BACKGROUND AND OBJECTIVE

Foreign body (FB) ingestion is a common pediatric concern in the Philippines, but local studies on flexible endoscopic management are lacking. This study aimed to describe the clinical profile and outcomes of children referred for flexible endoscopic management and identify factors associated with poor outcomes.

This retrospective cohort study included 145 patients agedRESULTS

Most FB ingestions (96.55%) were accidental, with coins as the most common FB (56.55%). Patients were admitted an average of 40.42 hours post-ingestion and referred for endoscopy within 9.28 hours. Flexible endoscopy was performed in 44.83% of cases, with a 98.46% success rate and an average procedure time of 32.25 minutes. Spontaneous passage occurred in 50.34% of cases. Poor outcomes were linked to age 48 hours; OR: 15.43, p = 0.0181), and prolonged procedures (>30 minutes; OR: 12, p = 0.0318). Good outcomes were associated with unremarkable physical exams (OR: 0.078; p = 0.0018), early admission (CONCLUSION

Flexible endoscopy is effective and safe for FB extraction in children. Early admission and timely intervention significantly improve outcomes, while delays and prolonged procedures increase the risk of complications.

BACKGROUND AND OBJECTIVE

Choledochal cysts (CC) are rare congenital, cystic dilations of the biliary tree occurring predominantly in Asian populations and in females. Patients are usually children presenting with any of the following: abdominal pain, palpable abdominal mass, and jaundice. Its congenital nature hints at a potential genetic cause. A possible causal gene is TP53, a tumor suppressor with a germline variant called rs201753350 (c.91G>A) that changed from a G allele to an A allele, decreasing the cell proliferation suppressing activity of its functional protein. Currently, there is no information on the TP53 rs201753350 germline variant available for the Filipino population. This study determined the prevalence of rs201753350 and the association between the functional G allele, the rs201753350 germline variant A allele, and the occurrence of CCs in Filipino pediatric patients in a tertiary government hospital.

Genomic DNA was extracted from blood samples of pediatric patients clinically diagnosed with CC. Controls were DNA samples collected from a previous study. The samples underwent PCR, electrophoresis, and sequencing.

A total of 109 participants (22 cases and 87 controls) were included in the study. The A allele (22.94%) occurs at a lower frequency than the G allele (77.06%) among both cases and controls. More individuals have a homozygous G/G genotype (54.13%) than a heterozygous A/G genotype (45.87%) while the homozygous A/A genotype was not observed. The estimated risk of choledochal cyst occurrence is significantly lower in individuals with the A allele (PR: 0.08, 95% CI: 0.01 – 0.55) and the A/G genotype (PR: 0.06, 95% CI: 0.01 – 0.40).

There is no significant evidence to suggest an association between the TP53 rs201753350 germline variant and the occurrence of choledochal cysts in Filipinos. It is recommended that other mutations within and beyond the TP53 gene be investigated for possible associations with choledochal cyst occurrence.

Schistosomiasis, a snail-borne disease caused by infection with a trematode parasite of the genus Schistosoma, is one of the most neglected tropical diseases in the world. One of its rare complications is hepatosplenic schistosomiasis which ultimately leads to fibrosis and presinusoidal portal hypertension.

We report a case of a 13-year-old Filipino male from Quezon City with previous one year residence in the endemic island of Leyte, presenting with melena. Diagnostic work-up revealed hepatosplenomegaly and periportal fibrosis with multiple hepatic nodules on ultrasound, positive Schistosoma japonicum eggs on Kato-Katz stool examination technique, and findings of esophageal varices on upper endoscopy. The patient was managed with praziquantel, propranolol, and endoscopic rubber band ligation of the esophageal varices, with note of resolution of bleeding, and improvement on sonographic liver findings.

The degree of liver fibrosis from schistosomiasis is affected by poorly understood mechanisms which affect its severity, progression, and complications, regardless of biosocial factors including egg burden and duration of parasite exposure. This is the first case report on a Filipino adolescent to document significant interval improvement, within four weeks of treatment, of the characteristic fibrotic pattern in hepatosplenic schistosomiasis. Hepatosplenic schistosomiasis is still often missed out as the diagnosis in patients who consult with common symptoms, and high index of suspicion is recommended for those with history of residence in endemic areas. Likewise, treatment focusing on parasite eradication can aid in promptly addressing the resulting fibrosis and its complications.

OBJECTIVE

Phenobarbital is an inductor of microsomal hepatic enzyme and used as choleretic for cholestatic liver disease to enhance bile flow. It is also used as a premedication for hepatobiliary scintigraphy (HIDA) scan to improve diagnostic accuracy for an obstructive liver disease. We reviewed the available literature on the use of Phenobarbital for treatment of cholestasis and its utility as a premedication for HIDA scan.

All published studies before June 30, 2023 that investigated the efficacy, effectiveness or safety of Phenobarbital in cholestatic jaundice and its effect on the accuracy of hepatobiliary scintigraphy in diagnosis of obstructive jaundice were included. Electronic databases were searched including MEDLINE via PubMed, Cochrane Library, medRxIV, BioRxIV, as well as the following registries for ongoing and completed trials: ClinicalTrials.gov (USA); ChiCTR.org. (China); and the WHO International Clinical Trials Registry Platform. We screened abstracts, reviewed full texts, and extracted relevant information on study design, settings, population and outcomes. There was no age and language restriction. Two reviewers independently rated the quality of included studies using: Joanna Briggs Institute critical appraisal tool for case reports, case series, and diagnostic accuracy; Newcastle – Ottawa Quality Assessment Scale for cohort studies, and Cochrane Risk of Bias for Randomized Trials. Risk of bias was appraised and GRADE certainty of evidence was judged. Pooled analysis was done using Stata 14 and reported as sensitivity and specificity.

Included were nine reports on Phenobarbital as treatment for cholestasis (one case report, five case series, one cohort and two randomized studies) and seven studies (four diagnostics, two cohorts, one randomized trial) on its use as a premedication for HIDA scan. The quality of case report and case series were considered fair; cohort studies as good; and diagnostic studies were included based on overall assessment. The randomized studies had some or high risk for bias due to concerns in randomization process, measurement of outcome, and risk in the selection of reported results.

There were 31 patients (16 adults and 15 children) from case reports and case series. Of the 16 adults, serum total bilirubin concentrations declined from 4 to 70% from baseline in 13 of 15 (87%) patients after Phenobarbital was given at 120 to 250 mg per day from 22 days to f ive months. Eleven of 14 with pruritus at onset also had improvement in intensity of itching. Of the 15 pediatric patients, ten (67%) showed a decrease from 10 to 60% of the baseline total bilirubin but not a normalization with Phenobarbital intake at a dose of 3 to 12 mg/kg/day from one to 21 months. Five of 14 children also had relief of itching after treatment.

Phenobarbital compared to Ursodeoxycholic acid had limited efficacy in reducing the bilirubin levels in neonates and young infants with cholestasis.

Phenobarbital compared to Ursodeoxycholic acid had limited efficacy in reducing the bilirubin levels in neonates and young infants with cholestasis.

Moderate certainty evidence showed that with Phenobarbital pretreatment, the hepatobiliary scan done on patients with neonatal cholestasis had 100% (CI 99.2, 100; I2 = 0.0%) sensitivity and 80.2% (CI 65.4, 92.1; I2 = 76.6%) specificity while no Phenobarbital pretreatment had 100% (94.9, 100; I2 = 0.0%) sensitivity and 89.5% (CI 77.0, 98.1; I2 = 11.4%) specificity. Adverse effects of Phenobarbital were drowsiness, lethargy, poor feeding, and irritability.

There was limited effectiveness of Phenobarbital in decreasing bilirubin levels in cholestatic liver disease. Moderate certainty evidence demonstrated that premedication with Phenobarbital did not improve the specificity of HIDA scan in the diagnosis of obstructive jaundice of infancy. Neurologic symptoms were observed with Phenobarbital intake.

Paradoxical response to anti-tuberculosis treatment, defined as clinical or radiologic worsening of pre-existing lesions or the development of new lesions while ongoing treatment, poses diagnostic dilemma. Intestinal perforation as a paradoxical response is rare. We report a 10-year-old female who presented with recurrent abdominal pain, anorexia, and bloody diarrhea, and was diagnosed with disseminated tuberculosis. She had marked improvement after one month of anti-tuberculosis treatment but developed a recurrence of initial symptoms on the third month of therapy and was treated for cecal perforation. Histopathology of cecum revealed chronic granulomatous inflammation. The patient improved after the surgery and the resumption of anti-tuberculosis medications. Recognition of paradoxical reactions and differentiating it from drug resistance of other pathology is important as these necessitates different management strategies.

BACKGROUND

Hepatitis B virus causes life-threatening chronic liver infection and increases the risk of death from cirrhosis and liver cancer. A three-dose series of universal HBV vaccination initiated from birth is effective against the disease. It is unclear if catch-up vaccination is also effective in those with incomplete or no HBV vaccination.

To review the evidence on the effect of HBV catch-up vaccination on children and adults to decrease HBV-related morbidity.

We searched MEDLINE, Cochrane CENTRAL, ChinaXiv, MedRXIV, BioRXIV, Google Scholar, and ongoing and completed trials on USA: https://clinicaltrials.gov/; China: http://www.chictr.org.cn/searchprojen.aspx, and WHO: https://www.who.int/clinical-trials-registry-platform. The last search date was 30 June 2023. We considered experimental or observational studies, meta-analysis/systematic reviews, completed trials and preprints that investigated the efficacy of catch-up HBV immunization in decreasing morbidity from hepatitis B infection including acute and chronic hepatitis B infection, liver cirrhosis, and hepatocellular carcinoma. There was no age and language restriction. Two reviewers independently rated the quality of included studies using Newcastle – Ottawa Quality Assessment Scale for cohort and crosssectional studies. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach was used to determine the certainty of evidence. Data was presented as number (%) for categorical values. Differences between the unvaccinated and vaccinated group was described as relative risk or odds ratio for categorical variables. Data was pooled using Review Manager 5.4.

A total of four observational studies were included, one of which had data in children and adults [two (one with data in adults) studies in children; 3 in adults]. The cross-sectional study was assessed as good quality; and the three cohorts as fair to good. In children, a high certainty evidence study showed that catch up vaccination in 9 to 18 years old decreased risk of HBsAg positivity [RR: 0.09 (0.004, 0.21)], reduced HBV DNA detection [RR: 0.084 (0.026, 0.273)], and increased antiHBs seroconversion [RR: 2.08 (1.84, 2.33)]. The quality of evidence was deemed high based on a large treatment effect. Another low certainty evidence study in Italy showed that HBV mass immunization in 0-10 years old decreased the prevalence of HBsAg anti-HBc and increased anti-HBs seroconversion after vaccination.

In adults, three low certainty evidence studies were included. Two studies showed decreased incidence of acute hepatitis B [OR: 0.08 (0.05, 0.12), I2 = 33%]. Another study demonstrated a decreased prevalence of hepatocellular carcinoma with HBV vaccination with the incidence ratio of vaccinated with chronically infected at 0.04 (0.02, 0.07) showing a large magnitude of benefit for vaccination against HCC when chronic HBV infection is prevented. The studies were deemed to have low quality due to issue of directness and study design.

HBV catch-up vaccination in adults is effective in decreasing the prevalence of acute hepatitis B and hepatocellular carcinoma. It likewise decreased the prevalence of HBsAg and anti-HBc, and provided anti-HBs protection in 0 to 18 years.

Objectives: The World Health Organization recently revised their recommendations and considered healthy children and adolescents as low priority group for COVID-19 vaccine. This review comprehensively assessed existing clinical evidence on COVID-19 vaccine in 12-17 years old. Methods: Included in this review were any type of study that investigated the efficacy, immunogenicity, safety, and effectiveness of COVID-19 vaccine on protection against SARS-COV-2 infection in 12-17 years old. Various electronic databases were searched up to March 15, 2023. Studies were screened, data extracted, risk of bias appraised, and certainty of evidence was judged using GRADE. Review Manager 5.4 was used to estimate pooled effects. Difference between the two groups was described as mean difference for continuous variables and as relative risk or odds ratio for categorical variables. Results: There were six randomized controlled trials and 16 effectiveness studies (8 cohorts and 8 case control). Low certainty evidence showed that BNT162b2 (Pfizer) was effective, immunogenic, and safe in healthy adolescents. There were 15 effectiveness studies on BNT162b2 (Pfizer) in healthy adolescent and one on immunocompromised patients. It was protective against infection with any of the variants, with higher protection against Delta than Omicron. BNT162b2 is protective against hospitalization and emergency and urgent care (high certainty); and critical care and MIS-C (low). Very low certainty evidence noted that BNT 162b2 was also immunogenic in 12-21 years old with rheumatic diseases while on immunomodulatory treatment but with possible increased exacerbation of illness. Low certainty evidence demonstrated that mRNA-1273 (Moderna) was effective, immunogenic, and safe. Low to very low certainty evidence were noted on the safety and immunogenicity of two vector base vaccines (ChAdOx1-19 and Ad5 vector COVID vaccine) and two inactivated vaccines (CoronaVac and BBIBP CorV). Conclusion There is presently low certainty evidence on the use of RNA vaccines in 12-17 years old. The recommendation on its use is weak. There is presently insufficient evidence for the use of inactivated and vector-based COVID-19 vaccines. Different countries should consider whether to vaccinate healthy adolescent without comprising the other recommended immunization and health priorities that are crucial for this age group. Other factors including cost-effectiveness of vaccination and disease burden should be accounted.
mRNA Vaccines ; Vaccines, Inactivated

Background: Children with COVID-19 may present with gastrointestinal (GI) symptoms and liver dysfunction. Objective: To determine the type and prevalence of gastrointestinal (GI) and hepatic manifestations of COVID-19 in children and its association with severity of illness. Methods: A systematic literature search was done from inception until January 4, 2021 using PubMed, Cochrane Library, Google Scholar and prepublication repositories with no language restrictions. Studies that reported the demographic and clinical features of children with COVID-19 and provided data on their GI and hepatic signs and symptoms were included. Prevalence of GI and hepatic manifestations were pooled using Stata14. Results: We included 58 studies with total of 4497 participants. Overall, one-third of children with COVID-19 presented with at least one GI symptom (33.8%; 95% confidence interval (CI) 23.0, 45.4; I2 97.5%; 42 studies, 3327 participants) with abdominal pain, nausea or vomiting, and diarrhea each occurring in approximately 20%. Children with severe COVID-19 were more likely to present with GI symptoms (odds ratio 2.59; 95% CI 1.35, 4.99; I2 24%; 4 studies, 773 participants). The pooled prevalence of elevated transaminases was 11% for both AST (11.3%, 95% CI 4.9, 19.3; I2 74.7%; 11 studies, 447 participants) and ALT (11.2%, 95% CI 7.1, 16.0; I2 40.8%; 15 studies, 513 participants). Hepatic findings such as jaundice (2-17%), hepatomegaly (2%) or behavioral changes (2%) from hepatic encephalopathy were variably reported by a few studies. The degree of heterogeneity was not improved on exclusion of studies with poor quality, but markedly improved on subgroup analysis according to geographical region and presence of MIS-C. Studies from China showed that children with COVID-19 had significantly lower pooled prevalence for any of the GI symptoms with low degree of heterogeneity, particularly for diarrhea, nausea/vomiting, and abdominal pain, all of which had I2 of 0%. Those with multisystem inflammatory syndrome in children (MIS-C) had significantly more common GI symptoms and increased transaminases than those without. Conclusion One-third of children with COVID-19 exhibit at least one GI symptom and more likely present in those with severe disease. Elevated transaminases were present in 10%. Prevalence of GI and hepatic manifestations were higher among children with MIS-C.
COVID-19 ; Liver Diseases

Background and Objective. Choledochal cysts (CC) are rare congenital, cystic dilations of the biliary tree occurring predominantly in Asian populations and in females. Patients are usually children presenting with any of the following: abdominal pain, palpable abdominal mass, and jaundice. Its congenital nature hints at a potential genetic cause. A possible causal gene is TP53, a tumor suppressor with a germline variant called rs201753350 (c.91G>A) that changed from a G allele to an A allele, decreasing the cell proliferation suppressing activity of its functional protein. Currently, there is no information on the TP53 rs201753350 germline variant available for the Filipino population. This study determined the prevalence of rs201753350 and the association between the functional G allele, the rs201753350 germline variant A allele, and the occurrence of CCs in Filipino pediatric patients in a tertiary government hospital. Methods. Genomic DNA was extracted from blood samples of pediatric patients clinically diagnosed with CC. Controls were DNA samples collected from a previous study. The samples underwent PCR, electrophoresis, and sequencing. Results. A total of 109 participants (22 cases and 87 controls) were included in the study. The A allele (22.94%) occurs at a lower frequency than the G allele (77.06%) among both cases and controls. More individuals have a homozygous G/G genotype (54.13%) than a heterozygous A/G genotype (45.87%) while the homozygous A/A genotype was not observed. The estimated risk of choledochal cyst occurrence is significantly lower in individuals with the A allele (PR: 0.08, 95% CI: 0.01 – 0.55) and the A/G genotype (PR: 0.06, 95% CI: 0.01 – 0.40). Conclusion. There is no significant evidence to suggest an association between the TP53 rs201753350 germline variant and the occurrence of choledochal cysts in Filipinos. It is recommended that other mutations within and beyond the TP53 gene be investigated for possible associations with choledochal cyst occurrence.
Jaundice

Jaundice in older children can occur when any obstruction is found within the bile ducts, either from bile stones, parasites, choledochal cysts and rarely, secondary to tumors. We present a previously well, 10-year-old Filipino boy with three-week history of progressive jaundice and tea-colored urine, and was initially assessed to have biliary ascariasis. Ultrasound showed a heterogeneous focus spanning the gallbladder neck and confirmed on endoscopic retrograde cholangiopancreatography as an exophytic mass at the ampulla of Vater. Tumor biopsy and immunohistochemical staining confirmed the diagnosis of Embryonal Rhabdomyosarcoma of the Bile Ducts. Chemotherapy was initiated to reduce the size of the tumor before any surgical intervention could be attempted. Despite chemotherapy, the tumor progressively grew. He acquired a respiratory infection which led to sepsis and his eventual demise. The disease should be considered in the differential diagnosis of a child with obstructive jaundice after exclusion of other more common causes.