While liver biopsy is the gold standard for assessing liver fibrosis, the optimal scoring system for Fontan-associated liver disease (FALD) is debated. This study was to determine the correlation and agreement between the METAVIR score, used for chronic hepatitis, and the Congestive Hepatic Fibrosis Score (CHFS), specifically designed for congestive hepatopathy. We conducted a retrospective review of liver biopsies from 38 Fontan patients. Pathologists independently evaluated each biopsy and assigned a METAVIR fibrosis score and a CHFS. Fontan patients, a mean age of 21 ± 6 years, have undergone the Fontan operation at a mean age of 8 ± 4 years. This established a mean postoperative interval of 13 ± 4 years at the time of study enrollment. When comparing the two scoring systems, the overall weight Kappa of 0.92 suggested perfect agreement between the two methods for assessing the degree of liver fibrosis. However, a subgroup analysis of weight kappa agreement revealed significant differences based on fibrosis severity. In the low-grade fibrosis group, the agreement was substantial agreement (kappa 0.70). In sharp contrast, the high-grade liver fibrosis group (METAVIR F3-F4 and CHFS stages 3–4) demonstrated perfect agreement (kappa 0.90) between the two scoring systems. Overall, METAVIR and CHFS demonstrate strong correlation and agreement. Differences observed in early-stage fibrosis likely arise from their distinct architectural emphases; portal-based in METAVIR versus centrilobular in CHFS.

Objective To compare water-assisted colonoscopy (WAC) using the water immersion technique with conventional carbon dioxide insufflation colonoscopy (CC) in novice endoscopists, focusing on procedure time, safety and learning curves.Methods We conducted a prospective, randomised (1:1), single-centre trial at Chiang Mai University Hospital, Thailand. Six gastroenterology fellows with <150 prior colonoscopies received standardised training before performing elective screening colonoscopies using either WAC or CC techniques. Patients were randomly assigned to WAC or CC groups. The primary outcome was caecal intubation time (CIT). Secondary outcomes included technical failure, procedural difficulty, patient discomfort, complications, withdrawal time and adenoma detection rate (ADR).Results Of 250 randomised patients, 230 completed the protocol (WAC, n=113; CC, n=117). Mean CIT was comparable between groups (10.6±4.2 min vs 9.8±3.9 min; p=0.35). Technical failure occurred in 6.2% of WAC and 5.1% of CC procedures, with no significant differences in procedural difficulty ratings, analgesic requirements or patient discomfort scores. ADR was similar between arms (40.7% vs 33.3%; p=0.25). Learning curves demonstrated parallel, progressive reductions in CIT among fellows in both groups.Conclusion WAC is a safe and effective alternative to CC for novice endoscopists, with similar procedure times, learning curves and safety profiles. These findings support the inclusion of WAC in gastroenterology training programmes.Trial registration number TCTR20230324001.

Functional cure is a goal for the treatment of chronic hepatitis B virus (HBV) infection; however, it is infrequently achieved with currently approved treatments. Here we provide a randomized evaluation of the small interfering RNA elebsiran, in combination with pegylated interferon alfa (PEG-IFNα), compared with PEG-IFNα monotherapy. In addition, this study evaluates the potential role of the HBV therapeutic vaccine BRII-179 in identifying immunologically responsive patients and improving hepatitis B surface antigen (HBsAg) loss rates. In part I (cohorts 1-3), virally suppressed participants with chronic HBV infection naive to BRII-179 were randomized 1:1:1 to receive 48 weekly doses of PEG-IFNα alone or in combination with 13 doses of elebsiran (200 mg or 100 mg) administered every 4 weeks. In part II (cohort 4), participants who had previously received 9 doses of elebsiran and BRII-179 in a prospective study (BRII-179-835-001) were categorized as BRII-179 anti-HBs responders or nonresponders based on their peak hepatitis B surface antibody (anti-HBs) levels (≥10 IU l-1 or <10 IU l-1, respectively) and subsequently received 13 doses of elebsiran 100 mg every 4 weeks plus 48 weekly doses of PEG-IFNα. Primary endpoints were HBsAg loss at the end of treatment (EOT) and 24 weeks post-EOT. In part I, at 24 weeks post-EOT, HBsAg loss was observed in 4 out of 19 (21.1%) participants receiving elebsiran 200 mg plus PEG-IFNα, 6 out of 18 (33.3%) participants receiving elebsiran 100 mg plus PEG-IFNα and 1 out of 18 (5.6%) participants receiving PEG-IFNα monotherapy. In part II, HBsAg loss was observed in 9 out of 31 (29.0%) participants at 24 weeks post-EOT, with a higher response among BRII-179 anti-HBs responders (8 out of 19 participants, 42.1%) compared with nonresponders (1 out of 12 participants, 8.3%). Elebsiran and PEG-IFNα combination therapy was generally safe and well tolerated. These results demonstrate an additive benefit of elebsiran when combined with PEG-IFNα in achieving sustained HBsAg loss. Furthermore, the increased HBsAg loss rate in BRII-179 anti-HBs responders suggests that BRII-179 may be a valuable tool for immunological profiling to optimize curative outcomes in patients with HBV infection. ClinicalTrials.gov registration: NCT05970289 .

ABSTRACT Background Gastrointestinal malignancy is a concerning etiology of iron deficiency anemia (IDA). The IDIOM model predicts gastrointestinal malignancy risk in IDA patients using age, sex, hemoglobin, and mean corpuscular volume (MCV) as parameters. This study aimed to evaluate the clinical characteristics of gastrointestinal malignancy and externally validate the IDIOM model in Thai IDA patients. Methods A retrospective cross‐sectional study was conducted on adult IDA patients who underwent gastrointestinal endoscopy at Chiang Mai University Hospital between 2019 and 2023. Clinical characteristics were compared between patients with and without gastrointestinal malignancy. The IDIOM model's performance was assessed with discrimination, calibration, and clinical usefulness. To improve its performance, the model was updated using recalibration and refitting methods. Results Among 474 IDA patients, 101 (21.3%) had gastrointestinal malignancy, predominantly colorectal cancer (n = 80, 16.9%). Patients with gastrointestinal malignancy were more likely to be male (54.5% vs. 41.3%, p = 0.018), older (65.0 vs. 59.1 years, p < 0.001), symptomatic (78.2% vs. 44.0%, p < 0.001), and had higher rates of positive fecal immunochemical tests (80.9% vs. 29.5%, p < 0.001) and lower MCV (68.0 vs. 71.8 fl, p = 0.002). External validation of the IDIOM model yielded an AuROC of 62.9% (95% CI, 56.8%–68.9%). The calibration assessment revealed both underestimation and extreme risk predictions. After updating, the AuROC improved to 67.2% (95% CI, 61.1%–73.3%). Conclusion Distinct clinical features should alert physicians to the possibility of underlying gastrointestinal malignancy in IDA patients. Given the limited performance of the IDIOM model in the Thai population, a region‐specific prediction model tailored to local clinical characteristics is needed.

AbstractBackground and AimFunctional dyspepsia (FD) remains a therapeutic challenge, and the efficacy of antispasmodic agents as adjunctive therapy is not well established. This study aimed to evaluate the efficacy and safety of pinaverium bromide added to omeprazole in treating refractory FD.MethodsWe conducted a randomized, placebo‐controlled trial in patients with refractory dyspepsia. Participants were randomly assigned to receive pinaverium (50 mg, 3 times/day, n = 36) or placebo (n = 36) in addition to omeprazole for 8 weeks. The primary endpoint was the responder rate for adequate relief. Secondary outcomes included the Global Overall Symptom Scale (GOSS), quality of life, and safety profile.ResultsNo statistically significant differences were observed in the adequate relief response rate between the pinaverium bromide and control group at week 2 (58.3% vs. 62.9%, P = 0.697), week 4 (62.9% vs. 78.1%, P = 0.173), week 6 (64.7% vs. 75.0%, P = 0.363), and week 8 (64.7% vs. 75.0%, P = 0.363). Additionally, there were no significant differences observed in the decline of symptom score between the two groups at week 4 (8.4 ± 7.6 vs. 7.7 ± 7.1, P = 0.702) and week 8 (10.9 ± 8.2 vs. 8.4 ± 7.2, P = 0.196). Similarly, there were no significant differences in terms of quality of life between the two groups. Adverse event rates were also comparable between the two groups.ConclusionPinaverium bromide was found to be safe in the treatment of refractory dyspepsia, but it did not demonstrate a significant benefit in improving symptoms.

Mitochondrial dysfunction and inflammation contribute to the pathophysiology of metabolic dysfunction-associated steatohepatitis (MASH). This study aims to evaluate the potential association between mitochondrial dynamics and cell death markers from peripheral blood mononuclear cells (PBMCs) and the presence of MASH with significant liver fibrosis among metabolic dysfunction-associated steatotic liver disease (MASLD) patients. Consecutive patients undergoing bariatric surgery from January to December 2022 were included. Patients with histologic steatosis were classified into MASH with significant fibrosis (F2-4) group or MASLD/MASH without significant fibrosis group (F0-1). Mitochondrial dynamic proteins and cell death markers were extracted from PBMCs. A total of 23 MASLD/MASH patients were included (significant fibrosis group, n = 7; without significant fibrosis group, n = 16). Of the mitochondrial dynamics and cell death markers evaluated, OPA1 protein, a marker of mitochondrial fusion is higher in MASH patients with significant fibrosis compared to those without (0.861 +/- 0.100 vs. 0.560 +/- 0.260 proportional to total protein, p = 0.001). Mitochondrial fusion/fission (OPA1/DRP1) ratio is significantly higher in MASH patients with significant fibrosis (1.072 +/- 0.307 vs. 0.634 +/- 0.313, p = 0.009). OPA1 (per 0.01 proportional to total protein) was associated with the presence of significant liver fibrosis with an OR of 1.08 (95%CI, 1.01-1.15, p = 0.035), and adjusted OR of 1.10 (95%CI, 1.00-1.21, p = 0.042). OPA1 from PBMCs is associated with MASH and substantial fibrosis. Future studies should explore if OPA1 could serve as a novel non-invasive liver fibrosis marker.

The reliability of various modalities for assessing and monitoring Fontan-associated liver disease compared to liver biopsy remains an intriguing subject of inquiry. Our objective was to assess the efficacy of multiple modalities in comparison to liver histology for evaluating liver fibrosis in post-Fontan patients. We conducted a cross-sectional study involving Fontan patients without known liver disease. Eligible patients underwent cardiac and hepatic evaluations, including ultrasound liver elastography, magnetic resonance elastography (MRE) of the liver, computerized tomography (CT) scan of the upper abdomen, echocardiography, cardiac catheterization, and liver biopsy. The severity of liver fibrosis was categorized using the METAVIR score derived from liver biopsy results: F0/F1 indicated no or mild fibrosis, F2 indicated significant fibrosis, F3 indicated advanced fibrosis and F4 indicated cirrhosis. A total of 38 patients (mean age 21 ± 6.5 years, 52.6

Background/Aims Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Iron overload is a condition involving excessive iron deposit in various organs, the liver being the main target organ for iron deposition and overload which are associated with significant liver morbidity and mortality. Iron overload can be categorized into primary and secondary causes. Primary iron overload, so-called hereditary hemochromatosis, is a well-recognized disease with available standard treatment recommendations. However, secondary iron overload is a more diverse disease with many unclear areas to be explored. Secondary iron overload is more prevalent than primary iron overload and occurs as a consequence of various causes which differ significantly across geographic regions. The main causes of secondary iron overload are iron-loading anemias, and chronic liver disease. The liver-related outcomes, patient outcomes, and treatment recommendations in these patients differ depending on the cause of iron overload. This review summarizes the causes, pathophysiology, liver-related outcomes, disease outcomes, and treatments of secondary iron overload.

The gold standard for determining the severity of liver disease in Fontan patients is now liver biopsy. Since it is an invasive procedure, this study determined the possibility of applying mitochondrial function from isolated peripheral blood mononuclear cells (PBMCs) as a non-invasive indicator of liver fibrosis. Fontan patients (n = 37) without known liver disease were analysed cross-sectionally. Patients were classified according to their histology using the METAVIR score as follows; F0/F1-no/mild fibrosis; F2-moderate fibrosis; and F3/F4-cirrhosis. Peripheral blood mononuclear cells were assessed for mitochondrial activity and apoptosis. This study did not find any significant differences in cardiac function among the groups according to liver histology. Interestingly, our findings indicated a significant decrease in maximal respiration and spare respiratory capacity, in both the moderate (F2) and cirrhosis (F3/F4) groups compared with the group without significant fibrosis (F0/F1). Moreover, the cirrhosis group exhibited higher levels of apoptosis and lower levels of live cells, compared with both the moderate and no significant fibrosis groups. In conclusion, the degree of liver fibrosis in Fontan patients is strongly correlated with mitochondrial dysfunction in PBMCs. Mitochondrial function and apoptosis could potentially serve as novel markers for tracking the progression of liver fibrosis in these patients.

favorable preclinical profile for clinical advancement.

All patients gave written informed consent.Primary outcomes were complete viral suppression (CVS, HBV DNA<20 IU/ml), biochemical response (BR, ALT<35/25 U/L men/women), and complete response (CVS+BR).Safety assessments included changes in estimated glomerular filtration rate (eGFR) and bone T-scores.Results: We enrolled 270 eligible patients.Mean age was 58.1 ± 10.6, 58.2% were male, 99.6% were Asian, 12.2% had cirrhosis, and 7.8% had chronic kidney disease (CKD).73.7% switched from entecavir monotherapy, 23% from TDF/adefovir-based therapy (7.8%: combination therapy), 3.3% from another nucleoside analogue, and mean duration of NA treatment prior to TAF was 7.5 ± 4.0 years.Between switch and week 96 follow-up, the proportions of patients with CVS (95.2% to 98.8%), BR (75.2% to 78.7%), and complete response (72.6% to 77.9%) significantly increased (all p < 0.001).As shown in Figure , comparing levels at switch vs. week 96 of follow-up, there was no significant difference in mean eGFR (88.4 ± 16.9 vs. 89.5 ± 16.3, p = 0.13) or the distribution of CKD stage ( p = 0.10).In contrast, between switch and 96-week after switch, mean T-scores significantly improved (from -1.43 ± 1.36 to -1.17 ± 1.38, p < 0.001), more patients had normal bone density (47% vs. 35%) and fewer patients had osteoporosis/osteopenia (53% vs. 65%) or osteoporosis (14% vs. 20%) ( p = 0.019, Figure ).In multivariable analysis, significant factors associated with worsening eGFR were age (adjusted odds ratio [aOR] 1.09, p = 0.004) and baseline eGFR, while male sex was associated with lower risk of developing osteopenia/osteoporosis (aOR 0.29, p = 0.020).Twelve patients (4.4%.15/270) did not complete week-96 follow-up.There were 15 SAEs (5.6%, 15/270) and none were related to TAF.Figure: Week 96 safety results of TAF after other NA treatment Conclusion: At 96-week following switch to TAF after an average of 7.5 years of treatment with other NA regimen, complete treatment response rated increased while renal function remained stable and bone density significantly improved.