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.

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

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.

Introduction

Piecemeal endoscopic mucosal resection (EMR) vs endoscopic submucosal dissection (ESD) has been a long standing debate in the endoscopic community worldwide with multiple studies done to evaluate the preferred method to manage large colorectal neoplasms. Piecemeal EMR with thermal ablation of the margin has been strongly advocated and reported by certain groups to be a simple, inexpensive and effective technique and this has been preferred widely due to its perceived ease of performance and shorter learning curve.¹ However, close, repeated surveillance colonoscopy is recommended even when the lesion is thought to have been completely resected² as residual tumors can cause interval cancers.³ Some groups, mainly from east Asian countries, have recommended en bloc resection by ESD due to significantly lower risk of local recurrence and precise pathological diagnosis.⁴ But its usage is limited due to concerns about risk of serious adverse events. With improvement in training and devices, colorectal ESD is now being performed by various centers globally. This study aims to report the outcomes of an international, multicenter study on colorectal ESD.

Aims & Methods

Patients who underwent colorectal ESD for lesions greater than 20mm between January 2022 to April 2024 from centers in USA, Japan, and India respectively were included in this study. Recurrent lesions after endoscopic therapy, neoplasms identified in patients with ulcerative colitis, and non-epithelial lesions were included. Primary outcomes were en bloc and R0 resection rate, delayed adverse events (bleeding/perforation), and local recurrence rate. Secondary outcomes were procedure time, lesion size, and pathology. Univariate and multivariate analysis were done to identify the risk factors for primary outcomes.

Results

309 patients (median size, 40(27.5-60)mm; location rectum 52.4%, left colon 26.2%, right colon 21.4%) were involved in this study. The en bloc resection rate was 96.1% and R0 resection rate was 90.3%. 3 patients experienced delayed bleeding which was managed endoscopically. 2 patients underwent surgery for delayed perforation. 6 patients had a local recurrence. 67(23%) patients had intramucosal carcinoma on pathology. Univariate analysis showed lesser procedure time (median(IQR) 145(80-236.25) vs 270(180-300) minutes, P= 0.005) and smaller lesion size (median(IQR) 40(26-56.25) vs 60(40-90) mm, P= 0.004) were significant factors for successful en bloc resection. However, lesser procedure time (median(IQR) 74(29.5-97.5) vs 150(82.5-240) minutes, P= 0.034) led to an increased delayed adverse event rate. Multivariate analysis using Cox regression showed en bloc resection (odds ratio 0.038; 95% confidence interval 0.003-0.421; P= 0.008) was an independent factor preventing local recurrence.

Conclusion

This international, multicenter study with data from three countries shows favorable outcomes for colorectal ESD for large lesions. The high en bloc and R0 resection rate, and low adverse event rate show increased global adaptation to this procedure. Reduced local recurrence is an added benefit. Data from a more centers globally will be valuable to establish ESD as the standard for large colorectal neoplasms.

References

1. Sidhu M, Shahidi N, Gupta S et al. Outcomes of thermal ablation of the mucosal defect margin after endoscopic mucosal resection: a prospective, international, multicenter trial of 1000 large nonpedunculated colorectal polyps. Gastroenterology. 2021 Jul 1;161(1):163-70.
2. Gupta S, Lieberman D, Anderson JC et al. Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc 2020;91:463-485.e5.
3. Rutter MD, Beintaris I, Valori R et al. World Endoscopy Organization Consensus Statements on Post-Colonoscopy and Post-Imaging Colorectal Cancer. Gastroenterology 2018;155:909-925.e3.
4. Ohata K, Kobayashi N, Sakai E et al. Long-term outcomes after endoscopic submucosal dissection for large colorectal epithelial neoplasms: a prospective, multicenter, cohort trial from Japan. Gastroenterology. 2022 Nov 1;163(5):1423-34.

Introduction

Liver fibrosis is the main prognostic driver and an independent risk factor for both hepatic and extrahepatic events and global mortality in patients with non-alcoholic fatty liver disease (NAFLD). Thus, many serum markers and scores for the assessment of fibrosis severity have been drawn up. Recently, researchers developed the easy Liver Fibrosis Test (eLIFT) and the BMI, AST/ALT ratio and Diabetes (BARD) score.

Aims & Methods

This study aimed to compare the eLIFT and the BARD scores with Transient Elastography for the assessment of liver fibrosis in obese patients with NAFLD.
We conducted a transversal study including obese patients recruited from the Department of Nutrition referred to our center for screening for liver steatosis and a non-invasive evaluation of liver fibrosis. We excluded patients who had pre-existing chronic liver disease, chronic alcohol consumers, or those with ongoing medication other than those for metabolic syndrome.
Demographic and clinical features of the participants were recorded. All participants underwent Transient Elastography (TE) and had their AST, ALT, gamma-glutamyl transferase (GGT), platelet count, and prothrombin time measured in a random blood sample, taken the same day of the TE. We calculated for each patient the eLIFT and BARD scores using standard formulas.
Liver stiffness measurements (LSM) used to define the risk for advanced fibrosis as low, indeterminate, and high, based on EASL guidelines 2021, were respectively: <8 kPa, ≥8 and < 12 kPa, and ≥12 kPa.
An eLIFT <8 indicated a low risk of advanced fibrosis, whereas a result ≥8 identified patients at risk of advanced fibrosis. The BARD score ranges from 0 to 4, considered low from 0 to 1 with a high negative predictive value (NPV) for advanced fibrosis, and considered high from 2 to 4 with a high risk of advanced fibrosis.

Results

A total of 213 obese patients with NAFLD were included, with a mean age of 49.04 ± 11.76 years, 88% were female. The mean body mass index (BMI) was 40.67 ± 10.16 kg/m² and the mean waist circumference (WC) was 115.07 ± 17.49 cm.
TE results revealed that 191 patients had a low risk of advanced fibrosis (89.7%), 13 had an indeterminate risk of advanced fibrosis (6.1%), and nine patients had a high risk of advanced fibrosis (4.2%). Using eLIFT, 195 patients were classified in the low-risk of advanced fibrosis group of which 187 had also a low risk based on TE and only 8 had a high risk of advanced fibrosis, which corresponds to a rate of sensitivity at 92.6%; specificity at 27.3%; NPV at 95.9%; and positive predictive value (PPV) at 16.7%.
The BARD score was low in 21 patients (9.9%) and high in 192 (90.1%). Among the 21 patients with a low BARD score, 19 had a low risk of advanced fibrosis based on LSM and two had a high risk of advanced fibrosis. In the group of patients with a high score, only nine had advanced fibrosis. Sensitivity was 8.5%; specificity was 90%; NPV was 94.4%; and PPV was 4.7%. Both scores had high NPV for a high risk of advanced fibrosis, but the BARD score had a lower sensibility than eLIFT, with better specificity.
AUROC were 0.515 (95% CI, 0.11-0.92) and 0.743 (95% CI, 0.49-0.99) for eLIFT and BARD scores, respectively.

Conclusion

Both eLIFT and BARD scores were useful for ruling out advanced fibrosis (NPV > 90%) in an obese population with NAFLD. As such, they are adequate for use in clinical practice or as a part of referral and follow-up programs.

Introduction

Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative strategy for chronic hepatitis B (CHB), but data on optimal biomarkers for post-treatment monitoring is limited.

Aims & Methods

With the aim to investigate whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR), this retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase (ALT) > 80 U/L with recurrent viremia. During follow-up, serum HBcrAg was evaluated as a time-varying variable in the Cox proportional hazard model.

Results

The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.1% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5-40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7-67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1% ‐ 62.4%). Time-varying HBcrAg levels were a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.43 per log U/mL; 95% CI, 1.16-1.76) in the multivariable model adjusted for EOT HBsAg level, anti-HBe antibody, and EOT ALT. During follow-up, HBcrAg < 1,000 U/mL predicted a low risk of subsequent CR (aHR, 0.31; 95% CI, 0.17-0.57).

Conclusion

Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be used to guide posttreatment monitoring.

References

1. Mak LY, Wong DK, Cheung KS, Seto WK, Lai CL, Yuen MF. Review article: Hepatitis B core-related antigen (HBcrAg): an emerging marker for chronic hepatitis B virus infection. Aliment Pharmacol Ther. 2018;47(1):43-54.
2. Hsu YC, Nguyen MH, Mo LR, Wu MS, Yang TH, Chen CC, et al. Combining hepatitis B core-related and surface antigens at end of nucleos(t)ide analogue treatment to predict off-therapy relapse risk. Aliment Pharmacol Ther. 2019;49(1):107-15.
3. Sonneveld MJ, Park JY, Kaewdech A, Seto WK, Tanaka Y, Carey I, et al. CREATE Study Group. Prediction of Sustained Response After Nucleo(s)tide Analogue Cessation Using HBsAg and HBcrAg Levels: A Multicenter Study (CREATE). Clin Gastroenterol Hepatol. 2022 Apr;20(4):e784-e793