Journal of Gastroenterology最新文献

Objectives: This study aimed to clarify the current clinico-epidemiological characteristics of acute pancreatitis (AP) in Japan.

Methods: We conducted a two-stage nationwide survey of patients with AP treated at selected hospitals in 2021, during the COVID-19 pandemic. The first stage estimated the total number of AP patients, while the second collected detailed clinical data.

Results: The estimated number of AP patients requiring hospitalization was 61,080, with an overall incidence rate of 49 per 100,000 persons, decreasing from 78,450 in 2016. Detailed clinical data were obtained for 4,375 patients, including 1,362 (31.1%) classified as severe. The male-to-female ratio was 2.0, with mean ages at onset of 60.1 years for males and 65.4 years for females. The three major causes were alcohol (31.2%), gallstones (22.5%), and idiopathic etiology (22.1%). The AP-associated in-hospital mortality rate was 2.1% in all AP and 5.3% in severe cases, down from 6.1% in the 2016 survey. Antibiotics were administered to 61.2% of mild cases, a significant reduction from 94.5% in 2016. Enteral nutrition was provided to 56.9% of severe cases, up from 31.8% in 2016. Among 124 patients undergoing interventional drainage for walled-off necrosis, 57 were treated using a step-up approach. Notably, no patients underwent upfront surgery as the initial treatment.

Conclusions: During the pandemic, the estimated number of AP cases requiring hospitalization declined for the first time in nearly four decades. Mortality in severe cases improved, and adherence to clinical guidelines on prophylactic antibiotics and enteral nutrition also improved, indicating enhanced management of AP in Japan.

Background: This study examines the influence of H. pylori eradication policies on gastric cancer incidence rates in Japan utilizing nationally representative registry data. It evaluates the impact of the H. pylori eradication policies introduced in 2000 and 2013, along with future eradication scenarios, on age-standardized gastric cancer rates.

Methods: Data from prefectural cancer registries and national health surveys were analyzed using Poisson regression and autoregressive integrated moving average models. Predictors such as H. pylori prevalence, alcohol consumption, salt intake, body mass index, and smoking prevalence were included. The study assessed past policies by comparing incidence rates with and without the policy changes of 2000 and 2013. Future policies were evaluated through five scenarios, incorporating the cumulative impact of eradication efforts from 2000 and 2013, and a projected 75% reduction by 2050. The evaluation also compared eradication targets for age groups 40-69 and 20-39.

Results: Past H. pylori eradication policies were associated with decreased age-standardized gastric cancer incidence rates in Japan, reducing the rate from a projected 39.3 per 100,000 without the 2000 and 2013 policies to 24.9 per 100,000 under current policies. Future policies, integrating the cumulative effects of the 2000 and 2013 eradication efforts and projecting a 75% reduction in H. pylori prevalence, were projected to further reduce gastric cancer incidence.

Conclusion: The H. pylori eradication policies of 2000 and 2013 have significantly reduced gastric cancer incidence rates in Japan. Model projections suggest that expanded eradication efforts could lead to additional reductions, further lowering the future burden of gastric cancer in Japan.

Background: Long-term effects of direct-acting antiviral (DAA) on hepatic reserve and prognosis in hepatitis C virus (HCV)-related decompensated cirrhosis remain unclear.

Methods: Ninety-four patients from a follow-up study of the Japanese phase 3 trial of DAA treatment for decompensated cirrhosis were included.

Results: Twelve, seventy-seven, and ten percent of patients had Child-Pugh class A/B/C, respectively. The sustained virologic response (SVR) rate was 93.6%. The proportion of Child-Pugh A patients was 21% at end of treatment (EOT), and 40%, 42%, 49%, 40% at 24 weeks, 1 year, 3 years, and 5 years after EOT, respectively. A significant breakpoint for Child-Pugh class improvement to A was observed between 24 weeks and 1 year after EOT. The proportions of patients with albumin levels > 3.5 g/dl increased from 11% (baseline) to 39% (5 years after EOT), and significant breakpoint for this improvement was observed between 12 and 24 weeks after EOT. During the 4.8 years from EOT, 19 patients died, and 1 underwent liver transplantation (LT). The five-year LT-free survival rate was 74.7%. Multivariate analysis identified virologic response and Child-Pugh class at 12 weeks after EOT as significant LT-free survival predictors. The four-year LT-free survival rates were 91.5% for SVR patients and 33.3% for virologic failure patients.

Conclusions: In HCV-related decompensated cirrhosis, 5 year LT-free survival rate after DAA was 74.7%, and viral clearance and post-treatment Child-Pugh class were associated with long-term prognosis. Child-Pugh class improved until 24 weeks after EOT, but little change was observed thereafter, which was closely associated with albumin levels.

Aim: We investigated the usefulness of serum CXCL10 levels for predicting prognosis in hepatitis C virus (HCV)-infected patients with compensated and decompensated cirrhosis (cLC and dLC) after direct-acting antiviral (DAA) therapy.

Methods: This nationwide multicenter study enrolled 212 HCV-associated LC patients, consisting of 113 cLC and 99 dLC patients, receiving DAA therapy, who had preserved serum samples. Serum CXCL10 levels were measured at pretreatment (pre-CXCL10) and posttreatment (12 or 24 weeks after the end of treatment: EOT12W or EOT24W) (post-CXCL10). We evaluated the relationship between these levels and liver transplantation (LT)-free overall survival (OS) and clinical outcomes.

Results: During the observational period (median: 37 months), 27 patients developed dLC events and 20 died. The post-CXCL10 levels were significantly higher in dLC than in cLC (P = 0.006) and among patients who died than those who survived (P < 0.001). The cutoff value of serum post-CXCL10 level for discriminating the occurrence of death (345 pg/mL) could predict LT-free OS in groups of all, cLC, and dLC patients (P < 0.001, P = 0.007, and P < 0.001, respectively). Multivariate analysis on factors associated with LT-free OS demonstrated that age (HR 1.076; P = 0.013), Child-Pugh score at EOT12W (HR 1.575; P = 0.009), and serum post-CXCL10 level (HR 1.003; P = 0.001) were independent factors.

Conclusions: The serum post-CXCL10 level was independently related to survival in HCV-associated LC patients.

Background: The incidence of gastric cancer among younger patients is increasing globally, with growing attention being paid to the role of homologous recombination deficiency (HRD). However, the effect of HRD on treatment outcomes and prognosis in this population remains unclear.

Methods: We analyzed clinical and genomic data from the Center for Cancer Genomics and Advanced Therapeutics database. Younger patients (≤ 39 years, n = 140) were compared with older patients (≥ 65 years, n = 1118) diagnosed with gastric cancer. This study focused on mutations in homologous recombination repair (HRR) genes and their association with tumor mutation burden (TMB), microsatellite instability (MSI), and treatment outcomes.

Results: In older patients, HRD was associated with higher TMB and microsatellite instability-high (MSI-H) status, whereas no such correlations were observed in younger patients. Notably, MSI-H status was not observed in the younger group. Younger patients with HRD had a significantly shorter time to treatment failure (TTF) and overall survival (OS) than those without HRD. Conversely, in older patients, there was no significant difference in TTF or OS based on HRD status.

Conclusion: HRR gene mutations influence genomic profiling, TMB, and MSI differently depending on the age of gastric cancer onset, suggesting potential effects on treatment efficacy and prognosis.

Background: Increasing evidence reveals that immune cells significantly contribute to metabolic dysfunction-associated steatotic liver disease (MASLD) progression. The patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M variant has been linked to hepatic inflammation and fibrosis; however, its role in immune cell infiltration and activation within the liver remains unclear.

Methods: Seventy patients with MASLD were prospectively enrolled. Genomic DNA was extracted from buccal swabs or liver biopsy samples, followed by single nucleotide polymorphism genotyping to determine the rs738409 SNP genotype at codon 148 of PNPLA3. Immunohistochemistry was conducted using CD3 and CD68 antibodies to quantify T cell and macrophage infiltration, respectively. Total RNA extracted from biopsy specimens was used for quantitative reverse transcription polymerase chain reaction to assess the expression of specific markers associated with immune cell activation.

Results: Among the 70 patients with MASLD, 34 had the GG genotype, whereas 21 and 15 had the GC and CC genotypes, respectively. The GG genotype group showed a higher proportion of advanced fibrosis (F3 or F4) than the GC + CC group (P = 0.051). GG genotype carriers exhibited significantly higher CD3⁺ and CD68⁺ cell counts in the periportal region than the GC/CC carriers (P < 0.05). The transcriptomic analysis revealed elevated expression of markers associated with chronic antigen stimulation and immune cell activation (CD8A, GZMB, CCL2, and TIMP1) in GG carriers compared with those of GC and CC (P < 0.05). Furthermore, correlations among various markers, including inflammatory, steatosis-associated, and fibrosis-associated markers, exhibited consistent positive correlations.

Conclusions: Our findings revealed that the PNPLA3 I148M variant and increased immune cell infiltration and activation were significantly correlated within the MASLD liver. Further studies are needed to elucidate the mechanistic links between this genetic variant and liver inflammation.

Background: Simple, accurate methods are required for diagnosing metabolic dysfunction-associated steatotic liver disease (MASLD). Although the fatty liver index (FLI) is a simple and useful biomarker for steatotic liver disease (SLD), its optimal cutoff values for diagnosing MASLD and MASLD with increased alcohol intake (MetALD) remain unclear.

Methods: This cross-sectional study included 2512 adults undergoing health checkups with abdominal ultrasonography (AUS) and vibration-controlled transient elastography (including control attenuation parameter [CAP]). We used CAP 268 dB/m as the cutoff for SLD diagnosis. We analyzed the diagnostic performance of FLI for MASLD and MetALD. Optimal cutoff values were determined using area under receiver operating characteristics curve (AUROC) and Youden index.

Results: Among 2512 individuals studied, 956 had SLD, including 648 with MASLD, 231 with MetALD, and 67 with alcohol-associated liver disease. The distribution of FLI values (< 30, 30-60, > 60) was 46%, 31%, and 23% in males and 83%, 12%, and 5%, in females. For MASLD, the AUROC and optimal FLI cutoff values were 0.786 and 26.7. When analyzing by sex, these values were 0.729 and 26.9 for males and 0.886 and 19.2 for females. For MetALD, the corresponding values were 0.835 and 34.5. When analyzing by sex, these values were 0.764 and 44.4 for males and 0.95and 30.8 for females. Diagnostic agreement rate between AUS and CAP was 78.3% in all, and 74.9% in males and 84.1% in females.

Conclusion: The optimal FLI cutoff for MetALD was higher than for MASLD, with noticeable sex differences observed.

Primary sclerosing cholangitis (PSC) is an idiopathic chronic cholestatic disease with a poor prognosis. As there were no specific biomarkers for diagnosing PSC, we developed diagnostic criteria in 2016 based on cholangiography and elevated biliary enzymes. Novel findings and knowledge have subsequently accumulated, and we now propose the 2024 diagnostic criteria, to overcome several limitations of the 2016 diagnostic criteria. The Intractable Hepato-Biliary Diseases Study Group in Japan of the Committee of Research on Measures for Intractable Diseases established a working group consisting of experts in PSC comprising gastroenterologists, endoscopists, hepatologists, liver-transplant surgeons, pediatric hepatologists, pathologists, and radiologists. This working group proposed the 2024 diagnostic criteria after several discussions and public hearings. There are additional diagnostic targets; small duct PSC, pediatric PSC, and PSC recurrence following liver transplantation differ from the 2016 diagnostic criteria, which were for diagnosing large duct PSC in adults. The 2024 diagnostic criteria facilitate the use of magnetic resonance cholangiography in addition to endoscopic retrograde cholangiography in imaging, and incorporate gamma-glutamyl transferase for evaluating cholestasis to diagnose pediatric patients. Furthermore, PSC recurrence following liver transplantation can be diagnosed based on a liver biopsy and characteristic biliary findings. We hope that the 2024 diagnostic criteria will help not only hepatologists treating adults but also general physicians, pediatric hepatologists, and liver-transplant surgeons who manage patients with various forms of PSC.

The underlying causes of irritable bowel syndrome (IBS) and functional dyspepsia (FD) have remained largely elusive, but emerging data suggest immune activation and loss of small intestinal homeostasis may explain a major subgroup. FD and IBS symptoms often overlap and may occur early in the post-prandial period, suggesting the origin of symptoms may be much higher in gastrointestinal tract than colon. There is strong evidence low-grade duodenal inflammation, comprising eosinophils and/or mast cells associated with increased permeability, is present at least in a major subset with FD and IBS. This hypothesis is further supported by evidence of circulating increased small intestinal homing T cells and altered duodenal microbiota. We hypothesize a major etiologic pathway whereby interaction of food with intestinal bacteria switches on small intestinal immune activation in FD and IBS leading to presentation of antigens to the mucosa. While the low FODMAP diet provides symptom relief in both IBS and FD, this diet notably also reduces common food protein antigens (e.g., wheat, milk, soy) and urinary histamine levels. The obvious but often overlooked fact that food ingestion usually requires the act of eating adds nuance to determining whether food components or eating itself induces symptoms and that both need to be considered in DGBI in clinical practice. The exciting observations about subtle inflammation in DGBIs offer hope for new diagnostic biomarkers, and if considered in the context of altered dietary patterns and validated against symptom responses, will pave the way for novel DGBI treatment options.

Background: The management and characteristics of ulcerative colitis (UC) have evolved over time. We aimed to clarify how changing clinical profiles and treatment options affect patient outcomes.

Methods: This retrospective multicenter study of 13 hospitals divided diagnostic era into six periods: Era 1 (before June 30, 1998) and five subsequent 5-year intervals, with Era 6 (July 1, 2018-June 30, 2023) representing the most recent period. We compared therapeutic trends and outcomes across diagnostic eras, including the risk of first systemic steroid, advanced therapy (ADT) use, colectomy, UC-associated neoplasia (UCAN), and extracolonic malignancies.

Results: We included 1,867 UC patients. The proportion of elderly onset cases was significantly higher in Eras 5-6 (13%) compared to Eras 1-4 (0%-8.1%). Aminosalicylate intolerance was significantly more frequent in Era 6 (10%) and was significantly associated with earlier systemic steroid and ADT use, though not with colectomy or UCAN. While prescribing patterns of conventional therapies remained unchanged, the preferred first-line ADT shifted from infliximab to vedolizumab in recent diagnostic years. The cumulative risk of colectomy and UCAN did not significantly differ between eras. However, the cumulative risk of extracolonic malignancy was significantly higher in recent diagnostic years and significantly associated with older age at diagnosis.

Conclusions: In the recent diagnostic era, the increase in elderly onset UC has been accompanied by a higher malignancy risk, favoring vedolizumab as first-line ADT, especially in elderly patients. Increased aminosalicylate intolerance has led to earlier initiation of systemic steroids and ADTs, which may contribute to improved outcomes.