Abstracts

Falk Gastro-Info 7/2021

Dunkel- bis hellblaue Grafik einer Tonspur-Frequenz auf orangem Hintergund.

Intestine

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Pregnancy and neonatal outcomes after fetal exposure to biologics and thiopurines among women with inflammatory bowel disease: Results of a prospective cohort study suggest that biologic, thiopurine or combination therapy exposure during pregnancy was not associated with increased adverse maternal or fetal outcomes at birth or infections in the first year of life. Higher disease activity was associated with risk of spontaneous abortion and preterm birth.

Gastroenterology. 2021;160(4):1131–9

Mahadevan U, Long MD, Kane SV, Roy A, Dubinsky MC, Sands BE, Cohen RD, Chambers CD, Sandborn WJ; Crohn’s Colitis Foundation Clinical Research Alliance

Pregnancy and neonatal outcomes after fetal exposure to biologics and thiopurines among women with inflammatory bowel disease

Background and aims: Pregnant women with inflammatory bowel disease (IBD) may require biologic or thiopurine therapy to control disease activity. Lack of safety data has led to therapy discontinuation during pregnancy, with health repercussions to mother and child.
Methods: Between 2007 and 2019, pregnant women with IBD were enrolled in a prospective, observational, multicenter study across the United States. The primary analysis was a comparison of 5 outcomes (congenital malformations, spontaneous abortions, preterm birth, low birth weight, and infant infections) among pregnancies exposed versus unexposed in utero to biologics, thiopurines, or a combination. Bivariate analyses followed by logistic regression models adjusted for relevant confounders were used to determine the independent effects of specific drug classes on outcomes of interest.
Results: Among 1490 completed pregnancies, there were 1431 live births. One-year infant outcomes were available in 1010. Exposure was to thiopurines (n = 242), biologics (n = 642), or both (n = 227) versus unexposed (n = 379). Drug exposure did not increase the rate of congenital malformations, spontaneous abortions, preterm birth, low birth weight, and infections during the first year of life. Higher disease activity was associated with risk of spontaneous abortion (hazard ratio = 3.41; 95% confidence interval [CI]: 1.51–7.69) and preterm birth with increased infant infection (odds ratio = 1.73; 95% CI: 1.19–2.51).

Conclusions: Biologic, thiopurine, or combination therapy exposure during pregnancy was not associated with increased adverse maternal or fetal outcomes at birth or in the first year of life. Therapy with these agents can be continued throughout pregnancy in women with inflammatory bowel disease to maintain disease control and reduce pregnancy-related adverse events.

U. Mahadevan, M.D., Division of Gastroenterology and Hepatology, University of California San Francisco, 1701 Divisadero Street #120, San Francisco, CA 94115, USA

E-Mail: uma.mahadevan@ucsf.edu

 

 

Risk for colorectal cancer among first-degree relatives of patients with colorectal polyps: Results of a nationwide population-based analysis from Sweden reveal that first-degree relatives of patients with colorectal polyps are still at higher risk of colorectal carcinoma and in particular early onset cancer, even after adjusting for family history of colorectal cancer.

BMJ. 2021;373:n877

Song M, Emilsson L, Roelstraete B, Ludvigsson JF

Risk of colorectal cancer in first-degree relatives of patients with colorectal polyps: Nationwide case-control study in Sweden

Objective: To assess the risk of colorectal cancer (CRC) in first-degree relatives (parents and full siblings) of patients with precursor lesions (polyps) for CRC.
Design: Case-control study.
Setting: Linkage to the multigeneration register and gastrointestinal ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) histopathology cohort in Sweden.
Participants: 68,060 patients with CRC and 333,753 matched controls.
Main outcome measures: Multivariable adjusted odds ratios (ORs) of CRC according to the number of first-degree relatives with a colorectal polyp and the histology of polyps and age at diagnosis in first-degree relatives. Subgroup analysis was also performed according to age at CRC diagnosis and evaluated the joint association of family history of colorectal polyps and family history of CRC.
Results: After adjusting for family history of CRC and other covariates, having a first-degree relative with a colorectal polyp (8.4% [5742/68,060] in cases and 5.7% [18,860/333,753] in controls) was associated with a higher risk of CRC (OR = 1.40, 95% confidence interval [CI]: 1.35–1.45). The ORs ranged from 1.23 for those with hyperplastic polyps to 1.44 for those with tubulovillous adenomas. To better put this risk in perspective, the age-specific absolute risk of colon and rectal cancers was estimated according to family history of polyps based on the 2018 national CRC incidence in Sweden. For example, the absolute risk of colon cancer in individuals aged 60–64 years with and without a family history of colorectal polyp was, respectively, 94.3 and 67.9 per 100,000 for men and 89.1 and 64.1 per 100,000 for women. The association between family history of polyps and CRC risk was strengthened by the increasing number of first-degree relatives with polyps (≥ 2 first-degree relatives: OR = 1.70, 95% CI: 1.52–1.90; p < 0.001 for trend) and decreasing age at polyp diagnosis (< 50 years: OR = 1.77, 95% CI: 1.57–1.99; p < 0.001 for trend). A particularly strong association was found for early-onset CRC diagnosed before age 50 years (≥ 2 first-degree relatives: OR = 3.34, 95% CI: 2.05–5.43; p = 0.002 for heterogeneity by age of CRC diagnosis). In the joint analysis, the OR of CRC for individuals with ≥ 2 first-degree relatives with polyps but no CRC was 1.79 (95% CI: 1.52–2.10), with 1 first-degree relative with CRC but no polyps was 1.70 (95% CI: 1.65–1.76), and with ≥ 2 first-degree relatives with both polyps and CRC was 5.00 (95% CI: 3.77–6.63; p < 0.001 for interaction).

Conclusions: After adjusting for family history of colorectal cancer (CRC), the siblings and children of patients with colorectal polyps are still at higher risk of CRC, particularly early-onset CRC. Early screening for CRC might be considered for first-degree relatives of patients with polyps.

Prof. Dr. J.F. Ludvigsson, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, 171 77 Stockholm, Sweden

E-Mail: jonas.ludvigsson@ki.se

 

 

Disease course, mortality and risk for colorectal cancer in patients with microsopic colitis (MC): Results from a nationwide population-based study from Denmark reveal that most MC patients have an uncomplicated and self-limited disease course. Only patients with severe colitis have a moderately elevated mortality while the risk for colorectal cancer is rather reduced.

J Crohns Colitis. 2021;15(4):594–602

Weimers P, Vedel Ankersen D, Lophaven S, Bonderup OK, Münch A, Leth Løkkegaard EC, Munkholm P, Burisch J

Disease activity patterns, mortality, and colorectal cancer risk in microscopic colitis: A Danish nationwide cohort study, 2001–2016

Background and aims: The disease course of microscopic colitis (MC), encompassing collagenous colitis (CC) and lymphocytic colitis (LC), is not well known. In a Danish nationwide cohort, the authors evaluated the disease activity patterns as well as the risk of colorectal cancer (CRC) and mortality based on disease severity.
Methods: All incident MC patients (n = 14,302) with a recorded diagnosis of CC (n = 8437) or LC (n = 5865) in the Danish Pathology Register, entered between 2001 and 2016, were matched to 10 reference individuals (n = 142,481). Incident cases of CRC after the index date were captured from the Danish Cancer Registry. Mortality data were ascertained from the Danish Registry of Causes of Death, and information about treatment was obtained from the Danish National Prescription Registry. The risk of CRC and mortality analyses were investigated by Cox regression and Kaplan-Meier estimates.
Results: A self-limiting or transient disease course was identified in 70.6% of LC patients and in 59.9% of CC patients (p < 0.001). Less than 5% of MC patients experienced a budesonide-refractory disease course and were treated with immunomodulators or biologic treatment. A total of 2926 (20.5%) MC patients and 24,632 (17.3%) reference individuals died during the study period. MC patients with a severe disease had a relative risk (RR) of mortality of 1.41 (95% confidence interval [CI]: 1.32–1.50) compared with reference individuals. Only 90 MC patients were diagnosed with CRC during follow-up, corresponding to an RR of 0.48 (95% CI: 0.39–0.60).

Conclusions: A majority of microscopic colitis patients experience an indolent disease course with a lower risk of developing colorectal cancer compared with the background population.

Dr. P. Weimers, Department of Gastroenterology, North Zealand University Hospital, Frederikssundsvej 30, 3600 Frederikssund, Denmark

E-Mail: malin.petra.ulfsdotter.weimers.01@regionh.dk


Liver/Bile

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Chronic hepatitis E virus infection: A current systematic review and meta-analysis on the therapy of chronic hepatitis E virus infection demonstrates that a reduction of immunosuppressive medication and treatment with ribavirin are safe, generally well tolerated and in 32% and 78% of patients, respectively, induce virus elimination. Treatment with pegylated interferon-alpha, in contrast, increases the risk of transplant rejection and should therefore be administered with great caution.

J Viral Hepat. 2021;28(3):454–63

Gorris M, van der Lecq BM, van Erpecum KJ, de Bruijne J

Treatment for chronic hepatitis E virus infection: A systematic review and meta-analysis

Hepatitis E virus infection can cause chronic hepatitis in immunocompromised patients with significant chance of progressive fibrosis and possibly cirrhosis. The aim of this systematic review was to summarize the efficacy and safety of the various treatment options for chronic hepatitis E. The authors performed a systematic literature search. The primary outcome measure was a sustained virological response (SVR). Secondary end points were rapid virological response (RVR), relapse rates, side effects and adverse events. 44 articles were included with a total of 582 patients. Reduction of immunosuppressive medication induced viral clearance in 55 of the 174 patients (32%). Meta-analysis of 395 patients showed a pooled SVR rate of 78% (95% confidence interval [CI]: 72–84%) after ribavirin treatment. 25% of the patients obtained a RVR, whereas a relapse occurred in 18% of the patients. Anemia during treatment led to dose reduction, use of erythropoietin and/or blood transfusion in 37% of the patients. A second treatment attempt with ribavirin led to a SVR in 39 of the 51 patients (76%). Pegylated interferon-α was administered to 13 patients and SVR was obtained in 85%. Two patients (15%) suffered from acute transplant rejection during treatment with interferon.

In conclusion, reduction of immunosuppressive medication and treatment with ribavirin is safe, generally well tolerated and induced viral clearance in 32% and 78% of patients, respectively. Therefore, ribavirin should be considered as first treatment step for chronic hepatitis E. Treatment with pegylated interferon-α increases the risk of transplant rejection and should therefore be administered with great caution.

M. Gorris, Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Meibergdreef 9, 1055 AZ Amsterdam, The Netherlands

E-Mail: m.gorris@amsterdamumc.nl

 

 

Non-alcoholic fatty liver disease (NAFLD) and acute on chronic liver failure (ACLF): NAFLD is the fastest rising etiology of cirrhosis associated with ACLF among patients listed in the United States. As the NAFLD population continues to grow and age, patients with NAFLD-ACLF will likely have the highest risk of waitlist mortality.

Hepatology. 2021;73(5):1932–44

Sundaram V, Jalan R, Shah P, Singal AK, Patel AA, Wu T, Noureddin M, Mahmud N, Wong RJ

Acute-on-chronic liver failure from non-alcoholic fatty liver disease: A growing and aging cohort with rising mortality

Background and aims: The authors assessed the burden of non-alcoholic fatty liver disease (NAFLD)-related acute-on-chronic liver failure (ACLF) among transplant candidates in the United States, along with waitlist outcomes for this population.
Approach and results: They analyzed the United Network for Organ Sharing registry from 2005 to 2017. Patients with ACLF were identified using the European Association for the Study of the Liver/Chronic Liver Failure criteria and categorized into NAFLD, alcohol-associated liver disease (ALD), and hepatitis C virus (HCV) infection. Linear regression and Chow's test were used to determine significance in trends and waitlist outcomes were evaluated using Fine and Gray's competing risks regression and Cox proportional hazards regression. Between 2005 and 2017, waitlist registrants for NAFLD-ACLF rose by 331.6% from 134 to 574 candidates (p < 0.001), representing the largest percentage increase in the study population. ALD-ACLF also increased by 206.3% (348–1066 registrants; p < 0.001), whereas HCV-ACLF declined by 45.2% (p < 0.001). As of 2017, the NAFLD-ACLF population consisted primarily of persons aged ≥ 60 years (54.1%), and linear regression demonstrated a significant rise in the proportion of patients aged ≥ 65 years in this group (β = 0.90; p = 0.011). Since 2014, NAFLD-ACLF grade 1 was associated with a greater risk of waitlist mortality relative to ALD-ACLF (subhazard ratio [SHR] = 1.24; 95% confidence interval [CI]: 1.05–1.44) and HCV-ACLF (SHR = 1.35; 95% CI: 1.08–1.71), among patients aged ≥ 60 years. Mortality was similar among the 3 groups for patients with ACLF grade 2 or 3.

Conclusions: Non-alcoholic fatty liver disease (NAFLD) is the fastest rising etiology of cirrhosis associated with acute-on-chronic liver failure (ACLF) among patients listed in the United States. As the NAFLD population continues to grow and age, patients with NAFLD-ACLF will likely have the highest risk of waitlist mortality.

V. Sundaram, M.D., Karsh Division of Gastroenterology and Hepatology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, 8900 Beverly Boulevard, Suite 250, Los Angeles, CA 09948, USA

E-Mail: vinay.sundaram@cshs.org

 

 

Acute severe autoimmune hepatitis (SA-AIH): A current retrospective multicenter study demonstrates that in AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of liver transplantation or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for liver transplantation. This score needs to be validated in a prospective cohort.

J Hepatol. 2021;74(6):1325–34

De Martin E, Coilly A, Chazouillères O, Roux O, Peron JM, Houssel-Debry P, Artru F, Silvain C, Ollivier-Hourmand I, Duvoux C, Heurgue A, Barge S, Ganne-Carrié N, Pageaux GP, Besch C, Bourlière M, Fontaine H, de Ledinghen V, Dumortier J, Conti F, Radenne S, Debette-Gratien M, Goria O, Durand F, Potier P, Di Martino V, Reboux N, Ichai P, Sebagh M, Mathurin P, Agostini H, Samuel D, Duclos-Vallée JC; FILFOIE consortium – France

Early liver transplantation for corticosteroid non-responders with acute severe autoimmune hepatitis: The SURFASA score

Background and aims: In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated.
Methods: This was a retrospective, multicenter study (2009–2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥ 1.5 and/or bilirubin > 200 μmol/l; iii) no previous history of AIH; iv) histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3–D0)/D0.
Results: A total of 128 patients were included, with a median age of 52 (39–62) years; 72% were female. Overall survival reached 88%. 115 patients (90%) received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] = 6.85, 95% confidence interval [CI]: 2.23–21.06; p < 0.001), Δ%3-INR ≥ 0.1% (OR = 6.97, 95% CI: 1.59–30.46; p < 0.01) and Δ%3-bilirubin ≥ -8% (OR = 5.14, 95% CI: 1.09–24.28; p < 0.04) were predictive of a non-response. The SURFASA (survival and prognostic factors for acute severe autoimmune hepatitis) score: -6.80+1.92∗(D0-INR)+1.94∗(Δ%3-INR)+1.64∗(Δ%3-bilirubin), created by combining these variables, was highly predictive of LT or death (area under the curve [AUC] 0.93) (88% specificity; 84% sensitivity) with a cut-off point of < -0.9. Below this cut-off, the chance of responding was 75%. With a score > 1.75, the risk of dying or being transplanted was between 85% and 100%.

Conclusion: In patients with acute severe autoimmune hepatitis (AS-AIH), international normalized ratio (INR) at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of liver transplantation (LT) or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort.

Dr. E. De Martin or Prof. Dr. J.-C. Duclos-Vallée, Centre Hépato-Biliaire, AP-HP, Hôpital Paul-Brousse, Inserm Unité 1193, Université Paris-Saclay, 12, avenue Paul Vaillant-Couturier, 94800 Villejuif, France

E-Mail: eleonora.demartin@aphp.fr

E-Mail: jean-charles.duclos-vallee@aphp.fr


Esophagus/Stomach/Duodenum

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Endoscopic radiofrequency ablation or surveillance in patients with Barrett’s esophagus with confirmed low-grade dysplasia: Radiofrequency ablation modestly reduced the prevalence of low-grade dysplasia as well as malignant progression risk at 3 years in a randomized multicenter trial involving 82 patients. The risk-benefit ratio of radiofrequency ablation should therefore be carefully weighted against surveillance in these patients.

Gut. 2021;70(6):1014–22

Barret M, Pioche M, Terris B, Ponchon T, Cholet F, Zerbib F, Chabrun E, Le Rhun M, Coron E, Giovannini M, Caillol F, Laugier R, Jacques J, Legros R, Boustiere C, Rahmi G, Metivier-Cesbron E, Vanbiervliet G, Bauret P, Escourrou J, Branche J, Jilet L, Abdoul H, Kaddour N, Leblanc S, Bensoussan M, Prat F, Chaussade S

Endoscopic radiofrequency ablation or surveillance in patients with Barrett's esophagus with confirmed low-grade dysplasia: A multicenter randomized trial

Objective: Due to an annual progression rate of Barrett's esophagus (BE) with low-grade dysplasia (LGD) between 9% and 13% per year endoscopic ablation therapy is preferred to surveillance. Since this recommendation is based on only 1 randomized trial, the authors aimed at checking these results by another multicenter randomized trial with a similar design.
Design: A prospective randomized study was performed in 14 centers comparing radiofrequency ablation (RFA) (maximum of 4 sessions) to annual endoscopic surveillance, including patients with a confirmed diagnosis of BE with LGD. Primary outcome was the prevalence of LGD at 3 years. Secondary outcomes were the prevalence of LGD at 1 year, the complete eradication of intestinal metaplasia (CE-IM) at 3 years, the rate of neoplastic progression at 3 years and the treatment-related morbidity.
Results: 125 patients were initially included, of whom 82 with confirmed LGD (76 men, mean age 62.3 years) were finally randomized, 40 patients in the RFA and 42 in the surveillance group. At 3 years, CE-IM rates were 35% versus 0% in the RFA and surveillance groups, respectively (p < 0.001). At the same time, the prevalence LGD was 34.3% (95% confidence interval [CI]: 18.6–50.0) in the RFA group versus 58.1% (95% CI: 40.7–75.4) in the surveillance group (odds ratio = 0.38; 95% CI: 0.14–1.02; p = 0.05). Neoplastic progression was found in 12.5% (RFA) versus 26.2% (surveillance; p = 0.15). The complication rate was maximal after the first RFA treatment (16.9%).

Conclusion: Radiofrequency ablation modestly reduced the prevalence of low-grade dysplasia (LGD) as well as progression risk at 3 years. The risk-benefit balance of endoscopic ablation therapy should therefore be carefully weighted against surveillance in patients with Barrett's esophagus with confirmed LGD.

Dr. M. Barret, Service de Gastroentérologie et Oncologie Digestive, Chirurgie Digestive Hépatobiliaire et Endocrinienne, Hôpital Cochin, AP-HP, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France

E-Mail: maximilien.barret@aphp.fr

 

 

Impact of metabolic-bariatric surgery on long-term survival: This meta-analysis involving more than 170.000 patients revealed that among adults with obesity, metabolic-bariatric surgery was associated with substantially lower all-cause mortality rates while life expectancy was increased by 9,3 years in patients with preexisting diabetes and 5,1 years in patients without diabetes.

Lancet. 2021;397(10287):1830–41

Syn NL, Cummings DE, Wang LZ, Lin DJ, Zhao JJ, Loh M, Koh ZJ, Chew CA, Loo YE, Tai BC, Kim G, So JB, Kaplan LM, Dixon JB, Shabbir A

Association of metabolic-bariatric surgery with long-term survival in adults with and without diabetes: A 1-stage meta-analysis of matched cohort and prospective controlled studies with 174,772 participants

Background: Metabolic-bariatric surgery delivers substantial weight loss and can induce remission or improvement of obesity-related risks and complications. However, more robust estimates of its effect on long-term mortality and life expectancy − especially stratified by pre-existing diabetes status − are needed to guide policy and facilitate patient counselling. The authors compared long-term survival outcomes of severely obese patients who received metabolic-bariatric surgery versus usual care.
Methods: They did a prespecified 1-stage meta-analysis using patient-level survival data reconstructed from prospective controlled trials and high-quality matched cohort studies. PubMed, Scopus, and Medline (via Ovid) were searched for randomized trials, prospective controlled studies, and matched cohort studies comparing all-cause mortality after metabolic-bariatric surgery versus non-surgical management of obesity published between inception and February 3, 2021. Also grey literature was searched by reviewing bibliographies of included studies as well as review articles. Shared-frailty (i.e., random-effects) and stratified Cox models were fitted to compare all-cause mortality of adults with obesity who underwent metabolic-bariatric surgery compared with matched controls who received usual care, taking into account clustering of participants at the study level. The authors also computed numbers needed to treat, and extrapolated life expectancy using Gompertz proportional-hazards modelling.
Findings: Among 1470 articles identified, 16 matched cohort studies and 1 prospective controlled trial were included in the analysis. 7712 deaths occurred during 1.2 million patient-years. In the overall population consisting 174,772 participants, metabolic-bariatric surgery was associated with a reduction in hazard rate of death of 49.2% (95% confidence interval [CI]: 46.3–51.9; p < 0.0001) and median life expectancy was 6.1 years (95% CI: 5.2–6.9) longer than usual care. In subgroup analyses, both individuals with (hazard ratio [HR] = 0.409, 95% CI: 0.370–0.453; p < 0.0001) or without (HR = 0.704, 95% CI: 0.588–0.843; p < 0.0001) baseline diabetes who underwent metabolic-bariatric surgery had lower rates of all-cause mortality, but the treatment effect was considerably greater for those with diabetes (between-subgroup I2 = 95.7%; p < 0.0001). Median life expectancy was 9.3 years (95% CI: 7.1–11.8) longer for patients with diabetes in the surgery group than the non-surgical group, whereas the life expectancy gain was 5.1 years (95% CI: 2.0–9.3) for patients without diabetes. The numbers needed to treat to prevent 1 additional death over a 10-year time frame were 8.4 (95% CI: 7.8–9.1) for adults with diabetes and 29.8 (95% CI: 21.2–56.8) for those without diabetes. Treatment effects did not appear to differ between gastric bypass, banding, and sleeve gastrectomy (I2 = 3.4%; p = 0.36). By leveraging the results of this meta-analysis and other published data, it was estimated that every 1.0% increase in metabolic-bariatric surgery utilization rates among the global pool of metabolic-bariatric candidates with and without diabetes could yield 5.1 million and 6.6 million potential life-years, respectively.

Interpretation: Among adults with obesity, metabolic-bariatric surgery is associated with substantially lower all-cause mortality rates and longer life expectancy than usual obesity management. Survival benefits are much more pronounced for people with pre-existing diabetes than those without.

Dr. A. Shabbir, Department of Surgery, University Surgical Cluster, National University Health System, Singapore 119228, Singapore

E-Mail: cfsasim@nus.edu.sg

 

 

Association between proton-pump inhibitor (PPI) therapy and diabetes: Results of prospective studies involving more than 200.000 participants reveal that regular use of PPIs was associated with a higher risk of type 2 diabetes and the risk increased with longer duration of use.

Gut. 2021;70(6):1070–7

Yuan J, He Q, Nguyen LH, Wong MCS, Huang J, Yu Y, Xia B, Tang Y, He Y, Zhang C

Regular use of proton-pump inhibitors and risk of type 2 diabetes: Results from 3 prospective cohort studies

Objective: The association between the regular use of proton-pump inhibitors (PPIs) and the risk of type 2 diabetes remains unclear, although a recent randomized controlled trial showed a trend towards increased risk. This study was undertaken to evaluate the regular use of PPIs and risk of type 2 diabetes.
Method: This is a prospective analysis of 204,689 participants free of diabetes in the Nurses' Health Study (NHS), NHS II and Health Professionals Follow-up Study (HPFS). Type 2 diabetes was confirmed using American Diabetes Association (ADA) diagnostic criteria. The authors evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, the presence of comorbidities, use of other medications and clinical indications.
Results: They documented 10,105 incident cases of diabetes over 2,127,471 person-years of follow-up. Regular PPI users had a 24% higher risk of diabetes than non-users (HR = 1.24, 95% confidence interval [CI]: 1.17–1.31). The risk of diabetes increased with duration of PPI use. Fully adjusted HRs were 1.05 (95% CI: 0.93–1.19) for participants who used PPIs for > 0–2 years and 1.26 (95% CI: 1.18–1.35) for participants who used PPIs for > 2 years compared with non-users.

Conclusions: Regular use of proton-pump inhibitors (PPIs) was associated with a higher risk of type 2 diabetes and the risk increased with longer duration of use. Physicians should therefore exercise caution when prescribing PPIs, particularly for long-term use.

Prof. Dr. C. Zhang oder Prof. Dr. Y. He, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China

E-Mail: zhchangh@mail.sysu.edu.cn

E-Mail: heyulong@mail.sysu.edu.cn


Pancreas

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Impact of SARS-CoV-2 infection on disease outcomes in patients with acute pancreatitis: Patients with acute pancreatitis and coexisting SARS-CoV-2 infection were at increased risk of severe pancreatitis disease course, worse clinical outcomes, prolonged hospital stay and high 30-day mortality in a prospective multicenter cohort study.

Gut. 2021;70(6):1061–9

Pandanaboyana S, Moir J, Leeds JS, Oppong K, Kanwar A, Marzouk A, Belgaumkar A, Gupta A, Siriwardena AK, Haque AR, Awan A, Balakrishnan A, Rawashdeh A, Ivanov B, Parmar C, Halloran CM, Caruana C, Borg CM, Gomez D, Damaskos D, Karavias D, Finch G, Ebied H, Pine JK, Skipworth JRA, Milburn J, Latif J, Ratnam Apollos J, El Kafsi J, Windsor JA, Roberts K, Wang K, Ravi K, Coats MV, Hollyman M, Phillips M, Okocha M, Wilson MSJ, Ameer NA, Kumar N, Shah N, Lapolla P, Magee C, Al-Sarireh B, Lunevicius R, Benhmida R, Singhal R, Balachandra S, Demirli Atıcı S, Jaunoo S, Dwerryhouse S, Boyce T, Charalampakis V, Kanakala V, Abbas Z, Nayar M; COVID PAN collaborative group

SARS-CoV-2 infection in acute pancreatitis increases disease severity and 30-day mortality: COVID PAN collaborative study

Objective: There is emerging evidence that the pancreas may be a target organ of SARS-CoV-2 infection. The aim of this study was to investigate the outcome of patients with acute pancreatitis (AP) and coexistent SARS-CoV-2 infection.
Design: A prospective international multicenter cohort study including consecutive patients admitted with AP during the current pandemic was undertaken. Primary outcome measure was severity of AP. Secondary outcome measures were etiology of AP, intensive care unit (ICU) admission, length of hospital stay, local complications, acute respiratory distress syndrome (ARDS), persistent organ failure and 30-day mortality. Multilevel logistic regression was used to compare the 2 groups.
Results: 1777 patients with AP were included during the study period from March 1 to July 23, 2020. 149 patients (8.3%) had concomitant SARS-CoV-2 infection. Overall, SARS-CoV-2-positive patients were older male patients and more likely to develop severe AP and ARDS (p < 0.001). Unadjusted analysis showed that SARS-CoV-2-positive patients with AP were more likely to require ICU admission (odds ratio [OR] = 5.21; p < 0.001), local complications (OR = 2.91; p < 0.001), persistent organ failure (OR = 7.32; p < 0.001), prolonged hospital stay (OR = 1.89; p < 0.001) and a higher 30-day mortality (OR = 6.56; p < 0.001). Adjusted analysis showed length of stay (OR = 1.32; p < 0.001), persistent organ failure (OR = 2.77; p < 0.003) and 30-day mortality (OR = 2.41; p < 0.04) were significantly higher in SARS-CoV-2 coinfection.

Conclusion: Patients with acute pancreatitis (AP) and coexistent SARS-CoV-2 infection are at increased risk of severe AP, worse clinical outcomes, prolonged length of hospital stay and high 30-day mortality.

Dr. M. Nayar, HPB Unit, Freeman Hospital, Freeman Road, High Heaton, Newcastle upon Tyne NE7 7DN, UK

E-Mail: manu.nayar@nhs.net