Cruz/Friburgo and Lerner classifications), nutritional status (WHO charts), and outcomes were recorded. Bivariate analyses used Mann-Whitney U and Kruskal-Wallis tests with Bonferroni correction; P < 0.05 was considered significant.

**Key Results:** Over 10 years, 57 patients (33 in Chile, 24 in Argentina) presented with liver-GI GVHD. Sixty-five percent were male; median age range 0–17 years (IQR 9). Acute lymphatic leukemia was the most common pre-transplant diagnosis (45.6%). Ninety percent had received 1 HSCT; transplant types were umbilical cord blood (40%), peripheral blood (32%), and bone marrow (28%); 72% had unrelated donors. GI GVHD occurred in 74%, liver GVHD in 11%, and combined liver-GI involvement in 15%. Other organs involved included skin (n=46), eyes (n=5), and lungs (n=3). Eighty percent of intestinal GVHD presented within the first 90 days post-transplant. Diarrhea (96%) and abdominal pain (55%) were the most frequent symptoms, followed by rectal bleeding (23%), vomiting (23%), and hematemesis (14%). Endoscopies were performed in 88% (45/51); 35% required a second endoscopy to confirm diagnosis. Normal-appearing mucosa was observed in 17% of upper GI endoscopies and 29% of colonoscopies. Endoscopic pathological findings were most common in the colon (62%). Patients with combined liver-GI involvement had greater severity on colonoscopic classification than those with GI involvement alone. All liver GVHD patients had elevated transaminases and bilirubin; only 30% manifested elevations within the first 90 days. Doppler ultrasound was normal in 11/14 cases. Nutritional status worsened from transplant to GVHD diagnosis: underweight increased from 5.3% to 15%, and 65% required parenteral nutrition (median duration 30 days). All patients received intravenous corticosteroids (1–2 mg/kg); 52/57 required second-line therapy (cyclosporine, tacrolimus, infliximab, mycophenolate). Overall mortality was 26%. Complications occurred in 56%, mostly infectious (fungal, bacteremia, viral). Two serious biopsy-related complications occurred: one duodenal intramural hematoma and one hepatic pseudoaneurysm requiring embolization. No significant association was found between endoscopic/histological severity and sex, transplant type, complications, or mortality; however, combined GI-liver involvement was associated with greater colonoscopic severity.

**Clinical Implications:** GI and liver GVHD are serious complications of HSCT with high morbidity and mortality (26% in this cohort). GI involvement typically presents early (within 90 days) with diarrhea and abdominal pain, while liver involvement occurs later and may indicate more severe disease. Endoscopic findings are variable and do not correlate directly with histology, supporting the need for biopsy regardless of mucosal appearance. Combined GI-liver involvement may predict greater target organ severity. Diagnostic procedures carry risks (e.g., duodenal hematoma, hepatic pseudoaneurysm) and should be performed with caution. Nutritional support is frequently required. These findings from two Latin American centers add pediatric-specific data to a field dominated by adult studies.