Cross-sectional Analysis of Outer Retinal Tubulation in Inherited Retinal Diseases: A Multicenter Study.

PURPOSE: This study aims to explore genetic variants that potentially lead to outer retinal tubulation (ORT), estimate the prevalence of ORT in these candidate genes, and investigate the clinical etiology of ORT in patients with inherited retinal diseases (IRDs), with respect to each gene. DESIGN: Retrospective cohort study. METHODS: A retrospective cross-sectional review was conducted on 565 patients with molecular diagnoses of IRD, confirming the presence of ORT as noted in each patient's respective spectral-domain optical coherence tomography (SD-OCT) imaging. Using SD-OCT imaging, the presence of ORT was analyzed in relation to specific genetic variants and phenotypic characteristics. Outcomes included the observed ORT frequencies across two gene-specific cohorts: non- retinal pigment epithelium (RPE)-specific genes, and RPE-specific genes; and to investigate the analogous characteristics caused by variants in these genes. RESULTS: Among the 565 patients included in this study, 104 exhibited ORT on SD-OCT. We observed ORT frequencies among the following genes from our patient cohort: 100% (23/23) forCHM, 100%(2/2) forPNPLA6, 100% (4/4) forRCBTB1, 100% formtDNA[100% (4/4) forMT-TL1and 100% (1/1) formtDNAdeletion], 100% (1/1) forOAT, 95.2% (20/21) forCYP4V2, 72.7% (8/11) forCHMfemale carriers, 66.7% (2/3) forC1QTNF5, 57.1% (8/14) forPROM1, 53.8% (7/13) forPRPH2, 42.9% (3/7) forCERKL, 28.6% (2/7) forCDHR1, 20% (1/5) forRPE65, 4% (18/445) forABCA4.In contrast, ORT was not observed in any patients with photoreceptor-specific gene variants, such asRHO(n=13),USH2A(n=118),EYS(n=70),PDE6B(n=10),PDE6A(n=4),and others. CONCLUSION: These results illustrate a compelling association between the presence of ORT and IRDs caused by variants in RPE-specific genes, as well as non-RPE-specific genes. In contrast, IRDs caused by photoreceptor-specific genes are typically not associated with ORT occurrence. Further analysis revealed that ORT tends to manifest in IRDs with milder intraretinal pigment migration (IPM), a finding that is typically associated with RPE-specific genes. These findings regarding ORT, genetic factors, atrophic patterns in the fundus, and IPM provide valuable insight into the complex etiology of IRDs. Future prospective studies are needed to further explore the association and underlying mechanisms of ORT in these contexts.

Baseline viral load and on-treatment hepatocellular carcinoma risk in chronic hepatitis B: A multinational cohort study.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) risk persists in chronic hepatitis B (CHB) patients despite antiviral therapy. The relationship between pre-treatment baseline hepatitis B virus (HBV) viral load and HCC risk during antiviral treatment remains uncertain. METHODS: This multinational cohort study aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in 20,826 noncirrhotic, hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with baseline HBV DNA levels ≥2,000 IU/mL (3.30 log10 IU/mL) who initiated entecavir or tenofovir treatment. The primary outcome was on-treatment HCC incidence, stratified by baseline HBV viral load as a categorical variable. RESULTS: In total, 663 patients developed HCC over a median follow-up of 4.1 years, with an incidence rate of 0.81 per 100 person-years (95% confidence interval [CI], 0.75-0.87). Baseline HBV viral load was significantly associated with HCC risk in a non-linear parabolic pattern, independent of other factors. Patients with baseline viral load between 6.00 and 7.00 log10 IU/mL had the highest on-treatment HCC risk (adjusted hazard ratio, 4.28; 95% CI, 2.15-8.52; P < .0001) compared to those with baseline viral load ≥8.00 log10 IU/mL, who exhibited the lowest HCC risk. CONCLUSION: Baseline viral load showed a significant, non-linear, parabolic association with HCC risk during antiviral treatment in noncirrhotic CHB patients. Early initiation of antiviral treatment based on HBV viral load may help prevent irreversible HCC risk accumulation in CHB patients.

Impact of HCV eradication by directly acting antivirals on glycemic indices in chronic hepatitis C patients -a nationwide Taiwan HCV registry.

BACKGROUND/AIMS: Hepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. METHODS: Data from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). RESULTS: Serum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00-1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48-3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05-1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000-1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006-1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52-4.45, P < 0.001). CONCLUSIONS: The HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

Morphological Change in Optical Coherence Tomography and Functional Outcomes in Epiretinal Membrane Peeling with or without SF6 Tamponade.

BACKGROUND: The present study compares the anatomical and functional outcomes (best-corrected visual acuity (BCVA) and central macular thickness (CMT)) among membrane peeling with or without SF6 tamponade in patients with epiretinal membrane. METHODS: We retrospectively reviewed patients diagnosed with macular pucker who underwent pars plana vitrectomy and membrane peeling in a tertiary center in Taiwan from January 2021 to December 2022. Subjects were categorized into with or without SF6 tamponade groups (SF6 group and BSS group). Postoperative intraocular pressure and complications were documented. Logistic regression analyses were performed to identify the prognostic factors during follow-up. RESULTS: A total of 89 eyes were enrolled, including 34 eyes in the BSS group and 55 eyes in the SF6 group. The mean age was 66 years old, and a female predilection was demonstrated. Both groups possessed statistically significant improvement in BCVA and CMT after the operation. There was no significant difference in CMT between the groups at any time of observation, yet we observed significant differences in baseline BCVA and BCVA at last follow-up among the two groups. Both groups yielded an approximate enhancement of LogMAR 0.3 in BCVA postoperatively. There was no significant difference noted in postoperative IOP between the two groups. CONCLUSION: Membrane peeling with or without SF6 tamponade yields comparable outcomes anatomically and functionally. This may indicate that SF6 tamponade for idiopathic macular pucker surgery may not provide extra benefit, and therefore warrants reconsideration as standard procedure.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

Ursodeoxycholic Acid Modulates the Interaction of miR-21 and Farnesoid X Receptor and NF-κB Signaling.

(1) Background: This study investigates the effects of Ursodeoxycholic acid (UDCA) on NF-κB signaling, farnesoid X receptor (FXR) singling, and microRNA-21 in HepG2 cells. (2) Methods: HepG2 cells were treated with lipopolysaccharide (LPS) to simulate hepatic inflammation. The investigation focused on the expression of NF-κB activation, which was analyzed using Western blot, confocal microscopy, and Electrophoretic Mobility-shift Assays (EMSA). Additionally, NF-κB and farnesoid X receptor (FXR) singling expressions of micro-RNA-21, COX-2, TNF-α, IL-6, cyp7A1, and shp were assessed by RT-PCR. (3) Results: UDCA effectively downregulated LPS-induced expressions of NF-κB/65, p65 phosphorylation, and also downregulated FXR activity by Western blot. Confocal microscopy and EMSA results confirmed UDCA's role in modulating NF-κB signaling. UDCA reduced the expressions of LPS-induced COX-2, TNF-α, and IL-6, which were related to NF-κB signaling. UDCA downregulated LPS-induced cyp7A1 gene expression and upregulated shp gene expression, demonstrating selective gene regulation via FXR. UDCA also significantly decreased micro-RNA 21 levels. (4) Conclusions: This study demonstrates UDCA's potent anti-inflammatory effects on NF-κB and FXR signaling pathways, and thus its potential to modulate hepatic inflammation and carcinogenesis through interactions with NF-κB and FXR. The decrease in micro-RNA 21 expression further underscores its therapeutic potential.

Switching to tenofovir alafenamide in patients with virologically suppressed chronic hepatitis B and renal or hepatic impairment: final week 96 results from an open-label, multicentre, phase 2 study.

BACKGROUND: Phase 3 studies in patients with chronic hepatitis B have shown tenofovir alafenamide to have non-inferior efficacy to tenofovir disoproxil fumarate, with improved renal and bone safety. We conducted this study to evaluate the safety and efficacy of switching to tenofovir alafenamide in participants with chronic hepatitis B and renal or hepatic impairment. METHODS: This open-label, multicentre, phase 2 study was done in eight countries or territories at 30 sites. We recruited adults (≥18 years) with chronic hepatitis B who were virally suppressed on nucleoside or nucleotide analogues and had renal impairment (part A: moderate or severe in cohort 1 [estimated glomerular filtration rate by the Cockcroft-Gault formula (eGFRCG) 15-59 mL/min] or end-stage renal disease [eGFRCG <15 mL/min] on haemodialysis in cohort 2) or hepatic impairment including decompensation (part B: Child-Turcotte-Pugh score 7-12). Participants switched to 25 mg of tenofovir alafenamide given orally once daily for 96 weeks. The primary endpoint was the proportion of participants with viral suppression (HBV DNA <20 IU/mL) at week 24 by missing-equals-failure analysis. Efficacy (full analysis set) and safety (safety analysis set) analyses included all enrolled participants who received at least one dose of the study drug. Week 96 safety was assessed, including renal and bone parameters. This trial is registered at ClinicalTrials.gov, NCT03180619, and is completed. FINDINGS: 124 participants (93 in part A [78 in cohort 1 and 15 in cohort 2] and 31 in part B) were enrolled between Aug 11, 2017, and Oct 17, 2018, and included in the full and safety analysis sets. 106 (85%) participants completed the study. There were 69 (74%) men and 24 (26%) women in part A and 21 (68%) men and ten (32%) women in part B. At week 24, 91 (97·8%, 95% CI 92·4 to 99·7) of 93 individuals in part A (76 [97·4%, 91·0 to 99·7] of 78 in cohort 1 and 15 [100·0%, 78·2 to 100·0] of 15 in cohort 2) and 31 (100·0%, 88·8 to 100·0) in part B had HBV DNA of less than 20 IU/mL. By week 96, the most common adverse event was upper respiratory tract infection, which occurred in 14 (15%) participants in part A and in six (19%) participants in part B. Serious adverse events occurred in 20 (22%) part A participants and in ten (32%) part B participants; none were related to treatment. No treatment-related deaths occurred. At week 96, median change in estimated glomerular filtration rate (Cockcroft-Gault method) was 1·0 mL/min (IQR -2·8 to 4·5) in cohort 1 and -2·4 mL/min (-11·4 to 10·7) in part B. Mean changes in spine and hip bone mineral density were 1·02% (SD 4·44) and 0·20% (3·25) in part A and -0·25% (3·91) and 0·28% (3·25) in part B. INTERPRETATION: Tenofovir alafenamide might offer continued antiviral efficacy and a favourable safety profile for patients with renal or hepatic impairment and chronic hepatitis B switching from tenofovir disoproxil fumarate or other antivirals. FUNDING: Gilead Sciences.

Occurrence of pendelluft during ventilator weaning with T piece correlated with increased mortality in difficult-to-wean patients.

BACKGROUND: Difficult-to-wean patients, typically identified as those failing the initial spontaneous breathing trial (SBT), face elevated mortality rates. Pendelluft, frequently observed in patients experiencing SBT failure, can be conveniently detected through bedside monitoring with electrical impedance tomography (EIT). This study aimed to explore the impact of pendelluft during SBT on difficult-to-wean patients. METHODS: This retrospective observational study included difficult-to-wean patients undergoing spontaneous T piece breathing, during which EIT data were collected. Pendelluft occurrence was defined when its amplitude exceeded 2.5% of global tidal impedance variation. Physiological parameters during SBT were retrospectively retrieved from the EIT Examination Report Form. Other clinical data including mechanical ventilation duration, length of ICU stay, length of hospital stay, and 28-day mortality were retrieved from patient records in the hospital information system for each subject. RESULTS: Pendelluft was observed in 72 (70.4%) of the 108 included patients, with 16 (14.8%) experiencing mortality by day 28. The pendelluft group exhibited significantly higher mortality (19.7% vs. 3.1%, p = 0.035), longer median mechanical ventilation duration [9 (5-15) vs. 7 (5-11) days, p = 0.041] and shorter ventilator-free days at day 28 [18 (4-22) vs. 20 (16-23) days, p = 0.043]. The presence of pendellfut was independently associated with increased mortality at day 28 (OR = 10.50, 95% confidence interval 1.21-90.99, p = 0.033). CONCLUSIONS: Pendelluft occurred in 70.4% of difficult-to-wean patients undergoing T piece spontaneous breathing. Pendelluft was associated with worse clinical outcomes, including prolonged mechanical ventilation and increased mortality in this population. Our findings underscore the significance of monitoring pendelluft using EIT during SBT for difficult-to-wean patients.

Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving fixed-dose pangenotypic direct-acting antivirals.

Early confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups. A total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving fixed-dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval [CI]: 98.0-98.9) and 100% (95% CI: 66.4-100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed-dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% [95% CI: 98.9-100] vs. 97.1% [95% CI: 96.2-97.8], p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off-treatment week 12 among patients with HCV who are treated with fixed-dose pangenotypic DAAs.

Early bedside detection of pulmonary perfusion defect by electrical impedance tomography after pulmonary endarterectomy.

Pulmonary endarterectomy (PEA) is the standard treatment for chronic thromboembolic pulmonary hypertension. However, it poses risks of perioperative vascular complications, which can lead to serious clinical outcomes. This study introduces a novel noninvasive and radiation-free clinical imaging tool, electrical impedance tomography (EIT), for real-time bedside assessment of lung perfusion after PEA. It identifies ventilation-perfusion mismatches arising from postoperative complications, particularly valuable for patients with hemodynamic instability, thus eliminating risks tied to CT room transfers. The article reports a case where EIT was used to identify an in-situ thrombosis post-PEA, marking the first such application. The emphasis is on early detection using EIT, which offers a promising approach for therapeutic interventions and improved postoperative evaluations.

Bleeding Risk of Cold Versus Hot Snare Polypectomy for Pedunculated Colorectal Polyps Measuring 10 mm or Less: Subgroup Analysis of a Large Randomized Controlled Trial.

INTRODUCTION: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions. METHODS: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp. RESULTS: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group. DISCUSSION: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm.

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

BACKGROUND/AIMS: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. METHODS: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development. RESULTS: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. CONCLUSION: Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Dynamic change of metabolic dysfunction-associated steatotic liver disease in patients with hepatitis C virus infection after achieving sustained virologic response with direct-acting antivirals.

BACKGROUND: Information on the dynamics of metabolic dysfunction-associated steatotic liver disease (MASLD) among hepatitis C virus patients achieving sustained virologic response (SVR12) with direct-acting antivirals (DAAs) is limited. METHODS: We enrolled 1512 eligible participants in this prospective study. MASLD was defined by a controlled attenuation parameter (CAP) of ≥248 dB/m utilizing vibration-controlled transient elastography in conjunction with presence of ≥1 cardiometabolic risk factor. The distribution of MASLD and the changes in CAP were evaluated before treatment and at SVR12. Forward stepwise logistic regression analyses were performed to determine factors significantly associated with the regression or emergence of MASLD. RESULTS: The prevalence of MASLD decreased from 45.0% before treatment to 36.1% at SVR12. Among 681 participants with MASLD before treatment, 144 (21%) exhibited MASLD regression at SVR12. Conversely, among 831 participants without MASLD before treatment, 9 (1.1%) developed MASLD at SVR12. Absence of type 2 diabetes (T2D) [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.13-2.65, p = 0.011], age > 50 years (OR: 1.73, 95% CI: 1.11-2.68, p = 0.015), and alanine transaminase (ALT) ≤ 2 times the upper limit of normal (ULN) (OR: 1.56; 95% CI: 1.03-2.37, p = 0.035) were associated with the regression of MASLD. Presence of T2D was associated with the emergence of MASLD (OR: 5.83, 95% CI: 1.51-22.56, p = 0.011). CONCLUSIONS: The prevalence of MASLD decreased after achieving SVR12 with DAAs. Patients with pre-existing T2D showed a diminished probability of MASLD regression and a heightened risk of MASLD emergence post-SVR12.

Real-World Efficacy and Safety of Universal 8-Week Glecaprevir/Pibrentasvir for Treatment-Naïve Patients from a Nationwide HCV Registry in Taiwan.

INTRODUCTION: Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). METHODS: The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. RESULTS: A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. CONCLUSION: Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

The Efficacy of Fat Grafting on Treating Post-Mastectomy Pain with and without Breast Reconstruction: A Systematic Review and Meta-Analysis.

Post-mastectomy pain syndrome (PMPS), characterized by persistent pain lasting at least three months following mastectomy, affects 20-50% of breast surgery patients, lacking effective treatment options. A review was conducted utilizing EMBASE, MEDLINE, and all evidence-based medicine reviews to evaluate the effect of fat grafting as a treatment option for PMPS from database inception to 29 April 2023 (PROSPERO ID: CRD42023422627). Nine studies and 812 patients in total were included in the review. The overall mean change in visual analog scale (VAS) was -3.6 in 285 patients following fat grafting and 0.5 in 147 control group patients. There was a significant reduction in VAS from baseline in the fat grafting group compared to the control group, n = 395, mean difference = -2.17 (95% CI, -2.95 to -1.39). This significant improvement was also noted in patients who underwent mastectomy without reconstruction. Common complications related to fat grafting include capsular contracture, seroma, hematoma, and infection. Surgeons should consider fat grafting as a treatment option for PMPS. However, future research is needed to substantiate this evidence and to identify timing, volume of fat grafting, and which patient cohort will benefit the most.

Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients.

BACKGROUND/AIMS: Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection. METHODS: Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days. RESULTS: A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were -2.9, -3.3, -3.5 and -0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was -2.9, -2.4, -2.0, and -0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events of mild or moderate severity with no discontinuations, serious AEs or deaths. CONCLUSION: In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.

Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: A multinational cohort study of HBeAg-positive patients.

BACKGROUND AND AIMS: A single-nation study reported that pretreatment HBV viral load is associated with on-treatment risk of HCC in patients who are HBeAg-positive without cirrhosis and with chronic hepatitis B initiating antiviral treatment. We aimed to validate the association between baseline HBV viral load and on-treatment HCC risk in a larger, multinational cohort. APPROACH AND RESULTS: Using a multinational cohort from Korea, Hong Kong, and Taiwan involving 7545 adult patients with HBeAg-positive, without cirrhosis and with chronic hepatitis B who started entecavir or tenofovir treatment with baseline HBV viral load ≥5.00 log 10 IU/mL, HCC risk was estimated by baseline viral load. HBV viral load was analyzed as a categorical variable. During continuous antiviral treatment (median, 4.28 y), HCC developed in 200 patients (incidence rate, 0.61 per 100 person-years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a nonlinear pattern. HCC risk was lowest with the highest baseline viral load (≥8.00 log 10 IU/mL; incidence rate, 0.10 per 100 person-years), but increased sharply as baseline viral load decreased. The adjusted HCC risk was 8.05 times higher (95% CI, 3.34-19.35) with baseline viral load ≥6.00 and <7.00 log 10 IU/mL (incidence rate, 1.38 per 100 person-years) compared with high (≥8.00 log 10 IU/mL) baseline viral load ( p <0.001). CONCLUSIONS: In a multinational cohort of adult patients with HBeAg-positive without cirrhosis and with chronic hepatitis B, baseline HBV viral load was significantly associated with HCC risk despite antiviral treatment. Patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC development.