Introduction

Irritable bowel syndrome (IBS) is among the most prevalent gastrointestinal conditions. However, its therapeutic management poses challenges, with many current recommendations resting on a low level of evidence.

Aims & Methods

Our objective is to conduct a systematic review with meta-analysis of randomized, double-blind, placebo-controlled trials to assess the efficacy of antidepressants in treating IBS. ​
Systematic review with meta-analysis performed according to PRISMA guidelines and registered on the PROSPERO platform (CRD42024502427). PubMed, EMBASE, and The Cochrane Library platforms were searched from inception to January 2024. Only randomized, double-blind, placebo-controlled trials, conducted in patients with IBS patients, with a minimum treatment period of 4 weeks, were included. The quality of evidence was assessed using the revised version of the Cochrane tool (RoB 2). A random-effects model was used. Heterogeneity was assessed by the I² statistics. Funnel plots and the Egger test were used to assess publication bias. Statistical analysis was performed using STATA v16.

Results

The search strategy identified 1340 studies, of which 16 were included, totaling 1428 patients. Among these studies, 733 patients were assigned to the antidepressant group and 698 to the placebo group. In the intervention group, 405 (55.3%) patients reported improvement, compared to only 227 (32.5%) patients in the placebo group. The meta-analysis showed that the use of antidepressants in patients with IBS provides a benefit in overall symptom improvement (OR=3.02; 95% CI 2.16-4.2) compared to placebo.
A subgroup analysis of 9 studies, comprising 1008 patients, assessed the efficacy of tricyclic antidepressants (TCAs) in the same setting and revealed similar results (OR=3.39, 95% CI 2.24-5.12), as did the sub-analysis of 6 studies (including 363 patients) evaluating the efficacy of selective serotonin reuptake inhibitors (SSRIs) (OR= OR=2.39, 95% CI 1.14-5.01). The efficacy also extends to patients refractory to first-line measures (6 studies including 713 patients) (OR=2.96, 95% CI 1.67-5.25) and to patients without psychopathology (8 studies including 471 patients) (OR=2.92, 95% CI 1.6-5.31). Concerning symptoms, a sub analysis also confirmed the efficacy of antidepressants specifically both in the improvement of abdominal pain (OR=4.33, 95% CI 2.1-8.93) and in abdominal distension (OR=2.68, 95% CI 1.42-5.04).
Only in the sub-analysis assessing the efficacy of SSRIs and of the improvement of abdominal pain, I² was slightly >60%, indicating substantial heterogeneity, but <75%. Causes of heterogeneity were searched. Publication bias was detected, and potential sources were identified. Sub-analysis without the studies identified as sources of this bias revealed similar results with lower heterogeneity.

Conclusion

Antidepressants, including both TCAs and SSRIs, demonstrate efficacy in patients with IBS, presenting a validated treatment option supported by evidence. Moreover, these medications can be beneficial to patients resistant to initial treatments and those lacking psychopathological symptoms.

References

Drossman DA, Tack J, Ford AC, Szigethy E, Törnblom H, Van Oudenhove L. Neuromodulators for Functional Gastrointestinal Disorders (Disorders of Gut−Brain Interaction): A Rome Foundation Working Team Report. Gastroenterology 2018;154:1140-1171.e1. https://doi.org/10.1053/j.gastro.2017.11.279.
Lacy BE, Pimentel M, Brenner DM, Chey WD, Keefer LA, Long MD, et al. ACG Clinical Guideline: Management of Irritable Bowel Syndrome. Am J Gastroenterol 2021;116:17–44. https://doi.org/10.14309/ajg.0000000000001036.
Lovell RM, Ford AC. Global Prevalence of and Risk Factors for Irritable Bowel Syndrome: A Meta-analysis. Clin Gastroenterol Hepatol 2012;10:712-721.e4. https://doi.org/10.1016/j.cgh.2012.02.029.
Vasant DH, Paine PA, Black CJ, Houghton LA, Everitt HA, Corsetti M, et al. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut 2021;70:1214–40. https://doi.org/10.1136/gutjnl-2021-324598.

Disclosure

FP received speaker fees from Abbvie, Falk, Ferring, Janssen, Pfizer, Pharmakern, Takeda and Tillotts. The other authors have no conflict of interest.

Introduction

Hepatitis E virus (HEV) infection in Europe is predominantly due to zoonotic genotype 3, transmitted via undercooked pork, game or shellfish (1,2). In the Helsinki and Uusimaa Hospital District (HUS), 70 laboratory-confirmed cases occurred from 2020–2024, with a pronounced peak in early 2024 (3). Seroprevalence in high-income countries ranges from ~6 % to > 50 %, increasing with age and swine exposure (1,2). While most infections are asymptomatic or mild, patients with underlying liver diseases may have more severe outcomes. Diagnosis relies on anti-HEV IgM/IgG serology and PCR detection of viral RNA (4).

Aims & Methods

Objective of this study is to investigate the epidemiology of hepatitis E virus (HEV), its clinical manifestations, and factors associated with hospitalization in the Helsinki University Hospital (HUS) area between 2020 and 2024. We conducted a retrospective registry study including all patients diagnosed with hepatitis E in the HUS area from January 2020 to December 2024. Data were collected from the electronic health record system, the laboratory database, and the shared contact-tracing software of the HUS Epidemiology Unit and Uusimaa welfare regions. Variables analyzed comprised demographic data, symptoms at presentation, key laboratory parameters (ALT, bilirubin, C-reactive protein), probable sources of infection, and details of hospitalization episodes.

Results

Study population: 70 patients (median age 58 years [IQR 45–67]; 58.6 % male).
Clinical manifestations: 92.2 % were symptomatic. The most frequent symptoms were fatigue (55.9 %), abdominal pain (47.5 %), nausea (45.8 %), and jaundice (42.6 %).
Laboratory findings: Median peak ALT was 1 153 U/L (IQR 544–1 538); median peak bilirubin 39 μmol/L (IQR 17–79); median peak CRP 22 mg/L (IQR 11–32).
Genotypes: Of 19 genotyped cases, 3c (21.1 %), 3e (21.1 %), and 3f (57.9 %), with genotype 3f predominant.
Infection sources: Cold-smoked sausages (e.g., mettwurst) were implicated in most domestic cases (69.6 % of identified sources), especially during the early 2024 outbreak. Other identified sources were unspecified meat products (6.5 %), berries (6.5 %), contact with wild animals (e.g., hunting, 4.3 %), blood transfusion (4.3 %), pork meat (4.3%), and game meat (4.3%).
Hospitalization: 50.7 % required ≥1 night of inpatient care. Hospitalized patients were older, had higher ALT, bilirubin, and CRP values, and more comorbidities than outpatients.
Predictors of hospital stay: In a multivariable zero-inflated negative binomial model, higher peak CRP was independently associated with longer hospital stay (β = 0.02; p = 0.005).

Conclusion

The early-2024 surge of HEV cases in the HUS area represents an internationally rare, large genotype 3 outbreak. Cold-smoked meat products were identified as the principal transmission route, although infections linked to blood transfusions, consumption of raw berries, and wildlife contact also occurred. Cases were disproportionately concentrated in men over 50 years of age. Among hospitalized patients, peak CRP emerged as the strongest predictor of inpatient care, and both mortality and incidence of hepatic insufficiency were relatively high given high sanitation standards in Finland. Further multicenter, inter-regional studies are needed to establish statistically robust risk factors for severe outcomes and to guide clinical and public health interventions.

References

1. Luo Q, Chen J, Zhang Y, Xu W, Liu Y, Xie C, ym. Viral hepatitis E: Clinical manifestations, treatment, and prevention. Liver Res. maaliskuuta 2024;8(1):11–21.
2. Hartl J, Otto B, Madden RG, Webb G, Woolson KL, Kriston L, ym. Hepatitis E Seroprevalence in Europe: A Meta-Analysis. Viruses. 6. elokuuta 2016;8(8):211.
3. THL. Terveyden ja hyvinvoinnin laitos. 2024 [referenced: 13. lokakuuta 2024]. Hepatiitti E-tapausten esiintyvyys Suomessa – THL. Available: https://thl.fi/aiheet/infektiotaudit-ja-rokotukset/taudit-ja-torjunta/taudit-ja-taudinaiheuttajat-a-o/hepatiitti-e/hepatiitti-e-tapausten-esiintyvyys-suomessa
4. Dalton HR, Kamar N, Baylis SA, Moradpour D, Wedemeyer H, Negro F. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol. kesäkuuta 2018;68(6):1256–71.

Introduction

Chronic intestinal pseudo-obstruction (CIPO) is a rare, heterogeneous, and challenging gastrointestinal motility disorder lacking clinical guidelines in adults.

Aims & Methods

We aimed to develop an international consensus among international experts in gut motility on the diagnosis and management of CIPO based on existing literature and expert opinion. Two experts from each continental motility society and experts on pathology, surgery, and nutritional aspects of CIPO were selected for participation. A list of >130 statements was drafted, subdivided into 11 topics. After revisions and validation by the experts of the list of statements, a systematic literature review was performed to summarize available data on every statement. Using a Delphi process of 3 voting rounds, consensus statements were identified (defined as >80% agreement).

Results

Consensus was reached for 77/139 statements. The panel defined CIPO as symptoms caused by severe small bowel dysmotility without mechanical obstruction, and with documented dilated intestine or air/fluid levels, mimicking mechanical obstruction. Pseudo-obstructive episodes or continuous pseudo-obstructive symptoms were considered a cardinal feature of CIPO. Abdominal pain, bloating, and distension were also considered cardinal symptoms, while nausea/vomiting, diarrhea, or constipation were considered associated symptoms.
Radiographic imaging was considered mandatory in the diagnostic work-up, to confirm intestinal dilation or air/fluid levels and to rule out mechanical obstruction.. No other diagnostic test was considered indispensable for the diagnosis, including endoscopy, manometry, or laparoscopy. Screening for secondary causes of CIPO, including systemic sclerosis, paraneoplastic disease, or infectious disease, was supported, with a possible role for transmural histology. Differential diagnoses, including drug adverse effects, adhesions, or enteric radiation, should be ruled out. The experts also recommended screening for complications such as nutritional deficiencies and osteoporosis.
Management requires dietary adjustment, with supplementation for deficiencies, and setting up home parenteral nutrition if enteral nutrition fails. Small intestinal bacterial overgrowth was recognized as a main contributor to symptom aggravation and should be treated by intermittent antibiotics without the need for breath testing confirmation in patients with CIPO. There was no consensus regarding choice or efficacy of drug therapy, including prokinetics (e.g. pyridostigmine, prucalopride), laxatives, or somatostatin analogs. Opioids and surgical resections should be avoided; although endoscopic or surgical decompression procedures may be helpful in acute or persisting pseudo-obstructive symptoms.

Conclusion

This expert consensus developed key statements for the definition, diagnosis, and treatment of CIPO in adult patients. It provides the opportunity to harmonize the management of these patients and to highlight the gaps in the current literature.

Disclosure

Jan Tack has given Scientific advice to Aclipse, Adare, AlfaSigma, Clasado, Danone, Falk, FitForMe, Ironwood, Kyowa Kirin, Menarini, Promed, Ricordati, Takeda, Truvion, Tsumura, Zealand Pharmaceuticals, has received research support from Biohit, Kiowa Kirin, ProMed, Sofar and Takeda, and has served on the Speaker bureau for Abbott, Bio-Codex, Mayoly, Menarini, ProMed, Reckitt-Benckiser, Schwabe, Takeda, Thai Meiji and Truvion Pharmaceuticals.