Introduction

Patients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of chronic kidney disease (CKD).

Aims & Methods

This study aimed to investigate whether the degree of steatosis and fibrosis is associated with an increased risk of CKD in patients with diabetes mellitus (DM). Between January and August 2023, 324 patients with DM were enrolled in the study, after excluding those with viral hepatitis, cirrhosis, and any cancers. Patients provided written informed consent, underwent several clinical measurements, and provided past medical histories. Body weight (BW), body mass index (BMI), waist circumference (WC), laboratory variables including serum creatinine and estimated glomerular filtration rate {eGFR, 175 × Serum Cr^-1.154× age^-0.203 × 1.212 (if patient is black) × 0.742 (if female)}, presence of hypertension, and dyslipidemia were investigated. The degree of steatosis was estimated using the fatty liver index {FLI, (e^{(0.953×ln(triglyceride, TG)+0.139×BMI+0.718×ln(gamma-glutamyltrasnsferase, GGT)+0.053×WC-15.745)})/(1+ e^{(0.953×ln(TG)+0.139×BMI+0.718×ln(GGT)+0.053×WC-15.745)})×100}, hepatic steatosis index {HSI, 8x(alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ratio+BMI (+2, if female; +2, if diabetes mellitus)}, and controlled attenuation parameter (CAP by FibroScan^®). The degree of fibrosis was estimated using fibrosis-4 (FIB-4) index, NAFLD fibrosis score (NFS), and liver stiffness (LS by FibroScan^®). CKD was defined as eGFR less than 60 mL/min/1.73m².

Results

The mean age of the patients was 57±12 years, and 54.9% (n=178) were male. The mean CAP and LS values were 276±50 dB/m and 7.0±3.7 kPa, respectively. CAP values were correlated with BW (r=0.524, p<0.001), BMI (r=0.625, p<0.001), WC (r=0.592, p<0.001), FLI (r=0.637, p<0.001), and HSI (r=0.653, p<0.001). LS values were correlated with BW (r=0.364, p<0.001), BMI (r=0.531, p<0.001), WC (r=0.46, p<001), and FIB-4 (r=0.3, p<0.001), but not correlated with NFS. Twenty-nine (8.9%) patients had CKD, of whom 14 were male. Patients with CKD were older (mean age: 63±11 vs. 56±12 years, p=0.005) and had a higher prevalence of hypertension (79.3% vs. 49.8%, p=0.002) compared to those without CKD. AST (29±22 vs. 30±20 IU/L), ALT (36±39 vs. 37±27 IU/L), GGT (40±30 vs. 44±73 IU/L), and HbA₁C (7.3±1.3 vs. 7.3±1.4%) were not different between the two groups. The prevalence of dyslipidemia (75.9% vs. 63.4%), BW (73±15 vs. 72±15 kg), BMI (28±4 vs. 27±5 kg/m²), and WC (92±11 vs. 90±11 cm) were also not different between the two groups. CAP value (273±55 vs. 276±50 dB/m), FLI (49±29 vs. 48±29), and HSI (40±7 vs. 39±7) were not different between the two groups. LS value (7.0±2.2 vs. 7.0±3.8 kPa), NFS (-1.0±1.3 vs. -1.2±2.6), and FIB-4 (1.3±0.6 vs. 1.2±0.8) were also not different between the two groups. Multivariate logistic analysis revealed that age [odds ratio (OR): 1.047, 95% confidence interval (CI): 1.008-1.088, p=0.019] and hypertension (OR: 3.260, 95% CI: 1.274-8.339, p<0.014) were the independent risk factors for CKD.

Conclusion

The steatosis estimated by CAP and the fibrosis estimated by LS were not associated with the risk of CKD in patients with DM.

Introduction

Acute pancreatitis is a multifactorial condition which despite showing a mild disease course in the majority of patients can be associated with significant morbidity and occasional fatality. Until lately, aggressive fluid expansion has been an undisputed aspect about managing the early stages of acute pancreatitis. Evidence produced by recent studies including the WATERFALL trial [1] supports a more conservative approach of fluid resuscitation given the fact that patients face significantly higher odds of relevant fluid overload while experiencing no benefit of their underlying condition. However, owing to strict inclusion criteria, results obtained from the WATERFALL trial only apply to patients with non-severe pancreatitis.

Aims & Methods

This retrospective monocentric study is thought to shed light on fluid-related complications in pancreatitis patients with any degree of severity. Altogether, n = 129 patients with all-cause acute pancreatitis including moderately severe and severe courses were enrolled and divided into 3 groups based on their cumulative fluid administration within the first 24 hrs (restrictive: < 3 L, moderate: 3 – 6 L, aggressive: > 6 L). Vital sign records and laboratory values were reported at defined time points (baseline, t = 48 hrs, t = 7 days). Fluid replacement was guided by institutional protocols with an initial bolus of 10 ml/kg, followed by a high-volume infusion rate of 4 ml/kg/h (< 24 hrs). Clinical response to fluid administration was monitored by changes in mean arterial pressure (> 65 mmHg), urine output (> 0,5 ml/kg/h), hematocrit (< 44 %), and blood urea nitrogen (< 25 mg/dl) at t = 12 and 24 hrs, respectively.

Results

The majority of patients were allocated to the group of moderate fluid resuscitation (n = 76, 58,9 %). At baseline, patients did not differ in systemic disease severity as indicated by SIRS and SOFA scores. Compared with a restrictive and moderate fluid regime, a significantly higher proportion of patients with moderately severe or severe pancreatitis associated with an acute peripancreatic fluid collection had previously been administered > 6 L fluids (> 6 L: 17/33, 52 % vs. < 3 L: 2/20, 10 % and 3 – 6 L: 24/76, 32 % vs., p = 0,001). Patients receiving > 6 L fluids were significantly more likely to show at least one radiological feature of pulmonary fluid overload (> 6 L: 15/33, 45 % vs. < 3 L: 2/10, 10 % and 3 – 6 L: 16/76, 21 %, p = 0.006), be transferred to intensive care unit (> 6 L: 18/33, 55 % vs. < 3 L: 2/20, 10 % and 3 – 6 L: 21/76, 28 %, p = 0,002), and require extended in-patient care (8, 6 – 11 days vs. 6, 4 – 7 days and 6, 4 – 10 days, p = 0,025). In addition, within 72 hrs after admission these patients had a significantly lower Horovitz ratio compared with restrictive and moderate group (> 6 L: 285, 239 – 337 vs. < 3 L: 360, 319 – 360 and 3 – 6 L: 337, 304 – 390, respectively, p = 0,003). At t = 48 hrs, C-reactive protein levels were significantly higher in patients with > 6 L (> 6 L: 164, 74 – 260 mg/l vs. < 3 L: 58, 4 – 162 mg/l and 3 – 6 L: 95, 13 – 183 mg/l) while serum albumin levels were significantly decreased (> 6 L: 30, 27 – 32 g/l vs. 3 6 L: 34, 31 – 36.5 g/l and 36, 33,5 – 41,5 g/l, p = 0,001).

Conclusion

Besides conferring a significantly higher risk of pulmonary edema, excessive fluid replacement is significantly associated with moderately severe or severe disease courses of acute pancreatitis, prolonged hospitalization, and need for intensive care. Although the retrospective design does not allow conclusions on causal relationships, results imply that excessive fluid resuscitation not only increases the risk of iatrogenic fluid overload but may additionally aggravate pancreatic inflammation. Our data suggest that further investigation on the appropriate fluid management in patients with moderate and severe acute pancreatitis is required.

References

[1] de-Madaria E, Buxbaum JL, Maisonneuve P, García García de Paredes A, Zapater P, Guilabert L, Vaillo-Rocamora A, Rodríguez-Gandía MÁ, Donate-Ortega J, Lozada-Hernández EE, Collazo Moreno AJR, Lira-Aguilar A, Llovet LP, Mehta R, Tandel R, Navarro P, Sánchez-Pardo AM, Sánchez-Marin C, Cobreros M, Fernández-Cabrera I, Casals-Seoane F, Casas Deza D, Lauret-Braña E, Martí-Marqués E, Camacho-Montaño LM, Ubieto V, Ganuza M, Bolado F; ERICA Consortium. Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis. N Engl J Med. 2022 Sep 15;387(11):989-1000. doi: 10.1056/NEJMoa2202884. PMID: 36103415.

Disclosure

All authors confirm that they have no conflict of interest.

Introduction

The overall burden of B / D and C viral hepatitis remains substantial, despite the major advances in the prevention and treatment of patients in recent years, due to comorbidities and complications associated with liver disease. In this context, the national screening program LIVE (RO) 2 aims to further assess all patients identified as positive for one of the hepatitis B / D / C viruses.

Aims & Methods

The study aimed to identify fortuitous pathologies discovered in patients with chronic viral B / D / C infection diagnosed in the LIVE (RO) screening program 2. We conducted a prospective study that included people from vulnerable groups (poor, uninsured, rural people, people in foster care, homeless, Roma population, people with disabilities, and suffering from alcohol or drug addiction) in different areas of North-Eastern Romania, between July 2021 - April 2023, during the national screening program LIVE (RO) 2-EAST. We also investigated the presence of newly discovered conditions in patients who tested positive and directed to the Institute of Gastroenterology and Hepatology in Iasi for the staging of liver disease and the establishment of antiviral treatment.

Results

The study group included 1176 patients, of which 422 men (35.8%) and 754 women (64.1%), aged between 35 and 83 years, with a mean age of 56.32 years. The predominant source of origin was rural (73.1%). Of the patients with positive RDTs, 635 (53.9%) patients were detected with HBsAg, 521 (44.3%) patients with anti-HCV antibodies, and 20 (1.7%) patients with anti-HVD antibodies. Of these, 215 patients (18.2%) were diagnosed with a new pathology associated with B / D / C viral infection. The most common pathologies discovered incidentally were liver cirrhosis (94, 43.7%), liver cysts (35, 16.2%), liver hemangiomas (29, 13.4%), gallstones (24, 11.1%), type II diabetes mellitus (T2DM) (15, 6.9%), uterine fibroids (9, 4.1%), hepatocellular carcinoma (7, 3.2%), choledochal lithiasis (2, 0.9%). In addition, the presence of fortuitous pathologies was higher among patients with HBV infection than in those with HCV infection (65.3% vs. 42.1%, p = 0.012). Among the risk factors associated with hepatocellular carcinoma (HCC) are chronic alcohol consumption (43%, compared to 19% in the group of patients without HCC), and the association of T2DM in 3 patients (31%, compared to 10% in the group of patients with HCC).

Conclusion

Patients with chronic B / D / C viral infection had a high prevalence of incidentally detected comorbidities, which necessitates the need for public health policies in vulnerable groups to promote access to existing health services to reduce the future burden of chronic diseases but also secondary complications of chronic liver disease.

Introduction

Diabetes mellitus (DM) is a substantial risk factor for pancreatic cancer (PC). Concurrently, aspirin has been implicated to have chemopreventive effect against cancer of digestive system. However, studies regarding the effect of aspirin on mitigating PC risk among DM populations remain scant.

Aims & Methods

We aimed to examine whether regular use of aspirin was associated with a reduced risk of PC after adjusting for known risk factors among type 2 diabetes (T2D) patients.

This was a territory-wide, retrospective cohort study of newly diagnosed T2D patients between 2001 and 2015 in Hong Kong. Exclusion criteria included <18 years old, history of PC, pancreatic neuroendocrine tumor, serous cystadenoma, chronic or acute pancreatitis, and pancreatic cyst. The outcome of interest was pancreatic cancer. Adjusted hazard ratios (aHRs) for outcomes associated with aspirin use were calculated using multivariable Cox regression models. Aspirin use was treated as a time-varying covariates (≥180 days use at each yearly interval) in the analysis to address and minimize immortal-time bias.

Results

We identified 342,920 T2D patients (52.2% male, mean age: 58.8±11.6 years), including 43,634 (12.7%) aspirin users. During a mean follow-up of 11.1±4.2 years, 1,114 (0.3%) patients developed PC, with an incidence rate of 2.92 per 10,000 person-years. Aspirin use was associated with a reduced PC risk (HR 0.55, 95%CI 0.46-0.66). When compared with the reference group (never use), a lower risk was observed with increasing frequency, with the exception of daily use. In addition, longer durations of aspirin use were associated with a progressively lower PC risks (HR 0.83, 95%CI 0.71-0.96, for less than five years of use; HR 0.56, 95%CI 0.45-0.69, for five to ten years of use; and HR 0.27, 95%CI 0.20-0.36, for ten or more years of use. Both frequency and duration of aspirin use demonstrated statistically significant trends (P_trend <0.001) (Table 1).

Table 1. HRs and 95% CIs for the association between frequency and duration of aspirin use and risk of pancreatic cancer

Aspirin use	No. of patients (n=342,920)	No. of PC (n=1,114)	HR (95% CI)	P*	Ptrend*
Frequency Never user	219,674	736	ref	-	<0.001
<Monthly use	13,809	52	0.66 (0.50-0.88)	0.004
Monthly to <weekly use	13.274	44	0.59 (0.43-0.80)	<0.001
Weekly to <daily use	73,232	201	0.54 (0.46-0.63)	<0.001
Daily use	22,931	81	0.90 (0.69-1.16)	0.401
Duration (years) Never user	219,674	736	ref	-	<0.001
<5	54,029	223	0.83 (0.71-0.96)	0.015
5 - <10	40,003	99	0.56 (0.45-0.69)	<0.001
≥10	29,214	56	0.27 (0.20-0.36)	<0.001

*Cox proportional hazards model was used to calculate the P values. Adjusted covariates included age, sex, lifestyle factors (body mass index, smoking, and alcohol use), metabolic disorders (dyslipidemia and hypertension), time-weighted mean HbA1c, DM complications, cardiovascular diseases, other anti-diabetic medications, non-aspirin non-steroidal anti-inflammatory drugs, and statins.
Abbreviation: CI, confidence interval; HR, hazard ratios; PC, pancreatic cancer; ref, reference

Conclusion

Aspirin use was associated with a reduction in PC risk among T2D patients, which was dependent on both frequency and duration of use. Notably, this trend was observed with increased frequency of use, with the exception of daily use. Further studies are warranted to assess long-term effects and potential risks.

Introduction

Hepatitis C has an important global impact in terms of morbidity, mortality and economic costs, being a real public health problem worldwide. The efficacy of the new direct-acting antivirals treatment determined the World Health Organization (WHO) to adopt the ambitious strategy for Global Health Sector on Viral Hepatitis in 2016, having as main objective to eliminate hepatitis C virus (HCV) by 2030. In response to this challenge, several countries have already initiated the micro-elimination strategy as part of the global C virus eradication program.

Aims & Methods

We aimed to evaluate the prevalence of HCV infection and risk factors in a Romanian village population-based screening and link these data to the antiviral treatment.We conducted a prospective study from 1 March2022 to 28 February 2023, based on a strategy as part of a project designed to educate, screen, treat and eliminate HCV infection in all adults, in a village located in Northeastern Romania. All demographic data and risk factors for HCV infection were collected through a questionnaire.

Results

In total, 3507 subjects were invited to be screened by rapid diagnostic orientation tests. Overall, 2945 (84%) subjects were tested, out of whom 78 (2.64%) were found with positive HCV antibodies and were scheduled for further evaluation in tertiary center of gastroenterology/hepatology, in order to be linked to care. A number of 66 (85%) subjects presented for evaluation and 55 (83%) had HCV RNA detectable. Of these, 54 (98%) completed antiviral treatment and 53 (99%) obtained sustained virological response. The main risk factors associated with chronic HCV infection were family history of HCV (OR=2.23, 95%CI=1.37–3.5, p<0.0001), professional exposure to blood products (OR=0.25, 95%CI=0.11-0.53, p<0.0001), blood transfusions performed before 1992 (OR=3.21, 95%CI=2.25-4.52, p<0.0001), abortions undergone before 1990 (OR=1.35, 95%CI=1.02-1.9, p<0.023), multiple surgical interventions (OR=1.32, 95%CI=1.05-1.72, p<0.038) and sharing personal hygiene objects (OR=1.45, 95%CI=1.12-1.73, p<0.002).

Conclusion

The elimination of hepatitis C worldwide has become a reality, with higher chances of success if micro-elimination strategies based on mass screening are adopted. At the same time, sustained effort it required from all. The development of screening programs can facilitate the cascade of care from diagnosis to treatment of all patients and the achievement of WHO objectives.

Introduction

It is unknown how stent types relate to clinical outcomes of endoscopic ultrasound (EUS)-guided drainage of pancreatic pseudocysts. This multicenter retrospective study aimed to compare the clinical outcomes between a lumen-apposing metal stent (LAMS) and a plastic stent.

Aims & Methods

Among 357 patients with pancreatic fluid collections in a large multi-institutional WONDERFUL consortium, we included 123 patients who received EUS-guided drainage of a pancreatic pseudocyst (16 and 107 cases with LAMS and plastic stent(s), respectively). We examined clinical treatment success, procedure-related adverse events, and pseudocyst recurrence.

Results

There were no differences between the groups regarding demographics (e.g., age and sex) and disease characteristics (e.g., size, encapsulation status, and the timing of drainage in relation to the onset of acute pancreatitis). The clinical success rates were comparable between the LAMS and plastic stent groups (94% vs. 87%, respectively; P = 0.40). The stent types were not associated with the time to clinical success (median, 25 days vs. 22 days for the LAMS and plastic stent groups, respectively; P = 0.56), the overall rate of procedure-related adverse events (0% vs. 5.6%, P = 0.33), or the rate of recurrence following clinical success (6.7% vs. 17%, P = 0.19).

Conclusion

In patients receiving EUS-guided drainage of pancreatic pseudocysts, clinical outcomes appeared to be comparable between the LAMS and plastic stent groups. If validated, our findings would support the feasibility of plastic stents in this patient population, which is a more cost-effective treatment modality than LAMSs. We, the WONDERFUL study group, have launched a randomized non-inferiority trial of plastic stents compared to a LAMS in this setting (NCT#06133023).

Disclosure

H.I. declares research funding from Boston Scientific Japan, Fujifilm, and Piolax Medical Devices; and honoraria from Boston Scientific Japan, Century Medical, Create Medic, Fujifilm, Gadelius Medical, Hitachi Medical, Japan Lifeline, Kaneka, Kawasumi Laboratories, Olympus Medical, Piolax Medical Devices, Sumitomo Bakelite, UMIDAS, and Zeon Medical; and contributions from Boston Scientific Japan, Gadelius Medical, Japan Lifeline, and Zeon Medical. Y.N. is an editorial board member of Digestive Endoscopy and declares research funding from Boston Scientific Japan, Century Medical, Fujifilm, Gadelius Medical, HOYA Pentax Medical, Hitachi Medical, Kaneka, and Medico’s Hirata; and honoraria from Boston Scientific Japan, Fujifilm, Gadelius Medical, Hitachi Medical, J-MIT, Medico’s Hirata, and Olympus Medical. This work was not supported by any of those companies. The other authors declare no conflicts of interest related to this article.

Introduction

The complex biology of pancreatic ductal adenocarcinoma (PDAC) remains a significant challenge and limits overcoming its dismal prognosis. The tumor microenvironment (TME), shaped by dynamic interactions between cancer-associated fibroblasts (CAFs), immune and tumor cells, plays a crucial role in PDAC pathogenesis. Our investigation into homologous recombination deficiency (HRD), caused by mutations in genes like ATM, revealed its role in promoting PDAC aggressiveness and triggering a pronounced desmoplastic reaction, suggesting a unique TME programing. We have shown that the loss of ATM in the neoplastic epithelium reprograms CAFs through the TGFβ signaling to promote cancer aggressiveness. Additionally, preliminary data revealed distinct immune profiles in ATM-deficient and proficient tumors.

Aims & Methods

To capture the immune profiles of ATM-deficient PDACs, and decipher specific oncogenic tumor–stroma interactions, we first conducted single cell-resolved multiomics analyses of murine ATM and/or P53-depleted PDACs. Histopathological analyses and validation using publicly available human datasets were performed to further characterize ATM loss-specific immune patterns in pancreatic cancer.

Results

Mouse tumor analyses, using single-nucleus multiomics RNA/ATAC sequencing and multiplex immunostainings, revealed alterations in immune cell contents, e.g. reduced macrophage populations and reduced M2 polarization in ATM-deficient tumors. ATM loss-specific immune molecular signatures were further investigated and correlated with human PDAC RNA sequencing data (TCGA, PanCancer Atlas). Molecular signatures and cell-cell communication inference revealed ATM-specific tumor–TME interactions and identified the TGFβ signaling as a core driver of the interplay between CAFs, immune cells, and a particularly aggressive EMT-like tumor cell subpopulation overrepresented in ATM-depleted tumors. Strikingly, we also observed distinct communication patterns between CAFs and immune cells. Finally, a combinatorial therapy targeting the TGFβ-driven tumor–stroma dialog reversed the cancer-promoting TME remodeling and exacerbated the therapeutic response to FOLFIRINOX in vivo, exclusively in ATM-deficient HRD PDACs.

Conclusion

Through single cell-resolved multiomics analyses of ATM-deficient PDACs, and validation in human cases, we unveil transcriptional, translational, and secretory regulatory events, shed light on the intricate interplay between tumor genetics and PDAC microenvironment, and pave the way for the elaboration of novel personalized therapies.