Differential Effects of Genetic Polymorphism on Comorbid Disease in Metabolic Dysfunction-Associated Steatotic Liver Disease.

BACKGROUND & AIMS: PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 have been associated with an increased risk of liver-related events (LREs) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, we investigated the combined effects of these variants on LREs. METHODS: The longitudinal multicenter cohort study enrolled 1178 patients with biopsy-proven MASLD. We calculated the genetic risk of hepatic fibrosis and LRE according to the impact of these variants. RESULTS: Patients with genetic fibrosis scores of 2, 3, and 4 or 5 were at greater risk than patients with scores of 0 or 1, with odds ratios of 2.45 (95% CI, 1.27-4.74), 2.14 (95% CI, 1.17-3.94), and 2.54 (95% CI, 1.35-4.77), respectively. Multivariate analysis revealed that PNPLA3 and TM6SF2, but not HSD17B13, were associated significantly with LRE development. The hazard ratio of the genetic high-risk group for LRE was 1.91 (95% CI, 1.20-3.04). The higher risk of LRE development in the genetic high-risk group also was seen in patients with F ≥ 3 or Fibrosis-4 index > 2.67. The hazard ratios of the genetic high-risk group for LRE were greater in patients without obesity, without diabetes, and of younger age compared with patients with obesity, with diabetes, or of older age, respectively. CONCLUSIONS: This combination of MASLD-related genetic variants is useful for predicting LREs in Japanese patients with MASLD. The genetic risk according to these variants is useful for LRE risk assessment, especially in patients without metabolic risk factors or in younger patients in Japan.

Hepatic inflammation and fibrosis are profiles related to mid-term mortality in biopsy-proven MASLD: A multicenter study in Japan.

AIMS: A multi-stakeholder consensus has proposed MASLD (metabolic dysfunction-associated steatotic liver disease). We aimed to investigate the pathological findings related to the mid-term mortality of patients with biopsy-proven MASLD in Japan. METHODS: We enrolled 1349 patients with biopsy-proven MASLD. The observational period was 8010 person years. We evaluated independent factors associated with mortality in patients with MASLD by Cox regression analysis. We also investigated pathological profiles related to mortality in patients with MASLD using data-mining analysis. RESULTS: The prevalence of MASH and stage 3/4 fibrosis was observed in 65.6% and 17.4%, respectively. Forty-five patients with MASLD died. Of these, liver-related events were the most common cause at 40% (n = 18), followed by extrahepatic malignancies at 26.7% (n = 12). Grade 2/3 lobular inflammation and stage 3/4 fibrosis had a 1.9-fold and 1.8-fold risk of mortality, respectively. In the decision-tree analysis, the profiles with the worst prognosis were characterised by Grade 2/3 hepatic inflammation, along with advanced ballooning (grade 1/2) and fibrosis (stage 3/4). This profile showed a mortality at 8.3%. Furthermore, the random forest analysis identified that hepatic fibrosis and inflammation were the first and second responsible factors for the mid-term prognosis of patients with MASLD. CONCLUSIONS: In patients with biopsy-proven MASLD, the prevalence of MASH and advanced fibrosis was approximately 65% and 20%, respectively. The leading cause of mortality was liver-related events. Hepatic inflammation and fibrosis were significant factors influencing mid-term mortality. These findings highlight the importance of targeting inflammation and fibrosis in the management of patients with MASLD.

Validation study of age-independent fibrosis score (Fibrosis-3 index) in patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Because the accuracy of the Fibrosis-4 (FIB-4) index for predicting liver fibrosis changes with age, the need for different cut-offs in various age groups has frequently been discussed. We developed the age-independent score, the Fibrosis-3 (FIB-3) index, and have shown its usefulness in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to validate the diagnostic ability of the FIB-3 index to predict fibrosis progression using a large new patient cohort. METHODS: The ability of the FIB-3 index to predict liver fibrosis was analyzed by comparing it with that of the FIB-4 index using data from 1398 patients with MASLD enrolled in the Asia-based clinical outcome NAFLD study. RESULTS: The areas under the receiver operating characteristic curves for predicting fibrosis stage F3 or higher were not different between the FIB-3 and FIB-4 indices in the entire cohort. Using the single ideal cut-offs of the indices (3.41 for FIB-3 index and 2.01 for FIB-4 index), the predictive accuracy of the FIB-3 index was not significantly different from that of the FIB-4 index among patients aged <60 years; however, the accuracy of the FIB-3 index was significantly higher than that of the FIB-4 index in those aged ≥60 years (0.645 and 0.529, respectively; p < 0.0001). CONCLUSION: The high ability of the FIB-3 index with a single cut-off to predict liver fibrosis in patients with MASLD was confirmed. The FIB-3 index could serve as a useful tool for assessing liver fibrosis regardless of age.

Reaction norm for genomic prediction of plant growth: modeling drought stress response in soybean.

KEY MESSAGE: We proposed models to predict the effects of genomic and environmental factors on daily soybean growth and applied them to soybean growth data obtained with unmanned aerial vehicles. Advances in high-throughput phenotyping technology have made it possible to obtain time-series plant growth data in field trials, enabling genotype-by-environment interaction (G × E) modeling of plant growth. Although the reaction norm is an effective method for quantitatively evaluating G × E and has been implemented in genomic prediction models, no reaction norm models have been applied to plant growth data. Here, we propose a novel reaction norm model for plant growth using spline and random forest models, in which daily growth is explained by environmental factors one day prior. The proposed model was applied to soybean canopy area and height to evaluate the influence of drought stress levels. Changes in the canopy area and height of 198 cultivars were measured by remote sensing using unmanned aerial vehicles. Multiple drought stress levels were set as treatments, and their time-series soil moisture was measured. The models were evaluated using three cross-validation schemes. Although accuracy of the proposed models did not surpass that of single-trait genomic prediction, the results suggest that our model can capture G × E, especially the latter growth period for the random forest model. Also, significant variations in the G × E of the canopy height during the early growth period were visualized using the spline model. This result indicates the effectiveness of the proposed models on plant growth data and the possibility of revealing G × E in various growth stages in plant breeding by applying statistical or machine learning models to time-series phenotype data.

Cancer screening programs in Japan: Progress and challenges.

National screening programs for gastric, colorectal, lung, breast, and cervical cancers are offered in Japan. The initial introduction of cancer screening programs was decided based on experts' opinions. Since 2003, the research groups funded by the National Cancer Center have published screening guidelines for gastric, colorectal, lung, prostate, cervical, and breast cancers. Although such guidelines have increasingly contributed to promoting evidence-based screening, it is still insufficient. Cancer screenings have mainly been provided in communities and workplaces. Compared with the average of OECD countries, participation rates in breast and cervical cancer screening are lower. Participation rates cannot be accurately calculated due to a lack of comprehensive cancer screening registries at the national level. Alternatively, estimates are derived from questionnaire surveys conducted on randomly selected samples from the national population. The quality assurance system has been limited to community-based screening and was not adapted to workplace screening until 2018. While there is a long history of cancer screening, the complex program delivery system might be a barrier to increasing the participation rate. Continued efforts are necessary to offer evidence-based cancer screening and establish an effective quality assurance system.

Mortality in patients with chronic hepatitis B treated with tenofovir or entecavir: A multinational study.

BACKGROUND AND AIM: The benefits of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in reducing the development of chronic hepatitis B (CHB)-related hepatocellular carcinoma remain controversial. Whether mortality rates differ between patients with CHB treated with ETV and those treated with TDF is unclear. METHODS: A total of 2542 patients with CHB treated with either ETV or TDF were recruited from a multinational cohort. A 1:1 propensity score matching was performed to balance the differences in baseline characteristics between the two patient groups. We aimed to compare the all-cause, liver-related, and non-liver-related mortality between patients receiving ETV and those receiving TDF. RESULTS: The annual incidence of all-cause mortality in the entire cohort was 1.0/100 person-years (follow-up, 15 757.5 person-years). Patients who received TDF were younger and had a higher body mass index, platelet count, hepatitis B virus deoxyribonucleic acid levels, and proportion of hepatitis B e-antigen seropositivity than those who received ETV. The factors associated with all-cause mortality were fibrosis-4 index > 6.5 (hazard ratio [HR]/confidence interval [CI]: 3.13/2.15-4.54, P < 0.001), age per year increase (HR/CI: 1.05/1.04-1.07, P < 0.001), alanine aminotransferase level per U/L increase (HR/CI: 0.997/0.996-0.999, P = 0.003), and γ-glutamyl transferase level per U/L increase (HR/CI: 1.002/1.001-1.003, P < 0.001). No significant difference in all-cause mortality was observed between the ETV and TDF groups (log-rank test, P = 0.69). After propensity score matching, no significant differences in all-cause, liver-related, or non-liver-related mortality were observed between the two groups. CONCLUSIONS: Long-term outcomes of all-cause mortality and liver-related and non-liver-related mortality did not differ between patients treated with ETV and those receiving TDF.

Meta-analysis: Prevalence and impact of alcohol abstinence in alcohol-associated cirrhosis.

BACKGROUND: Although alcohol abstinence may be an effective intervention for alcohol-associated cirrhosis, its association with prognosis has not been systematically assessed or quantified. AIMS: To determine the prevalence of alcohol abstinence, factors associated with alcohol abstinence and the impact of abstinence on morbidity and overall survival in people with alcohol-associated cirrhosis. METHODS: We searched Medline and Embase from inception to 15 April 2023 for prospective and retrospective cohort studies describing alcohol abstinence in people with known alcohol-associated cirrhosis. Meta-analysis of proportions for pooled estimates was performed. The method of inverse variance, employing a random-effects model, was used to pool the hazard ratio (HR) comparing outcomes of abstinent against non-abstinent individuals with alcohol-associated cirrhosis. RESULTS: We included 19 studies involving 18,833 people with alcohol-associated cirrhosis. The prevalence of alcohol abstinence was 53.8% (CI: 44.6%-62.7%). Over a mean follow-up duration of 48.6 months, individuals who continued to consume alcohol had significantly lower overall survival compared to those who were abstinent (HR: 0.611, 95% CI: 0.506-0.738). These findings remained consistent in sensitivity/subgroup analysis for the presence of decompensation, study design and studies that assessed abstinence throughout follow-up. Alcohol abstinence was associated with a significantly lower risk of hepatic decompensation (HR: 0.612, 95% CI: 0.473-0.792). CONCLUSIONS: Alcohol abstinence is associated with substantial improvement in overall survival in alcohol-associated cirrhosis. However, only half of the individuals with known alcohol-associated cirrhosis are abstinent.

TYK2 signaling promotes the development of autoreactive CD8+ cytotoxic T lymphocytes and type 1 diabetes.

Tyrosine kinase 2 (TYK2), a member of the JAK family, has attracted attention as a potential therapeutic target for autoimmune diseases. However, the role of TYK2 in CD8+ T cells and autoimmune type 1 diabetes (T1D) is poorly understood. In this study, we generate Tyk2 gene knockout non-obese diabetes (NOD) mice and demonstrate that the loss of Tyk2 inhibits the development of autoreactive CD8+ T-BET+ cytotoxic T lymphocytes (CTLs) by impairing IL-12 signaling in CD8+ T cells and the CD8+ resident dendritic cell-driven cross-priming of CTLs in the pancreatic lymph node (PLN). Tyk2-deficient CTLs display reduced cytotoxicity. Increased inflammatory responses in ß-cells with aging are dampened by Tyk2 deficiency. Furthermore, treatment with BMS-986165, a selective TYK2 inhibitor, inhibits the expansion of T-BET+ CTLs, inflammation in ß-cells and the onset of autoimmune T1D in NOD mice. Thus, our study reveals the diverse roles of TYK2 in driving the pathogenesis of T1D.

Cancer screening in Japan 2 years after the COVID-19 pandemic: Changes in participation, 2017-2021.

Objectives: The impact of the coronavirus disease (COVID-19) pandemic on cancer screening has become a global concern; compared with pre-pandemic levels, the number of individuals who underwent population-based cancer screening in Japan decreased by 10-30% in fiscal year (FY)2020. Therefore, it is important to monitor subsequent changes in the number of participants. Methods: This descriptive study analysed data from a national database to determine changes from 2017 to 2021 in the number of people screened for gastric cancer (upper gastrointestinal [UGI] series or endoscopy), colorectal cancer (faecal immunochemical test), lung cancer (chest X-ray), breast cancer (mammography), and cervical cancer (Pap smear). Results: Compared with the pre-pandemic period (FY 2017-2019), the number of participants in screening programmes in FY2021 decreased maximally for the gastric cancer UGI series (2.8 million to 2.2 million; -23.3 %), followed by those for lung cancer (7.9 million to 7.3 million; -8.2 %), colorectal cancer (8.4 million to 7.8 million; -7.3 %), breast cancer (3.1 million to 3.0 million; -4.5 %), and cervical cancer (4.3 million to 4.1 million; -3.2 %). Conversely, the number of people screened for endoscopic gastric cancer screening increased (1.0 million to 1.2 million; +13.1 %). Conclusions: The number of participants, which decreased sharply immediately after the onset of the COVID-19 pandemic, recovered only slightly in FY2021 and did not return to pre-pandemic levels yet, except for endoscopic gastric cancer screening. Therefore, the impact of this decline in participation in cancer-detection programmes and changes in mortality should be monitored carefully.

Transcriptome Analysis of Rice Root Tips Reveals Auxin, Gibberellin and Ethylene Signaling Underlying Nutritropism.

Nutritropism is a positive tropism toward nutrients in plant roots. An NH4+ gradient is a nutritropic stimulus in rice (Oryza sativa L.). When rice roots are exposed to an NH4+ gradient generated around nutrient sources, root tips bend toward and coil around the sources. The molecular mechanisms are largely unknown. Here, we analyzed the transcriptomes of the inside and outside of bending root tips exhibiting nutritropism to reveal nutritropic signal transduction. Tissues facing the nutrient sources (inside) and away (outside) were separately collected by laser microdissection. Principal component analysis revealed distinct transcriptome patterns between the two tissues. Annotations of 153 differentially expressed genes implied that auxin, gibberellin and ethylene signaling were activated differentially between the sides of the root tips under nutritropism. Exogenous application of transport and/or biosynthesis inhibitors of these phytohormones largely inhibited the nutritropism. Thus, signaling and de novo biosynthesis of the three phytohormones are necessary for nutritropism. Expression patterns of IAA genes implied that auxins accumulated more in the inside tissues, meaning that ammonium stimulus is transduced to auxin signaling in nutritropism similar to gravity stimulus in gravitropism. SAUR and expansin genes, which are known to control cell wall modification and to promote cell elongation in shoot gravitropism, were highly expressed in the inside tissues rather than the outside tissues, and our transcriptome data are unexplainable for differential elongation in root nutritropism.

Prognosis of biopsy-confirmed metabolic dysfunction- associated steatotic liver disease: A sub-analysis of the CLIONE study.

BACKGROUND/AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) was recently proposed as an alternative disease concept to nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prognosis of patients with biopsy-confirmed MASLD using data from a multicenter study. METHODS: This was a sub-analysis of the Clinical Outcome Nonalcoholic Fatty Liver Disease (CLIONE) study that included 1,398 patients with NAFLD. Liver biopsy specimens were pathologically diagnosed and histologically scored using the NASH Clinical Research Network system, the FLIP algorithm, and the SAF score. Patients who met at least one cardiometabolic criterion were diagnosed with MASLD. RESULTS: Approximately 99% of cases (n=1,381) were classified as MASLD. Patients with no cardiometabolic risk (n=17) had a significantly lower BMI than patients with MASLD (20.9 kg/m2 vs. 28.0 kg/m2, P<0.001), in addition to significantly lower levels of inflammation, ballooning, NAFLD activity score, and fibrosis stage based on liver histology. These 17 patients had a median follow-up of 5.9 years, equivalent to 115 person-years, with no deaths, liver-related events, cardiovascular events, or extrahepatic cancers. The results showed that the prognosis for pure MASLD was similar to that for the original CLIONE cohort, with 47 deaths and one patient who underwent orthotopic liver transplantation. The leading cause of death was extrahepatic cancer (n=10), while the leading causes of liver-related death were liver failure (n=9), hepatocellular carcinoma (n=8), and cholangiocarcinoma (n=4). CONCLUSION: Approximately 99% of NAFLD cases were considered MASLD based on the 2023 liver disease nomenclature. The NAFLD-only group, which is not encompassed by MASLD, had a relatively mild histopathologic severity and a favorable prognosis. Consequently, the prognosis of MASLD is similar to that previously reported for NAFLD.

Racial and ethnic disparities in untreated patients with hepatitis C virus-related hepatocellular carcinoma but not in those with sustained virologic response.

BACKGROUND: Racial and ethnic disparities exist for hepatitis C virus (HCV) treatment and hepatocellular carcinoma (HCC) survival. AIM: To evaluate the impact of HCV treatment on such disparities. METHODS: In a retrospective cohort study, we analysed 6069 patients with HCV-related HCC (54.2% Asian, 30.1% White, 8.5% Black, and 7.3% Hispanic) from centres in the United States and Asia. RESULTS: The mean age was 61, 60, 59 and 68, respectively, for White, Black, Hispanic and Asian patients. Black patients were most likely to have Barcelona Clinic Liver Cancer stage D, vascular invasion and distant metastasis (23% vs. 5%-15%, 20% vs. 10%-17% and 10% vs. 5%-7%, respectively; all p < 0.0001). Treatment rate with direct-acting antiviral agents (DAA) was 35.9% for Asian, 34.9% for White, 30.3% for Hispanic (30.3%), and 18.7% for Black patients (p < 0.0001). Among those untreated or without sustained virologic response (SVR), 10-year survival rates were 35.4, 27.5, 19.3 and 14.0, respectively, for Asian, Hispanic, White and Black patients (p < 0.0001). There were no statistically significant differences among those with SVR (p = 0.44). On multivariable analysis adjusted for relevant confounders, there was no statistically significant association between survival and being Hispanic (aHR: 0.68, p = 0.26) or Black (aHR: 1.18, p = 0.60) versus White. There was a significant association between being Asian American and survival (aHR: 0.24, p = 0.001; non-U.S. Asian: aHR: 0.66, p = 0.05), and for SVR (aHR: 0.30, p < 0.0001). CONCLUSION: DAA treatment rates were suboptimal. Racial and ethnic disparities resolved with HCV cure. Early diagnosis and improved access to HCV treatment is needed for all patients with HCV infection.

Mutational analysis of the transmembrane α4-helix of Bacillus thuringiensis mosquito-larvicidal Cry4Aa toxin.

Cry4Aa, produced by Bacillus thuringiensis subsp. israelensis, exhibits specific toxicity to larvae of medically important mosquito genera. Cry4Aa functions as a pore-forming toxin, and a helical hairpin (α4-loop-α5) of domain I is believed to be the transmembrane domain that forms toxin pores. Pore formation is considered to be a central mode of Cry4Aa action, but the relationship between pore formation and toxicity is poorly understood. In the present study, we constructed Cry4Aa mutants in which each polar amino acid residues within the transmembrane α4 helix was replaced with glutamic acid. Bioassays using Culex pipiens mosquito larvae and subsequent ion permeability measurements using symmetric KCl solution revealed an apparent correlation between toxicity and toxin pore conductance for most of the Cry4Aa mutants. In contrast, the Cry4Aa mutant H178E was a clear exception, almost losing its toxicity but still exhibiting a moderately high conductivity of about 60% of the wild-type. Furthermore, the conductance of the pore formed by the N190E mutant (about 50% of the wild-type) was close to that of H178E, but the toxicity was significantly higher than that of H178E. Ion selectivity measurements using asymmetric KCl solution revealed a significant decrease in cation selectivity of toxin pores formed by H178E compared to N190E. Our data suggest that the toxicity of Cry4Aa is primarily pore related. The formation of toxin pores that are highly ion-permeable and also highly cation-selective may enhance the influx of cations and water into the target cell, thereby facilitating the eventual death of mosquito larvae.

Barriers to lifestyle modification in patients with non-alcoholic fatty liver disease: a scoping review.

Objective: Non-alcoholic fatty liver disease is common worldwide, and lifestyle modifications are key to its treatment. This study aimed to identify the barriers to lifestyle modifications in patients with non-alcoholic fatty liver disease and to organize the results using the Capability Opportunity Motivation-Behavior (COM-B) model. Materials and Methods: The framework of Arksey and O' Malley was used in this scoping review. We searched PubMed, Scopus, and the Cochrane Library without language restrictions for reports published up to September 11, 2022, including peer-reviewed literature reporting barriers to lifestyle modifications in patients with non-alcoholic fatty liver disease. Patient-reported barriers were analyzed inductively and organized into the components (capability, opportunity, and motivation) of the COM-B model. Results: The literature search yielded 583 articles, of which seven qualitative studies, four quantitative studies, and one mixed-methods study met the inclusion criteria. Lack of time, lack of information on the diagnosis and management of non-alcoholic fatty liver disease, negative perceptions of the prescribed exercise and diet, physical symptoms interfering with the behavior, presence of comorbidities, and lack of family cooperation were frequently reported as barriers. Conclusion: The results of this study may contribute to the development of appropriate care and education strategies to promote behavioral changes in patients with non-alcoholic fatty liver disease.

A feasibility study of provider-level implementation strategies to improve access to colorectal cancer screening for patients with schizophrenia: ACCESS2 (N-EQUITY 2104) trial.

BACKGROUND: People with schizophrenia have a lower colorectal screening rate than the general population. A previous study reported an intervention using case management to encourage colorectal cancer screening for patients with schizophrenia in psychiatric outpatient settings. In this feasibility study, we developed provider-level implementation strategies and evaluated the feasibility of conducting a definitive trial in terms of the penetration of the intervention assessed at the patient level. Additionally, we examined the fidelity of strategies to implement the intervention at the provider level in a routine clinical psychiatric setting. METHODS: This was a multicenter, single-arm feasibility study with medical staff at psychiatric hospitals in Japan. The provider-level implementation strategies developed in this study included three key elements (organizing an implementation team appointed by the facility director, interactive assistance using a clear guide that outlines who in the hospital should do what, and developing accessible educational materials) to overcome major barriers to implementation of the intervention and four additional elements (progress monitoring, joint meetings and information sharing among participating sites, adaptation of encouragement methods to specific contexts, and education of on-site staff), with reference to the elements identified in the Expert Recommendations for Implementing Change (ERIC). The feasibility of the strategies was evaluated by the proportion of patients who were eligible for encouragement (patients with schizophrenia aged 40, 50, or 60) who received encouragement. We set the goal of providing encouragement to at least 40% of eligible patients at each site. RESULTS: Two public and four private psychiatric hospitals in Okayama and Shimane prefectures participated in this study. Regarding fidelity, all elements of the strategies were conducted as planned. Following the procedures in the guide, each team prepared and provided encouragement according to their own facility and region. Penetration, defined as the proportion of eligible patients who received encouragement, ranged from 33.3 to 100%; five of the six facilities achieved the target proportion. CONCLUSIONS: The provider-level implementation strategies to implement encouragement were feasible in terms of penetration of the intervention assessed at the patient level. The results support the feasibility of proceeding with a future definitive trial of these strategies. TRIAL REGISTRATION: jRCT, jRCT1060220026 . Registered on 06/04/2022.

Risk factors of early adverse events associated with endoscopic ultrasound-guided hepaticogastrostomy using self-expandable metal stent.

Background and study aims This retrospective study aimed to investigate risk factors for early adverse events (AEs) associated with endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) using self-expandable metal stents (SEMS). Patients and methods The clinical success rate, technical success rate, and early AEs were assessed at two hospitals from 2010 to 2022. The analysis focused on risk factors associated with cholangitis, peritonitis, and SEMS migration. Results Technical success was achieved in all cases (94/94), and clinical success was 96.8% (91/94). Post-procedural acute cholangitis occurred in 12.8%of cases (12/94). However, no statistically significant risk factors were identified for cholangitis or biliary tract infection. Peritonitis occurred in only 2.1% of cases (2/94). Univariate analysis, using a 1.5 cm cut-off for the distance between the liver and gastrointestinal tract, revealed significant risk factors: braided-type SEMS, bile duct diameter (especially >4 mm), 6 mm diameter SEMS, and tract dilation ( P= 0.001, P= 0.020, P =0.023, and P =0.046, respectively). Adjusting the cut-offs to 2 cm underscored braided-type SEMS and tract dilation as risk factors ( P =0.002 and P =0.046, respectively). With 2.5-cm cut-offs, only braided-type SEMS remained significant ( P =0.018). Mortality within 14 and 30 days following EUS-HGS was 5.3% (5/94) and 16.0% (15/94), respectively. Conclusions EUS-HGS using SEMS demonstrated high technical and clinical success rates. Laser-cut SEMS may be superior in preventing early AEs.

Comparative effectiveness of sodium-glucose co-transporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors on liver function in patients with type 2 diabetes in Japan: A real-world data analysis.

AIM: To compare the effects of sodium-glucose co-transporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) on liver function in patients with type 2 diabetes (T2D) in Japan. MATERIALS AND METHODS: This was a Japanese retrospective cohort study using the RWD Database (1 January 2015 to 24 September 2021). Patients newly treated with an SGLT2i or a DPP4i were matched 1:4 (SGLT2i:DPP4i) using propensity score. The primary endpoint was the change from baseline to 1 year after the index date in alanine aminotransferase (ALT). Secondary endpoints included change from baseline in various laboratory test results, including the Fibrosis-4 (FIB-4) index, aspartate aminotransferase, gamma-glutamyl transpeptidase (GGT), albumin and HbA1c. Endpoints were compared between treatment groups using Welch's t-test in the full population and in subgroups stratified by baseline characteristics. RESULTS: Baseline characteristics of 955 and 3063 matched patients newly treated with an SGLT2i and a DPP4i, respectively, were well balanced. Patients receiving an SGLT2i had significantly greater reductions in ALT, FIB-4 index and GGT and a significantly greater increase in albumin than patients receiving a DPP4i. A significantly greater change from baseline in ALT was observed in the SGLT2i group than in the DPP4i group among subgroups with lower baseline FIB-4 index and HbA1c. CONCLUSIONS: In this study, improvements in various measures, including ALT, the FIB-4 index, GGT and albumin, were observed with SGLT2is compared with DPP4is, suggesting that SGLT2is may provide hepatoprotective benefits, including the prevention of liver fibrosis, in patients with T2D in Japan.