Introduction

Faecal incontinence (FI) is a common problem, affecting about 9% of Western populations. However, only a few patients seek consultation and the number of such patients reaching hospital care is unknown. Current treatment pathways are poorly evidence based and are thought to vary greatly between different countries.

Aims & Methods

Background: The aim of this study was to evaluate the incidence of fecal incontinence (FI) in patients attending colorectal clinics in a global setting, treatment choices and accessibility to diagnostic and treatment tools.

Methods: An international, multi-center snapshot audit was performed in an 8-week period between January 9, 2023 and March 28, 2023. All eligible cross-sectional data was recorded. Data was entered and saved in a REDCap secured database. Two physician- and center-level surveys were filled for current practice evaluation.

Results

1,813 outpatients with FI from 110 hospitals, from 35 countries were included in this audit. Majority of patients with FI were females, parous, and in age range 50-70. Patients most commonly waited 1 to 3 years until seen in outpatient clinic. Etiology skewed toward anal injury and rectal prolapse. Stress incontinence was diagnosed more common than urge incontinence (36% vs 23% respectively). Majority of patients received previous treatment (n=222 (61%)), which mostly included pelvic floor physiotherapy (n=149), bowel retraining with biofeedback (n=114), and nurse-led continence support (n=90). Sacral nerve stimulation was the most commonly performed procedure (n=114/395) for FI in outpatient clinics, followed by sphincterocplastty (n=87/395). Endoanal ultrasound (n=206/1,226) as well as anorectal manometry (n=185/1,1226) are the basic diagnostic tools used to diagnose FI in outpatient settings. More than a half (56%) of clincs have access to pelvic floor MDT. The majority of physicians offer surgical treatment (colostomy or sphincter repair) for FI.

Conclusion

Patients FI wait 1-3 years until attending colorectal clinics. Anal injury and rectal prolapse are the main causes of FI. FI treatment consists of conservative and surgical treatment, and there has not been a single best treatment option.

Clinical Case Summary

A 29-year-old woman with an uncontrolled type 1 diabetes, hypothyroidism and cocaine use presented to the emergency department for evaluation of abdominal pain, nausea and vomiting. Her vital signs included temperature 36,3°C; heart rate 99 bpm; respiratory rate 16 pm and blood pressure 92/58 mmHg. Physical examination was notable for a thin, anicteric woman who was not in acute distress. The abdomen was nondistended and soft with diffusely tenderness and a smooth palpable liver 3 to 4 cm below the costal margin.
Laboratory studies was significant for glucose 539 mg/dL, alkaline phosphatase 153 U/L, gamma-GT 44 U/L, lactate 42,1 mg/dL, arterial pH 7,32 and HbA1c 11%.
Coronal section of the Computed Tomography showed a severe hepatomegaly with a midclavicular craniocaudal diameter of 18 cm. Cross-sectional Computed Tomography showed a severe hepatomegaly reaching deep into the left hemi-abdomen.
Extended laboratory workup could made an inherited iron-overload disorder, autoimmune hepatitis, celiac sprue, thyroid disease, primary biliary cirrhosis, chronic hepatitis B and C, Wilsons’s disease and alpha-1-antitrypsine deficiency less probable.
A Haematoxylin-and-eosin staining on liver-biopsy specimen revealed glycogenated nuclei and diffusely swollen hepatocytes with pale cytoplasm. Periodic acid-Schiff stain shows hepatocytes strongly and diffusely positive, suggesting that the hepatocytes were swollen with glycogen, consistent with glycogenic hepatopathy. There were no arguments for non-alcoholic steatohepatitis, autoimmune or drug-induced hepatitis.
The patient was treated with aggressive intravenous fluid resuscitation and insulin therapy with improvement of the abdominal pain and normalization of the liver tests, lactate and glucose level after 24 hours. This case calls attention to glycogenic hepatopathy as an underrecognized cause of hepatomegaly in patients with poorly controlled type 1 diabetes.

References

1. Sharma B, Antoine M, Shah M, Nagales Nagamos R, John S. Glycogenic Hepatopathy. ACG Case Rep J. 2019 Jul 17;6(7):e00115. doi: 10.14309/crj.0000000000000115. PMID: 31620518; PMCID: PMC6722368.
2. Sherigar JM, Castro J, Yin YM, Guss D, Mohanty SR. Glycogenic hepatopathy: A narrative review. World J Hepatol. 2018 Feb 27;10(2):172-185. doi: 10.4254/wjh.v10.i2.172. PMID: 29527255; PMCID: PMC5838438.
3. Sweetser S, Kraichely RE. The bright liver of glycogenic hepatopathy. Hepatology. 2010 Feb;51(2):711-2. doi: 10.1002/hep.23402. PMID: 19957373.
4. Mauriac P. Gros ventre, hepatomegalie, troubles de las croissance chez les enfants diabetiques traits depuis plusieurs annes par l'insuline. Gax Hebd Med Bordeaux 1930; 26: 402– 410.

Disclosure

The authors have no potential conflict of interest relevant to this clinical case to be reported.

Introduction

GLIMMER (NCT02966834) was a Phase 2b study of the ileal bile acid transport (IBAT) inhibitor, linerixibat, for treatment of cholestatic pruritus in primary biliary cholangitis (PBC). The study included 147 patients: the largest trial in this population to date. GLIMMER had few restrictions on concomitant medications with the exceptions of other IBAT inhibitors, bile acid sequestrants and obeticholic acid; stable doses of other treatments were permitted.

Aims & Methods

In this analysis we explore the pruritus treatment history of patients entering GLIMMER. Investigators recorded details of prior and concomitant use of itch medications on the electronic case report form. For categorisation of prior and/or concomitant itch medication: prior only included patients who had tried and stopped at ≥1 pruritus medication before first study treatment and were not using anything else during treatment with linerixibat/placebo; concomitant only included patients who had used ≥1 pruritus medication in the past, which they continued to use during treatment; prior and concomitant included patients who had tried and stopped ≥1 pruritus medication prior to the study and, continued to use ≥1 pruritus medication during treatment with linerixibat/placebo. This post hoc analysis included all treatments prescribed for itch; guideline treatments were defined as bile acid sequestrants, naloxone, naltrexone, nalmefene, nalfurafine, sertraline, rifampicin or gabapentin. Pruritus severity was defined using worst itch numeric rating scale (NRS).

Results

At baseline, 24% of patients had mild (NRS <4), 52% moderate (NRS ≥4–<7) and 25% severe (NRS ≥7–10) pruritus. Mean age at baseline was 55.8 years but varied by itch severity, with mild patients being older (60.1 years) than those with moderate and severe pruritus (56.8 and 49.6 years, respectively). Median duration of pruritus at baseline was 6.3 years and those with mild pruritus tended to have a longer history than those with moderate or severe itch. Overall, a large proportion of patients were never previously treated: 37% (n = 55) had no prior/concomitant itch medications. Similar proportions of patients, 24% (n = 36) and 26% (n = 38), had received only prior itch medications or received prior and concomitant treatment for pruritus, respectively; 12% (n = 18) of patients were using only concomitant itch medications. Only 25% of patients were treated with cholestyramine, despite it being the guideline-recommended first-line therapy. Treatment history differed by baseline itch severity: 43% of mild patients had no prior or concomitant treatment versus 28% of severe patients. However, differences were less marked for concomitant pruritus therapy use: 43%, 36% and 39% of mild, moderate and severe patients, respectively, continued concomitant itch medicines in GLIMMER. The majority of concomitant itch treatments were non-guideline recommended, with only 39% receiving guideline treatments.

Conclusion

Consistent with the literature, increased itch severity is associated with younger age. Many patients do not receive treatment despite lengthy history of pruritus, while prior use of cholestyramine is limited despite its position in treatment guidelines.
Funding: GSK (201000).
Encore statement: This abstract was originally presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting on November 7, 2022, this encore is presented on behalf of the original authors with their permission.

Disclosure

HTS, AC, MMM, AJW and AR are employees of, and hold shares in GSK. SD is an employee of GSK.

Introduction

Spontaneous bacterial peritonitis (SBP) is defined by the presence of a polymorphonuclear count in ascitic fluid (PMN-A) above 250 cells/µL. However, this cut-off has been determined empirically and its value has been questioned. In this study, we aimed to determine the prognostic value of PMN-A and leukocytes in ascitic fluid (LEUC-A) of an index paracentesis without criteria for SBP, in predicting the subsequent development of SBP and death.

Aims & Methods

A retrospective study (2019-2022) including all patients with cirrhosis and ascites, who underwent paracentesis, was conducted. Patients were stratified by PMN (PMN-A-low: <125/µL; PMN-A-intermediate: 125-250/µL; PMN-A-SBP: ≥250/µL) and LEUC values (LEUC-A-low: <250/µL; LEUC-A-intermediate: 250-500/µL; LEUC-A-SBP: ≥500/µL) in the ascitic fluid of the index paracentesis. The incidence of SBP and mortality were estimated at one year. Statistics: Kruskal-Wallis test, chi-square, and Kaplan-Meier curve analysis.

Results

A total of 101 patients were included (mean age: 64.2± 9.8 years-old; male: 85.1%). The baseline characteristics of the LEUC-A and PMN-A subgroups were comparable, with the exception of C-reactive protein (p=0.02 and p=0.012, respectively). At index paracentesis, patients on prophylactic antibiotic therapy had lower PMN-A values (p=0.017). After exclusion of patients with SBP at the index paracentesis, an association between mortality, intermediate LEUC-A (81.5% vs. 43.8%, p=0.002) and intermediate PMN-A values (93.8% vs. 52.9%, p=0.003) was verified. Additionally, a higher one-year mortality rate was observed in the presence of PMN-A>125/µL (log-rank p=0.001) and LEUC-A>250/µL (log-rank p=0.004). On the other hand, only patients with LEUC-A-intermediate (LEUC-A: 55.6% vs. 12.5%, p<0.001) showed an association with the development of subsequent SBP. However, both patients with LEUC-A>250/µL (log-rank p=0.002) and those with PMN-A>125/µL (log-rank p=0.02) had a higher risk of SBP at one year.

Conclusion

The presence of LEUC-A>250/µL and PMN-A>125/µL seems to be associated with a higher risk of developing SBP and subsequent mortality. These findings may warrant review of the current indications for initiation of prophylactic antibiotic therapy in patients without SBP.

References

1. Simbrunner B, Röthenbacher A, Haslacher H, et al. Ascitic fluid polymorphic nuclear cell count impacts on outcome of cirrhotic patients with ascites. United European Gastroenterol J. 2019;7(5):651-661.
2. European Association for the Study of the Liver. European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406-460.
3. Schwabl P, Bucsics T, Soucek K, et al. Risk factors for development of spontaneous bacterial peritonitis and subsequent mortality in cirrhotic patients with ascites. Liver Int. 2015;35(9):2121-2128.

Introduction

Hepatocellular carcinoma (HCC) is one of the main indication for liver transplantation (LT) worldwide, however, despite various proposed selection criteria, HCC recurrence rate after LT remains up to 20%. An earlier diagnosis allows for more effective treatments and survival benefit. Recently, the RETREAT score has been proposed showing high accuracy.

Aims & Methods

Our aim was to validate the RETREAT score in a single center cohort.
This is a retrospective study including patients who underwent LT for HCC at Padua University-Hospital between January 2016 and December 2018. Clinical and radiological data before and after LT (aFP, liver function according to MELD and CHILD score, tumor morphology, downstaging and/or bridging treatments) and explant pathology features were collected. RETREAT and TTV/aFP scores, based on explant pathology, were calculated. Cox regression and LogRank models have been used for the association between HCC scores and tumor recurrence.

Results

During the study period, 123 patients underwent LT for HCC (HCV 35%, median MELD 11). After HCC diagnosis, 115 patients (93%) underwent downstaging (47% ≥2 treatments), and 64 of them (56%) received bridging therapies. The median aFP at LT was 4.8 ng/mL. On explant pathology, microvascular invasion was found in 27%, G3 nodules in 30%. On explant pathology, 65 patients (53%) were Milan-out, 44 patients (36%) were TTV/aFP-out, 77 patients (62%) had a RETREAT score ≥2. During the follow-up of 50 months (IQR 39-60), 16 patients (13%) showed post-transplant HCC recurrence, at median time of 14 months (IQR 8-36); 75% of them had extrahepatic recurrence. RETREAT score was associated with the risk of HCC recurrence (p<0.001, HR 1.703, 95%CI 1.30-2.22). Patients with RETREAT score 0-1, 2-4 and 5-8 had a 1 year-HCC recurrence of 2%, 4% and 21%, respectively (log-rank<0.001). TTV/AFP has not been associated with HCC recurrence (p=0.680).

Conclusion

RETREAT score is a reliable tool to improve the selection of patients at higher risk of HCC recurrence and to guide the post-LT management, defining shorten tumor surveillance post-LT. Thus, an earlier diagnosis of tumor recurrence might allow more efficacious treatments and patient survival benefit.

Introduction

The best risk-stratification strategy to predict liver-related outcomes (LROs) in the population remains unclear. The Chronic Liver Disease (CLivD) risk score was recently developed and validated to predict LROs in the population. It could thus identify the at-risk population that warrants liver fibrosis screening with non-invasive tests such as FIB-4. The ClivD score is based on age, sex, waist-hip ratio, alcohol use, smoking, diabetes, and gamma-glutamyltransferase measurement.

Aims & Methods

We investigated the combined/sequential use of the ClivD score and FIB-4 for stratifying the risk for LROs in the UK Biobank population.
From the UK Biobank data, we identified 362,330 individuals with no baseline liver disease and data available to calculate the CLivD score and FIB-4. LROs were ascertained through linkage with electronic healthcare registries for hospitalizations, cancers, and deaths related to compensated or decompensated liver cirrhosis or hepatocellular carcinoma. Discrimination performance was assessed by 10-year competing-risk area-under-the-curve (AUC) values and absolute cumulative risks by the cumulative incidence functions considering death without liver disease as a competing-risk event.

Results

Mean age was 56.6 years (SD 8.1), 48% were men, mean BMI 27.2 kg/m2 (SD 4.6), 5% had diabetes, mean alcohol intake was 16.7 g/week (SD 16.6), and 10% were current smokers.
During a median follow-up of 12.6 years (IQR 12.0-13.4), there were 1285 incident LROs. Both the CLivD score and FIB-4 were significantly associated with LROs (P<0.001). The 10-year AUC-value of the CLivD score was 0.80 (95% CI 0.80-0.80) and of FIB-4, 0.75 (95% CI 0.75-0.75) for the prediction of LROs. The predictive performance of FIB-4 improved as a function of increasing CLivD scores: 10-year AUC values of FIB-4 were 0.61 in the minimal-risk CLivD subgroup as compared to 0.81 in the high-risk CLivD subgroup (Table). This effect modification of CLivD for FIB-4’s discrimination performance was also evident for absolute risks. Namely, within the minimal-risk CLivD subgroup, 10-year cumulative incidences of LROs ranged from 0.05% to 0.3% between low and high FIB-4 strata (Table). In contrast, within the high-risk CLivD subgroup, 10-year cumulative incidences of LROs ranged from 1.7% to 21.6% between low and high FIB-4 strata.

Conclusion

Defining the at-risk population by the CLivD score markedly improves the predictive performance of FIB-4. Thus, sequential use of the CLivD score and FIB-4 emerges as a simple way to stratify the population regarding the risk for LRO.