Introduction

Hepatic encephalopathy (HE) is a disorder of the central nervous system caused by liver insufficiency and/or portosystemic shunting, manifesting as a wide spectrum of neurological or psychiatric abnormalities ranging from subclinical alterations to coma. In this pilot study, we compared the efficacy of intravenous(IV) L-Ornithine-L-Aspartate( LOLA) versus oral LOLA in patients with chronic liver disease (CLD) with overt HE(OHE).

Aims & Methods

40 patients with CLD with OHE were randomized to IV LOLA and oral LOLA in ratio of 1:1. Patients were monitored for grade of HE and serial level of serum ammonia was monitored from first day of starting LOLA (IV or Oral) till 5^th day. The objective was to compare the efficacy of IV versus oral LOLA in clinical improvement of grade of HE and its correlation with serum ammonia levels.

Results

The baseline characteristics of patients in both the groups were comparable, majority were male and had history of significant alcohol intake. Most patients were CLD with CTP-C. The change in ammonia level from day 1 to day 5 among the IV LOLA group was 55.4± 32.58 µmol/L as compared to 60.75± 13.82 µmol/L in the oral LOLA group. The correlation between ammonia level and grade of HE, r-value was 0.702 on day 1 and 0.682 on day5 between the two groups (p <0.001). Significant reductions in levels of ammonia was seen in both the groups from day 1 to day 5(P< 0.001).

Conclusion

The use of LOLA (IV and /or Oral) was effective in serial reductions of ammonia levels and improvement in the grades of HE. CTRI/2020/12/029943

Clinical Case Summary

For decompensated advanced chronic liver disease (dACLD) individuals, the onset of refractory ascites (RA) represents a dramatic event (6-month survival rate < 50%). In this setting, a relevant proportion of RA patients develop Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI) with limited therapeutic and survival chances.
An 81-year-old female dACLD RA patient was admitted to our department to receive large-volume paracentesis (LVP). Eradicated HCV infection, type II diabetes, and chronic obstructive pulmonary disease were her comorbidities.
The AKI onset imposed the intravenous (i.v.) human albumin (HA) (1 g/kg/die) administration, followed by the proper dosage of terlipressin (for HRS-AKI) within the first 72 hours (h), subsequently discontinued due to the persistence of anuria and the worsening of respiratory failure.
To simultaneously address uremic symptoms and facilitate ascites drainage, a Tenckhoff catheter was placed, and peritoneal dialysis (PD) started with a single icodextrin dwell, resulting in the removal of 14 L of ascites and an improvement in AKI within the subsequent 72h. After one week, she was discharged, receiving a specific PD schedule. After the readmission due to the difficulties in administering i.v. HA, we proposed administering HA via the intraperitoneal route, creating an HA-enriched PD (PD+HA) home-performable schedule by adding two vials of 100 ml of HA 20% to 800 ml of icodextrin solution (40 g in 1000 ml/die; lasting: 12 hours; frequency: every other day) (Figure 1).
The patient has been performing this PD schedule for 12 months (~0.5 L of ascites is discharged every other day before performing PD+HA dwell). During the follow-up, no PD-related complications (e.g., peritonitis) and liver-related events requiring hospitalization have been observed.
We report the first successful use of PD+HA, highlighting the cruciality of a multidisciplinary (hepatologists-nephrologists) approach in the management of dACLD-RA HRS-AKI patients.

References

1. Moreau, R.; Delègue, P.; Pessione, F.; Hillaire, S.; Durand, F.; Lebrec, D.; Valla, D.-C. Clinical Characteristics and Outcome of Patients with Cirrhosis and Refractory Ascites. Liver Int 2004, 24, 457–464, doi:10.1111/j.1478-3231.2004.0991.x.
2. Moore, K.P.; Wong, F.; Gines, P.; Bernardi, M.; Ochs, A.; Salerno, F.; Angeli, P.; Porayko, M.; Moreau, R.; Garcia-Tsao, G.; et al. The Management of Ascites in Cirrhosis: Report on the Consensus Conference of the International Ascites Club. Hepatology 2003, 38, 258–266, doi:10.1053/jhep.2003.50315.
3. Nadim, M.K.; Kellum, J.A.; Forni, L.; Francoz, C.; Asrani, S.K.; Ostermann, M.; Allegretti, A.S.; Neyra, J.A.; Olson, J.C.; Piano, S.; et al. Acute Kidney Injury in Patients with Cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) Joint Multidisciplinary Consensus Meeting. J Hepatol 2024, 81, 163–183, doi:10.1016/j.jhep.2024.03.031
4. Brown, E.A.; Blake, P.G.; Boudville, N.; Davies, S.; de Arteaga, J.; Dong, J.; Finkelstein, F.; Foo, M.; Hurst, H.; Johnson, D.W.; et al. International Society for Peritoneal Dialysis Practice Recommendations: Prescribing High-Quality Goal-Directed Peritoneal Dialysis. Perit Dial Int 2020, 40, 244–253, doi:10.1177/0896860819895364.

Introduction

Hepatocellular carcinoma (HCC) is one of the most common and second most lethal liver cancer in the world (1). Unfortunately, only 18% of patients bearing HCC have a 5-year survival rate, which places it as the second most lethal cancer, preceded only pancreatic cancer (2). Therefore, a strategy that could reduce mortality from HCC is to develop an early diagnosis approach based on identifying new biomarkers. Based on a previous transcriptomic study in our lab, which revealed that annexins gene expression was modified in microdissected HCC nodules (3). Annexins A1, A2, A5, A8, and A10 belong to the A family of annexins that are Ca²⁺-regulated phospholipid-binding proteins. Members of this family can be peripherally coupled to the surface of negatively charged membranes when they are calcium-linked. This capability provides them with membrane-bound functions, such as organization, transport, and interaction with the actin cytoskeleton (4). The rat hepatocarcinogenesis model, induced with diethylnitrosamine (DEN), has proven to be highly effective in replicating the development of cirrhosis and heterogeneous multinodular HCC within 18 weeks. DEN's alkylating properties induce chronic liver damage, leading to inflammation and fibrosis that are associated with cirrhosis and HCC. This closely resembles the development of HCC in humans (5, 6).

Aims & Methods

We aimed to further investigate the expression profile of five annexin genes in a well-established animal model of hepatocarcinogenesis associated with cirrhosis and to identify potential serological markers for early HCC. The gene expression products of annexin were analyzed by RT-qPCR and western blots. Both mRNA and proteins were extracted from rat liver tissue at preneoplastic stages at 6 and 12 weeks and neoplasia at 18 and 22 weeks. Also, immunofluorescence was performed on rat liver samples and compared to HCC of clinical origin. Plasma samples were collected from the experimental model, and we used the ELISA technique to measure the serum levels of Annexin A1, A2, and A5.

Results

A gradual increase of annexin A1, A2, A5, and A10 was observed in liver of hepatocarcinogenesis-induced animals compared to normal liver both at mRNA and protein levels, being a statistically significant increase for annexin A1 and A5 since week 6 of the hepatocarcinogenesis model. In contrast, annexin A8 showed a significant decrease in protein levels. The histological location of annexin A1, A2, and A5 was in the tumor cells. The cellular location for annexin A1 and A5 observed in the cytoplasm and membrane of normal hepatocytes showed a re-localization to the nucleus of neoplastic cells. Notably, a significant increase in the plasma level of annexin A5 from week 12 was detected, with a gradual increase until week 22 in the hepatocarcinogenesis model. Moreover, the plasmatic level of annexin A5 significantly correlated (r² = 0.8203) with the hepatic Annexin A5 level. Using the TCGA database, we found that the expression of ANXA2 (HR = 1.7, p = 0.0046) and ANXA5 (HR = 1.8, p = 0.00077) was associated with poor survival in HCC patients.

Conclusion

The results suggest that the expression profile of annexin A1, A5, and A10 may serve as early tumor markers, whereas annexin A2 and A8 could be used as markers of hepatocellular carcinoma progression, given their expression changes during advanced stages of hepatocarcinogenesis. Significantly, the presence of annexin A5 in the plasma of model animals suggests its potential as a biomarker for hepatocarcinogenesis.

References

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49.
2. Villanueva A. Hepatocellular Carcinoma. N Engl J Med. 2019;380(15):1450-62.
3. Castro-Gil MP, Torres-Mena JE, Salgado RM, Munoz-Montero SA, Martinez-Garces JM, Lopez-Torres CD, et al. The transcriptome of early GGT/KRT19-positive hepatocellular carcinoma reveals a downregulated gene expression profile associated with fatty acid metabolism. Genomics. 2022;114(1):72-83.
4. Gerke V, Moss SE. Annexins: from structure to function. Physiol Rev. 2002;82(2):331-71.
5. Schiffer E, Housset C, Cacheux W, Wendum D, Desbois-Mouthon C, Rey C, et al. Gefitinib, an EGFR inhibitor, prevents hepatocellular carcinoma development in the rat liver with cirrhosis. Hepatology. 2005;41(2):307-14.
6. Sánchez-Rodríguez R, Torres-Mena JE, Quintanar-Jurado V, Chagoya-Hazas V, Rojas Del Castillo E, Del Pozo Yauner L, et al. Ptgr1 expression is regulated by NRF2 in rat hepatocarcinogenesis and promotes cell proliferation and resistance to oxidative stress. Free Radic Biol Med. 2017;102:87-99.

Clinical Case Summary

Introduction: Cirrhosis complicated by portal hypertension often leads to gastrointestinal bleeding, predominantly from esophageal varices. However, the occurrence of lower GI bleeding from rectal varices and angiodysplasias represents a rarer and more complex clinical scenario. We report the case of a 62-year-old man with cirrhosis and multiple vascular anomalies requiring multidisciplinary management.
Patient observation: The patient, with a history of Type 2 diabetes, coronary artery disease, and prior cholecystectomy, was diagnosed with cirrhosis of presumed autoimmune origin, despite non-confirmatory liver biopsy. He experienced recurrent upper GI bleeding from esophageal varices, managed with beta-blocker therapy. More recently, a massive lower GI bleed led to endoscopic assessment revealing gigantic rectal varices and diffuse colonic angiodysplasias. Stabilisation was achieved by treating the angioddysplasias endoscopically with APC.
Figure 1&2: endoscopic images
Discussion: This case illustrates the difficulty of managing complex portal hypertension complications. While beta-blockers reduce bleeding risk from esophageal varices, rectal varices and angiodysplasias pose additional therapeutic challenges. Endoscopic sclerotherapy, band ligation, or embolization may be required, but their efficacy in diffuse vascular anomalies remains limited. The presence of multiple bleeding sources demands vigilant surveillance and individualized management strategies. Moreover, coexisting comorbidities like diabetes and cardiovascular disease complicate procedural risks and therapeutic decisions.
Conclusion: Managing cirrhosis complicated by giant rectal varices and angiodysplasias requires a multidisciplinary and tailored approach. This case highlights the importance of ongoing surveillance, optimized medical therapy, and readiness for endoscopic or interventional radiology techniques to prevent further decompensations and preserve quality of life.

Introduction

The endoscopic transpapillary bile duct brushing cytology and biliary forceps biopsy with endoscopic retrograde cholangiopancreatography are generally performed for pathological diagnosis of biliary strictures. The sensitivity of the conventional cytology and biopsy was reported to be 30% to 81%. The diagnosis of biliary strictures may not be reached, especially of those caused by pancreatic cancer.

Aims & Methods

The Trefle (Piolax Medical Devices, Yokohama, Japan) is a new device that consists of looped metallic wires to scrape and aspirate the tissue along with bile juice. The aim of the study was tocompare the diagnostic performance of the new device with that of conventional cytology and biopsy. A total of 264 cases with biliary stricture underwent transpapillary biopsy and cytology between 2012 and 2021, of which 124 were diagnosed using the new device. We retrospectively analyzed the diagnostic utility of the new device compared with that of conventional cytology and biopsy.

Results

The locations of biliary strictures were perihilar in 73 cases and distal in 191 cases. Of the 264 cases, 195 were diagnosed with a malignant stricture. 122 cases had biliary cancer, whereas 72 had pancreatic cancer. The sensitivity of the new device and the conventional cytology and biopsy was 61% and 55%, respectively. Adding a biopsy to the new device increases the sensitivity to 89%. In the cases with biliary strictures caused by pancreatic cancer, the sensitivity of the new device and the conventional cytology and biopsy was 49% and 39%, respectively.

Conclusion

Our study suggests that the new device was more useful than conventional cytology and biopsy for the pathological diagnosis of biliary strictures, especially those caused by pancreatic cancer. Adding a biopsy to the new device to the new device is expected to increase sensitivity.

References

1) Sakuma Y, Kodama Y, Sogabe Y et al. Diagnostic performance of a new endoscopic scraper for malignant biliary strictures:a multicenter prospective study. Gastrointest Endosc 2017; 85: 371-9.
2)Meara R S, Jhala D, Eloubeidi M A et al. Endoscopic ultrasound-guided FNA biopsy of bile duct and gallbladder: analysis of 53 cases. Cytopathology. 2006;17:42–9.

Disclosure

No COI

Introduction

The "Antimicrobial Resistance in Acute Cholangitis" (ARISE) study is a prospective investigation focused on the antimicrobial resistance patterns in patients with acute cholangitis undergoing ERCP. Conducted across multiple tertiary gastroenterology centers in Romania, this study aims to identify, analyze, and mitigate the challenges posed by multidrug-resistant (MDR) organisms in managing acute cholangitis.

Aims & Methods

Data collected included microbial cultures from bile samples, patient demographics, clinical outcomes, and antibiotic resistance profiles. From the study's onset in January 2024, 138 eligible patients were identified as having positive bile cultures. Among these patients, the predominant symptoms included abdominal pain (82.6%), jaundice (71%), and fever or shaking chills (36.2%). The diagnosis of acute cholangitis was established using TG18 criteria.

Results

Bile cultures were positive in 71.0% of cases. The most frequently isolated bacteria were Escherichia coli, found in 23.2% of positive cultures, followed closely by Enterococcus spp., present in 22.5% of cases. Klebsiella pneumoniae was also notably prevalent, identified in 7.2% of the bile samples. Ciprofloxacin showed the highest resistance rate among the tested antibiotics, with a resistance rate of 23.9%. Ampicillin and gentamicin displayed significant resistance rates at 10.9% and 18.8%, respectively. Piperacillin/tazobactam and trimethoprim/sulfamethoxazole each showed a resistance rate of 15.2%. The study's data on tigecycline and linezolid showed lower resistance rates, with tigecycline maintaining a sensitivity rate of 20.3% and linezolid at 19.6% in cultures where testing was applicable. In comparison, their resistance rates were only 0.7% for each. Multidrug resistance was identified in a significant fraction of isolates, with 15.2% of samples. A concerning finding was the presence of MDR strains of Escherichia coli, which exhibited resistance rates to ampicillin (21.0% sensitivity, 10.9% resistance) and amoxicillin/clavulanic acid (17.4% sensitivity, 14.5% resistance).

Conclusion

We observed a concerning prevalence of MDR organisms in acute cholangitis cases, particularly against antibiotics such as ampicillin, gentamicin, and ciprofloxacin, with a high incidence of MDR Escherichia coli strains.