Natural History of Chronic Hepatitis B Infection Among Chinese Children and Young Adults: A Single-Center Experience.

OBJECTIVES: There are limited data on the natural history of chronic hepatitis B virus (HBV) infection in Asian American children. The aim of the present study was to describe a single-center experience of chronic HBV infection in Chinese American patients in New York City. METHODS: A retrospective chart review was conducted for patients with chronic HBV infection who had pediatric visits from 2006 to 2017. Clinical and laboratory data were collected to characterize the status of HBV infection and its disease course both cross-sectionally and longitudinally. Available maternal charts were reviewed. RESULTS: Of the total 353 patients, 72 patients (20%) were US-born. Positive hepatitis B envelope antigen (HBeAg) was documented in 208 patients (58%). Three phases of chronic HBV infection were categorized for 329 patients: immune-tolerant 112 (34%), HBeAg-positive immune-active 47 (14%), and inactive carrier 82 (25%). The remaining 88 patients (27%) did not fit into a particular category with 26 of 88 patients meeting the criteria for inactive carrier except for mildly elevated alanine aminotransferase. Age and liver enzyme levels were significantly different between HBeAg-positive and HBeAg-negative groups (P < 0.05). Among 179 patients followed for ≥5 years, the spontaneous seroconversion rate was 38%. In eight patients with linked maternal data, all children completed the HBV vaccine series and seven of eight received hepatitis B immunoglobulin. All mothers were HBeAg-positive with high HBV DNA and had no anti-viral therapy during pregnancy. CONCLUSIONS: Both immune-tolerant and inactive carrier phases were common for chronic HBV infection with a spontaneous seroconversion rate of 38%. All US-born patients were born in the era of implemented universal immune-prophylaxis.

Helicobacter pylori Infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage by Whole-Genome Sequencing.

The emergence of drug resistance in Helicobacter pylori has resulted in a greater need for susceptibility-guided treatment. While the alleles associated with resistance to clarithromycin and levofloxacin have been defined, there are limited data regarding the molecular mechanisms underlying resistance to other antimicrobials. Using H. pylori isolates from 42 clinical specimens, we compared phenotypic and whole-genome sequencing (WGS)-based detection of resistance. Phenotypic resistance correlated with the presence of alleles of 23S rRNA (A2142G/A2143G) for clarithromycin (kappa coefficient, 0.84; 95% confidence interval [CI], 0.67 to 1.0) and gyrA (N87I/N87K/D91Y/D91N/D91G/D99N) for levofloxacin (kappa coefficient, 0.90; 95% CI, 0.77 to 1.0). Phenotypic resistance to amoxicillin in three isolates correlated with mutations in pbp1, pbp2, and/or pbp3 within coding regions near known amoxicillin binding motifs. All isolates were phenotypically susceptible to tetracycline, although four bore a mutation in 16S rRNA (A926G). For metronidazole, nonsense mutations and R16H substitutions in rdxA correlated with phenotypic resistance (kappa coefficient, 0.76; 95% CI, 0.56 to 0.96). Previously identified mutations in the rpoB rifampin resistance-determining region (RRDR) were not present, but 14 novel mutations outside the RRDR were found in rifampin-resistant isolates. WGS also allowed for strain lineage determination, which may be important for future studies in associating precise MICs with specific resistance alleles. In summary, WGS allows for broad analyses of H. pylori isolates, and our findings support the use of WGS for the detection of clarithromycin and levofloxacin resistance. Additional studies are warranted to better define mutations conferring resistance to amoxicillin, tetracycline, and rifampin, but combinatorial analyses for rdxA gene truncations and R16H mutations have utility for determining metronidazole resistance.

A single centre experience of treatment outcomes for Helicobacter pylori infection among inner-city children and adolescents.

AIM: This study assessed treatment outcomes of Helicobacter pylori (H pylori) infection among inner-city children. METHODS: This was a retrospective study of patients aged 1-21 years who underwent initial treatment for H pylori infection from 2011 to 2015. We included patients who completed 2 weeks of treatment with documented adequate compliance after H pylori infection was diagnosed. Treatment outcomes were measured based on stool H pylori antigen and/or histology. RESULTS: Of the total 261 patients diagnosed with H pylori, 239 completed the first-line treatment. The regimens used included amoxicillin/clarithromycin/proton pump inhibitor (PPI) in 207/239 patients (86.6%), amoxicillin/metronidazole/PPI in 14/239 patients (5.8%) and other regimens in 18/239 patients (7.5%). H pylori eradication status was tested in 111/207 (53.6%) patients treated with amoxicillin/clarithromycin/PPI, and the eradication was achieved in 84/111(75.7%) patients. The treatment success rates for amoxicillin/metronidazole/PPI and other regimens were 71.4% (5/7) and 63.6% (7/11), respectively. There was no statistical significance of post-treatment stool H pylori antigen results between PPI (n = 31) and no PPI (n = 43) users. CONCLUSION: The study showed an eradication rate of 75.7% with the regimen amoxicillin/clarithromycin/PPI suggesting significant antibiotic resistance in our population. The use of PPI did not influence post-treatment stool H pylori antigen results.

Helicobacter pylori serology testing is a useful diagnostic screening tool for symptomatic inner city children.

AIM: This study assessed the Helicobacter pylori (H. pylori) serum antibody test as a diagnostic screening tool in symptomatic inner city children. METHODS: This was a retrospective study of patients aged one to 18 years who were referred to our paediatric gastroenterology department from 2009 to 2013. We included all patients who had H. pylori serum antibodies and/or faecal antigens who underwent esophagogastroduodenoscopy (EGD) for histology, with or without a gastric tissue rapid urease test. RESULTS: A total of 395 patients had EGDs carried out to evaluate epigastric pain, heartburn and nausea or vomiting, and their overall socio-economic Z-score was -2.62. The histology was positive for H. pylori infection in 52 of 395 patients (13%), and epigastric pain was documented in 45 of these 52 patients (87%). Compared to histology, the serum H. pylori antibody test had a sensitivity of 88.4% and a specificity of 93.4%. The tissue rapid urease test and faecal antigen test had sensitivities of 89.3% and 55.6% and specificities of 89.9% and 98.9%, respectively. CONCLUSION: The serum H. pylori antibody test had high sensitivity and specificity, and it was a good diagnostic screening tool in our study. Epigastric pain was strongly associated with a current H. pylori infection in our population.

Treatment of acquired aplastic anemia in patients with acute liver failure occurring concurrently: a case series.

The association between acquired aplastic anemia (AA) and hepatitis/acute liver failure has been well characterized as AA temporally after the presentation of acute hepatitis. In this case series we report 2 cases of patients who present with AA occurring simultaneously with the development of acute liver failure. This is among only a few reported cases known to date in which AA occurs simultaneously with impending liver failure. More importantly, this is the first report that demonstrates the feasibility of administering immunosuppressive therapy before complete resolution of the hepatic dysfunction and with excellent results. Both of our cases avoided orthotopic liver transplantation through the use of timely immunosuppressive therapy, demonstrating the potential role of medical management to avoid transplantation in these patients. Previous studies have suggested a link between an unidentified viral process and immune dysregulation that may lead to the development of AA after acute hepatitis. These 2 cases support the rationale that in our patients the 2 disease processes may share a common etiology and encourage further research into the complex pathogenic mechanism affecting these 2 different organ systems at varying points in time.

CLINICAL COURSE OF A UNIQUE CASE OF ALLGROVE SYNDROME AND CHALLENGES OF HYPOGLYCEMIA MANAGEMENT.

OBJECTIVE: Allgrove syndrome (AS), also known as triple-A syndrome, is a rare disorder characterized by alacrima, achalasia, adrenal insufficiency, and other manifestations such as problems related to growth, puberty, and neuropsychological development. Although the genetics of this disorder have been studied extensively in recent decades, clinical information is still lacking. METHODS: We present a unique case of AS from which we have gained significant insight into its clinical course, especially the management of hypoglycemia. RESULTS: The patient initially presented with altered mental status at age 3 which was found to be due to hypoglycemia. Laboratory values confirmed primary adrenal insufficiency with isolated glucocorticoid deficiency. With additional history of alacrima, a genetic test was obtained which confirmed the diagnosis of AS. For over 10 years, we have been following her growth, puberty, and development. We experienced some challenges in managing her hypoglycemia initially. Certain metabolic effects of steroid overdose were noted. To resolve this problem, we found dextrose supplementation quite effective. CONCLUSION: The rarity and isolated glucocorticoid deficiency of AS pose clinical challenges for initial diagnosis. Hypoglycemia associated with alacrima should alert the suspicion of AS. Management of hypoglycemia in AS is complicated by achalasia and may benefit from incorporation of both glucocorticoid and dextrose supplementation to prevent side effects of steroid overdose.

FTF and LRH-1, two related but different transcription factors in human Caco-2 cells: their different roles in the regulation of bile acid transport.

The apical sodium dependent bile acid transporter (ASBT) mediates ileal bile acid reabsorption. The transcription factors, liver receptor homologue-1 (LRH-1:mouse) and fetoprotein transcription factor (FTF:human), are presumably orthologues. Bile-acid induced negative feedback regulation of mouse (m) and human (h) ASBT occurs via LRH-1 and RAR/RXR, respectively. hASBT has a potential FTF cis-element, although its functional role is unknown. hASBT and mASBT promoter constructs and an FTF cis-element mutated hASBT (hASBT/FTFmu) were assessed in human Caco-2 cells treated with chenodeoxycholic acid (CDCA) and/or co-transfected with hFTF, mLRH-1, or specific small interfering FTF or LRH-1 RNA (siFTF or siLRH). Basal promoter activity was reduced in hASBT/FTFmu, although bile acid response persisted. hFTF activated hASBT but not mASBT, while mLRH-1 activated mASBT but not hASBT. siFTF reduced hASBT but not mASBT activity; siLRH reduced mASBT but not hASBT activity. siLRH but not siFTF abrogated bile acid responsiveness. Electrophoretic mobility shift assays demonstrated distinct and specific binding of the mLRH-1 or hFTF cis-elements. In conclusion, FTF and LRH-1 are two related but different transcription factors in human Caco-2 cells, suggesting that they may be homologues and not orthologues. FTF is not involved directly in bile acid mediated negative feedback regulation of the ASBT.