Introduction

Acute-on-chronic liver failure ( ACLF) is a severe form of acute decompensation of chronic liver disease with a high short-term mortality rate. It is characterized by excessive systemic inflammatory response and extrahepatic multiorgan failures (1). Previously published data have shown that therapeutic plasma exchange (TPE) decreases mortality rate in patients with ACLF reducing cytokine levels, serum bilirubin, and coagulopathy (2,3).

Aims & Methods

This retrospective study was conducted at the University Clinical Center of Serbia. All patients diagnosed with ACLF according to the EASL criteria and treated with TPE from January 2021 to January 2024 were included. (1) The main indication for providing TPE was serum bilirubin level >12 mg/dl with no improvement to standard medical treatment (SMT). The following scores were calculated at the hospital admission: Model for end-stage liver disease (MELD), Model for end-stage liver disease-Sodium (MELD-Na), Chronic Liver Failure Consortium- acute-on-chronic liver failure (CLIF-C ACLF). All patients were followed for 90 days. MELD and MELD-Na scores were calculated as well on the day 28.
The aims of this study were: assessment of 28-day and 90-day survival in patients with ACLF, the impact of TPE on MELD, and MELD-Na score.

Results

The study included 40 patients in whom SMT did not lead to improvement, of which 32 (80%) were male and 8 (20%) were female with a median age of 45.5 ( 39.75-58.5) years. The most frequent cause of liver cirrhosis was alcohol ( n=28; 70%), followed by Wilson disease (n=4; 10%), metabolic dysfunction-associated fatty liver disease ( MAFLD) (n=3; 7,5%), autoimmune hepatitis ( n=2; 5%), primary biliary cholangitis ( n=2; %%), AIH/ PSC syndrome overlap (n=1; 2.5%). Eighteen patients (45%) were previously diagnosed with acute decompensation ( Table 1). The average number of performed TPEs was 6±12.73. In alcohol-related liver disease (ALD) cirrhosis, alcoholic hepatitis was the main cause of ACLF in 22 (78.5%) patients. Twenty-two patients (55%) were diagnosed with Community-acquired infections. At admission, the average MELD and MELD-Na scores were 28.5±6.43 and 31±6.21. The mean MELD and MELD-Na scores in surviving patients after 28 days were 24.3 ±7.78 and 25.52±7.58, respectively. The average CLIF C-ACLF score at admission was 47±8.07. ACLF grade 1 was observed in 20 patients (50%), ACLF grade 2 in 18, (45%), and ACLF grade 3 in 2 (5%). The 28-day mortality in this study group was 37.5% (n=15), with 25% (n=5) in ACLF grade 1, 44.4%(n=8) in ACLF grade 2, and 100% (n=2) in ACLF grade 3. Ninety-day mortality was 62.5% (n=25). Regarding the ACLF grade, the following 90-day mortality was observed: grade 1-45%( n=9), grade 2-77.8%( n=14), and grade 3-100 (n=2). With the use of TPE in addition to SMT, a statistically significant decrease in MELD and MELD-Na as well was observed after 28 days (p <0.01).

Conclusion

TPE may be a beneficial treatment option for patients who do not respond to SMT, but in our study, short-term mortality is still high. New prospective randomized studies with a larger number of subjects are needed to examine this therapeutic modality accurately.

References

1. European Association for the Study of the Liver (2023). EASL Clinical Practice Guidelines on acute-on-chronic liver failure. Journal of Hepatology, 79(2), 461–491.
2. Mao WL, Chen Y, Chen YM, Li LJ. Changes of serum cytokine levels in patients with acute on chronic liver failure treated by plasma exchange. J Clin Gastroenterol. 2011;45:551–555.
3. Chris-Olaiya A, Kapoor A, Ricci KS, Lindenmeyer CC. Therapeutic plasma exchange in liver failure. World J Hepatol. 2021;13(8):904-915.

Disclosure

There is no conflict of interest.

Clinical Case Summary

A 64-year-old woman with a prior diagnosis of type I achalasia underwent Heller myotomy with Dor fundoplication in 2015, which resulted in the resolution of dysphagia and regurgitation. However, she kept experiencing chest pain, which partially improved with nitro-glycerine. In 2018, due to worsening pain, she underwent high-resolution oesophageal manometry (HROM), which demonstrated absent peristalsis without oesophageal pressurization. Also, upper endoscopy was unremarkable, and timed barium swallow (TBS) revealed some tertiary contractions. By 2019, the patient received botulinum toxin injections with partial improvement. Another TBS performed in 2023 showed tertiary contractions in the distal third of the oesophagus, contributing to mild oesophageal emptying delay but without stasis. In 2024, repeat HROM revealed pan-oesophageal pressurization, except in the distal-most centimetres of the oesophagus. During rapid drink challenge, the patient reported pain. Given these findings, she was proposed for peroral endoscopic myotomy (POEM) to extend the myotomy proximally. In August 2024, she underwent a complete distal oesophageal myotomy, including the lower oesophageal sphincter and cardia. Endoscopic assessment in November showed no evidence of stasis, esophagitis, or resistance at the cardia. Latest clinical evaluation in March 2025 confirmed complete resolution of chest pain.
Conclusion: Non-cardiac chest pain is a less common yet challenging symptom to manage in achalasia. Its persistence after disease-directed treatment has been described in the literature, with its primary risk factor being its presence preoperatively¹. However, comparative data on different therapeutic approaches for achalasia-related chest pain remain limited. To our knowledge, only two similar cases have been reported in which pain persisted after Heller myotomy but improved following POEM, probably linked to the inadequate or incomplete myotomy of the oesophageal muscle layer^2,3.

References

1. Olvera-Prado H, et al. Predictive factors associated with the persistence of chest pain in post-laparoscopic myotomy and fundoplication in patients with achalasia. Front Med (Lausanne). 2022 Oct 14;9:941581.
2. Miftahussurur M, Tandan M, Makmun D, Nabi Z. Peroral Endoscopic Myotomy in a Patient with Achalasia Cardia with Prior Heller's Myotomy. Case Rep Gastroenterol. 2020 Jan 22;14(1):48-55.
3. Sato C, et al. Salvage therapy for postoperative residual chest pain due to esophageal achalasia. SAGES 2017 Annual Meeting in Houston [Abstract], https://www.sages.org/meetings/annual-meeting/abstracts-archive/salvage-therapy-for-postoperative-residual-chest-pain-due-to-esophageal-achalasia/

Introduction

Duodenal stump fistula (DSF) represents a significant complication that can arise following gastrectomy, with a prevalence ranging from 1.0% to 2.5%. This condition is characterised by a high mortality risk (12.5% to 28%) and a high morbidity rate (75%). In instances where conservative management has proven ineffective, percutaneous transhepatic biliary drainage (PTBD) emerges as a valuable intervention. This procedure involves the aspiration of bile, thereby reducing duodenal pressure and diminishing fistula output. However, it is important to note that PTBD does necessitate a prolonged healing period and frequently requires subsequent treatments, such as percutaneous or endoscopic injection of glue. The prolonged hospitalization is also to be considered in these patients, in which the resolution of the fistula generally requires a period of between 60 and 240 days.
The objective of this study was to ascertain the viability and effectiveness of a pioneering technique involving percutaneous DFS embolization with ethylene vinyl alcohol copolymer (EVOH) in combination with an occlusion balloon, utilised in the management of DSF following gastrectomy for malignant or benign indications.

Aims & Methods

The present study encompassed patients with a diagnosis of DSF, as determined by the presence of duodenal juice in the surgical drainage or its leakage through the abdominal wall. This diagnosis was confirmed through surgical approach and/or a computerised tomography (CT) scan. A retrospective analysis was conducted on 15 consecutive patients who underwent PTB-A embolization with Ethylene-Vinyl Alcohol Copolymer (EVOH) as a treatment for DSF, following the failure of medical, surgical, or endoscopic interventions.
An analysis was conducted of clinical and technical success, morbidity and mortality.

Results

The population under scrutiny comprised 10 female and 5 male subjects. Furthermore, it is noteworthy that 74% of patients underwent surgery for a malignant lesion. In the present study, a total of 13 patients underwent subtotal gastrectomy. In all cases, technical success was achieved. A positive outcome was achieved in 11 out of 15 patients following a single treatment. In 4 cases, patients required further treatment to achieve complete fistula healing. In the course of treatment, it was observed that a single patient required four treatment sessions to achieve complete healing. No procedure-related complications or mortalities were recorded. No recurrence of the fistula was observed in the population under study. Radiological follow-up was conducted at one or three months following the procedure for a total of 11 patients. 2 patients expired prior to the scheduled follow-up due to unrelated causes, while 2 patients failed to attend the control appointment.

Conclusion

PTB-A embolization with EVOH of duodenal stump fistula seems to be an effective treatment for DSF, with prompt recovery, no mortality and short hospitalization after the procedure.

References

1. Orsenigo E,et al. Duodenal stump fistula after gastric surgery for malignancies: a retrospective analysis of risk factors in a single centre experience. Gastric Cancer. 2014 Oct;17(4):733-44. doi: 10.1007/s10120-013-0327-x.

2. Paik HJ, et al. Duodenal stump fistula after gastrectomy for gastric cancer: risk factors, prevention, and management. Ann Surg Treat Res. 2016 Mar;90(3):157-63. doi: 10.4174/astr.2016.90.3.157.

3. Gu L, et al. Risk Factors for Duodenal Stump Leakage after Laparoscopic Gastrectomy for Gastric Cancer. J Gastric Cancer. 2020 Mar;20(1):81-94. doi: 10.5230/jgc.2020.20.e4.

4. Naito R, et al. Retrograde drainage for duodenal stump leakage using ileal decompression tube guided by double-balloon endoscopy: a novel case report. Surg Case Rep. 2024 Feb 18;10(1):44. doi: 10.1186/s40792-024-01842-9.

5. Aurello P, et al. Management of duodenal stump fistula after gastrectomy for gastric cancer: Systematic review. World J Gastroenterol. 2015 Jun 28;21(24):7571-6. doi: 10.3748/wjg.v21.i24.7571.

6. Zizzo M, et al. Management of duodenal stump fistula after gastrectomy for malignant disease: a systematic review of the literature. BMC Surg. 2019 May 28;19(1):55. doi: 10.1186/s12893-019-0520-x.

7. Cozzaglio L, et al. Percutaneous transhepatic biliary drainage and occlusion balloon in the management of duodenal stump fistula. J Gastrointest Surg. 2011 Nov;15(11):1977-81. doi: 10.1007/s11605-011-1668-6.

Introduction

H. pylori eradication therapy induces significant alterations in the gut microbiome. While probiotics have been extensively studied as a potential strategy to mitigate microbiota-related consequences of antibiotics, their efficacy remains a subject of debate.

Aims & Methods

The aim of our study was to evaluate the influence of butyric acid+inulin supplements on gut microbiota changes (including gut microbiota taxonomic composition, functional potential, and gut resistome) induced by H.pylori eradication therapy. A total of 22 H. pylori-positive patients aged 19 to 64 years were enrolled in the study. Patients were randomized into two H. pylori eradication regimens: 1) ECAB-14: esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, and bismuthate tripotassium dicitrate 240 mg, twice daily, orally, for 14 days. 2) ECAB-Z-14: esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, and bismuthate tripotassium dicitrate 240 mg, twice daily, along with butyric acid+inulin (Zacofalk) supplementation (two tablets daily, each containing 250 mg of butyric acid and 250 mg of inulin), orally, for 14 days. Stool samples were collected from each subject at three time points: prior to eradication therapy (I), after therapy completion (II), and one month post-therapy (III). Total DNA from fecal samples was isolated for whole genome sequencing using the Illumina NextSeq 500 platform.

Results

Gut Microbiota Alpha Diversity (Shannon Index): Immediately after eradication therapy, both the ECAB-14 and ECAB-Z-14 groups experienced a significant decrease in gut microbiota alpha diversity compared to the initial level: (2.46 ± 1.06) vs. (3.75 ± 0.342), p = 0.0029, and (3.22 ± 0.73) vs. (3.82 ± 0.30), p = 0.037, respectively. After one month, the Shannon index was restored to the baseline level in the ECAB-Z-14 treatment group: no statistically significant differences were identified between time points III and I [(3.71 ± 0.33) vs. (3.82 ± 0.30), p = 0.206]. However, even a month after therapy, the ECAB-14 treatment group still exhibited a lower Shannon index than the baseline level [(3.27 ± 0.39) vs. (3.75 ± 0.342), p = 0.019].
Functional Potential Alterations: In the ECAB-Z-14 treatment group, less pronounced alterations in gut microbiota functional potential were observed. Specifically, 72 metabolic pathways changed immediately after eradication therapy. In contrast, the ECAB-14 group showed impact on 112 signaling pathways.
Butyrate Production Genes: The abundance of genes associated with butyrate production decreased only in the ECAB-14 treatment group. However, in the ECAB-Z-14 treatment group, the abundance of genes responsible for butyrate production remained stable.
Antibiotic Resistance Genes: The prevalence of gut microbiota antibiotic resistance genes increased significantly in both treatment groups immediately after eradication. Notably, more severe alterations were observed in the ECAB-14 treatment group, where the abundance of 73 antibiotic resistance genes significantly increased. Meanwhile, the ECAB-Z-14 group showed an increase in only 50 antibiotic resistance genes immediately after eradication therapy.

Conclusion

H. pylori eradication therapy significantly affects gut microbiota composition, functional potential, and increases the abundance of antibiotic resistance genes. However, the addition of butyric acid+inulin supplements to the H. pylori eradication regime may mitigate these effects.