Mortality following elective and emergency colectomy in patients with cirrhosis: a population-based cohort study from England

Background Patients with cirrhosis undergoing colectomy have a higher risk of postoperative mortality, but contemporary estimates are lacking and data on associated risk and longer term outcomes are limited. This study aimed to quantify the risk of mortality following colectomy by urgency of surgery and stage of cirrhosis. Data sources. Linked primary and secondary-care electronic healthcare data from England were used to identify all patients undergoing colectomy from January 2001 to December 2017. These patients were classified by the absence or presence of cirrhosis and severity. Case fatality rates at 90 days and 1 year were calculated, and cox regression was used to estimate the hazard ratio of postoperative mortality controlling for age, gender and co-morbidity. Results Of the total, 36,380 patients undergoing colectomy, 248 (0.7%) had liver cirrhosis, and 70% of those had compensated cirrhosis. Following elective colectomy, 90-day case fatality was 4% in those without cirrhosis, 7% in compensated cirrhosis and 10% in decompensated cirrhosis. Following emergency colectomy, 90-day case fatality was higher; it was 16% in those without cirrhosis, 35% in compensated cirrhosis and 41% in decompensated cirrhosis. This corresponded to an adjusted 2.57 fold (95% CI 1.75–3.76) and 3.43 fold (95% CI 2.02–5.83) increased mortality risk in those with compensated and decompensated cirrhosis, respectively. This higher case fatality in patients with cirrhosis persisted at 1 year. Conclusion Patients with cirrhosis undergoing emergency colectomy have a higher mortality risk than those undergoing elective colectomy both at 90 days and 1 year. The greatest mortality risk at 90 days was in those with decompensation undergoing emergency surgery.

O2 Mortality following elective and emergency colorectal surgery in patients with cirrhosis: a population-based cohort study

Introduction This population based cohort study, aimed to quantify the risk of mortality following colectomy in patients with cirrhosis by urgency of surgery and stage of cirrhosis. Method Linked primary and secondary-care electronic healthcare data from England was used to identify all patients undergoing colectomy from January 2001 to December 2017. Patients were classified into three cohorts, non-cirrhotics, compensated cirrhotics and decompensated cirrhosis and followed up for 90-days from the date of surgery. Cox proportional hazards models were used to estimate the hazard ratio (HR) of postoperative mortality. Result A total of 36380 eligible patients were included. Of these, 248(0.7%) had liver cirrhosis and 70% had compensated disease. The proportion undergoing a colectomy who had a diagnosis of cirrhosis increased from 0.40% in 2001 to 1.07% in 2017 (χ2(16, N = 36380)=50.53, P < 0.0001). Following elective colectomy, 90-day case fatality was 4% in non-cirrhotics , 7% in compensated cirrhotics and 10% in decompensated cirrhotics. Following emergency colectomy 90-day case fatality was higher, it was 16% in non-cirrhotics, 35% in compensated cirrhotics and 41% in decompensated cirrhotics. This corresponded to an adjusted 2-fold (HR 2.57(95% CI 1.75–3.76)) and 3-fold (3.43(95% CI 2.02–5.83)) increased mortality rate in compensated and decompensated cirrhotics respectively compared to non-cirrhotics following emergency colectomy. Conclusion Over the study period, the proportion of patients undergoing colectomy who had liver cirrhosis increased to 1 in every 100 colectomies. The 90-day case fatality rates were high in all patients with cirrhosis in both emergency and elective settings but the greatest mortality risk was seen in those with decompensation following emergency surgery. Take-home Message 1 in 100 colectomy procedures are in patients with cirrhosis. These cirrhotic patients have a very high risk of postoperative mortality, especially, emergency colectomy in patients with decompensated cirrhosis.

P302 Serum IL-6 is associated with treatment refractoriness in acute severe ulcerative colitis

Background Response to therapy in acute severe ulcerative colitis (ASUC) is highly variable ranging from steroid response to salvage therapy failure and emergency colectomy. Biomarkers that accurately predict outcomes in ASUC early in the admission may help improve its management. We aimed to ascertain whether peripheral serum cytokine levels on admission correlate with refractoriness to medical therapy. Methods Peripheral blood was collected from 34 subjects, including 29 patients with ASUC on admission (baseline) and 5 healthy controls. All patients with ASUC received intravenous steroids, with those refractory to steroids going on to receive infliximab (IFX) salvage. Eight cytokines were measured at baseline using a multiplexed cytokine assay (Bio-Rad). Clinical response to steroids and/or to the first IFX dose was assessed and used to classify patients based on increasing order of disease refractoriness (steroid-responders, IFX-responders and IFX non-responders). These groups were then evaluated to check for correlations with baseline cytokine levels. Results Our cohort consisted of steroid responders (n=9), IFX responders (n=12) and IFX non-responders (n=8). Median serum IL-6 level was 1.6 pg/mL (IQR:1.6-2.1) in healthy controls compared to 2.7 pg/mL (IQR:1.4-6.3) in ASUC (p=0.3). In patients with ASUC, there was a positive correlation between IL-6 and treatment refractoriness (Spearman’s correlation [rs]=0.56, p=0.002). Compared with steroid responders (1.36 pg/mL), serum IL-6 was significantly higher in both IFX responders and IFX non-responders (3.44 and 5.50 pg/mL, p=0.02 and p=0.009 respectively) (Fig 1). Patients with ASUC had higher serum IL-8 compared to healthy controls (17.8 vs 6.9 pg/mL, p=0.005). There was no correlation between IL-8 levels and ASUC treatment refractoriness (rs=0.22, p=0.3). Similarly, there was no difference in IL-8 levels in ASUC patients when classified by treatment response (Kruskal Wallis, p=0.5). Serum TNF level did not differ between healthy controls and patients with ASUC (19.5 and 22.2pg/mL, p=0.5). TNF levels did not correlate with treatment refractoriness in ASUC (rs=-0.06, p=0.75) and there were no differences between the ASUC response groups (p=0.6). Levels of GM-CSF, IFN-g, IL-2, IL-4 and IL-10 were predominantly below the detection limit of each assay. Conclusion In this ASUC cohort, serum IL-6 level on admission correlated with treatment refractoriness and may help identify patients at higher risk of requiring salvage therapy as well as those at higher risk of failing IFX. Further studies are needed to elucidate the function of IL-6 in ASUC and whether it may represent a potential predictor of outcomes in ASUC.

How to manage: acute severe colitis

Acute severe ulcerative colitis (ASUC) is a medical emergency which is associated with significant morbidity and a mortality rate of 1%. ASUC requires prompt recognition and treatment. Optimal management includes admission to a specialist gastrointestinal unit and joint management with colorectal surgeons. Patients need to be screened for concomitant infections and thromboprophylaxis should be administered to mitigate against the elevated risk of thromboembolism. Corticosteroids are still the preferred initial medical therapy but approximately 30%–40% of patients fail steroid therapy and require rescue medical therapy with either infliximab or cyclosporine. Emergency colectomy is required in a timely manner for patients who fail rescue medical therapy to minimise the risk of adverse post-operative outcomes. We discuss current and emerging evidence in the management of ASUC and outline management approaches for clinicians involved in managing ASUC.

Tofacitinib in Treatment-Refractory Moderate to Severe Ulcerative Colitis: Real-World Experience from a Retrospective Multicenter Observational Study

(1) Background: Tofacitinib is approved in Europe for the treatment of adults with moderately to severely active ulcerative colitis since 2018. Real-world efficacy and safety data are currently scarce. (2) Methods: We performed a retrospective multicenter study at three German tertiary outpatient clinics for inflammatory bowel diseases and included all patients who started tofacitinib therapy between August 2018 and March 2020. The primary endpoint was a combined endpoint of steroid-free clinical remission, steroid-free clinical response, or clinical response at week 8. Secondary endpoints were biochemical response at week 8, as well as steroid-free clinical remission, steroid-free clinical response or clinical response at week 24, respectively, adverse events by week 24, and need for colectomy by the end of follow-up. (3) Results: Thirty-eight patients with moderate-to-severe ulcerative colitis were included. Eleven patients (28.9%) achieved steroid-free clinical remission at week 8. Fifty-three percent of the patients were primary non-responders at week 8. Three severe adverse events (pneumonia, hospitalization for aggravation of ulcerative colitis, emergency colectomy due to colon perforation), and 12 adverse events were documented by week 8 of therapy. By the end of follow-up, seven patients (18.4%) had undergone colectomy.