Predictors of Functional Cure of Chronic Hepatitis B Virus Infection: A Long-Term Follow-Up Study.

BACKGROUND & AIMS: A functional cure is an essential endpoint in the management of patients with chronic hepatitis B virus (HBV) infection. We evaluated the cumulative probability and predictors of functional cure in patients with chronic HBV infection after hepatitis B e antigen (HBeAg) seroconversion. METHODS: We retrospectively analyzed 413 (249 males and 164 females) initially HBeAg-positive chronic HBV-infected patients who were followed up for a mean of 26.36 ± 0.53 years. All underwent HBeAg seroconversion during follow-up. A functional cure was defined as durable HBsAg and HBV DNA loss without antiviral treatment for more than 24 weeks. RESULTS: After 10,888 person-years of follow-up, the cumulative probability of functional cure was 14.53% (n = 60). There were 24 (40%) subjects with functional cure after antiviral therapy. The annual functional cure rate was 0.55% per person-year, and increased to 0.96% per person-year after HBeAg seroconversion. In subjects with functional cure, the HBsAg and HBV DNA titers after HBeAg seroconversion were positively correlated with the time to functional cure (P < .001 and < .001, respectively). Multivariate Cox proportional hazards analysis of the cohort revealed that HBeAg seroconversion at <18 years of age, high-genetic-barrier nucleos(t)ide analogue(s) therapy before HBeAg seroconversion, and a serum HBsAg titer <1000 IU/mL at 18 months after HBeAg seroconversion were significant predictors of functional cure (P < .001, .001, and .001, respectively). CONCLUSIONS: In a cohort of chronic HBV-infected patients with long-term follow-up, HBeAg seroconversion in childhood, high-genetic-barrier nucleos(t)ide analogue(s) therapy, and low HBsAg titers after HBeAg seroconversion were significant predictors of functional cure.

Management of Crohn's disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023.

Crohn's disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.

Management of ulcerative colitis in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023.

Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.

Gut Bifidobacterium longum is associated with better native liver survival in patients with biliary atresia.

Background & Aims: The gut microbiome plays an important role in liver diseases, but its specific impact on biliary atresia (BA) remains to be explored. We aimed to investigate the microbial signature in the early life of patients with BA and to analyze its influence on long-term outcomes. Methods: Fecal samples (n = 42) were collected from infants with BA before and after Kasai portoenterostomy (KPE). The stool microbiota was analyzed using 16S rRNA next-generation sequencing and compared with that of age-matched healthy controls (HCs). Shotgun metagenomic sequencing analysis was employed to confirm the bacterial composition in 10 fecal samples before KPE. The correlation of the microbiome signature with liver function and long-term outcomes was assessed. Results: In the 16S rRNA next-generation sequencing analysis of fecal microbiota, the alpha and beta diversity analyses revealed significant differences between HCs and patients with BA before and after KPE. The difference in microbial composition analyzed by linear discriminant analysis and random forest classification revealed that the abundance of Bifidobacterium longum (B. longum) was significantly lower in patients before and after KPE than in HCs. The abundance of B. longum was negatively correlated with the gamma-glutamyltransferase level after KPE (p <0.05). Patients with early detectable B. longum had significantly lower total and direct bilirubin 3 months after KPE (p <0.005) and had a significantly lower liver transplantation rate (hazard ratio: 0.16, 95% CI 0.03-0.83, p = 0.029). Shotgun metagenomic sequencing also revealed that patients with BA and detectable B. longum had reduced total and direct bilirubin after KPE. Conclusion: The gut microbiome of patients with BA differed from that of HCs, with a notable abundance of B. longum in early infancy correlating with better long-term outcomes. Impact and implications: Bifidobacterium longum (B. longum) is a beneficial bacterium commonly found in the human gut. It has been studied for its potential impacts on various health conditions. In patients with biliary atresia, we found that a greater abundance of B. longum in the fecal microbiome is associated with improved clinical outcomes. This suggests that early colonization and increasing B. longum levels in the gut could be a therapeutic strategy to improve the prognosis of patients with biliary atresia.

Performance of Baveno VII criteria for the screening of varices needing treatment in patients with biliary atresia.

OBJECTIVE: Biliary atresia (BA) is the leading cause of liver cirrhosis and chronic liver insufficiency in children in the world. Gastroesophageal varices bleeding is an ominous complication of cirrhosis in BA patients and is associated with high morbidity and mortality. In this study, we aimed to investigate the utility of noninvasive Baveno VI and Baveno VII criteria for the screening of varices need treatment (VNT) and the need for liver transplantation in BA patients. METHODS: This study enrolled 48 BA patients (23 females and 25 males) who underwent an esophagogastroduodenoscopy (EGD) and transient elastography at a mean age of 11.18 ± 1.48 years; the clinical data were surveyed in a retrospective design. RESULTS: The sensitivity and negative predictive value of Baveno VI and Baveno VII criteria for the prediction of VNT in BA patients are both 100% and 100%, respectively. The VNT missing rate of Baveno VI and Baveno VII criteria are both 0% in our cohort. The Baveno VI, expanded Baveno VI, and Baveno VII criteria are also predictive of the need for liver transplantation in our cohort (OR = 10.33, 4.24, and 21.33; p = 0.009, 0.03, and 0.007, respectively). CONCLUSION: The Baveno VI and Baveno VII criteria are useful for the screening of VNT and minimize non-necessary invasive EGD in BA patients with low VNT missing rates. The Baveno VI, expanded Baveno VI, and Baveno VII criteria are associated with the need for liver transplantation.

Prevalence of functional esophageal disorders and associated clinical characteristics in patients with proton-pump-inhibitor-unresponsive reflux symptoms.

BACKGROUND AND AIM: Patients with proton-pump-inhibitor (PPI)-unresponsive reflux symptoms, often caused by functional esophageal disorders (FED), are frequently encountered in clinical practice. We aimed to investigate the prevalence of FED and its associated clinical characteristics in patients with PPI-unresponsive reflux symptoms. METHODS: We retrospectively identified patients who were evaluated for persistent typical reflux symptoms, despite ≥8 weeks of PPI treatment, at the National Taiwan University Hospital from 2014 to 2023. All patients underwent a comprehensive evaluation comprising validated gastroesophageal reflux disease (GERD) symptom questionnaires, 5-item Brief Symptom Rating Scale (BSRS-5), Pittsburgh Sleep Quality Index (PSQI), esophagogastroduodenoscopy, high-resolution impedance manometry, and 24-h impedance-pH monitoring off PPI therapy. Diagnosis of FED and non-erosive reflux disease (NERD) was based on the Rome IV criteria. RESULTS: We analyzed 190 patients [46.8% male, median age 52 (interquartile range, 42-61) years], of whom 32 (16.8%) had NERD and 158 (83.2%) had FED (57.9% with functional heartburn and 25.3% with reflux hypersensitivity). Patients with FED had a lower body mass index than those with NERD and a higher prevalence of psychological comorbidities and poor sleep quality than healthy volunteers. The severity of reflux symptoms among FED patients was significantly associated with the severity of psychological comorbidities and sleep quality. CONCLUSIONS: A notably high prevalence (83.2%) of FED was observed among patients experiencing PPI-unresponsive reflux symptoms. Patients with FED had a higher level of psychological distress and diminished sleep quality, both of which were associated with reflux symptom severity.

Early predictors of intestinal complications in pediatric-onset Crohn's disease: A long-term cohort study in Taiwan.

PURPOSE: Identifying reliable prognostic factors for pediatric-onset Crohn's disease (CD) is important for guiding early treatment. This study aimed to evaluate the validity of various clinical parameters for predicting long-term intestinal complications in pediatric-onset CD patients with CD in Taiwan. METHODS: This was a single-center, retrospective study. Patients diagnosed with CD under 18 years of age at our hospital between January 1999 and December 2021 were enrolled. The baseline clinical variables and the Pediatric Crohn's Disease Activity Index (PCDAI) were obtained. Patients were categorized into low-, medium-, or high-risk groups based on the 2020 European Crohn's and Colitis Organization and European Society for Pediatric Gastroenterology Hepatology and Nutrition (ECCO-ESPGHAN) guidelines. The primary endpoint was the occurrence of new intestinal complications. RESULTS: Among 53 enrolled patients (33 males and 20 females), 8 patients (33.96%) developed intestinal complications during the follow-up period (median 6.42 years, 3.17-9.75 years). Patients in the initial ECCO-ESPGHAN medium- or high-risk group had a 4.71-fold higher risk of intestinal complications than those in the low-risk group [hazard ratio = 4.71, p = 0.023] after adjusting for PCDAI in the multivariate Cox proportional hazard analysis. The other clinical variables did not reach statistical significance in predicting intestinal complications. The positive and negative predictive values of the ECCO-ESPGHAN stratification method for intestinal complications were 48.15% and 80.77%, respectively. CONCLUSIONS: ECCO-ESPGHAN risk stratification is an effective early predictor of long-term intestinal complications in the Taiwanese population and may be used in clinical practice to guide early advanced therapy.

Clinical experience of infantile hepatic hemangioma.

PURPOSE: To describe the clinical presentation, treatment preference, and relevant complications of infantile hepatic hemangioma (IHH) in propranolol era. METHODS: The National Taiwan University Hospital integrated Medical Database (NTUH-iMD) was used to enroll twenty-one cases of IHH diagnosed from 2006 to 2020. Medical charts were retrospectively reviewed. RESULTS: In nine patients (42.9%), IHH was found incidentally, and in seven patients (33%), it was detected during postnatal self-paid ultrasonography. Focal disease was determined in 17 patients, multifocal disease in 1 patient, and diffuse disease in 3 patients. Patients with diffuse disease had a lower hemoglobulin level than patients with focal IHH (9.38 vs. 12.6 mg/dL, p = 0.045). Two patients had Kasabach-Merritt phenomenon (KMP), one had hypothyroidism, and one had both. All patients with KMP had focal hepatic hemangiomas. Among the 17 patients with focal IHH, nine were prescribed propranolol, one was treated by surgical resection of the tumor, and the others had expectant management. All patients with multifocal and diffuse IHH were administered propranolol. One infant (7.7%) treated with propranolol had bradycardia initially but it subsided after dose adjustment. CONCLUSIONS: Most IHH is found incidentally or detected during postnatal ultrasonography screening. Patients with large focal lesions should also be screened for associated complications. Propranolol is the drug of choice and a safe therapeutic option for IHH, especially for focal tumors >5 cm as well as multifocal and diffuse lesions.

Survey of hepatitis B virus infection status after 35 years of universal vaccination implementation in Taiwan.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) vaccination programs in Taiwan are one of the earliest programs in the world and have largely reduced the prevalence of HBV infection. We aimed to demonstrate the vaccination efficacy after 35 years and identify gaps toward HBV elimination. METHODS: A total of 4717 individuals aged 1-60 years were recruited from four administrative regions based on the proportion of population distribution. Serum levels of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were assessed. HBV viral load, genotypes and HBsAg 'ɑ' determinant variants were evaluated if indicated. RESULTS: After 35 years of vaccination, the overall seropositivity rates for HBsAg and anti-HBc in Taiwan were 4.05% and 21.3%, respectively. The vaccinated birth cohorts exhibited significantly lower seropositivity rates for both markers compared to the unvaccinated birth cohorts (HBsAg: 0.64% vs. 9.78%; anti-HBc: 2.1% vs. 53.55%, respectively; p < 0.0001). Maternal transmission was identified as the main route of HBV infection in breakthrough cases. Additionally, increased prevalences of genotype C and HBsAg escape mutants were observed. CONCLUSION: The 35-year universal HBV vaccination program effectively reduced the burden of HBV infection, but complete eradication of HBV infection has not yet been achieved. In addition to immunization, comprehensive screening and antiviral therapy for infected individuals, especially for pregnant women, are crucial strategies to eliminate HBV.

The incidence of Clostridium difficile infection in children with and without inflammatory bowel diseases: A single-center study in Taiwan from 2006 to 2019.

BACKGROUND: The incidence of Clostridium difficile infection (CDI) is increasing around the world, and patients with inflammatory bowel disease (IBD) have a higher risk of obtaining CDI. The data on the incidence rate of CDI in the Asian pediatric IBD population was lacking. METHODS: We retrospectively collected data from a tertiary medical center in Taipei, Taiwan. All patients aged 1-18 years old who visited the outpatient department or were admitted to our hospital between 2006 and 2019 were included. CDI was defined as positive stool C. difficile toxin or C. difficile culture results with appropriate antibiotic use within the range of 7 days prior or 14 days after the result. RESULTS: We compared the average annual incidence of CDI before and after 2013. The average incidence of community-acquired CDI (CA-CDI) increased from 0.063 to 0.564 cases per 1,000 visits, with a rate ratio (RR) of 8.82 (95% CI 5.74-14.38). In patients with IBD, the rate increased from 26.738 to 278.873 cases per 1,000 visits (RR=10.12, 95% CI: 4.57-29.02). The average incidence rate increased from 0.685 to 1.874 cases per 1,000 admissions in pediatric general patients (RR = 2.72, 95% CI 1.82-4.20) and from 14.706 to 62.500 cases per 1,000 admissions in pediatric IBD patients (RR = 3.77, 95% CI 0.71-93.53). CONCLUSIONS: Both CA-CDI and healthcare facility-onset CDI (HO-CDI) were increasing substantially in the pediatric population over the past decade in Taiwan. Compared to the general pediatric population, pediatric IBD patients had a much higher incidence of CDI.

CTLA-4 haplotype predicts HBsAg and HBcrAg levels and HBeAg seroconversion age in children with chronic HBV infection.

Background & Aim: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) attenuates cytotoxic T lymphocyte (CTL) activation. This study was performed to examine the relationships between CTLA-4 genotypes/haplotypes, hepatitis B surface antigen (HBsAg), and hepatitis B core-related antigen (HBcrAg) levels, and their potential impact on the clinical course of chronic HBV infection. Methods: We recruited 145 treatment-naïve patients with genotype B or C chronic HBV infection who were initially hepatitis B e-antigen (HBeAg)-positive and had been followed from a mean age of 7.08 years for a total of 4,787 person-years in the study cohort. We also recruited another 69 treatment-naïve adults with genotype B or C chronic HBV infection as a validation cohort. We assessed the CTLA-4 gene single nucleotide polymorphisms rs4553808 (-A1661G)/rs5742909 (-C318T) in both cohorts, and the serum HBsAg and HBcrAg levels in the study cohort. Results: CTLA-4 promoter haplotypes were associated with HBsAg and HBcrAg levels at 10 and 15 years of age in the study cohort. Patients with the CTLA-4 AA/CC haplotype showed earlier spontaneous HBeAg seroconversion (hazard ratio = 1.58; p = 0.02), and a more rapid annual decline in the serum HBsAg level than other patients (0.09 vs. 0.03 log10 IU/ml/year, p = 0.02). The CTLA-4 AA/CC haplotype was also predictive of HBeAg seroconversion in the validation cohort (p = 0.01). Conclusions: Chronic HBV-infected patients with a CTLA-4 AA/CC haplotype had lower serum HBsAg and HBcrAg levels in childhood and earlier spontaneous HBeAg seroconversion. Impact and implications: The role of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in chronic HBV-infected children has not been studied previously. In a very long-term cohort followed from childhood to adulthood, we showed that CTLA-4 haplotypes are associated with HBV biomarker levels in childhood and are correlated with the clinical course of chronic HBV infection. CTLA-4 pathway may serve as a future target for the development of therapeutic agents against HBV infection.

Exacerbated gastrointestinal symptoms and long COVID in IBD patients with SARS-CoV-2 infection: A multi-center study from taiwan.

BACKGROUND/PURPOSE: Limited studies have addressed the exacerbation of symptoms and long COVID in inflammatory bowel disease (IBD) patients following non-severe COVID-19 infection, particularly with post-COVID-19 vaccination. We aim to investigate factors associated with exacerbated gastrointestinal symptoms (EGS) and long COVID in IBD patients with non-severe COVID-19, which is most common situation in daily practice. METHODS: This is an observational study by multiple centers in Taiwan from May 2020 to March 2023. We collected clinical manifestation, data, and medication information from IBD patients with non-severe COVID-19. EGS was defined as increased frequency of diarrhea, bloody stool, and abdomen pain within 14 days after SARS-COV-2 infection. Long COVID was defined following the guidelines of the World Health Organization. RESULTS: Out of 90 patients, most of them (88.9%) received at least standard two doses of COVID-19 vaccination and the majority (87.8%) were mild diseases of COVID-19.30% of patients experienced EGS during COVID-19 with higher ESR levels serving as a predictive factor (Odds ratio: 3.6, 95% confidence interval: 1.2-10.5, P = 0.02). 38.1% of those patients developed long COVID. The patients who experienced EGS during COVID-19 and with a history of longer IBD duration showed a significant association with long COVID (p = 0.03 and p = 0.02). CONCLUSION: Our study revealed that EGS and long COVID occurred in one third of IBD patients with non-severe COVID-19, even though most of them had received the standard plus booster vaccination. We identified associated factors for EGS and long COVID, emphasizing the importance of post-COVID-19 follow-up in IBD patients.

Correction: Impact of the Coronavirus Disease 2019 Pandemic on Pediatric Gastrointestinal Endoscopy: A Questionnaire-based Internet Survey of 162 Institutional Experiences in Asia Pacific.

[This corrects the article on p. 291 in vol. 26, PMID: 38025493.].

The magnetic resonance imaging and age-adjusted matrix metalloproteinase-7 assist the diagnosis of biliary atresia.

BACKGROUND: We investigated the utilities of the liver-to-psoas apparent diffusion coefficient ratios (LTPAR) yielded by diffusion-weighted magnetic resonance imaging (DWMRI) and the age-adjusted serum matrix metalloproteinase-7 (MMP-7) for the diagnosis of biliary atresia (BA) in cholestatic infants. METHODS: In total, 170 cholestatic infants were recruited, of whom 50 (29.41%) were diagnosed with BA after cholestatic workups. The LTPAR and MMP7 levels were assessed. RESULTS: The LTPAR was significantly lower in BA infants, and the age-adjusted MMP7 ratio was significantly higher, compared to other cholestatic infants (both p < 0.001). Receiver operating characteristic curve analysis yielded a cutoff > 0.1 ng/mL.day for the age-adjusted MMP-7 ratio, and an LTPAR < 1.01 for the optimal prediction of BA (both p < 0.001). Univariate logistic regression analysis revealed that both an age-adjusted MMP-7 ratio > 0.1 ng/mL.day and an LTPAR < 1.01 were significant predictors of BA among cholestatic infants (odds ratio = 30.98 and 13.28; p < 0.001 and < 0.001, respectively). The significance of the age-adjusted MMP-7 ratio and the LTPAR persisted on multivariate logistic regression analysis after adjusting for sex and the serum gamma-glutamyl transferase level (p < 0.001 and < 0.001, respectively). The negative predictive values (NPVs) for BA were 91.49% and 94.17%, respectively, for the LTPAR and age-adjusted MMP-7 ratio. CONCLUSION: The age-adjusted MMP-7 ratio and the LTPAR are both significant non-invasive predictors of BA. The consideration of both serum and imaging parameters may enhance BA diagnostic performance in cholestatic infants.

Clinical utility of anal sphincter relaxation integral in water-perfused and solid-state high-resolution anorectal manometry.

BACKGROUND/PURPOSE: We investigated the diagnostic performance of the anal sphincter relaxation integral (ASRI) for infants with Hirschsprung's disease (HD). METHODS: We performed water-perfused high-resolution anorectal manometry (HRAM) in 18 infants (9 with HD), and solid-state HRAM in another 18 infants (4 with HD). We calculated the ASRI during the rectoanal inhibitory reflex (RAIR) maneuver at pressure cutoffs of <10 mmHg (ASRI 10) and <15 mmHg (ASRI 15). We investigated the diagnostic performance of the ASRI for HD in infants undergoing water-perfused and solid-state HRAM. RESULTS: HD infants who underwent either water-perfused or solid-state HRAM had significantly lower ASRI 10 and ASRI 15 values, compared with non-HD infants (P < 0.05 and P < 0.05, respectively). Using the water-perfused HRAM system, ASRI 10 and ASRI 15 values of <7 and <29 mmHg s.cm, respectively, exhibited good diagnostic performance for HD (88.89% and 88.89%, respectively). Receiver operating characteristic curve analysis indicated that ASRI 10 and ASRI 15 values of <5.5 and <20 mmHg s.cm, respectively, were optimal for the diagnosis of HD infants when using the solid-state HRAM system, with high diagnostic accuracies of 83.33% and 83.33%, respectively. CONCLUSION: ASRI may assist the diagnosis of HD infants using either water-perfused or solid-state HRAM. These systems require different catheter-specific ASRI cutoffs for the prediction of HD.

Effect of peroral endoscopic myotomy on growth and esophageal motility for pediatric esophageal achalasia.

BACKGROUND/PURPOSE: Peroral endoscopic myotomy (POEM), a novel minimally invasive treatment for esophageal achalasia, has been shown to be effective and safe for both adult and pediatric patients. However, studies on its application in children in Taiwan and its impact on growth and esophageal motility are lacking. METHODS: We conducted a retrospective study on consecutive pediatric patients who were diagnosed with esophageal achalasia at National Taiwan University Hospital and underwent POEM during 2015-2022. Disease characteristics and treatment outcomes were analyzed. RESULTS: Ten patients (age 16.9 ± 3.1 years), nine newly diagnosed and one previously treated with pneumatic dilatation, underwent POEM for achalasia (type I/II/III: 3/7/0). Average symptom duration before diagnosis was 19.4 ± 19.9 months, mean POEM procedure time was 83.6 ± 30.7 min, and clinical success (Eckardt score ≤3) was achieved in all patients. Eight patients experienced mild adverse events during POEM, but none required further endoscopic or surgical intervention. Over a mean follow-up period of 3.7 ± 1.6 years, mean Eckardt score decreased significantly from 5.7 ± 2.4 to 1.1 ± 0.7 (p = 0.0001). The BMI z-score also increased significantly after POEM (p = 0.023). Five patients received follow-up high-resolution impedance manometry (HRIM), and all had improved lower esophageal sphincter resting pressures (p = 0.011), body contractility, and bolus transit (p = 0.019). CONCLUSION: POEM is an effective and safe treatment for pediatric achalasia in Taiwan. Early diagnosis and treatment with POEM may help to restore esophageal function and nutrition status in children.

Antagonism Between Gut Ruminococcus gnavus and Akkermansia muciniphila Modulates the Progression of Chronic Hepatitis B.

BACKGROUND & AIMS: A long immune-tolerant (IT) phase lasting for decades and delayed HBeAg seroconversion (HBe-SC) in patients with chronic hepatitis B (CHB) increase the risk of liver diseases. Early entry into the immune-active (IA) phase and HBe-SC confers a favorable clinical outcome with an unknown mechanism. We aimed to identify factor(s) triggering IA entry and HBe-SC in the natural history of CHB. METHODS: To study the relevance of gut microbiota evolution in the risk of CHB activity, fecal samples were collected from CHB patients (n = 102) in different disease phases. A hepatitis B virus (HBV)-hydrodynamic injection (HDI) mouse model was therefore established in several mouse strains and germ-free mice, and multiplatform metabolomic and bacteriologic assays were performed. RESULTS: Ruminococcus gnavus was the most abundant species in CHB patients in the IT phase, whereas Akkermansia muciniphila was predominantly enriched in IA patients and associated with alanine aminotransferase flares, HBeAg loss, and early HBe-SC. HBV-HDI mouse models recapitulated this human finding. Increased cholesterol-to-bile acids (BAs) metabolism was found in IT patients because R gnavus encodes bile salt hydrolase to deconjugate primary BAs and augment BAs total pool for facilitating HBV persistence and prolonging the IT course. A muciniphila counteracted this activity through the direct removal of cholesterol. The secretome metabolites of A muciniphila, which contained small molecules structurally similar to apigenin, lovastatin, ribavirin, etc., inhibited the growth and the function of R gnavus to allow HBV elimination. CONCLUSIONS: R gnavus and A muciniphila play opposite roles in HBV infection. A muciniphila metabolites, which benefit the elimination of HBV, may contribute to future anti-HBV strategies.

The prevalence and impact of small intestine bacterial overgrowth in biliary atresia patients.

BACKGROUND: Acute cholangitis is an ominous complication in biliary atresia (BA) patients. We investigated the prevalence of small intestine bacterial overgrowth (SIBO) in BA patients and its role in predicting acute cholangitis. METHODS: There are 69 BA patients with native liver recruited into this study prospectively. They received hydrogen and methane-based breath testing (HMBT) to detect SIBO after recruitment and were followed prospectively in our institute. RESULTS: There are 16 (23.19%) subjects detected to have SIBO by HMBT. BA subjects with SIBO were noted to have higher serum alanine aminotransferase levels than others without SIBO (P = 0.03). The risk of acute cholangitis is significantly higher in BA patients with SIBO than in others without SIBO (62.50% vs. 15.09%, P < 0.001). The logistic regression analysis demonstrated that BA subjects with SIBO have a higher risk of acute cholangitis than others without SIBO (odds ratio = 9.38, P = 0.001). Cox's proportional hazard analysis further confirmed the phenomena in survival analysis (hazard ratio = 6.43, P < 0.001). CONCLUSIONS: The prevalence of SIBO in BA patients is 23.19% in this study. The presence of SIBO is associated with the occurrence of acute cholangitis in BA patients. IMPACT: What is the key message of your article? Acute cholangitis is common in BA, and is associated with SIBO after hepatoportoenterostomy in this study. What does it add to the existing literature? This study demonstrated that SIBO is common in BA after hepatoportoenterostomy, and is predictive of acute cholangitis and elevated serum ALT levels in BA. What is the impact? This prospective cohort study provides data regarding the significance of SIBO on the risk of acute cholangitis in BA patients.

Characteristics of Esophageal Motility and Associated Symptom Profiles in Patients with Esophageal Diverticulum: A Study Based on High-Resolution Impedance Manometry.

BACKGROUND: Esophageal diverticulum (ED) is an uncommon structural disorder with heterogenous manifestations and elusive pathophysiology. Our aim was to investigate esophageal motility and associated symptom profiles in patients with ED based on high-resolution impedance manometry (HRIM). METHODS: Consecutive patients with ED referred to our motility laboratory between 2015 to 2022 were identified in our electronic database. All patients were evaluated based on an upper endoscopy, HRIM, and standardized symptom questionnaires. Patients with ED were further stratified into upper, middle, and lower (epiphrenic) cases. Esophageal motility was evaluated with HRIM and the updated Chicago Classification v4.0. RESULTS: Twenty-four patients with ED (9 upper, 4 middle, and 11 epiphrenic) were analyzed. Patients with ED were generally older (mean: 65 ± 13.3 years) and predominantly women (58.3%). Most ED cases were unilaterally located (95.8%) and left-side predominant (62.5%). Mean symptom duration was 20 months (range: 1-120) and the most common symptoms were dysphagia (70.8%) and regurgitation (37.5%). Erosive esophagitis was noted in 16 patients (69.6%), while barium stasis was noted in 5 patients (20.8%). Fourteen patients (58.3%) were diagnosed with esophageal motility disorders using HRIM, with achalasia being the most common diagnosis (n = 5, 20.8%). Patients with epiphrenic diverticulum had significantly higher symptom scores and achalasia prevalence. CONCLUSION: Patients with ED tended to be older and was associated with a high prevalence of EMD. A multi-disciplinary evaluation, including complete anatomical and motility surveys, may help clarify the underlying pathophysiology and tailor further treatment strategies.

Impact of the Coronavirus Disease 2019 Pandemic on Pediatric Gastrointestinal Endoscopy: A Questionnaire-based Internet Survey of 162 Institutional Experiences in Asia Pacific.

Purpose: The impact of coronavirus 2019 (COVID-19) on gastrointestinal (GI) endoscopy procedures in adults has been reported, with a drastic reduction in the number of procedures. However, there are no sufficient data regarding the impact on pediatric GI endoscopy. Here, we aimed to report that impact in the Asia-Pacific region. Methods: A questionnaire-based internet survey was conducted from June to November 2021 among pediatric endoscopy institutions in the Asia-Pacific region, with each institution providing a single response. Overall, 25 questions focused on the impact of the number of procedures conducted, the usage of personal protective equipment (PPE), and endoscopy training programs during the pandemic. Results: A total of 162 institutions across 13 countries in the Asia-Pacific region participated in the study, and 133 (82.1%) institutions underwent procedure changes since the emergence of COVID-19. The number of esophagogastroduodenoscopy and ileocolonoscopy procedures decreased in 118/133 (88.7%) and 112/133 (84.2%) institutions, respectively. Endoscopy for patient with positive COVID-19 in an emergency or urgent cases still carried out in 102/162 (62.9%) institutions. Screening of COVID-19 for all patients before endoscopy was done across 110/162 (67.9%) institutions. PPE recommendations varied among institutions. Pediatric gastrointestinal endoscopy training programs were discontinued in 127/162 (78.4%) institutions. Conclusion: This study reports the impact of the COVID-19 pandemic on pediatric gastrointestinal endoscopy in the Asia-Pacific region. There has been a significant reduction in the number of endoscopic procedures and relevant training programs.