Background: The effect of analgesic modalities on short‐term outcomes in acute pancreatitis remains unknown. However, preclinical models have raised safety concerns regarding opioid use in patients with acute pancreatitis.Objective: This study aimed to assess the association between analgesics, particularly opioids, and severity and mortality in hospitalised patients with acute pancreatitis.Methods: This prospective multicentre cohort study recruited consecutive patients admitted with a first episode of acute pancreatitis between April 1 and 30 June 2022, with a 1‐month follow‐up. Data on aetiology, clinical course, and analgesic treatment were collected. The primary outcome was the association between opioid analgesia and acute pancreatitis severity, which was analysed using univariate and multivariate analyses.Results: Among a total of 1768 patients, included from 118 centres across 27 countries, 1036 (59%) had opioids administered on admission day, and 167 (9%) received opioids after admission day. On univariate analysis, moderately severe or severe acute pancreatitis was associated with male sex, Asian ethnicity, alcohol aetiology, comorbidity, predicted severe acute pancreatitis, higher pain scores, longer pain duration and opioid treatment (all p < 0.001). On multivariate analysis, comorbidity, alcohol aetiology, longer pain duration and higher pain scores increased the risk of moderately severe or severe acute pancreatitis (all p < 0.001). Furthermore, opioids administered after admission day (but not on admission day) doubled the risk of moderately severe or severe disease (OR 2.07 (95% CI, 1.29–3.33); p = 0.003). Opioid treatment for 6 days or more was an independent risk factor for moderately severe or severe acute pancreatitis (OR 3.21 (95% CI, 2.16–4.79; p < 0.001). On univariate analysis, longer opioid duration was associated with mortality.Conclusion: Opioid treatment increased the risk of more severe acute pancreatitis only when administered after admission day or for 6 days or more. Future randomised studies should re‐evaluate whether opioids might be safe in acute pancreatitis.

Soluble CD 163 (sCD163) is released from activated liver macrophages in chronic viral hepatitis C (HCV) and serum levels reflect liver disease severity. The impact of direct-acting antiviral (DAA)-therapy on sCD163-levels and the ability of sCD163 to predict the presence of liver fibrosis remain unclear. In a combined observational and prospective study, we aimed to investigate changes in sCD163 with DAA-treatment, to investigate associations between sCD163 and histopathological activity and fibrosis and to validate the sCD163-based fibrosis score in HCV-patients. We examined three groups of patients: an Australian (n = 28) treated with pegylated-interferon and a first-generation DAA, a Danish (n = 38) treated with sofosbuvir-based DAA-regimens and a Japanese (n = 562) assessed for activity and fibrosis (Metavir scoring system) in liver biopsies. Serum sCD163-levels were quantified by ELISA. Thirteen (46%) of the Australian patients achieved sustained virological response (SVR) and only these patients had significant decreases in sCD163-levels (2.7 (95%CI:1.9-3.6) vs. 4.1(2.9-5.7) mg L - 1, p = .008). In the Danish group, 37 (97%) patients achieved SVR at 12-weeks post-treatment with 32% reduction in sCD163-levels (5.0 (4.3-5.8) vs. 7.4 (6.3-8.7), p < .001). The decline was rapid and persisted 12 months after treatment cessation (p < .007). sCD163 levels increased in parallel with inflammatory activity and fibrosis (p < .001). The sCD163-based fibrosis score outperformed established fibrosis scores for significant fibrosis (areas under the receiver operating characteristics curves (AUROCs): 0.79 (0.75-0.83) vs. aspartate aminotransferase to platelet ratio index (APRI) 0.73 (0.69-0.77), Fibrosis-4 (FIB-4) 0.74 (0.70-0.78), p < .001). sCD163-levels decline rapidly with successful DAA therapy and are associated with histological inflammatory activity and fibrosis, confirming a key role for macrophages in HCV inflammation and fibrosis and supporting sCD163 as a biomarker of treatment response.

Background: Since there is no current international consensus on the optimal approach for pain management in acute pancreatitis (AP), analgesic practices may vary across different healthcare settings. Objective: This study explored global disparities in analgesic use, in particular opioids, during admission and at discharge in hospitalised AP patients. Methods: This was a post hoc analysis of the prospective PAINAP database, which included all admissions for AP between April and June 2022 with a 1‐month follow‐up. Demographic details, analgesic use, and clinical outcomes were recorded during admission and at discharge. Odds ratios (ORs) for opioid use during admission and at discharge were identified using multivariable regression analyses. Results: Amongst the 1864 patients (52% males, median age 56 (interquartile range, 41–71)) across three different continents, simple analgesics were predominantly used as the primary analgesic (70%). Opioid use during admission was lowest in European centres (67%). Admission in Asian (OR, 2.53 (95% confidence interval (CI), 1.59–4.04), p < 0.001), and Australian (OR, 5.81 (95% CI, 3.19–10.56), p < 0.001) centres was associated with opioid administration during admission compared with European centres. Increased pain severity, longer pre‐admission pain duration, organ failure, and longer length of admission increased opioid use during admission. At discharge, Asian (OR, 2.01 (95% CI, 1.40–2.88), p < 0.001) and Australian (OR, 1.91 (95% CI, 1.28–2.85), p = 0.002) centres were associated with opioid prescription compared with European centres. Increased pain severity, longer pre‐admission pain duration, acute necrotic collections, and walled‐off necrosis also increased the likelihood of opioid prescription at discharge. Conclusion: There are substantial intercontinental differences in opioid use for AP pain. Accordingly, there is a need for international guidelines on pain management in AP.

Purpose: Abdominal pain is common in patients with chronic pancreatitis (CP), but management is challenging – possibly due to altered pain processing within the central nervous system rendering conventional treatments ineffective. We hypothesized that many patients with painful CP have generalized hyperalgesia correlating with central neuronal hyperexcitability. Patients and Methods: Seventeen CP patients with pain and 20 matched healthy controls underwent experimental pain testing, including repeated pain stimuli (temporal summation), pressure algometry performed in dermatomes with same spinal innervation as the pancreatic gland (pancreatic areas) and remote dermatomes (control areas), a cold pressor test and a conditioned pain modulation paradigm. To probe central neuronal excitability, the nociceptive withdrawal reflex was elicited by electrical stimulation of the plantar skin, and electromyography was obtained from the ipsilateral anterior tibial muscle together with somatosensory evoked brain potentials. Results: Compared to healthy controls, patients with painful CP had generalized hyperalgesia as evidenced by 45% lower pressure pain detection thresholds (P< 0.05) and decreased cold pressor endurance time (120 vs 180 seconds, P< 0.001). In patients, reflex thresholds were lower (14 vs 23 mA, P=0.02), and electromyographic responses were increased (16.4 vs 9.7, P=0.04) during the withdrawal reflex, reflecting predominantly spinal hyperexcitability. Evoked brain potentials did not differ between groups. A positive correlation was found between reflex thresholds and cold pressor endurance time (ρ=0.71, P=0.004). Conclusion: We demonstrated somatic hyperalgesia in patients with painful CP associated with spinal hyperexcitability. This highlights that management should be directed at central mechanisms using, eg, gabapentinoids or serotonin-noradrenaline reuptake inhibitors.