Introduction

In order to meet the requirements of the WHO, namely - the eradication of viral hepatitis by 2030, UMF “Grigore T. Popa” from Iasi together with ARAS and the Hospital “St. Spiridon" from Iasi, carries out since 2020 the project "LIVE(RO) 2 - Integrated regional program for prevention, early detection (screening), diagnosis and targeting treatment of patients with chronic liver disease secondary to viral infections with liver viruses B/D and C in the North-East and South-East regions”.

Aims & Methods

This study aimed to assess the epidemiological characteristics of the vulnerable population in the eastern part of the country diagnosed with chronic B/D and C viral infection. Between July 2021 and April 2023, we performed a prospective screening of chronic viral hepatitis B/D and C in vulnerable people in the counties of North-East and South-East of Romania, within the national program LIVE(RO) 2 - EST. Rapid diagnostic tests were used to detect HBs antigen (HBsAg) and anti-HCV antibodies (HCVA): HBV (Wama Immuno-Rapid HBV®) and HCV (Wama Immuno-Rapid HCV®). Rapid test-positive patients were tested for HBV DNA and HCV RNA and those eligible under the national protocol were treated with antivirals.

Results

The study included 55593 individuals tested rapidly, of which 2160 (3.8%) patients were tested positive (1120 women, 1040 men, mean age 55.86 ± 6.023 years, predominantly rural background - 76.19%). Of these, 1077 (49.8%) were HBsAg positive, 918 (42.5%) with HCV positive needle, 37 (1.7%) HBV/HCV coinfection and 128 (5.9%) HBV/VHD coinfection. HBV-DNA was performed in 724 (67.3%) individuals, of which 452 (62.5%) subjects > 2,000 children/ml. Also, 518 (54.3%) patients with HCV-positive Ac had detectable HCV RNA, of which 375 (72.3%) received antiviral treatment. Depending on the ethnicity, the prevalence of viral infection was 4.29% in Roma people and 3.23% in Romanian people. Among the vulnerable groups determined by work, inactive people (27.7%), uninsured people (11.2%), unskilled people (1.87%), unemployed people (0.6%) and people working in agriculture (0.59%) were predominantly tested. Among the special vulnerable groups, people with disabilities (3.99%), people addicted to alcohol (2.43%) and people with a minimum income (1.21%) were predominantly tested.

Conclusion

The high prevalence of B/D and C viral infection in the vulnerable population tested in the North-East and South-East Region of Romania compared to the rest of the population, indicates the significant viral spread of the infection in these people, a condition that requires further testing and the need for policies public health in vulnerable groups to promote access to existing health services and early initiation of optimal antiviral treatment.

Introduction

Primary sclerosing cholangitis (PSC) is an idiopathic cholestatic disease. Recent genome-wide studies (GWAS) have identified about 30 disease susceptible genes to PSC. We investigated the expression profiles of these genes in the liver biopsy samples of the patients with PSC, and revealed that the expression of TNFRSF14, which is a one of the risk genes for PSC, was upregulated in the biliary epithelial cell (BEC) of PSC compared to that in normal liver tissue and primary biliary cholangitis (PBC) liver tissue. TNFRSF14 is a member of the tumor necrosis factor receptor superfamily associated with inflammation and fibrosis. We also clarified that the expression of LIGHT, an active ligand for TNFRSF14, was elevated in the BEC of PSC^１). These molecules are mainly expressed on lymphocytes, and in other inflammatory diseases, many reports have mentioned to the associations between these molecules in the sera and the disease progression.

Aims & Methods

Aims: In this study, we aimed to evaluate the concentrations of these molecules in the sera and bile of PSC.
Methods: The concentrations of soluble TNFRSF14 and LIGHT in the sera and bile were measured by enzyme-linked immunosorbent assay. The samples were collected from the following cases:
• Serum: 73 patients with PSC, 35 patients with PBC and 53 healthy controls.
• Bile: 15 patients with PSC, 12 patients with malignant biliary obstruction (MBO), 19 patients with biliary lithiasis (BL).
The bile samples were obtained during endoscopic retrograde cholangiopancreatography. The median values of the serum (s) and bile (b) concentrations of each group were evaluated by Mann-Whittney U test.

Results

sTNFRSF14 in the PSC group was significantly higher than those in the healthy controls (6.301 v.s. 4,247 pg/mL, P < 0.001) and the PBC group (4,987 pg/mL, P < 0.001).
sLIGHT in the PSC group was 87 pg/mL, which was higher than those in the healthy controls (61 pg/mL, P = 0.012), and was comparable to those in the PBC group (106 pg/mL, P = 0.142).
bTNFRSF14 in the PSC group was 2,005 pg/mL, showing no significant difference compared to those in the MBO (1,794 pg/mL, P = 0.516) and the BL group (1,987 pg/mL, P = 0.504).
bLIGHT in the PSC group was 523 pg/mL, remarkably higher than those in the MBO (82 pg/mL, P < 0.001) and the BL group (268 pg/mL, P = 0.024).

Conclusion

sTNFRSF14 in the PSC group was higher than those in the healthy control and the PBC group, and this result was equivalent to the previous report about the upregulated expression in the liver biopsy samples. While soluble LIGHT was secreted non-specifically in the sera of cholestatic liver disease, the elevated bile concentration of LIGHT can be involved in in the unique biology of PSC. ​Further research is needed to elucidate the involvement of these two molecules in the pathogenesis of PSC.

References

1) Digestive Liver Disease 2024 Feb;56(2):305-311.

Clinical Case Summary

Introduction: Zenker's diverticulum (ZD) is a rare oesophageal disorder characterised by oropharyngeal dysphagia and regurgitation. Flexible endoscopic techniques are being increasingly utilised as first-line management. For those requiring revisional repair, Zenker peroral endoscopic myotomy (Z-POEM) offers a potentially safer and more effective alternative to surgery but requires fine-tuning the myotomy. Here, we describe a revisional Z-POEM procedure using a novel two-point myotomy with extension into the cervical oesophagus.
Case Report: A 74-year-old man was referred with recurrent symptoms of dysphagia, regurgitation, and halitosis following a Z-POEM two years previously. His Kothari-Haber score was 6 and his Charlson co-morbidity index was 4. Barium swallow confirmed a residual 2 cm pouch. He underwent a repeat Z-POEM with a transparent conical distal attachment. Initial dissection with the Dual J knife (Olympus) was complicated by marked submucosal fibrosis, which revealed a thick muscular septum. Due to its thickness and orientation, a two-point full-thickness myotomy was performed with extension 3 cm into the cervical oesophagus. The intervening muscle was removed with a 10 mm snare before endoscopic closure of the mucosotomy with clips and X-Tack (Boston Scientific). He was discharged the following day on a modified diet without complication.
Discussion: Revisional ZD repair can be difficult, but Z-POEM offers a minimally invasive endoscopic option to ensure a controlled myotomy under direct vision. Revisional flexible endoscopic procedures are becoming increasingly common in the management of ZD, which means it is essential third space endoscopists can fine-tune their myotomy considering the anatomy, degree of submucosal fibrosis, and septal thickness. We have shown that a modified two-point myotomy is a potential strategy in the presence of these adverse anatomical features to reduce the risk of a residual bar and improve procedural outcomes.

References

1. Endoscopic image of the recurrent pharyngeal pouch.
2. Endoscopic image of two-point full-thickness myotomy.
3. Endoscopic image of the snare being used to remove intervening muscle.
4. Endoscopic image of X-Tack closure in the oropharynx.

Disclosure

RH declares educational grants to support research infrastructure from Cook medical, Odin Vision, Pentax medical, Endogastric Solutions, Apollo Endosurgery, Medtronic, and Aqua Medical.