Introduction

HBeAg-negative chronic hepatitis B virus (HBV) infection (inactive carriers) is defined by: Normal ALT levels, minimal Fibrosis and/or low necrotic-inflammatory activity assessed by Fibroscan/Liver Biopsy and a Viral load (VL) <2000 ui/ml. An increase in VL in inactive carriers remains common.

Aims & Methods

The objective of our study is to determine the importance of regular VL monitoring in untreated inactive carriers with VL fluctuations between 2000 and 20000 ui/ml, and to evaluate the effectiveness of antiviral treatment.
This is a prospective, descriptive study conducted from 2018 to 2023, covering a 5-year period. The study involved all patients who were monitored in our gastroenterology department for chronic hepatitis B virus infection with negative Hbe Ag, and whose viral load (VL) fluctuated between 2000 and 20000ui/ml without cytolysis or worsening of fibrosis, and without any underlying cause identified.
Patients who had hepatitis D virus superinfection, those who were scheduled for immunosuppressive treatment, and pregnant patients were excluded from the study.

Results

A total of 64 patients with HBeAg-negative chronic HBV infection were followed up, median age was 47 years with extremes of 20 - 75 years and a sex ratio M /F of 1.
Initially, all patients were provided with a monitoring control. During the follow-up period, 21 patients showed an increase in VL, ranging from 2000 to 20000 ui /ml. These patients were divided into 2 groups: The 1st group representing 28.5% of the patients (n = 6) were treated with nucleotide analogues (Tenofovir 300mg/day), while the 2nd group represents 71.4% of the patients (n =15) remained under monitoring alone.
During 2 year follow-up, 83% of patients in the first group (n=5) achieved a negative VL, while only one patient had a decrease in VL after antiviral treatment. None of these patients showed seroconversion.
In the 2nd group, the VL remained fluctuating without exceeding 20000ui/ml and there was no evidence of clinical worsening or abnormal liver function tests during the follow up period.

Conclusion

Increased VL in inactive carriers is far from rare; there is no clear consensus on the required monitoring. However, the results of our study suggest that antiviral treatment may be effective in suppressing viral replication. These results also highlight the importance of close monitoring of VL in untreated patients. Despite the promising results of our study, it is essential to conduct a larger and more comprehensive study to further validate and confirm our findings.

Introduction

The PAN-PROMISE symptom score is the first patient-reported outcome (PROM) in acute pancreatitis (AP), and it was developed and validated in a prospective cohort of patients to be used as an endpoint in research. The aim of this study was to assess the performance of the score in a large randomized controlled trial (RCT) and its association with well-established AP endpoints.

Aims & Methods

This is an ancillary study of the WATERFALL trial, where PAN-PROMISE was evaluated at baseline, 24, 48 and 72 hours. The study examined the association between PAN-PROMISE with stablished endpoints in AP: severity, pancreatic and/or peripancreatic fat necrosis (necrosis), infected necrosis, intensive care unit (ICU) admission, persistent organ failure (POF), prolonged hospital stay and mortality. Areas under the ROC curve (AUC) were calculated and used to compare baseline PAN-PROMISE and baseline Bedside Index for Severity in AP (BISAP) for the prediction of these endpoints.

Results

248 patients from the WATERFALL trial were included. A statistically significant association was found between PAN-PROMISE and severity, necrosis, POF, ICU admission, and prolonged hospital stay at all checkpoints (p<0.05). Higher scores were also significantly associated with infected pancreatic necrosis at 24, 48, and 72h and death at baseline and 24 hours. PAN-PROMISE baseline score had a higher AUC than BISAP for severity and necrosis, but the results were not statistically significant.

Conclusion

In the context of a RCT, the PAN-PROMISE score, a patient-centered measure, has been validated with established AP outcomes and as an endpoint for future clinical trials.

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

Chronic pancreatitis (CP) is a progressive inflammatory disorder currently diagnosed by morphologic features. In contrast, an accurate diagnosis of early CP (ECP) is not possible using imaging criteria alone. Therefore, specific biomarkers are needed to assist ECP diagnosis. Metabolomics and its branch lipidomics are ‘omic’ disciplines that present a close association between metabolites and phenotype.

Aims & Methods

The aim of this study is to evaluate potential metabolic differences between patients with ECP and two control groups, CP and healthy controls (HC), determining the metabolome of human serum and PJ in ECP, as well as possible phenotypical biomarkers of these EPC patients using UHPLC-MS.
Thirty-three patients were included: 11 healthy controls (HC), 12 ECP and 10 CP, according to Rosemont criteria (0-2, 3-4 or ≥5, respectively; CAEIG 2018/537). PJ samples were obtained through endoscopic pancreatic function test and serum samples were obtained just before the previously mentioned test. Separate UHPLC-MS platforms were used:
1) fatty acyls, bile acids, steroids and lysoglycerophospholipids;
2) glycerolipids, glycerophospholipids, sterol lipids and sphingolipids, and
3) amino acids. Multivariate (principal components analysis, PCA) and univariate (log2FC) data analysis were performed. Significant differences were assessed using the Student’s t-test or Wilcoxon-Mann-Whitney test. Three levels of significance were considered (p < 0.05, 0.01, and 0.001).

Results

The most remarkable differences in PJ samples were found in several oxidized fatty acids (oxFA), which were increased in ECP. Besides, the analysis of serum samples showed:
1) levels of several amino acids were increased in ECP/CP when compared to HC;
2) oxFA were increased in ECP when compared to HC; and
3) levels of several ether-linked lysophosphatidylcholines (ether-LPC) and ether-linked lysophosphatidylethanolamines (ether-LPE) were reduced in ECP.

Conclusion

Our results showed alterations in circulating levels of some amino acids in ECP/CP; indeed, these alterations are known to modulate pancreatic function. Lipid metabolism dysregulation in cells with CP suggests that changes in blood lipidome could contribute to the development of pancreatic cancer. In line with this, circulating levels of some ether-LPC were significantly decreased in ECP. Oxidative stress is intimately related to the pathogenesis of CP. The increment in circulating levels of oxFA in ECP was also confirmed in PJ. Subsequently, measuring the levels of oxidized fatty acids could be a useful biomarker for the disease in both serum and PJ samples.

Disclosure

Julio Iglesias-Garcia. Advisor Fujifilm

Introduction

Pancreatic cancer (PC) are associated with notably poor prognoses.The clinical practice guidelines for PC list several risk factors of PC, including diabetes among them. Diabetic patients, who regularly visit the hospital, present a practical opportunity for pancreatic surveillance. Effective surveillance for PC could be achieved by identifying diabetic patients at high-risk for PC who already require regular hospital visits. Nevertheless, there is a notable lack of research on pancreatic cancer risk factors within the diabetic population.

Aims & Methods

This study aimed to identify risk factors for pancreatic cancer in diabetic patients using a longitudinal cohort from the Shizuoka Kokuho database, spanning April 2012 to September 2021. Diabetic patients were identified and monitored for the onset of pancreatic cancer. Factors analyzed included age, sex, the Elixhauser comorbidity index, and specific comorbidities. Statistical analyses involved univariate and multivariate Cox proportional hazards regression.

Results

The Shizuoka Kokuho database, which comprises 2,654,567 individuals, identified 212,775 as diabetic patients. Of these patients, 1,755 developed pancreatic cancer during the observation period, which had a median duration of 5.1 years and a maximum of 8.5 years. The annual incidence rate of pancreatic cancer in this group was 166.7 cases per 100,000 person-years [95% CI: 158.9–174.5].
Identified candidate risk factors included older age, male sex, coexisting liver disease, cardiac arrhythmias, hypertension, chronic pancreatitis, and pancreatic cystic lesions, each with p-values below 0.05. These variables were subsequently incorporated into a multivariate model.
The multivariable regression results indicated that older age and male gender were associated with an increased risk of pancreatic cancer (HR: 1.267 [95% CI: 1.150–1.395]). Liver disease emerged as a notable risk factor (HR: 1.13 [95% CI: 1.01–1.26]). Significant correlations were found between the onset of PC and both chronic pancreatitis (HR: 1.98 [95% CI: 1.48–2.64]) and pancreatic cystic disease (HR: 4.79 [95% CI: 3.43–6.67]). Neither the type of diabetes nor the presence of diabetic comorbidities was associated with the onset of PC.

Conclusion

This cohort study has identified key risk factors for pancreatic cancer in diabetic patients. Findings indicate that advanced age, male sex, a history of liver disease, chronic pancreatitis, and pancreatic cystic lesions significantly increase the risk of pancreatic cancer in this population. These insights underscore the importance of targeted surveillance for early detection of pancreatic cancer in diabetic patients, particularly those with these risk factors.

Introduction

Over the last two decades, there has been a rise in the diagnosis of Branch Duct Intraductal Papillary Mucinous Neoplasms (BD-IPMN), incidental findings posing potential neoplastic risks. Multiple guidelines, notably the International Association of Pancreatology (IAP)' revised in Fukuoka in 2017, have been suggested to optimize risk management. However, the intricate nature of these guidelines makes adherence challenging, raising uncertainties regarding their application in clinical practice.

Aims & Methods

This study aimed to assess adherence to the 2017 IAP guidelines, identify factors associated with non-compliance, and analyze the impact of divergent strategies on clinical outcomes and costs. Clinical and histopathological data from 2017 to 2023 were retrospectively collected from four tertiary centers in Northern Italy, focusing on patients with suspected BD-IPMN. Multivariate logistic regressions were employed to analyze factors influencing divergent strategies from the IAP guidelines and assess their consequences on clinical outcomes, survival, and costs. Surveillance strategies were considered aggressive if deviating to a narrower surveillance timing or indicating higher-level examinations than recommended by the IAP guidelines. Conservative approach was defined as suggesting extended surveillance timing or indicating lower-level examinations than specified by the IAP.

Results

Of the 333 enrolled patients with a total of 1400 visits and a median follow-up of 4 years, 54% received recommendations deviating from the guidelines, predominantly in an aggressive direction (53.7%). Protective factors for deviation were an Age-adjusted Charlson Comorbidity Index (ACCI) above 4 (OR 0.44, 95% CI 0.33-0.58, p < 0.001) and larger initial IPMN size (OR 0.22, 95% CI 0.17-0.28, p < 0.001), while divergent approach increased by 25% every two years of follow-up (OR 1.25, 95% CI 1.11-1.41, p < 0.001). Conservative divergences, occurring in 25% of cases, were associated with the presence of High-Risk Stigmata (HRS) (OR 5.79, 95% CI 1.82-18.50, p = 0.003) and female gender (OR 1.55, 95% CI 1.25-2.04, p = 0.001). Notably, divergent strategies did not lead to different rates of IPMN-related mortality (2.5% vs 2.4%, p = 1). However, they resulted in increased surveillance costs, escalating from 720 [407-1253] to 878 [664-1181] euros per patient over three years (p = 0.001).

Conclusion

In conclusion, adherence to the IAP guidelines in clinical practice was low, predominantly exhibiting deviations in an aggressive direction. This non-adherence significantly increased costs compared to those projected by following the recommended guidelines.